Hypnosis Modulates Activity in Brain Structures Involved in the...

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Hypnosis Modulates Activity in Brain Structures Involved in the Regulation of Consciousness Pierre Rainville 1 , Robert K. Hofbauer 2 , M. Catherine Bushnell 2 , Gary H. Duncan 1 , and Donald D. Price 3 Abstract & The notion of consciousness is at the core of an ongoing debate on the existence and nature of hypnotic states. Previously, we have described changes in brain activity associated with hypnosis (Rainville, Hofbauer, Paus, Duncan, Bushnell, & Price, 1999). Here, we replicate and extend those findings using positron emission tomography (PET) in 10 normal volunteers. Immediately after each of 8 PET scans performed before (4 scans) and after (4 scans) the induction of hypnosis, subjects rated their perceived level of ‘‘mental relaxation’’ and ‘‘mental absorption,’’ two of the key dimen- sions describing the experience of being hypnotized. Regres- sion analyses between regional cerebral blood flow (rCBF) and self-ratings confirm the hypothesized involvement of the anterior cingulate cortex (ACC), the thalamus, and the ponto-mesencephalic brainstem in the production of hypnotic states. Hypnotic relaxation further involved an increase in occipital rCBF that is consistent with our previous interpreta- tion that hypnotic states are characterized by a decrease in cortical arousal and a reduction in cross-modality suppression (disinhibition). In contrast, increases in mental absorption during hypnosis were associated with rCBF increases in a distributed network of cortical and subcortical structures previously described as the brain’s attentional system. These findings are discussed in support of a state theory of hypnosis in which the basic changes in phenomenal experience produced by hypnotic induction reflect, at least in part, the modulation of activity within brain areas critically involved in the regulation of consciousness. & INTRODUCTION Modern popular views on the phenomenon of hypno- sis are largely dominated by the idea that the ‘‘hypno- tist’’ possesses an otherwise unspecified ability to induce ‘‘sleep-like states’’ within which individuals appear to behave like automatons. In contrast, con- temporary scientific theories of hypnosis emphasize (a) the changes in phenomenal experience (e.g., Price, 1996), (b) the engagement or disengagement of spe- cific neurocognitive processes and the effect on per- formance and psychophysiological activity (e.g., attention, executive control; Gruzelier, 1998; Crawford, 1994), (c) the contextual cues and psychosocial inter- action between the participant and the hypnotist (e.g., Coe & Sarbin, 1977), or (d) the individual psychological characteristics predicting hypnotic susceptibility (e.g., Crawford & Gruzelier, 1992). These accounts differ in their main causative explanations of hypnotic phenom- ena and provide the background for an ongoing debate on whether or not hypnosis constitutes a distinct state of consciousness. The combination of experiential measures (e.g., self- rating of subjective experience; Varela & Shear, 1999; Price & Barrell, 1980) and psychophysiological methods (e.g., functional brain imaging) has recently contributed some unique information on the neurophysiological correlates of (1) multiple pain dimensions (Hofbauer, Rainville, Duncan, & Bushnell, 2001; Rainville, Duncan, Price, Carrier, & Bushnell, 1997), (2) the feeling of ‘‘remembering’’ versus ‘‘knowing’’ in studies of memory (e.g., Henson, Rugg, Shallice, Joseph, & Dolan, 1999), and (3) the individuals’ self-confidence in their responses (e.g., Henson, Rugg, Shallice, & Dolan, 2000). These methods have also provided strong support for the notion that hypnotic suggestions can indeed modulate auditory perception (Szechtman, Woody, Bowers, & Nahmias, 1998), visual perception (Kosslyn, Thompson, Costantini-Ferrando, Alpert, & Spiegel, 2000), and pain (e.g. Willoch et al., 2000; De Pascalis, Magurano, & Bellusci, 1999; Crawford et al., 1998; Rainville et al., 1997). However, these studies have examined the effects of specific hypnotic suggestions on ‘‘contents of con- sciousness’’ and have not directly assessed the more general status of hypnosis as an altered ‘‘state of con- sciousness’’ (see a version of the proposed distinction between contents and ‘‘background’’ states of conscious- ness in Chalmers, 2000). 1 Universite´ de Montre´al, 2 McGill University, 3 University of Florida © 2002 Massachusetts Institute of Technology Journal of Cognitive Neuroscience 14:6, pp. 887–901

Transcript of Hypnosis Modulates Activity in Brain Structures Involved in the...

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Hypnosis Modulates Activity in Brain Structures Involvedin the Regulation of Consciousness

Pierre Rainville1 Robert K Hofbauer2 M Catherine Bushnell2Gary H Duncan1 and Donald D Price3

Abstract

amp The notion of consciousness is at the core of an ongoingdebate on the existence and nature of hypnotic statesPreviously we have described changes in brain activityassociated with hypnosis (Rainville Hofbauer Paus DuncanBushnell amp Price 1999) Here we replicate and extend thosefindings using positron emission tomography (PET) in 10normal volunteers Immediately after each of 8 PET scansperformed before (4 scans) and after (4 scans) the induction ofhypnosis subjects rated their perceived level of lsquolsquomentalrelaxationrsquorsquo and lsquolsquomental absorptionrsquorsquo two of the key dimen-sions describing the experience of being hypnotized Regres-sion analyses between regional cerebral blood flow (rCBF) andself-ratings confirm the hypothesized involvement of theanterior cingulate cortex (ACC) the thalamus and the

ponto-mesencephalic brainstem in the production of hypnoticstates Hypnotic relaxation further involved an increase inoccipital rCBF that is consistent with our previous interpreta-tion that hypnotic states are characterized by a decrease incortical arousal and a reduction in cross-modality suppression(disinhibition) In contrast increases in mental absorptionduring hypnosis were associated with rCBF increases in adistributed network of cortical and subcortical structurespreviously described as the brainrsquos attentional system Thesefindings are discussed in support of a state theory of hypnosisin which the basic changes in phenomenal experienceproduced by hypnotic induction reflect at least in part themodulation of activity within brain areas critically involved inthe regulation of consciousness amp

INTRODUCTION

Modern popular views on the phenomenon of hypno-sis are largely dominated by the idea that the lsquolsquohypno-tistrsquorsquo possesses an otherwise unspecified ability toinduce lsquolsquosleep-like statesrsquorsquo within which individualsappear to behave like automatons In contrast con-temporary scientific theories of hypnosis emphasize (a)the changes in phenomenal experience (eg Price1996) (b) the engagement or disengagement of spe-cific neurocognitive processes and the effect on per-formance and psychophysiological activity (egattention executive control Gruzelier 1998 Crawford1994) (c) the contextual cues and psychosocial inter-action between the participant and the hypnotist (egCoe amp Sarbin 1977) or (d) the individual psychologicalcharacteristics predicting hypnotic susceptibility (egCrawford amp Gruzelier 1992) These accounts differ intheir main causative explanations of hypnotic phenom-ena and provide the background for an ongoing debateon whether or not hypnosis constitutes a distinct stateof consciousness

The combination of experiential measures (eg self-rating of subjective experience Varela amp Shear 1999Price amp Barrell 1980) and psychophysiological methods(eg functional brain imaging) has recently contributedsome unique information on the neurophysiologicalcorrelates of (1) multiple pain dimensions (HofbauerRainville Duncan amp Bushnell 2001 Rainville DuncanPrice Carrier amp Bushnell 1997) (2) the feeling oflsquolsquorememberingrsquorsquo versus lsquolsquoknowingrsquorsquo in studies of memory(eg Henson Rugg Shallice Joseph amp Dolan 1999)and (3) the individualsrsquo self-confidence in their responses(eg Henson Rugg Shallice amp Dolan 2000) Thesemethods have also provided strong support for thenotion that hypnotic suggestions can indeed modulateauditory perception (Szechtman Woody Bowers ampNahmias 1998) visual perception (Kosslyn ThompsonCostantini-Ferrando Alpert amp Spiegel 2000) and pain(eg Willoch et al 2000 De Pascalis Magurano ampBellusci 1999 Crawford et al 1998 Rainville et al1997) However these studies have examined the effectsof specific hypnotic suggestions on lsquolsquocontents of con-sciousnessrsquorsquo and have not directly assessed the moregeneral status of hypnosis as an altered lsquolsquostate of con-sciousnessrsquorsquo (see a version of the proposed distinctionbetween contents and lsquolsquobackgroundrsquorsquo states of conscious-ness in Chalmers 2000)

1Universite de Montreal 2McGill University 3University ofFlorida

copy 2002 Massachusetts Institute of Technology Journal of Cognitive Neuroscience 146 pp 887ndash901

Neurophenomenology of Hypnotic States

Hypnotic states may be described most adequately bythe global changes produced in subjective experienceand possibly in self-representation as these may beessential and ubiquitous to all hypnosis-related phenom-ena Studies of hypnosis using experiential analyses haveidentified a series of dimensions that characterize hyp-notic states (Price 1996) These dimensions include (1)feelings of deep mental relaxation (2) mental absorp-tion (3) a diminished tendency to judge monitor andcensor (4) a suspension of usual orientation towardtime location andor sense of self and (5) the experi-ence of onersquos own response as automatic or extra-volitional Notably those effects are not restricted tospecific sensory modalities or specific lsquolsquocontentsrsquorsquo ofconsciousness and pertain largely to the subjectsrsquo rep-resentation monitoring and regulation of their ownbody-self and mental state These alterations in lsquolsquoself-representationrsquorsquo possibly underlying the changes insubjective experience provide some support for thenotion that hypnosis is a distinct lsquolsquostatersquorsquo of conscious-ness to the extent that self-representation is likely toplay a key role in basic aspects of consciousness (egMetzinger 2000 Damasio 1999) The identification andexperimental manipulation of these basic dimensions ofexperience using hypnosis may further provide someleverage to investigate the neural correlates of back-ground states of consciousness (see Chalmers 2000)

At least two of the identified experiential dimensionsmental relaxation and mental absorption can be readilyassociated with specific instructions used to inducehypnosis Hypnotic relaxation results from direct in-structions for relaxation and suggestions for pleasantbody feelings (eg warmth and heaviness) drowsinessand mental ease Mental absorption is likely induced bysuggestions for continuous focus on the hypnotistrsquosvoice and on the conveyed instructions and by sugges-tions for decreased orientation to and interest in otherirrelevant external sources of stimulation and sponta-neous thoughts Consistently mental absorption hasbeen described as a state of lsquolsquototal attention that fullyengages onersquos representational resources and resultsin imperviousness to distracting eventsrsquorsquo (Tellegen ampAtkinson 1974)

In the present study 10 normal volunteers rated theirlevel of relaxation and mental absorption immediatelyafter each of 8 positron emission tomography (PET)scans performed before (4 scans) and during (4 scans)hypnosis The subjectrsquos left hand was immersed in eitherwarm or painfully hot water during each scan andthe variance associated with this stimulation factor wasremoved in all regional cerebral blood flow (rCBF)analyses reported here (ANCOVA pain-related activityis the subject of a separate report Hofbauer et al 2001)The reliability of the effects of hypnotic induction onbrain activity is first assessed by comparing the present

results with those obtained in our previous study (Rain-ville Hofbauer et al 1999) The present report furtherexamines the cerebral correlates of hypnotically inducedchanges in the subjective experience of mental relaxationand mental absorption using regression analyses of rCBFon self-ratings Directed searches are conducted on theanterior cingulate cortex (ACC) and the thalamus be-cause of their suggested involvement in attention cort-ical arousal and self-regulation and based on previousstudies showing coactivation in these areas following theinduction of hypnosis (Maquet et al 1999 see Table 1and Appendix in Rainville Hofbauer et al 1999) Thebrainstem is further included as a specific search areabased on the critical implication of brainstem nuclei inthe regulation of conscious states and on their impor-tant interactions with the thalamus and the ACC in theregulation of sleep ndashwakefulness and attention (egAston-Jones Rajkowski amp Cohen 1999 Kinomura Lars-son Gulyas amp Roland 1996 Steriade amp McCarley 1990)Additional changes in cerebral activity are examinedusing global searches over the entire brain

RESULTS

Hypnosis-Related Changes in Mental Relaxationand Mental Absorption

The induction of hypnosis produced significant in-creases in self-ratings of both mental relaxation andmental absorption (Figure 1) Likewise both experien-tial measures showed modest but significant correla-tions with a standardized measure of individualhypnotic susceptibility (Stanford Hypnotic SusceptibilityScalemdashForm A [SHSS-A] mental relaxation SpearmanrsquosR = 38 p lt 01 mental absorption SpearmanrsquosR = 27 p lt 05) These results and additional con-vergent evidence in the same subjects or in differentsubjects using the same method indicate that theprocedure was effective in inducing hypnotic states

0 0

2 0

4 0

6 0

8 0

Relaxation Absorption

No

rmal

ized

Sel

f-R

atin

g (

+SE

M)

BaselineHypnosis

p = 001p lt 0001

Figure 1 Hypnosis-related changes in mental relaxation andabsorption Self-rated relaxation and absorption (normalized within-subjects) increased significantly following the induction of hypnosis(see p values)

888 Journal of Cognitive Neuroscience Volume 14 Number 6

(Hofbauer et al 2001 Rainville et al 1997 RainvilleCarrier Hofbauer Bushnell amp Duncan 1999 RainvilleHofbauer et al 1999)

Heart rate measured before and during scans did notchange significantly following the induction of hypnosis(see Hofbauer et al 2001)

Reliability of Hypnosis-Related Changes in rCBF

The reliability of the effects of hypnosis on cerebralactivity was examined by comparing the results of asubtraction analysis (Hypnosis minus Baseline condi-tions) with those of our previous study (see Table 2 inRainville Hofbauer et al 1999) Our current resultsreplicated the previously reported rCBF increases inboth occipital lobes the right Sylvian region (peaks inthe inferior frontal and superior temporal gyri) the leftinsula (more anterior and bilateral in the present study)and the right ACC However ACC activation was moreextensive here with significant clusters of activatedvoxels covering multiple areas of the ACC and peaksfound in both the right and left hemispheres inthe middle rostral and perigenual ACC The frontalincreases in rCBF extended further bilaterally in thecentral region and in the medial frontal and prefrontalareas (superior frontal and orbito-frontal) Decreases in

rCBF observed in our previous study were replicated inthe right inferior parietal lobule the precuneus and theleft posterior temporal cortices (bilateral here) Theeffects previously reported and not replicated here arethe increases in the right parietal operculum and thedecreases in the medial frontal cortex and the posteriorcingulate gyrus (here medial parietal decreases werelimited to the precuneus) Occipital increases in rCBFwere again stronger in the warm stimulation conditionand prefrontal increases were stronger in the painfulstimulation condition These results largely confirm thereliability of the changes in rCBF associated with theinduction of hypnosis

Mental Relaxation- and Absorption-Related Effects

Directed Search over the Brainstem the Thalamus andthe ACC

The functional role of particular structures thought to beinvolved in the production of hypnosis was assessed byanalyzing the degree of correlation between rCBF inthese regions and subjectsrsquo estimates of the experientialindices of hypnosis (mental relaxation and absorption)(Table 1 Figure 2) Increases in mental relaxation werecorrelated with rCBF decreases in the mesencephalictegmentum of the brainstem (Figure 2A) and with

Table 1 Peak t Values Observed in the Directed Search Areas in Regression Analyses on Self-Ratings and Thalamic rCBF

Relaxation Relaxation-Specific Absorption Absorption-SpecificThalamus

Covariation

Brainstem iexcl267(iexcl3 iexcl33 iexcl12)

iexcl281(iexcl1 iexcl38 iexcl17)

ns +278(1 iexcl26 iexcl22)

+312(13 iexcl26 iexcl15)

+287(3 iexcl32 iexcl24)

Thalamus ns iexcl368(iexcl3 iexcl16 12)

+260(iexcl1 iexcl18 12)

+445(iexcl3 iexcl16 12)

+350(17 iexcl11 2)

ACC

mid +260(1 15 35)

ns ns ns +387(8 13 44)

rostral ns iexcl368(5 37 45a)

+345(1 29 30)

+432(3 32 39a)

+382(1 43 32a)

perigenual +302(5 34 9)

ns +296(8 32 9)

ns ns

Regression models were used to evaluate the slope of the relationship between relaxation or absorption ratings and rCBF Relaxation-specific andabsorption-specific effects were further tested after accounting for variance associated with absorption and relaxation respectively (see Methods)Thalamic covariations were tested in a regression model evaluating the relationship between rCBF in the thalamus at the site of absorption-specificactivity and rCBF in the brainstem the rest of the thalamus and the ACC Stereotaxic coordinates are given for each peak according to the atlas ofTalairach and Tournoux (1988) (x y z = lateral anterior superior)

ns = no significant peak found (iexcl258 lt t lt 258 p gt 01)

p lt 01 p lt 001 p lt 0001 (uncorrected p values)aPeak is over the right medial superior frontal gyrus within a cluster extending into the ACC at the site of significant absorption-related effect(x y z = 1 29 30)

Rainville et al 889

increases in the middle and perigenual ACC (Figure 2B)Increases in absorption were correlated with rCBFincreases in the thalamus and in the rostral and peri-genual ACC (Figure 2C)

The specificity of any changes in the rCBF associatedwith either mental relaxation (relaxation-specific) orabsorption (absorption-specific) was further examinedusing ANCOVA (see Methods) to remove the varianceshared with the other factormdashabsorption and relaxa-tion respectively (Table 1) Relaxation-specific negativecorrelations were found in the brainstem in the thala-mus and in the superior frontal gyrus in a clusterof significant voxels extending over the rostral ACCAbsorption-specific effects confirmed the significant pos-itive correlation between mental absorption and rCBFin the thalamus and in the rostral ACC and furtherrevealed a significant positive peak in the upper ponsof the brainstem (Figure 2D Table 1) Although mentalrelaxation and absorption both increased during hyp-nosis these results demonstrate that the negative cor-relation in the mesencephalic brainstem and thethalamus appears to be exclusively associated with

mental relaxation while the positive correlations inthe upper pons the thalamus and the mid-ACC appearto be exclusively associated with mental absorption

Global Searches

Results of the global searches show additional differ-ences between the patterns of activity related to mentalrelaxation and absorption In the frontal lobe increasesin prefrontal rCBF were positively correlated primarilywith mental absorption (Table 2) while increases in theprecentral region were positively correlated with bothrelaxation (Figure 3A) and absorption (Table 2) Con-sistently after removing the variance shared betweenmental relaxation and absorption positive absorption-specific correlations (Table 2 Figure 3B) and negativerelaxation-specific correlations (Table 2) were observedin prefrontal areas while most precentral effects did notreach significance

Posterior cortical areas displayed a mixed pattern ofresults Negative correlations observed in both temporallobes were more reliably related to mental relaxation

Figure 2 Statistical (t) maps overlaid on a midsagittal view of a single-subject MRI anatomical image showing the location of significant positive(red arrows) and negative (blue arrow) regression slopes between rCBF and self-ratings in the three regions of interest (brainstem thalamus andACC see Methods) (A) A negative regression peak is found with relaxation in the mesencephalic tegmentum and (B) positive regression peaksare found in the middle (mACC) and perigenual (pACC) portion of the ACC (note the reversal of the color scale) (C) Positive regression peaksare found with absorption in the thalamus and in the rostral ACC (rACC) and pACC (D) The regression of rCBF on absorption ratings afteraccounting for relaxation-related effects confirmed the positive regression peaks specific to absorption in the thalamus and rACC This analysisfurther revealed an additional positive peak in the upper pons Color scales in C and D are as in B Stereotaxic coordinates of peaks are reportedin Table 1

890 Journal of Cognitive Neuroscience Volume 14 Number 6

than absorption and the relaxation-related effects heldafter accounting for variance in absorption (Table 2mdashrelaxation-specific) Additional sites of relaxation-specificeffects included negative correlations in the right parie-tal operculum and lobule and positive correlations in theright precuneus the left inferior parietal lobule and thebilateral occipital cortices (Table 2mdashrelaxation-specific)

The effects associated with absorption in the posteri-or cortices were strikingly different from the effects ofrelaxation After accounting for relaxation-related var-iance we observed both positive and negative absorp-tion-specific correlations in both the right and leftparietal lobules (see Table 2mdashabsorption-specific) Inthe inferior parietal lobules positive and negative cor-relations dominated in the right and left hemispheresrespectively (Figure 3B) Strong negative correlationswere also observed over the right precuneus theposterior cingulate cortex and both occipital lobes(Figure 3B)

Additional statistical trends directly relevant to ourhypotheses were also observed in the somatosensorycortices where rCBF was negatively correlated with men-tal relaxation (see Figure 3A right S1 peak coordinates44 iexcl35 59 t = iexcl286 p-uncorrected = 014 clusterp = 06 left S1 iexcl44 iexcl21 16 t = iexcl251 p-uncorrected =026 cluster analysis p gt 10 right parietal operculumS2 48 iexcl21 24 t = iexcl351 p-uncorrected = 003 clusterp gt 10 right posterior insula 44 iexcl4 15 t = iexcl296p-uncorrected = 011 cluster p gt 10)

Covariations with Thalamic rCBF

In our previous study thalamic activity was found tobe correlated with hypnosis-related ACC activity (seeTable 2 and Appendix in Rainville Hofbauer et al1999) and several studies suggest a pivotal role of thethalamus in arousal attention and consciousness andin the interaction between the brainstem and the ACC(eg Paus et al 1997 Paus 2001 Portas HowsemanJosephs Turner amp Frith 1998 Hofle et al 1997) Herewe tested the association between absorption-relatedactivity in the thalamus and activity in other sites ofabsorption-related changes using a covariation analysiscentered on the absorption-specific peak in the thala-mus reported in Table 1 Absorption-specific sites in thebrainstem (upper pons) and the ACC showed significantcovariations with thalamic rCBF (Table 1) Additionalregions where rCBF showed a positive correlation withthalamic rCBF included bilateral frontal sites in theinferior middle and superior frontal gyri extendingmedially into the right ACC and the right insula(Table 3) Many of those peak locations matched frontalsites specifically related to mental absorption (italicizedin Table 2) A strong positive peak was also observed inthe right inferior parietal lobule precisely at the loca-tion where rCBF correlated strongly and specificallywith mental absorption (compare Table 2 absorption-

specific and Table 3) Areas displaying negative corre-lation with thalamic rCBF were found bilaterally in theoccipital lobes consistent with the absorption-specificeffects reported in Table 2

DISCUSSION

The approach used in this study provided a descriptionof cerebral activity associated with specific changes inphenomenal experience produced by a standard hyp-notic induction We discuss in turn the evidence for theproduction of hypnotic phenomena the reliability ofhypnosis-related effects the effects associated with men-tal relaxation and absorption and the implications ofour results for a state theory of hypnosis

Hypnosis and Phenomenal Experience

The induction of hypnosis produced the expectedincreases in both mental relaxation and absorptionThese changes were positively correlated (see Methods)as predicted by the experiential model of hypnosisproposed by Price (1996) and the ability to maintainhypnotic relaxation and absorption depended upon thesubjectsrsquo hypnotic susceptibility The higher levels ofabsorption maintained in highly hypnotizable subjectsare consistent with the positive association betweenabsorption attentional processes and hypnotizabilitysuggested in previous studies (Crawford 1994 Baltha-zard amp Woody 1992 Tellegen amp Atkinson 1974) Theseresults and additional convergent observations de-scribed in our previous report of pain-related effects(Hofbauer et al 2001) and from several experimentsusing similar methodology (Rainville et al 1997 Rain-ville Carrier et al 1999) confirmed the reliable produc-tion of hypnotic phenomena

Reliability of Hypnosis-Related Effects on rCBF

The experimental conditions examined here and in thefirst 8 scans in our previous study were identicalmdashthesame hypnotic induction procedure was applied by twodifferent experimenters and the two separate groups ofsubjects tested had comparable mean hypnotic suscep-tibility scores (Rainville Hofbauer et al 1999) Theresults of the subtraction analysis largely replicated ourprevious findings as well as those reported by Maquetet al (1999) In comparison to our previous experimentdifferences in the methods were limited to the additionof relaxation and absorption ratings after the scans Thelarger areas of frontal activation including the precentralregion and the more restricted occipital activationobserved here may reflect the emphasis put on hypnoticrelaxation and absorption during the scans As thesedimensions of experience characterize standard hypno-tic induction procedures we submit that these differ-ences further emphasize the functional significance of

Rainville et al 891

Tab

le2

R

esul

tsof

the

Glo

bal

Sear

ches

ofC

ereb

ral

Regi

ons

whe

rerC

BF

Show

eda

Sign

ifica

ntR

egre

ssio

nw

ithR

elax

atio

nan

dAb

sorp

tion

Regi

onP

eak

Loca

tion

Rela

xati

onRe

laxa

tion

-Spe

cifi

cAb

sorp

tion

Abs

orpt

ion

-Spe

cifi

c

xy

zt

xy

zt

xy

zt

xy

zt

Fron

tal

(F)

RF

Pole

(BA

10)

ndash34

562

iexcliexcl4

81

ndash28

555

+4

21

Rla

tF

Orb

ital

g(B

A11

)ndash

1946

iexcl20

iexcliexcl4

29

ndash19

44iexcl

20+

47

5

Rm

iddl

eF

g(B

A46

)ndash

3646

26iexcl

381

ndash34

4626

+3

79

Rin

fF

g(B

A47

)ndash

ndash47

34iexcl

18+

373

ndash

Rin

fF

g(B

A45

)ndash

478

15iexcl

386

5520

11+

352

ndash

Ra

nt

insu

lai

nf

Fg

(BA

144

4)ndash

4015

6iexcl

377

4310

2+

358

4013

5+

48

1

Rsu

pF

gc

ingu

late

g(B

A8

32)

ndash5

3745

iexcl3

68ndash

332

39+

43

2

Rsu

pF

g(B

A6)

ndashndash

1320

59+

369

1522

57+

43

3

Rm

edia

lsu

pF

g(B

A6)

ndashndash

3iexcl

466

+4

23

3iexcl

766

+3

92

Lla

tF

Orb

ital

g(B

A11

)ndash

ndashiexcl

3041

iexcl21

+3

68iexcl

3143

iexcl18

+3

76

Lm

iddl

eF

g(B

A8)

ndashndash

iexcl46

1535

+4

10iexcl

4410

29+

328

Lm

iddl

eF

g(B

A46

)ndash

ndashiexcl

3637

18+

43

8iexcl

3839

24+

407

La

nt

insu

lai

nf

Fg

(BA

144

4)ndash

ndashndash

iexcl34

817

+4

25

Lsu

pF

g(B

A6)

ndashndash

ndashiexcl

266

56+

416

Lsu

p

Fg

(BA

6)ndash

ndashiexcl

11iexcl

466

+3

68ndash

Cen

tral

Rp

rece

ntra

lg

(BA

4)54

iexcl4

53+

51

6ndash

52iexcl

453

+5

05

ndash

Rp

rece

ntra

lg

(BA

4)42

iexcl7

50+

49

4ndash

ndashndash

Rp

rep

ostc

entr

alg

(BA

41

3)ndash

ndash36

iexcl16

36+

378

ndash

Lpr

ecen

tral

mid

dle

Fg

(BA

46)

iexcl35

iexcl6

53+

398

ndashndash

ndash

Lpr

ecen

tral

g(B

A4)

iexcl47

iexcl16

47+

44

3ndash

iexcl48

iexcl14

50+

43

6ndash

Lpr

epo

stce

ntra

lg

(BA

41

3)ndash

iexcl30

iexcl37

60+

403

ndash

Tem

pora

l(T

)R

mid

dle

T

g(B

A21

)60

iexcl33

iexcl15

iexcl5

71

59iexcl

33iexcl

13iexcliexcl

55

1ndash

ndash

Rm

iddl

eT

g

(BA

37)

56iexcl

45iexcl

9iexcl

59

1ndash

55iexcl

47iexcl

6iexcliexcl

44

1ndash

Lpa

rahi

ppoc

amp

alg

(BA

353

6)iexcl

36iexcl

23iexcl

18iexcl

413

ndashndash

ndash

Lin

fT

g

fusi

form

g(B

A37

)iexcl

52iexcl

42iexcl

20iexcl

52

4iexcl

59iexcl

44iexcl

12iexcliexcl

43

3iexcl

48iexcl

44iexcl

20iexcliexcl

44

6ndash

892 Journal of Cognitive Neuroscience Volume 14 Number 6

Pari

etal

(P)

RP

oper

culu

m(B

A40

)ndash

32iexcl

3027

iexcl3

55ndash

ndash

Rin

fP

lo

bule

(BA

40)

ndash56

iexcl40

50iexcl

377

ndash56

iexcl44

50+

42

4

RP

lobu

le(B

A40

7)

39iexcl

4945

iexcl4

87

ndash38

iexcl47

45iexcliexcl

44

334

iexcl56

42+

383

Rsu

pP

lobu

le(B

A7)

ndashndash

21iexcl

5062

iexcliexcl4

45

21iexcl

5260

iexcl4

09

Rpr

ecun

eus

(BA

7)ndash

5iexcl

5645

+5

33

ndash5

iexcl56

45iexcliexcl

51

0

Prec

uneu

sp

ost

Cin

gg

(BA

731

)ndash

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0iexcl

649

iexcliexcl5

05

Lin

fP

lobu

le(B

A40

)ndash

iexcl30

iexcl37

60+

403

ndashiexcl

35iexcl

3550

iexcliexcl4

48

Lin

fP

lobu

le(B

A40

)ndash

ndashndash

iexcl52

iexcl56

47+

370

Occ

ipit

al(O

)Li

ngua

lg

pos

tC

ing

g(B

A18

31)

ndash0

iexcl66

9+

42

6ndash

ndash

Rin

fO

g

(BA

19)

ndash43

iexcl71

iexcl6

+3

6843

iexcl75

5iexcliexcl

44

443

iexcl75

iexcl3

iexcliexcl5

17

Rli

ngu

alg

(BA

18)

ndash4

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3+

46

4ndash

7iexcl

782

iexcliexcl4

68

Rcu

neu

s(B

A18

)ndash

12iexcl

8327

+5

20

ndashndash

Rsu

pO

g

(BA

19)

ndash17

iexcl81

38+

55

9ndash

15iexcl

8033

iexcliexcl6

02

Rsu

pO

g

(BA

19)

30iexcl

8726

+4

07

RO

po

le(B

A18

)ndash

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929

+4

85

ndash27

iexcl92

8iexcliexcl

53

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Lfu

sifo

rmg

(BA

181

9)ndash

iexcl40

iexcl78

iexcl3

+3

59ndash

iexcl40

iexcl76

iexcl3

iexcliexcl4

46

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pO

g

prec

un

eus

(BA

197

)ndash

iexcl13

iexcl88

38+

407

iexcl8

iexcl76

36iexcliexcl

42

3iexcl

13iexcl

8739

iexcliexcl5

18

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gual

g(B

A18

)c

ereb

ellu

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ndashiexcl

17iexcl

76iexcl

18iexcl

351

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form

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A18

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ndashiexcl

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47

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83iexcl

11iexcliexcl

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(BA

19)

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8327

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905

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ng

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BF

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ngs

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gnifi

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ns

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Met

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eaks

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sign

ific

ant

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ter

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Met

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ith

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ere

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ions

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hth

alam

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BF

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und

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ita

lici

zed

(see

Tab

le3

and

Met

hods

)P

eak

loca

tion

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eba

sed

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est

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las

of

Tal

aira

chan

dT

ourn

oux

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8)(x

=la

tera

ly

=an

teri

or

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rior

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ages

(BA

=pr

obab

leB

rodm

annrsquo

sar

eaL

=

left

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=

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tg

=gy

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ant

=an

teri

or

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t=

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p=

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rior

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f=

infe

rior

)

Rainville et al 893

the underlying processes in the production of hypnoticstates as discussed below

Role of the Brainstem the Thalamus and the ACCin Hypnosis

Results of the regression analyses suggest that neuralactivity in the brainstem the thalamus and the ACCcontributes to the experience of being hypnotized Therelaxation-specific negative correlations in the mesen-

cephalic brainstem and the thalamus may reflect thewell-established contribution of brainstem and thalamicnuclei to the regulation of wakefulness and corticalarousal In functional brain imaging studies rCBFdecreases in the brainstem and the thalamus have beenassociated with decreased vigilance (Paus et al 1997)sleep (Kajimura et al 1999 Braun et al 1997 Hofleet al 1997 Maquet et al 1997) and the loss ofconsciousness produced by the anesthetic propofol(Fiset et al 1999) These effects and to some extent

Figure 3 Brain regionsshowing positive (redarrowheads) and negative(blue arrowheads) regres-sion peaks between rCBFand self-ratings of (A)relaxation and (B) absorp-tion after accounting forrelaxation-related variance(absorption-specific)Statistical t maps are super-imposed on the averageanatomical MRI (left is onthe left side) Slice locationsare indicated on the 3-Danatomical image of asingle subjectrsquos anatomicalMRI (A-positive) Positiverelaxation-related effectsare shown in the centralregion bilaterally (horizon-tal slice on the left) Apositive peak is shown inthe right superior occipitalgyrus (SOg) (coronal viewon the right note scalechange) (A-negative)A negative relaxation-related effect in the rightposterior parietal cortexis shown in horizontal(first from left) coronal(second) and lateralsagittal (third) views Theplus sign indicates the moreanterior location of thepeak positive regression inthe analysis of absorption-related effects as shown inB Additional negative cor-relations are shown in thebilateral middle and inferiortemporal gyri (second) andin the right somatosensorycortices (S1 S2 insula)(B-positive) A positiveabsorption-specific peak isshown in the right inferiorparietal lobule (first fromleft) The minus sign indicates the more posterior location of the negative regression peak in the analysis of relaxation-related effects as shown in

A Other peaks are shown on the midsagittal view in the thalamus and the anterior cingulate cortex (second from left) and in the left lenticularnuclei and bilateral prefrontal cortices (last three cuts from left) (B-negative) Negative absorption-related effects are shown in the left inferiorparietal lobule (first from left) in both occipital lobes (second and third from left) and in the precuneus (first and third) Stereotaxic coordinates ofpeaks are reported in Table 3 (see relaxation- and absorption-specific)

894 Journal of Cognitive Neuroscience Volume 14 Number 6

the present relaxation-related decrease in brainstemrCBF may reflect an attenuation of activity withinbrainstem cholinergic nuclei Such reduction has beenobserved during slow EEG activity before the onset ofsleep and during slow-wave sleep in animal studies(Steriade amp McCarley 1990) Consistent with this pos-sibility we previously reported an increase in slow(delta) EEG activity following hypnotic induction (Rain-ville Hofbauer et al 1999) Although hypnotic andsleep states are clearly distinct certain neurophysiolog-

ical mechanisms may be involved to a varying degree inthe production of both states

The positive association specifically observed betweenmental absorption and rCBF in the upper pons and thethalamus contrasts with the above relaxation-relatedeffect and is consistent with previous reports of atten-tion-related brain activation (Kinomura et al 1996) Thisactivity may reflect the involvement of the noradrenergicsystem of the locus coeruleus in focused attentionand possibly in the interaction between cortical arousal

Table 3 Cerebral Sites of Covariation with Thalamic rCBF at the Absorption-Specific Peak Coordinates (x = iexcl27 y = iexcl160z = 120)

Region Peak Location x y z t

Frontal (F) R medial sup F gACC (BA 624) 1 43 32 +382

R anterior cingulate gsup F g (BA 326) 8 13 44 +387

R inf F g (BA 44) 51 12 8 +387

R ant insula (BA 14) 38 12 5 +412

R sup F g (BA 6) 16 20 59 +371

R medial sup F g (BA 6) 3 iexcl6 63 +498

R medial sup F g (BA 6) 11 iexcl23 53 +412

L middle F g (BA 46) iexcl38 46 23 +381

L middle F g (BA 46) iexcl31 39 39 +374

L inf F g (BA 44) iexcl43 6 12 +430

L sup F g (BA 6) iexcl19 20 53 +340

L medial sup F g (BA 6) iexcl5 17 65 +353

L sup F g (BA 6) iexcl20 12 65 +283

Parietal R inf parietal lobule (BA 40) 56 iexcl44 50 +519

Occipital (O) R fusiform g (BA 19) 26 iexcl62 iexcl30 iexcliexcl515

R lingual g (BA 18) 7 iexcl78 6 iexcliexcl623

R sup O g (BA 19) 19 iexcl85 30 iexcliexcl714

R O pole (BA 18) 27 iexcl90 9 iexcliexcl751

L cuneus (BA 18) iexcl11 iexcl83 29 iexcliexcl633

L O pole (BA 18) iexcl23 iexcl88 6 iexcliexcl793

Subcortical R thalamus 17 iexcl11 2 +350

R brainstem 13 iexcl26 iexcl15 +312

R medial brainstem 3 iexcl32 iexcl24 +287

L cerebellum iexcl4 iexcl57 iexcl21 +409

L globus pallidus iexcl20 iexcl1 iexcl2 +302

L caudate nucleus iexcl12 6 20 +291

Positive and negative regression slopes are significant at sites listed based on cluster or peak analyses (peak t threshold ltgtplusmn370 in bold allpeaks reported with t lt 370 are within a significant cluster see Methods) Peaks in italic are also reported in Table 1 See legends to Tables 1 and 2and Methods for further explanation

Rainville et al 895

and attentional processes (ie increased attentionabsorption concurrent with decreased cortical arousalincreased relaxation) (Aston-Jones et al 1999) Theindirect nature of the rCBF measures and the relativelypoor resolution of the PET method require somecaution in evaluating the possible anatomo-functionalimplications of our results in the brainstem Howeverthe convergent findings observed in other brain imag-ing studies and the observations provided in animalstudies support the notion that ascending cholinergicand noradrenergic pathways may contribute differen-tially to the multiple dimensions of experience thatcharacterize hypnosis

The overall pattern of results found in the ACC likelyreflects the heterogeneity of functions associated withthis area (Devinsky Morrell amp Vogt 1995) The locationof the most posterior relaxation-related peak in the ACC(mACC) is consistent with our previous observationof ACC activation during hypnosis (Rainville Hofbaueret al 1999) This relaxation-related peak is only slightlyanterior to the motor area of the caudal ACC (Picard ampStrick 1996) and may be involved in the installment of arelaxed state (also see precentral area below) In con-trast a positive absorption-specific effect was observedin a more rostral region of the ACC (rACC) close to anegative relaxation-specific correlation (see Table 1)This area of the ACC has previously been involved inexecutive attention in the detection of errors and in themonitoring of conflict between competing cognitiveprocesses (Bush Luu amp Posner 2000 Cohen Botvinickamp Carter 2000 Badgaiyan amp Posner 1998 Posner ampRothbart 1998) A meta-analysis of PET studies inves-tigating cognitive functions further suggested that theincrease in activity within this sector of the ACC isrelated to the difficulty of the task performed (PausKoski Caramanos amp Westbury 1998) Our findings areconsistent with these propositions to the extent thatthe engagement of the cognitive and neurophysiologicalprocesses implied in each of those accounts may beaccompanied by a subjective experience of increasedmental absorption

The coordinated pattern of rCBF changes in thebrainstem the thalamus and the ACC may reflect theinterrelationships between the multiple components of anetwork (eg Paus et al 1997) herein shown to beassociated with the feeling of being lsquolsquomentally absorbedrsquorsquoThe precise location of the observed absorption-specificthalamic peak is consistent with an involvement of theintralaminar and medio-dorsal nuclei which have recip-rocal connections with the ACC (Vogt amp Gabriel 1993)The finding that the coordinated activity in the thalamusand the ACC is disrupted in persistent vegetative states isconsistent with the notion that these structures work intandem to regulate consciousness (Laureys et al 2000also see Jeanmonod Magnin amp Morel 1996) Further-more a functional interaction between arousal andattentional processes has been reported in the thalamus

where the putative attention-related activity associatedwith the performance of a simple visual discriminationtask was found to increase in states of low arousal (Portaset al 1998) This increase in thalamic activity wassuggested (1) to reflect a compensatory mechanism thatpermitted the maintenance of stable levels of perform-ance in states of low arousal and (2) to prevent thegeneralized thalamo-cortical synchronization that wouldlead to sleep Here the opposite effects of relaxation andabsorption on thalamic activity may reflect this compen-satory mechanism that maintains high levels of focusedattention in deeply relaxed subjects during hypnosisThis function may be critical not only in hypnosis butalso in other conditions of deep relaxation distinct fromboth sleep and normal wakefulness such as meditativestates (Lou et al 1999) Furthermore the coactivation ofthe ACC and the ponto-mesencephalic brainstem mayreflect the contribution of the ACC to the regulation ofattention-related activity in the locus coeruleus (Cohenet al 2000) The positive regression found with absorp-tion in the ponto-mesencephalic brainstem and themore robust regression observed in the thalamus andthe ACC after accounting for relaxation-related changes(absorption-specific Table 1) further substantiate thepossibility that brainstem and thalamic nuclei interactwith the ACC to regulate the interaction between atten-tion and cortical arousal Taken together these resultsare consistent with a contribution of brainstem nucleithe intralaminar and medio-dorsal nuclei of the thala-mus and the ACC to the changes in phenomenalexperience that characterize hypnotic states

Additional Relaxation- and Absorption-RelatedChanges in rCBF

Relaxation-Related Activity

We observed strong relaxation-related increases in rCBFin the precentral gyrus bilaterally and reciprocaldecreases in somatosensory areas (S1 S2 and insula)Precentral and premotor activation has been reportedduring hypnosis in an independent study (Maquet et al1999) and precentral rCBF was correlated with the rCBFmeasured at the ACC site of hypnosis-related activity inour previous study (see Appendix in Rainville Hofbaueret al 1999) Similar increases in activity in motor andpremotor areas have been associated with voluntarymuscular relaxation (Toma et al 1999) but the presentresults may reflect more than physical relaxation

All standard hypnotic procedures include instructionsfor relaxation However the specific contribution ofmuscular relaxation and decreased arousal to the pro-duction of hypnotic states is unclear as hypnotic phe-nomena have been produced during muscular exercise(Banyai amp Hilgard 1976) and with suggestions of active-alertness (Vingoe 1968 1973) Here the absence ofsignificant effect of hypnosis on heart rate indicates thatchanges in cerebral activity did not correlate with

896 Journal of Cognitive Neuroscience Volume 14 Number 6

changes in peripheral arousal and suggests that subjectswere already physically relaxed in the baseline controlcondition This implies that the hypnosis-inducedchanges in self-ratings of relaxation may not simplyreflect changes in lsquolsquoperipheralrsquorsquo arousal but may attestmore specifically of an increase in lsquolsquomentalrsquorsquo relaxationand a reduction in lsquolsquocorticalrsquorsquo arousal This is consistentwith Pricersquos experiential model of hypnosis (see Intro-duction) and with our previous study showing anincrease in slow (delta) EEG activity during hypnosis

Relaxation-related effects observed outside primarysomatomotor areas may partly reflect subjective feelingsof mental ease more closely In the subtraction analysishypnosis-related decreases were found in the rightlateral posterior parietal rCBF both here (x y z 40iexcl52 44) and in our previous study (x y z 46 iexcl50 42from Table 1 in Rainville Hofbauer et al 1999) Herethese changes were strongly but not specifically asso-ciated with relaxation (x y z 39 iexcl49 45 see Table 2Figure 3A) Furthermore after accounting for absorp-tion-related variance right prefrontal activity was neg-atively correlated with relaxation (Table 2) Thoseadditional changes in the right posterior parietal cortexand the right prefrontal cortices may contribute to thesubjective feelings of mental ease rather than or inaddition to physical relaxation

Fronto-Parietal Attention Networks

Absorption-related activity was widespread and bilateralin the prefrontal cortices but peaks were generallystronger in the right hemisphere Positive regressionpeaks were maximal in the ventrolateral frontal corticesover the inferior frontal gyrus and in the anterior insulaA positive absorption-related regression peak was alsosignificant in the right inferior parietal lobule Theseareas also displayed strong coactivation with absorption-related thalamic activity Very similar patterns of activa-tion have been associated with attentional processes intasks involving visual (eg Coull Frackowiak amp Frith1998) auditory (Paus et al 1997) and somatosensorystimuli (Peyron et al 1999) Notably the location of thepositive parietal peak observed here closely matches theactivation sites reported in those studies and the site ofcovariation with the right ventrolateral attention-relatedactivity reported in Paus et al (1997) suggesting theactivation of a similar network The coordinated absorp-tion-related activity observed here in the brainstem thethalamus the ACC the right inferior frontal gyrus andthe right inferior parietal lobule provides very strongevidence that mental absorption is an experiential cor-relate of the activation of the brainrsquos lsquolsquoexecutive atten-tional networkrsquorsquo and suggests that this system plays acritical role in the production of hypnotic states

Negative absorption-related regression peaks werealso found in both the right and left lateral parietalcortices and in the precuneus (see Table 2) These

effects were largely independent of thalamic activity asindicated by the absence of significant effects at theselocations in the covariation analysis (Table 3) The rightposterior parietal cortex has been suggested to con-stitute a vigilanceorientation system (Pardo Fox ampRaichle 1991) and hypnosis-related decreases in thisarea may reflect a relative disengagement towardexternal sources of stimulation Right and left posteriorparietal cortices at the precise sites of relaxation- andabsorption-related decrease in rCBF have been sug-gested to contribute to the monitoring of externalspace and time respectively (Gitelman et al 19961999 Kim et al 1999 Coull amp Nobre 1998 Nobreet al 1997) Although these functions were notdirectly assessed in this experiment the hypnoticinduction procedure includes specific instructions fordecreased orientation to and interest in irrelevantexternal sources of stimulation and previous observa-tions suggest that hypnotic relaxation and absorptionare precursors to some alterations in spatio-temporalorientation and monitoring (Price 1996) Thus wespeculate that those additional experiential changesmay be consequent to relaxation- and absorption-related decreases in posterior parietal activity

Relaxation- and Absorption-Related Effects onOccipital rCBF

The subtraction analysis confirmed the reliability of thehypnosis-related increase in occipital rCBF reported inour previous study (Rainville Hofbauer et al 1999) Wenow show that this effect was associated with the sub-jective experience of hypnotic relaxation (see Table 2relaxation-specific) Consistently our previous studydemonstrated a coupling between occipital increases inrCBF and increases in slow (delta) EEG activity duringhypnosis Similar increases in occipital rCBF andor slowEEG activity had been observed in another study onhypnosis (Maquet et al 1999) and in states of decreasedvigilance (Paus et al 1997) meditation (Lou et al 1999)and slow wave sleep (Kajimura et al 1999 Hofle et al1997) These effects are consistent with our previousproposition that hypnotic induction produces a globaldecrease in cross-modality suppression in unattendedsensory channels leading to a relative disinhibitionof cortical activity (see Paus et al 1997 KawashimaOrsquoSullivan amp Roland 1995)

In contrast negative correlations between rCBF andmental absorption were observed over both occipitallobes (Table 2 Figure 3B) Consistently occipital rCBFwas correlated negatively with thalamic rCBF at theabsorption-specific site (Table 3) These contrastingeffects imply that variations in occipital rCBF are asso-ciated with separate portions of the variance in relaxa-tion and absorption (Note that although absorptionand relaxation were significantly correlated the variancein absorption was largely independent of relaxation see

Rainville et al 897

Methods) For a given level of relaxation the increasein hypnotic absorption could reflect the concurrentengagement of the lsquolsquoexecutive attentional networkrsquorsquowhich exerts an opposite effect over brain areas sub-serving unattended sensory channels (ie a relativefacilitation of cross-modality suppression)

Hypnosis as a State of Consciousness

The representation of the body-self is central to theneurophenomenology of consciousness (Metzinger2000) In the Introduction we have proposed that theinduction of hypnosis produces global changes in sub-jective experience reflecting a modulation of basicaspects of the body-self representation Consistentlythe PET results indicate that hypnosis involves changesin activity within brain structures essential for the basicregulation of states of consciousness self-monitoringand self-regulation Furthermore changes in relaxationand absorption are precursors (although they may notbe essential) to other hypnosis-related effects such asthe diminished tendency to judge monitor and censorthe suspension of usual orientation toward time loca-tion andor sense of self and the experience of onersquosown response as automatic or extra-volitional (Price1996) These dimensions of experience also rely criticallyon self-representation and may depend at least partly oncerebral areas shown here to be involved in hypnosisAmong those changes the increased feeling of automa-ticity an altered feeling of agency may be the mostdistinctive aspect of hypnotic phenomenology (Weitzen-hoffer 1980) Interestingly the sense of agency hasrecently been suggested to involve areas that displayconsistent changes in activity during hypnosis such asthe right inferior parietal cortex the precuneus and thesomatosensory cortices (Blakemore amp Decety 2001Ruby amp Decety 2001) The modulation of activityobserved here within those areas is consistent withthe interpretation that hypnosis produces changes inself-representation construed as an essential element forconscious experience

Conclusion

The present study used self-ratings of subjective feelingsof mental relaxation and mental absorption to map brainareas involved in hypnosis We replicated previous find-ings and further demonstrated that hypnotic relaxationand absorption reflect changes in brain activity withinregions involved in the control of consciousness statesand in self-regulation such as the brainstem the thala-mus and the ACC The coordinated activity within thesestructures and other absorption-related areas such asthe ventrolateral frontal and right posterior parietalcortices has been previously shown to underlie theregulation of the content of consciousness throughmechanisms of executive attention We must recognize

that our findings are correlative in nature and arerelevant to hypnosis to the extent that mental relaxationand absorption are conceived as basic experientialdimensions that characterize hypnotic phenomenaWe further speculate that these changes in subjectiveexperience and brain activity may contribute to otherhypnosis-related effects such as the altered feeling ofagency experienced during hypnosis These findings areconsistent with the notion that hypnotic states areachieved through the modulation of activity within adistributed network of cerebral structures involved inthe regulation of consciousness states

METHODS

Subjects

Ten right-handed subjects (4 men 6 women) wereselected from a group of 22 volunteers as a part of astudy on the hypnotic modulation of pain (Hofbaueret al 2001) Hypnotic susceptibility was assessed usingthe SHSS-A administered between scans (range 111ndash1011 mean plusmn SD 69 plusmn28) The Ethics Committee ofthe Montreal Neurological Institute (MNI) approved allprocedures and subjects signed a consent form describ-ing the procedure and affirming their right to withdrawfrom the experiment without prejudice

Experimental Procedure

We report the results obtained in eight scans acquired ina restful baseline and hypnosis condition Hypnoticinduction started immediately after Scan 4 and wassustained in the remaining scans by repeating inductioninstructions between scans Instructions included sug-gestions for (1) increased physical and mental relaxa-tion (2) comfortable feeling of warmth heaviness anddrowsiness (3) sustained passive attention to theexperimenterrsquos voice and to the instructions and (4)decreased concern with and orientation to external andinternal (mental) sources of distraction No specificinstruction for visual imagery was included During allscans the subjectsrsquo eyes were closed and their left handwas immersed in warm or painfully hot water Pain-related activation and four additional scans performedwith suggestions for pain modulation are reported else-where (Hofbauer et al 2001)

Self-Ratings of Mental Relaxation and Absorption

After each scan subjects were instructed to rate (0ndash10)(1) their level of tensionndashrelaxation with lsquolsquo10 being themost relaxed and at ease you can bersquorsquo and (2) their levelof sustained focus of attention with lsquolsquo10 being the mostabsorbed and the largest amount of sustained focusedattention you can gatherrsquorsquo Ratings of relaxation andabsorption were transformed using the rank within sub-jects to (1) control for individual differences (2) prevent

898 Journal of Cognitive Neuroscience Volume 14 Number 6

scaling biases and (3) parallel the analysis of rCBF dataSubjects rated pain on separate scales (0ndash100) Hypno-sis-related increases in relaxation and absorption did notinteract with the stimulation condition (pain vs warmstimulation prsquos gt 10) neither relaxation nor absorptioncorrelated significantly with pain ratings (all prsquos gt 10)and pain was not altered by hypnosis alone [t(9) = 069p = 51]

PET Imaging Methods

rCBF was measured using the H215O bolus injection

method (10 millicuriesscan) without arterial blood sam-pling (Herscovitch Markham amp Raichle 1983) with ahigh-resolution PET scanner operated in 3-D acquisitionmode (Siemens ECAT HR+ 63 slices) Stimulus onsetwas simultaneous with bolus injection and 1-min acquis-ition scans started about 15 sec postinjection (interscaninterval of 12ndash15 min) Data from the first 40 sec ofacquisition were reconstructed and analyzed Each sub-ject also underwent a high-resolution anatomical MRI(160 1-mm sagittal slices acquired on a Philips 15-TGyroscan system) Each PET and MRI volume wasaligned and transformed using software developed atthe MNI to match the MNI standardized Talairach space(Collins Neelin Peters amp Evans 1994 Talairach ampTournoux 1988) PET volumes were smoothed (FWHM= 14 mm) and normalized to the average brain countPeak and cluster analyses were performed (FristonWorsley Frackowiak Mazziotta amp Evans 1994 WorsleyEvans Marrett amp Neelin 1992)

Reliability of Hypnosis-Related Effects

A first analysis was performed using the subtractionmethod (Hypnosis minus Baseline) to evaluate thereliability of the effects reported in our previous study(Table 2 in Rainville Hofbauer et al 1999) We consid-ered that hypnosis-related changes in rCBF were repli-cated when a significant peak was observed within oneresel (Worsley et al 1992) of the peak sites reported inour previous study or when the peak sites were within asignificant cluster

Regression of rCBF on Self-Ratings of Relaxationand Absorption

Regression analyses were used to test the relationbetween ratings and rCBF (GLM) Subject- and stimu-lus-related effects were removed first (ANCOVA) andthe significance of the regression slope between thecovariate of interest and rCBF was estimated usingt tests Relaxation-specific and absorption-specific effectswere further tested using ANCOVAs to remove thevariance shared between absorption and relaxation(R2 = 42 p lt 001) The statistical criterion was setto t gt 258 (two-tailed uncorrected p lt 01) in the

directed searches restricted to the brainstem the thala-mus and the ACC (Table 1 Figure 2) Global searcheffects are significant ( p lt 05) based on peak (t valuegt 420) andor clusters analysis after a correction formultiple comparisons over the gray matter volume(uncorrected p lt 0001) (Table 2 Figure 3)

Thalamic Covariations

A covariation analysis was performed in which the rCBFmeasured in the thalamus was used as the covariate ofinterest after accounting for subject- and stimulus-related variance (ANCOVA see Tables 1 and 3) Becausewe were mainly interested in the relationship betweenthe activity in the thalamus and other absorption-relatedsites the threshold for statistical significance was set tot = 370 ( p = 05 uncorrected p lt 0008) based on thevolume defined by the sum of clusters of voxels showingsignificant absorption-specific effects (186 cm3 seeWorsley et al 1992)

Acknowledgments

We thank R Adolphs S Anderson A Bechara A R DamasioH Damasio Susan Lutgendorf J Parvizi and D Tranel fortheir comments on preliminary versions of the manuscriptPET analyses were performed using the software DOTdeveloped by Sylvain Milot and the MINC programs developedby Peter Neelin at the McConnell Brain Imaging Center of theMontreal Neurological Institute This study was supported bythe Medical Research Council (MRC) of Canada Dr Rainvillewas supported by the Medical Research Council of Canada andthe Human Frontier Science Program and Dr Hofbauer wassupported by the Fonds pour la recherche en sante du Quebecand the Royal Victoria Hospital Research Institute

Reprint requests should be sent to Pierre Rainville Faculte deMedecine dentaire Universite de Montreal CP 6128 SuccCentre-ville Montreal Qc H3C 3J7 Canada or via e-mailpierrerainvilleumontrealca

REFERENCES

Aston-Jones G Rajkowski J amp Cohen J (1999) Role of locuscoeruleus in attention and behavioral flexibility BiologicalPsychiatry 46 1309 ndash1320

Badgaiyan R D amp Posner M I (1998) Mapping the cingulatecortex in response selection and monitoring Neuroimage7 255 ndash260

Balthazard C G amp Woody E Z (1992) The spectral analysisof hypnotic performance with respect to lsquolsquoabsorptionrsquorsquoInternational Journal of Clinical and ExperimentalHypnosis 40 21ndash43

Banyai E I amp Hilgard E R (1976) A comparison ofactive-alert hypnotic induction with traditional relaxationinduction Journal of Abnormal Psychology 85 218 ndash224

Blakemore S J amp Decety J (2001) From the perception ofaction to the understanding of intention Nature ReviewsNeuroscience 2 561 ndash567

Braun A R Balkin T J Wesenten N J Carson R EVarga M Baldwin P Selbie S Belenky G amp HerscovitchP (1997) Regional cerebral blood flow throughout the

Rainville et al 899

sleep ndashwake cycle An H2(15)O PET study Brain 1201173 ndash1197

Bush G Luu P amp Posner M I (2000) Cognitive andemotional influences in anterior cingulate cortex Trendsin Cognitive Sciences 4 215 ndash222

Chalmers D J (2000) What is a neural correlate ofconsciousness In T Metzinger (Ed) Neural correlatesof consciousness Empirical and conceptual questions(pp 17ndash39) Cambridge MIT Press

Coe W C amp Sarbin T R (1977) Hypnosis from thestandpoint of a contextualist Annals of the New YorkAcademy of Sciences 296 2ndash13

Cohen J D Botvinick M amp Carter C S (2000) Anteriorcingulate and prefrontal cortex Whorsquos in control NatureNeuroscience 3 421 ndash423

Collins D L Neelin P Peters T M amp Evans A C (1994)Automatic 3D intersubject registration of MR volumetric datain standardized Talairach space Journal of ComputerAssisted Tomography 18 192 ndash205

Coull J T Frackowiak R S amp Frith C D (1998) Monitoringfor target objects Activation of right frontal and parietalcortices with increasing time on task Neuropsychologia 361325 ndash1334

Coull J T amp Nobre A C (1998) Where and when to payattention The neural systems for directing attention tospatial locations and to time intervals as revealed by bothPET and fMRI Journal of Neuroscience 18 7426 ndash7435

Crawford H J (1994) Brain dynamics and hypnosisAttentional and disattentional processes InternationalJournal of Clinical and Experimental Hypnosis 42204 ndash232

Crawford H J amp Gruzelier J H (1992) A midstream view ofthe neuropsychophysiology of hypnosis Recent researchand future directions In E Fromm amp M R Nash (Eds)Contemporary hypnosis research (pp 227 ndash266) New YorkGuilford Press

Crawford H J Knebel T Kaplan L Vendemia J M C XieM Jamison S amp Pribram K H (1998) Hypnotic analgesia1 Somatosensory event-related potential changes to noxiousstimuli and 2 Transfer learning to reduce chronic low backpain International Journal of Clinical and ExperimentalHypnosis 46 92ndash132

Damasio A R (1999) The feeling of what happens Body andemotion and the making of consciousness New YorkHartcourt Brace

De Pascalis V Magurano M R amp Bellusci A (1999) Painperception somatosensory event-related potentials andskin conductance responses to painful stimuli in high midand low hypnotizable subjects Effects of differential painreduction strategies Pain 83 499 ndash508

Devinsky O Morrell M J amp Vogt B A (1995) Contributionsof anterior cingulate cortex to behaviour Brain 118279 ndash306

Fiset P Paus T Daloze T Plourde G Meuret PBonhomme V Hajj-Ali N Backman S B amp Evans A C(1999) Brain mechanisms of propofol-induced loss ofconsciousness in humans A positron emission tomographicstudy Journal of Neuroscience 19 5505 ndash5513

Friston K J Worsley K J Frackowiak R S J Mazziotta J Camp Evans A C (1994) Assessing the significance of focalactivation using their spatial extent Human Brain Mapping1 214ndash220

Gitelman D R Alpert N M Kosslyn S Daffner K ScintoL Thompson W amp Mesulam M M (1996) Functionalimaging of human right hemispheric activation forexploratory movements Annals of Neurology 39 174ndash179

Gitelman D R Nobre A C Parrish T B LaBar K S KimY H Meyer J R amp Mesulam M (1999) A large-scale

distributed network for covert spatial attention Furtheranatomical delineation based on stringent behavioural andcognitive controls Brain 122 1093 ndash1106

Gruzelier J (1998) A working model of the neurophysiologyof hypnosis A review of evidence Contemporary Hypnosis15 3ndash21

Henson R N A Rugg M D Shallice T amp Dolan R J (2000)Confidence in recognition memory for words Dissociatingright prefrontal roles in episodic retrieval Journal ofCognitive Neuroscience 12 913 ndash923

Henson R N A Rugg M D Shallice T Joseph O ampDolan R J (1999) Recollection and familiarity inrecognition memory An event-related functional magneticresonance imaging study Journal of Neuroscience 193962 ndash3972

Herscovitch P Markham J amp Raichle M E (1983) Brainblood flow measured with intravenous H2(15)O I Theoryand error analysis Journal of Nuclear Medicine 24782 ndash789

Hofbauer R K Rainville P Duncan G H amp Bushnell M C(2001) Cortical representation of the sensory dimension ofpain Journal of Neurophysiology 86 402 ndash411

Hofle N Paus T Reutens D Fiset P Gotman J EvansA C amp Jones B E (1997) Regional cerebral blood flowchanges as a function of delta and spindle activity duringslow wave sleep in humans Journal of Neuroscience 174800 ndash4808

Jeanmonod D Magnin M amp Morel A (1996) Low-thresholdcalcium spike bursts in the human thalamus Commonphysiopathology for sensory motor and limbic positivesymptoms Brain 119 363ndash375

Kajimura N Uchiyama M Takayama Y Uchida S Uema TKato M Sekimoto M Watanabe T Nakajima THorikoshi S Ogawa K Nishikawa M Hiroki M Kudo YMatsuda H Okawa M amp Takahashi K (1999) Activityof midbrain reticular formation and neocortex during theprogression of human non-rapid eye movement sleepJournal of Neuroscience 19 10065 ndash10073

Kawashima R OrsquoSullivan B T amp Roland P E (1995)Positron-emission tomography studies of cross-modalityinhibition in selective attentional tasks Closing the lsquolsquomindrsquoseyersquorsquo Proceedings of the National Academy of SciencesUSA 92 5969 ndash5972

Kim Y H Gitelman D R Nobre A C Parrish T BLaBar K S amp Mesulam M M (1999) The large-scaleneural network for spatial attention displays multifunctionaloverlap but differential asymmetry Neuroimage 9269 ndash277

Kinomura S Larsson J Gulyas B amp Roland P E (1996)Activation by attention of the human reticular formationand thalamic intralaminar nuclei Science 271 512ndash515

Kosslyn S M Thompson W L Costantini-Ferrando M FAlpert N M amp Spiegel D (2000) Hypnotic visual illusionalters color processing in the brain American Journal ofPsychiatry 157 1279 ndash1284

Laureys S Faymonville M E Luxen A Lamy M Franck Gamp Maquet P (2000) Restoration of thalamocorticalconnectivity after recovery from persistent vegetative stateLancet 355 1790ndash1791

Lou H C Kjaer T W Friberg L Wildschiodtz G Holm Samp Nowak M (1999) A 15OndashH2O PET study of meditationand the resting state of normal consciousness HumanBrain Mapping 7 98ndash105

Maquet P Degueldre C Delfiore G Aerts J Peters J MLuxen A amp Franck G (1997) Functional neuroanatomyof human slow wave sleep Journal of Neuroscience 172807 ndash2812

Maquet P Faymonville M E Degueldre C Delfiore G

900 Journal of Cognitive Neuroscience Volume 14 Number 6

Franck G Luxen A amp Lamy M (1999) Functionalneuroanatomy of hypnotic state Biological Psychiatry 45327 ndash333

Metzinger T (2000) The subjectivity of subjective experienceA representationalist analysis of the first-person perspectiveIn T Metzinger (Ed) Neural correlates of consciousnessEmprical and conceptual questions (pp 285 ndash306)Cambridge MIT Press

Nobre A C Sebestyen G N Gitelman D R MesulamM M Frackowiak R S amp Frith C D (1997) Functionallocalization of the system for visuospatial attention usingpositron emission tomography Brain 120 515 ndash533

Pardo J V Fox P T amp Raichle M E (1991) Localization of ahuman system for sustained attention by positron emissiontomography Nature 349 61ndash64

Paus T (2001) Primate anterior cingulate cortex Wheremotor control drive and cognition interface NatureReviews Neuroscience 2 417 ndash424

Paus T Koski L Caramanos Z amp Westbury C (1998)Regional differences in the effects of task difficulty andmotor output on blood flow response in the human anteriorcingulate cortex A review of 107 PET activation studiesNeuroReport 9 R37ndashR47

Paus T Zatorre R J Hofle N Caramanos Z Gotman JPetrides M amp Evans A C (1997) Time-related changesin neural systems underlying attention and arousal duringthe performance of an auditory vigilance task Journal ofCognitive Neuroscience 9 392ndash408

Peyron R Garcia-Larrea L Gregoire M C Costes NConvers P Lavenne F Mauguiere F Michel D ampLaurent B (1999) Haemodynamic brain responses to acutepain in humansmdashSensory and attentional networks Brain122 1765 ndash1779

Picard N amp Strick P L (1996) Motor areas of the medial wallA review of their location and functional activation CerebralCortex 6 342 ndash353

Portas C M Howseman A M Josephs O Turner R ampFrith C D (1998) A specific role for the thalamus inmediating the interaction of attention and arousal inhumans Journal of Neuroscience 18 8979 ndash8989

Posner M I amp Rothbart M K (1998) Attentionself-regulation and consciousness Philosophical

Transactions of the Royal Society of London Series BBiological Sciences 353 1915 ndash1927

Price D D (1996) Hypnotic analgesia Psychological andneural mechanisms In J Barber (Ed) Hypnosis andsuggestions in the treatment of pain (pp 67ndash84) NewYork Norton

Price D D amp Barrell J J (1980) An experiential approachwith quantitative methods A research paradigm Journal ofHumanistic Psychology 20 75ndash95

Rainville P Carrier B Hofbauer R K Bushnell M C ampDuncan G H (1999) Dissociation of pain sensory andaffective dimensions using hypnotic modulation Pain 82159 ndash171

Rainville P Duncan G H Price D D Carrier B ampBushnell M C (1997) Pain affect encoded in humananterior cingulate but not somatosensory cortex Science277 968 ndash971

Rainville P Hofbauer R K Paus T Duncan G H BushnellM C amp Price D D (1999) Cerebral mechanisms ofhypnotic induction and suggestion Journal of CognitiveNeuroscience 11 110ndash125

Ruby P amp Decety J (2001) Effect of subjective perspectivetaking during simulation of action A PET investigation ofagency Nature Neuroscience 4 546 ndash550

Steriade M amp McCarley R W (1990) Brainstem control ofwakefulness and sleep New York Plenum

Szechtman H Woody E Bowers K S amp Nahmias C(1998) Where the imaginal appears real A positronemission tomography study of auditory hallucinationsProceedings of the National Academy of Sciences USA95 1956 ndash1960

Talairach J amp Tournoux P (1988) Co-planar stereotaxicatlas of the human brain New York Thieme

Tellegen A amp Atkinson G (1974) Openness to absorbingand self-altering experiences (lsquolsquoabsorptionrsquorsquo) a trait relatedto hypnotic susceptibility Journal of Abnormal Psychology83 268 ndash277

Toma K Honda M Hanakawa T Okada T Fukuyama HIkeda A Nishizawa S Konishi J amp Shibasaki H (1999)Activities of the primary and supplementary motor areasincrease in preparation and execution of voluntary musclerelaxation An event-related fMRI study Journal ofNeuroscience 19 3527 ndash3534

Varela F J amp Shear J (1999) First-person methodologiesWhat why and how Journal of Consciousness Studies 61ndash14

Vingoe F J (1968) The development of a group alert-trancescale International Journal of Clinical and ExperimentalHypnosis 16 120 ndash132

Vingoe F J (1973) Comparison of the Harvard Group Scaleof Hypnotic Susceptibility Form A and the Group AlertTrance Scale in a university population InternationalJournal of Clinical and Experimental Hypnosis 21169 ndash179

Vogt B A amp Gabriel M (1993) Neurobiology of cingulatecortex and limbic thalamus A comprehensive handbookBoston Birkauser

Weitzenhoffer A M (1980) Hypnotic susceptibility revisitedAmerican Journal of Clinical Hypnosis 22 130 ndash146

Willoch F Rosen G Tolle T R Oslashye I Wester H J BernerN Schwaiger M amp Bartenstein P (2000) Phantom limbpain in the human brain Unravelling neural circuitries ofphantom limb pain sensations using positron emissiontomography Annals of Neurology 48 842 ndash849

Worsley K J Evans A C Marrett S amp Neelin P (1992)A three-dimensional statistical analysis for CBF activationstudies in human brain Journal of Cerebral Blood Flow andMetabolism 12 900 ndash918

Rainville et al 901

Page 2: Hypnosis Modulates Activity in Brain Structures Involved in the …pineda/COGS175/readings/Rain... · 2005. 2. 28. · Hypnosis Modulates Activity in Brain Structures Involved in

Neurophenomenology of Hypnotic States

Hypnotic states may be described most adequately bythe global changes produced in subjective experienceand possibly in self-representation as these may beessential and ubiquitous to all hypnosis-related phenom-ena Studies of hypnosis using experiential analyses haveidentified a series of dimensions that characterize hyp-notic states (Price 1996) These dimensions include (1)feelings of deep mental relaxation (2) mental absorp-tion (3) a diminished tendency to judge monitor andcensor (4) a suspension of usual orientation towardtime location andor sense of self and (5) the experi-ence of onersquos own response as automatic or extra-volitional Notably those effects are not restricted tospecific sensory modalities or specific lsquolsquocontentsrsquorsquo ofconsciousness and pertain largely to the subjectsrsquo rep-resentation monitoring and regulation of their ownbody-self and mental state These alterations in lsquolsquoself-representationrsquorsquo possibly underlying the changes insubjective experience provide some support for thenotion that hypnosis is a distinct lsquolsquostatersquorsquo of conscious-ness to the extent that self-representation is likely toplay a key role in basic aspects of consciousness (egMetzinger 2000 Damasio 1999) The identification andexperimental manipulation of these basic dimensions ofexperience using hypnosis may further provide someleverage to investigate the neural correlates of back-ground states of consciousness (see Chalmers 2000)

At least two of the identified experiential dimensionsmental relaxation and mental absorption can be readilyassociated with specific instructions used to inducehypnosis Hypnotic relaxation results from direct in-structions for relaxation and suggestions for pleasantbody feelings (eg warmth and heaviness) drowsinessand mental ease Mental absorption is likely induced bysuggestions for continuous focus on the hypnotistrsquosvoice and on the conveyed instructions and by sugges-tions for decreased orientation to and interest in otherirrelevant external sources of stimulation and sponta-neous thoughts Consistently mental absorption hasbeen described as a state of lsquolsquototal attention that fullyengages onersquos representational resources and resultsin imperviousness to distracting eventsrsquorsquo (Tellegen ampAtkinson 1974)

In the present study 10 normal volunteers rated theirlevel of relaxation and mental absorption immediatelyafter each of 8 positron emission tomography (PET)scans performed before (4 scans) and during (4 scans)hypnosis The subjectrsquos left hand was immersed in eitherwarm or painfully hot water during each scan andthe variance associated with this stimulation factor wasremoved in all regional cerebral blood flow (rCBF)analyses reported here (ANCOVA pain-related activityis the subject of a separate report Hofbauer et al 2001)The reliability of the effects of hypnotic induction onbrain activity is first assessed by comparing the present

results with those obtained in our previous study (Rain-ville Hofbauer et al 1999) The present report furtherexamines the cerebral correlates of hypnotically inducedchanges in the subjective experience of mental relaxationand mental absorption using regression analyses of rCBFon self-ratings Directed searches are conducted on theanterior cingulate cortex (ACC) and the thalamus be-cause of their suggested involvement in attention cort-ical arousal and self-regulation and based on previousstudies showing coactivation in these areas following theinduction of hypnosis (Maquet et al 1999 see Table 1and Appendix in Rainville Hofbauer et al 1999) Thebrainstem is further included as a specific search areabased on the critical implication of brainstem nuclei inthe regulation of conscious states and on their impor-tant interactions with the thalamus and the ACC in theregulation of sleep ndashwakefulness and attention (egAston-Jones Rajkowski amp Cohen 1999 Kinomura Lars-son Gulyas amp Roland 1996 Steriade amp McCarley 1990)Additional changes in cerebral activity are examinedusing global searches over the entire brain

RESULTS

Hypnosis-Related Changes in Mental Relaxationand Mental Absorption

The induction of hypnosis produced significant in-creases in self-ratings of both mental relaxation andmental absorption (Figure 1) Likewise both experien-tial measures showed modest but significant correla-tions with a standardized measure of individualhypnotic susceptibility (Stanford Hypnotic SusceptibilityScalemdashForm A [SHSS-A] mental relaxation SpearmanrsquosR = 38 p lt 01 mental absorption SpearmanrsquosR = 27 p lt 05) These results and additional con-vergent evidence in the same subjects or in differentsubjects using the same method indicate that theprocedure was effective in inducing hypnotic states

0 0

2 0

4 0

6 0

8 0

Relaxation Absorption

No

rmal

ized

Sel

f-R

atin

g (

+SE

M)

BaselineHypnosis

p = 001p lt 0001

Figure 1 Hypnosis-related changes in mental relaxation andabsorption Self-rated relaxation and absorption (normalized within-subjects) increased significantly following the induction of hypnosis(see p values)

888 Journal of Cognitive Neuroscience Volume 14 Number 6

(Hofbauer et al 2001 Rainville et al 1997 RainvilleCarrier Hofbauer Bushnell amp Duncan 1999 RainvilleHofbauer et al 1999)

Heart rate measured before and during scans did notchange significantly following the induction of hypnosis(see Hofbauer et al 2001)

Reliability of Hypnosis-Related Changes in rCBF

The reliability of the effects of hypnosis on cerebralactivity was examined by comparing the results of asubtraction analysis (Hypnosis minus Baseline condi-tions) with those of our previous study (see Table 2 inRainville Hofbauer et al 1999) Our current resultsreplicated the previously reported rCBF increases inboth occipital lobes the right Sylvian region (peaks inthe inferior frontal and superior temporal gyri) the leftinsula (more anterior and bilateral in the present study)and the right ACC However ACC activation was moreextensive here with significant clusters of activatedvoxels covering multiple areas of the ACC and peaksfound in both the right and left hemispheres inthe middle rostral and perigenual ACC The frontalincreases in rCBF extended further bilaterally in thecentral region and in the medial frontal and prefrontalareas (superior frontal and orbito-frontal) Decreases in

rCBF observed in our previous study were replicated inthe right inferior parietal lobule the precuneus and theleft posterior temporal cortices (bilateral here) Theeffects previously reported and not replicated here arethe increases in the right parietal operculum and thedecreases in the medial frontal cortex and the posteriorcingulate gyrus (here medial parietal decreases werelimited to the precuneus) Occipital increases in rCBFwere again stronger in the warm stimulation conditionand prefrontal increases were stronger in the painfulstimulation condition These results largely confirm thereliability of the changes in rCBF associated with theinduction of hypnosis

Mental Relaxation- and Absorption-Related Effects

Directed Search over the Brainstem the Thalamus andthe ACC

The functional role of particular structures thought to beinvolved in the production of hypnosis was assessed byanalyzing the degree of correlation between rCBF inthese regions and subjectsrsquo estimates of the experientialindices of hypnosis (mental relaxation and absorption)(Table 1 Figure 2) Increases in mental relaxation werecorrelated with rCBF decreases in the mesencephalictegmentum of the brainstem (Figure 2A) and with

Table 1 Peak t Values Observed in the Directed Search Areas in Regression Analyses on Self-Ratings and Thalamic rCBF

Relaxation Relaxation-Specific Absorption Absorption-SpecificThalamus

Covariation

Brainstem iexcl267(iexcl3 iexcl33 iexcl12)

iexcl281(iexcl1 iexcl38 iexcl17)

ns +278(1 iexcl26 iexcl22)

+312(13 iexcl26 iexcl15)

+287(3 iexcl32 iexcl24)

Thalamus ns iexcl368(iexcl3 iexcl16 12)

+260(iexcl1 iexcl18 12)

+445(iexcl3 iexcl16 12)

+350(17 iexcl11 2)

ACC

mid +260(1 15 35)

ns ns ns +387(8 13 44)

rostral ns iexcl368(5 37 45a)

+345(1 29 30)

+432(3 32 39a)

+382(1 43 32a)

perigenual +302(5 34 9)

ns +296(8 32 9)

ns ns

Regression models were used to evaluate the slope of the relationship between relaxation or absorption ratings and rCBF Relaxation-specific andabsorption-specific effects were further tested after accounting for variance associated with absorption and relaxation respectively (see Methods)Thalamic covariations were tested in a regression model evaluating the relationship between rCBF in the thalamus at the site of absorption-specificactivity and rCBF in the brainstem the rest of the thalamus and the ACC Stereotaxic coordinates are given for each peak according to the atlas ofTalairach and Tournoux (1988) (x y z = lateral anterior superior)

ns = no significant peak found (iexcl258 lt t lt 258 p gt 01)

p lt 01 p lt 001 p lt 0001 (uncorrected p values)aPeak is over the right medial superior frontal gyrus within a cluster extending into the ACC at the site of significant absorption-related effect(x y z = 1 29 30)

Rainville et al 889

increases in the middle and perigenual ACC (Figure 2B)Increases in absorption were correlated with rCBFincreases in the thalamus and in the rostral and peri-genual ACC (Figure 2C)

The specificity of any changes in the rCBF associatedwith either mental relaxation (relaxation-specific) orabsorption (absorption-specific) was further examinedusing ANCOVA (see Methods) to remove the varianceshared with the other factormdashabsorption and relaxa-tion respectively (Table 1) Relaxation-specific negativecorrelations were found in the brainstem in the thala-mus and in the superior frontal gyrus in a clusterof significant voxels extending over the rostral ACCAbsorption-specific effects confirmed the significant pos-itive correlation between mental absorption and rCBFin the thalamus and in the rostral ACC and furtherrevealed a significant positive peak in the upper ponsof the brainstem (Figure 2D Table 1) Although mentalrelaxation and absorption both increased during hyp-nosis these results demonstrate that the negative cor-relation in the mesencephalic brainstem and thethalamus appears to be exclusively associated with

mental relaxation while the positive correlations inthe upper pons the thalamus and the mid-ACC appearto be exclusively associated with mental absorption

Global Searches

Results of the global searches show additional differ-ences between the patterns of activity related to mentalrelaxation and absorption In the frontal lobe increasesin prefrontal rCBF were positively correlated primarilywith mental absorption (Table 2) while increases in theprecentral region were positively correlated with bothrelaxation (Figure 3A) and absorption (Table 2) Con-sistently after removing the variance shared betweenmental relaxation and absorption positive absorption-specific correlations (Table 2 Figure 3B) and negativerelaxation-specific correlations (Table 2) were observedin prefrontal areas while most precentral effects did notreach significance

Posterior cortical areas displayed a mixed pattern ofresults Negative correlations observed in both temporallobes were more reliably related to mental relaxation

Figure 2 Statistical (t) maps overlaid on a midsagittal view of a single-subject MRI anatomical image showing the location of significant positive(red arrows) and negative (blue arrow) regression slopes between rCBF and self-ratings in the three regions of interest (brainstem thalamus andACC see Methods) (A) A negative regression peak is found with relaxation in the mesencephalic tegmentum and (B) positive regression peaksare found in the middle (mACC) and perigenual (pACC) portion of the ACC (note the reversal of the color scale) (C) Positive regression peaksare found with absorption in the thalamus and in the rostral ACC (rACC) and pACC (D) The regression of rCBF on absorption ratings afteraccounting for relaxation-related effects confirmed the positive regression peaks specific to absorption in the thalamus and rACC This analysisfurther revealed an additional positive peak in the upper pons Color scales in C and D are as in B Stereotaxic coordinates of peaks are reportedin Table 1

890 Journal of Cognitive Neuroscience Volume 14 Number 6

than absorption and the relaxation-related effects heldafter accounting for variance in absorption (Table 2mdashrelaxation-specific) Additional sites of relaxation-specificeffects included negative correlations in the right parie-tal operculum and lobule and positive correlations in theright precuneus the left inferior parietal lobule and thebilateral occipital cortices (Table 2mdashrelaxation-specific)

The effects associated with absorption in the posteri-or cortices were strikingly different from the effects ofrelaxation After accounting for relaxation-related var-iance we observed both positive and negative absorp-tion-specific correlations in both the right and leftparietal lobules (see Table 2mdashabsorption-specific) Inthe inferior parietal lobules positive and negative cor-relations dominated in the right and left hemispheresrespectively (Figure 3B) Strong negative correlationswere also observed over the right precuneus theposterior cingulate cortex and both occipital lobes(Figure 3B)

Additional statistical trends directly relevant to ourhypotheses were also observed in the somatosensorycortices where rCBF was negatively correlated with men-tal relaxation (see Figure 3A right S1 peak coordinates44 iexcl35 59 t = iexcl286 p-uncorrected = 014 clusterp = 06 left S1 iexcl44 iexcl21 16 t = iexcl251 p-uncorrected =026 cluster analysis p gt 10 right parietal operculumS2 48 iexcl21 24 t = iexcl351 p-uncorrected = 003 clusterp gt 10 right posterior insula 44 iexcl4 15 t = iexcl296p-uncorrected = 011 cluster p gt 10)

Covariations with Thalamic rCBF

In our previous study thalamic activity was found tobe correlated with hypnosis-related ACC activity (seeTable 2 and Appendix in Rainville Hofbauer et al1999) and several studies suggest a pivotal role of thethalamus in arousal attention and consciousness andin the interaction between the brainstem and the ACC(eg Paus et al 1997 Paus 2001 Portas HowsemanJosephs Turner amp Frith 1998 Hofle et al 1997) Herewe tested the association between absorption-relatedactivity in the thalamus and activity in other sites ofabsorption-related changes using a covariation analysiscentered on the absorption-specific peak in the thala-mus reported in Table 1 Absorption-specific sites in thebrainstem (upper pons) and the ACC showed significantcovariations with thalamic rCBF (Table 1) Additionalregions where rCBF showed a positive correlation withthalamic rCBF included bilateral frontal sites in theinferior middle and superior frontal gyri extendingmedially into the right ACC and the right insula(Table 3) Many of those peak locations matched frontalsites specifically related to mental absorption (italicizedin Table 2) A strong positive peak was also observed inthe right inferior parietal lobule precisely at the loca-tion where rCBF correlated strongly and specificallywith mental absorption (compare Table 2 absorption-

specific and Table 3) Areas displaying negative corre-lation with thalamic rCBF were found bilaterally in theoccipital lobes consistent with the absorption-specificeffects reported in Table 2

DISCUSSION

The approach used in this study provided a descriptionof cerebral activity associated with specific changes inphenomenal experience produced by a standard hyp-notic induction We discuss in turn the evidence for theproduction of hypnotic phenomena the reliability ofhypnosis-related effects the effects associated with men-tal relaxation and absorption and the implications ofour results for a state theory of hypnosis

Hypnosis and Phenomenal Experience

The induction of hypnosis produced the expectedincreases in both mental relaxation and absorptionThese changes were positively correlated (see Methods)as predicted by the experiential model of hypnosisproposed by Price (1996) and the ability to maintainhypnotic relaxation and absorption depended upon thesubjectsrsquo hypnotic susceptibility The higher levels ofabsorption maintained in highly hypnotizable subjectsare consistent with the positive association betweenabsorption attentional processes and hypnotizabilitysuggested in previous studies (Crawford 1994 Baltha-zard amp Woody 1992 Tellegen amp Atkinson 1974) Theseresults and additional convergent observations de-scribed in our previous report of pain-related effects(Hofbauer et al 2001) and from several experimentsusing similar methodology (Rainville et al 1997 Rain-ville Carrier et al 1999) confirmed the reliable produc-tion of hypnotic phenomena

Reliability of Hypnosis-Related Effects on rCBF

The experimental conditions examined here and in thefirst 8 scans in our previous study were identicalmdashthesame hypnotic induction procedure was applied by twodifferent experimenters and the two separate groups ofsubjects tested had comparable mean hypnotic suscep-tibility scores (Rainville Hofbauer et al 1999) Theresults of the subtraction analysis largely replicated ourprevious findings as well as those reported by Maquetet al (1999) In comparison to our previous experimentdifferences in the methods were limited to the additionof relaxation and absorption ratings after the scans Thelarger areas of frontal activation including the precentralregion and the more restricted occipital activationobserved here may reflect the emphasis put on hypnoticrelaxation and absorption during the scans As thesedimensions of experience characterize standard hypno-tic induction procedures we submit that these differ-ences further emphasize the functional significance of

Rainville et al 891

Tab

le2

R

esul

tsof

the

Glo

bal

Sear

ches

ofC

ereb

ral

Regi

ons

whe

rerC

BF

Show

eda

Sign

ifica

ntR

egre

ssio

nw

ithR

elax

atio

nan

dAb

sorp

tion

Regi

onP

eak

Loca

tion

Rela

xati

onRe

laxa

tion

-Spe

cifi

cAb

sorp

tion

Abs

orpt

ion

-Spe

cifi

c

xy

zt

xy

zt

xy

zt

xy

zt

Fron

tal

(F)

RF

Pole

(BA

10)

ndash34

562

iexcliexcl4

81

ndash28

555

+4

21

Rla

tF

Orb

ital

g(B

A11

)ndash

1946

iexcl20

iexcliexcl4

29

ndash19

44iexcl

20+

47

5

Rm

iddl

eF

g(B

A46

)ndash

3646

26iexcl

381

ndash34

4626

+3

79

Rin

fF

g(B

A47

)ndash

ndash47

34iexcl

18+

373

ndash

Rin

fF

g(B

A45

)ndash

478

15iexcl

386

5520

11+

352

ndash

Ra

nt

insu

lai

nf

Fg

(BA

144

4)ndash

4015

6iexcl

377

4310

2+

358

4013

5+

48

1

Rsu

pF

gc

ingu

late

g(B

A8

32)

ndash5

3745

iexcl3

68ndash

332

39+

43

2

Rsu

pF

g(B

A6)

ndashndash

1320

59+

369

1522

57+

43

3

Rm

edia

lsu

pF

g(B

A6)

ndashndash

3iexcl

466

+4

23

3iexcl

766

+3

92

Lla

tF

Orb

ital

g(B

A11

)ndash

ndashiexcl

3041

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+3

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3143

iexcl18

+3

76

Lm

iddl

eF

g(B

A8)

ndashndash

iexcl46

1535

+4

10iexcl

4410

29+

328

Lm

iddl

eF

g(B

A46

)ndash

ndashiexcl

3637

18+

43

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3839

24+

407

La

nt

insu

lai

nf

Fg

(BA

144

4)ndash

ndashndash

iexcl34

817

+4

25

Lsu

pF

g(B

A6)

ndashndash

ndashiexcl

266

56+

416

Lsu

p

Fg

(BA

6)ndash

ndashiexcl

11iexcl

466

+3

68ndash

Cen

tral

Rp

rece

ntra

lg

(BA

4)54

iexcl4

53+

51

6ndash

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453

+5

05

ndash

Rp

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ntra

lg

(BA

4)42

iexcl7

50+

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4ndash

ndashndash

Rp

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entr

alg

(BA

41

3)ndash

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iexcl16

36+

378

ndash

Lpr

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tral

mid

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Fg

(BA

46)

iexcl35

iexcl6

53+

398

ndashndash

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Lpr

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tral

g(B

A4)

iexcl47

iexcl16

47+

44

3ndash

iexcl48

iexcl14

50+

43

6ndash

Lpr

epo

stce

ntra

lg

(BA

41

3)ndash

iexcl30

iexcl37

60+

403

ndash

Tem

pora

l(T

)R

mid

dle

T

g(B

A21

)60

iexcl33

iexcl15

iexcl5

71

59iexcl

33iexcl

13iexcliexcl

55

1ndash

ndash

Rm

iddl

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(BA

37)

56iexcl

45iexcl

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55iexcl

47iexcl

6iexcliexcl

44

1ndash

Lpa

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amp

alg

(BA

353

6)iexcl

36iexcl

23iexcl

18iexcl

413

ndashndash

ndash

Lin

fT

g

fusi

form

g(B

A37

)iexcl

52iexcl

42iexcl

20iexcl

52

4iexcl

59iexcl

44iexcl

12iexcliexcl

43

3iexcl

48iexcl

44iexcl

20iexcliexcl

44

6ndash

892 Journal of Cognitive Neuroscience Volume 14 Number 6

Pari

etal

(P)

RP

oper

culu

m(B

A40

)ndash

32iexcl

3027

iexcl3

55ndash

ndash

Rin

fP

lo

bule

(BA

40)

ndash56

iexcl40

50iexcl

377

ndash56

iexcl44

50+

42

4

RP

lobu

le(B

A40

7)

39iexcl

4945

iexcl4

87

ndash38

iexcl47

45iexcliexcl

44

334

iexcl56

42+

383

Rsu

pP

lobu

le(B

A7)

ndashndash

21iexcl

5062

iexcliexcl4

45

21iexcl

5260

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09

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ecun

eus

(BA

7)ndash

5iexcl

5645

+5

33

ndash5

iexcl56

45iexcliexcl

51

0

Prec

uneu

sp

ost

Cin

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(BA

731

)ndash

ndashndash

0iexcl

649

iexcliexcl5

05

Lin

fP

lobu

le(B

A40

)ndash

iexcl30

iexcl37

60+

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ndashiexcl

35iexcl

3550

iexcliexcl4

48

Lin

fP

lobu

le(B

A40

)ndash

ndashndash

iexcl52

iexcl56

47+

370

Occ

ipit

al(O

)Li

ngua

lg

pos

tC

ing

g(B

A18

31)

ndash0

iexcl66

9+

42

6ndash

ndash

Rin

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g

(BA

19)

ndash43

iexcl71

iexcl6

+3

6843

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5iexcliexcl

44

443

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17

Rli

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alg

(BA

18)

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782

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68

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neu

s(B

A18

)ndash

12iexcl

8327

+5

20

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g

(BA

19)

ndash17

iexcl81

38+

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15iexcl

8033

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02

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(BA

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8726

+4

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A18

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929

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(BA

181

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+3

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prec

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eus

(BA

197

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36iexcliexcl

42

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8739

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g(B

A18

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ereb

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17iexcl

76iexcl

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351

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A18

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(BA

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8327

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A18

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Rel

axat

ion

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ecifi

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tio

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ific

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ng

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ance

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edw

ith

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rpti

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xati

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ecti

vely

(AN

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eM

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od

s)T

he

linea

rsl

op

ebe

twee

nrC

BF

and

rati

ngs

issi

gnifi

can

tatp

eak

loca

tio

ns

liste

d(t

thre

sho

ld=

plusmn4

20i

nb

old

see

Met

hod

s)P

eaks

wit

htgt

+3

50or

tlt

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50w

ith

ina

sign

ific

ant

clus

ter

(see

Met

hods

)are

also

indi

cate

dw

ith

thei

rco

ordi

nate

sP

eaks

clos

eto

or

wit

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regi

ons

wh

ere

sign

ific

ant

cova

riat

ions

wit

hth

alam

icrC

BF

wer

efo

und

are

ita

lici

zed

(see

Tab

le3

and

Met

hods

)P

eak

loca

tion

sar

eba

sed

onth

est

ereo

taxi

cat

las

of

Tal

aira

chan

dT

ourn

oux

(198

8)(x

=la

tera

ly

=an

teri

or

z=

supe

rior

)an

don

mor

phol

ogi

cal

lan

dmar

kson

the

mer

ged

PE

Tndash

MR

Iim

ages

(BA

=pr

obab

leB

rodm

annrsquo

sar

eaL

=

left

R

=

righ

tg

=gy

rus

ant

=an

teri

or

pos

t=

post

erio

rsu

p=

supe

rior

in

f=

infe

rior

)

Rainville et al 893

the underlying processes in the production of hypnoticstates as discussed below

Role of the Brainstem the Thalamus and the ACCin Hypnosis

Results of the regression analyses suggest that neuralactivity in the brainstem the thalamus and the ACCcontributes to the experience of being hypnotized Therelaxation-specific negative correlations in the mesen-

cephalic brainstem and the thalamus may reflect thewell-established contribution of brainstem and thalamicnuclei to the regulation of wakefulness and corticalarousal In functional brain imaging studies rCBFdecreases in the brainstem and the thalamus have beenassociated with decreased vigilance (Paus et al 1997)sleep (Kajimura et al 1999 Braun et al 1997 Hofleet al 1997 Maquet et al 1997) and the loss ofconsciousness produced by the anesthetic propofol(Fiset et al 1999) These effects and to some extent

Figure 3 Brain regionsshowing positive (redarrowheads) and negative(blue arrowheads) regres-sion peaks between rCBFand self-ratings of (A)relaxation and (B) absorp-tion after accounting forrelaxation-related variance(absorption-specific)Statistical t maps are super-imposed on the averageanatomical MRI (left is onthe left side) Slice locationsare indicated on the 3-Danatomical image of asingle subjectrsquos anatomicalMRI (A-positive) Positiverelaxation-related effectsare shown in the centralregion bilaterally (horizon-tal slice on the left) Apositive peak is shown inthe right superior occipitalgyrus (SOg) (coronal viewon the right note scalechange) (A-negative)A negative relaxation-related effect in the rightposterior parietal cortexis shown in horizontal(first from left) coronal(second) and lateralsagittal (third) views Theplus sign indicates the moreanterior location of thepeak positive regression inthe analysis of absorption-related effects as shown inB Additional negative cor-relations are shown in thebilateral middle and inferiortemporal gyri (second) andin the right somatosensorycortices (S1 S2 insula)(B-positive) A positiveabsorption-specific peak isshown in the right inferiorparietal lobule (first fromleft) The minus sign indicates the more posterior location of the negative regression peak in the analysis of relaxation-related effects as shown in

A Other peaks are shown on the midsagittal view in the thalamus and the anterior cingulate cortex (second from left) and in the left lenticularnuclei and bilateral prefrontal cortices (last three cuts from left) (B-negative) Negative absorption-related effects are shown in the left inferiorparietal lobule (first from left) in both occipital lobes (second and third from left) and in the precuneus (first and third) Stereotaxic coordinates ofpeaks are reported in Table 3 (see relaxation- and absorption-specific)

894 Journal of Cognitive Neuroscience Volume 14 Number 6

the present relaxation-related decrease in brainstemrCBF may reflect an attenuation of activity withinbrainstem cholinergic nuclei Such reduction has beenobserved during slow EEG activity before the onset ofsleep and during slow-wave sleep in animal studies(Steriade amp McCarley 1990) Consistent with this pos-sibility we previously reported an increase in slow(delta) EEG activity following hypnotic induction (Rain-ville Hofbauer et al 1999) Although hypnotic andsleep states are clearly distinct certain neurophysiolog-

ical mechanisms may be involved to a varying degree inthe production of both states

The positive association specifically observed betweenmental absorption and rCBF in the upper pons and thethalamus contrasts with the above relaxation-relatedeffect and is consistent with previous reports of atten-tion-related brain activation (Kinomura et al 1996) Thisactivity may reflect the involvement of the noradrenergicsystem of the locus coeruleus in focused attentionand possibly in the interaction between cortical arousal

Table 3 Cerebral Sites of Covariation with Thalamic rCBF at the Absorption-Specific Peak Coordinates (x = iexcl27 y = iexcl160z = 120)

Region Peak Location x y z t

Frontal (F) R medial sup F gACC (BA 624) 1 43 32 +382

R anterior cingulate gsup F g (BA 326) 8 13 44 +387

R inf F g (BA 44) 51 12 8 +387

R ant insula (BA 14) 38 12 5 +412

R sup F g (BA 6) 16 20 59 +371

R medial sup F g (BA 6) 3 iexcl6 63 +498

R medial sup F g (BA 6) 11 iexcl23 53 +412

L middle F g (BA 46) iexcl38 46 23 +381

L middle F g (BA 46) iexcl31 39 39 +374

L inf F g (BA 44) iexcl43 6 12 +430

L sup F g (BA 6) iexcl19 20 53 +340

L medial sup F g (BA 6) iexcl5 17 65 +353

L sup F g (BA 6) iexcl20 12 65 +283

Parietal R inf parietal lobule (BA 40) 56 iexcl44 50 +519

Occipital (O) R fusiform g (BA 19) 26 iexcl62 iexcl30 iexcliexcl515

R lingual g (BA 18) 7 iexcl78 6 iexcliexcl623

R sup O g (BA 19) 19 iexcl85 30 iexcliexcl714

R O pole (BA 18) 27 iexcl90 9 iexcliexcl751

L cuneus (BA 18) iexcl11 iexcl83 29 iexcliexcl633

L O pole (BA 18) iexcl23 iexcl88 6 iexcliexcl793

Subcortical R thalamus 17 iexcl11 2 +350

R brainstem 13 iexcl26 iexcl15 +312

R medial brainstem 3 iexcl32 iexcl24 +287

L cerebellum iexcl4 iexcl57 iexcl21 +409

L globus pallidus iexcl20 iexcl1 iexcl2 +302

L caudate nucleus iexcl12 6 20 +291

Positive and negative regression slopes are significant at sites listed based on cluster or peak analyses (peak t threshold ltgtplusmn370 in bold allpeaks reported with t lt 370 are within a significant cluster see Methods) Peaks in italic are also reported in Table 1 See legends to Tables 1 and 2and Methods for further explanation

Rainville et al 895

and attentional processes (ie increased attentionabsorption concurrent with decreased cortical arousalincreased relaxation) (Aston-Jones et al 1999) Theindirect nature of the rCBF measures and the relativelypoor resolution of the PET method require somecaution in evaluating the possible anatomo-functionalimplications of our results in the brainstem Howeverthe convergent findings observed in other brain imag-ing studies and the observations provided in animalstudies support the notion that ascending cholinergicand noradrenergic pathways may contribute differen-tially to the multiple dimensions of experience thatcharacterize hypnosis

The overall pattern of results found in the ACC likelyreflects the heterogeneity of functions associated withthis area (Devinsky Morrell amp Vogt 1995) The locationof the most posterior relaxation-related peak in the ACC(mACC) is consistent with our previous observationof ACC activation during hypnosis (Rainville Hofbaueret al 1999) This relaxation-related peak is only slightlyanterior to the motor area of the caudal ACC (Picard ampStrick 1996) and may be involved in the installment of arelaxed state (also see precentral area below) In con-trast a positive absorption-specific effect was observedin a more rostral region of the ACC (rACC) close to anegative relaxation-specific correlation (see Table 1)This area of the ACC has previously been involved inexecutive attention in the detection of errors and in themonitoring of conflict between competing cognitiveprocesses (Bush Luu amp Posner 2000 Cohen Botvinickamp Carter 2000 Badgaiyan amp Posner 1998 Posner ampRothbart 1998) A meta-analysis of PET studies inves-tigating cognitive functions further suggested that theincrease in activity within this sector of the ACC isrelated to the difficulty of the task performed (PausKoski Caramanos amp Westbury 1998) Our findings areconsistent with these propositions to the extent thatthe engagement of the cognitive and neurophysiologicalprocesses implied in each of those accounts may beaccompanied by a subjective experience of increasedmental absorption

The coordinated pattern of rCBF changes in thebrainstem the thalamus and the ACC may reflect theinterrelationships between the multiple components of anetwork (eg Paus et al 1997) herein shown to beassociated with the feeling of being lsquolsquomentally absorbedrsquorsquoThe precise location of the observed absorption-specificthalamic peak is consistent with an involvement of theintralaminar and medio-dorsal nuclei which have recip-rocal connections with the ACC (Vogt amp Gabriel 1993)The finding that the coordinated activity in the thalamusand the ACC is disrupted in persistent vegetative states isconsistent with the notion that these structures work intandem to regulate consciousness (Laureys et al 2000also see Jeanmonod Magnin amp Morel 1996) Further-more a functional interaction between arousal andattentional processes has been reported in the thalamus

where the putative attention-related activity associatedwith the performance of a simple visual discriminationtask was found to increase in states of low arousal (Portaset al 1998) This increase in thalamic activity wassuggested (1) to reflect a compensatory mechanism thatpermitted the maintenance of stable levels of perform-ance in states of low arousal and (2) to prevent thegeneralized thalamo-cortical synchronization that wouldlead to sleep Here the opposite effects of relaxation andabsorption on thalamic activity may reflect this compen-satory mechanism that maintains high levels of focusedattention in deeply relaxed subjects during hypnosisThis function may be critical not only in hypnosis butalso in other conditions of deep relaxation distinct fromboth sleep and normal wakefulness such as meditativestates (Lou et al 1999) Furthermore the coactivation ofthe ACC and the ponto-mesencephalic brainstem mayreflect the contribution of the ACC to the regulation ofattention-related activity in the locus coeruleus (Cohenet al 2000) The positive regression found with absorp-tion in the ponto-mesencephalic brainstem and themore robust regression observed in the thalamus andthe ACC after accounting for relaxation-related changes(absorption-specific Table 1) further substantiate thepossibility that brainstem and thalamic nuclei interactwith the ACC to regulate the interaction between atten-tion and cortical arousal Taken together these resultsare consistent with a contribution of brainstem nucleithe intralaminar and medio-dorsal nuclei of the thala-mus and the ACC to the changes in phenomenalexperience that characterize hypnotic states

Additional Relaxation- and Absorption-RelatedChanges in rCBF

Relaxation-Related Activity

We observed strong relaxation-related increases in rCBFin the precentral gyrus bilaterally and reciprocaldecreases in somatosensory areas (S1 S2 and insula)Precentral and premotor activation has been reportedduring hypnosis in an independent study (Maquet et al1999) and precentral rCBF was correlated with the rCBFmeasured at the ACC site of hypnosis-related activity inour previous study (see Appendix in Rainville Hofbaueret al 1999) Similar increases in activity in motor andpremotor areas have been associated with voluntarymuscular relaxation (Toma et al 1999) but the presentresults may reflect more than physical relaxation

All standard hypnotic procedures include instructionsfor relaxation However the specific contribution ofmuscular relaxation and decreased arousal to the pro-duction of hypnotic states is unclear as hypnotic phe-nomena have been produced during muscular exercise(Banyai amp Hilgard 1976) and with suggestions of active-alertness (Vingoe 1968 1973) Here the absence ofsignificant effect of hypnosis on heart rate indicates thatchanges in cerebral activity did not correlate with

896 Journal of Cognitive Neuroscience Volume 14 Number 6

changes in peripheral arousal and suggests that subjectswere already physically relaxed in the baseline controlcondition This implies that the hypnosis-inducedchanges in self-ratings of relaxation may not simplyreflect changes in lsquolsquoperipheralrsquorsquo arousal but may attestmore specifically of an increase in lsquolsquomentalrsquorsquo relaxationand a reduction in lsquolsquocorticalrsquorsquo arousal This is consistentwith Pricersquos experiential model of hypnosis (see Intro-duction) and with our previous study showing anincrease in slow (delta) EEG activity during hypnosis

Relaxation-related effects observed outside primarysomatomotor areas may partly reflect subjective feelingsof mental ease more closely In the subtraction analysishypnosis-related decreases were found in the rightlateral posterior parietal rCBF both here (x y z 40iexcl52 44) and in our previous study (x y z 46 iexcl50 42from Table 1 in Rainville Hofbauer et al 1999) Herethese changes were strongly but not specifically asso-ciated with relaxation (x y z 39 iexcl49 45 see Table 2Figure 3A) Furthermore after accounting for absorp-tion-related variance right prefrontal activity was neg-atively correlated with relaxation (Table 2) Thoseadditional changes in the right posterior parietal cortexand the right prefrontal cortices may contribute to thesubjective feelings of mental ease rather than or inaddition to physical relaxation

Fronto-Parietal Attention Networks

Absorption-related activity was widespread and bilateralin the prefrontal cortices but peaks were generallystronger in the right hemisphere Positive regressionpeaks were maximal in the ventrolateral frontal corticesover the inferior frontal gyrus and in the anterior insulaA positive absorption-related regression peak was alsosignificant in the right inferior parietal lobule Theseareas also displayed strong coactivation with absorption-related thalamic activity Very similar patterns of activa-tion have been associated with attentional processes intasks involving visual (eg Coull Frackowiak amp Frith1998) auditory (Paus et al 1997) and somatosensorystimuli (Peyron et al 1999) Notably the location of thepositive parietal peak observed here closely matches theactivation sites reported in those studies and the site ofcovariation with the right ventrolateral attention-relatedactivity reported in Paus et al (1997) suggesting theactivation of a similar network The coordinated absorp-tion-related activity observed here in the brainstem thethalamus the ACC the right inferior frontal gyrus andthe right inferior parietal lobule provides very strongevidence that mental absorption is an experiential cor-relate of the activation of the brainrsquos lsquolsquoexecutive atten-tional networkrsquorsquo and suggests that this system plays acritical role in the production of hypnotic states

Negative absorption-related regression peaks werealso found in both the right and left lateral parietalcortices and in the precuneus (see Table 2) These

effects were largely independent of thalamic activity asindicated by the absence of significant effects at theselocations in the covariation analysis (Table 3) The rightposterior parietal cortex has been suggested to con-stitute a vigilanceorientation system (Pardo Fox ampRaichle 1991) and hypnosis-related decreases in thisarea may reflect a relative disengagement towardexternal sources of stimulation Right and left posteriorparietal cortices at the precise sites of relaxation- andabsorption-related decrease in rCBF have been sug-gested to contribute to the monitoring of externalspace and time respectively (Gitelman et al 19961999 Kim et al 1999 Coull amp Nobre 1998 Nobreet al 1997) Although these functions were notdirectly assessed in this experiment the hypnoticinduction procedure includes specific instructions fordecreased orientation to and interest in irrelevantexternal sources of stimulation and previous observa-tions suggest that hypnotic relaxation and absorptionare precursors to some alterations in spatio-temporalorientation and monitoring (Price 1996) Thus wespeculate that those additional experiential changesmay be consequent to relaxation- and absorption-related decreases in posterior parietal activity

Relaxation- and Absorption-Related Effects onOccipital rCBF

The subtraction analysis confirmed the reliability of thehypnosis-related increase in occipital rCBF reported inour previous study (Rainville Hofbauer et al 1999) Wenow show that this effect was associated with the sub-jective experience of hypnotic relaxation (see Table 2relaxation-specific) Consistently our previous studydemonstrated a coupling between occipital increases inrCBF and increases in slow (delta) EEG activity duringhypnosis Similar increases in occipital rCBF andor slowEEG activity had been observed in another study onhypnosis (Maquet et al 1999) and in states of decreasedvigilance (Paus et al 1997) meditation (Lou et al 1999)and slow wave sleep (Kajimura et al 1999 Hofle et al1997) These effects are consistent with our previousproposition that hypnotic induction produces a globaldecrease in cross-modality suppression in unattendedsensory channels leading to a relative disinhibitionof cortical activity (see Paus et al 1997 KawashimaOrsquoSullivan amp Roland 1995)

In contrast negative correlations between rCBF andmental absorption were observed over both occipitallobes (Table 2 Figure 3B) Consistently occipital rCBFwas correlated negatively with thalamic rCBF at theabsorption-specific site (Table 3) These contrastingeffects imply that variations in occipital rCBF are asso-ciated with separate portions of the variance in relaxa-tion and absorption (Note that although absorptionand relaxation were significantly correlated the variancein absorption was largely independent of relaxation see

Rainville et al 897

Methods) For a given level of relaxation the increasein hypnotic absorption could reflect the concurrentengagement of the lsquolsquoexecutive attentional networkrsquorsquowhich exerts an opposite effect over brain areas sub-serving unattended sensory channels (ie a relativefacilitation of cross-modality suppression)

Hypnosis as a State of Consciousness

The representation of the body-self is central to theneurophenomenology of consciousness (Metzinger2000) In the Introduction we have proposed that theinduction of hypnosis produces global changes in sub-jective experience reflecting a modulation of basicaspects of the body-self representation Consistentlythe PET results indicate that hypnosis involves changesin activity within brain structures essential for the basicregulation of states of consciousness self-monitoringand self-regulation Furthermore changes in relaxationand absorption are precursors (although they may notbe essential) to other hypnosis-related effects such asthe diminished tendency to judge monitor and censorthe suspension of usual orientation toward time loca-tion andor sense of self and the experience of onersquosown response as automatic or extra-volitional (Price1996) These dimensions of experience also rely criticallyon self-representation and may depend at least partly oncerebral areas shown here to be involved in hypnosisAmong those changes the increased feeling of automa-ticity an altered feeling of agency may be the mostdistinctive aspect of hypnotic phenomenology (Weitzen-hoffer 1980) Interestingly the sense of agency hasrecently been suggested to involve areas that displayconsistent changes in activity during hypnosis such asthe right inferior parietal cortex the precuneus and thesomatosensory cortices (Blakemore amp Decety 2001Ruby amp Decety 2001) The modulation of activityobserved here within those areas is consistent withthe interpretation that hypnosis produces changes inself-representation construed as an essential element forconscious experience

Conclusion

The present study used self-ratings of subjective feelingsof mental relaxation and mental absorption to map brainareas involved in hypnosis We replicated previous find-ings and further demonstrated that hypnotic relaxationand absorption reflect changes in brain activity withinregions involved in the control of consciousness statesand in self-regulation such as the brainstem the thala-mus and the ACC The coordinated activity within thesestructures and other absorption-related areas such asthe ventrolateral frontal and right posterior parietalcortices has been previously shown to underlie theregulation of the content of consciousness throughmechanisms of executive attention We must recognize

that our findings are correlative in nature and arerelevant to hypnosis to the extent that mental relaxationand absorption are conceived as basic experientialdimensions that characterize hypnotic phenomenaWe further speculate that these changes in subjectiveexperience and brain activity may contribute to otherhypnosis-related effects such as the altered feeling ofagency experienced during hypnosis These findings areconsistent with the notion that hypnotic states areachieved through the modulation of activity within adistributed network of cerebral structures involved inthe regulation of consciousness states

METHODS

Subjects

Ten right-handed subjects (4 men 6 women) wereselected from a group of 22 volunteers as a part of astudy on the hypnotic modulation of pain (Hofbaueret al 2001) Hypnotic susceptibility was assessed usingthe SHSS-A administered between scans (range 111ndash1011 mean plusmn SD 69 plusmn28) The Ethics Committee ofthe Montreal Neurological Institute (MNI) approved allprocedures and subjects signed a consent form describ-ing the procedure and affirming their right to withdrawfrom the experiment without prejudice

Experimental Procedure

We report the results obtained in eight scans acquired ina restful baseline and hypnosis condition Hypnoticinduction started immediately after Scan 4 and wassustained in the remaining scans by repeating inductioninstructions between scans Instructions included sug-gestions for (1) increased physical and mental relaxa-tion (2) comfortable feeling of warmth heaviness anddrowsiness (3) sustained passive attention to theexperimenterrsquos voice and to the instructions and (4)decreased concern with and orientation to external andinternal (mental) sources of distraction No specificinstruction for visual imagery was included During allscans the subjectsrsquo eyes were closed and their left handwas immersed in warm or painfully hot water Pain-related activation and four additional scans performedwith suggestions for pain modulation are reported else-where (Hofbauer et al 2001)

Self-Ratings of Mental Relaxation and Absorption

After each scan subjects were instructed to rate (0ndash10)(1) their level of tensionndashrelaxation with lsquolsquo10 being themost relaxed and at ease you can bersquorsquo and (2) their levelof sustained focus of attention with lsquolsquo10 being the mostabsorbed and the largest amount of sustained focusedattention you can gatherrsquorsquo Ratings of relaxation andabsorption were transformed using the rank within sub-jects to (1) control for individual differences (2) prevent

898 Journal of Cognitive Neuroscience Volume 14 Number 6

scaling biases and (3) parallel the analysis of rCBF dataSubjects rated pain on separate scales (0ndash100) Hypno-sis-related increases in relaxation and absorption did notinteract with the stimulation condition (pain vs warmstimulation prsquos gt 10) neither relaxation nor absorptioncorrelated significantly with pain ratings (all prsquos gt 10)and pain was not altered by hypnosis alone [t(9) = 069p = 51]

PET Imaging Methods

rCBF was measured using the H215O bolus injection

method (10 millicuriesscan) without arterial blood sam-pling (Herscovitch Markham amp Raichle 1983) with ahigh-resolution PET scanner operated in 3-D acquisitionmode (Siemens ECAT HR+ 63 slices) Stimulus onsetwas simultaneous with bolus injection and 1-min acquis-ition scans started about 15 sec postinjection (interscaninterval of 12ndash15 min) Data from the first 40 sec ofacquisition were reconstructed and analyzed Each sub-ject also underwent a high-resolution anatomical MRI(160 1-mm sagittal slices acquired on a Philips 15-TGyroscan system) Each PET and MRI volume wasaligned and transformed using software developed atthe MNI to match the MNI standardized Talairach space(Collins Neelin Peters amp Evans 1994 Talairach ampTournoux 1988) PET volumes were smoothed (FWHM= 14 mm) and normalized to the average brain countPeak and cluster analyses were performed (FristonWorsley Frackowiak Mazziotta amp Evans 1994 WorsleyEvans Marrett amp Neelin 1992)

Reliability of Hypnosis-Related Effects

A first analysis was performed using the subtractionmethod (Hypnosis minus Baseline) to evaluate thereliability of the effects reported in our previous study(Table 2 in Rainville Hofbauer et al 1999) We consid-ered that hypnosis-related changes in rCBF were repli-cated when a significant peak was observed within oneresel (Worsley et al 1992) of the peak sites reported inour previous study or when the peak sites were within asignificant cluster

Regression of rCBF on Self-Ratings of Relaxationand Absorption

Regression analyses were used to test the relationbetween ratings and rCBF (GLM) Subject- and stimu-lus-related effects were removed first (ANCOVA) andthe significance of the regression slope between thecovariate of interest and rCBF was estimated usingt tests Relaxation-specific and absorption-specific effectswere further tested using ANCOVAs to remove thevariance shared between absorption and relaxation(R2 = 42 p lt 001) The statistical criterion was setto t gt 258 (two-tailed uncorrected p lt 01) in the

directed searches restricted to the brainstem the thala-mus and the ACC (Table 1 Figure 2) Global searcheffects are significant ( p lt 05) based on peak (t valuegt 420) andor clusters analysis after a correction formultiple comparisons over the gray matter volume(uncorrected p lt 0001) (Table 2 Figure 3)

Thalamic Covariations

A covariation analysis was performed in which the rCBFmeasured in the thalamus was used as the covariate ofinterest after accounting for subject- and stimulus-related variance (ANCOVA see Tables 1 and 3) Becausewe were mainly interested in the relationship betweenthe activity in the thalamus and other absorption-relatedsites the threshold for statistical significance was set tot = 370 ( p = 05 uncorrected p lt 0008) based on thevolume defined by the sum of clusters of voxels showingsignificant absorption-specific effects (186 cm3 seeWorsley et al 1992)

Acknowledgments

We thank R Adolphs S Anderson A Bechara A R DamasioH Damasio Susan Lutgendorf J Parvizi and D Tranel fortheir comments on preliminary versions of the manuscriptPET analyses were performed using the software DOTdeveloped by Sylvain Milot and the MINC programs developedby Peter Neelin at the McConnell Brain Imaging Center of theMontreal Neurological Institute This study was supported bythe Medical Research Council (MRC) of Canada Dr Rainvillewas supported by the Medical Research Council of Canada andthe Human Frontier Science Program and Dr Hofbauer wassupported by the Fonds pour la recherche en sante du Quebecand the Royal Victoria Hospital Research Institute

Reprint requests should be sent to Pierre Rainville Faculte deMedecine dentaire Universite de Montreal CP 6128 SuccCentre-ville Montreal Qc H3C 3J7 Canada or via e-mailpierrerainvilleumontrealca

REFERENCES

Aston-Jones G Rajkowski J amp Cohen J (1999) Role of locuscoeruleus in attention and behavioral flexibility BiologicalPsychiatry 46 1309 ndash1320

Badgaiyan R D amp Posner M I (1998) Mapping the cingulatecortex in response selection and monitoring Neuroimage7 255 ndash260

Balthazard C G amp Woody E Z (1992) The spectral analysisof hypnotic performance with respect to lsquolsquoabsorptionrsquorsquoInternational Journal of Clinical and ExperimentalHypnosis 40 21ndash43

Banyai E I amp Hilgard E R (1976) A comparison ofactive-alert hypnotic induction with traditional relaxationinduction Journal of Abnormal Psychology 85 218 ndash224

Blakemore S J amp Decety J (2001) From the perception ofaction to the understanding of intention Nature ReviewsNeuroscience 2 561 ndash567

Braun A R Balkin T J Wesenten N J Carson R EVarga M Baldwin P Selbie S Belenky G amp HerscovitchP (1997) Regional cerebral blood flow throughout the

Rainville et al 899

sleep ndashwake cycle An H2(15)O PET study Brain 1201173 ndash1197

Bush G Luu P amp Posner M I (2000) Cognitive andemotional influences in anterior cingulate cortex Trendsin Cognitive Sciences 4 215 ndash222

Chalmers D J (2000) What is a neural correlate ofconsciousness In T Metzinger (Ed) Neural correlatesof consciousness Empirical and conceptual questions(pp 17ndash39) Cambridge MIT Press

Coe W C amp Sarbin T R (1977) Hypnosis from thestandpoint of a contextualist Annals of the New YorkAcademy of Sciences 296 2ndash13

Cohen J D Botvinick M amp Carter C S (2000) Anteriorcingulate and prefrontal cortex Whorsquos in control NatureNeuroscience 3 421 ndash423

Collins D L Neelin P Peters T M amp Evans A C (1994)Automatic 3D intersubject registration of MR volumetric datain standardized Talairach space Journal of ComputerAssisted Tomography 18 192 ndash205

Coull J T Frackowiak R S amp Frith C D (1998) Monitoringfor target objects Activation of right frontal and parietalcortices with increasing time on task Neuropsychologia 361325 ndash1334

Coull J T amp Nobre A C (1998) Where and when to payattention The neural systems for directing attention tospatial locations and to time intervals as revealed by bothPET and fMRI Journal of Neuroscience 18 7426 ndash7435

Crawford H J (1994) Brain dynamics and hypnosisAttentional and disattentional processes InternationalJournal of Clinical and Experimental Hypnosis 42204 ndash232

Crawford H J amp Gruzelier J H (1992) A midstream view ofthe neuropsychophysiology of hypnosis Recent researchand future directions In E Fromm amp M R Nash (Eds)Contemporary hypnosis research (pp 227 ndash266) New YorkGuilford Press

Crawford H J Knebel T Kaplan L Vendemia J M C XieM Jamison S amp Pribram K H (1998) Hypnotic analgesia1 Somatosensory event-related potential changes to noxiousstimuli and 2 Transfer learning to reduce chronic low backpain International Journal of Clinical and ExperimentalHypnosis 46 92ndash132

Damasio A R (1999) The feeling of what happens Body andemotion and the making of consciousness New YorkHartcourt Brace

De Pascalis V Magurano M R amp Bellusci A (1999) Painperception somatosensory event-related potentials andskin conductance responses to painful stimuli in high midand low hypnotizable subjects Effects of differential painreduction strategies Pain 83 499 ndash508

Devinsky O Morrell M J amp Vogt B A (1995) Contributionsof anterior cingulate cortex to behaviour Brain 118279 ndash306

Fiset P Paus T Daloze T Plourde G Meuret PBonhomme V Hajj-Ali N Backman S B amp Evans A C(1999) Brain mechanisms of propofol-induced loss ofconsciousness in humans A positron emission tomographicstudy Journal of Neuroscience 19 5505 ndash5513

Friston K J Worsley K J Frackowiak R S J Mazziotta J Camp Evans A C (1994) Assessing the significance of focalactivation using their spatial extent Human Brain Mapping1 214ndash220

Gitelman D R Alpert N M Kosslyn S Daffner K ScintoL Thompson W amp Mesulam M M (1996) Functionalimaging of human right hemispheric activation forexploratory movements Annals of Neurology 39 174ndash179

Gitelman D R Nobre A C Parrish T B LaBar K S KimY H Meyer J R amp Mesulam M (1999) A large-scale

distributed network for covert spatial attention Furtheranatomical delineation based on stringent behavioural andcognitive controls Brain 122 1093 ndash1106

Gruzelier J (1998) A working model of the neurophysiologyof hypnosis A review of evidence Contemporary Hypnosis15 3ndash21

Henson R N A Rugg M D Shallice T amp Dolan R J (2000)Confidence in recognition memory for words Dissociatingright prefrontal roles in episodic retrieval Journal ofCognitive Neuroscience 12 913 ndash923

Henson R N A Rugg M D Shallice T Joseph O ampDolan R J (1999) Recollection and familiarity inrecognition memory An event-related functional magneticresonance imaging study Journal of Neuroscience 193962 ndash3972

Herscovitch P Markham J amp Raichle M E (1983) Brainblood flow measured with intravenous H2(15)O I Theoryand error analysis Journal of Nuclear Medicine 24782 ndash789

Hofbauer R K Rainville P Duncan G H amp Bushnell M C(2001) Cortical representation of the sensory dimension ofpain Journal of Neurophysiology 86 402 ndash411

Hofle N Paus T Reutens D Fiset P Gotman J EvansA C amp Jones B E (1997) Regional cerebral blood flowchanges as a function of delta and spindle activity duringslow wave sleep in humans Journal of Neuroscience 174800 ndash4808

Jeanmonod D Magnin M amp Morel A (1996) Low-thresholdcalcium spike bursts in the human thalamus Commonphysiopathology for sensory motor and limbic positivesymptoms Brain 119 363ndash375

Kajimura N Uchiyama M Takayama Y Uchida S Uema TKato M Sekimoto M Watanabe T Nakajima THorikoshi S Ogawa K Nishikawa M Hiroki M Kudo YMatsuda H Okawa M amp Takahashi K (1999) Activityof midbrain reticular formation and neocortex during theprogression of human non-rapid eye movement sleepJournal of Neuroscience 19 10065 ndash10073

Kawashima R OrsquoSullivan B T amp Roland P E (1995)Positron-emission tomography studies of cross-modalityinhibition in selective attentional tasks Closing the lsquolsquomindrsquoseyersquorsquo Proceedings of the National Academy of SciencesUSA 92 5969 ndash5972

Kim Y H Gitelman D R Nobre A C Parrish T BLaBar K S amp Mesulam M M (1999) The large-scaleneural network for spatial attention displays multifunctionaloverlap but differential asymmetry Neuroimage 9269 ndash277

Kinomura S Larsson J Gulyas B amp Roland P E (1996)Activation by attention of the human reticular formationand thalamic intralaminar nuclei Science 271 512ndash515

Kosslyn S M Thompson W L Costantini-Ferrando M FAlpert N M amp Spiegel D (2000) Hypnotic visual illusionalters color processing in the brain American Journal ofPsychiatry 157 1279 ndash1284

Laureys S Faymonville M E Luxen A Lamy M Franck Gamp Maquet P (2000) Restoration of thalamocorticalconnectivity after recovery from persistent vegetative stateLancet 355 1790ndash1791

Lou H C Kjaer T W Friberg L Wildschiodtz G Holm Samp Nowak M (1999) A 15OndashH2O PET study of meditationand the resting state of normal consciousness HumanBrain Mapping 7 98ndash105

Maquet P Degueldre C Delfiore G Aerts J Peters J MLuxen A amp Franck G (1997) Functional neuroanatomyof human slow wave sleep Journal of Neuroscience 172807 ndash2812

Maquet P Faymonville M E Degueldre C Delfiore G

900 Journal of Cognitive Neuroscience Volume 14 Number 6

Franck G Luxen A amp Lamy M (1999) Functionalneuroanatomy of hypnotic state Biological Psychiatry 45327 ndash333

Metzinger T (2000) The subjectivity of subjective experienceA representationalist analysis of the first-person perspectiveIn T Metzinger (Ed) Neural correlates of consciousnessEmprical and conceptual questions (pp 285 ndash306)Cambridge MIT Press

Nobre A C Sebestyen G N Gitelman D R MesulamM M Frackowiak R S amp Frith C D (1997) Functionallocalization of the system for visuospatial attention usingpositron emission tomography Brain 120 515 ndash533

Pardo J V Fox P T amp Raichle M E (1991) Localization of ahuman system for sustained attention by positron emissiontomography Nature 349 61ndash64

Paus T (2001) Primate anterior cingulate cortex Wheremotor control drive and cognition interface NatureReviews Neuroscience 2 417 ndash424

Paus T Koski L Caramanos Z amp Westbury C (1998)Regional differences in the effects of task difficulty andmotor output on blood flow response in the human anteriorcingulate cortex A review of 107 PET activation studiesNeuroReport 9 R37ndashR47

Paus T Zatorre R J Hofle N Caramanos Z Gotman JPetrides M amp Evans A C (1997) Time-related changesin neural systems underlying attention and arousal duringthe performance of an auditory vigilance task Journal ofCognitive Neuroscience 9 392ndash408

Peyron R Garcia-Larrea L Gregoire M C Costes NConvers P Lavenne F Mauguiere F Michel D ampLaurent B (1999) Haemodynamic brain responses to acutepain in humansmdashSensory and attentional networks Brain122 1765 ndash1779

Picard N amp Strick P L (1996) Motor areas of the medial wallA review of their location and functional activation CerebralCortex 6 342 ndash353

Portas C M Howseman A M Josephs O Turner R ampFrith C D (1998) A specific role for the thalamus inmediating the interaction of attention and arousal inhumans Journal of Neuroscience 18 8979 ndash8989

Posner M I amp Rothbart M K (1998) Attentionself-regulation and consciousness Philosophical

Transactions of the Royal Society of London Series BBiological Sciences 353 1915 ndash1927

Price D D (1996) Hypnotic analgesia Psychological andneural mechanisms In J Barber (Ed) Hypnosis andsuggestions in the treatment of pain (pp 67ndash84) NewYork Norton

Price D D amp Barrell J J (1980) An experiential approachwith quantitative methods A research paradigm Journal ofHumanistic Psychology 20 75ndash95

Rainville P Carrier B Hofbauer R K Bushnell M C ampDuncan G H (1999) Dissociation of pain sensory andaffective dimensions using hypnotic modulation Pain 82159 ndash171

Rainville P Duncan G H Price D D Carrier B ampBushnell M C (1997) Pain affect encoded in humananterior cingulate but not somatosensory cortex Science277 968 ndash971

Rainville P Hofbauer R K Paus T Duncan G H BushnellM C amp Price D D (1999) Cerebral mechanisms ofhypnotic induction and suggestion Journal of CognitiveNeuroscience 11 110ndash125

Ruby P amp Decety J (2001) Effect of subjective perspectivetaking during simulation of action A PET investigation ofagency Nature Neuroscience 4 546 ndash550

Steriade M amp McCarley R W (1990) Brainstem control ofwakefulness and sleep New York Plenum

Szechtman H Woody E Bowers K S amp Nahmias C(1998) Where the imaginal appears real A positronemission tomography study of auditory hallucinationsProceedings of the National Academy of Sciences USA95 1956 ndash1960

Talairach J amp Tournoux P (1988) Co-planar stereotaxicatlas of the human brain New York Thieme

Tellegen A amp Atkinson G (1974) Openness to absorbingand self-altering experiences (lsquolsquoabsorptionrsquorsquo) a trait relatedto hypnotic susceptibility Journal of Abnormal Psychology83 268 ndash277

Toma K Honda M Hanakawa T Okada T Fukuyama HIkeda A Nishizawa S Konishi J amp Shibasaki H (1999)Activities of the primary and supplementary motor areasincrease in preparation and execution of voluntary musclerelaxation An event-related fMRI study Journal ofNeuroscience 19 3527 ndash3534

Varela F J amp Shear J (1999) First-person methodologiesWhat why and how Journal of Consciousness Studies 61ndash14

Vingoe F J (1968) The development of a group alert-trancescale International Journal of Clinical and ExperimentalHypnosis 16 120 ndash132

Vingoe F J (1973) Comparison of the Harvard Group Scaleof Hypnotic Susceptibility Form A and the Group AlertTrance Scale in a university population InternationalJournal of Clinical and Experimental Hypnosis 21169 ndash179

Vogt B A amp Gabriel M (1993) Neurobiology of cingulatecortex and limbic thalamus A comprehensive handbookBoston Birkauser

Weitzenhoffer A M (1980) Hypnotic susceptibility revisitedAmerican Journal of Clinical Hypnosis 22 130 ndash146

Willoch F Rosen G Tolle T R Oslashye I Wester H J BernerN Schwaiger M amp Bartenstein P (2000) Phantom limbpain in the human brain Unravelling neural circuitries ofphantom limb pain sensations using positron emissiontomography Annals of Neurology 48 842 ndash849

Worsley K J Evans A C Marrett S amp Neelin P (1992)A three-dimensional statistical analysis for CBF activationstudies in human brain Journal of Cerebral Blood Flow andMetabolism 12 900 ndash918

Rainville et al 901

Page 3: Hypnosis Modulates Activity in Brain Structures Involved in the …pineda/COGS175/readings/Rain... · 2005. 2. 28. · Hypnosis Modulates Activity in Brain Structures Involved in

(Hofbauer et al 2001 Rainville et al 1997 RainvilleCarrier Hofbauer Bushnell amp Duncan 1999 RainvilleHofbauer et al 1999)

Heart rate measured before and during scans did notchange significantly following the induction of hypnosis(see Hofbauer et al 2001)

Reliability of Hypnosis-Related Changes in rCBF

The reliability of the effects of hypnosis on cerebralactivity was examined by comparing the results of asubtraction analysis (Hypnosis minus Baseline condi-tions) with those of our previous study (see Table 2 inRainville Hofbauer et al 1999) Our current resultsreplicated the previously reported rCBF increases inboth occipital lobes the right Sylvian region (peaks inthe inferior frontal and superior temporal gyri) the leftinsula (more anterior and bilateral in the present study)and the right ACC However ACC activation was moreextensive here with significant clusters of activatedvoxels covering multiple areas of the ACC and peaksfound in both the right and left hemispheres inthe middle rostral and perigenual ACC The frontalincreases in rCBF extended further bilaterally in thecentral region and in the medial frontal and prefrontalareas (superior frontal and orbito-frontal) Decreases in

rCBF observed in our previous study were replicated inthe right inferior parietal lobule the precuneus and theleft posterior temporal cortices (bilateral here) Theeffects previously reported and not replicated here arethe increases in the right parietal operculum and thedecreases in the medial frontal cortex and the posteriorcingulate gyrus (here medial parietal decreases werelimited to the precuneus) Occipital increases in rCBFwere again stronger in the warm stimulation conditionand prefrontal increases were stronger in the painfulstimulation condition These results largely confirm thereliability of the changes in rCBF associated with theinduction of hypnosis

Mental Relaxation- and Absorption-Related Effects

Directed Search over the Brainstem the Thalamus andthe ACC

The functional role of particular structures thought to beinvolved in the production of hypnosis was assessed byanalyzing the degree of correlation between rCBF inthese regions and subjectsrsquo estimates of the experientialindices of hypnosis (mental relaxation and absorption)(Table 1 Figure 2) Increases in mental relaxation werecorrelated with rCBF decreases in the mesencephalictegmentum of the brainstem (Figure 2A) and with

Table 1 Peak t Values Observed in the Directed Search Areas in Regression Analyses on Self-Ratings and Thalamic rCBF

Relaxation Relaxation-Specific Absorption Absorption-SpecificThalamus

Covariation

Brainstem iexcl267(iexcl3 iexcl33 iexcl12)

iexcl281(iexcl1 iexcl38 iexcl17)

ns +278(1 iexcl26 iexcl22)

+312(13 iexcl26 iexcl15)

+287(3 iexcl32 iexcl24)

Thalamus ns iexcl368(iexcl3 iexcl16 12)

+260(iexcl1 iexcl18 12)

+445(iexcl3 iexcl16 12)

+350(17 iexcl11 2)

ACC

mid +260(1 15 35)

ns ns ns +387(8 13 44)

rostral ns iexcl368(5 37 45a)

+345(1 29 30)

+432(3 32 39a)

+382(1 43 32a)

perigenual +302(5 34 9)

ns +296(8 32 9)

ns ns

Regression models were used to evaluate the slope of the relationship between relaxation or absorption ratings and rCBF Relaxation-specific andabsorption-specific effects were further tested after accounting for variance associated with absorption and relaxation respectively (see Methods)Thalamic covariations were tested in a regression model evaluating the relationship between rCBF in the thalamus at the site of absorption-specificactivity and rCBF in the brainstem the rest of the thalamus and the ACC Stereotaxic coordinates are given for each peak according to the atlas ofTalairach and Tournoux (1988) (x y z = lateral anterior superior)

ns = no significant peak found (iexcl258 lt t lt 258 p gt 01)

p lt 01 p lt 001 p lt 0001 (uncorrected p values)aPeak is over the right medial superior frontal gyrus within a cluster extending into the ACC at the site of significant absorption-related effect(x y z = 1 29 30)

Rainville et al 889

increases in the middle and perigenual ACC (Figure 2B)Increases in absorption were correlated with rCBFincreases in the thalamus and in the rostral and peri-genual ACC (Figure 2C)

The specificity of any changes in the rCBF associatedwith either mental relaxation (relaxation-specific) orabsorption (absorption-specific) was further examinedusing ANCOVA (see Methods) to remove the varianceshared with the other factormdashabsorption and relaxa-tion respectively (Table 1) Relaxation-specific negativecorrelations were found in the brainstem in the thala-mus and in the superior frontal gyrus in a clusterof significant voxels extending over the rostral ACCAbsorption-specific effects confirmed the significant pos-itive correlation between mental absorption and rCBFin the thalamus and in the rostral ACC and furtherrevealed a significant positive peak in the upper ponsof the brainstem (Figure 2D Table 1) Although mentalrelaxation and absorption both increased during hyp-nosis these results demonstrate that the negative cor-relation in the mesencephalic brainstem and thethalamus appears to be exclusively associated with

mental relaxation while the positive correlations inthe upper pons the thalamus and the mid-ACC appearto be exclusively associated with mental absorption

Global Searches

Results of the global searches show additional differ-ences between the patterns of activity related to mentalrelaxation and absorption In the frontal lobe increasesin prefrontal rCBF were positively correlated primarilywith mental absorption (Table 2) while increases in theprecentral region were positively correlated with bothrelaxation (Figure 3A) and absorption (Table 2) Con-sistently after removing the variance shared betweenmental relaxation and absorption positive absorption-specific correlations (Table 2 Figure 3B) and negativerelaxation-specific correlations (Table 2) were observedin prefrontal areas while most precentral effects did notreach significance

Posterior cortical areas displayed a mixed pattern ofresults Negative correlations observed in both temporallobes were more reliably related to mental relaxation

Figure 2 Statistical (t) maps overlaid on a midsagittal view of a single-subject MRI anatomical image showing the location of significant positive(red arrows) and negative (blue arrow) regression slopes between rCBF and self-ratings in the three regions of interest (brainstem thalamus andACC see Methods) (A) A negative regression peak is found with relaxation in the mesencephalic tegmentum and (B) positive regression peaksare found in the middle (mACC) and perigenual (pACC) portion of the ACC (note the reversal of the color scale) (C) Positive regression peaksare found with absorption in the thalamus and in the rostral ACC (rACC) and pACC (D) The regression of rCBF on absorption ratings afteraccounting for relaxation-related effects confirmed the positive regression peaks specific to absorption in the thalamus and rACC This analysisfurther revealed an additional positive peak in the upper pons Color scales in C and D are as in B Stereotaxic coordinates of peaks are reportedin Table 1

890 Journal of Cognitive Neuroscience Volume 14 Number 6

than absorption and the relaxation-related effects heldafter accounting for variance in absorption (Table 2mdashrelaxation-specific) Additional sites of relaxation-specificeffects included negative correlations in the right parie-tal operculum and lobule and positive correlations in theright precuneus the left inferior parietal lobule and thebilateral occipital cortices (Table 2mdashrelaxation-specific)

The effects associated with absorption in the posteri-or cortices were strikingly different from the effects ofrelaxation After accounting for relaxation-related var-iance we observed both positive and negative absorp-tion-specific correlations in both the right and leftparietal lobules (see Table 2mdashabsorption-specific) Inthe inferior parietal lobules positive and negative cor-relations dominated in the right and left hemispheresrespectively (Figure 3B) Strong negative correlationswere also observed over the right precuneus theposterior cingulate cortex and both occipital lobes(Figure 3B)

Additional statistical trends directly relevant to ourhypotheses were also observed in the somatosensorycortices where rCBF was negatively correlated with men-tal relaxation (see Figure 3A right S1 peak coordinates44 iexcl35 59 t = iexcl286 p-uncorrected = 014 clusterp = 06 left S1 iexcl44 iexcl21 16 t = iexcl251 p-uncorrected =026 cluster analysis p gt 10 right parietal operculumS2 48 iexcl21 24 t = iexcl351 p-uncorrected = 003 clusterp gt 10 right posterior insula 44 iexcl4 15 t = iexcl296p-uncorrected = 011 cluster p gt 10)

Covariations with Thalamic rCBF

In our previous study thalamic activity was found tobe correlated with hypnosis-related ACC activity (seeTable 2 and Appendix in Rainville Hofbauer et al1999) and several studies suggest a pivotal role of thethalamus in arousal attention and consciousness andin the interaction between the brainstem and the ACC(eg Paus et al 1997 Paus 2001 Portas HowsemanJosephs Turner amp Frith 1998 Hofle et al 1997) Herewe tested the association between absorption-relatedactivity in the thalamus and activity in other sites ofabsorption-related changes using a covariation analysiscentered on the absorption-specific peak in the thala-mus reported in Table 1 Absorption-specific sites in thebrainstem (upper pons) and the ACC showed significantcovariations with thalamic rCBF (Table 1) Additionalregions where rCBF showed a positive correlation withthalamic rCBF included bilateral frontal sites in theinferior middle and superior frontal gyri extendingmedially into the right ACC and the right insula(Table 3) Many of those peak locations matched frontalsites specifically related to mental absorption (italicizedin Table 2) A strong positive peak was also observed inthe right inferior parietal lobule precisely at the loca-tion where rCBF correlated strongly and specificallywith mental absorption (compare Table 2 absorption-

specific and Table 3) Areas displaying negative corre-lation with thalamic rCBF were found bilaterally in theoccipital lobes consistent with the absorption-specificeffects reported in Table 2

DISCUSSION

The approach used in this study provided a descriptionof cerebral activity associated with specific changes inphenomenal experience produced by a standard hyp-notic induction We discuss in turn the evidence for theproduction of hypnotic phenomena the reliability ofhypnosis-related effects the effects associated with men-tal relaxation and absorption and the implications ofour results for a state theory of hypnosis

Hypnosis and Phenomenal Experience

The induction of hypnosis produced the expectedincreases in both mental relaxation and absorptionThese changes were positively correlated (see Methods)as predicted by the experiential model of hypnosisproposed by Price (1996) and the ability to maintainhypnotic relaxation and absorption depended upon thesubjectsrsquo hypnotic susceptibility The higher levels ofabsorption maintained in highly hypnotizable subjectsare consistent with the positive association betweenabsorption attentional processes and hypnotizabilitysuggested in previous studies (Crawford 1994 Baltha-zard amp Woody 1992 Tellegen amp Atkinson 1974) Theseresults and additional convergent observations de-scribed in our previous report of pain-related effects(Hofbauer et al 2001) and from several experimentsusing similar methodology (Rainville et al 1997 Rain-ville Carrier et al 1999) confirmed the reliable produc-tion of hypnotic phenomena

Reliability of Hypnosis-Related Effects on rCBF

The experimental conditions examined here and in thefirst 8 scans in our previous study were identicalmdashthesame hypnotic induction procedure was applied by twodifferent experimenters and the two separate groups ofsubjects tested had comparable mean hypnotic suscep-tibility scores (Rainville Hofbauer et al 1999) Theresults of the subtraction analysis largely replicated ourprevious findings as well as those reported by Maquetet al (1999) In comparison to our previous experimentdifferences in the methods were limited to the additionof relaxation and absorption ratings after the scans Thelarger areas of frontal activation including the precentralregion and the more restricted occipital activationobserved here may reflect the emphasis put on hypnoticrelaxation and absorption during the scans As thesedimensions of experience characterize standard hypno-tic induction procedures we submit that these differ-ences further emphasize the functional significance of

Rainville et al 891

Tab

le2

R

esul

tsof

the

Glo

bal

Sear

ches

ofC

ereb

ral

Regi

ons

whe

rerC

BF

Show

eda

Sign

ifica

ntR

egre

ssio

nw

ithR

elax

atio

nan

dAb

sorp

tion

Regi

onP

eak

Loca

tion

Rela

xati

onRe

laxa

tion

-Spe

cifi

cAb

sorp

tion

Abs

orpt

ion

-Spe

cifi

c

xy

zt

xy

zt

xy

zt

xy

zt

Fron

tal

(F)

RF

Pole

(BA

10)

ndash34

562

iexcliexcl4

81

ndash28

555

+4

21

Rla

tF

Orb

ital

g(B

A11

)ndash

1946

iexcl20

iexcliexcl4

29

ndash19

44iexcl

20+

47

5

Rm

iddl

eF

g(B

A46

)ndash

3646

26iexcl

381

ndash34

4626

+3

79

Rin

fF

g(B

A47

)ndash

ndash47

34iexcl

18+

373

ndash

Rin

fF

g(B

A45

)ndash

478

15iexcl

386

5520

11+

352

ndash

Ra

nt

insu

lai

nf

Fg

(BA

144

4)ndash

4015

6iexcl

377

4310

2+

358

4013

5+

48

1

Rsu

pF

gc

ingu

late

g(B

A8

32)

ndash5

3745

iexcl3

68ndash

332

39+

43

2

Rsu

pF

g(B

A6)

ndashndash

1320

59+

369

1522

57+

43

3

Rm

edia

lsu

pF

g(B

A6)

ndashndash

3iexcl

466

+4

23

3iexcl

766

+3

92

Lla

tF

Orb

ital

g(B

A11

)ndash

ndashiexcl

3041

iexcl21

+3

68iexcl

3143

iexcl18

+3

76

Lm

iddl

eF

g(B

A8)

ndashndash

iexcl46

1535

+4

10iexcl

4410

29+

328

Lm

iddl

eF

g(B

A46

)ndash

ndashiexcl

3637

18+

43

8iexcl

3839

24+

407

La

nt

insu

lai

nf

Fg

(BA

144

4)ndash

ndashndash

iexcl34

817

+4

25

Lsu

pF

g(B

A6)

ndashndash

ndashiexcl

266

56+

416

Lsu

p

Fg

(BA

6)ndash

ndashiexcl

11iexcl

466

+3

68ndash

Cen

tral

Rp

rece

ntra

lg

(BA

4)54

iexcl4

53+

51

6ndash

52iexcl

453

+5

05

ndash

Rp

rece

ntra

lg

(BA

4)42

iexcl7

50+

49

4ndash

ndashndash

Rp

rep

ostc

entr

alg

(BA

41

3)ndash

ndash36

iexcl16

36+

378

ndash

Lpr

ecen

tral

mid

dle

Fg

(BA

46)

iexcl35

iexcl6

53+

398

ndashndash

ndash

Lpr

ecen

tral

g(B

A4)

iexcl47

iexcl16

47+

44

3ndash

iexcl48

iexcl14

50+

43

6ndash

Lpr

epo

stce

ntra

lg

(BA

41

3)ndash

iexcl30

iexcl37

60+

403

ndash

Tem

pora

l(T

)R

mid

dle

T

g(B

A21

)60

iexcl33

iexcl15

iexcl5

71

59iexcl

33iexcl

13iexcliexcl

55

1ndash

ndash

Rm

iddl

eT

g

(BA

37)

56iexcl

45iexcl

9iexcl

59

1ndash

55iexcl

47iexcl

6iexcliexcl

44

1ndash

Lpa

rahi

ppoc

amp

alg

(BA

353

6)iexcl

36iexcl

23iexcl

18iexcl

413

ndashndash

ndash

Lin

fT

g

fusi

form

g(B

A37

)iexcl

52iexcl

42iexcl

20iexcl

52

4iexcl

59iexcl

44iexcl

12iexcliexcl

43

3iexcl

48iexcl

44iexcl

20iexcliexcl

44

6ndash

892 Journal of Cognitive Neuroscience Volume 14 Number 6

Pari

etal

(P)

RP

oper

culu

m(B

A40

)ndash

32iexcl

3027

iexcl3

55ndash

ndash

Rin

fP

lo

bule

(BA

40)

ndash56

iexcl40

50iexcl

377

ndash56

iexcl44

50+

42

4

RP

lobu

le(B

A40

7)

39iexcl

4945

iexcl4

87

ndash38

iexcl47

45iexcliexcl

44

334

iexcl56

42+

383

Rsu

pP

lobu

le(B

A7)

ndashndash

21iexcl

5062

iexcliexcl4

45

21iexcl

5260

iexcl4

09

Rpr

ecun

eus

(BA

7)ndash

5iexcl

5645

+5

33

ndash5

iexcl56

45iexcliexcl

51

0

Prec

uneu

sp

ost

Cin

gg

(BA

731

)ndash

ndashndash

0iexcl

649

iexcliexcl5

05

Lin

fP

lobu

le(B

A40

)ndash

iexcl30

iexcl37

60+

403

ndashiexcl

35iexcl

3550

iexcliexcl4

48

Lin

fP

lobu

le(B

A40

)ndash

ndashndash

iexcl52

iexcl56

47+

370

Occ

ipit

al(O

)Li

ngua

lg

pos

tC

ing

g(B

A18

31)

ndash0

iexcl66

9+

42

6ndash

ndash

Rin

fO

g

(BA

19)

ndash43

iexcl71

iexcl6

+3

6843

iexcl75

5iexcliexcl

44

443

iexcl75

iexcl3

iexcliexcl5

17

Rli

ngu

alg

(BA

18)

ndash4

iexcl76

3+

46

4ndash

7iexcl

782

iexcliexcl4

68

Rcu

neu

s(B

A18

)ndash

12iexcl

8327

+5

20

ndashndash

Rsu

pO

g

(BA

19)

ndash17

iexcl81

38+

55

9ndash

15iexcl

8033

iexcliexcl6

02

Rsu

pO

g

(BA

19)

30iexcl

8726

+4

07

RO

po

le(B

A18

)ndash

27iexcl

929

+4

85

ndash27

iexcl92

8iexcliexcl

53

5

Lfu

sifo

rmg

(BA

181

9)ndash

iexcl40

iexcl78

iexcl3

+3

59ndash

iexcl40

iexcl76

iexcl3

iexcliexcl4

46

Lsu

pO

g

prec

un

eus

(BA

197

)ndash

iexcl13

iexcl88

38+

407

iexcl8

iexcl76

36iexcliexcl

42

3iexcl

13iexcl

8739

iexcliexcl5

18

Llin

gual

g(B

A18

)c

ereb

ellu

mndash

ndashiexcl

17iexcl

76iexcl

18iexcl

351

ndash

Llin

gual

fusi

form

g(B

A18

19)

ndashiexcl

15iexcl

78iexcl

3+

47

2iexcl

27iexcl

83iexcl

11iexcliexcl

42

2iexcl

16iexcl

80iexcl

2iexcliexcl

56

2

Lsu

pO

g

(BA

19)

ndashiexcl

27iexcl

8327

+3

98ndash

iexcl27

iexcl83

29iexcl

419

LO

po

le(B

A18

)ndash

iexcl24

iexcl90

8+

53

8iexcl

26iexcl

880

iexcl4

18iexcl

24iexcl

905

iexcliexcl6

50

Subc

orti

cal

Tha

lam

us(s

eeT

able

1)ndash

iexcl3

iexcl16

12iexcl

368

ndashiexcl

3iexcl

1612

+4

45

Rpu

tam

enndash

ndash21

iexcl7

5+

401

24iexcl

46

+3

57

Lgl

obu

spa

llidu

sndash

ndashiexcl

19iexcl

13

+3

68iexcl

21iexcl

12

+4

41

Lce

rebe

llum

ndashiexcl

9iexcl

88iexcl

23iexcliexcl

42

9ndash

ndash

Rel

axat

ion

-sp

ecifi

can

dab

sorp

tio

n-s

pec

ific

effe

cts

wer

eex

amin

edaf

ter

rem

ovi

ng

the

vari

ance

asso

ciat

edw

ith

abso

rpti

on

and

rela

xati

on

resp

ecti

vely

(AN

CO

VA

se

eM

eth

od

s)T

he

linea

rsl

op

ebe

twee

nrC

BF

and

rati

ngs

issi

gnifi

can

tatp

eak

loca

tio

ns

liste

d(t

thre

sho

ld=

plusmn4

20i

nb

old

see

Met

hod

s)P

eaks

wit

htgt

+3

50or

tlt

iexcl3

50w

ith

ina

sign

ific

ant

clus

ter

(see

Met

hods

)are

also

indi

cate

dw

ith

thei

rco

ordi

nate

sP

eaks

clos

eto

or

wit

hin

regi

ons

wh

ere

sign

ific

ant

cova

riat

ions

wit

hth

alam

icrC

BF

wer

efo

und

are

ita

lici

zed

(see

Tab

le3

and

Met

hods

)P

eak

loca

tion

sar

eba

sed

onth

est

ereo

taxi

cat

las

of

Tal

aira

chan

dT

ourn

oux

(198

8)(x

=la

tera

ly

=an

teri

or

z=

supe

rior

)an

don

mor

phol

ogi

cal

lan

dmar

kson

the

mer

ged

PE

Tndash

MR

Iim

ages

(BA

=pr

obab

leB

rodm

annrsquo

sar

eaL

=

left

R

=

righ

tg

=gy

rus

ant

=an

teri

or

pos

t=

post

erio

rsu

p=

supe

rior

in

f=

infe

rior

)

Rainville et al 893

the underlying processes in the production of hypnoticstates as discussed below

Role of the Brainstem the Thalamus and the ACCin Hypnosis

Results of the regression analyses suggest that neuralactivity in the brainstem the thalamus and the ACCcontributes to the experience of being hypnotized Therelaxation-specific negative correlations in the mesen-

cephalic brainstem and the thalamus may reflect thewell-established contribution of brainstem and thalamicnuclei to the regulation of wakefulness and corticalarousal In functional brain imaging studies rCBFdecreases in the brainstem and the thalamus have beenassociated with decreased vigilance (Paus et al 1997)sleep (Kajimura et al 1999 Braun et al 1997 Hofleet al 1997 Maquet et al 1997) and the loss ofconsciousness produced by the anesthetic propofol(Fiset et al 1999) These effects and to some extent

Figure 3 Brain regionsshowing positive (redarrowheads) and negative(blue arrowheads) regres-sion peaks between rCBFand self-ratings of (A)relaxation and (B) absorp-tion after accounting forrelaxation-related variance(absorption-specific)Statistical t maps are super-imposed on the averageanatomical MRI (left is onthe left side) Slice locationsare indicated on the 3-Danatomical image of asingle subjectrsquos anatomicalMRI (A-positive) Positiverelaxation-related effectsare shown in the centralregion bilaterally (horizon-tal slice on the left) Apositive peak is shown inthe right superior occipitalgyrus (SOg) (coronal viewon the right note scalechange) (A-negative)A negative relaxation-related effect in the rightposterior parietal cortexis shown in horizontal(first from left) coronal(second) and lateralsagittal (third) views Theplus sign indicates the moreanterior location of thepeak positive regression inthe analysis of absorption-related effects as shown inB Additional negative cor-relations are shown in thebilateral middle and inferiortemporal gyri (second) andin the right somatosensorycortices (S1 S2 insula)(B-positive) A positiveabsorption-specific peak isshown in the right inferiorparietal lobule (first fromleft) The minus sign indicates the more posterior location of the negative regression peak in the analysis of relaxation-related effects as shown in

A Other peaks are shown on the midsagittal view in the thalamus and the anterior cingulate cortex (second from left) and in the left lenticularnuclei and bilateral prefrontal cortices (last three cuts from left) (B-negative) Negative absorption-related effects are shown in the left inferiorparietal lobule (first from left) in both occipital lobes (second and third from left) and in the precuneus (first and third) Stereotaxic coordinates ofpeaks are reported in Table 3 (see relaxation- and absorption-specific)

894 Journal of Cognitive Neuroscience Volume 14 Number 6

the present relaxation-related decrease in brainstemrCBF may reflect an attenuation of activity withinbrainstem cholinergic nuclei Such reduction has beenobserved during slow EEG activity before the onset ofsleep and during slow-wave sleep in animal studies(Steriade amp McCarley 1990) Consistent with this pos-sibility we previously reported an increase in slow(delta) EEG activity following hypnotic induction (Rain-ville Hofbauer et al 1999) Although hypnotic andsleep states are clearly distinct certain neurophysiolog-

ical mechanisms may be involved to a varying degree inthe production of both states

The positive association specifically observed betweenmental absorption and rCBF in the upper pons and thethalamus contrasts with the above relaxation-relatedeffect and is consistent with previous reports of atten-tion-related brain activation (Kinomura et al 1996) Thisactivity may reflect the involvement of the noradrenergicsystem of the locus coeruleus in focused attentionand possibly in the interaction between cortical arousal

Table 3 Cerebral Sites of Covariation with Thalamic rCBF at the Absorption-Specific Peak Coordinates (x = iexcl27 y = iexcl160z = 120)

Region Peak Location x y z t

Frontal (F) R medial sup F gACC (BA 624) 1 43 32 +382

R anterior cingulate gsup F g (BA 326) 8 13 44 +387

R inf F g (BA 44) 51 12 8 +387

R ant insula (BA 14) 38 12 5 +412

R sup F g (BA 6) 16 20 59 +371

R medial sup F g (BA 6) 3 iexcl6 63 +498

R medial sup F g (BA 6) 11 iexcl23 53 +412

L middle F g (BA 46) iexcl38 46 23 +381

L middle F g (BA 46) iexcl31 39 39 +374

L inf F g (BA 44) iexcl43 6 12 +430

L sup F g (BA 6) iexcl19 20 53 +340

L medial sup F g (BA 6) iexcl5 17 65 +353

L sup F g (BA 6) iexcl20 12 65 +283

Parietal R inf parietal lobule (BA 40) 56 iexcl44 50 +519

Occipital (O) R fusiform g (BA 19) 26 iexcl62 iexcl30 iexcliexcl515

R lingual g (BA 18) 7 iexcl78 6 iexcliexcl623

R sup O g (BA 19) 19 iexcl85 30 iexcliexcl714

R O pole (BA 18) 27 iexcl90 9 iexcliexcl751

L cuneus (BA 18) iexcl11 iexcl83 29 iexcliexcl633

L O pole (BA 18) iexcl23 iexcl88 6 iexcliexcl793

Subcortical R thalamus 17 iexcl11 2 +350

R brainstem 13 iexcl26 iexcl15 +312

R medial brainstem 3 iexcl32 iexcl24 +287

L cerebellum iexcl4 iexcl57 iexcl21 +409

L globus pallidus iexcl20 iexcl1 iexcl2 +302

L caudate nucleus iexcl12 6 20 +291

Positive and negative regression slopes are significant at sites listed based on cluster or peak analyses (peak t threshold ltgtplusmn370 in bold allpeaks reported with t lt 370 are within a significant cluster see Methods) Peaks in italic are also reported in Table 1 See legends to Tables 1 and 2and Methods for further explanation

Rainville et al 895

and attentional processes (ie increased attentionabsorption concurrent with decreased cortical arousalincreased relaxation) (Aston-Jones et al 1999) Theindirect nature of the rCBF measures and the relativelypoor resolution of the PET method require somecaution in evaluating the possible anatomo-functionalimplications of our results in the brainstem Howeverthe convergent findings observed in other brain imag-ing studies and the observations provided in animalstudies support the notion that ascending cholinergicand noradrenergic pathways may contribute differen-tially to the multiple dimensions of experience thatcharacterize hypnosis

The overall pattern of results found in the ACC likelyreflects the heterogeneity of functions associated withthis area (Devinsky Morrell amp Vogt 1995) The locationof the most posterior relaxation-related peak in the ACC(mACC) is consistent with our previous observationof ACC activation during hypnosis (Rainville Hofbaueret al 1999) This relaxation-related peak is only slightlyanterior to the motor area of the caudal ACC (Picard ampStrick 1996) and may be involved in the installment of arelaxed state (also see precentral area below) In con-trast a positive absorption-specific effect was observedin a more rostral region of the ACC (rACC) close to anegative relaxation-specific correlation (see Table 1)This area of the ACC has previously been involved inexecutive attention in the detection of errors and in themonitoring of conflict between competing cognitiveprocesses (Bush Luu amp Posner 2000 Cohen Botvinickamp Carter 2000 Badgaiyan amp Posner 1998 Posner ampRothbart 1998) A meta-analysis of PET studies inves-tigating cognitive functions further suggested that theincrease in activity within this sector of the ACC isrelated to the difficulty of the task performed (PausKoski Caramanos amp Westbury 1998) Our findings areconsistent with these propositions to the extent thatthe engagement of the cognitive and neurophysiologicalprocesses implied in each of those accounts may beaccompanied by a subjective experience of increasedmental absorption

The coordinated pattern of rCBF changes in thebrainstem the thalamus and the ACC may reflect theinterrelationships between the multiple components of anetwork (eg Paus et al 1997) herein shown to beassociated with the feeling of being lsquolsquomentally absorbedrsquorsquoThe precise location of the observed absorption-specificthalamic peak is consistent with an involvement of theintralaminar and medio-dorsal nuclei which have recip-rocal connections with the ACC (Vogt amp Gabriel 1993)The finding that the coordinated activity in the thalamusand the ACC is disrupted in persistent vegetative states isconsistent with the notion that these structures work intandem to regulate consciousness (Laureys et al 2000also see Jeanmonod Magnin amp Morel 1996) Further-more a functional interaction between arousal andattentional processes has been reported in the thalamus

where the putative attention-related activity associatedwith the performance of a simple visual discriminationtask was found to increase in states of low arousal (Portaset al 1998) This increase in thalamic activity wassuggested (1) to reflect a compensatory mechanism thatpermitted the maintenance of stable levels of perform-ance in states of low arousal and (2) to prevent thegeneralized thalamo-cortical synchronization that wouldlead to sleep Here the opposite effects of relaxation andabsorption on thalamic activity may reflect this compen-satory mechanism that maintains high levels of focusedattention in deeply relaxed subjects during hypnosisThis function may be critical not only in hypnosis butalso in other conditions of deep relaxation distinct fromboth sleep and normal wakefulness such as meditativestates (Lou et al 1999) Furthermore the coactivation ofthe ACC and the ponto-mesencephalic brainstem mayreflect the contribution of the ACC to the regulation ofattention-related activity in the locus coeruleus (Cohenet al 2000) The positive regression found with absorp-tion in the ponto-mesencephalic brainstem and themore robust regression observed in the thalamus andthe ACC after accounting for relaxation-related changes(absorption-specific Table 1) further substantiate thepossibility that brainstem and thalamic nuclei interactwith the ACC to regulate the interaction between atten-tion and cortical arousal Taken together these resultsare consistent with a contribution of brainstem nucleithe intralaminar and medio-dorsal nuclei of the thala-mus and the ACC to the changes in phenomenalexperience that characterize hypnotic states

Additional Relaxation- and Absorption-RelatedChanges in rCBF

Relaxation-Related Activity

We observed strong relaxation-related increases in rCBFin the precentral gyrus bilaterally and reciprocaldecreases in somatosensory areas (S1 S2 and insula)Precentral and premotor activation has been reportedduring hypnosis in an independent study (Maquet et al1999) and precentral rCBF was correlated with the rCBFmeasured at the ACC site of hypnosis-related activity inour previous study (see Appendix in Rainville Hofbaueret al 1999) Similar increases in activity in motor andpremotor areas have been associated with voluntarymuscular relaxation (Toma et al 1999) but the presentresults may reflect more than physical relaxation

All standard hypnotic procedures include instructionsfor relaxation However the specific contribution ofmuscular relaxation and decreased arousal to the pro-duction of hypnotic states is unclear as hypnotic phe-nomena have been produced during muscular exercise(Banyai amp Hilgard 1976) and with suggestions of active-alertness (Vingoe 1968 1973) Here the absence ofsignificant effect of hypnosis on heart rate indicates thatchanges in cerebral activity did not correlate with

896 Journal of Cognitive Neuroscience Volume 14 Number 6

changes in peripheral arousal and suggests that subjectswere already physically relaxed in the baseline controlcondition This implies that the hypnosis-inducedchanges in self-ratings of relaxation may not simplyreflect changes in lsquolsquoperipheralrsquorsquo arousal but may attestmore specifically of an increase in lsquolsquomentalrsquorsquo relaxationand a reduction in lsquolsquocorticalrsquorsquo arousal This is consistentwith Pricersquos experiential model of hypnosis (see Intro-duction) and with our previous study showing anincrease in slow (delta) EEG activity during hypnosis

Relaxation-related effects observed outside primarysomatomotor areas may partly reflect subjective feelingsof mental ease more closely In the subtraction analysishypnosis-related decreases were found in the rightlateral posterior parietal rCBF both here (x y z 40iexcl52 44) and in our previous study (x y z 46 iexcl50 42from Table 1 in Rainville Hofbauer et al 1999) Herethese changes were strongly but not specifically asso-ciated with relaxation (x y z 39 iexcl49 45 see Table 2Figure 3A) Furthermore after accounting for absorp-tion-related variance right prefrontal activity was neg-atively correlated with relaxation (Table 2) Thoseadditional changes in the right posterior parietal cortexand the right prefrontal cortices may contribute to thesubjective feelings of mental ease rather than or inaddition to physical relaxation

Fronto-Parietal Attention Networks

Absorption-related activity was widespread and bilateralin the prefrontal cortices but peaks were generallystronger in the right hemisphere Positive regressionpeaks were maximal in the ventrolateral frontal corticesover the inferior frontal gyrus and in the anterior insulaA positive absorption-related regression peak was alsosignificant in the right inferior parietal lobule Theseareas also displayed strong coactivation with absorption-related thalamic activity Very similar patterns of activa-tion have been associated with attentional processes intasks involving visual (eg Coull Frackowiak amp Frith1998) auditory (Paus et al 1997) and somatosensorystimuli (Peyron et al 1999) Notably the location of thepositive parietal peak observed here closely matches theactivation sites reported in those studies and the site ofcovariation with the right ventrolateral attention-relatedactivity reported in Paus et al (1997) suggesting theactivation of a similar network The coordinated absorp-tion-related activity observed here in the brainstem thethalamus the ACC the right inferior frontal gyrus andthe right inferior parietal lobule provides very strongevidence that mental absorption is an experiential cor-relate of the activation of the brainrsquos lsquolsquoexecutive atten-tional networkrsquorsquo and suggests that this system plays acritical role in the production of hypnotic states

Negative absorption-related regression peaks werealso found in both the right and left lateral parietalcortices and in the precuneus (see Table 2) These

effects were largely independent of thalamic activity asindicated by the absence of significant effects at theselocations in the covariation analysis (Table 3) The rightposterior parietal cortex has been suggested to con-stitute a vigilanceorientation system (Pardo Fox ampRaichle 1991) and hypnosis-related decreases in thisarea may reflect a relative disengagement towardexternal sources of stimulation Right and left posteriorparietal cortices at the precise sites of relaxation- andabsorption-related decrease in rCBF have been sug-gested to contribute to the monitoring of externalspace and time respectively (Gitelman et al 19961999 Kim et al 1999 Coull amp Nobre 1998 Nobreet al 1997) Although these functions were notdirectly assessed in this experiment the hypnoticinduction procedure includes specific instructions fordecreased orientation to and interest in irrelevantexternal sources of stimulation and previous observa-tions suggest that hypnotic relaxation and absorptionare precursors to some alterations in spatio-temporalorientation and monitoring (Price 1996) Thus wespeculate that those additional experiential changesmay be consequent to relaxation- and absorption-related decreases in posterior parietal activity

Relaxation- and Absorption-Related Effects onOccipital rCBF

The subtraction analysis confirmed the reliability of thehypnosis-related increase in occipital rCBF reported inour previous study (Rainville Hofbauer et al 1999) Wenow show that this effect was associated with the sub-jective experience of hypnotic relaxation (see Table 2relaxation-specific) Consistently our previous studydemonstrated a coupling between occipital increases inrCBF and increases in slow (delta) EEG activity duringhypnosis Similar increases in occipital rCBF andor slowEEG activity had been observed in another study onhypnosis (Maquet et al 1999) and in states of decreasedvigilance (Paus et al 1997) meditation (Lou et al 1999)and slow wave sleep (Kajimura et al 1999 Hofle et al1997) These effects are consistent with our previousproposition that hypnotic induction produces a globaldecrease in cross-modality suppression in unattendedsensory channels leading to a relative disinhibitionof cortical activity (see Paus et al 1997 KawashimaOrsquoSullivan amp Roland 1995)

In contrast negative correlations between rCBF andmental absorption were observed over both occipitallobes (Table 2 Figure 3B) Consistently occipital rCBFwas correlated negatively with thalamic rCBF at theabsorption-specific site (Table 3) These contrastingeffects imply that variations in occipital rCBF are asso-ciated with separate portions of the variance in relaxa-tion and absorption (Note that although absorptionand relaxation were significantly correlated the variancein absorption was largely independent of relaxation see

Rainville et al 897

Methods) For a given level of relaxation the increasein hypnotic absorption could reflect the concurrentengagement of the lsquolsquoexecutive attentional networkrsquorsquowhich exerts an opposite effect over brain areas sub-serving unattended sensory channels (ie a relativefacilitation of cross-modality suppression)

Hypnosis as a State of Consciousness

The representation of the body-self is central to theneurophenomenology of consciousness (Metzinger2000) In the Introduction we have proposed that theinduction of hypnosis produces global changes in sub-jective experience reflecting a modulation of basicaspects of the body-self representation Consistentlythe PET results indicate that hypnosis involves changesin activity within brain structures essential for the basicregulation of states of consciousness self-monitoringand self-regulation Furthermore changes in relaxationand absorption are precursors (although they may notbe essential) to other hypnosis-related effects such asthe diminished tendency to judge monitor and censorthe suspension of usual orientation toward time loca-tion andor sense of self and the experience of onersquosown response as automatic or extra-volitional (Price1996) These dimensions of experience also rely criticallyon self-representation and may depend at least partly oncerebral areas shown here to be involved in hypnosisAmong those changes the increased feeling of automa-ticity an altered feeling of agency may be the mostdistinctive aspect of hypnotic phenomenology (Weitzen-hoffer 1980) Interestingly the sense of agency hasrecently been suggested to involve areas that displayconsistent changes in activity during hypnosis such asthe right inferior parietal cortex the precuneus and thesomatosensory cortices (Blakemore amp Decety 2001Ruby amp Decety 2001) The modulation of activityobserved here within those areas is consistent withthe interpretation that hypnosis produces changes inself-representation construed as an essential element forconscious experience

Conclusion

The present study used self-ratings of subjective feelingsof mental relaxation and mental absorption to map brainareas involved in hypnosis We replicated previous find-ings and further demonstrated that hypnotic relaxationand absorption reflect changes in brain activity withinregions involved in the control of consciousness statesand in self-regulation such as the brainstem the thala-mus and the ACC The coordinated activity within thesestructures and other absorption-related areas such asthe ventrolateral frontal and right posterior parietalcortices has been previously shown to underlie theregulation of the content of consciousness throughmechanisms of executive attention We must recognize

that our findings are correlative in nature and arerelevant to hypnosis to the extent that mental relaxationand absorption are conceived as basic experientialdimensions that characterize hypnotic phenomenaWe further speculate that these changes in subjectiveexperience and brain activity may contribute to otherhypnosis-related effects such as the altered feeling ofagency experienced during hypnosis These findings areconsistent with the notion that hypnotic states areachieved through the modulation of activity within adistributed network of cerebral structures involved inthe regulation of consciousness states

METHODS

Subjects

Ten right-handed subjects (4 men 6 women) wereselected from a group of 22 volunteers as a part of astudy on the hypnotic modulation of pain (Hofbaueret al 2001) Hypnotic susceptibility was assessed usingthe SHSS-A administered between scans (range 111ndash1011 mean plusmn SD 69 plusmn28) The Ethics Committee ofthe Montreal Neurological Institute (MNI) approved allprocedures and subjects signed a consent form describ-ing the procedure and affirming their right to withdrawfrom the experiment without prejudice

Experimental Procedure

We report the results obtained in eight scans acquired ina restful baseline and hypnosis condition Hypnoticinduction started immediately after Scan 4 and wassustained in the remaining scans by repeating inductioninstructions between scans Instructions included sug-gestions for (1) increased physical and mental relaxa-tion (2) comfortable feeling of warmth heaviness anddrowsiness (3) sustained passive attention to theexperimenterrsquos voice and to the instructions and (4)decreased concern with and orientation to external andinternal (mental) sources of distraction No specificinstruction for visual imagery was included During allscans the subjectsrsquo eyes were closed and their left handwas immersed in warm or painfully hot water Pain-related activation and four additional scans performedwith suggestions for pain modulation are reported else-where (Hofbauer et al 2001)

Self-Ratings of Mental Relaxation and Absorption

After each scan subjects were instructed to rate (0ndash10)(1) their level of tensionndashrelaxation with lsquolsquo10 being themost relaxed and at ease you can bersquorsquo and (2) their levelof sustained focus of attention with lsquolsquo10 being the mostabsorbed and the largest amount of sustained focusedattention you can gatherrsquorsquo Ratings of relaxation andabsorption were transformed using the rank within sub-jects to (1) control for individual differences (2) prevent

898 Journal of Cognitive Neuroscience Volume 14 Number 6

scaling biases and (3) parallel the analysis of rCBF dataSubjects rated pain on separate scales (0ndash100) Hypno-sis-related increases in relaxation and absorption did notinteract with the stimulation condition (pain vs warmstimulation prsquos gt 10) neither relaxation nor absorptioncorrelated significantly with pain ratings (all prsquos gt 10)and pain was not altered by hypnosis alone [t(9) = 069p = 51]

PET Imaging Methods

rCBF was measured using the H215O bolus injection

method (10 millicuriesscan) without arterial blood sam-pling (Herscovitch Markham amp Raichle 1983) with ahigh-resolution PET scanner operated in 3-D acquisitionmode (Siemens ECAT HR+ 63 slices) Stimulus onsetwas simultaneous with bolus injection and 1-min acquis-ition scans started about 15 sec postinjection (interscaninterval of 12ndash15 min) Data from the first 40 sec ofacquisition were reconstructed and analyzed Each sub-ject also underwent a high-resolution anatomical MRI(160 1-mm sagittal slices acquired on a Philips 15-TGyroscan system) Each PET and MRI volume wasaligned and transformed using software developed atthe MNI to match the MNI standardized Talairach space(Collins Neelin Peters amp Evans 1994 Talairach ampTournoux 1988) PET volumes were smoothed (FWHM= 14 mm) and normalized to the average brain countPeak and cluster analyses were performed (FristonWorsley Frackowiak Mazziotta amp Evans 1994 WorsleyEvans Marrett amp Neelin 1992)

Reliability of Hypnosis-Related Effects

A first analysis was performed using the subtractionmethod (Hypnosis minus Baseline) to evaluate thereliability of the effects reported in our previous study(Table 2 in Rainville Hofbauer et al 1999) We consid-ered that hypnosis-related changes in rCBF were repli-cated when a significant peak was observed within oneresel (Worsley et al 1992) of the peak sites reported inour previous study or when the peak sites were within asignificant cluster

Regression of rCBF on Self-Ratings of Relaxationand Absorption

Regression analyses were used to test the relationbetween ratings and rCBF (GLM) Subject- and stimu-lus-related effects were removed first (ANCOVA) andthe significance of the regression slope between thecovariate of interest and rCBF was estimated usingt tests Relaxation-specific and absorption-specific effectswere further tested using ANCOVAs to remove thevariance shared between absorption and relaxation(R2 = 42 p lt 001) The statistical criterion was setto t gt 258 (two-tailed uncorrected p lt 01) in the

directed searches restricted to the brainstem the thala-mus and the ACC (Table 1 Figure 2) Global searcheffects are significant ( p lt 05) based on peak (t valuegt 420) andor clusters analysis after a correction formultiple comparisons over the gray matter volume(uncorrected p lt 0001) (Table 2 Figure 3)

Thalamic Covariations

A covariation analysis was performed in which the rCBFmeasured in the thalamus was used as the covariate ofinterest after accounting for subject- and stimulus-related variance (ANCOVA see Tables 1 and 3) Becausewe were mainly interested in the relationship betweenthe activity in the thalamus and other absorption-relatedsites the threshold for statistical significance was set tot = 370 ( p = 05 uncorrected p lt 0008) based on thevolume defined by the sum of clusters of voxels showingsignificant absorption-specific effects (186 cm3 seeWorsley et al 1992)

Acknowledgments

We thank R Adolphs S Anderson A Bechara A R DamasioH Damasio Susan Lutgendorf J Parvizi and D Tranel fortheir comments on preliminary versions of the manuscriptPET analyses were performed using the software DOTdeveloped by Sylvain Milot and the MINC programs developedby Peter Neelin at the McConnell Brain Imaging Center of theMontreal Neurological Institute This study was supported bythe Medical Research Council (MRC) of Canada Dr Rainvillewas supported by the Medical Research Council of Canada andthe Human Frontier Science Program and Dr Hofbauer wassupported by the Fonds pour la recherche en sante du Quebecand the Royal Victoria Hospital Research Institute

Reprint requests should be sent to Pierre Rainville Faculte deMedecine dentaire Universite de Montreal CP 6128 SuccCentre-ville Montreal Qc H3C 3J7 Canada or via e-mailpierrerainvilleumontrealca

REFERENCES

Aston-Jones G Rajkowski J amp Cohen J (1999) Role of locuscoeruleus in attention and behavioral flexibility BiologicalPsychiatry 46 1309 ndash1320

Badgaiyan R D amp Posner M I (1998) Mapping the cingulatecortex in response selection and monitoring Neuroimage7 255 ndash260

Balthazard C G amp Woody E Z (1992) The spectral analysisof hypnotic performance with respect to lsquolsquoabsorptionrsquorsquoInternational Journal of Clinical and ExperimentalHypnosis 40 21ndash43

Banyai E I amp Hilgard E R (1976) A comparison ofactive-alert hypnotic induction with traditional relaxationinduction Journal of Abnormal Psychology 85 218 ndash224

Blakemore S J amp Decety J (2001) From the perception ofaction to the understanding of intention Nature ReviewsNeuroscience 2 561 ndash567

Braun A R Balkin T J Wesenten N J Carson R EVarga M Baldwin P Selbie S Belenky G amp HerscovitchP (1997) Regional cerebral blood flow throughout the

Rainville et al 899

sleep ndashwake cycle An H2(15)O PET study Brain 1201173 ndash1197

Bush G Luu P amp Posner M I (2000) Cognitive andemotional influences in anterior cingulate cortex Trendsin Cognitive Sciences 4 215 ndash222

Chalmers D J (2000) What is a neural correlate ofconsciousness In T Metzinger (Ed) Neural correlatesof consciousness Empirical and conceptual questions(pp 17ndash39) Cambridge MIT Press

Coe W C amp Sarbin T R (1977) Hypnosis from thestandpoint of a contextualist Annals of the New YorkAcademy of Sciences 296 2ndash13

Cohen J D Botvinick M amp Carter C S (2000) Anteriorcingulate and prefrontal cortex Whorsquos in control NatureNeuroscience 3 421 ndash423

Collins D L Neelin P Peters T M amp Evans A C (1994)Automatic 3D intersubject registration of MR volumetric datain standardized Talairach space Journal of ComputerAssisted Tomography 18 192 ndash205

Coull J T Frackowiak R S amp Frith C D (1998) Monitoringfor target objects Activation of right frontal and parietalcortices with increasing time on task Neuropsychologia 361325 ndash1334

Coull J T amp Nobre A C (1998) Where and when to payattention The neural systems for directing attention tospatial locations and to time intervals as revealed by bothPET and fMRI Journal of Neuroscience 18 7426 ndash7435

Crawford H J (1994) Brain dynamics and hypnosisAttentional and disattentional processes InternationalJournal of Clinical and Experimental Hypnosis 42204 ndash232

Crawford H J amp Gruzelier J H (1992) A midstream view ofthe neuropsychophysiology of hypnosis Recent researchand future directions In E Fromm amp M R Nash (Eds)Contemporary hypnosis research (pp 227 ndash266) New YorkGuilford Press

Crawford H J Knebel T Kaplan L Vendemia J M C XieM Jamison S amp Pribram K H (1998) Hypnotic analgesia1 Somatosensory event-related potential changes to noxiousstimuli and 2 Transfer learning to reduce chronic low backpain International Journal of Clinical and ExperimentalHypnosis 46 92ndash132

Damasio A R (1999) The feeling of what happens Body andemotion and the making of consciousness New YorkHartcourt Brace

De Pascalis V Magurano M R amp Bellusci A (1999) Painperception somatosensory event-related potentials andskin conductance responses to painful stimuli in high midand low hypnotizable subjects Effects of differential painreduction strategies Pain 83 499 ndash508

Devinsky O Morrell M J amp Vogt B A (1995) Contributionsof anterior cingulate cortex to behaviour Brain 118279 ndash306

Fiset P Paus T Daloze T Plourde G Meuret PBonhomme V Hajj-Ali N Backman S B amp Evans A C(1999) Brain mechanisms of propofol-induced loss ofconsciousness in humans A positron emission tomographicstudy Journal of Neuroscience 19 5505 ndash5513

Friston K J Worsley K J Frackowiak R S J Mazziotta J Camp Evans A C (1994) Assessing the significance of focalactivation using their spatial extent Human Brain Mapping1 214ndash220

Gitelman D R Alpert N M Kosslyn S Daffner K ScintoL Thompson W amp Mesulam M M (1996) Functionalimaging of human right hemispheric activation forexploratory movements Annals of Neurology 39 174ndash179

Gitelman D R Nobre A C Parrish T B LaBar K S KimY H Meyer J R amp Mesulam M (1999) A large-scale

distributed network for covert spatial attention Furtheranatomical delineation based on stringent behavioural andcognitive controls Brain 122 1093 ndash1106

Gruzelier J (1998) A working model of the neurophysiologyof hypnosis A review of evidence Contemporary Hypnosis15 3ndash21

Henson R N A Rugg M D Shallice T amp Dolan R J (2000)Confidence in recognition memory for words Dissociatingright prefrontal roles in episodic retrieval Journal ofCognitive Neuroscience 12 913 ndash923

Henson R N A Rugg M D Shallice T Joseph O ampDolan R J (1999) Recollection and familiarity inrecognition memory An event-related functional magneticresonance imaging study Journal of Neuroscience 193962 ndash3972

Herscovitch P Markham J amp Raichle M E (1983) Brainblood flow measured with intravenous H2(15)O I Theoryand error analysis Journal of Nuclear Medicine 24782 ndash789

Hofbauer R K Rainville P Duncan G H amp Bushnell M C(2001) Cortical representation of the sensory dimension ofpain Journal of Neurophysiology 86 402 ndash411

Hofle N Paus T Reutens D Fiset P Gotman J EvansA C amp Jones B E (1997) Regional cerebral blood flowchanges as a function of delta and spindle activity duringslow wave sleep in humans Journal of Neuroscience 174800 ndash4808

Jeanmonod D Magnin M amp Morel A (1996) Low-thresholdcalcium spike bursts in the human thalamus Commonphysiopathology for sensory motor and limbic positivesymptoms Brain 119 363ndash375

Kajimura N Uchiyama M Takayama Y Uchida S Uema TKato M Sekimoto M Watanabe T Nakajima THorikoshi S Ogawa K Nishikawa M Hiroki M Kudo YMatsuda H Okawa M amp Takahashi K (1999) Activityof midbrain reticular formation and neocortex during theprogression of human non-rapid eye movement sleepJournal of Neuroscience 19 10065 ndash10073

Kawashima R OrsquoSullivan B T amp Roland P E (1995)Positron-emission tomography studies of cross-modalityinhibition in selective attentional tasks Closing the lsquolsquomindrsquoseyersquorsquo Proceedings of the National Academy of SciencesUSA 92 5969 ndash5972

Kim Y H Gitelman D R Nobre A C Parrish T BLaBar K S amp Mesulam M M (1999) The large-scaleneural network for spatial attention displays multifunctionaloverlap but differential asymmetry Neuroimage 9269 ndash277

Kinomura S Larsson J Gulyas B amp Roland P E (1996)Activation by attention of the human reticular formationand thalamic intralaminar nuclei Science 271 512ndash515

Kosslyn S M Thompson W L Costantini-Ferrando M FAlpert N M amp Spiegel D (2000) Hypnotic visual illusionalters color processing in the brain American Journal ofPsychiatry 157 1279 ndash1284

Laureys S Faymonville M E Luxen A Lamy M Franck Gamp Maquet P (2000) Restoration of thalamocorticalconnectivity after recovery from persistent vegetative stateLancet 355 1790ndash1791

Lou H C Kjaer T W Friberg L Wildschiodtz G Holm Samp Nowak M (1999) A 15OndashH2O PET study of meditationand the resting state of normal consciousness HumanBrain Mapping 7 98ndash105

Maquet P Degueldre C Delfiore G Aerts J Peters J MLuxen A amp Franck G (1997) Functional neuroanatomyof human slow wave sleep Journal of Neuroscience 172807 ndash2812

Maquet P Faymonville M E Degueldre C Delfiore G

900 Journal of Cognitive Neuroscience Volume 14 Number 6

Franck G Luxen A amp Lamy M (1999) Functionalneuroanatomy of hypnotic state Biological Psychiatry 45327 ndash333

Metzinger T (2000) The subjectivity of subjective experienceA representationalist analysis of the first-person perspectiveIn T Metzinger (Ed) Neural correlates of consciousnessEmprical and conceptual questions (pp 285 ndash306)Cambridge MIT Press

Nobre A C Sebestyen G N Gitelman D R MesulamM M Frackowiak R S amp Frith C D (1997) Functionallocalization of the system for visuospatial attention usingpositron emission tomography Brain 120 515 ndash533

Pardo J V Fox P T amp Raichle M E (1991) Localization of ahuman system for sustained attention by positron emissiontomography Nature 349 61ndash64

Paus T (2001) Primate anterior cingulate cortex Wheremotor control drive and cognition interface NatureReviews Neuroscience 2 417 ndash424

Paus T Koski L Caramanos Z amp Westbury C (1998)Regional differences in the effects of task difficulty andmotor output on blood flow response in the human anteriorcingulate cortex A review of 107 PET activation studiesNeuroReport 9 R37ndashR47

Paus T Zatorre R J Hofle N Caramanos Z Gotman JPetrides M amp Evans A C (1997) Time-related changesin neural systems underlying attention and arousal duringthe performance of an auditory vigilance task Journal ofCognitive Neuroscience 9 392ndash408

Peyron R Garcia-Larrea L Gregoire M C Costes NConvers P Lavenne F Mauguiere F Michel D ampLaurent B (1999) Haemodynamic brain responses to acutepain in humansmdashSensory and attentional networks Brain122 1765 ndash1779

Picard N amp Strick P L (1996) Motor areas of the medial wallA review of their location and functional activation CerebralCortex 6 342 ndash353

Portas C M Howseman A M Josephs O Turner R ampFrith C D (1998) A specific role for the thalamus inmediating the interaction of attention and arousal inhumans Journal of Neuroscience 18 8979 ndash8989

Posner M I amp Rothbart M K (1998) Attentionself-regulation and consciousness Philosophical

Transactions of the Royal Society of London Series BBiological Sciences 353 1915 ndash1927

Price D D (1996) Hypnotic analgesia Psychological andneural mechanisms In J Barber (Ed) Hypnosis andsuggestions in the treatment of pain (pp 67ndash84) NewYork Norton

Price D D amp Barrell J J (1980) An experiential approachwith quantitative methods A research paradigm Journal ofHumanistic Psychology 20 75ndash95

Rainville P Carrier B Hofbauer R K Bushnell M C ampDuncan G H (1999) Dissociation of pain sensory andaffective dimensions using hypnotic modulation Pain 82159 ndash171

Rainville P Duncan G H Price D D Carrier B ampBushnell M C (1997) Pain affect encoded in humananterior cingulate but not somatosensory cortex Science277 968 ndash971

Rainville P Hofbauer R K Paus T Duncan G H BushnellM C amp Price D D (1999) Cerebral mechanisms ofhypnotic induction and suggestion Journal of CognitiveNeuroscience 11 110ndash125

Ruby P amp Decety J (2001) Effect of subjective perspectivetaking during simulation of action A PET investigation ofagency Nature Neuroscience 4 546 ndash550

Steriade M amp McCarley R W (1990) Brainstem control ofwakefulness and sleep New York Plenum

Szechtman H Woody E Bowers K S amp Nahmias C(1998) Where the imaginal appears real A positronemission tomography study of auditory hallucinationsProceedings of the National Academy of Sciences USA95 1956 ndash1960

Talairach J amp Tournoux P (1988) Co-planar stereotaxicatlas of the human brain New York Thieme

Tellegen A amp Atkinson G (1974) Openness to absorbingand self-altering experiences (lsquolsquoabsorptionrsquorsquo) a trait relatedto hypnotic susceptibility Journal of Abnormal Psychology83 268 ndash277

Toma K Honda M Hanakawa T Okada T Fukuyama HIkeda A Nishizawa S Konishi J amp Shibasaki H (1999)Activities of the primary and supplementary motor areasincrease in preparation and execution of voluntary musclerelaxation An event-related fMRI study Journal ofNeuroscience 19 3527 ndash3534

Varela F J amp Shear J (1999) First-person methodologiesWhat why and how Journal of Consciousness Studies 61ndash14

Vingoe F J (1968) The development of a group alert-trancescale International Journal of Clinical and ExperimentalHypnosis 16 120 ndash132

Vingoe F J (1973) Comparison of the Harvard Group Scaleof Hypnotic Susceptibility Form A and the Group AlertTrance Scale in a university population InternationalJournal of Clinical and Experimental Hypnosis 21169 ndash179

Vogt B A amp Gabriel M (1993) Neurobiology of cingulatecortex and limbic thalamus A comprehensive handbookBoston Birkauser

Weitzenhoffer A M (1980) Hypnotic susceptibility revisitedAmerican Journal of Clinical Hypnosis 22 130 ndash146

Willoch F Rosen G Tolle T R Oslashye I Wester H J BernerN Schwaiger M amp Bartenstein P (2000) Phantom limbpain in the human brain Unravelling neural circuitries ofphantom limb pain sensations using positron emissiontomography Annals of Neurology 48 842 ndash849

Worsley K J Evans A C Marrett S amp Neelin P (1992)A three-dimensional statistical analysis for CBF activationstudies in human brain Journal of Cerebral Blood Flow andMetabolism 12 900 ndash918

Rainville et al 901

Page 4: Hypnosis Modulates Activity in Brain Structures Involved in the …pineda/COGS175/readings/Rain... · 2005. 2. 28. · Hypnosis Modulates Activity in Brain Structures Involved in

increases in the middle and perigenual ACC (Figure 2B)Increases in absorption were correlated with rCBFincreases in the thalamus and in the rostral and peri-genual ACC (Figure 2C)

The specificity of any changes in the rCBF associatedwith either mental relaxation (relaxation-specific) orabsorption (absorption-specific) was further examinedusing ANCOVA (see Methods) to remove the varianceshared with the other factormdashabsorption and relaxa-tion respectively (Table 1) Relaxation-specific negativecorrelations were found in the brainstem in the thala-mus and in the superior frontal gyrus in a clusterof significant voxels extending over the rostral ACCAbsorption-specific effects confirmed the significant pos-itive correlation between mental absorption and rCBFin the thalamus and in the rostral ACC and furtherrevealed a significant positive peak in the upper ponsof the brainstem (Figure 2D Table 1) Although mentalrelaxation and absorption both increased during hyp-nosis these results demonstrate that the negative cor-relation in the mesencephalic brainstem and thethalamus appears to be exclusively associated with

mental relaxation while the positive correlations inthe upper pons the thalamus and the mid-ACC appearto be exclusively associated with mental absorption

Global Searches

Results of the global searches show additional differ-ences between the patterns of activity related to mentalrelaxation and absorption In the frontal lobe increasesin prefrontal rCBF were positively correlated primarilywith mental absorption (Table 2) while increases in theprecentral region were positively correlated with bothrelaxation (Figure 3A) and absorption (Table 2) Con-sistently after removing the variance shared betweenmental relaxation and absorption positive absorption-specific correlations (Table 2 Figure 3B) and negativerelaxation-specific correlations (Table 2) were observedin prefrontal areas while most precentral effects did notreach significance

Posterior cortical areas displayed a mixed pattern ofresults Negative correlations observed in both temporallobes were more reliably related to mental relaxation

Figure 2 Statistical (t) maps overlaid on a midsagittal view of a single-subject MRI anatomical image showing the location of significant positive(red arrows) and negative (blue arrow) regression slopes between rCBF and self-ratings in the three regions of interest (brainstem thalamus andACC see Methods) (A) A negative regression peak is found with relaxation in the mesencephalic tegmentum and (B) positive regression peaksare found in the middle (mACC) and perigenual (pACC) portion of the ACC (note the reversal of the color scale) (C) Positive regression peaksare found with absorption in the thalamus and in the rostral ACC (rACC) and pACC (D) The regression of rCBF on absorption ratings afteraccounting for relaxation-related effects confirmed the positive regression peaks specific to absorption in the thalamus and rACC This analysisfurther revealed an additional positive peak in the upper pons Color scales in C and D are as in B Stereotaxic coordinates of peaks are reportedin Table 1

890 Journal of Cognitive Neuroscience Volume 14 Number 6

than absorption and the relaxation-related effects heldafter accounting for variance in absorption (Table 2mdashrelaxation-specific) Additional sites of relaxation-specificeffects included negative correlations in the right parie-tal operculum and lobule and positive correlations in theright precuneus the left inferior parietal lobule and thebilateral occipital cortices (Table 2mdashrelaxation-specific)

The effects associated with absorption in the posteri-or cortices were strikingly different from the effects ofrelaxation After accounting for relaxation-related var-iance we observed both positive and negative absorp-tion-specific correlations in both the right and leftparietal lobules (see Table 2mdashabsorption-specific) Inthe inferior parietal lobules positive and negative cor-relations dominated in the right and left hemispheresrespectively (Figure 3B) Strong negative correlationswere also observed over the right precuneus theposterior cingulate cortex and both occipital lobes(Figure 3B)

Additional statistical trends directly relevant to ourhypotheses were also observed in the somatosensorycortices where rCBF was negatively correlated with men-tal relaxation (see Figure 3A right S1 peak coordinates44 iexcl35 59 t = iexcl286 p-uncorrected = 014 clusterp = 06 left S1 iexcl44 iexcl21 16 t = iexcl251 p-uncorrected =026 cluster analysis p gt 10 right parietal operculumS2 48 iexcl21 24 t = iexcl351 p-uncorrected = 003 clusterp gt 10 right posterior insula 44 iexcl4 15 t = iexcl296p-uncorrected = 011 cluster p gt 10)

Covariations with Thalamic rCBF

In our previous study thalamic activity was found tobe correlated with hypnosis-related ACC activity (seeTable 2 and Appendix in Rainville Hofbauer et al1999) and several studies suggest a pivotal role of thethalamus in arousal attention and consciousness andin the interaction between the brainstem and the ACC(eg Paus et al 1997 Paus 2001 Portas HowsemanJosephs Turner amp Frith 1998 Hofle et al 1997) Herewe tested the association between absorption-relatedactivity in the thalamus and activity in other sites ofabsorption-related changes using a covariation analysiscentered on the absorption-specific peak in the thala-mus reported in Table 1 Absorption-specific sites in thebrainstem (upper pons) and the ACC showed significantcovariations with thalamic rCBF (Table 1) Additionalregions where rCBF showed a positive correlation withthalamic rCBF included bilateral frontal sites in theinferior middle and superior frontal gyri extendingmedially into the right ACC and the right insula(Table 3) Many of those peak locations matched frontalsites specifically related to mental absorption (italicizedin Table 2) A strong positive peak was also observed inthe right inferior parietal lobule precisely at the loca-tion where rCBF correlated strongly and specificallywith mental absorption (compare Table 2 absorption-

specific and Table 3) Areas displaying negative corre-lation with thalamic rCBF were found bilaterally in theoccipital lobes consistent with the absorption-specificeffects reported in Table 2

DISCUSSION

The approach used in this study provided a descriptionof cerebral activity associated with specific changes inphenomenal experience produced by a standard hyp-notic induction We discuss in turn the evidence for theproduction of hypnotic phenomena the reliability ofhypnosis-related effects the effects associated with men-tal relaxation and absorption and the implications ofour results for a state theory of hypnosis

Hypnosis and Phenomenal Experience

The induction of hypnosis produced the expectedincreases in both mental relaxation and absorptionThese changes were positively correlated (see Methods)as predicted by the experiential model of hypnosisproposed by Price (1996) and the ability to maintainhypnotic relaxation and absorption depended upon thesubjectsrsquo hypnotic susceptibility The higher levels ofabsorption maintained in highly hypnotizable subjectsare consistent with the positive association betweenabsorption attentional processes and hypnotizabilitysuggested in previous studies (Crawford 1994 Baltha-zard amp Woody 1992 Tellegen amp Atkinson 1974) Theseresults and additional convergent observations de-scribed in our previous report of pain-related effects(Hofbauer et al 2001) and from several experimentsusing similar methodology (Rainville et al 1997 Rain-ville Carrier et al 1999) confirmed the reliable produc-tion of hypnotic phenomena

Reliability of Hypnosis-Related Effects on rCBF

The experimental conditions examined here and in thefirst 8 scans in our previous study were identicalmdashthesame hypnotic induction procedure was applied by twodifferent experimenters and the two separate groups ofsubjects tested had comparable mean hypnotic suscep-tibility scores (Rainville Hofbauer et al 1999) Theresults of the subtraction analysis largely replicated ourprevious findings as well as those reported by Maquetet al (1999) In comparison to our previous experimentdifferences in the methods were limited to the additionof relaxation and absorption ratings after the scans Thelarger areas of frontal activation including the precentralregion and the more restricted occipital activationobserved here may reflect the emphasis put on hypnoticrelaxation and absorption during the scans As thesedimensions of experience characterize standard hypno-tic induction procedures we submit that these differ-ences further emphasize the functional significance of

Rainville et al 891

Tab

le2

R

esul

tsof

the

Glo

bal

Sear

ches

ofC

ereb

ral

Regi

ons

whe

rerC

BF

Show

eda

Sign

ifica

ntR

egre

ssio

nw

ithR

elax

atio

nan

dAb

sorp

tion

Regi

onP

eak

Loca

tion

Rela

xati

onRe

laxa

tion

-Spe

cifi

cAb

sorp

tion

Abs

orpt

ion

-Spe

cifi

c

xy

zt

xy

zt

xy

zt

xy

zt

Fron

tal

(F)

RF

Pole

(BA

10)

ndash34

562

iexcliexcl4

81

ndash28

555

+4

21

Rla

tF

Orb

ital

g(B

A11

)ndash

1946

iexcl20

iexcliexcl4

29

ndash19

44iexcl

20+

47

5

Rm

iddl

eF

g(B

A46

)ndash

3646

26iexcl

381

ndash34

4626

+3

79

Rin

fF

g(B

A47

)ndash

ndash47

34iexcl

18+

373

ndash

Rin

fF

g(B

A45

)ndash

478

15iexcl

386

5520

11+

352

ndash

Ra

nt

insu

lai

nf

Fg

(BA

144

4)ndash

4015

6iexcl

377

4310

2+

358

4013

5+

48

1

Rsu

pF

gc

ingu

late

g(B

A8

32)

ndash5

3745

iexcl3

68ndash

332

39+

43

2

Rsu

pF

g(B

A6)

ndashndash

1320

59+

369

1522

57+

43

3

Rm

edia

lsu

pF

g(B

A6)

ndashndash

3iexcl

466

+4

23

3iexcl

766

+3

92

Lla

tF

Orb

ital

g(B

A11

)ndash

ndashiexcl

3041

iexcl21

+3

68iexcl

3143

iexcl18

+3

76

Lm

iddl

eF

g(B

A8)

ndashndash

iexcl46

1535

+4

10iexcl

4410

29+

328

Lm

iddl

eF

g(B

A46

)ndash

ndashiexcl

3637

18+

43

8iexcl

3839

24+

407

La

nt

insu

lai

nf

Fg

(BA

144

4)ndash

ndashndash

iexcl34

817

+4

25

Lsu

pF

g(B

A6)

ndashndash

ndashiexcl

266

56+

416

Lsu

p

Fg

(BA

6)ndash

ndashiexcl

11iexcl

466

+3

68ndash

Cen

tral

Rp

rece

ntra

lg

(BA

4)54

iexcl4

53+

51

6ndash

52iexcl

453

+5

05

ndash

Rp

rece

ntra

lg

(BA

4)42

iexcl7

50+

49

4ndash

ndashndash

Rp

rep

ostc

entr

alg

(BA

41

3)ndash

ndash36

iexcl16

36+

378

ndash

Lpr

ecen

tral

mid

dle

Fg

(BA

46)

iexcl35

iexcl6

53+

398

ndashndash

ndash

Lpr

ecen

tral

g(B

A4)

iexcl47

iexcl16

47+

44

3ndash

iexcl48

iexcl14

50+

43

6ndash

Lpr

epo

stce

ntra

lg

(BA

41

3)ndash

iexcl30

iexcl37

60+

403

ndash

Tem

pora

l(T

)R

mid

dle

T

g(B

A21

)60

iexcl33

iexcl15

iexcl5

71

59iexcl

33iexcl

13iexcliexcl

55

1ndash

ndash

Rm

iddl

eT

g

(BA

37)

56iexcl

45iexcl

9iexcl

59

1ndash

55iexcl

47iexcl

6iexcliexcl

44

1ndash

Lpa

rahi

ppoc

amp

alg

(BA

353

6)iexcl

36iexcl

23iexcl

18iexcl

413

ndashndash

ndash

Lin

fT

g

fusi

form

g(B

A37

)iexcl

52iexcl

42iexcl

20iexcl

52

4iexcl

59iexcl

44iexcl

12iexcliexcl

43

3iexcl

48iexcl

44iexcl

20iexcliexcl

44

6ndash

892 Journal of Cognitive Neuroscience Volume 14 Number 6

Pari

etal

(P)

RP

oper

culu

m(B

A40

)ndash

32iexcl

3027

iexcl3

55ndash

ndash

Rin

fP

lo

bule

(BA

40)

ndash56

iexcl40

50iexcl

377

ndash56

iexcl44

50+

42

4

RP

lobu

le(B

A40

7)

39iexcl

4945

iexcl4

87

ndash38

iexcl47

45iexcliexcl

44

334

iexcl56

42+

383

Rsu

pP

lobu

le(B

A7)

ndashndash

21iexcl

5062

iexcliexcl4

45

21iexcl

5260

iexcl4

09

Rpr

ecun

eus

(BA

7)ndash

5iexcl

5645

+5

33

ndash5

iexcl56

45iexcliexcl

51

0

Prec

uneu

sp

ost

Cin

gg

(BA

731

)ndash

ndashndash

0iexcl

649

iexcliexcl5

05

Lin

fP

lobu

le(B

A40

)ndash

iexcl30

iexcl37

60+

403

ndashiexcl

35iexcl

3550

iexcliexcl4

48

Lin

fP

lobu

le(B

A40

)ndash

ndashndash

iexcl52

iexcl56

47+

370

Occ

ipit

al(O

)Li

ngua

lg

pos

tC

ing

g(B

A18

31)

ndash0

iexcl66

9+

42

6ndash

ndash

Rin

fO

g

(BA

19)

ndash43

iexcl71

iexcl6

+3

6843

iexcl75

5iexcliexcl

44

443

iexcl75

iexcl3

iexcliexcl5

17

Rli

ngu

alg

(BA

18)

ndash4

iexcl76

3+

46

4ndash

7iexcl

782

iexcliexcl4

68

Rcu

neu

s(B

A18

)ndash

12iexcl

8327

+5

20

ndashndash

Rsu

pO

g

(BA

19)

ndash17

iexcl81

38+

55

9ndash

15iexcl

8033

iexcliexcl6

02

Rsu

pO

g

(BA

19)

30iexcl

8726

+4

07

RO

po

le(B

A18

)ndash

27iexcl

929

+4

85

ndash27

iexcl92

8iexcliexcl

53

5

Lfu

sifo

rmg

(BA

181

9)ndash

iexcl40

iexcl78

iexcl3

+3

59ndash

iexcl40

iexcl76

iexcl3

iexcliexcl4

46

Lsu

pO

g

prec

un

eus

(BA

197

)ndash

iexcl13

iexcl88

38+

407

iexcl8

iexcl76

36iexcliexcl

42

3iexcl

13iexcl

8739

iexcliexcl5

18

Llin

gual

g(B

A18

)c

ereb

ellu

mndash

ndashiexcl

17iexcl

76iexcl

18iexcl

351

ndash

Llin

gual

fusi

form

g(B

A18

19)

ndashiexcl

15iexcl

78iexcl

3+

47

2iexcl

27iexcl

83iexcl

11iexcliexcl

42

2iexcl

16iexcl

80iexcl

2iexcliexcl

56

2

Lsu

pO

g

(BA

19)

ndashiexcl

27iexcl

8327

+3

98ndash

iexcl27

iexcl83

29iexcl

419

LO

po

le(B

A18

)ndash

iexcl24

iexcl90

8+

53

8iexcl

26iexcl

880

iexcl4

18iexcl

24iexcl

905

iexcliexcl6

50

Subc

orti

cal

Tha

lam

us(s

eeT

able

1)ndash

iexcl3

iexcl16

12iexcl

368

ndashiexcl

3iexcl

1612

+4

45

Rpu

tam

enndash

ndash21

iexcl7

5+

401

24iexcl

46

+3

57

Lgl

obu

spa

llidu

sndash

ndashiexcl

19iexcl

13

+3

68iexcl

21iexcl

12

+4

41

Lce

rebe

llum

ndashiexcl

9iexcl

88iexcl

23iexcliexcl

42

9ndash

ndash

Rel

axat

ion

-sp

ecifi

can

dab

sorp

tio

n-s

pec

ific

effe

cts

wer

eex

amin

edaf

ter

rem

ovi

ng

the

vari

ance

asso

ciat

edw

ith

abso

rpti

on

and

rela

xati

on

resp

ecti

vely

(AN

CO

VA

se

eM

eth

od

s)T

he

linea

rsl

op

ebe

twee

nrC

BF

and

rati

ngs

issi

gnifi

can

tatp

eak

loca

tio

ns

liste

d(t

thre

sho

ld=

plusmn4

20i

nb

old

see

Met

hod

s)P

eaks

wit

htgt

+3

50or

tlt

iexcl3

50w

ith

ina

sign

ific

ant

clus

ter

(see

Met

hods

)are

also

indi

cate

dw

ith

thei

rco

ordi

nate

sP

eaks

clos

eto

or

wit

hin

regi

ons

wh

ere

sign

ific

ant

cova

riat

ions

wit

hth

alam

icrC

BF

wer

efo

und

are

ita

lici

zed

(see

Tab

le3

and

Met

hods

)P

eak

loca

tion

sar

eba

sed

onth

est

ereo

taxi

cat

las

of

Tal

aira

chan

dT

ourn

oux

(198

8)(x

=la

tera

ly

=an

teri

or

z=

supe

rior

)an

don

mor

phol

ogi

cal

lan

dmar

kson

the

mer

ged

PE

Tndash

MR

Iim

ages

(BA

=pr

obab

leB

rodm

annrsquo

sar

eaL

=

left

R

=

righ

tg

=gy

rus

ant

=an

teri

or

pos

t=

post

erio

rsu

p=

supe

rior

in

f=

infe

rior

)

Rainville et al 893

the underlying processes in the production of hypnoticstates as discussed below

Role of the Brainstem the Thalamus and the ACCin Hypnosis

Results of the regression analyses suggest that neuralactivity in the brainstem the thalamus and the ACCcontributes to the experience of being hypnotized Therelaxation-specific negative correlations in the mesen-

cephalic brainstem and the thalamus may reflect thewell-established contribution of brainstem and thalamicnuclei to the regulation of wakefulness and corticalarousal In functional brain imaging studies rCBFdecreases in the brainstem and the thalamus have beenassociated with decreased vigilance (Paus et al 1997)sleep (Kajimura et al 1999 Braun et al 1997 Hofleet al 1997 Maquet et al 1997) and the loss ofconsciousness produced by the anesthetic propofol(Fiset et al 1999) These effects and to some extent

Figure 3 Brain regionsshowing positive (redarrowheads) and negative(blue arrowheads) regres-sion peaks between rCBFand self-ratings of (A)relaxation and (B) absorp-tion after accounting forrelaxation-related variance(absorption-specific)Statistical t maps are super-imposed on the averageanatomical MRI (left is onthe left side) Slice locationsare indicated on the 3-Danatomical image of asingle subjectrsquos anatomicalMRI (A-positive) Positiverelaxation-related effectsare shown in the centralregion bilaterally (horizon-tal slice on the left) Apositive peak is shown inthe right superior occipitalgyrus (SOg) (coronal viewon the right note scalechange) (A-negative)A negative relaxation-related effect in the rightposterior parietal cortexis shown in horizontal(first from left) coronal(second) and lateralsagittal (third) views Theplus sign indicates the moreanterior location of thepeak positive regression inthe analysis of absorption-related effects as shown inB Additional negative cor-relations are shown in thebilateral middle and inferiortemporal gyri (second) andin the right somatosensorycortices (S1 S2 insula)(B-positive) A positiveabsorption-specific peak isshown in the right inferiorparietal lobule (first fromleft) The minus sign indicates the more posterior location of the negative regression peak in the analysis of relaxation-related effects as shown in

A Other peaks are shown on the midsagittal view in the thalamus and the anterior cingulate cortex (second from left) and in the left lenticularnuclei and bilateral prefrontal cortices (last three cuts from left) (B-negative) Negative absorption-related effects are shown in the left inferiorparietal lobule (first from left) in both occipital lobes (second and third from left) and in the precuneus (first and third) Stereotaxic coordinates ofpeaks are reported in Table 3 (see relaxation- and absorption-specific)

894 Journal of Cognitive Neuroscience Volume 14 Number 6

the present relaxation-related decrease in brainstemrCBF may reflect an attenuation of activity withinbrainstem cholinergic nuclei Such reduction has beenobserved during slow EEG activity before the onset ofsleep and during slow-wave sleep in animal studies(Steriade amp McCarley 1990) Consistent with this pos-sibility we previously reported an increase in slow(delta) EEG activity following hypnotic induction (Rain-ville Hofbauer et al 1999) Although hypnotic andsleep states are clearly distinct certain neurophysiolog-

ical mechanisms may be involved to a varying degree inthe production of both states

The positive association specifically observed betweenmental absorption and rCBF in the upper pons and thethalamus contrasts with the above relaxation-relatedeffect and is consistent with previous reports of atten-tion-related brain activation (Kinomura et al 1996) Thisactivity may reflect the involvement of the noradrenergicsystem of the locus coeruleus in focused attentionand possibly in the interaction between cortical arousal

Table 3 Cerebral Sites of Covariation with Thalamic rCBF at the Absorption-Specific Peak Coordinates (x = iexcl27 y = iexcl160z = 120)

Region Peak Location x y z t

Frontal (F) R medial sup F gACC (BA 624) 1 43 32 +382

R anterior cingulate gsup F g (BA 326) 8 13 44 +387

R inf F g (BA 44) 51 12 8 +387

R ant insula (BA 14) 38 12 5 +412

R sup F g (BA 6) 16 20 59 +371

R medial sup F g (BA 6) 3 iexcl6 63 +498

R medial sup F g (BA 6) 11 iexcl23 53 +412

L middle F g (BA 46) iexcl38 46 23 +381

L middle F g (BA 46) iexcl31 39 39 +374

L inf F g (BA 44) iexcl43 6 12 +430

L sup F g (BA 6) iexcl19 20 53 +340

L medial sup F g (BA 6) iexcl5 17 65 +353

L sup F g (BA 6) iexcl20 12 65 +283

Parietal R inf parietal lobule (BA 40) 56 iexcl44 50 +519

Occipital (O) R fusiform g (BA 19) 26 iexcl62 iexcl30 iexcliexcl515

R lingual g (BA 18) 7 iexcl78 6 iexcliexcl623

R sup O g (BA 19) 19 iexcl85 30 iexcliexcl714

R O pole (BA 18) 27 iexcl90 9 iexcliexcl751

L cuneus (BA 18) iexcl11 iexcl83 29 iexcliexcl633

L O pole (BA 18) iexcl23 iexcl88 6 iexcliexcl793

Subcortical R thalamus 17 iexcl11 2 +350

R brainstem 13 iexcl26 iexcl15 +312

R medial brainstem 3 iexcl32 iexcl24 +287

L cerebellum iexcl4 iexcl57 iexcl21 +409

L globus pallidus iexcl20 iexcl1 iexcl2 +302

L caudate nucleus iexcl12 6 20 +291

Positive and negative regression slopes are significant at sites listed based on cluster or peak analyses (peak t threshold ltgtplusmn370 in bold allpeaks reported with t lt 370 are within a significant cluster see Methods) Peaks in italic are also reported in Table 1 See legends to Tables 1 and 2and Methods for further explanation

Rainville et al 895

and attentional processes (ie increased attentionabsorption concurrent with decreased cortical arousalincreased relaxation) (Aston-Jones et al 1999) Theindirect nature of the rCBF measures and the relativelypoor resolution of the PET method require somecaution in evaluating the possible anatomo-functionalimplications of our results in the brainstem Howeverthe convergent findings observed in other brain imag-ing studies and the observations provided in animalstudies support the notion that ascending cholinergicand noradrenergic pathways may contribute differen-tially to the multiple dimensions of experience thatcharacterize hypnosis

The overall pattern of results found in the ACC likelyreflects the heterogeneity of functions associated withthis area (Devinsky Morrell amp Vogt 1995) The locationof the most posterior relaxation-related peak in the ACC(mACC) is consistent with our previous observationof ACC activation during hypnosis (Rainville Hofbaueret al 1999) This relaxation-related peak is only slightlyanterior to the motor area of the caudal ACC (Picard ampStrick 1996) and may be involved in the installment of arelaxed state (also see precentral area below) In con-trast a positive absorption-specific effect was observedin a more rostral region of the ACC (rACC) close to anegative relaxation-specific correlation (see Table 1)This area of the ACC has previously been involved inexecutive attention in the detection of errors and in themonitoring of conflict between competing cognitiveprocesses (Bush Luu amp Posner 2000 Cohen Botvinickamp Carter 2000 Badgaiyan amp Posner 1998 Posner ampRothbart 1998) A meta-analysis of PET studies inves-tigating cognitive functions further suggested that theincrease in activity within this sector of the ACC isrelated to the difficulty of the task performed (PausKoski Caramanos amp Westbury 1998) Our findings areconsistent with these propositions to the extent thatthe engagement of the cognitive and neurophysiologicalprocesses implied in each of those accounts may beaccompanied by a subjective experience of increasedmental absorption

The coordinated pattern of rCBF changes in thebrainstem the thalamus and the ACC may reflect theinterrelationships between the multiple components of anetwork (eg Paus et al 1997) herein shown to beassociated with the feeling of being lsquolsquomentally absorbedrsquorsquoThe precise location of the observed absorption-specificthalamic peak is consistent with an involvement of theintralaminar and medio-dorsal nuclei which have recip-rocal connections with the ACC (Vogt amp Gabriel 1993)The finding that the coordinated activity in the thalamusand the ACC is disrupted in persistent vegetative states isconsistent with the notion that these structures work intandem to regulate consciousness (Laureys et al 2000also see Jeanmonod Magnin amp Morel 1996) Further-more a functional interaction between arousal andattentional processes has been reported in the thalamus

where the putative attention-related activity associatedwith the performance of a simple visual discriminationtask was found to increase in states of low arousal (Portaset al 1998) This increase in thalamic activity wassuggested (1) to reflect a compensatory mechanism thatpermitted the maintenance of stable levels of perform-ance in states of low arousal and (2) to prevent thegeneralized thalamo-cortical synchronization that wouldlead to sleep Here the opposite effects of relaxation andabsorption on thalamic activity may reflect this compen-satory mechanism that maintains high levels of focusedattention in deeply relaxed subjects during hypnosisThis function may be critical not only in hypnosis butalso in other conditions of deep relaxation distinct fromboth sleep and normal wakefulness such as meditativestates (Lou et al 1999) Furthermore the coactivation ofthe ACC and the ponto-mesencephalic brainstem mayreflect the contribution of the ACC to the regulation ofattention-related activity in the locus coeruleus (Cohenet al 2000) The positive regression found with absorp-tion in the ponto-mesencephalic brainstem and themore robust regression observed in the thalamus andthe ACC after accounting for relaxation-related changes(absorption-specific Table 1) further substantiate thepossibility that brainstem and thalamic nuclei interactwith the ACC to regulate the interaction between atten-tion and cortical arousal Taken together these resultsare consistent with a contribution of brainstem nucleithe intralaminar and medio-dorsal nuclei of the thala-mus and the ACC to the changes in phenomenalexperience that characterize hypnotic states

Additional Relaxation- and Absorption-RelatedChanges in rCBF

Relaxation-Related Activity

We observed strong relaxation-related increases in rCBFin the precentral gyrus bilaterally and reciprocaldecreases in somatosensory areas (S1 S2 and insula)Precentral and premotor activation has been reportedduring hypnosis in an independent study (Maquet et al1999) and precentral rCBF was correlated with the rCBFmeasured at the ACC site of hypnosis-related activity inour previous study (see Appendix in Rainville Hofbaueret al 1999) Similar increases in activity in motor andpremotor areas have been associated with voluntarymuscular relaxation (Toma et al 1999) but the presentresults may reflect more than physical relaxation

All standard hypnotic procedures include instructionsfor relaxation However the specific contribution ofmuscular relaxation and decreased arousal to the pro-duction of hypnotic states is unclear as hypnotic phe-nomena have been produced during muscular exercise(Banyai amp Hilgard 1976) and with suggestions of active-alertness (Vingoe 1968 1973) Here the absence ofsignificant effect of hypnosis on heart rate indicates thatchanges in cerebral activity did not correlate with

896 Journal of Cognitive Neuroscience Volume 14 Number 6

changes in peripheral arousal and suggests that subjectswere already physically relaxed in the baseline controlcondition This implies that the hypnosis-inducedchanges in self-ratings of relaxation may not simplyreflect changes in lsquolsquoperipheralrsquorsquo arousal but may attestmore specifically of an increase in lsquolsquomentalrsquorsquo relaxationand a reduction in lsquolsquocorticalrsquorsquo arousal This is consistentwith Pricersquos experiential model of hypnosis (see Intro-duction) and with our previous study showing anincrease in slow (delta) EEG activity during hypnosis

Relaxation-related effects observed outside primarysomatomotor areas may partly reflect subjective feelingsof mental ease more closely In the subtraction analysishypnosis-related decreases were found in the rightlateral posterior parietal rCBF both here (x y z 40iexcl52 44) and in our previous study (x y z 46 iexcl50 42from Table 1 in Rainville Hofbauer et al 1999) Herethese changes were strongly but not specifically asso-ciated with relaxation (x y z 39 iexcl49 45 see Table 2Figure 3A) Furthermore after accounting for absorp-tion-related variance right prefrontal activity was neg-atively correlated with relaxation (Table 2) Thoseadditional changes in the right posterior parietal cortexand the right prefrontal cortices may contribute to thesubjective feelings of mental ease rather than or inaddition to physical relaxation

Fronto-Parietal Attention Networks

Absorption-related activity was widespread and bilateralin the prefrontal cortices but peaks were generallystronger in the right hemisphere Positive regressionpeaks were maximal in the ventrolateral frontal corticesover the inferior frontal gyrus and in the anterior insulaA positive absorption-related regression peak was alsosignificant in the right inferior parietal lobule Theseareas also displayed strong coactivation with absorption-related thalamic activity Very similar patterns of activa-tion have been associated with attentional processes intasks involving visual (eg Coull Frackowiak amp Frith1998) auditory (Paus et al 1997) and somatosensorystimuli (Peyron et al 1999) Notably the location of thepositive parietal peak observed here closely matches theactivation sites reported in those studies and the site ofcovariation with the right ventrolateral attention-relatedactivity reported in Paus et al (1997) suggesting theactivation of a similar network The coordinated absorp-tion-related activity observed here in the brainstem thethalamus the ACC the right inferior frontal gyrus andthe right inferior parietal lobule provides very strongevidence that mental absorption is an experiential cor-relate of the activation of the brainrsquos lsquolsquoexecutive atten-tional networkrsquorsquo and suggests that this system plays acritical role in the production of hypnotic states

Negative absorption-related regression peaks werealso found in both the right and left lateral parietalcortices and in the precuneus (see Table 2) These

effects were largely independent of thalamic activity asindicated by the absence of significant effects at theselocations in the covariation analysis (Table 3) The rightposterior parietal cortex has been suggested to con-stitute a vigilanceorientation system (Pardo Fox ampRaichle 1991) and hypnosis-related decreases in thisarea may reflect a relative disengagement towardexternal sources of stimulation Right and left posteriorparietal cortices at the precise sites of relaxation- andabsorption-related decrease in rCBF have been sug-gested to contribute to the monitoring of externalspace and time respectively (Gitelman et al 19961999 Kim et al 1999 Coull amp Nobre 1998 Nobreet al 1997) Although these functions were notdirectly assessed in this experiment the hypnoticinduction procedure includes specific instructions fordecreased orientation to and interest in irrelevantexternal sources of stimulation and previous observa-tions suggest that hypnotic relaxation and absorptionare precursors to some alterations in spatio-temporalorientation and monitoring (Price 1996) Thus wespeculate that those additional experiential changesmay be consequent to relaxation- and absorption-related decreases in posterior parietal activity

Relaxation- and Absorption-Related Effects onOccipital rCBF

The subtraction analysis confirmed the reliability of thehypnosis-related increase in occipital rCBF reported inour previous study (Rainville Hofbauer et al 1999) Wenow show that this effect was associated with the sub-jective experience of hypnotic relaxation (see Table 2relaxation-specific) Consistently our previous studydemonstrated a coupling between occipital increases inrCBF and increases in slow (delta) EEG activity duringhypnosis Similar increases in occipital rCBF andor slowEEG activity had been observed in another study onhypnosis (Maquet et al 1999) and in states of decreasedvigilance (Paus et al 1997) meditation (Lou et al 1999)and slow wave sleep (Kajimura et al 1999 Hofle et al1997) These effects are consistent with our previousproposition that hypnotic induction produces a globaldecrease in cross-modality suppression in unattendedsensory channels leading to a relative disinhibitionof cortical activity (see Paus et al 1997 KawashimaOrsquoSullivan amp Roland 1995)

In contrast negative correlations between rCBF andmental absorption were observed over both occipitallobes (Table 2 Figure 3B) Consistently occipital rCBFwas correlated negatively with thalamic rCBF at theabsorption-specific site (Table 3) These contrastingeffects imply that variations in occipital rCBF are asso-ciated with separate portions of the variance in relaxa-tion and absorption (Note that although absorptionand relaxation were significantly correlated the variancein absorption was largely independent of relaxation see

Rainville et al 897

Methods) For a given level of relaxation the increasein hypnotic absorption could reflect the concurrentengagement of the lsquolsquoexecutive attentional networkrsquorsquowhich exerts an opposite effect over brain areas sub-serving unattended sensory channels (ie a relativefacilitation of cross-modality suppression)

Hypnosis as a State of Consciousness

The representation of the body-self is central to theneurophenomenology of consciousness (Metzinger2000) In the Introduction we have proposed that theinduction of hypnosis produces global changes in sub-jective experience reflecting a modulation of basicaspects of the body-self representation Consistentlythe PET results indicate that hypnosis involves changesin activity within brain structures essential for the basicregulation of states of consciousness self-monitoringand self-regulation Furthermore changes in relaxationand absorption are precursors (although they may notbe essential) to other hypnosis-related effects such asthe diminished tendency to judge monitor and censorthe suspension of usual orientation toward time loca-tion andor sense of self and the experience of onersquosown response as automatic or extra-volitional (Price1996) These dimensions of experience also rely criticallyon self-representation and may depend at least partly oncerebral areas shown here to be involved in hypnosisAmong those changes the increased feeling of automa-ticity an altered feeling of agency may be the mostdistinctive aspect of hypnotic phenomenology (Weitzen-hoffer 1980) Interestingly the sense of agency hasrecently been suggested to involve areas that displayconsistent changes in activity during hypnosis such asthe right inferior parietal cortex the precuneus and thesomatosensory cortices (Blakemore amp Decety 2001Ruby amp Decety 2001) The modulation of activityobserved here within those areas is consistent withthe interpretation that hypnosis produces changes inself-representation construed as an essential element forconscious experience

Conclusion

The present study used self-ratings of subjective feelingsof mental relaxation and mental absorption to map brainareas involved in hypnosis We replicated previous find-ings and further demonstrated that hypnotic relaxationand absorption reflect changes in brain activity withinregions involved in the control of consciousness statesand in self-regulation such as the brainstem the thala-mus and the ACC The coordinated activity within thesestructures and other absorption-related areas such asthe ventrolateral frontal and right posterior parietalcortices has been previously shown to underlie theregulation of the content of consciousness throughmechanisms of executive attention We must recognize

that our findings are correlative in nature and arerelevant to hypnosis to the extent that mental relaxationand absorption are conceived as basic experientialdimensions that characterize hypnotic phenomenaWe further speculate that these changes in subjectiveexperience and brain activity may contribute to otherhypnosis-related effects such as the altered feeling ofagency experienced during hypnosis These findings areconsistent with the notion that hypnotic states areachieved through the modulation of activity within adistributed network of cerebral structures involved inthe regulation of consciousness states

METHODS

Subjects

Ten right-handed subjects (4 men 6 women) wereselected from a group of 22 volunteers as a part of astudy on the hypnotic modulation of pain (Hofbaueret al 2001) Hypnotic susceptibility was assessed usingthe SHSS-A administered between scans (range 111ndash1011 mean plusmn SD 69 plusmn28) The Ethics Committee ofthe Montreal Neurological Institute (MNI) approved allprocedures and subjects signed a consent form describ-ing the procedure and affirming their right to withdrawfrom the experiment without prejudice

Experimental Procedure

We report the results obtained in eight scans acquired ina restful baseline and hypnosis condition Hypnoticinduction started immediately after Scan 4 and wassustained in the remaining scans by repeating inductioninstructions between scans Instructions included sug-gestions for (1) increased physical and mental relaxa-tion (2) comfortable feeling of warmth heaviness anddrowsiness (3) sustained passive attention to theexperimenterrsquos voice and to the instructions and (4)decreased concern with and orientation to external andinternal (mental) sources of distraction No specificinstruction for visual imagery was included During allscans the subjectsrsquo eyes were closed and their left handwas immersed in warm or painfully hot water Pain-related activation and four additional scans performedwith suggestions for pain modulation are reported else-where (Hofbauer et al 2001)

Self-Ratings of Mental Relaxation and Absorption

After each scan subjects were instructed to rate (0ndash10)(1) their level of tensionndashrelaxation with lsquolsquo10 being themost relaxed and at ease you can bersquorsquo and (2) their levelof sustained focus of attention with lsquolsquo10 being the mostabsorbed and the largest amount of sustained focusedattention you can gatherrsquorsquo Ratings of relaxation andabsorption were transformed using the rank within sub-jects to (1) control for individual differences (2) prevent

898 Journal of Cognitive Neuroscience Volume 14 Number 6

scaling biases and (3) parallel the analysis of rCBF dataSubjects rated pain on separate scales (0ndash100) Hypno-sis-related increases in relaxation and absorption did notinteract with the stimulation condition (pain vs warmstimulation prsquos gt 10) neither relaxation nor absorptioncorrelated significantly with pain ratings (all prsquos gt 10)and pain was not altered by hypnosis alone [t(9) = 069p = 51]

PET Imaging Methods

rCBF was measured using the H215O bolus injection

method (10 millicuriesscan) without arterial blood sam-pling (Herscovitch Markham amp Raichle 1983) with ahigh-resolution PET scanner operated in 3-D acquisitionmode (Siemens ECAT HR+ 63 slices) Stimulus onsetwas simultaneous with bolus injection and 1-min acquis-ition scans started about 15 sec postinjection (interscaninterval of 12ndash15 min) Data from the first 40 sec ofacquisition were reconstructed and analyzed Each sub-ject also underwent a high-resolution anatomical MRI(160 1-mm sagittal slices acquired on a Philips 15-TGyroscan system) Each PET and MRI volume wasaligned and transformed using software developed atthe MNI to match the MNI standardized Talairach space(Collins Neelin Peters amp Evans 1994 Talairach ampTournoux 1988) PET volumes were smoothed (FWHM= 14 mm) and normalized to the average brain countPeak and cluster analyses were performed (FristonWorsley Frackowiak Mazziotta amp Evans 1994 WorsleyEvans Marrett amp Neelin 1992)

Reliability of Hypnosis-Related Effects

A first analysis was performed using the subtractionmethod (Hypnosis minus Baseline) to evaluate thereliability of the effects reported in our previous study(Table 2 in Rainville Hofbauer et al 1999) We consid-ered that hypnosis-related changes in rCBF were repli-cated when a significant peak was observed within oneresel (Worsley et al 1992) of the peak sites reported inour previous study or when the peak sites were within asignificant cluster

Regression of rCBF on Self-Ratings of Relaxationand Absorption

Regression analyses were used to test the relationbetween ratings and rCBF (GLM) Subject- and stimu-lus-related effects were removed first (ANCOVA) andthe significance of the regression slope between thecovariate of interest and rCBF was estimated usingt tests Relaxation-specific and absorption-specific effectswere further tested using ANCOVAs to remove thevariance shared between absorption and relaxation(R2 = 42 p lt 001) The statistical criterion was setto t gt 258 (two-tailed uncorrected p lt 01) in the

directed searches restricted to the brainstem the thala-mus and the ACC (Table 1 Figure 2) Global searcheffects are significant ( p lt 05) based on peak (t valuegt 420) andor clusters analysis after a correction formultiple comparisons over the gray matter volume(uncorrected p lt 0001) (Table 2 Figure 3)

Thalamic Covariations

A covariation analysis was performed in which the rCBFmeasured in the thalamus was used as the covariate ofinterest after accounting for subject- and stimulus-related variance (ANCOVA see Tables 1 and 3) Becausewe were mainly interested in the relationship betweenthe activity in the thalamus and other absorption-relatedsites the threshold for statistical significance was set tot = 370 ( p = 05 uncorrected p lt 0008) based on thevolume defined by the sum of clusters of voxels showingsignificant absorption-specific effects (186 cm3 seeWorsley et al 1992)

Acknowledgments

We thank R Adolphs S Anderson A Bechara A R DamasioH Damasio Susan Lutgendorf J Parvizi and D Tranel fortheir comments on preliminary versions of the manuscriptPET analyses were performed using the software DOTdeveloped by Sylvain Milot and the MINC programs developedby Peter Neelin at the McConnell Brain Imaging Center of theMontreal Neurological Institute This study was supported bythe Medical Research Council (MRC) of Canada Dr Rainvillewas supported by the Medical Research Council of Canada andthe Human Frontier Science Program and Dr Hofbauer wassupported by the Fonds pour la recherche en sante du Quebecand the Royal Victoria Hospital Research Institute

Reprint requests should be sent to Pierre Rainville Faculte deMedecine dentaire Universite de Montreal CP 6128 SuccCentre-ville Montreal Qc H3C 3J7 Canada or via e-mailpierrerainvilleumontrealca

REFERENCES

Aston-Jones G Rajkowski J amp Cohen J (1999) Role of locuscoeruleus in attention and behavioral flexibility BiologicalPsychiatry 46 1309 ndash1320

Badgaiyan R D amp Posner M I (1998) Mapping the cingulatecortex in response selection and monitoring Neuroimage7 255 ndash260

Balthazard C G amp Woody E Z (1992) The spectral analysisof hypnotic performance with respect to lsquolsquoabsorptionrsquorsquoInternational Journal of Clinical and ExperimentalHypnosis 40 21ndash43

Banyai E I amp Hilgard E R (1976) A comparison ofactive-alert hypnotic induction with traditional relaxationinduction Journal of Abnormal Psychology 85 218 ndash224

Blakemore S J amp Decety J (2001) From the perception ofaction to the understanding of intention Nature ReviewsNeuroscience 2 561 ndash567

Braun A R Balkin T J Wesenten N J Carson R EVarga M Baldwin P Selbie S Belenky G amp HerscovitchP (1997) Regional cerebral blood flow throughout the

Rainville et al 899

sleep ndashwake cycle An H2(15)O PET study Brain 1201173 ndash1197

Bush G Luu P amp Posner M I (2000) Cognitive andemotional influences in anterior cingulate cortex Trendsin Cognitive Sciences 4 215 ndash222

Chalmers D J (2000) What is a neural correlate ofconsciousness In T Metzinger (Ed) Neural correlatesof consciousness Empirical and conceptual questions(pp 17ndash39) Cambridge MIT Press

Coe W C amp Sarbin T R (1977) Hypnosis from thestandpoint of a contextualist Annals of the New YorkAcademy of Sciences 296 2ndash13

Cohen J D Botvinick M amp Carter C S (2000) Anteriorcingulate and prefrontal cortex Whorsquos in control NatureNeuroscience 3 421 ndash423

Collins D L Neelin P Peters T M amp Evans A C (1994)Automatic 3D intersubject registration of MR volumetric datain standardized Talairach space Journal of ComputerAssisted Tomography 18 192 ndash205

Coull J T Frackowiak R S amp Frith C D (1998) Monitoringfor target objects Activation of right frontal and parietalcortices with increasing time on task Neuropsychologia 361325 ndash1334

Coull J T amp Nobre A C (1998) Where and when to payattention The neural systems for directing attention tospatial locations and to time intervals as revealed by bothPET and fMRI Journal of Neuroscience 18 7426 ndash7435

Crawford H J (1994) Brain dynamics and hypnosisAttentional and disattentional processes InternationalJournal of Clinical and Experimental Hypnosis 42204 ndash232

Crawford H J amp Gruzelier J H (1992) A midstream view ofthe neuropsychophysiology of hypnosis Recent researchand future directions In E Fromm amp M R Nash (Eds)Contemporary hypnosis research (pp 227 ndash266) New YorkGuilford Press

Crawford H J Knebel T Kaplan L Vendemia J M C XieM Jamison S amp Pribram K H (1998) Hypnotic analgesia1 Somatosensory event-related potential changes to noxiousstimuli and 2 Transfer learning to reduce chronic low backpain International Journal of Clinical and ExperimentalHypnosis 46 92ndash132

Damasio A R (1999) The feeling of what happens Body andemotion and the making of consciousness New YorkHartcourt Brace

De Pascalis V Magurano M R amp Bellusci A (1999) Painperception somatosensory event-related potentials andskin conductance responses to painful stimuli in high midand low hypnotizable subjects Effects of differential painreduction strategies Pain 83 499 ndash508

Devinsky O Morrell M J amp Vogt B A (1995) Contributionsof anterior cingulate cortex to behaviour Brain 118279 ndash306

Fiset P Paus T Daloze T Plourde G Meuret PBonhomme V Hajj-Ali N Backman S B amp Evans A C(1999) Brain mechanisms of propofol-induced loss ofconsciousness in humans A positron emission tomographicstudy Journal of Neuroscience 19 5505 ndash5513

Friston K J Worsley K J Frackowiak R S J Mazziotta J Camp Evans A C (1994) Assessing the significance of focalactivation using their spatial extent Human Brain Mapping1 214ndash220

Gitelman D R Alpert N M Kosslyn S Daffner K ScintoL Thompson W amp Mesulam M M (1996) Functionalimaging of human right hemispheric activation forexploratory movements Annals of Neurology 39 174ndash179

Gitelman D R Nobre A C Parrish T B LaBar K S KimY H Meyer J R amp Mesulam M (1999) A large-scale

distributed network for covert spatial attention Furtheranatomical delineation based on stringent behavioural andcognitive controls Brain 122 1093 ndash1106

Gruzelier J (1998) A working model of the neurophysiologyof hypnosis A review of evidence Contemporary Hypnosis15 3ndash21

Henson R N A Rugg M D Shallice T amp Dolan R J (2000)Confidence in recognition memory for words Dissociatingright prefrontal roles in episodic retrieval Journal ofCognitive Neuroscience 12 913 ndash923

Henson R N A Rugg M D Shallice T Joseph O ampDolan R J (1999) Recollection and familiarity inrecognition memory An event-related functional magneticresonance imaging study Journal of Neuroscience 193962 ndash3972

Herscovitch P Markham J amp Raichle M E (1983) Brainblood flow measured with intravenous H2(15)O I Theoryand error analysis Journal of Nuclear Medicine 24782 ndash789

Hofbauer R K Rainville P Duncan G H amp Bushnell M C(2001) Cortical representation of the sensory dimension ofpain Journal of Neurophysiology 86 402 ndash411

Hofle N Paus T Reutens D Fiset P Gotman J EvansA C amp Jones B E (1997) Regional cerebral blood flowchanges as a function of delta and spindle activity duringslow wave sleep in humans Journal of Neuroscience 174800 ndash4808

Jeanmonod D Magnin M amp Morel A (1996) Low-thresholdcalcium spike bursts in the human thalamus Commonphysiopathology for sensory motor and limbic positivesymptoms Brain 119 363ndash375

Kajimura N Uchiyama M Takayama Y Uchida S Uema TKato M Sekimoto M Watanabe T Nakajima THorikoshi S Ogawa K Nishikawa M Hiroki M Kudo YMatsuda H Okawa M amp Takahashi K (1999) Activityof midbrain reticular formation and neocortex during theprogression of human non-rapid eye movement sleepJournal of Neuroscience 19 10065 ndash10073

Kawashima R OrsquoSullivan B T amp Roland P E (1995)Positron-emission tomography studies of cross-modalityinhibition in selective attentional tasks Closing the lsquolsquomindrsquoseyersquorsquo Proceedings of the National Academy of SciencesUSA 92 5969 ndash5972

Kim Y H Gitelman D R Nobre A C Parrish T BLaBar K S amp Mesulam M M (1999) The large-scaleneural network for spatial attention displays multifunctionaloverlap but differential asymmetry Neuroimage 9269 ndash277

Kinomura S Larsson J Gulyas B amp Roland P E (1996)Activation by attention of the human reticular formationand thalamic intralaminar nuclei Science 271 512ndash515

Kosslyn S M Thompson W L Costantini-Ferrando M FAlpert N M amp Spiegel D (2000) Hypnotic visual illusionalters color processing in the brain American Journal ofPsychiatry 157 1279 ndash1284

Laureys S Faymonville M E Luxen A Lamy M Franck Gamp Maquet P (2000) Restoration of thalamocorticalconnectivity after recovery from persistent vegetative stateLancet 355 1790ndash1791

Lou H C Kjaer T W Friberg L Wildschiodtz G Holm Samp Nowak M (1999) A 15OndashH2O PET study of meditationand the resting state of normal consciousness HumanBrain Mapping 7 98ndash105

Maquet P Degueldre C Delfiore G Aerts J Peters J MLuxen A amp Franck G (1997) Functional neuroanatomyof human slow wave sleep Journal of Neuroscience 172807 ndash2812

Maquet P Faymonville M E Degueldre C Delfiore G

900 Journal of Cognitive Neuroscience Volume 14 Number 6

Franck G Luxen A amp Lamy M (1999) Functionalneuroanatomy of hypnotic state Biological Psychiatry 45327 ndash333

Metzinger T (2000) The subjectivity of subjective experienceA representationalist analysis of the first-person perspectiveIn T Metzinger (Ed) Neural correlates of consciousnessEmprical and conceptual questions (pp 285 ndash306)Cambridge MIT Press

Nobre A C Sebestyen G N Gitelman D R MesulamM M Frackowiak R S amp Frith C D (1997) Functionallocalization of the system for visuospatial attention usingpositron emission tomography Brain 120 515 ndash533

Pardo J V Fox P T amp Raichle M E (1991) Localization of ahuman system for sustained attention by positron emissiontomography Nature 349 61ndash64

Paus T (2001) Primate anterior cingulate cortex Wheremotor control drive and cognition interface NatureReviews Neuroscience 2 417 ndash424

Paus T Koski L Caramanos Z amp Westbury C (1998)Regional differences in the effects of task difficulty andmotor output on blood flow response in the human anteriorcingulate cortex A review of 107 PET activation studiesNeuroReport 9 R37ndashR47

Paus T Zatorre R J Hofle N Caramanos Z Gotman JPetrides M amp Evans A C (1997) Time-related changesin neural systems underlying attention and arousal duringthe performance of an auditory vigilance task Journal ofCognitive Neuroscience 9 392ndash408

Peyron R Garcia-Larrea L Gregoire M C Costes NConvers P Lavenne F Mauguiere F Michel D ampLaurent B (1999) Haemodynamic brain responses to acutepain in humansmdashSensory and attentional networks Brain122 1765 ndash1779

Picard N amp Strick P L (1996) Motor areas of the medial wallA review of their location and functional activation CerebralCortex 6 342 ndash353

Portas C M Howseman A M Josephs O Turner R ampFrith C D (1998) A specific role for the thalamus inmediating the interaction of attention and arousal inhumans Journal of Neuroscience 18 8979 ndash8989

Posner M I amp Rothbart M K (1998) Attentionself-regulation and consciousness Philosophical

Transactions of the Royal Society of London Series BBiological Sciences 353 1915 ndash1927

Price D D (1996) Hypnotic analgesia Psychological andneural mechanisms In J Barber (Ed) Hypnosis andsuggestions in the treatment of pain (pp 67ndash84) NewYork Norton

Price D D amp Barrell J J (1980) An experiential approachwith quantitative methods A research paradigm Journal ofHumanistic Psychology 20 75ndash95

Rainville P Carrier B Hofbauer R K Bushnell M C ampDuncan G H (1999) Dissociation of pain sensory andaffective dimensions using hypnotic modulation Pain 82159 ndash171

Rainville P Duncan G H Price D D Carrier B ampBushnell M C (1997) Pain affect encoded in humananterior cingulate but not somatosensory cortex Science277 968 ndash971

Rainville P Hofbauer R K Paus T Duncan G H BushnellM C amp Price D D (1999) Cerebral mechanisms ofhypnotic induction and suggestion Journal of CognitiveNeuroscience 11 110ndash125

Ruby P amp Decety J (2001) Effect of subjective perspectivetaking during simulation of action A PET investigation ofagency Nature Neuroscience 4 546 ndash550

Steriade M amp McCarley R W (1990) Brainstem control ofwakefulness and sleep New York Plenum

Szechtman H Woody E Bowers K S amp Nahmias C(1998) Where the imaginal appears real A positronemission tomography study of auditory hallucinationsProceedings of the National Academy of Sciences USA95 1956 ndash1960

Talairach J amp Tournoux P (1988) Co-planar stereotaxicatlas of the human brain New York Thieme

Tellegen A amp Atkinson G (1974) Openness to absorbingand self-altering experiences (lsquolsquoabsorptionrsquorsquo) a trait relatedto hypnotic susceptibility Journal of Abnormal Psychology83 268 ndash277

Toma K Honda M Hanakawa T Okada T Fukuyama HIkeda A Nishizawa S Konishi J amp Shibasaki H (1999)Activities of the primary and supplementary motor areasincrease in preparation and execution of voluntary musclerelaxation An event-related fMRI study Journal ofNeuroscience 19 3527 ndash3534

Varela F J amp Shear J (1999) First-person methodologiesWhat why and how Journal of Consciousness Studies 61ndash14

Vingoe F J (1968) The development of a group alert-trancescale International Journal of Clinical and ExperimentalHypnosis 16 120 ndash132

Vingoe F J (1973) Comparison of the Harvard Group Scaleof Hypnotic Susceptibility Form A and the Group AlertTrance Scale in a university population InternationalJournal of Clinical and Experimental Hypnosis 21169 ndash179

Vogt B A amp Gabriel M (1993) Neurobiology of cingulatecortex and limbic thalamus A comprehensive handbookBoston Birkauser

Weitzenhoffer A M (1980) Hypnotic susceptibility revisitedAmerican Journal of Clinical Hypnosis 22 130 ndash146

Willoch F Rosen G Tolle T R Oslashye I Wester H J BernerN Schwaiger M amp Bartenstein P (2000) Phantom limbpain in the human brain Unravelling neural circuitries ofphantom limb pain sensations using positron emissiontomography Annals of Neurology 48 842 ndash849

Worsley K J Evans A C Marrett S amp Neelin P (1992)A three-dimensional statistical analysis for CBF activationstudies in human brain Journal of Cerebral Blood Flow andMetabolism 12 900 ndash918

Rainville et al 901

Page 5: Hypnosis Modulates Activity in Brain Structures Involved in the …pineda/COGS175/readings/Rain... · 2005. 2. 28. · Hypnosis Modulates Activity in Brain Structures Involved in

than absorption and the relaxation-related effects heldafter accounting for variance in absorption (Table 2mdashrelaxation-specific) Additional sites of relaxation-specificeffects included negative correlations in the right parie-tal operculum and lobule and positive correlations in theright precuneus the left inferior parietal lobule and thebilateral occipital cortices (Table 2mdashrelaxation-specific)

The effects associated with absorption in the posteri-or cortices were strikingly different from the effects ofrelaxation After accounting for relaxation-related var-iance we observed both positive and negative absorp-tion-specific correlations in both the right and leftparietal lobules (see Table 2mdashabsorption-specific) Inthe inferior parietal lobules positive and negative cor-relations dominated in the right and left hemispheresrespectively (Figure 3B) Strong negative correlationswere also observed over the right precuneus theposterior cingulate cortex and both occipital lobes(Figure 3B)

Additional statistical trends directly relevant to ourhypotheses were also observed in the somatosensorycortices where rCBF was negatively correlated with men-tal relaxation (see Figure 3A right S1 peak coordinates44 iexcl35 59 t = iexcl286 p-uncorrected = 014 clusterp = 06 left S1 iexcl44 iexcl21 16 t = iexcl251 p-uncorrected =026 cluster analysis p gt 10 right parietal operculumS2 48 iexcl21 24 t = iexcl351 p-uncorrected = 003 clusterp gt 10 right posterior insula 44 iexcl4 15 t = iexcl296p-uncorrected = 011 cluster p gt 10)

Covariations with Thalamic rCBF

In our previous study thalamic activity was found tobe correlated with hypnosis-related ACC activity (seeTable 2 and Appendix in Rainville Hofbauer et al1999) and several studies suggest a pivotal role of thethalamus in arousal attention and consciousness andin the interaction between the brainstem and the ACC(eg Paus et al 1997 Paus 2001 Portas HowsemanJosephs Turner amp Frith 1998 Hofle et al 1997) Herewe tested the association between absorption-relatedactivity in the thalamus and activity in other sites ofabsorption-related changes using a covariation analysiscentered on the absorption-specific peak in the thala-mus reported in Table 1 Absorption-specific sites in thebrainstem (upper pons) and the ACC showed significantcovariations with thalamic rCBF (Table 1) Additionalregions where rCBF showed a positive correlation withthalamic rCBF included bilateral frontal sites in theinferior middle and superior frontal gyri extendingmedially into the right ACC and the right insula(Table 3) Many of those peak locations matched frontalsites specifically related to mental absorption (italicizedin Table 2) A strong positive peak was also observed inthe right inferior parietal lobule precisely at the loca-tion where rCBF correlated strongly and specificallywith mental absorption (compare Table 2 absorption-

specific and Table 3) Areas displaying negative corre-lation with thalamic rCBF were found bilaterally in theoccipital lobes consistent with the absorption-specificeffects reported in Table 2

DISCUSSION

The approach used in this study provided a descriptionof cerebral activity associated with specific changes inphenomenal experience produced by a standard hyp-notic induction We discuss in turn the evidence for theproduction of hypnotic phenomena the reliability ofhypnosis-related effects the effects associated with men-tal relaxation and absorption and the implications ofour results for a state theory of hypnosis

Hypnosis and Phenomenal Experience

The induction of hypnosis produced the expectedincreases in both mental relaxation and absorptionThese changes were positively correlated (see Methods)as predicted by the experiential model of hypnosisproposed by Price (1996) and the ability to maintainhypnotic relaxation and absorption depended upon thesubjectsrsquo hypnotic susceptibility The higher levels ofabsorption maintained in highly hypnotizable subjectsare consistent with the positive association betweenabsorption attentional processes and hypnotizabilitysuggested in previous studies (Crawford 1994 Baltha-zard amp Woody 1992 Tellegen amp Atkinson 1974) Theseresults and additional convergent observations de-scribed in our previous report of pain-related effects(Hofbauer et al 2001) and from several experimentsusing similar methodology (Rainville et al 1997 Rain-ville Carrier et al 1999) confirmed the reliable produc-tion of hypnotic phenomena

Reliability of Hypnosis-Related Effects on rCBF

The experimental conditions examined here and in thefirst 8 scans in our previous study were identicalmdashthesame hypnotic induction procedure was applied by twodifferent experimenters and the two separate groups ofsubjects tested had comparable mean hypnotic suscep-tibility scores (Rainville Hofbauer et al 1999) Theresults of the subtraction analysis largely replicated ourprevious findings as well as those reported by Maquetet al (1999) In comparison to our previous experimentdifferences in the methods were limited to the additionof relaxation and absorption ratings after the scans Thelarger areas of frontal activation including the precentralregion and the more restricted occipital activationobserved here may reflect the emphasis put on hypnoticrelaxation and absorption during the scans As thesedimensions of experience characterize standard hypno-tic induction procedures we submit that these differ-ences further emphasize the functional significance of

Rainville et al 891

Tab

le2

R

esul

tsof

the

Glo

bal

Sear

ches

ofC

ereb

ral

Regi

ons

whe

rerC

BF

Show

eda

Sign

ifica

ntR

egre

ssio

nw

ithR

elax

atio

nan

dAb

sorp

tion

Regi

onP

eak

Loca

tion

Rela

xati

onRe

laxa

tion

-Spe

cifi

cAb

sorp

tion

Abs

orpt

ion

-Spe

cifi

c

xy

zt

xy

zt

xy

zt

xy

zt

Fron

tal

(F)

RF

Pole

(BA

10)

ndash34

562

iexcliexcl4

81

ndash28

555

+4

21

Rla

tF

Orb

ital

g(B

A11

)ndash

1946

iexcl20

iexcliexcl4

29

ndash19

44iexcl

20+

47

5

Rm

iddl

eF

g(B

A46

)ndash

3646

26iexcl

381

ndash34

4626

+3

79

Rin

fF

g(B

A47

)ndash

ndash47

34iexcl

18+

373

ndash

Rin

fF

g(B

A45

)ndash

478

15iexcl

386

5520

11+

352

ndash

Ra

nt

insu

lai

nf

Fg

(BA

144

4)ndash

4015

6iexcl

377

4310

2+

358

4013

5+

48

1

Rsu

pF

gc

ingu

late

g(B

A8

32)

ndash5

3745

iexcl3

68ndash

332

39+

43

2

Rsu

pF

g(B

A6)

ndashndash

1320

59+

369

1522

57+

43

3

Rm

edia

lsu

pF

g(B

A6)

ndashndash

3iexcl

466

+4

23

3iexcl

766

+3

92

Lla

tF

Orb

ital

g(B

A11

)ndash

ndashiexcl

3041

iexcl21

+3

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3143

iexcl18

+3

76

Lm

iddl

eF

g(B

A8)

ndashndash

iexcl46

1535

+4

10iexcl

4410

29+

328

Lm

iddl

eF

g(B

A46

)ndash

ndashiexcl

3637

18+

43

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3839

24+

407

La

nt

insu

lai

nf

Fg

(BA

144

4)ndash

ndashndash

iexcl34

817

+4

25

Lsu

pF

g(B

A6)

ndashndash

ndashiexcl

266

56+

416

Lsu

p

Fg

(BA

6)ndash

ndashiexcl

11iexcl

466

+3

68ndash

Cen

tral

Rp

rece

ntra

lg

(BA

4)54

iexcl4

53+

51

6ndash

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453

+5

05

ndash

Rp

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lg

(BA

4)42

iexcl7

50+

49

4ndash

ndashndash

Rp

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entr

alg

(BA

41

3)ndash

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iexcl16

36+

378

ndash

Lpr

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tral

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Fg

(BA

46)

iexcl35

iexcl6

53+

398

ndashndash

ndash

Lpr

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tral

g(B

A4)

iexcl47

iexcl16

47+

44

3ndash

iexcl48

iexcl14

50+

43

6ndash

Lpr

epo

stce

ntra

lg

(BA

41

3)ndash

iexcl30

iexcl37

60+

403

ndash

Tem

pora

l(T

)R

mid

dle

T

g(B

A21

)60

iexcl33

iexcl15

iexcl5

71

59iexcl

33iexcl

13iexcliexcl

55

1ndash

ndash

Rm

iddl

eT

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(BA

37)

56iexcl

45iexcl

9iexcl

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1ndash

55iexcl

47iexcl

6iexcliexcl

44

1ndash

Lpa

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ppoc

amp

alg

(BA

353

6)iexcl

36iexcl

23iexcl

18iexcl

413

ndashndash

ndash

Lin

fT

g

fusi

form

g(B

A37

)iexcl

52iexcl

42iexcl

20iexcl

52

4iexcl

59iexcl

44iexcl

12iexcliexcl

43

3iexcl

48iexcl

44iexcl

20iexcliexcl

44

6ndash

892 Journal of Cognitive Neuroscience Volume 14 Number 6

Pari

etal

(P)

RP

oper

culu

m(B

A40

)ndash

32iexcl

3027

iexcl3

55ndash

ndash

Rin

fP

lo

bule

(BA

40)

ndash56

iexcl40

50iexcl

377

ndash56

iexcl44

50+

42

4

RP

lobu

le(B

A40

7)

39iexcl

4945

iexcl4

87

ndash38

iexcl47

45iexcliexcl

44

334

iexcl56

42+

383

Rsu

pP

lobu

le(B

A7)

ndashndash

21iexcl

5062

iexcliexcl4

45

21iexcl

5260

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09

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ecun

eus

(BA

7)ndash

5iexcl

5645

+5

33

ndash5

iexcl56

45iexcliexcl

51

0

Prec

uneu

sp

ost

Cin

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(BA

731

)ndash

ndashndash

0iexcl

649

iexcliexcl5

05

Lin

fP

lobu

le(B

A40

)ndash

iexcl30

iexcl37

60+

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ndashiexcl

35iexcl

3550

iexcliexcl4

48

Lin

fP

lobu

le(B

A40

)ndash

ndashndash

iexcl52

iexcl56

47+

370

Occ

ipit

al(O

)Li

ngua

lg

pos

tC

ing

g(B

A18

31)

ndash0

iexcl66

9+

42

6ndash

ndash

Rin

fO

g

(BA

19)

ndash43

iexcl71

iexcl6

+3

6843

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5iexcliexcl

44

443

iexcl75

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17

Rli

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alg

(BA

18)

ndash4

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782

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68

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neu

s(B

A18

)ndash

12iexcl

8327

+5

20

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pO

g

(BA

19)

ndash17

iexcl81

38+

55

9ndash

15iexcl

8033

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02

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(BA

19)

30iexcl

8726

+4

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le(B

A18

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929

+4

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8iexcliexcl

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rmg

(BA

181

9)ndash

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+3

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g

prec

un

eus

(BA

197

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iexcl76

36iexcliexcl

42

3iexcl

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8739

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gual

g(B

A18

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ereb

ellu

mndash

ndashiexcl

17iexcl

76iexcl

18iexcl

351

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A18

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83iexcl

11iexcliexcl

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(BA

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8327

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A18

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able

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+4

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Rel

axat

ion

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ecifi

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tio

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ific

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cts

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ng

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ance

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ciat

edw

ith

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xati

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ecti

vely

(AN

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se

eM

eth

od

s)T

he

linea

rsl

op

ebe

twee

nrC

BF

and

rati

ngs

issi

gnifi

can

tatp

eak

loca

tio

ns

liste

d(t

thre

sho

ld=

plusmn4

20i

nb

old

see

Met

hod

s)P

eaks

wit

htgt

+3

50or

tlt

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50w

ith

ina

sign

ific

ant

clus

ter

(see

Met

hods

)are

also

indi

cate

dw

ith

thei

rco

ordi

nate

sP

eaks

clos

eto

or

wit

hin

regi

ons

wh

ere

sign

ific

ant

cova

riat

ions

wit

hth

alam

icrC

BF

wer

efo

und

are

ita

lici

zed

(see

Tab

le3

and

Met

hods

)P

eak

loca

tion

sar

eba

sed

onth

est

ereo

taxi

cat

las

of

Tal

aira

chan

dT

ourn

oux

(198

8)(x

=la

tera

ly

=an

teri

or

z=

supe

rior

)an

don

mor

phol

ogi

cal

lan

dmar

kson

the

mer

ged

PE

Tndash

MR

Iim

ages

(BA

=pr

obab

leB

rodm

annrsquo

sar

eaL

=

left

R

=

righ

tg

=gy

rus

ant

=an

teri

or

pos

t=

post

erio

rsu

p=

supe

rior

in

f=

infe

rior

)

Rainville et al 893

the underlying processes in the production of hypnoticstates as discussed below

Role of the Brainstem the Thalamus and the ACCin Hypnosis

Results of the regression analyses suggest that neuralactivity in the brainstem the thalamus and the ACCcontributes to the experience of being hypnotized Therelaxation-specific negative correlations in the mesen-

cephalic brainstem and the thalamus may reflect thewell-established contribution of brainstem and thalamicnuclei to the regulation of wakefulness and corticalarousal In functional brain imaging studies rCBFdecreases in the brainstem and the thalamus have beenassociated with decreased vigilance (Paus et al 1997)sleep (Kajimura et al 1999 Braun et al 1997 Hofleet al 1997 Maquet et al 1997) and the loss ofconsciousness produced by the anesthetic propofol(Fiset et al 1999) These effects and to some extent

Figure 3 Brain regionsshowing positive (redarrowheads) and negative(blue arrowheads) regres-sion peaks between rCBFand self-ratings of (A)relaxation and (B) absorp-tion after accounting forrelaxation-related variance(absorption-specific)Statistical t maps are super-imposed on the averageanatomical MRI (left is onthe left side) Slice locationsare indicated on the 3-Danatomical image of asingle subjectrsquos anatomicalMRI (A-positive) Positiverelaxation-related effectsare shown in the centralregion bilaterally (horizon-tal slice on the left) Apositive peak is shown inthe right superior occipitalgyrus (SOg) (coronal viewon the right note scalechange) (A-negative)A negative relaxation-related effect in the rightposterior parietal cortexis shown in horizontal(first from left) coronal(second) and lateralsagittal (third) views Theplus sign indicates the moreanterior location of thepeak positive regression inthe analysis of absorption-related effects as shown inB Additional negative cor-relations are shown in thebilateral middle and inferiortemporal gyri (second) andin the right somatosensorycortices (S1 S2 insula)(B-positive) A positiveabsorption-specific peak isshown in the right inferiorparietal lobule (first fromleft) The minus sign indicates the more posterior location of the negative regression peak in the analysis of relaxation-related effects as shown in

A Other peaks are shown on the midsagittal view in the thalamus and the anterior cingulate cortex (second from left) and in the left lenticularnuclei and bilateral prefrontal cortices (last three cuts from left) (B-negative) Negative absorption-related effects are shown in the left inferiorparietal lobule (first from left) in both occipital lobes (second and third from left) and in the precuneus (first and third) Stereotaxic coordinates ofpeaks are reported in Table 3 (see relaxation- and absorption-specific)

894 Journal of Cognitive Neuroscience Volume 14 Number 6

the present relaxation-related decrease in brainstemrCBF may reflect an attenuation of activity withinbrainstem cholinergic nuclei Such reduction has beenobserved during slow EEG activity before the onset ofsleep and during slow-wave sleep in animal studies(Steriade amp McCarley 1990) Consistent with this pos-sibility we previously reported an increase in slow(delta) EEG activity following hypnotic induction (Rain-ville Hofbauer et al 1999) Although hypnotic andsleep states are clearly distinct certain neurophysiolog-

ical mechanisms may be involved to a varying degree inthe production of both states

The positive association specifically observed betweenmental absorption and rCBF in the upper pons and thethalamus contrasts with the above relaxation-relatedeffect and is consistent with previous reports of atten-tion-related brain activation (Kinomura et al 1996) Thisactivity may reflect the involvement of the noradrenergicsystem of the locus coeruleus in focused attentionand possibly in the interaction between cortical arousal

Table 3 Cerebral Sites of Covariation with Thalamic rCBF at the Absorption-Specific Peak Coordinates (x = iexcl27 y = iexcl160z = 120)

Region Peak Location x y z t

Frontal (F) R medial sup F gACC (BA 624) 1 43 32 +382

R anterior cingulate gsup F g (BA 326) 8 13 44 +387

R inf F g (BA 44) 51 12 8 +387

R ant insula (BA 14) 38 12 5 +412

R sup F g (BA 6) 16 20 59 +371

R medial sup F g (BA 6) 3 iexcl6 63 +498

R medial sup F g (BA 6) 11 iexcl23 53 +412

L middle F g (BA 46) iexcl38 46 23 +381

L middle F g (BA 46) iexcl31 39 39 +374

L inf F g (BA 44) iexcl43 6 12 +430

L sup F g (BA 6) iexcl19 20 53 +340

L medial sup F g (BA 6) iexcl5 17 65 +353

L sup F g (BA 6) iexcl20 12 65 +283

Parietal R inf parietal lobule (BA 40) 56 iexcl44 50 +519

Occipital (O) R fusiform g (BA 19) 26 iexcl62 iexcl30 iexcliexcl515

R lingual g (BA 18) 7 iexcl78 6 iexcliexcl623

R sup O g (BA 19) 19 iexcl85 30 iexcliexcl714

R O pole (BA 18) 27 iexcl90 9 iexcliexcl751

L cuneus (BA 18) iexcl11 iexcl83 29 iexcliexcl633

L O pole (BA 18) iexcl23 iexcl88 6 iexcliexcl793

Subcortical R thalamus 17 iexcl11 2 +350

R brainstem 13 iexcl26 iexcl15 +312

R medial brainstem 3 iexcl32 iexcl24 +287

L cerebellum iexcl4 iexcl57 iexcl21 +409

L globus pallidus iexcl20 iexcl1 iexcl2 +302

L caudate nucleus iexcl12 6 20 +291

Positive and negative regression slopes are significant at sites listed based on cluster or peak analyses (peak t threshold ltgtplusmn370 in bold allpeaks reported with t lt 370 are within a significant cluster see Methods) Peaks in italic are also reported in Table 1 See legends to Tables 1 and 2and Methods for further explanation

Rainville et al 895

and attentional processes (ie increased attentionabsorption concurrent with decreased cortical arousalincreased relaxation) (Aston-Jones et al 1999) Theindirect nature of the rCBF measures and the relativelypoor resolution of the PET method require somecaution in evaluating the possible anatomo-functionalimplications of our results in the brainstem Howeverthe convergent findings observed in other brain imag-ing studies and the observations provided in animalstudies support the notion that ascending cholinergicand noradrenergic pathways may contribute differen-tially to the multiple dimensions of experience thatcharacterize hypnosis

The overall pattern of results found in the ACC likelyreflects the heterogeneity of functions associated withthis area (Devinsky Morrell amp Vogt 1995) The locationof the most posterior relaxation-related peak in the ACC(mACC) is consistent with our previous observationof ACC activation during hypnosis (Rainville Hofbaueret al 1999) This relaxation-related peak is only slightlyanterior to the motor area of the caudal ACC (Picard ampStrick 1996) and may be involved in the installment of arelaxed state (also see precentral area below) In con-trast a positive absorption-specific effect was observedin a more rostral region of the ACC (rACC) close to anegative relaxation-specific correlation (see Table 1)This area of the ACC has previously been involved inexecutive attention in the detection of errors and in themonitoring of conflict between competing cognitiveprocesses (Bush Luu amp Posner 2000 Cohen Botvinickamp Carter 2000 Badgaiyan amp Posner 1998 Posner ampRothbart 1998) A meta-analysis of PET studies inves-tigating cognitive functions further suggested that theincrease in activity within this sector of the ACC isrelated to the difficulty of the task performed (PausKoski Caramanos amp Westbury 1998) Our findings areconsistent with these propositions to the extent thatthe engagement of the cognitive and neurophysiologicalprocesses implied in each of those accounts may beaccompanied by a subjective experience of increasedmental absorption

The coordinated pattern of rCBF changes in thebrainstem the thalamus and the ACC may reflect theinterrelationships between the multiple components of anetwork (eg Paus et al 1997) herein shown to beassociated with the feeling of being lsquolsquomentally absorbedrsquorsquoThe precise location of the observed absorption-specificthalamic peak is consistent with an involvement of theintralaminar and medio-dorsal nuclei which have recip-rocal connections with the ACC (Vogt amp Gabriel 1993)The finding that the coordinated activity in the thalamusand the ACC is disrupted in persistent vegetative states isconsistent with the notion that these structures work intandem to regulate consciousness (Laureys et al 2000also see Jeanmonod Magnin amp Morel 1996) Further-more a functional interaction between arousal andattentional processes has been reported in the thalamus

where the putative attention-related activity associatedwith the performance of a simple visual discriminationtask was found to increase in states of low arousal (Portaset al 1998) This increase in thalamic activity wassuggested (1) to reflect a compensatory mechanism thatpermitted the maintenance of stable levels of perform-ance in states of low arousal and (2) to prevent thegeneralized thalamo-cortical synchronization that wouldlead to sleep Here the opposite effects of relaxation andabsorption on thalamic activity may reflect this compen-satory mechanism that maintains high levels of focusedattention in deeply relaxed subjects during hypnosisThis function may be critical not only in hypnosis butalso in other conditions of deep relaxation distinct fromboth sleep and normal wakefulness such as meditativestates (Lou et al 1999) Furthermore the coactivation ofthe ACC and the ponto-mesencephalic brainstem mayreflect the contribution of the ACC to the regulation ofattention-related activity in the locus coeruleus (Cohenet al 2000) The positive regression found with absorp-tion in the ponto-mesencephalic brainstem and themore robust regression observed in the thalamus andthe ACC after accounting for relaxation-related changes(absorption-specific Table 1) further substantiate thepossibility that brainstem and thalamic nuclei interactwith the ACC to regulate the interaction between atten-tion and cortical arousal Taken together these resultsare consistent with a contribution of brainstem nucleithe intralaminar and medio-dorsal nuclei of the thala-mus and the ACC to the changes in phenomenalexperience that characterize hypnotic states

Additional Relaxation- and Absorption-RelatedChanges in rCBF

Relaxation-Related Activity

We observed strong relaxation-related increases in rCBFin the precentral gyrus bilaterally and reciprocaldecreases in somatosensory areas (S1 S2 and insula)Precentral and premotor activation has been reportedduring hypnosis in an independent study (Maquet et al1999) and precentral rCBF was correlated with the rCBFmeasured at the ACC site of hypnosis-related activity inour previous study (see Appendix in Rainville Hofbaueret al 1999) Similar increases in activity in motor andpremotor areas have been associated with voluntarymuscular relaxation (Toma et al 1999) but the presentresults may reflect more than physical relaxation

All standard hypnotic procedures include instructionsfor relaxation However the specific contribution ofmuscular relaxation and decreased arousal to the pro-duction of hypnotic states is unclear as hypnotic phe-nomena have been produced during muscular exercise(Banyai amp Hilgard 1976) and with suggestions of active-alertness (Vingoe 1968 1973) Here the absence ofsignificant effect of hypnosis on heart rate indicates thatchanges in cerebral activity did not correlate with

896 Journal of Cognitive Neuroscience Volume 14 Number 6

changes in peripheral arousal and suggests that subjectswere already physically relaxed in the baseline controlcondition This implies that the hypnosis-inducedchanges in self-ratings of relaxation may not simplyreflect changes in lsquolsquoperipheralrsquorsquo arousal but may attestmore specifically of an increase in lsquolsquomentalrsquorsquo relaxationand a reduction in lsquolsquocorticalrsquorsquo arousal This is consistentwith Pricersquos experiential model of hypnosis (see Intro-duction) and with our previous study showing anincrease in slow (delta) EEG activity during hypnosis

Relaxation-related effects observed outside primarysomatomotor areas may partly reflect subjective feelingsof mental ease more closely In the subtraction analysishypnosis-related decreases were found in the rightlateral posterior parietal rCBF both here (x y z 40iexcl52 44) and in our previous study (x y z 46 iexcl50 42from Table 1 in Rainville Hofbauer et al 1999) Herethese changes were strongly but not specifically asso-ciated with relaxation (x y z 39 iexcl49 45 see Table 2Figure 3A) Furthermore after accounting for absorp-tion-related variance right prefrontal activity was neg-atively correlated with relaxation (Table 2) Thoseadditional changes in the right posterior parietal cortexand the right prefrontal cortices may contribute to thesubjective feelings of mental ease rather than or inaddition to physical relaxation

Fronto-Parietal Attention Networks

Absorption-related activity was widespread and bilateralin the prefrontal cortices but peaks were generallystronger in the right hemisphere Positive regressionpeaks were maximal in the ventrolateral frontal corticesover the inferior frontal gyrus and in the anterior insulaA positive absorption-related regression peak was alsosignificant in the right inferior parietal lobule Theseareas also displayed strong coactivation with absorption-related thalamic activity Very similar patterns of activa-tion have been associated with attentional processes intasks involving visual (eg Coull Frackowiak amp Frith1998) auditory (Paus et al 1997) and somatosensorystimuli (Peyron et al 1999) Notably the location of thepositive parietal peak observed here closely matches theactivation sites reported in those studies and the site ofcovariation with the right ventrolateral attention-relatedactivity reported in Paus et al (1997) suggesting theactivation of a similar network The coordinated absorp-tion-related activity observed here in the brainstem thethalamus the ACC the right inferior frontal gyrus andthe right inferior parietal lobule provides very strongevidence that mental absorption is an experiential cor-relate of the activation of the brainrsquos lsquolsquoexecutive atten-tional networkrsquorsquo and suggests that this system plays acritical role in the production of hypnotic states

Negative absorption-related regression peaks werealso found in both the right and left lateral parietalcortices and in the precuneus (see Table 2) These

effects were largely independent of thalamic activity asindicated by the absence of significant effects at theselocations in the covariation analysis (Table 3) The rightposterior parietal cortex has been suggested to con-stitute a vigilanceorientation system (Pardo Fox ampRaichle 1991) and hypnosis-related decreases in thisarea may reflect a relative disengagement towardexternal sources of stimulation Right and left posteriorparietal cortices at the precise sites of relaxation- andabsorption-related decrease in rCBF have been sug-gested to contribute to the monitoring of externalspace and time respectively (Gitelman et al 19961999 Kim et al 1999 Coull amp Nobre 1998 Nobreet al 1997) Although these functions were notdirectly assessed in this experiment the hypnoticinduction procedure includes specific instructions fordecreased orientation to and interest in irrelevantexternal sources of stimulation and previous observa-tions suggest that hypnotic relaxation and absorptionare precursors to some alterations in spatio-temporalorientation and monitoring (Price 1996) Thus wespeculate that those additional experiential changesmay be consequent to relaxation- and absorption-related decreases in posterior parietal activity

Relaxation- and Absorption-Related Effects onOccipital rCBF

The subtraction analysis confirmed the reliability of thehypnosis-related increase in occipital rCBF reported inour previous study (Rainville Hofbauer et al 1999) Wenow show that this effect was associated with the sub-jective experience of hypnotic relaxation (see Table 2relaxation-specific) Consistently our previous studydemonstrated a coupling between occipital increases inrCBF and increases in slow (delta) EEG activity duringhypnosis Similar increases in occipital rCBF andor slowEEG activity had been observed in another study onhypnosis (Maquet et al 1999) and in states of decreasedvigilance (Paus et al 1997) meditation (Lou et al 1999)and slow wave sleep (Kajimura et al 1999 Hofle et al1997) These effects are consistent with our previousproposition that hypnotic induction produces a globaldecrease in cross-modality suppression in unattendedsensory channels leading to a relative disinhibitionof cortical activity (see Paus et al 1997 KawashimaOrsquoSullivan amp Roland 1995)

In contrast negative correlations between rCBF andmental absorption were observed over both occipitallobes (Table 2 Figure 3B) Consistently occipital rCBFwas correlated negatively with thalamic rCBF at theabsorption-specific site (Table 3) These contrastingeffects imply that variations in occipital rCBF are asso-ciated with separate portions of the variance in relaxa-tion and absorption (Note that although absorptionand relaxation were significantly correlated the variancein absorption was largely independent of relaxation see

Rainville et al 897

Methods) For a given level of relaxation the increasein hypnotic absorption could reflect the concurrentengagement of the lsquolsquoexecutive attentional networkrsquorsquowhich exerts an opposite effect over brain areas sub-serving unattended sensory channels (ie a relativefacilitation of cross-modality suppression)

Hypnosis as a State of Consciousness

The representation of the body-self is central to theneurophenomenology of consciousness (Metzinger2000) In the Introduction we have proposed that theinduction of hypnosis produces global changes in sub-jective experience reflecting a modulation of basicaspects of the body-self representation Consistentlythe PET results indicate that hypnosis involves changesin activity within brain structures essential for the basicregulation of states of consciousness self-monitoringand self-regulation Furthermore changes in relaxationand absorption are precursors (although they may notbe essential) to other hypnosis-related effects such asthe diminished tendency to judge monitor and censorthe suspension of usual orientation toward time loca-tion andor sense of self and the experience of onersquosown response as automatic or extra-volitional (Price1996) These dimensions of experience also rely criticallyon self-representation and may depend at least partly oncerebral areas shown here to be involved in hypnosisAmong those changes the increased feeling of automa-ticity an altered feeling of agency may be the mostdistinctive aspect of hypnotic phenomenology (Weitzen-hoffer 1980) Interestingly the sense of agency hasrecently been suggested to involve areas that displayconsistent changes in activity during hypnosis such asthe right inferior parietal cortex the precuneus and thesomatosensory cortices (Blakemore amp Decety 2001Ruby amp Decety 2001) The modulation of activityobserved here within those areas is consistent withthe interpretation that hypnosis produces changes inself-representation construed as an essential element forconscious experience

Conclusion

The present study used self-ratings of subjective feelingsof mental relaxation and mental absorption to map brainareas involved in hypnosis We replicated previous find-ings and further demonstrated that hypnotic relaxationand absorption reflect changes in brain activity withinregions involved in the control of consciousness statesand in self-regulation such as the brainstem the thala-mus and the ACC The coordinated activity within thesestructures and other absorption-related areas such asthe ventrolateral frontal and right posterior parietalcortices has been previously shown to underlie theregulation of the content of consciousness throughmechanisms of executive attention We must recognize

that our findings are correlative in nature and arerelevant to hypnosis to the extent that mental relaxationand absorption are conceived as basic experientialdimensions that characterize hypnotic phenomenaWe further speculate that these changes in subjectiveexperience and brain activity may contribute to otherhypnosis-related effects such as the altered feeling ofagency experienced during hypnosis These findings areconsistent with the notion that hypnotic states areachieved through the modulation of activity within adistributed network of cerebral structures involved inthe regulation of consciousness states

METHODS

Subjects

Ten right-handed subjects (4 men 6 women) wereselected from a group of 22 volunteers as a part of astudy on the hypnotic modulation of pain (Hofbaueret al 2001) Hypnotic susceptibility was assessed usingthe SHSS-A administered between scans (range 111ndash1011 mean plusmn SD 69 plusmn28) The Ethics Committee ofthe Montreal Neurological Institute (MNI) approved allprocedures and subjects signed a consent form describ-ing the procedure and affirming their right to withdrawfrom the experiment without prejudice

Experimental Procedure

We report the results obtained in eight scans acquired ina restful baseline and hypnosis condition Hypnoticinduction started immediately after Scan 4 and wassustained in the remaining scans by repeating inductioninstructions between scans Instructions included sug-gestions for (1) increased physical and mental relaxa-tion (2) comfortable feeling of warmth heaviness anddrowsiness (3) sustained passive attention to theexperimenterrsquos voice and to the instructions and (4)decreased concern with and orientation to external andinternal (mental) sources of distraction No specificinstruction for visual imagery was included During allscans the subjectsrsquo eyes were closed and their left handwas immersed in warm or painfully hot water Pain-related activation and four additional scans performedwith suggestions for pain modulation are reported else-where (Hofbauer et al 2001)

Self-Ratings of Mental Relaxation and Absorption

After each scan subjects were instructed to rate (0ndash10)(1) their level of tensionndashrelaxation with lsquolsquo10 being themost relaxed and at ease you can bersquorsquo and (2) their levelof sustained focus of attention with lsquolsquo10 being the mostabsorbed and the largest amount of sustained focusedattention you can gatherrsquorsquo Ratings of relaxation andabsorption were transformed using the rank within sub-jects to (1) control for individual differences (2) prevent

898 Journal of Cognitive Neuroscience Volume 14 Number 6

scaling biases and (3) parallel the analysis of rCBF dataSubjects rated pain on separate scales (0ndash100) Hypno-sis-related increases in relaxation and absorption did notinteract with the stimulation condition (pain vs warmstimulation prsquos gt 10) neither relaxation nor absorptioncorrelated significantly with pain ratings (all prsquos gt 10)and pain was not altered by hypnosis alone [t(9) = 069p = 51]

PET Imaging Methods

rCBF was measured using the H215O bolus injection

method (10 millicuriesscan) without arterial blood sam-pling (Herscovitch Markham amp Raichle 1983) with ahigh-resolution PET scanner operated in 3-D acquisitionmode (Siemens ECAT HR+ 63 slices) Stimulus onsetwas simultaneous with bolus injection and 1-min acquis-ition scans started about 15 sec postinjection (interscaninterval of 12ndash15 min) Data from the first 40 sec ofacquisition were reconstructed and analyzed Each sub-ject also underwent a high-resolution anatomical MRI(160 1-mm sagittal slices acquired on a Philips 15-TGyroscan system) Each PET and MRI volume wasaligned and transformed using software developed atthe MNI to match the MNI standardized Talairach space(Collins Neelin Peters amp Evans 1994 Talairach ampTournoux 1988) PET volumes were smoothed (FWHM= 14 mm) and normalized to the average brain countPeak and cluster analyses were performed (FristonWorsley Frackowiak Mazziotta amp Evans 1994 WorsleyEvans Marrett amp Neelin 1992)

Reliability of Hypnosis-Related Effects

A first analysis was performed using the subtractionmethod (Hypnosis minus Baseline) to evaluate thereliability of the effects reported in our previous study(Table 2 in Rainville Hofbauer et al 1999) We consid-ered that hypnosis-related changes in rCBF were repli-cated when a significant peak was observed within oneresel (Worsley et al 1992) of the peak sites reported inour previous study or when the peak sites were within asignificant cluster

Regression of rCBF on Self-Ratings of Relaxationand Absorption

Regression analyses were used to test the relationbetween ratings and rCBF (GLM) Subject- and stimu-lus-related effects were removed first (ANCOVA) andthe significance of the regression slope between thecovariate of interest and rCBF was estimated usingt tests Relaxation-specific and absorption-specific effectswere further tested using ANCOVAs to remove thevariance shared between absorption and relaxation(R2 = 42 p lt 001) The statistical criterion was setto t gt 258 (two-tailed uncorrected p lt 01) in the

directed searches restricted to the brainstem the thala-mus and the ACC (Table 1 Figure 2) Global searcheffects are significant ( p lt 05) based on peak (t valuegt 420) andor clusters analysis after a correction formultiple comparisons over the gray matter volume(uncorrected p lt 0001) (Table 2 Figure 3)

Thalamic Covariations

A covariation analysis was performed in which the rCBFmeasured in the thalamus was used as the covariate ofinterest after accounting for subject- and stimulus-related variance (ANCOVA see Tables 1 and 3) Becausewe were mainly interested in the relationship betweenthe activity in the thalamus and other absorption-relatedsites the threshold for statistical significance was set tot = 370 ( p = 05 uncorrected p lt 0008) based on thevolume defined by the sum of clusters of voxels showingsignificant absorption-specific effects (186 cm3 seeWorsley et al 1992)

Acknowledgments

We thank R Adolphs S Anderson A Bechara A R DamasioH Damasio Susan Lutgendorf J Parvizi and D Tranel fortheir comments on preliminary versions of the manuscriptPET analyses were performed using the software DOTdeveloped by Sylvain Milot and the MINC programs developedby Peter Neelin at the McConnell Brain Imaging Center of theMontreal Neurological Institute This study was supported bythe Medical Research Council (MRC) of Canada Dr Rainvillewas supported by the Medical Research Council of Canada andthe Human Frontier Science Program and Dr Hofbauer wassupported by the Fonds pour la recherche en sante du Quebecand the Royal Victoria Hospital Research Institute

Reprint requests should be sent to Pierre Rainville Faculte deMedecine dentaire Universite de Montreal CP 6128 SuccCentre-ville Montreal Qc H3C 3J7 Canada or via e-mailpierrerainvilleumontrealca

REFERENCES

Aston-Jones G Rajkowski J amp Cohen J (1999) Role of locuscoeruleus in attention and behavioral flexibility BiologicalPsychiatry 46 1309 ndash1320

Badgaiyan R D amp Posner M I (1998) Mapping the cingulatecortex in response selection and monitoring Neuroimage7 255 ndash260

Balthazard C G amp Woody E Z (1992) The spectral analysisof hypnotic performance with respect to lsquolsquoabsorptionrsquorsquoInternational Journal of Clinical and ExperimentalHypnosis 40 21ndash43

Banyai E I amp Hilgard E R (1976) A comparison ofactive-alert hypnotic induction with traditional relaxationinduction Journal of Abnormal Psychology 85 218 ndash224

Blakemore S J amp Decety J (2001) From the perception ofaction to the understanding of intention Nature ReviewsNeuroscience 2 561 ndash567

Braun A R Balkin T J Wesenten N J Carson R EVarga M Baldwin P Selbie S Belenky G amp HerscovitchP (1997) Regional cerebral blood flow throughout the

Rainville et al 899

sleep ndashwake cycle An H2(15)O PET study Brain 1201173 ndash1197

Bush G Luu P amp Posner M I (2000) Cognitive andemotional influences in anterior cingulate cortex Trendsin Cognitive Sciences 4 215 ndash222

Chalmers D J (2000) What is a neural correlate ofconsciousness In T Metzinger (Ed) Neural correlatesof consciousness Empirical and conceptual questions(pp 17ndash39) Cambridge MIT Press

Coe W C amp Sarbin T R (1977) Hypnosis from thestandpoint of a contextualist Annals of the New YorkAcademy of Sciences 296 2ndash13

Cohen J D Botvinick M amp Carter C S (2000) Anteriorcingulate and prefrontal cortex Whorsquos in control NatureNeuroscience 3 421 ndash423

Collins D L Neelin P Peters T M amp Evans A C (1994)Automatic 3D intersubject registration of MR volumetric datain standardized Talairach space Journal of ComputerAssisted Tomography 18 192 ndash205

Coull J T Frackowiak R S amp Frith C D (1998) Monitoringfor target objects Activation of right frontal and parietalcortices with increasing time on task Neuropsychologia 361325 ndash1334

Coull J T amp Nobre A C (1998) Where and when to payattention The neural systems for directing attention tospatial locations and to time intervals as revealed by bothPET and fMRI Journal of Neuroscience 18 7426 ndash7435

Crawford H J (1994) Brain dynamics and hypnosisAttentional and disattentional processes InternationalJournal of Clinical and Experimental Hypnosis 42204 ndash232

Crawford H J amp Gruzelier J H (1992) A midstream view ofthe neuropsychophysiology of hypnosis Recent researchand future directions In E Fromm amp M R Nash (Eds)Contemporary hypnosis research (pp 227 ndash266) New YorkGuilford Press

Crawford H J Knebel T Kaplan L Vendemia J M C XieM Jamison S amp Pribram K H (1998) Hypnotic analgesia1 Somatosensory event-related potential changes to noxiousstimuli and 2 Transfer learning to reduce chronic low backpain International Journal of Clinical and ExperimentalHypnosis 46 92ndash132

Damasio A R (1999) The feeling of what happens Body andemotion and the making of consciousness New YorkHartcourt Brace

De Pascalis V Magurano M R amp Bellusci A (1999) Painperception somatosensory event-related potentials andskin conductance responses to painful stimuli in high midand low hypnotizable subjects Effects of differential painreduction strategies Pain 83 499 ndash508

Devinsky O Morrell M J amp Vogt B A (1995) Contributionsof anterior cingulate cortex to behaviour Brain 118279 ndash306

Fiset P Paus T Daloze T Plourde G Meuret PBonhomme V Hajj-Ali N Backman S B amp Evans A C(1999) Brain mechanisms of propofol-induced loss ofconsciousness in humans A positron emission tomographicstudy Journal of Neuroscience 19 5505 ndash5513

Friston K J Worsley K J Frackowiak R S J Mazziotta J Camp Evans A C (1994) Assessing the significance of focalactivation using their spatial extent Human Brain Mapping1 214ndash220

Gitelman D R Alpert N M Kosslyn S Daffner K ScintoL Thompson W amp Mesulam M M (1996) Functionalimaging of human right hemispheric activation forexploratory movements Annals of Neurology 39 174ndash179

Gitelman D R Nobre A C Parrish T B LaBar K S KimY H Meyer J R amp Mesulam M (1999) A large-scale

distributed network for covert spatial attention Furtheranatomical delineation based on stringent behavioural andcognitive controls Brain 122 1093 ndash1106

Gruzelier J (1998) A working model of the neurophysiologyof hypnosis A review of evidence Contemporary Hypnosis15 3ndash21

Henson R N A Rugg M D Shallice T amp Dolan R J (2000)Confidence in recognition memory for words Dissociatingright prefrontal roles in episodic retrieval Journal ofCognitive Neuroscience 12 913 ndash923

Henson R N A Rugg M D Shallice T Joseph O ampDolan R J (1999) Recollection and familiarity inrecognition memory An event-related functional magneticresonance imaging study Journal of Neuroscience 193962 ndash3972

Herscovitch P Markham J amp Raichle M E (1983) Brainblood flow measured with intravenous H2(15)O I Theoryand error analysis Journal of Nuclear Medicine 24782 ndash789

Hofbauer R K Rainville P Duncan G H amp Bushnell M C(2001) Cortical representation of the sensory dimension ofpain Journal of Neurophysiology 86 402 ndash411

Hofle N Paus T Reutens D Fiset P Gotman J EvansA C amp Jones B E (1997) Regional cerebral blood flowchanges as a function of delta and spindle activity duringslow wave sleep in humans Journal of Neuroscience 174800 ndash4808

Jeanmonod D Magnin M amp Morel A (1996) Low-thresholdcalcium spike bursts in the human thalamus Commonphysiopathology for sensory motor and limbic positivesymptoms Brain 119 363ndash375

Kajimura N Uchiyama M Takayama Y Uchida S Uema TKato M Sekimoto M Watanabe T Nakajima THorikoshi S Ogawa K Nishikawa M Hiroki M Kudo YMatsuda H Okawa M amp Takahashi K (1999) Activityof midbrain reticular formation and neocortex during theprogression of human non-rapid eye movement sleepJournal of Neuroscience 19 10065 ndash10073

Kawashima R OrsquoSullivan B T amp Roland P E (1995)Positron-emission tomography studies of cross-modalityinhibition in selective attentional tasks Closing the lsquolsquomindrsquoseyersquorsquo Proceedings of the National Academy of SciencesUSA 92 5969 ndash5972

Kim Y H Gitelman D R Nobre A C Parrish T BLaBar K S amp Mesulam M M (1999) The large-scaleneural network for spatial attention displays multifunctionaloverlap but differential asymmetry Neuroimage 9269 ndash277

Kinomura S Larsson J Gulyas B amp Roland P E (1996)Activation by attention of the human reticular formationand thalamic intralaminar nuclei Science 271 512ndash515

Kosslyn S M Thompson W L Costantini-Ferrando M FAlpert N M amp Spiegel D (2000) Hypnotic visual illusionalters color processing in the brain American Journal ofPsychiatry 157 1279 ndash1284

Laureys S Faymonville M E Luxen A Lamy M Franck Gamp Maquet P (2000) Restoration of thalamocorticalconnectivity after recovery from persistent vegetative stateLancet 355 1790ndash1791

Lou H C Kjaer T W Friberg L Wildschiodtz G Holm Samp Nowak M (1999) A 15OndashH2O PET study of meditationand the resting state of normal consciousness HumanBrain Mapping 7 98ndash105

Maquet P Degueldre C Delfiore G Aerts J Peters J MLuxen A amp Franck G (1997) Functional neuroanatomyof human slow wave sleep Journal of Neuroscience 172807 ndash2812

Maquet P Faymonville M E Degueldre C Delfiore G

900 Journal of Cognitive Neuroscience Volume 14 Number 6

Franck G Luxen A amp Lamy M (1999) Functionalneuroanatomy of hypnotic state Biological Psychiatry 45327 ndash333

Metzinger T (2000) The subjectivity of subjective experienceA representationalist analysis of the first-person perspectiveIn T Metzinger (Ed) Neural correlates of consciousnessEmprical and conceptual questions (pp 285 ndash306)Cambridge MIT Press

Nobre A C Sebestyen G N Gitelman D R MesulamM M Frackowiak R S amp Frith C D (1997) Functionallocalization of the system for visuospatial attention usingpositron emission tomography Brain 120 515 ndash533

Pardo J V Fox P T amp Raichle M E (1991) Localization of ahuman system for sustained attention by positron emissiontomography Nature 349 61ndash64

Paus T (2001) Primate anterior cingulate cortex Wheremotor control drive and cognition interface NatureReviews Neuroscience 2 417 ndash424

Paus T Koski L Caramanos Z amp Westbury C (1998)Regional differences in the effects of task difficulty andmotor output on blood flow response in the human anteriorcingulate cortex A review of 107 PET activation studiesNeuroReport 9 R37ndashR47

Paus T Zatorre R J Hofle N Caramanos Z Gotman JPetrides M amp Evans A C (1997) Time-related changesin neural systems underlying attention and arousal duringthe performance of an auditory vigilance task Journal ofCognitive Neuroscience 9 392ndash408

Peyron R Garcia-Larrea L Gregoire M C Costes NConvers P Lavenne F Mauguiere F Michel D ampLaurent B (1999) Haemodynamic brain responses to acutepain in humansmdashSensory and attentional networks Brain122 1765 ndash1779

Picard N amp Strick P L (1996) Motor areas of the medial wallA review of their location and functional activation CerebralCortex 6 342 ndash353

Portas C M Howseman A M Josephs O Turner R ampFrith C D (1998) A specific role for the thalamus inmediating the interaction of attention and arousal inhumans Journal of Neuroscience 18 8979 ndash8989

Posner M I amp Rothbart M K (1998) Attentionself-regulation and consciousness Philosophical

Transactions of the Royal Society of London Series BBiological Sciences 353 1915 ndash1927

Price D D (1996) Hypnotic analgesia Psychological andneural mechanisms In J Barber (Ed) Hypnosis andsuggestions in the treatment of pain (pp 67ndash84) NewYork Norton

Price D D amp Barrell J J (1980) An experiential approachwith quantitative methods A research paradigm Journal ofHumanistic Psychology 20 75ndash95

Rainville P Carrier B Hofbauer R K Bushnell M C ampDuncan G H (1999) Dissociation of pain sensory andaffective dimensions using hypnotic modulation Pain 82159 ndash171

Rainville P Duncan G H Price D D Carrier B ampBushnell M C (1997) Pain affect encoded in humananterior cingulate but not somatosensory cortex Science277 968 ndash971

Rainville P Hofbauer R K Paus T Duncan G H BushnellM C amp Price D D (1999) Cerebral mechanisms ofhypnotic induction and suggestion Journal of CognitiveNeuroscience 11 110ndash125

Ruby P amp Decety J (2001) Effect of subjective perspectivetaking during simulation of action A PET investigation ofagency Nature Neuroscience 4 546 ndash550

Steriade M amp McCarley R W (1990) Brainstem control ofwakefulness and sleep New York Plenum

Szechtman H Woody E Bowers K S amp Nahmias C(1998) Where the imaginal appears real A positronemission tomography study of auditory hallucinationsProceedings of the National Academy of Sciences USA95 1956 ndash1960

Talairach J amp Tournoux P (1988) Co-planar stereotaxicatlas of the human brain New York Thieme

Tellegen A amp Atkinson G (1974) Openness to absorbingand self-altering experiences (lsquolsquoabsorptionrsquorsquo) a trait relatedto hypnotic susceptibility Journal of Abnormal Psychology83 268 ndash277

Toma K Honda M Hanakawa T Okada T Fukuyama HIkeda A Nishizawa S Konishi J amp Shibasaki H (1999)Activities of the primary and supplementary motor areasincrease in preparation and execution of voluntary musclerelaxation An event-related fMRI study Journal ofNeuroscience 19 3527 ndash3534

Varela F J amp Shear J (1999) First-person methodologiesWhat why and how Journal of Consciousness Studies 61ndash14

Vingoe F J (1968) The development of a group alert-trancescale International Journal of Clinical and ExperimentalHypnosis 16 120 ndash132

Vingoe F J (1973) Comparison of the Harvard Group Scaleof Hypnotic Susceptibility Form A and the Group AlertTrance Scale in a university population InternationalJournal of Clinical and Experimental Hypnosis 21169 ndash179

Vogt B A amp Gabriel M (1993) Neurobiology of cingulatecortex and limbic thalamus A comprehensive handbookBoston Birkauser

Weitzenhoffer A M (1980) Hypnotic susceptibility revisitedAmerican Journal of Clinical Hypnosis 22 130 ndash146

Willoch F Rosen G Tolle T R Oslashye I Wester H J BernerN Schwaiger M amp Bartenstein P (2000) Phantom limbpain in the human brain Unravelling neural circuitries ofphantom limb pain sensations using positron emissiontomography Annals of Neurology 48 842 ndash849

Worsley K J Evans A C Marrett S amp Neelin P (1992)A three-dimensional statistical analysis for CBF activationstudies in human brain Journal of Cerebral Blood Flow andMetabolism 12 900 ndash918

Rainville et al 901

Page 6: Hypnosis Modulates Activity in Brain Structures Involved in the …pineda/COGS175/readings/Rain... · 2005. 2. 28. · Hypnosis Modulates Activity in Brain Structures Involved in

Tab

le2

R

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tsof

the

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bal

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ches

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ral

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ons

whe

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Fron

tal

(F)

RF

Pole

(BA

10)

ndash34

562

iexcliexcl4

81

ndash28

555

+4

21

Rla

tF

Orb

ital

g(B

A11

)ndash

1946

iexcl20

iexcliexcl4

29

ndash19

44iexcl

20+

47

5

Rm

iddl

eF

g(B

A46

)ndash

3646

26iexcl

381

ndash34

4626

+3

79

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fF

g(B

A47

)ndash

ndash47

34iexcl

18+

373

ndash

Rin

fF

g(B

A45

)ndash

478

15iexcl

386

5520

11+

352

ndash

Ra

nt

insu

lai

nf

Fg

(BA

144

4)ndash

4015

6iexcl

377

4310

2+

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4013

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1

Rsu

pF

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ingu

late

g(B

A8

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A6)

ndashndash

1320

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1522

57+

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lsu

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g(B

A6)

ndashndash

3iexcl

466

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Orb

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A11

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3041

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A46

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ndashiexcl

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18+

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8iexcl

3839

24+

407

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nt

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(BA

144

4)ndash

ndashndash

iexcl34

817

+4

25

Lsu

pF

g(B

A6)

ndashndash

ndashiexcl

266

56+

416

Lsu

p

Fg

(BA

6)ndash

ndashiexcl

11iexcl

466

+3

68ndash

Cen

tral

Rp

rece

ntra

lg

(BA

4)54

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53+

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(BA

4)42

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50+

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mid

dle

Fg

(BA

46)

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53+

398

ndashndash

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Lpr

ecen

tral

g(B

A4)

iexcl47

iexcl16

47+

44

3ndash

iexcl48

iexcl14

50+

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6ndash

Lpr

epo

stce

ntra

lg

(BA

41

3)ndash

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iexcl37

60+

403

ndash

Tem

pora

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)R

mid

dle

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g(B

A21

)60

iexcl33

iexcl15

iexcl5

71

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55

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Rm

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(BA

37)

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20iexcliexcl

44

6ndash

892 Journal of Cognitive Neuroscience Volume 14 Number 6

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etal

(P)

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m(B

A40

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32iexcl

3027

iexcl3

55ndash

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Rin

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5062

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(BA

7)ndash

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5645

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Prec

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Cin

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(BA

731

)ndash

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Lin

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Lin

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A40

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ndashndash

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Occ

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ing

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A18

31)

ndash0

iexcl66

9+

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(BA

19)

ndash43

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6843

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44

443

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17

Rli

ngu

alg

(BA

18)

ndash4

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3+

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4ndash

7iexcl

782

iexcliexcl4

68

Rcu

neu

s(B

A18

)ndash

12iexcl

8327

+5

20

ndashndash

Rsu

pO

g

(BA

19)

ndash17

iexcl81

38+

55

9ndash

15iexcl

8033

iexcliexcl6

02

Rsu

pO

g

(BA

19)

30iexcl

8726

+4

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RO

po

le(B

A18

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929

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8iexcliexcl

53

5

Lfu

sifo

rmg

(BA

181

9)ndash

iexcl40

iexcl78

iexcl3

+3

59ndash

iexcl40

iexcl76

iexcl3

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46

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(BA

197

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36iexcliexcl

42

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8739

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18

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ndashiexcl

17iexcl

76iexcl

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351

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ndashiexcl

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Rainville et al 893

the underlying processes in the production of hypnoticstates as discussed below

Role of the Brainstem the Thalamus and the ACCin Hypnosis

Results of the regression analyses suggest that neuralactivity in the brainstem the thalamus and the ACCcontributes to the experience of being hypnotized Therelaxation-specific negative correlations in the mesen-

cephalic brainstem and the thalamus may reflect thewell-established contribution of brainstem and thalamicnuclei to the regulation of wakefulness and corticalarousal In functional brain imaging studies rCBFdecreases in the brainstem and the thalamus have beenassociated with decreased vigilance (Paus et al 1997)sleep (Kajimura et al 1999 Braun et al 1997 Hofleet al 1997 Maquet et al 1997) and the loss ofconsciousness produced by the anesthetic propofol(Fiset et al 1999) These effects and to some extent

Figure 3 Brain regionsshowing positive (redarrowheads) and negative(blue arrowheads) regres-sion peaks between rCBFand self-ratings of (A)relaxation and (B) absorp-tion after accounting forrelaxation-related variance(absorption-specific)Statistical t maps are super-imposed on the averageanatomical MRI (left is onthe left side) Slice locationsare indicated on the 3-Danatomical image of asingle subjectrsquos anatomicalMRI (A-positive) Positiverelaxation-related effectsare shown in the centralregion bilaterally (horizon-tal slice on the left) Apositive peak is shown inthe right superior occipitalgyrus (SOg) (coronal viewon the right note scalechange) (A-negative)A negative relaxation-related effect in the rightposterior parietal cortexis shown in horizontal(first from left) coronal(second) and lateralsagittal (third) views Theplus sign indicates the moreanterior location of thepeak positive regression inthe analysis of absorption-related effects as shown inB Additional negative cor-relations are shown in thebilateral middle and inferiortemporal gyri (second) andin the right somatosensorycortices (S1 S2 insula)(B-positive) A positiveabsorption-specific peak isshown in the right inferiorparietal lobule (first fromleft) The minus sign indicates the more posterior location of the negative regression peak in the analysis of relaxation-related effects as shown in

A Other peaks are shown on the midsagittal view in the thalamus and the anterior cingulate cortex (second from left) and in the left lenticularnuclei and bilateral prefrontal cortices (last three cuts from left) (B-negative) Negative absorption-related effects are shown in the left inferiorparietal lobule (first from left) in both occipital lobes (second and third from left) and in the precuneus (first and third) Stereotaxic coordinates ofpeaks are reported in Table 3 (see relaxation- and absorption-specific)

894 Journal of Cognitive Neuroscience Volume 14 Number 6

the present relaxation-related decrease in brainstemrCBF may reflect an attenuation of activity withinbrainstem cholinergic nuclei Such reduction has beenobserved during slow EEG activity before the onset ofsleep and during slow-wave sleep in animal studies(Steriade amp McCarley 1990) Consistent with this pos-sibility we previously reported an increase in slow(delta) EEG activity following hypnotic induction (Rain-ville Hofbauer et al 1999) Although hypnotic andsleep states are clearly distinct certain neurophysiolog-

ical mechanisms may be involved to a varying degree inthe production of both states

The positive association specifically observed betweenmental absorption and rCBF in the upper pons and thethalamus contrasts with the above relaxation-relatedeffect and is consistent with previous reports of atten-tion-related brain activation (Kinomura et al 1996) Thisactivity may reflect the involvement of the noradrenergicsystem of the locus coeruleus in focused attentionand possibly in the interaction between cortical arousal

Table 3 Cerebral Sites of Covariation with Thalamic rCBF at the Absorption-Specific Peak Coordinates (x = iexcl27 y = iexcl160z = 120)

Region Peak Location x y z t

Frontal (F) R medial sup F gACC (BA 624) 1 43 32 +382

R anterior cingulate gsup F g (BA 326) 8 13 44 +387

R inf F g (BA 44) 51 12 8 +387

R ant insula (BA 14) 38 12 5 +412

R sup F g (BA 6) 16 20 59 +371

R medial sup F g (BA 6) 3 iexcl6 63 +498

R medial sup F g (BA 6) 11 iexcl23 53 +412

L middle F g (BA 46) iexcl38 46 23 +381

L middle F g (BA 46) iexcl31 39 39 +374

L inf F g (BA 44) iexcl43 6 12 +430

L sup F g (BA 6) iexcl19 20 53 +340

L medial sup F g (BA 6) iexcl5 17 65 +353

L sup F g (BA 6) iexcl20 12 65 +283

Parietal R inf parietal lobule (BA 40) 56 iexcl44 50 +519

Occipital (O) R fusiform g (BA 19) 26 iexcl62 iexcl30 iexcliexcl515

R lingual g (BA 18) 7 iexcl78 6 iexcliexcl623

R sup O g (BA 19) 19 iexcl85 30 iexcliexcl714

R O pole (BA 18) 27 iexcl90 9 iexcliexcl751

L cuneus (BA 18) iexcl11 iexcl83 29 iexcliexcl633

L O pole (BA 18) iexcl23 iexcl88 6 iexcliexcl793

Subcortical R thalamus 17 iexcl11 2 +350

R brainstem 13 iexcl26 iexcl15 +312

R medial brainstem 3 iexcl32 iexcl24 +287

L cerebellum iexcl4 iexcl57 iexcl21 +409

L globus pallidus iexcl20 iexcl1 iexcl2 +302

L caudate nucleus iexcl12 6 20 +291

Positive and negative regression slopes are significant at sites listed based on cluster or peak analyses (peak t threshold ltgtplusmn370 in bold allpeaks reported with t lt 370 are within a significant cluster see Methods) Peaks in italic are also reported in Table 1 See legends to Tables 1 and 2and Methods for further explanation

Rainville et al 895

and attentional processes (ie increased attentionabsorption concurrent with decreased cortical arousalincreased relaxation) (Aston-Jones et al 1999) Theindirect nature of the rCBF measures and the relativelypoor resolution of the PET method require somecaution in evaluating the possible anatomo-functionalimplications of our results in the brainstem Howeverthe convergent findings observed in other brain imag-ing studies and the observations provided in animalstudies support the notion that ascending cholinergicand noradrenergic pathways may contribute differen-tially to the multiple dimensions of experience thatcharacterize hypnosis

The overall pattern of results found in the ACC likelyreflects the heterogeneity of functions associated withthis area (Devinsky Morrell amp Vogt 1995) The locationof the most posterior relaxation-related peak in the ACC(mACC) is consistent with our previous observationof ACC activation during hypnosis (Rainville Hofbaueret al 1999) This relaxation-related peak is only slightlyanterior to the motor area of the caudal ACC (Picard ampStrick 1996) and may be involved in the installment of arelaxed state (also see precentral area below) In con-trast a positive absorption-specific effect was observedin a more rostral region of the ACC (rACC) close to anegative relaxation-specific correlation (see Table 1)This area of the ACC has previously been involved inexecutive attention in the detection of errors and in themonitoring of conflict between competing cognitiveprocesses (Bush Luu amp Posner 2000 Cohen Botvinickamp Carter 2000 Badgaiyan amp Posner 1998 Posner ampRothbart 1998) A meta-analysis of PET studies inves-tigating cognitive functions further suggested that theincrease in activity within this sector of the ACC isrelated to the difficulty of the task performed (PausKoski Caramanos amp Westbury 1998) Our findings areconsistent with these propositions to the extent thatthe engagement of the cognitive and neurophysiologicalprocesses implied in each of those accounts may beaccompanied by a subjective experience of increasedmental absorption

The coordinated pattern of rCBF changes in thebrainstem the thalamus and the ACC may reflect theinterrelationships between the multiple components of anetwork (eg Paus et al 1997) herein shown to beassociated with the feeling of being lsquolsquomentally absorbedrsquorsquoThe precise location of the observed absorption-specificthalamic peak is consistent with an involvement of theintralaminar and medio-dorsal nuclei which have recip-rocal connections with the ACC (Vogt amp Gabriel 1993)The finding that the coordinated activity in the thalamusand the ACC is disrupted in persistent vegetative states isconsistent with the notion that these structures work intandem to regulate consciousness (Laureys et al 2000also see Jeanmonod Magnin amp Morel 1996) Further-more a functional interaction between arousal andattentional processes has been reported in the thalamus

where the putative attention-related activity associatedwith the performance of a simple visual discriminationtask was found to increase in states of low arousal (Portaset al 1998) This increase in thalamic activity wassuggested (1) to reflect a compensatory mechanism thatpermitted the maintenance of stable levels of perform-ance in states of low arousal and (2) to prevent thegeneralized thalamo-cortical synchronization that wouldlead to sleep Here the opposite effects of relaxation andabsorption on thalamic activity may reflect this compen-satory mechanism that maintains high levels of focusedattention in deeply relaxed subjects during hypnosisThis function may be critical not only in hypnosis butalso in other conditions of deep relaxation distinct fromboth sleep and normal wakefulness such as meditativestates (Lou et al 1999) Furthermore the coactivation ofthe ACC and the ponto-mesencephalic brainstem mayreflect the contribution of the ACC to the regulation ofattention-related activity in the locus coeruleus (Cohenet al 2000) The positive regression found with absorp-tion in the ponto-mesencephalic brainstem and themore robust regression observed in the thalamus andthe ACC after accounting for relaxation-related changes(absorption-specific Table 1) further substantiate thepossibility that brainstem and thalamic nuclei interactwith the ACC to regulate the interaction between atten-tion and cortical arousal Taken together these resultsare consistent with a contribution of brainstem nucleithe intralaminar and medio-dorsal nuclei of the thala-mus and the ACC to the changes in phenomenalexperience that characterize hypnotic states

Additional Relaxation- and Absorption-RelatedChanges in rCBF

Relaxation-Related Activity

We observed strong relaxation-related increases in rCBFin the precentral gyrus bilaterally and reciprocaldecreases in somatosensory areas (S1 S2 and insula)Precentral and premotor activation has been reportedduring hypnosis in an independent study (Maquet et al1999) and precentral rCBF was correlated with the rCBFmeasured at the ACC site of hypnosis-related activity inour previous study (see Appendix in Rainville Hofbaueret al 1999) Similar increases in activity in motor andpremotor areas have been associated with voluntarymuscular relaxation (Toma et al 1999) but the presentresults may reflect more than physical relaxation

All standard hypnotic procedures include instructionsfor relaxation However the specific contribution ofmuscular relaxation and decreased arousal to the pro-duction of hypnotic states is unclear as hypnotic phe-nomena have been produced during muscular exercise(Banyai amp Hilgard 1976) and with suggestions of active-alertness (Vingoe 1968 1973) Here the absence ofsignificant effect of hypnosis on heart rate indicates thatchanges in cerebral activity did not correlate with

896 Journal of Cognitive Neuroscience Volume 14 Number 6

changes in peripheral arousal and suggests that subjectswere already physically relaxed in the baseline controlcondition This implies that the hypnosis-inducedchanges in self-ratings of relaxation may not simplyreflect changes in lsquolsquoperipheralrsquorsquo arousal but may attestmore specifically of an increase in lsquolsquomentalrsquorsquo relaxationand a reduction in lsquolsquocorticalrsquorsquo arousal This is consistentwith Pricersquos experiential model of hypnosis (see Intro-duction) and with our previous study showing anincrease in slow (delta) EEG activity during hypnosis

Relaxation-related effects observed outside primarysomatomotor areas may partly reflect subjective feelingsof mental ease more closely In the subtraction analysishypnosis-related decreases were found in the rightlateral posterior parietal rCBF both here (x y z 40iexcl52 44) and in our previous study (x y z 46 iexcl50 42from Table 1 in Rainville Hofbauer et al 1999) Herethese changes were strongly but not specifically asso-ciated with relaxation (x y z 39 iexcl49 45 see Table 2Figure 3A) Furthermore after accounting for absorp-tion-related variance right prefrontal activity was neg-atively correlated with relaxation (Table 2) Thoseadditional changes in the right posterior parietal cortexand the right prefrontal cortices may contribute to thesubjective feelings of mental ease rather than or inaddition to physical relaxation

Fronto-Parietal Attention Networks

Absorption-related activity was widespread and bilateralin the prefrontal cortices but peaks were generallystronger in the right hemisphere Positive regressionpeaks were maximal in the ventrolateral frontal corticesover the inferior frontal gyrus and in the anterior insulaA positive absorption-related regression peak was alsosignificant in the right inferior parietal lobule Theseareas also displayed strong coactivation with absorption-related thalamic activity Very similar patterns of activa-tion have been associated with attentional processes intasks involving visual (eg Coull Frackowiak amp Frith1998) auditory (Paus et al 1997) and somatosensorystimuli (Peyron et al 1999) Notably the location of thepositive parietal peak observed here closely matches theactivation sites reported in those studies and the site ofcovariation with the right ventrolateral attention-relatedactivity reported in Paus et al (1997) suggesting theactivation of a similar network The coordinated absorp-tion-related activity observed here in the brainstem thethalamus the ACC the right inferior frontal gyrus andthe right inferior parietal lobule provides very strongevidence that mental absorption is an experiential cor-relate of the activation of the brainrsquos lsquolsquoexecutive atten-tional networkrsquorsquo and suggests that this system plays acritical role in the production of hypnotic states

Negative absorption-related regression peaks werealso found in both the right and left lateral parietalcortices and in the precuneus (see Table 2) These

effects were largely independent of thalamic activity asindicated by the absence of significant effects at theselocations in the covariation analysis (Table 3) The rightposterior parietal cortex has been suggested to con-stitute a vigilanceorientation system (Pardo Fox ampRaichle 1991) and hypnosis-related decreases in thisarea may reflect a relative disengagement towardexternal sources of stimulation Right and left posteriorparietal cortices at the precise sites of relaxation- andabsorption-related decrease in rCBF have been sug-gested to contribute to the monitoring of externalspace and time respectively (Gitelman et al 19961999 Kim et al 1999 Coull amp Nobre 1998 Nobreet al 1997) Although these functions were notdirectly assessed in this experiment the hypnoticinduction procedure includes specific instructions fordecreased orientation to and interest in irrelevantexternal sources of stimulation and previous observa-tions suggest that hypnotic relaxation and absorptionare precursors to some alterations in spatio-temporalorientation and monitoring (Price 1996) Thus wespeculate that those additional experiential changesmay be consequent to relaxation- and absorption-related decreases in posterior parietal activity

Relaxation- and Absorption-Related Effects onOccipital rCBF

The subtraction analysis confirmed the reliability of thehypnosis-related increase in occipital rCBF reported inour previous study (Rainville Hofbauer et al 1999) Wenow show that this effect was associated with the sub-jective experience of hypnotic relaxation (see Table 2relaxation-specific) Consistently our previous studydemonstrated a coupling between occipital increases inrCBF and increases in slow (delta) EEG activity duringhypnosis Similar increases in occipital rCBF andor slowEEG activity had been observed in another study onhypnosis (Maquet et al 1999) and in states of decreasedvigilance (Paus et al 1997) meditation (Lou et al 1999)and slow wave sleep (Kajimura et al 1999 Hofle et al1997) These effects are consistent with our previousproposition that hypnotic induction produces a globaldecrease in cross-modality suppression in unattendedsensory channels leading to a relative disinhibitionof cortical activity (see Paus et al 1997 KawashimaOrsquoSullivan amp Roland 1995)

In contrast negative correlations between rCBF andmental absorption were observed over both occipitallobes (Table 2 Figure 3B) Consistently occipital rCBFwas correlated negatively with thalamic rCBF at theabsorption-specific site (Table 3) These contrastingeffects imply that variations in occipital rCBF are asso-ciated with separate portions of the variance in relaxa-tion and absorption (Note that although absorptionand relaxation were significantly correlated the variancein absorption was largely independent of relaxation see

Rainville et al 897

Methods) For a given level of relaxation the increasein hypnotic absorption could reflect the concurrentengagement of the lsquolsquoexecutive attentional networkrsquorsquowhich exerts an opposite effect over brain areas sub-serving unattended sensory channels (ie a relativefacilitation of cross-modality suppression)

Hypnosis as a State of Consciousness

The representation of the body-self is central to theneurophenomenology of consciousness (Metzinger2000) In the Introduction we have proposed that theinduction of hypnosis produces global changes in sub-jective experience reflecting a modulation of basicaspects of the body-self representation Consistentlythe PET results indicate that hypnosis involves changesin activity within brain structures essential for the basicregulation of states of consciousness self-monitoringand self-regulation Furthermore changes in relaxationand absorption are precursors (although they may notbe essential) to other hypnosis-related effects such asthe diminished tendency to judge monitor and censorthe suspension of usual orientation toward time loca-tion andor sense of self and the experience of onersquosown response as automatic or extra-volitional (Price1996) These dimensions of experience also rely criticallyon self-representation and may depend at least partly oncerebral areas shown here to be involved in hypnosisAmong those changes the increased feeling of automa-ticity an altered feeling of agency may be the mostdistinctive aspect of hypnotic phenomenology (Weitzen-hoffer 1980) Interestingly the sense of agency hasrecently been suggested to involve areas that displayconsistent changes in activity during hypnosis such asthe right inferior parietal cortex the precuneus and thesomatosensory cortices (Blakemore amp Decety 2001Ruby amp Decety 2001) The modulation of activityobserved here within those areas is consistent withthe interpretation that hypnosis produces changes inself-representation construed as an essential element forconscious experience

Conclusion

The present study used self-ratings of subjective feelingsof mental relaxation and mental absorption to map brainareas involved in hypnosis We replicated previous find-ings and further demonstrated that hypnotic relaxationand absorption reflect changes in brain activity withinregions involved in the control of consciousness statesand in self-regulation such as the brainstem the thala-mus and the ACC The coordinated activity within thesestructures and other absorption-related areas such asthe ventrolateral frontal and right posterior parietalcortices has been previously shown to underlie theregulation of the content of consciousness throughmechanisms of executive attention We must recognize

that our findings are correlative in nature and arerelevant to hypnosis to the extent that mental relaxationand absorption are conceived as basic experientialdimensions that characterize hypnotic phenomenaWe further speculate that these changes in subjectiveexperience and brain activity may contribute to otherhypnosis-related effects such as the altered feeling ofagency experienced during hypnosis These findings areconsistent with the notion that hypnotic states areachieved through the modulation of activity within adistributed network of cerebral structures involved inthe regulation of consciousness states

METHODS

Subjects

Ten right-handed subjects (4 men 6 women) wereselected from a group of 22 volunteers as a part of astudy on the hypnotic modulation of pain (Hofbaueret al 2001) Hypnotic susceptibility was assessed usingthe SHSS-A administered between scans (range 111ndash1011 mean plusmn SD 69 plusmn28) The Ethics Committee ofthe Montreal Neurological Institute (MNI) approved allprocedures and subjects signed a consent form describ-ing the procedure and affirming their right to withdrawfrom the experiment without prejudice

Experimental Procedure

We report the results obtained in eight scans acquired ina restful baseline and hypnosis condition Hypnoticinduction started immediately after Scan 4 and wassustained in the remaining scans by repeating inductioninstructions between scans Instructions included sug-gestions for (1) increased physical and mental relaxa-tion (2) comfortable feeling of warmth heaviness anddrowsiness (3) sustained passive attention to theexperimenterrsquos voice and to the instructions and (4)decreased concern with and orientation to external andinternal (mental) sources of distraction No specificinstruction for visual imagery was included During allscans the subjectsrsquo eyes were closed and their left handwas immersed in warm or painfully hot water Pain-related activation and four additional scans performedwith suggestions for pain modulation are reported else-where (Hofbauer et al 2001)

Self-Ratings of Mental Relaxation and Absorption

After each scan subjects were instructed to rate (0ndash10)(1) their level of tensionndashrelaxation with lsquolsquo10 being themost relaxed and at ease you can bersquorsquo and (2) their levelof sustained focus of attention with lsquolsquo10 being the mostabsorbed and the largest amount of sustained focusedattention you can gatherrsquorsquo Ratings of relaxation andabsorption were transformed using the rank within sub-jects to (1) control for individual differences (2) prevent

898 Journal of Cognitive Neuroscience Volume 14 Number 6

scaling biases and (3) parallel the analysis of rCBF dataSubjects rated pain on separate scales (0ndash100) Hypno-sis-related increases in relaxation and absorption did notinteract with the stimulation condition (pain vs warmstimulation prsquos gt 10) neither relaxation nor absorptioncorrelated significantly with pain ratings (all prsquos gt 10)and pain was not altered by hypnosis alone [t(9) = 069p = 51]

PET Imaging Methods

rCBF was measured using the H215O bolus injection

method (10 millicuriesscan) without arterial blood sam-pling (Herscovitch Markham amp Raichle 1983) with ahigh-resolution PET scanner operated in 3-D acquisitionmode (Siemens ECAT HR+ 63 slices) Stimulus onsetwas simultaneous with bolus injection and 1-min acquis-ition scans started about 15 sec postinjection (interscaninterval of 12ndash15 min) Data from the first 40 sec ofacquisition were reconstructed and analyzed Each sub-ject also underwent a high-resolution anatomical MRI(160 1-mm sagittal slices acquired on a Philips 15-TGyroscan system) Each PET and MRI volume wasaligned and transformed using software developed atthe MNI to match the MNI standardized Talairach space(Collins Neelin Peters amp Evans 1994 Talairach ampTournoux 1988) PET volumes were smoothed (FWHM= 14 mm) and normalized to the average brain countPeak and cluster analyses were performed (FristonWorsley Frackowiak Mazziotta amp Evans 1994 WorsleyEvans Marrett amp Neelin 1992)

Reliability of Hypnosis-Related Effects

A first analysis was performed using the subtractionmethod (Hypnosis minus Baseline) to evaluate thereliability of the effects reported in our previous study(Table 2 in Rainville Hofbauer et al 1999) We consid-ered that hypnosis-related changes in rCBF were repli-cated when a significant peak was observed within oneresel (Worsley et al 1992) of the peak sites reported inour previous study or when the peak sites were within asignificant cluster

Regression of rCBF on Self-Ratings of Relaxationand Absorption

Regression analyses were used to test the relationbetween ratings and rCBF (GLM) Subject- and stimu-lus-related effects were removed first (ANCOVA) andthe significance of the regression slope between thecovariate of interest and rCBF was estimated usingt tests Relaxation-specific and absorption-specific effectswere further tested using ANCOVAs to remove thevariance shared between absorption and relaxation(R2 = 42 p lt 001) The statistical criterion was setto t gt 258 (two-tailed uncorrected p lt 01) in the

directed searches restricted to the brainstem the thala-mus and the ACC (Table 1 Figure 2) Global searcheffects are significant ( p lt 05) based on peak (t valuegt 420) andor clusters analysis after a correction formultiple comparisons over the gray matter volume(uncorrected p lt 0001) (Table 2 Figure 3)

Thalamic Covariations

A covariation analysis was performed in which the rCBFmeasured in the thalamus was used as the covariate ofinterest after accounting for subject- and stimulus-related variance (ANCOVA see Tables 1 and 3) Becausewe were mainly interested in the relationship betweenthe activity in the thalamus and other absorption-relatedsites the threshold for statistical significance was set tot = 370 ( p = 05 uncorrected p lt 0008) based on thevolume defined by the sum of clusters of voxels showingsignificant absorption-specific effects (186 cm3 seeWorsley et al 1992)

Acknowledgments

We thank R Adolphs S Anderson A Bechara A R DamasioH Damasio Susan Lutgendorf J Parvizi and D Tranel fortheir comments on preliminary versions of the manuscriptPET analyses were performed using the software DOTdeveloped by Sylvain Milot and the MINC programs developedby Peter Neelin at the McConnell Brain Imaging Center of theMontreal Neurological Institute This study was supported bythe Medical Research Council (MRC) of Canada Dr Rainvillewas supported by the Medical Research Council of Canada andthe Human Frontier Science Program and Dr Hofbauer wassupported by the Fonds pour la recherche en sante du Quebecand the Royal Victoria Hospital Research Institute

Reprint requests should be sent to Pierre Rainville Faculte deMedecine dentaire Universite de Montreal CP 6128 SuccCentre-ville Montreal Qc H3C 3J7 Canada or via e-mailpierrerainvilleumontrealca

REFERENCES

Aston-Jones G Rajkowski J amp Cohen J (1999) Role of locuscoeruleus in attention and behavioral flexibility BiologicalPsychiatry 46 1309 ndash1320

Badgaiyan R D amp Posner M I (1998) Mapping the cingulatecortex in response selection and monitoring Neuroimage7 255 ndash260

Balthazard C G amp Woody E Z (1992) The spectral analysisof hypnotic performance with respect to lsquolsquoabsorptionrsquorsquoInternational Journal of Clinical and ExperimentalHypnosis 40 21ndash43

Banyai E I amp Hilgard E R (1976) A comparison ofactive-alert hypnotic induction with traditional relaxationinduction Journal of Abnormal Psychology 85 218 ndash224

Blakemore S J amp Decety J (2001) From the perception ofaction to the understanding of intention Nature ReviewsNeuroscience 2 561 ndash567

Braun A R Balkin T J Wesenten N J Carson R EVarga M Baldwin P Selbie S Belenky G amp HerscovitchP (1997) Regional cerebral blood flow throughout the

Rainville et al 899

sleep ndashwake cycle An H2(15)O PET study Brain 1201173 ndash1197

Bush G Luu P amp Posner M I (2000) Cognitive andemotional influences in anterior cingulate cortex Trendsin Cognitive Sciences 4 215 ndash222

Chalmers D J (2000) What is a neural correlate ofconsciousness In T Metzinger (Ed) Neural correlatesof consciousness Empirical and conceptual questions(pp 17ndash39) Cambridge MIT Press

Coe W C amp Sarbin T R (1977) Hypnosis from thestandpoint of a contextualist Annals of the New YorkAcademy of Sciences 296 2ndash13

Cohen J D Botvinick M amp Carter C S (2000) Anteriorcingulate and prefrontal cortex Whorsquos in control NatureNeuroscience 3 421 ndash423

Collins D L Neelin P Peters T M amp Evans A C (1994)Automatic 3D intersubject registration of MR volumetric datain standardized Talairach space Journal of ComputerAssisted Tomography 18 192 ndash205

Coull J T Frackowiak R S amp Frith C D (1998) Monitoringfor target objects Activation of right frontal and parietalcortices with increasing time on task Neuropsychologia 361325 ndash1334

Coull J T amp Nobre A C (1998) Where and when to payattention The neural systems for directing attention tospatial locations and to time intervals as revealed by bothPET and fMRI Journal of Neuroscience 18 7426 ndash7435

Crawford H J (1994) Brain dynamics and hypnosisAttentional and disattentional processes InternationalJournal of Clinical and Experimental Hypnosis 42204 ndash232

Crawford H J amp Gruzelier J H (1992) A midstream view ofthe neuropsychophysiology of hypnosis Recent researchand future directions In E Fromm amp M R Nash (Eds)Contemporary hypnosis research (pp 227 ndash266) New YorkGuilford Press

Crawford H J Knebel T Kaplan L Vendemia J M C XieM Jamison S amp Pribram K H (1998) Hypnotic analgesia1 Somatosensory event-related potential changes to noxiousstimuli and 2 Transfer learning to reduce chronic low backpain International Journal of Clinical and ExperimentalHypnosis 46 92ndash132

Damasio A R (1999) The feeling of what happens Body andemotion and the making of consciousness New YorkHartcourt Brace

De Pascalis V Magurano M R amp Bellusci A (1999) Painperception somatosensory event-related potentials andskin conductance responses to painful stimuli in high midand low hypnotizable subjects Effects of differential painreduction strategies Pain 83 499 ndash508

Devinsky O Morrell M J amp Vogt B A (1995) Contributionsof anterior cingulate cortex to behaviour Brain 118279 ndash306

Fiset P Paus T Daloze T Plourde G Meuret PBonhomme V Hajj-Ali N Backman S B amp Evans A C(1999) Brain mechanisms of propofol-induced loss ofconsciousness in humans A positron emission tomographicstudy Journal of Neuroscience 19 5505 ndash5513

Friston K J Worsley K J Frackowiak R S J Mazziotta J Camp Evans A C (1994) Assessing the significance of focalactivation using their spatial extent Human Brain Mapping1 214ndash220

Gitelman D R Alpert N M Kosslyn S Daffner K ScintoL Thompson W amp Mesulam M M (1996) Functionalimaging of human right hemispheric activation forexploratory movements Annals of Neurology 39 174ndash179

Gitelman D R Nobre A C Parrish T B LaBar K S KimY H Meyer J R amp Mesulam M (1999) A large-scale

distributed network for covert spatial attention Furtheranatomical delineation based on stringent behavioural andcognitive controls Brain 122 1093 ndash1106

Gruzelier J (1998) A working model of the neurophysiologyof hypnosis A review of evidence Contemporary Hypnosis15 3ndash21

Henson R N A Rugg M D Shallice T amp Dolan R J (2000)Confidence in recognition memory for words Dissociatingright prefrontal roles in episodic retrieval Journal ofCognitive Neuroscience 12 913 ndash923

Henson R N A Rugg M D Shallice T Joseph O ampDolan R J (1999) Recollection and familiarity inrecognition memory An event-related functional magneticresonance imaging study Journal of Neuroscience 193962 ndash3972

Herscovitch P Markham J amp Raichle M E (1983) Brainblood flow measured with intravenous H2(15)O I Theoryand error analysis Journal of Nuclear Medicine 24782 ndash789

Hofbauer R K Rainville P Duncan G H amp Bushnell M C(2001) Cortical representation of the sensory dimension ofpain Journal of Neurophysiology 86 402 ndash411

Hofle N Paus T Reutens D Fiset P Gotman J EvansA C amp Jones B E (1997) Regional cerebral blood flowchanges as a function of delta and spindle activity duringslow wave sleep in humans Journal of Neuroscience 174800 ndash4808

Jeanmonod D Magnin M amp Morel A (1996) Low-thresholdcalcium spike bursts in the human thalamus Commonphysiopathology for sensory motor and limbic positivesymptoms Brain 119 363ndash375

Kajimura N Uchiyama M Takayama Y Uchida S Uema TKato M Sekimoto M Watanabe T Nakajima THorikoshi S Ogawa K Nishikawa M Hiroki M Kudo YMatsuda H Okawa M amp Takahashi K (1999) Activityof midbrain reticular formation and neocortex during theprogression of human non-rapid eye movement sleepJournal of Neuroscience 19 10065 ndash10073

Kawashima R OrsquoSullivan B T amp Roland P E (1995)Positron-emission tomography studies of cross-modalityinhibition in selective attentional tasks Closing the lsquolsquomindrsquoseyersquorsquo Proceedings of the National Academy of SciencesUSA 92 5969 ndash5972

Kim Y H Gitelman D R Nobre A C Parrish T BLaBar K S amp Mesulam M M (1999) The large-scaleneural network for spatial attention displays multifunctionaloverlap but differential asymmetry Neuroimage 9269 ndash277

Kinomura S Larsson J Gulyas B amp Roland P E (1996)Activation by attention of the human reticular formationand thalamic intralaminar nuclei Science 271 512ndash515

Kosslyn S M Thompson W L Costantini-Ferrando M FAlpert N M amp Spiegel D (2000) Hypnotic visual illusionalters color processing in the brain American Journal ofPsychiatry 157 1279 ndash1284

Laureys S Faymonville M E Luxen A Lamy M Franck Gamp Maquet P (2000) Restoration of thalamocorticalconnectivity after recovery from persistent vegetative stateLancet 355 1790ndash1791

Lou H C Kjaer T W Friberg L Wildschiodtz G Holm Samp Nowak M (1999) A 15OndashH2O PET study of meditationand the resting state of normal consciousness HumanBrain Mapping 7 98ndash105

Maquet P Degueldre C Delfiore G Aerts J Peters J MLuxen A amp Franck G (1997) Functional neuroanatomyof human slow wave sleep Journal of Neuroscience 172807 ndash2812

Maquet P Faymonville M E Degueldre C Delfiore G

900 Journal of Cognitive Neuroscience Volume 14 Number 6

Franck G Luxen A amp Lamy M (1999) Functionalneuroanatomy of hypnotic state Biological Psychiatry 45327 ndash333

Metzinger T (2000) The subjectivity of subjective experienceA representationalist analysis of the first-person perspectiveIn T Metzinger (Ed) Neural correlates of consciousnessEmprical and conceptual questions (pp 285 ndash306)Cambridge MIT Press

Nobre A C Sebestyen G N Gitelman D R MesulamM M Frackowiak R S amp Frith C D (1997) Functionallocalization of the system for visuospatial attention usingpositron emission tomography Brain 120 515 ndash533

Pardo J V Fox P T amp Raichle M E (1991) Localization of ahuman system for sustained attention by positron emissiontomography Nature 349 61ndash64

Paus T (2001) Primate anterior cingulate cortex Wheremotor control drive and cognition interface NatureReviews Neuroscience 2 417 ndash424

Paus T Koski L Caramanos Z amp Westbury C (1998)Regional differences in the effects of task difficulty andmotor output on blood flow response in the human anteriorcingulate cortex A review of 107 PET activation studiesNeuroReport 9 R37ndashR47

Paus T Zatorre R J Hofle N Caramanos Z Gotman JPetrides M amp Evans A C (1997) Time-related changesin neural systems underlying attention and arousal duringthe performance of an auditory vigilance task Journal ofCognitive Neuroscience 9 392ndash408

Peyron R Garcia-Larrea L Gregoire M C Costes NConvers P Lavenne F Mauguiere F Michel D ampLaurent B (1999) Haemodynamic brain responses to acutepain in humansmdashSensory and attentional networks Brain122 1765 ndash1779

Picard N amp Strick P L (1996) Motor areas of the medial wallA review of their location and functional activation CerebralCortex 6 342 ndash353

Portas C M Howseman A M Josephs O Turner R ampFrith C D (1998) A specific role for the thalamus inmediating the interaction of attention and arousal inhumans Journal of Neuroscience 18 8979 ndash8989

Posner M I amp Rothbart M K (1998) Attentionself-regulation and consciousness Philosophical

Transactions of the Royal Society of London Series BBiological Sciences 353 1915 ndash1927

Price D D (1996) Hypnotic analgesia Psychological andneural mechanisms In J Barber (Ed) Hypnosis andsuggestions in the treatment of pain (pp 67ndash84) NewYork Norton

Price D D amp Barrell J J (1980) An experiential approachwith quantitative methods A research paradigm Journal ofHumanistic Psychology 20 75ndash95

Rainville P Carrier B Hofbauer R K Bushnell M C ampDuncan G H (1999) Dissociation of pain sensory andaffective dimensions using hypnotic modulation Pain 82159 ndash171

Rainville P Duncan G H Price D D Carrier B ampBushnell M C (1997) Pain affect encoded in humananterior cingulate but not somatosensory cortex Science277 968 ndash971

Rainville P Hofbauer R K Paus T Duncan G H BushnellM C amp Price D D (1999) Cerebral mechanisms ofhypnotic induction and suggestion Journal of CognitiveNeuroscience 11 110ndash125

Ruby P amp Decety J (2001) Effect of subjective perspectivetaking during simulation of action A PET investigation ofagency Nature Neuroscience 4 546 ndash550

Steriade M amp McCarley R W (1990) Brainstem control ofwakefulness and sleep New York Plenum

Szechtman H Woody E Bowers K S amp Nahmias C(1998) Where the imaginal appears real A positronemission tomography study of auditory hallucinationsProceedings of the National Academy of Sciences USA95 1956 ndash1960

Talairach J amp Tournoux P (1988) Co-planar stereotaxicatlas of the human brain New York Thieme

Tellegen A amp Atkinson G (1974) Openness to absorbingand self-altering experiences (lsquolsquoabsorptionrsquorsquo) a trait relatedto hypnotic susceptibility Journal of Abnormal Psychology83 268 ndash277

Toma K Honda M Hanakawa T Okada T Fukuyama HIkeda A Nishizawa S Konishi J amp Shibasaki H (1999)Activities of the primary and supplementary motor areasincrease in preparation and execution of voluntary musclerelaxation An event-related fMRI study Journal ofNeuroscience 19 3527 ndash3534

Varela F J amp Shear J (1999) First-person methodologiesWhat why and how Journal of Consciousness Studies 61ndash14

Vingoe F J (1968) The development of a group alert-trancescale International Journal of Clinical and ExperimentalHypnosis 16 120 ndash132

Vingoe F J (1973) Comparison of the Harvard Group Scaleof Hypnotic Susceptibility Form A and the Group AlertTrance Scale in a university population InternationalJournal of Clinical and Experimental Hypnosis 21169 ndash179

Vogt B A amp Gabriel M (1993) Neurobiology of cingulatecortex and limbic thalamus A comprehensive handbookBoston Birkauser

Weitzenhoffer A M (1980) Hypnotic susceptibility revisitedAmerican Journal of Clinical Hypnosis 22 130 ndash146

Willoch F Rosen G Tolle T R Oslashye I Wester H J BernerN Schwaiger M amp Bartenstein P (2000) Phantom limbpain in the human brain Unravelling neural circuitries ofphantom limb pain sensations using positron emissiontomography Annals of Neurology 48 842 ndash849

Worsley K J Evans A C Marrett S amp Neelin P (1992)A three-dimensional statistical analysis for CBF activationstudies in human brain Journal of Cerebral Blood Flow andMetabolism 12 900 ndash918

Rainville et al 901

Page 7: Hypnosis Modulates Activity in Brain Structures Involved in the …pineda/COGS175/readings/Rain... · 2005. 2. 28. · Hypnosis Modulates Activity in Brain Structures Involved in

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Rainville et al 893

the underlying processes in the production of hypnoticstates as discussed below

Role of the Brainstem the Thalamus and the ACCin Hypnosis

Results of the regression analyses suggest that neuralactivity in the brainstem the thalamus and the ACCcontributes to the experience of being hypnotized Therelaxation-specific negative correlations in the mesen-

cephalic brainstem and the thalamus may reflect thewell-established contribution of brainstem and thalamicnuclei to the regulation of wakefulness and corticalarousal In functional brain imaging studies rCBFdecreases in the brainstem and the thalamus have beenassociated with decreased vigilance (Paus et al 1997)sleep (Kajimura et al 1999 Braun et al 1997 Hofleet al 1997 Maquet et al 1997) and the loss ofconsciousness produced by the anesthetic propofol(Fiset et al 1999) These effects and to some extent

Figure 3 Brain regionsshowing positive (redarrowheads) and negative(blue arrowheads) regres-sion peaks between rCBFand self-ratings of (A)relaxation and (B) absorp-tion after accounting forrelaxation-related variance(absorption-specific)Statistical t maps are super-imposed on the averageanatomical MRI (left is onthe left side) Slice locationsare indicated on the 3-Danatomical image of asingle subjectrsquos anatomicalMRI (A-positive) Positiverelaxation-related effectsare shown in the centralregion bilaterally (horizon-tal slice on the left) Apositive peak is shown inthe right superior occipitalgyrus (SOg) (coronal viewon the right note scalechange) (A-negative)A negative relaxation-related effect in the rightposterior parietal cortexis shown in horizontal(first from left) coronal(second) and lateralsagittal (third) views Theplus sign indicates the moreanterior location of thepeak positive regression inthe analysis of absorption-related effects as shown inB Additional negative cor-relations are shown in thebilateral middle and inferiortemporal gyri (second) andin the right somatosensorycortices (S1 S2 insula)(B-positive) A positiveabsorption-specific peak isshown in the right inferiorparietal lobule (first fromleft) The minus sign indicates the more posterior location of the negative regression peak in the analysis of relaxation-related effects as shown in

A Other peaks are shown on the midsagittal view in the thalamus and the anterior cingulate cortex (second from left) and in the left lenticularnuclei and bilateral prefrontal cortices (last three cuts from left) (B-negative) Negative absorption-related effects are shown in the left inferiorparietal lobule (first from left) in both occipital lobes (second and third from left) and in the precuneus (first and third) Stereotaxic coordinates ofpeaks are reported in Table 3 (see relaxation- and absorption-specific)

894 Journal of Cognitive Neuroscience Volume 14 Number 6

the present relaxation-related decrease in brainstemrCBF may reflect an attenuation of activity withinbrainstem cholinergic nuclei Such reduction has beenobserved during slow EEG activity before the onset ofsleep and during slow-wave sleep in animal studies(Steriade amp McCarley 1990) Consistent with this pos-sibility we previously reported an increase in slow(delta) EEG activity following hypnotic induction (Rain-ville Hofbauer et al 1999) Although hypnotic andsleep states are clearly distinct certain neurophysiolog-

ical mechanisms may be involved to a varying degree inthe production of both states

The positive association specifically observed betweenmental absorption and rCBF in the upper pons and thethalamus contrasts with the above relaxation-relatedeffect and is consistent with previous reports of atten-tion-related brain activation (Kinomura et al 1996) Thisactivity may reflect the involvement of the noradrenergicsystem of the locus coeruleus in focused attentionand possibly in the interaction between cortical arousal

Table 3 Cerebral Sites of Covariation with Thalamic rCBF at the Absorption-Specific Peak Coordinates (x = iexcl27 y = iexcl160z = 120)

Region Peak Location x y z t

Frontal (F) R medial sup F gACC (BA 624) 1 43 32 +382

R anterior cingulate gsup F g (BA 326) 8 13 44 +387

R inf F g (BA 44) 51 12 8 +387

R ant insula (BA 14) 38 12 5 +412

R sup F g (BA 6) 16 20 59 +371

R medial sup F g (BA 6) 3 iexcl6 63 +498

R medial sup F g (BA 6) 11 iexcl23 53 +412

L middle F g (BA 46) iexcl38 46 23 +381

L middle F g (BA 46) iexcl31 39 39 +374

L inf F g (BA 44) iexcl43 6 12 +430

L sup F g (BA 6) iexcl19 20 53 +340

L medial sup F g (BA 6) iexcl5 17 65 +353

L sup F g (BA 6) iexcl20 12 65 +283

Parietal R inf parietal lobule (BA 40) 56 iexcl44 50 +519

Occipital (O) R fusiform g (BA 19) 26 iexcl62 iexcl30 iexcliexcl515

R lingual g (BA 18) 7 iexcl78 6 iexcliexcl623

R sup O g (BA 19) 19 iexcl85 30 iexcliexcl714

R O pole (BA 18) 27 iexcl90 9 iexcliexcl751

L cuneus (BA 18) iexcl11 iexcl83 29 iexcliexcl633

L O pole (BA 18) iexcl23 iexcl88 6 iexcliexcl793

Subcortical R thalamus 17 iexcl11 2 +350

R brainstem 13 iexcl26 iexcl15 +312

R medial brainstem 3 iexcl32 iexcl24 +287

L cerebellum iexcl4 iexcl57 iexcl21 +409

L globus pallidus iexcl20 iexcl1 iexcl2 +302

L caudate nucleus iexcl12 6 20 +291

Positive and negative regression slopes are significant at sites listed based on cluster or peak analyses (peak t threshold ltgtplusmn370 in bold allpeaks reported with t lt 370 are within a significant cluster see Methods) Peaks in italic are also reported in Table 1 See legends to Tables 1 and 2and Methods for further explanation

Rainville et al 895

and attentional processes (ie increased attentionabsorption concurrent with decreased cortical arousalincreased relaxation) (Aston-Jones et al 1999) Theindirect nature of the rCBF measures and the relativelypoor resolution of the PET method require somecaution in evaluating the possible anatomo-functionalimplications of our results in the brainstem Howeverthe convergent findings observed in other brain imag-ing studies and the observations provided in animalstudies support the notion that ascending cholinergicand noradrenergic pathways may contribute differen-tially to the multiple dimensions of experience thatcharacterize hypnosis

The overall pattern of results found in the ACC likelyreflects the heterogeneity of functions associated withthis area (Devinsky Morrell amp Vogt 1995) The locationof the most posterior relaxation-related peak in the ACC(mACC) is consistent with our previous observationof ACC activation during hypnosis (Rainville Hofbaueret al 1999) This relaxation-related peak is only slightlyanterior to the motor area of the caudal ACC (Picard ampStrick 1996) and may be involved in the installment of arelaxed state (also see precentral area below) In con-trast a positive absorption-specific effect was observedin a more rostral region of the ACC (rACC) close to anegative relaxation-specific correlation (see Table 1)This area of the ACC has previously been involved inexecutive attention in the detection of errors and in themonitoring of conflict between competing cognitiveprocesses (Bush Luu amp Posner 2000 Cohen Botvinickamp Carter 2000 Badgaiyan amp Posner 1998 Posner ampRothbart 1998) A meta-analysis of PET studies inves-tigating cognitive functions further suggested that theincrease in activity within this sector of the ACC isrelated to the difficulty of the task performed (PausKoski Caramanos amp Westbury 1998) Our findings areconsistent with these propositions to the extent thatthe engagement of the cognitive and neurophysiologicalprocesses implied in each of those accounts may beaccompanied by a subjective experience of increasedmental absorption

The coordinated pattern of rCBF changes in thebrainstem the thalamus and the ACC may reflect theinterrelationships between the multiple components of anetwork (eg Paus et al 1997) herein shown to beassociated with the feeling of being lsquolsquomentally absorbedrsquorsquoThe precise location of the observed absorption-specificthalamic peak is consistent with an involvement of theintralaminar and medio-dorsal nuclei which have recip-rocal connections with the ACC (Vogt amp Gabriel 1993)The finding that the coordinated activity in the thalamusand the ACC is disrupted in persistent vegetative states isconsistent with the notion that these structures work intandem to regulate consciousness (Laureys et al 2000also see Jeanmonod Magnin amp Morel 1996) Further-more a functional interaction between arousal andattentional processes has been reported in the thalamus

where the putative attention-related activity associatedwith the performance of a simple visual discriminationtask was found to increase in states of low arousal (Portaset al 1998) This increase in thalamic activity wassuggested (1) to reflect a compensatory mechanism thatpermitted the maintenance of stable levels of perform-ance in states of low arousal and (2) to prevent thegeneralized thalamo-cortical synchronization that wouldlead to sleep Here the opposite effects of relaxation andabsorption on thalamic activity may reflect this compen-satory mechanism that maintains high levels of focusedattention in deeply relaxed subjects during hypnosisThis function may be critical not only in hypnosis butalso in other conditions of deep relaxation distinct fromboth sleep and normal wakefulness such as meditativestates (Lou et al 1999) Furthermore the coactivation ofthe ACC and the ponto-mesencephalic brainstem mayreflect the contribution of the ACC to the regulation ofattention-related activity in the locus coeruleus (Cohenet al 2000) The positive regression found with absorp-tion in the ponto-mesencephalic brainstem and themore robust regression observed in the thalamus andthe ACC after accounting for relaxation-related changes(absorption-specific Table 1) further substantiate thepossibility that brainstem and thalamic nuclei interactwith the ACC to regulate the interaction between atten-tion and cortical arousal Taken together these resultsare consistent with a contribution of brainstem nucleithe intralaminar and medio-dorsal nuclei of the thala-mus and the ACC to the changes in phenomenalexperience that characterize hypnotic states

Additional Relaxation- and Absorption-RelatedChanges in rCBF

Relaxation-Related Activity

We observed strong relaxation-related increases in rCBFin the precentral gyrus bilaterally and reciprocaldecreases in somatosensory areas (S1 S2 and insula)Precentral and premotor activation has been reportedduring hypnosis in an independent study (Maquet et al1999) and precentral rCBF was correlated with the rCBFmeasured at the ACC site of hypnosis-related activity inour previous study (see Appendix in Rainville Hofbaueret al 1999) Similar increases in activity in motor andpremotor areas have been associated with voluntarymuscular relaxation (Toma et al 1999) but the presentresults may reflect more than physical relaxation

All standard hypnotic procedures include instructionsfor relaxation However the specific contribution ofmuscular relaxation and decreased arousal to the pro-duction of hypnotic states is unclear as hypnotic phe-nomena have been produced during muscular exercise(Banyai amp Hilgard 1976) and with suggestions of active-alertness (Vingoe 1968 1973) Here the absence ofsignificant effect of hypnosis on heart rate indicates thatchanges in cerebral activity did not correlate with

896 Journal of Cognitive Neuroscience Volume 14 Number 6

changes in peripheral arousal and suggests that subjectswere already physically relaxed in the baseline controlcondition This implies that the hypnosis-inducedchanges in self-ratings of relaxation may not simplyreflect changes in lsquolsquoperipheralrsquorsquo arousal but may attestmore specifically of an increase in lsquolsquomentalrsquorsquo relaxationand a reduction in lsquolsquocorticalrsquorsquo arousal This is consistentwith Pricersquos experiential model of hypnosis (see Intro-duction) and with our previous study showing anincrease in slow (delta) EEG activity during hypnosis

Relaxation-related effects observed outside primarysomatomotor areas may partly reflect subjective feelingsof mental ease more closely In the subtraction analysishypnosis-related decreases were found in the rightlateral posterior parietal rCBF both here (x y z 40iexcl52 44) and in our previous study (x y z 46 iexcl50 42from Table 1 in Rainville Hofbauer et al 1999) Herethese changes were strongly but not specifically asso-ciated with relaxation (x y z 39 iexcl49 45 see Table 2Figure 3A) Furthermore after accounting for absorp-tion-related variance right prefrontal activity was neg-atively correlated with relaxation (Table 2) Thoseadditional changes in the right posterior parietal cortexand the right prefrontal cortices may contribute to thesubjective feelings of mental ease rather than or inaddition to physical relaxation

Fronto-Parietal Attention Networks

Absorption-related activity was widespread and bilateralin the prefrontal cortices but peaks were generallystronger in the right hemisphere Positive regressionpeaks were maximal in the ventrolateral frontal corticesover the inferior frontal gyrus and in the anterior insulaA positive absorption-related regression peak was alsosignificant in the right inferior parietal lobule Theseareas also displayed strong coactivation with absorption-related thalamic activity Very similar patterns of activa-tion have been associated with attentional processes intasks involving visual (eg Coull Frackowiak amp Frith1998) auditory (Paus et al 1997) and somatosensorystimuli (Peyron et al 1999) Notably the location of thepositive parietal peak observed here closely matches theactivation sites reported in those studies and the site ofcovariation with the right ventrolateral attention-relatedactivity reported in Paus et al (1997) suggesting theactivation of a similar network The coordinated absorp-tion-related activity observed here in the brainstem thethalamus the ACC the right inferior frontal gyrus andthe right inferior parietal lobule provides very strongevidence that mental absorption is an experiential cor-relate of the activation of the brainrsquos lsquolsquoexecutive atten-tional networkrsquorsquo and suggests that this system plays acritical role in the production of hypnotic states

Negative absorption-related regression peaks werealso found in both the right and left lateral parietalcortices and in the precuneus (see Table 2) These

effects were largely independent of thalamic activity asindicated by the absence of significant effects at theselocations in the covariation analysis (Table 3) The rightposterior parietal cortex has been suggested to con-stitute a vigilanceorientation system (Pardo Fox ampRaichle 1991) and hypnosis-related decreases in thisarea may reflect a relative disengagement towardexternal sources of stimulation Right and left posteriorparietal cortices at the precise sites of relaxation- andabsorption-related decrease in rCBF have been sug-gested to contribute to the monitoring of externalspace and time respectively (Gitelman et al 19961999 Kim et al 1999 Coull amp Nobre 1998 Nobreet al 1997) Although these functions were notdirectly assessed in this experiment the hypnoticinduction procedure includes specific instructions fordecreased orientation to and interest in irrelevantexternal sources of stimulation and previous observa-tions suggest that hypnotic relaxation and absorptionare precursors to some alterations in spatio-temporalorientation and monitoring (Price 1996) Thus wespeculate that those additional experiential changesmay be consequent to relaxation- and absorption-related decreases in posterior parietal activity

Relaxation- and Absorption-Related Effects onOccipital rCBF

The subtraction analysis confirmed the reliability of thehypnosis-related increase in occipital rCBF reported inour previous study (Rainville Hofbauer et al 1999) Wenow show that this effect was associated with the sub-jective experience of hypnotic relaxation (see Table 2relaxation-specific) Consistently our previous studydemonstrated a coupling between occipital increases inrCBF and increases in slow (delta) EEG activity duringhypnosis Similar increases in occipital rCBF andor slowEEG activity had been observed in another study onhypnosis (Maquet et al 1999) and in states of decreasedvigilance (Paus et al 1997) meditation (Lou et al 1999)and slow wave sleep (Kajimura et al 1999 Hofle et al1997) These effects are consistent with our previousproposition that hypnotic induction produces a globaldecrease in cross-modality suppression in unattendedsensory channels leading to a relative disinhibitionof cortical activity (see Paus et al 1997 KawashimaOrsquoSullivan amp Roland 1995)

In contrast negative correlations between rCBF andmental absorption were observed over both occipitallobes (Table 2 Figure 3B) Consistently occipital rCBFwas correlated negatively with thalamic rCBF at theabsorption-specific site (Table 3) These contrastingeffects imply that variations in occipital rCBF are asso-ciated with separate portions of the variance in relaxa-tion and absorption (Note that although absorptionand relaxation were significantly correlated the variancein absorption was largely independent of relaxation see

Rainville et al 897

Methods) For a given level of relaxation the increasein hypnotic absorption could reflect the concurrentengagement of the lsquolsquoexecutive attentional networkrsquorsquowhich exerts an opposite effect over brain areas sub-serving unattended sensory channels (ie a relativefacilitation of cross-modality suppression)

Hypnosis as a State of Consciousness

The representation of the body-self is central to theneurophenomenology of consciousness (Metzinger2000) In the Introduction we have proposed that theinduction of hypnosis produces global changes in sub-jective experience reflecting a modulation of basicaspects of the body-self representation Consistentlythe PET results indicate that hypnosis involves changesin activity within brain structures essential for the basicregulation of states of consciousness self-monitoringand self-regulation Furthermore changes in relaxationand absorption are precursors (although they may notbe essential) to other hypnosis-related effects such asthe diminished tendency to judge monitor and censorthe suspension of usual orientation toward time loca-tion andor sense of self and the experience of onersquosown response as automatic or extra-volitional (Price1996) These dimensions of experience also rely criticallyon self-representation and may depend at least partly oncerebral areas shown here to be involved in hypnosisAmong those changes the increased feeling of automa-ticity an altered feeling of agency may be the mostdistinctive aspect of hypnotic phenomenology (Weitzen-hoffer 1980) Interestingly the sense of agency hasrecently been suggested to involve areas that displayconsistent changes in activity during hypnosis such asthe right inferior parietal cortex the precuneus and thesomatosensory cortices (Blakemore amp Decety 2001Ruby amp Decety 2001) The modulation of activityobserved here within those areas is consistent withthe interpretation that hypnosis produces changes inself-representation construed as an essential element forconscious experience

Conclusion

The present study used self-ratings of subjective feelingsof mental relaxation and mental absorption to map brainareas involved in hypnosis We replicated previous find-ings and further demonstrated that hypnotic relaxationand absorption reflect changes in brain activity withinregions involved in the control of consciousness statesand in self-regulation such as the brainstem the thala-mus and the ACC The coordinated activity within thesestructures and other absorption-related areas such asthe ventrolateral frontal and right posterior parietalcortices has been previously shown to underlie theregulation of the content of consciousness throughmechanisms of executive attention We must recognize

that our findings are correlative in nature and arerelevant to hypnosis to the extent that mental relaxationand absorption are conceived as basic experientialdimensions that characterize hypnotic phenomenaWe further speculate that these changes in subjectiveexperience and brain activity may contribute to otherhypnosis-related effects such as the altered feeling ofagency experienced during hypnosis These findings areconsistent with the notion that hypnotic states areachieved through the modulation of activity within adistributed network of cerebral structures involved inthe regulation of consciousness states

METHODS

Subjects

Ten right-handed subjects (4 men 6 women) wereselected from a group of 22 volunteers as a part of astudy on the hypnotic modulation of pain (Hofbaueret al 2001) Hypnotic susceptibility was assessed usingthe SHSS-A administered between scans (range 111ndash1011 mean plusmn SD 69 plusmn28) The Ethics Committee ofthe Montreal Neurological Institute (MNI) approved allprocedures and subjects signed a consent form describ-ing the procedure and affirming their right to withdrawfrom the experiment without prejudice

Experimental Procedure

We report the results obtained in eight scans acquired ina restful baseline and hypnosis condition Hypnoticinduction started immediately after Scan 4 and wassustained in the remaining scans by repeating inductioninstructions between scans Instructions included sug-gestions for (1) increased physical and mental relaxa-tion (2) comfortable feeling of warmth heaviness anddrowsiness (3) sustained passive attention to theexperimenterrsquos voice and to the instructions and (4)decreased concern with and orientation to external andinternal (mental) sources of distraction No specificinstruction for visual imagery was included During allscans the subjectsrsquo eyes were closed and their left handwas immersed in warm or painfully hot water Pain-related activation and four additional scans performedwith suggestions for pain modulation are reported else-where (Hofbauer et al 2001)

Self-Ratings of Mental Relaxation and Absorption

After each scan subjects were instructed to rate (0ndash10)(1) their level of tensionndashrelaxation with lsquolsquo10 being themost relaxed and at ease you can bersquorsquo and (2) their levelof sustained focus of attention with lsquolsquo10 being the mostabsorbed and the largest amount of sustained focusedattention you can gatherrsquorsquo Ratings of relaxation andabsorption were transformed using the rank within sub-jects to (1) control for individual differences (2) prevent

898 Journal of Cognitive Neuroscience Volume 14 Number 6

scaling biases and (3) parallel the analysis of rCBF dataSubjects rated pain on separate scales (0ndash100) Hypno-sis-related increases in relaxation and absorption did notinteract with the stimulation condition (pain vs warmstimulation prsquos gt 10) neither relaxation nor absorptioncorrelated significantly with pain ratings (all prsquos gt 10)and pain was not altered by hypnosis alone [t(9) = 069p = 51]

PET Imaging Methods

rCBF was measured using the H215O bolus injection

method (10 millicuriesscan) without arterial blood sam-pling (Herscovitch Markham amp Raichle 1983) with ahigh-resolution PET scanner operated in 3-D acquisitionmode (Siemens ECAT HR+ 63 slices) Stimulus onsetwas simultaneous with bolus injection and 1-min acquis-ition scans started about 15 sec postinjection (interscaninterval of 12ndash15 min) Data from the first 40 sec ofacquisition were reconstructed and analyzed Each sub-ject also underwent a high-resolution anatomical MRI(160 1-mm sagittal slices acquired on a Philips 15-TGyroscan system) Each PET and MRI volume wasaligned and transformed using software developed atthe MNI to match the MNI standardized Talairach space(Collins Neelin Peters amp Evans 1994 Talairach ampTournoux 1988) PET volumes were smoothed (FWHM= 14 mm) and normalized to the average brain countPeak and cluster analyses were performed (FristonWorsley Frackowiak Mazziotta amp Evans 1994 WorsleyEvans Marrett amp Neelin 1992)

Reliability of Hypnosis-Related Effects

A first analysis was performed using the subtractionmethod (Hypnosis minus Baseline) to evaluate thereliability of the effects reported in our previous study(Table 2 in Rainville Hofbauer et al 1999) We consid-ered that hypnosis-related changes in rCBF were repli-cated when a significant peak was observed within oneresel (Worsley et al 1992) of the peak sites reported inour previous study or when the peak sites were within asignificant cluster

Regression of rCBF on Self-Ratings of Relaxationand Absorption

Regression analyses were used to test the relationbetween ratings and rCBF (GLM) Subject- and stimu-lus-related effects were removed first (ANCOVA) andthe significance of the regression slope between thecovariate of interest and rCBF was estimated usingt tests Relaxation-specific and absorption-specific effectswere further tested using ANCOVAs to remove thevariance shared between absorption and relaxation(R2 = 42 p lt 001) The statistical criterion was setto t gt 258 (two-tailed uncorrected p lt 01) in the

directed searches restricted to the brainstem the thala-mus and the ACC (Table 1 Figure 2) Global searcheffects are significant ( p lt 05) based on peak (t valuegt 420) andor clusters analysis after a correction formultiple comparisons over the gray matter volume(uncorrected p lt 0001) (Table 2 Figure 3)

Thalamic Covariations

A covariation analysis was performed in which the rCBFmeasured in the thalamus was used as the covariate ofinterest after accounting for subject- and stimulus-related variance (ANCOVA see Tables 1 and 3) Becausewe were mainly interested in the relationship betweenthe activity in the thalamus and other absorption-relatedsites the threshold for statistical significance was set tot = 370 ( p = 05 uncorrected p lt 0008) based on thevolume defined by the sum of clusters of voxels showingsignificant absorption-specific effects (186 cm3 seeWorsley et al 1992)

Acknowledgments

We thank R Adolphs S Anderson A Bechara A R DamasioH Damasio Susan Lutgendorf J Parvizi and D Tranel fortheir comments on preliminary versions of the manuscriptPET analyses were performed using the software DOTdeveloped by Sylvain Milot and the MINC programs developedby Peter Neelin at the McConnell Brain Imaging Center of theMontreal Neurological Institute This study was supported bythe Medical Research Council (MRC) of Canada Dr Rainvillewas supported by the Medical Research Council of Canada andthe Human Frontier Science Program and Dr Hofbauer wassupported by the Fonds pour la recherche en sante du Quebecand the Royal Victoria Hospital Research Institute

Reprint requests should be sent to Pierre Rainville Faculte deMedecine dentaire Universite de Montreal CP 6128 SuccCentre-ville Montreal Qc H3C 3J7 Canada or via e-mailpierrerainvilleumontrealca

REFERENCES

Aston-Jones G Rajkowski J amp Cohen J (1999) Role of locuscoeruleus in attention and behavioral flexibility BiologicalPsychiatry 46 1309 ndash1320

Badgaiyan R D amp Posner M I (1998) Mapping the cingulatecortex in response selection and monitoring Neuroimage7 255 ndash260

Balthazard C G amp Woody E Z (1992) The spectral analysisof hypnotic performance with respect to lsquolsquoabsorptionrsquorsquoInternational Journal of Clinical and ExperimentalHypnosis 40 21ndash43

Banyai E I amp Hilgard E R (1976) A comparison ofactive-alert hypnotic induction with traditional relaxationinduction Journal of Abnormal Psychology 85 218 ndash224

Blakemore S J amp Decety J (2001) From the perception ofaction to the understanding of intention Nature ReviewsNeuroscience 2 561 ndash567

Braun A R Balkin T J Wesenten N J Carson R EVarga M Baldwin P Selbie S Belenky G amp HerscovitchP (1997) Regional cerebral blood flow throughout the

Rainville et al 899

sleep ndashwake cycle An H2(15)O PET study Brain 1201173 ndash1197

Bush G Luu P amp Posner M I (2000) Cognitive andemotional influences in anterior cingulate cortex Trendsin Cognitive Sciences 4 215 ndash222

Chalmers D J (2000) What is a neural correlate ofconsciousness In T Metzinger (Ed) Neural correlatesof consciousness Empirical and conceptual questions(pp 17ndash39) Cambridge MIT Press

Coe W C amp Sarbin T R (1977) Hypnosis from thestandpoint of a contextualist Annals of the New YorkAcademy of Sciences 296 2ndash13

Cohen J D Botvinick M amp Carter C S (2000) Anteriorcingulate and prefrontal cortex Whorsquos in control NatureNeuroscience 3 421 ndash423

Collins D L Neelin P Peters T M amp Evans A C (1994)Automatic 3D intersubject registration of MR volumetric datain standardized Talairach space Journal of ComputerAssisted Tomography 18 192 ndash205

Coull J T Frackowiak R S amp Frith C D (1998) Monitoringfor target objects Activation of right frontal and parietalcortices with increasing time on task Neuropsychologia 361325 ndash1334

Coull J T amp Nobre A C (1998) Where and when to payattention The neural systems for directing attention tospatial locations and to time intervals as revealed by bothPET and fMRI Journal of Neuroscience 18 7426 ndash7435

Crawford H J (1994) Brain dynamics and hypnosisAttentional and disattentional processes InternationalJournal of Clinical and Experimental Hypnosis 42204 ndash232

Crawford H J amp Gruzelier J H (1992) A midstream view ofthe neuropsychophysiology of hypnosis Recent researchand future directions In E Fromm amp M R Nash (Eds)Contemporary hypnosis research (pp 227 ndash266) New YorkGuilford Press

Crawford H J Knebel T Kaplan L Vendemia J M C XieM Jamison S amp Pribram K H (1998) Hypnotic analgesia1 Somatosensory event-related potential changes to noxiousstimuli and 2 Transfer learning to reduce chronic low backpain International Journal of Clinical and ExperimentalHypnosis 46 92ndash132

Damasio A R (1999) The feeling of what happens Body andemotion and the making of consciousness New YorkHartcourt Brace

De Pascalis V Magurano M R amp Bellusci A (1999) Painperception somatosensory event-related potentials andskin conductance responses to painful stimuli in high midand low hypnotizable subjects Effects of differential painreduction strategies Pain 83 499 ndash508

Devinsky O Morrell M J amp Vogt B A (1995) Contributionsof anterior cingulate cortex to behaviour Brain 118279 ndash306

Fiset P Paus T Daloze T Plourde G Meuret PBonhomme V Hajj-Ali N Backman S B amp Evans A C(1999) Brain mechanisms of propofol-induced loss ofconsciousness in humans A positron emission tomographicstudy Journal of Neuroscience 19 5505 ndash5513

Friston K J Worsley K J Frackowiak R S J Mazziotta J Camp Evans A C (1994) Assessing the significance of focalactivation using their spatial extent Human Brain Mapping1 214ndash220

Gitelman D R Alpert N M Kosslyn S Daffner K ScintoL Thompson W amp Mesulam M M (1996) Functionalimaging of human right hemispheric activation forexploratory movements Annals of Neurology 39 174ndash179

Gitelman D R Nobre A C Parrish T B LaBar K S KimY H Meyer J R amp Mesulam M (1999) A large-scale

distributed network for covert spatial attention Furtheranatomical delineation based on stringent behavioural andcognitive controls Brain 122 1093 ndash1106

Gruzelier J (1998) A working model of the neurophysiologyof hypnosis A review of evidence Contemporary Hypnosis15 3ndash21

Henson R N A Rugg M D Shallice T amp Dolan R J (2000)Confidence in recognition memory for words Dissociatingright prefrontal roles in episodic retrieval Journal ofCognitive Neuroscience 12 913 ndash923

Henson R N A Rugg M D Shallice T Joseph O ampDolan R J (1999) Recollection and familiarity inrecognition memory An event-related functional magneticresonance imaging study Journal of Neuroscience 193962 ndash3972

Herscovitch P Markham J amp Raichle M E (1983) Brainblood flow measured with intravenous H2(15)O I Theoryand error analysis Journal of Nuclear Medicine 24782 ndash789

Hofbauer R K Rainville P Duncan G H amp Bushnell M C(2001) Cortical representation of the sensory dimension ofpain Journal of Neurophysiology 86 402 ndash411

Hofle N Paus T Reutens D Fiset P Gotman J EvansA C amp Jones B E (1997) Regional cerebral blood flowchanges as a function of delta and spindle activity duringslow wave sleep in humans Journal of Neuroscience 174800 ndash4808

Jeanmonod D Magnin M amp Morel A (1996) Low-thresholdcalcium spike bursts in the human thalamus Commonphysiopathology for sensory motor and limbic positivesymptoms Brain 119 363ndash375

Kajimura N Uchiyama M Takayama Y Uchida S Uema TKato M Sekimoto M Watanabe T Nakajima THorikoshi S Ogawa K Nishikawa M Hiroki M Kudo YMatsuda H Okawa M amp Takahashi K (1999) Activityof midbrain reticular formation and neocortex during theprogression of human non-rapid eye movement sleepJournal of Neuroscience 19 10065 ndash10073

Kawashima R OrsquoSullivan B T amp Roland P E (1995)Positron-emission tomography studies of cross-modalityinhibition in selective attentional tasks Closing the lsquolsquomindrsquoseyersquorsquo Proceedings of the National Academy of SciencesUSA 92 5969 ndash5972

Kim Y H Gitelman D R Nobre A C Parrish T BLaBar K S amp Mesulam M M (1999) The large-scaleneural network for spatial attention displays multifunctionaloverlap but differential asymmetry Neuroimage 9269 ndash277

Kinomura S Larsson J Gulyas B amp Roland P E (1996)Activation by attention of the human reticular formationand thalamic intralaminar nuclei Science 271 512ndash515

Kosslyn S M Thompson W L Costantini-Ferrando M FAlpert N M amp Spiegel D (2000) Hypnotic visual illusionalters color processing in the brain American Journal ofPsychiatry 157 1279 ndash1284

Laureys S Faymonville M E Luxen A Lamy M Franck Gamp Maquet P (2000) Restoration of thalamocorticalconnectivity after recovery from persistent vegetative stateLancet 355 1790ndash1791

Lou H C Kjaer T W Friberg L Wildschiodtz G Holm Samp Nowak M (1999) A 15OndashH2O PET study of meditationand the resting state of normal consciousness HumanBrain Mapping 7 98ndash105

Maquet P Degueldre C Delfiore G Aerts J Peters J MLuxen A amp Franck G (1997) Functional neuroanatomyof human slow wave sleep Journal of Neuroscience 172807 ndash2812

Maquet P Faymonville M E Degueldre C Delfiore G

900 Journal of Cognitive Neuroscience Volume 14 Number 6

Franck G Luxen A amp Lamy M (1999) Functionalneuroanatomy of hypnotic state Biological Psychiatry 45327 ndash333

Metzinger T (2000) The subjectivity of subjective experienceA representationalist analysis of the first-person perspectiveIn T Metzinger (Ed) Neural correlates of consciousnessEmprical and conceptual questions (pp 285 ndash306)Cambridge MIT Press

Nobre A C Sebestyen G N Gitelman D R MesulamM M Frackowiak R S amp Frith C D (1997) Functionallocalization of the system for visuospatial attention usingpositron emission tomography Brain 120 515 ndash533

Pardo J V Fox P T amp Raichle M E (1991) Localization of ahuman system for sustained attention by positron emissiontomography Nature 349 61ndash64

Paus T (2001) Primate anterior cingulate cortex Wheremotor control drive and cognition interface NatureReviews Neuroscience 2 417 ndash424

Paus T Koski L Caramanos Z amp Westbury C (1998)Regional differences in the effects of task difficulty andmotor output on blood flow response in the human anteriorcingulate cortex A review of 107 PET activation studiesNeuroReport 9 R37ndashR47

Paus T Zatorre R J Hofle N Caramanos Z Gotman JPetrides M amp Evans A C (1997) Time-related changesin neural systems underlying attention and arousal duringthe performance of an auditory vigilance task Journal ofCognitive Neuroscience 9 392ndash408

Peyron R Garcia-Larrea L Gregoire M C Costes NConvers P Lavenne F Mauguiere F Michel D ampLaurent B (1999) Haemodynamic brain responses to acutepain in humansmdashSensory and attentional networks Brain122 1765 ndash1779

Picard N amp Strick P L (1996) Motor areas of the medial wallA review of their location and functional activation CerebralCortex 6 342 ndash353

Portas C M Howseman A M Josephs O Turner R ampFrith C D (1998) A specific role for the thalamus inmediating the interaction of attention and arousal inhumans Journal of Neuroscience 18 8979 ndash8989

Posner M I amp Rothbart M K (1998) Attentionself-regulation and consciousness Philosophical

Transactions of the Royal Society of London Series BBiological Sciences 353 1915 ndash1927

Price D D (1996) Hypnotic analgesia Psychological andneural mechanisms In J Barber (Ed) Hypnosis andsuggestions in the treatment of pain (pp 67ndash84) NewYork Norton

Price D D amp Barrell J J (1980) An experiential approachwith quantitative methods A research paradigm Journal ofHumanistic Psychology 20 75ndash95

Rainville P Carrier B Hofbauer R K Bushnell M C ampDuncan G H (1999) Dissociation of pain sensory andaffective dimensions using hypnotic modulation Pain 82159 ndash171

Rainville P Duncan G H Price D D Carrier B ampBushnell M C (1997) Pain affect encoded in humananterior cingulate but not somatosensory cortex Science277 968 ndash971

Rainville P Hofbauer R K Paus T Duncan G H BushnellM C amp Price D D (1999) Cerebral mechanisms ofhypnotic induction and suggestion Journal of CognitiveNeuroscience 11 110ndash125

Ruby P amp Decety J (2001) Effect of subjective perspectivetaking during simulation of action A PET investigation ofagency Nature Neuroscience 4 546 ndash550

Steriade M amp McCarley R W (1990) Brainstem control ofwakefulness and sleep New York Plenum

Szechtman H Woody E Bowers K S amp Nahmias C(1998) Where the imaginal appears real A positronemission tomography study of auditory hallucinationsProceedings of the National Academy of Sciences USA95 1956 ndash1960

Talairach J amp Tournoux P (1988) Co-planar stereotaxicatlas of the human brain New York Thieme

Tellegen A amp Atkinson G (1974) Openness to absorbingand self-altering experiences (lsquolsquoabsorptionrsquorsquo) a trait relatedto hypnotic susceptibility Journal of Abnormal Psychology83 268 ndash277

Toma K Honda M Hanakawa T Okada T Fukuyama HIkeda A Nishizawa S Konishi J amp Shibasaki H (1999)Activities of the primary and supplementary motor areasincrease in preparation and execution of voluntary musclerelaxation An event-related fMRI study Journal ofNeuroscience 19 3527 ndash3534

Varela F J amp Shear J (1999) First-person methodologiesWhat why and how Journal of Consciousness Studies 61ndash14

Vingoe F J (1968) The development of a group alert-trancescale International Journal of Clinical and ExperimentalHypnosis 16 120 ndash132

Vingoe F J (1973) Comparison of the Harvard Group Scaleof Hypnotic Susceptibility Form A and the Group AlertTrance Scale in a university population InternationalJournal of Clinical and Experimental Hypnosis 21169 ndash179

Vogt B A amp Gabriel M (1993) Neurobiology of cingulatecortex and limbic thalamus A comprehensive handbookBoston Birkauser

Weitzenhoffer A M (1980) Hypnotic susceptibility revisitedAmerican Journal of Clinical Hypnosis 22 130 ndash146

Willoch F Rosen G Tolle T R Oslashye I Wester H J BernerN Schwaiger M amp Bartenstein P (2000) Phantom limbpain in the human brain Unravelling neural circuitries ofphantom limb pain sensations using positron emissiontomography Annals of Neurology 48 842 ndash849

Worsley K J Evans A C Marrett S amp Neelin P (1992)A three-dimensional statistical analysis for CBF activationstudies in human brain Journal of Cerebral Blood Flow andMetabolism 12 900 ndash918

Rainville et al 901

Page 8: Hypnosis Modulates Activity in Brain Structures Involved in the …pineda/COGS175/readings/Rain... · 2005. 2. 28. · Hypnosis Modulates Activity in Brain Structures Involved in

the underlying processes in the production of hypnoticstates as discussed below

Role of the Brainstem the Thalamus and the ACCin Hypnosis

Results of the regression analyses suggest that neuralactivity in the brainstem the thalamus and the ACCcontributes to the experience of being hypnotized Therelaxation-specific negative correlations in the mesen-

cephalic brainstem and the thalamus may reflect thewell-established contribution of brainstem and thalamicnuclei to the regulation of wakefulness and corticalarousal In functional brain imaging studies rCBFdecreases in the brainstem and the thalamus have beenassociated with decreased vigilance (Paus et al 1997)sleep (Kajimura et al 1999 Braun et al 1997 Hofleet al 1997 Maquet et al 1997) and the loss ofconsciousness produced by the anesthetic propofol(Fiset et al 1999) These effects and to some extent

Figure 3 Brain regionsshowing positive (redarrowheads) and negative(blue arrowheads) regres-sion peaks between rCBFand self-ratings of (A)relaxation and (B) absorp-tion after accounting forrelaxation-related variance(absorption-specific)Statistical t maps are super-imposed on the averageanatomical MRI (left is onthe left side) Slice locationsare indicated on the 3-Danatomical image of asingle subjectrsquos anatomicalMRI (A-positive) Positiverelaxation-related effectsare shown in the centralregion bilaterally (horizon-tal slice on the left) Apositive peak is shown inthe right superior occipitalgyrus (SOg) (coronal viewon the right note scalechange) (A-negative)A negative relaxation-related effect in the rightposterior parietal cortexis shown in horizontal(first from left) coronal(second) and lateralsagittal (third) views Theplus sign indicates the moreanterior location of thepeak positive regression inthe analysis of absorption-related effects as shown inB Additional negative cor-relations are shown in thebilateral middle and inferiortemporal gyri (second) andin the right somatosensorycortices (S1 S2 insula)(B-positive) A positiveabsorption-specific peak isshown in the right inferiorparietal lobule (first fromleft) The minus sign indicates the more posterior location of the negative regression peak in the analysis of relaxation-related effects as shown in

A Other peaks are shown on the midsagittal view in the thalamus and the anterior cingulate cortex (second from left) and in the left lenticularnuclei and bilateral prefrontal cortices (last three cuts from left) (B-negative) Negative absorption-related effects are shown in the left inferiorparietal lobule (first from left) in both occipital lobes (second and third from left) and in the precuneus (first and third) Stereotaxic coordinates ofpeaks are reported in Table 3 (see relaxation- and absorption-specific)

894 Journal of Cognitive Neuroscience Volume 14 Number 6

the present relaxation-related decrease in brainstemrCBF may reflect an attenuation of activity withinbrainstem cholinergic nuclei Such reduction has beenobserved during slow EEG activity before the onset ofsleep and during slow-wave sleep in animal studies(Steriade amp McCarley 1990) Consistent with this pos-sibility we previously reported an increase in slow(delta) EEG activity following hypnotic induction (Rain-ville Hofbauer et al 1999) Although hypnotic andsleep states are clearly distinct certain neurophysiolog-

ical mechanisms may be involved to a varying degree inthe production of both states

The positive association specifically observed betweenmental absorption and rCBF in the upper pons and thethalamus contrasts with the above relaxation-relatedeffect and is consistent with previous reports of atten-tion-related brain activation (Kinomura et al 1996) Thisactivity may reflect the involvement of the noradrenergicsystem of the locus coeruleus in focused attentionand possibly in the interaction between cortical arousal

Table 3 Cerebral Sites of Covariation with Thalamic rCBF at the Absorption-Specific Peak Coordinates (x = iexcl27 y = iexcl160z = 120)

Region Peak Location x y z t

Frontal (F) R medial sup F gACC (BA 624) 1 43 32 +382

R anterior cingulate gsup F g (BA 326) 8 13 44 +387

R inf F g (BA 44) 51 12 8 +387

R ant insula (BA 14) 38 12 5 +412

R sup F g (BA 6) 16 20 59 +371

R medial sup F g (BA 6) 3 iexcl6 63 +498

R medial sup F g (BA 6) 11 iexcl23 53 +412

L middle F g (BA 46) iexcl38 46 23 +381

L middle F g (BA 46) iexcl31 39 39 +374

L inf F g (BA 44) iexcl43 6 12 +430

L sup F g (BA 6) iexcl19 20 53 +340

L medial sup F g (BA 6) iexcl5 17 65 +353

L sup F g (BA 6) iexcl20 12 65 +283

Parietal R inf parietal lobule (BA 40) 56 iexcl44 50 +519

Occipital (O) R fusiform g (BA 19) 26 iexcl62 iexcl30 iexcliexcl515

R lingual g (BA 18) 7 iexcl78 6 iexcliexcl623

R sup O g (BA 19) 19 iexcl85 30 iexcliexcl714

R O pole (BA 18) 27 iexcl90 9 iexcliexcl751

L cuneus (BA 18) iexcl11 iexcl83 29 iexcliexcl633

L O pole (BA 18) iexcl23 iexcl88 6 iexcliexcl793

Subcortical R thalamus 17 iexcl11 2 +350

R brainstem 13 iexcl26 iexcl15 +312

R medial brainstem 3 iexcl32 iexcl24 +287

L cerebellum iexcl4 iexcl57 iexcl21 +409

L globus pallidus iexcl20 iexcl1 iexcl2 +302

L caudate nucleus iexcl12 6 20 +291

Positive and negative regression slopes are significant at sites listed based on cluster or peak analyses (peak t threshold ltgtplusmn370 in bold allpeaks reported with t lt 370 are within a significant cluster see Methods) Peaks in italic are also reported in Table 1 See legends to Tables 1 and 2and Methods for further explanation

Rainville et al 895

and attentional processes (ie increased attentionabsorption concurrent with decreased cortical arousalincreased relaxation) (Aston-Jones et al 1999) Theindirect nature of the rCBF measures and the relativelypoor resolution of the PET method require somecaution in evaluating the possible anatomo-functionalimplications of our results in the brainstem Howeverthe convergent findings observed in other brain imag-ing studies and the observations provided in animalstudies support the notion that ascending cholinergicand noradrenergic pathways may contribute differen-tially to the multiple dimensions of experience thatcharacterize hypnosis

The overall pattern of results found in the ACC likelyreflects the heterogeneity of functions associated withthis area (Devinsky Morrell amp Vogt 1995) The locationof the most posterior relaxation-related peak in the ACC(mACC) is consistent with our previous observationof ACC activation during hypnosis (Rainville Hofbaueret al 1999) This relaxation-related peak is only slightlyanterior to the motor area of the caudal ACC (Picard ampStrick 1996) and may be involved in the installment of arelaxed state (also see precentral area below) In con-trast a positive absorption-specific effect was observedin a more rostral region of the ACC (rACC) close to anegative relaxation-specific correlation (see Table 1)This area of the ACC has previously been involved inexecutive attention in the detection of errors and in themonitoring of conflict between competing cognitiveprocesses (Bush Luu amp Posner 2000 Cohen Botvinickamp Carter 2000 Badgaiyan amp Posner 1998 Posner ampRothbart 1998) A meta-analysis of PET studies inves-tigating cognitive functions further suggested that theincrease in activity within this sector of the ACC isrelated to the difficulty of the task performed (PausKoski Caramanos amp Westbury 1998) Our findings areconsistent with these propositions to the extent thatthe engagement of the cognitive and neurophysiologicalprocesses implied in each of those accounts may beaccompanied by a subjective experience of increasedmental absorption

The coordinated pattern of rCBF changes in thebrainstem the thalamus and the ACC may reflect theinterrelationships between the multiple components of anetwork (eg Paus et al 1997) herein shown to beassociated with the feeling of being lsquolsquomentally absorbedrsquorsquoThe precise location of the observed absorption-specificthalamic peak is consistent with an involvement of theintralaminar and medio-dorsal nuclei which have recip-rocal connections with the ACC (Vogt amp Gabriel 1993)The finding that the coordinated activity in the thalamusand the ACC is disrupted in persistent vegetative states isconsistent with the notion that these structures work intandem to regulate consciousness (Laureys et al 2000also see Jeanmonod Magnin amp Morel 1996) Further-more a functional interaction between arousal andattentional processes has been reported in the thalamus

where the putative attention-related activity associatedwith the performance of a simple visual discriminationtask was found to increase in states of low arousal (Portaset al 1998) This increase in thalamic activity wassuggested (1) to reflect a compensatory mechanism thatpermitted the maintenance of stable levels of perform-ance in states of low arousal and (2) to prevent thegeneralized thalamo-cortical synchronization that wouldlead to sleep Here the opposite effects of relaxation andabsorption on thalamic activity may reflect this compen-satory mechanism that maintains high levels of focusedattention in deeply relaxed subjects during hypnosisThis function may be critical not only in hypnosis butalso in other conditions of deep relaxation distinct fromboth sleep and normal wakefulness such as meditativestates (Lou et al 1999) Furthermore the coactivation ofthe ACC and the ponto-mesencephalic brainstem mayreflect the contribution of the ACC to the regulation ofattention-related activity in the locus coeruleus (Cohenet al 2000) The positive regression found with absorp-tion in the ponto-mesencephalic brainstem and themore robust regression observed in the thalamus andthe ACC after accounting for relaxation-related changes(absorption-specific Table 1) further substantiate thepossibility that brainstem and thalamic nuclei interactwith the ACC to regulate the interaction between atten-tion and cortical arousal Taken together these resultsare consistent with a contribution of brainstem nucleithe intralaminar and medio-dorsal nuclei of the thala-mus and the ACC to the changes in phenomenalexperience that characterize hypnotic states

Additional Relaxation- and Absorption-RelatedChanges in rCBF

Relaxation-Related Activity

We observed strong relaxation-related increases in rCBFin the precentral gyrus bilaterally and reciprocaldecreases in somatosensory areas (S1 S2 and insula)Precentral and premotor activation has been reportedduring hypnosis in an independent study (Maquet et al1999) and precentral rCBF was correlated with the rCBFmeasured at the ACC site of hypnosis-related activity inour previous study (see Appendix in Rainville Hofbaueret al 1999) Similar increases in activity in motor andpremotor areas have been associated with voluntarymuscular relaxation (Toma et al 1999) but the presentresults may reflect more than physical relaxation

All standard hypnotic procedures include instructionsfor relaxation However the specific contribution ofmuscular relaxation and decreased arousal to the pro-duction of hypnotic states is unclear as hypnotic phe-nomena have been produced during muscular exercise(Banyai amp Hilgard 1976) and with suggestions of active-alertness (Vingoe 1968 1973) Here the absence ofsignificant effect of hypnosis on heart rate indicates thatchanges in cerebral activity did not correlate with

896 Journal of Cognitive Neuroscience Volume 14 Number 6

changes in peripheral arousal and suggests that subjectswere already physically relaxed in the baseline controlcondition This implies that the hypnosis-inducedchanges in self-ratings of relaxation may not simplyreflect changes in lsquolsquoperipheralrsquorsquo arousal but may attestmore specifically of an increase in lsquolsquomentalrsquorsquo relaxationand a reduction in lsquolsquocorticalrsquorsquo arousal This is consistentwith Pricersquos experiential model of hypnosis (see Intro-duction) and with our previous study showing anincrease in slow (delta) EEG activity during hypnosis

Relaxation-related effects observed outside primarysomatomotor areas may partly reflect subjective feelingsof mental ease more closely In the subtraction analysishypnosis-related decreases were found in the rightlateral posterior parietal rCBF both here (x y z 40iexcl52 44) and in our previous study (x y z 46 iexcl50 42from Table 1 in Rainville Hofbauer et al 1999) Herethese changes were strongly but not specifically asso-ciated with relaxation (x y z 39 iexcl49 45 see Table 2Figure 3A) Furthermore after accounting for absorp-tion-related variance right prefrontal activity was neg-atively correlated with relaxation (Table 2) Thoseadditional changes in the right posterior parietal cortexand the right prefrontal cortices may contribute to thesubjective feelings of mental ease rather than or inaddition to physical relaxation

Fronto-Parietal Attention Networks

Absorption-related activity was widespread and bilateralin the prefrontal cortices but peaks were generallystronger in the right hemisphere Positive regressionpeaks were maximal in the ventrolateral frontal corticesover the inferior frontal gyrus and in the anterior insulaA positive absorption-related regression peak was alsosignificant in the right inferior parietal lobule Theseareas also displayed strong coactivation with absorption-related thalamic activity Very similar patterns of activa-tion have been associated with attentional processes intasks involving visual (eg Coull Frackowiak amp Frith1998) auditory (Paus et al 1997) and somatosensorystimuli (Peyron et al 1999) Notably the location of thepositive parietal peak observed here closely matches theactivation sites reported in those studies and the site ofcovariation with the right ventrolateral attention-relatedactivity reported in Paus et al (1997) suggesting theactivation of a similar network The coordinated absorp-tion-related activity observed here in the brainstem thethalamus the ACC the right inferior frontal gyrus andthe right inferior parietal lobule provides very strongevidence that mental absorption is an experiential cor-relate of the activation of the brainrsquos lsquolsquoexecutive atten-tional networkrsquorsquo and suggests that this system plays acritical role in the production of hypnotic states

Negative absorption-related regression peaks werealso found in both the right and left lateral parietalcortices and in the precuneus (see Table 2) These

effects were largely independent of thalamic activity asindicated by the absence of significant effects at theselocations in the covariation analysis (Table 3) The rightposterior parietal cortex has been suggested to con-stitute a vigilanceorientation system (Pardo Fox ampRaichle 1991) and hypnosis-related decreases in thisarea may reflect a relative disengagement towardexternal sources of stimulation Right and left posteriorparietal cortices at the precise sites of relaxation- andabsorption-related decrease in rCBF have been sug-gested to contribute to the monitoring of externalspace and time respectively (Gitelman et al 19961999 Kim et al 1999 Coull amp Nobre 1998 Nobreet al 1997) Although these functions were notdirectly assessed in this experiment the hypnoticinduction procedure includes specific instructions fordecreased orientation to and interest in irrelevantexternal sources of stimulation and previous observa-tions suggest that hypnotic relaxation and absorptionare precursors to some alterations in spatio-temporalorientation and monitoring (Price 1996) Thus wespeculate that those additional experiential changesmay be consequent to relaxation- and absorption-related decreases in posterior parietal activity

Relaxation- and Absorption-Related Effects onOccipital rCBF

The subtraction analysis confirmed the reliability of thehypnosis-related increase in occipital rCBF reported inour previous study (Rainville Hofbauer et al 1999) Wenow show that this effect was associated with the sub-jective experience of hypnotic relaxation (see Table 2relaxation-specific) Consistently our previous studydemonstrated a coupling between occipital increases inrCBF and increases in slow (delta) EEG activity duringhypnosis Similar increases in occipital rCBF andor slowEEG activity had been observed in another study onhypnosis (Maquet et al 1999) and in states of decreasedvigilance (Paus et al 1997) meditation (Lou et al 1999)and slow wave sleep (Kajimura et al 1999 Hofle et al1997) These effects are consistent with our previousproposition that hypnotic induction produces a globaldecrease in cross-modality suppression in unattendedsensory channels leading to a relative disinhibitionof cortical activity (see Paus et al 1997 KawashimaOrsquoSullivan amp Roland 1995)

In contrast negative correlations between rCBF andmental absorption were observed over both occipitallobes (Table 2 Figure 3B) Consistently occipital rCBFwas correlated negatively with thalamic rCBF at theabsorption-specific site (Table 3) These contrastingeffects imply that variations in occipital rCBF are asso-ciated with separate portions of the variance in relaxa-tion and absorption (Note that although absorptionand relaxation were significantly correlated the variancein absorption was largely independent of relaxation see

Rainville et al 897

Methods) For a given level of relaxation the increasein hypnotic absorption could reflect the concurrentengagement of the lsquolsquoexecutive attentional networkrsquorsquowhich exerts an opposite effect over brain areas sub-serving unattended sensory channels (ie a relativefacilitation of cross-modality suppression)

Hypnosis as a State of Consciousness

The representation of the body-self is central to theneurophenomenology of consciousness (Metzinger2000) In the Introduction we have proposed that theinduction of hypnosis produces global changes in sub-jective experience reflecting a modulation of basicaspects of the body-self representation Consistentlythe PET results indicate that hypnosis involves changesin activity within brain structures essential for the basicregulation of states of consciousness self-monitoringand self-regulation Furthermore changes in relaxationand absorption are precursors (although they may notbe essential) to other hypnosis-related effects such asthe diminished tendency to judge monitor and censorthe suspension of usual orientation toward time loca-tion andor sense of self and the experience of onersquosown response as automatic or extra-volitional (Price1996) These dimensions of experience also rely criticallyon self-representation and may depend at least partly oncerebral areas shown here to be involved in hypnosisAmong those changes the increased feeling of automa-ticity an altered feeling of agency may be the mostdistinctive aspect of hypnotic phenomenology (Weitzen-hoffer 1980) Interestingly the sense of agency hasrecently been suggested to involve areas that displayconsistent changes in activity during hypnosis such asthe right inferior parietal cortex the precuneus and thesomatosensory cortices (Blakemore amp Decety 2001Ruby amp Decety 2001) The modulation of activityobserved here within those areas is consistent withthe interpretation that hypnosis produces changes inself-representation construed as an essential element forconscious experience

Conclusion

The present study used self-ratings of subjective feelingsof mental relaxation and mental absorption to map brainareas involved in hypnosis We replicated previous find-ings and further demonstrated that hypnotic relaxationand absorption reflect changes in brain activity withinregions involved in the control of consciousness statesand in self-regulation such as the brainstem the thala-mus and the ACC The coordinated activity within thesestructures and other absorption-related areas such asthe ventrolateral frontal and right posterior parietalcortices has been previously shown to underlie theregulation of the content of consciousness throughmechanisms of executive attention We must recognize

that our findings are correlative in nature and arerelevant to hypnosis to the extent that mental relaxationand absorption are conceived as basic experientialdimensions that characterize hypnotic phenomenaWe further speculate that these changes in subjectiveexperience and brain activity may contribute to otherhypnosis-related effects such as the altered feeling ofagency experienced during hypnosis These findings areconsistent with the notion that hypnotic states areachieved through the modulation of activity within adistributed network of cerebral structures involved inthe regulation of consciousness states

METHODS

Subjects

Ten right-handed subjects (4 men 6 women) wereselected from a group of 22 volunteers as a part of astudy on the hypnotic modulation of pain (Hofbaueret al 2001) Hypnotic susceptibility was assessed usingthe SHSS-A administered between scans (range 111ndash1011 mean plusmn SD 69 plusmn28) The Ethics Committee ofthe Montreal Neurological Institute (MNI) approved allprocedures and subjects signed a consent form describ-ing the procedure and affirming their right to withdrawfrom the experiment without prejudice

Experimental Procedure

We report the results obtained in eight scans acquired ina restful baseline and hypnosis condition Hypnoticinduction started immediately after Scan 4 and wassustained in the remaining scans by repeating inductioninstructions between scans Instructions included sug-gestions for (1) increased physical and mental relaxa-tion (2) comfortable feeling of warmth heaviness anddrowsiness (3) sustained passive attention to theexperimenterrsquos voice and to the instructions and (4)decreased concern with and orientation to external andinternal (mental) sources of distraction No specificinstruction for visual imagery was included During allscans the subjectsrsquo eyes were closed and their left handwas immersed in warm or painfully hot water Pain-related activation and four additional scans performedwith suggestions for pain modulation are reported else-where (Hofbauer et al 2001)

Self-Ratings of Mental Relaxation and Absorption

After each scan subjects were instructed to rate (0ndash10)(1) their level of tensionndashrelaxation with lsquolsquo10 being themost relaxed and at ease you can bersquorsquo and (2) their levelof sustained focus of attention with lsquolsquo10 being the mostabsorbed and the largest amount of sustained focusedattention you can gatherrsquorsquo Ratings of relaxation andabsorption were transformed using the rank within sub-jects to (1) control for individual differences (2) prevent

898 Journal of Cognitive Neuroscience Volume 14 Number 6

scaling biases and (3) parallel the analysis of rCBF dataSubjects rated pain on separate scales (0ndash100) Hypno-sis-related increases in relaxation and absorption did notinteract with the stimulation condition (pain vs warmstimulation prsquos gt 10) neither relaxation nor absorptioncorrelated significantly with pain ratings (all prsquos gt 10)and pain was not altered by hypnosis alone [t(9) = 069p = 51]

PET Imaging Methods

rCBF was measured using the H215O bolus injection

method (10 millicuriesscan) without arterial blood sam-pling (Herscovitch Markham amp Raichle 1983) with ahigh-resolution PET scanner operated in 3-D acquisitionmode (Siemens ECAT HR+ 63 slices) Stimulus onsetwas simultaneous with bolus injection and 1-min acquis-ition scans started about 15 sec postinjection (interscaninterval of 12ndash15 min) Data from the first 40 sec ofacquisition were reconstructed and analyzed Each sub-ject also underwent a high-resolution anatomical MRI(160 1-mm sagittal slices acquired on a Philips 15-TGyroscan system) Each PET and MRI volume wasaligned and transformed using software developed atthe MNI to match the MNI standardized Talairach space(Collins Neelin Peters amp Evans 1994 Talairach ampTournoux 1988) PET volumes were smoothed (FWHM= 14 mm) and normalized to the average brain countPeak and cluster analyses were performed (FristonWorsley Frackowiak Mazziotta amp Evans 1994 WorsleyEvans Marrett amp Neelin 1992)

Reliability of Hypnosis-Related Effects

A first analysis was performed using the subtractionmethod (Hypnosis minus Baseline) to evaluate thereliability of the effects reported in our previous study(Table 2 in Rainville Hofbauer et al 1999) We consid-ered that hypnosis-related changes in rCBF were repli-cated when a significant peak was observed within oneresel (Worsley et al 1992) of the peak sites reported inour previous study or when the peak sites were within asignificant cluster

Regression of rCBF on Self-Ratings of Relaxationand Absorption

Regression analyses were used to test the relationbetween ratings and rCBF (GLM) Subject- and stimu-lus-related effects were removed first (ANCOVA) andthe significance of the regression slope between thecovariate of interest and rCBF was estimated usingt tests Relaxation-specific and absorption-specific effectswere further tested using ANCOVAs to remove thevariance shared between absorption and relaxation(R2 = 42 p lt 001) The statistical criterion was setto t gt 258 (two-tailed uncorrected p lt 01) in the

directed searches restricted to the brainstem the thala-mus and the ACC (Table 1 Figure 2) Global searcheffects are significant ( p lt 05) based on peak (t valuegt 420) andor clusters analysis after a correction formultiple comparisons over the gray matter volume(uncorrected p lt 0001) (Table 2 Figure 3)

Thalamic Covariations

A covariation analysis was performed in which the rCBFmeasured in the thalamus was used as the covariate ofinterest after accounting for subject- and stimulus-related variance (ANCOVA see Tables 1 and 3) Becausewe were mainly interested in the relationship betweenthe activity in the thalamus and other absorption-relatedsites the threshold for statistical significance was set tot = 370 ( p = 05 uncorrected p lt 0008) based on thevolume defined by the sum of clusters of voxels showingsignificant absorption-specific effects (186 cm3 seeWorsley et al 1992)

Acknowledgments

We thank R Adolphs S Anderson A Bechara A R DamasioH Damasio Susan Lutgendorf J Parvizi and D Tranel fortheir comments on preliminary versions of the manuscriptPET analyses were performed using the software DOTdeveloped by Sylvain Milot and the MINC programs developedby Peter Neelin at the McConnell Brain Imaging Center of theMontreal Neurological Institute This study was supported bythe Medical Research Council (MRC) of Canada Dr Rainvillewas supported by the Medical Research Council of Canada andthe Human Frontier Science Program and Dr Hofbauer wassupported by the Fonds pour la recherche en sante du Quebecand the Royal Victoria Hospital Research Institute

Reprint requests should be sent to Pierre Rainville Faculte deMedecine dentaire Universite de Montreal CP 6128 SuccCentre-ville Montreal Qc H3C 3J7 Canada or via e-mailpierrerainvilleumontrealca

REFERENCES

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Badgaiyan R D amp Posner M I (1998) Mapping the cingulatecortex in response selection and monitoring Neuroimage7 255 ndash260

Balthazard C G amp Woody E Z (1992) The spectral analysisof hypnotic performance with respect to lsquolsquoabsorptionrsquorsquoInternational Journal of Clinical and ExperimentalHypnosis 40 21ndash43

Banyai E I amp Hilgard E R (1976) A comparison ofactive-alert hypnotic induction with traditional relaxationinduction Journal of Abnormal Psychology 85 218 ndash224

Blakemore S J amp Decety J (2001) From the perception ofaction to the understanding of intention Nature ReviewsNeuroscience 2 561 ndash567

Braun A R Balkin T J Wesenten N J Carson R EVarga M Baldwin P Selbie S Belenky G amp HerscovitchP (1997) Regional cerebral blood flow throughout the

Rainville et al 899

sleep ndashwake cycle An H2(15)O PET study Brain 1201173 ndash1197

Bush G Luu P amp Posner M I (2000) Cognitive andemotional influences in anterior cingulate cortex Trendsin Cognitive Sciences 4 215 ndash222

Chalmers D J (2000) What is a neural correlate ofconsciousness In T Metzinger (Ed) Neural correlatesof consciousness Empirical and conceptual questions(pp 17ndash39) Cambridge MIT Press

Coe W C amp Sarbin T R (1977) Hypnosis from thestandpoint of a contextualist Annals of the New YorkAcademy of Sciences 296 2ndash13

Cohen J D Botvinick M amp Carter C S (2000) Anteriorcingulate and prefrontal cortex Whorsquos in control NatureNeuroscience 3 421 ndash423

Collins D L Neelin P Peters T M amp Evans A C (1994)Automatic 3D intersubject registration of MR volumetric datain standardized Talairach space Journal of ComputerAssisted Tomography 18 192 ndash205

Coull J T Frackowiak R S amp Frith C D (1998) Monitoringfor target objects Activation of right frontal and parietalcortices with increasing time on task Neuropsychologia 361325 ndash1334

Coull J T amp Nobre A C (1998) Where and when to payattention The neural systems for directing attention tospatial locations and to time intervals as revealed by bothPET and fMRI Journal of Neuroscience 18 7426 ndash7435

Crawford H J (1994) Brain dynamics and hypnosisAttentional and disattentional processes InternationalJournal of Clinical and Experimental Hypnosis 42204 ndash232

Crawford H J amp Gruzelier J H (1992) A midstream view ofthe neuropsychophysiology of hypnosis Recent researchand future directions In E Fromm amp M R Nash (Eds)Contemporary hypnosis research (pp 227 ndash266) New YorkGuilford Press

Crawford H J Knebel T Kaplan L Vendemia J M C XieM Jamison S amp Pribram K H (1998) Hypnotic analgesia1 Somatosensory event-related potential changes to noxiousstimuli and 2 Transfer learning to reduce chronic low backpain International Journal of Clinical and ExperimentalHypnosis 46 92ndash132

Damasio A R (1999) The feeling of what happens Body andemotion and the making of consciousness New YorkHartcourt Brace

De Pascalis V Magurano M R amp Bellusci A (1999) Painperception somatosensory event-related potentials andskin conductance responses to painful stimuli in high midand low hypnotizable subjects Effects of differential painreduction strategies Pain 83 499 ndash508

Devinsky O Morrell M J amp Vogt B A (1995) Contributionsof anterior cingulate cortex to behaviour Brain 118279 ndash306

Fiset P Paus T Daloze T Plourde G Meuret PBonhomme V Hajj-Ali N Backman S B amp Evans A C(1999) Brain mechanisms of propofol-induced loss ofconsciousness in humans A positron emission tomographicstudy Journal of Neuroscience 19 5505 ndash5513

Friston K J Worsley K J Frackowiak R S J Mazziotta J Camp Evans A C (1994) Assessing the significance of focalactivation using their spatial extent Human Brain Mapping1 214ndash220

Gitelman D R Alpert N M Kosslyn S Daffner K ScintoL Thompson W amp Mesulam M M (1996) Functionalimaging of human right hemispheric activation forexploratory movements Annals of Neurology 39 174ndash179

Gitelman D R Nobre A C Parrish T B LaBar K S KimY H Meyer J R amp Mesulam M (1999) A large-scale

distributed network for covert spatial attention Furtheranatomical delineation based on stringent behavioural andcognitive controls Brain 122 1093 ndash1106

Gruzelier J (1998) A working model of the neurophysiologyof hypnosis A review of evidence Contemporary Hypnosis15 3ndash21

Henson R N A Rugg M D Shallice T amp Dolan R J (2000)Confidence in recognition memory for words Dissociatingright prefrontal roles in episodic retrieval Journal ofCognitive Neuroscience 12 913 ndash923

Henson R N A Rugg M D Shallice T Joseph O ampDolan R J (1999) Recollection and familiarity inrecognition memory An event-related functional magneticresonance imaging study Journal of Neuroscience 193962 ndash3972

Herscovitch P Markham J amp Raichle M E (1983) Brainblood flow measured with intravenous H2(15)O I Theoryand error analysis Journal of Nuclear Medicine 24782 ndash789

Hofbauer R K Rainville P Duncan G H amp Bushnell M C(2001) Cortical representation of the sensory dimension ofpain Journal of Neurophysiology 86 402 ndash411

Hofle N Paus T Reutens D Fiset P Gotman J EvansA C amp Jones B E (1997) Regional cerebral blood flowchanges as a function of delta and spindle activity duringslow wave sleep in humans Journal of Neuroscience 174800 ndash4808

Jeanmonod D Magnin M amp Morel A (1996) Low-thresholdcalcium spike bursts in the human thalamus Commonphysiopathology for sensory motor and limbic positivesymptoms Brain 119 363ndash375

Kajimura N Uchiyama M Takayama Y Uchida S Uema TKato M Sekimoto M Watanabe T Nakajima THorikoshi S Ogawa K Nishikawa M Hiroki M Kudo YMatsuda H Okawa M amp Takahashi K (1999) Activityof midbrain reticular formation and neocortex during theprogression of human non-rapid eye movement sleepJournal of Neuroscience 19 10065 ndash10073

Kawashima R OrsquoSullivan B T amp Roland P E (1995)Positron-emission tomography studies of cross-modalityinhibition in selective attentional tasks Closing the lsquolsquomindrsquoseyersquorsquo Proceedings of the National Academy of SciencesUSA 92 5969 ndash5972

Kim Y H Gitelman D R Nobre A C Parrish T BLaBar K S amp Mesulam M M (1999) The large-scaleneural network for spatial attention displays multifunctionaloverlap but differential asymmetry Neuroimage 9269 ndash277

Kinomura S Larsson J Gulyas B amp Roland P E (1996)Activation by attention of the human reticular formationand thalamic intralaminar nuclei Science 271 512ndash515

Kosslyn S M Thompson W L Costantini-Ferrando M FAlpert N M amp Spiegel D (2000) Hypnotic visual illusionalters color processing in the brain American Journal ofPsychiatry 157 1279 ndash1284

Laureys S Faymonville M E Luxen A Lamy M Franck Gamp Maquet P (2000) Restoration of thalamocorticalconnectivity after recovery from persistent vegetative stateLancet 355 1790ndash1791

Lou H C Kjaer T W Friberg L Wildschiodtz G Holm Samp Nowak M (1999) A 15OndashH2O PET study of meditationand the resting state of normal consciousness HumanBrain Mapping 7 98ndash105

Maquet P Degueldre C Delfiore G Aerts J Peters J MLuxen A amp Franck G (1997) Functional neuroanatomyof human slow wave sleep Journal of Neuroscience 172807 ndash2812

Maquet P Faymonville M E Degueldre C Delfiore G

900 Journal of Cognitive Neuroscience Volume 14 Number 6

Franck G Luxen A amp Lamy M (1999) Functionalneuroanatomy of hypnotic state Biological Psychiatry 45327 ndash333

Metzinger T (2000) The subjectivity of subjective experienceA representationalist analysis of the first-person perspectiveIn T Metzinger (Ed) Neural correlates of consciousnessEmprical and conceptual questions (pp 285 ndash306)Cambridge MIT Press

Nobre A C Sebestyen G N Gitelman D R MesulamM M Frackowiak R S amp Frith C D (1997) Functionallocalization of the system for visuospatial attention usingpositron emission tomography Brain 120 515 ndash533

Pardo J V Fox P T amp Raichle M E (1991) Localization of ahuman system for sustained attention by positron emissiontomography Nature 349 61ndash64

Paus T (2001) Primate anterior cingulate cortex Wheremotor control drive and cognition interface NatureReviews Neuroscience 2 417 ndash424

Paus T Koski L Caramanos Z amp Westbury C (1998)Regional differences in the effects of task difficulty andmotor output on blood flow response in the human anteriorcingulate cortex A review of 107 PET activation studiesNeuroReport 9 R37ndashR47

Paus T Zatorre R J Hofle N Caramanos Z Gotman JPetrides M amp Evans A C (1997) Time-related changesin neural systems underlying attention and arousal duringthe performance of an auditory vigilance task Journal ofCognitive Neuroscience 9 392ndash408

Peyron R Garcia-Larrea L Gregoire M C Costes NConvers P Lavenne F Mauguiere F Michel D ampLaurent B (1999) Haemodynamic brain responses to acutepain in humansmdashSensory and attentional networks Brain122 1765 ndash1779

Picard N amp Strick P L (1996) Motor areas of the medial wallA review of their location and functional activation CerebralCortex 6 342 ndash353

Portas C M Howseman A M Josephs O Turner R ampFrith C D (1998) A specific role for the thalamus inmediating the interaction of attention and arousal inhumans Journal of Neuroscience 18 8979 ndash8989

Posner M I amp Rothbart M K (1998) Attentionself-regulation and consciousness Philosophical

Transactions of the Royal Society of London Series BBiological Sciences 353 1915 ndash1927

Price D D (1996) Hypnotic analgesia Psychological andneural mechanisms In J Barber (Ed) Hypnosis andsuggestions in the treatment of pain (pp 67ndash84) NewYork Norton

Price D D amp Barrell J J (1980) An experiential approachwith quantitative methods A research paradigm Journal ofHumanistic Psychology 20 75ndash95

Rainville P Carrier B Hofbauer R K Bushnell M C ampDuncan G H (1999) Dissociation of pain sensory andaffective dimensions using hypnotic modulation Pain 82159 ndash171

Rainville P Duncan G H Price D D Carrier B ampBushnell M C (1997) Pain affect encoded in humananterior cingulate but not somatosensory cortex Science277 968 ndash971

Rainville P Hofbauer R K Paus T Duncan G H BushnellM C amp Price D D (1999) Cerebral mechanisms ofhypnotic induction and suggestion Journal of CognitiveNeuroscience 11 110ndash125

Ruby P amp Decety J (2001) Effect of subjective perspectivetaking during simulation of action A PET investigation ofagency Nature Neuroscience 4 546 ndash550

Steriade M amp McCarley R W (1990) Brainstem control ofwakefulness and sleep New York Plenum

Szechtman H Woody E Bowers K S amp Nahmias C(1998) Where the imaginal appears real A positronemission tomography study of auditory hallucinationsProceedings of the National Academy of Sciences USA95 1956 ndash1960

Talairach J amp Tournoux P (1988) Co-planar stereotaxicatlas of the human brain New York Thieme

Tellegen A amp Atkinson G (1974) Openness to absorbingand self-altering experiences (lsquolsquoabsorptionrsquorsquo) a trait relatedto hypnotic susceptibility Journal of Abnormal Psychology83 268 ndash277

Toma K Honda M Hanakawa T Okada T Fukuyama HIkeda A Nishizawa S Konishi J amp Shibasaki H (1999)Activities of the primary and supplementary motor areasincrease in preparation and execution of voluntary musclerelaxation An event-related fMRI study Journal ofNeuroscience 19 3527 ndash3534

Varela F J amp Shear J (1999) First-person methodologiesWhat why and how Journal of Consciousness Studies 61ndash14

Vingoe F J (1968) The development of a group alert-trancescale International Journal of Clinical and ExperimentalHypnosis 16 120 ndash132

Vingoe F J (1973) Comparison of the Harvard Group Scaleof Hypnotic Susceptibility Form A and the Group AlertTrance Scale in a university population InternationalJournal of Clinical and Experimental Hypnosis 21169 ndash179

Vogt B A amp Gabriel M (1993) Neurobiology of cingulatecortex and limbic thalamus A comprehensive handbookBoston Birkauser

Weitzenhoffer A M (1980) Hypnotic susceptibility revisitedAmerican Journal of Clinical Hypnosis 22 130 ndash146

Willoch F Rosen G Tolle T R Oslashye I Wester H J BernerN Schwaiger M amp Bartenstein P (2000) Phantom limbpain in the human brain Unravelling neural circuitries ofphantom limb pain sensations using positron emissiontomography Annals of Neurology 48 842 ndash849

Worsley K J Evans A C Marrett S amp Neelin P (1992)A three-dimensional statistical analysis for CBF activationstudies in human brain Journal of Cerebral Blood Flow andMetabolism 12 900 ndash918

Rainville et al 901

Page 9: Hypnosis Modulates Activity in Brain Structures Involved in the …pineda/COGS175/readings/Rain... · 2005. 2. 28. · Hypnosis Modulates Activity in Brain Structures Involved in

the present relaxation-related decrease in brainstemrCBF may reflect an attenuation of activity withinbrainstem cholinergic nuclei Such reduction has beenobserved during slow EEG activity before the onset ofsleep and during slow-wave sleep in animal studies(Steriade amp McCarley 1990) Consistent with this pos-sibility we previously reported an increase in slow(delta) EEG activity following hypnotic induction (Rain-ville Hofbauer et al 1999) Although hypnotic andsleep states are clearly distinct certain neurophysiolog-

ical mechanisms may be involved to a varying degree inthe production of both states

The positive association specifically observed betweenmental absorption and rCBF in the upper pons and thethalamus contrasts with the above relaxation-relatedeffect and is consistent with previous reports of atten-tion-related brain activation (Kinomura et al 1996) Thisactivity may reflect the involvement of the noradrenergicsystem of the locus coeruleus in focused attentionand possibly in the interaction between cortical arousal

Table 3 Cerebral Sites of Covariation with Thalamic rCBF at the Absorption-Specific Peak Coordinates (x = iexcl27 y = iexcl160z = 120)

Region Peak Location x y z t

Frontal (F) R medial sup F gACC (BA 624) 1 43 32 +382

R anterior cingulate gsup F g (BA 326) 8 13 44 +387

R inf F g (BA 44) 51 12 8 +387

R ant insula (BA 14) 38 12 5 +412

R sup F g (BA 6) 16 20 59 +371

R medial sup F g (BA 6) 3 iexcl6 63 +498

R medial sup F g (BA 6) 11 iexcl23 53 +412

L middle F g (BA 46) iexcl38 46 23 +381

L middle F g (BA 46) iexcl31 39 39 +374

L inf F g (BA 44) iexcl43 6 12 +430

L sup F g (BA 6) iexcl19 20 53 +340

L medial sup F g (BA 6) iexcl5 17 65 +353

L sup F g (BA 6) iexcl20 12 65 +283

Parietal R inf parietal lobule (BA 40) 56 iexcl44 50 +519

Occipital (O) R fusiform g (BA 19) 26 iexcl62 iexcl30 iexcliexcl515

R lingual g (BA 18) 7 iexcl78 6 iexcliexcl623

R sup O g (BA 19) 19 iexcl85 30 iexcliexcl714

R O pole (BA 18) 27 iexcl90 9 iexcliexcl751

L cuneus (BA 18) iexcl11 iexcl83 29 iexcliexcl633

L O pole (BA 18) iexcl23 iexcl88 6 iexcliexcl793

Subcortical R thalamus 17 iexcl11 2 +350

R brainstem 13 iexcl26 iexcl15 +312

R medial brainstem 3 iexcl32 iexcl24 +287

L cerebellum iexcl4 iexcl57 iexcl21 +409

L globus pallidus iexcl20 iexcl1 iexcl2 +302

L caudate nucleus iexcl12 6 20 +291

Positive and negative regression slopes are significant at sites listed based on cluster or peak analyses (peak t threshold ltgtplusmn370 in bold allpeaks reported with t lt 370 are within a significant cluster see Methods) Peaks in italic are also reported in Table 1 See legends to Tables 1 and 2and Methods for further explanation

Rainville et al 895

and attentional processes (ie increased attentionabsorption concurrent with decreased cortical arousalincreased relaxation) (Aston-Jones et al 1999) Theindirect nature of the rCBF measures and the relativelypoor resolution of the PET method require somecaution in evaluating the possible anatomo-functionalimplications of our results in the brainstem Howeverthe convergent findings observed in other brain imag-ing studies and the observations provided in animalstudies support the notion that ascending cholinergicand noradrenergic pathways may contribute differen-tially to the multiple dimensions of experience thatcharacterize hypnosis

The overall pattern of results found in the ACC likelyreflects the heterogeneity of functions associated withthis area (Devinsky Morrell amp Vogt 1995) The locationof the most posterior relaxation-related peak in the ACC(mACC) is consistent with our previous observationof ACC activation during hypnosis (Rainville Hofbaueret al 1999) This relaxation-related peak is only slightlyanterior to the motor area of the caudal ACC (Picard ampStrick 1996) and may be involved in the installment of arelaxed state (also see precentral area below) In con-trast a positive absorption-specific effect was observedin a more rostral region of the ACC (rACC) close to anegative relaxation-specific correlation (see Table 1)This area of the ACC has previously been involved inexecutive attention in the detection of errors and in themonitoring of conflict between competing cognitiveprocesses (Bush Luu amp Posner 2000 Cohen Botvinickamp Carter 2000 Badgaiyan amp Posner 1998 Posner ampRothbart 1998) A meta-analysis of PET studies inves-tigating cognitive functions further suggested that theincrease in activity within this sector of the ACC isrelated to the difficulty of the task performed (PausKoski Caramanos amp Westbury 1998) Our findings areconsistent with these propositions to the extent thatthe engagement of the cognitive and neurophysiologicalprocesses implied in each of those accounts may beaccompanied by a subjective experience of increasedmental absorption

The coordinated pattern of rCBF changes in thebrainstem the thalamus and the ACC may reflect theinterrelationships between the multiple components of anetwork (eg Paus et al 1997) herein shown to beassociated with the feeling of being lsquolsquomentally absorbedrsquorsquoThe precise location of the observed absorption-specificthalamic peak is consistent with an involvement of theintralaminar and medio-dorsal nuclei which have recip-rocal connections with the ACC (Vogt amp Gabriel 1993)The finding that the coordinated activity in the thalamusand the ACC is disrupted in persistent vegetative states isconsistent with the notion that these structures work intandem to regulate consciousness (Laureys et al 2000also see Jeanmonod Magnin amp Morel 1996) Further-more a functional interaction between arousal andattentional processes has been reported in the thalamus

where the putative attention-related activity associatedwith the performance of a simple visual discriminationtask was found to increase in states of low arousal (Portaset al 1998) This increase in thalamic activity wassuggested (1) to reflect a compensatory mechanism thatpermitted the maintenance of stable levels of perform-ance in states of low arousal and (2) to prevent thegeneralized thalamo-cortical synchronization that wouldlead to sleep Here the opposite effects of relaxation andabsorption on thalamic activity may reflect this compen-satory mechanism that maintains high levels of focusedattention in deeply relaxed subjects during hypnosisThis function may be critical not only in hypnosis butalso in other conditions of deep relaxation distinct fromboth sleep and normal wakefulness such as meditativestates (Lou et al 1999) Furthermore the coactivation ofthe ACC and the ponto-mesencephalic brainstem mayreflect the contribution of the ACC to the regulation ofattention-related activity in the locus coeruleus (Cohenet al 2000) The positive regression found with absorp-tion in the ponto-mesencephalic brainstem and themore robust regression observed in the thalamus andthe ACC after accounting for relaxation-related changes(absorption-specific Table 1) further substantiate thepossibility that brainstem and thalamic nuclei interactwith the ACC to regulate the interaction between atten-tion and cortical arousal Taken together these resultsare consistent with a contribution of brainstem nucleithe intralaminar and medio-dorsal nuclei of the thala-mus and the ACC to the changes in phenomenalexperience that characterize hypnotic states

Additional Relaxation- and Absorption-RelatedChanges in rCBF

Relaxation-Related Activity

We observed strong relaxation-related increases in rCBFin the precentral gyrus bilaterally and reciprocaldecreases in somatosensory areas (S1 S2 and insula)Precentral and premotor activation has been reportedduring hypnosis in an independent study (Maquet et al1999) and precentral rCBF was correlated with the rCBFmeasured at the ACC site of hypnosis-related activity inour previous study (see Appendix in Rainville Hofbaueret al 1999) Similar increases in activity in motor andpremotor areas have been associated with voluntarymuscular relaxation (Toma et al 1999) but the presentresults may reflect more than physical relaxation

All standard hypnotic procedures include instructionsfor relaxation However the specific contribution ofmuscular relaxation and decreased arousal to the pro-duction of hypnotic states is unclear as hypnotic phe-nomena have been produced during muscular exercise(Banyai amp Hilgard 1976) and with suggestions of active-alertness (Vingoe 1968 1973) Here the absence ofsignificant effect of hypnosis on heart rate indicates thatchanges in cerebral activity did not correlate with

896 Journal of Cognitive Neuroscience Volume 14 Number 6

changes in peripheral arousal and suggests that subjectswere already physically relaxed in the baseline controlcondition This implies that the hypnosis-inducedchanges in self-ratings of relaxation may not simplyreflect changes in lsquolsquoperipheralrsquorsquo arousal but may attestmore specifically of an increase in lsquolsquomentalrsquorsquo relaxationand a reduction in lsquolsquocorticalrsquorsquo arousal This is consistentwith Pricersquos experiential model of hypnosis (see Intro-duction) and with our previous study showing anincrease in slow (delta) EEG activity during hypnosis

Relaxation-related effects observed outside primarysomatomotor areas may partly reflect subjective feelingsof mental ease more closely In the subtraction analysishypnosis-related decreases were found in the rightlateral posterior parietal rCBF both here (x y z 40iexcl52 44) and in our previous study (x y z 46 iexcl50 42from Table 1 in Rainville Hofbauer et al 1999) Herethese changes were strongly but not specifically asso-ciated with relaxation (x y z 39 iexcl49 45 see Table 2Figure 3A) Furthermore after accounting for absorp-tion-related variance right prefrontal activity was neg-atively correlated with relaxation (Table 2) Thoseadditional changes in the right posterior parietal cortexand the right prefrontal cortices may contribute to thesubjective feelings of mental ease rather than or inaddition to physical relaxation

Fronto-Parietal Attention Networks

Absorption-related activity was widespread and bilateralin the prefrontal cortices but peaks were generallystronger in the right hemisphere Positive regressionpeaks were maximal in the ventrolateral frontal corticesover the inferior frontal gyrus and in the anterior insulaA positive absorption-related regression peak was alsosignificant in the right inferior parietal lobule Theseareas also displayed strong coactivation with absorption-related thalamic activity Very similar patterns of activa-tion have been associated with attentional processes intasks involving visual (eg Coull Frackowiak amp Frith1998) auditory (Paus et al 1997) and somatosensorystimuli (Peyron et al 1999) Notably the location of thepositive parietal peak observed here closely matches theactivation sites reported in those studies and the site ofcovariation with the right ventrolateral attention-relatedactivity reported in Paus et al (1997) suggesting theactivation of a similar network The coordinated absorp-tion-related activity observed here in the brainstem thethalamus the ACC the right inferior frontal gyrus andthe right inferior parietal lobule provides very strongevidence that mental absorption is an experiential cor-relate of the activation of the brainrsquos lsquolsquoexecutive atten-tional networkrsquorsquo and suggests that this system plays acritical role in the production of hypnotic states

Negative absorption-related regression peaks werealso found in both the right and left lateral parietalcortices and in the precuneus (see Table 2) These

effects were largely independent of thalamic activity asindicated by the absence of significant effects at theselocations in the covariation analysis (Table 3) The rightposterior parietal cortex has been suggested to con-stitute a vigilanceorientation system (Pardo Fox ampRaichle 1991) and hypnosis-related decreases in thisarea may reflect a relative disengagement towardexternal sources of stimulation Right and left posteriorparietal cortices at the precise sites of relaxation- andabsorption-related decrease in rCBF have been sug-gested to contribute to the monitoring of externalspace and time respectively (Gitelman et al 19961999 Kim et al 1999 Coull amp Nobre 1998 Nobreet al 1997) Although these functions were notdirectly assessed in this experiment the hypnoticinduction procedure includes specific instructions fordecreased orientation to and interest in irrelevantexternal sources of stimulation and previous observa-tions suggest that hypnotic relaxation and absorptionare precursors to some alterations in spatio-temporalorientation and monitoring (Price 1996) Thus wespeculate that those additional experiential changesmay be consequent to relaxation- and absorption-related decreases in posterior parietal activity

Relaxation- and Absorption-Related Effects onOccipital rCBF

The subtraction analysis confirmed the reliability of thehypnosis-related increase in occipital rCBF reported inour previous study (Rainville Hofbauer et al 1999) Wenow show that this effect was associated with the sub-jective experience of hypnotic relaxation (see Table 2relaxation-specific) Consistently our previous studydemonstrated a coupling between occipital increases inrCBF and increases in slow (delta) EEG activity duringhypnosis Similar increases in occipital rCBF andor slowEEG activity had been observed in another study onhypnosis (Maquet et al 1999) and in states of decreasedvigilance (Paus et al 1997) meditation (Lou et al 1999)and slow wave sleep (Kajimura et al 1999 Hofle et al1997) These effects are consistent with our previousproposition that hypnotic induction produces a globaldecrease in cross-modality suppression in unattendedsensory channels leading to a relative disinhibitionof cortical activity (see Paus et al 1997 KawashimaOrsquoSullivan amp Roland 1995)

In contrast negative correlations between rCBF andmental absorption were observed over both occipitallobes (Table 2 Figure 3B) Consistently occipital rCBFwas correlated negatively with thalamic rCBF at theabsorption-specific site (Table 3) These contrastingeffects imply that variations in occipital rCBF are asso-ciated with separate portions of the variance in relaxa-tion and absorption (Note that although absorptionand relaxation were significantly correlated the variancein absorption was largely independent of relaxation see

Rainville et al 897

Methods) For a given level of relaxation the increasein hypnotic absorption could reflect the concurrentengagement of the lsquolsquoexecutive attentional networkrsquorsquowhich exerts an opposite effect over brain areas sub-serving unattended sensory channels (ie a relativefacilitation of cross-modality suppression)

Hypnosis as a State of Consciousness

The representation of the body-self is central to theneurophenomenology of consciousness (Metzinger2000) In the Introduction we have proposed that theinduction of hypnosis produces global changes in sub-jective experience reflecting a modulation of basicaspects of the body-self representation Consistentlythe PET results indicate that hypnosis involves changesin activity within brain structures essential for the basicregulation of states of consciousness self-monitoringand self-regulation Furthermore changes in relaxationand absorption are precursors (although they may notbe essential) to other hypnosis-related effects such asthe diminished tendency to judge monitor and censorthe suspension of usual orientation toward time loca-tion andor sense of self and the experience of onersquosown response as automatic or extra-volitional (Price1996) These dimensions of experience also rely criticallyon self-representation and may depend at least partly oncerebral areas shown here to be involved in hypnosisAmong those changes the increased feeling of automa-ticity an altered feeling of agency may be the mostdistinctive aspect of hypnotic phenomenology (Weitzen-hoffer 1980) Interestingly the sense of agency hasrecently been suggested to involve areas that displayconsistent changes in activity during hypnosis such asthe right inferior parietal cortex the precuneus and thesomatosensory cortices (Blakemore amp Decety 2001Ruby amp Decety 2001) The modulation of activityobserved here within those areas is consistent withthe interpretation that hypnosis produces changes inself-representation construed as an essential element forconscious experience

Conclusion

The present study used self-ratings of subjective feelingsof mental relaxation and mental absorption to map brainareas involved in hypnosis We replicated previous find-ings and further demonstrated that hypnotic relaxationand absorption reflect changes in brain activity withinregions involved in the control of consciousness statesand in self-regulation such as the brainstem the thala-mus and the ACC The coordinated activity within thesestructures and other absorption-related areas such asthe ventrolateral frontal and right posterior parietalcortices has been previously shown to underlie theregulation of the content of consciousness throughmechanisms of executive attention We must recognize

that our findings are correlative in nature and arerelevant to hypnosis to the extent that mental relaxationand absorption are conceived as basic experientialdimensions that characterize hypnotic phenomenaWe further speculate that these changes in subjectiveexperience and brain activity may contribute to otherhypnosis-related effects such as the altered feeling ofagency experienced during hypnosis These findings areconsistent with the notion that hypnotic states areachieved through the modulation of activity within adistributed network of cerebral structures involved inthe regulation of consciousness states

METHODS

Subjects

Ten right-handed subjects (4 men 6 women) wereselected from a group of 22 volunteers as a part of astudy on the hypnotic modulation of pain (Hofbaueret al 2001) Hypnotic susceptibility was assessed usingthe SHSS-A administered between scans (range 111ndash1011 mean plusmn SD 69 plusmn28) The Ethics Committee ofthe Montreal Neurological Institute (MNI) approved allprocedures and subjects signed a consent form describ-ing the procedure and affirming their right to withdrawfrom the experiment without prejudice

Experimental Procedure

We report the results obtained in eight scans acquired ina restful baseline and hypnosis condition Hypnoticinduction started immediately after Scan 4 and wassustained in the remaining scans by repeating inductioninstructions between scans Instructions included sug-gestions for (1) increased physical and mental relaxa-tion (2) comfortable feeling of warmth heaviness anddrowsiness (3) sustained passive attention to theexperimenterrsquos voice and to the instructions and (4)decreased concern with and orientation to external andinternal (mental) sources of distraction No specificinstruction for visual imagery was included During allscans the subjectsrsquo eyes were closed and their left handwas immersed in warm or painfully hot water Pain-related activation and four additional scans performedwith suggestions for pain modulation are reported else-where (Hofbauer et al 2001)

Self-Ratings of Mental Relaxation and Absorption

After each scan subjects were instructed to rate (0ndash10)(1) their level of tensionndashrelaxation with lsquolsquo10 being themost relaxed and at ease you can bersquorsquo and (2) their levelof sustained focus of attention with lsquolsquo10 being the mostabsorbed and the largest amount of sustained focusedattention you can gatherrsquorsquo Ratings of relaxation andabsorption were transformed using the rank within sub-jects to (1) control for individual differences (2) prevent

898 Journal of Cognitive Neuroscience Volume 14 Number 6

scaling biases and (3) parallel the analysis of rCBF dataSubjects rated pain on separate scales (0ndash100) Hypno-sis-related increases in relaxation and absorption did notinteract with the stimulation condition (pain vs warmstimulation prsquos gt 10) neither relaxation nor absorptioncorrelated significantly with pain ratings (all prsquos gt 10)and pain was not altered by hypnosis alone [t(9) = 069p = 51]

PET Imaging Methods

rCBF was measured using the H215O bolus injection

method (10 millicuriesscan) without arterial blood sam-pling (Herscovitch Markham amp Raichle 1983) with ahigh-resolution PET scanner operated in 3-D acquisitionmode (Siemens ECAT HR+ 63 slices) Stimulus onsetwas simultaneous with bolus injection and 1-min acquis-ition scans started about 15 sec postinjection (interscaninterval of 12ndash15 min) Data from the first 40 sec ofacquisition were reconstructed and analyzed Each sub-ject also underwent a high-resolution anatomical MRI(160 1-mm sagittal slices acquired on a Philips 15-TGyroscan system) Each PET and MRI volume wasaligned and transformed using software developed atthe MNI to match the MNI standardized Talairach space(Collins Neelin Peters amp Evans 1994 Talairach ampTournoux 1988) PET volumes were smoothed (FWHM= 14 mm) and normalized to the average brain countPeak and cluster analyses were performed (FristonWorsley Frackowiak Mazziotta amp Evans 1994 WorsleyEvans Marrett amp Neelin 1992)

Reliability of Hypnosis-Related Effects

A first analysis was performed using the subtractionmethod (Hypnosis minus Baseline) to evaluate thereliability of the effects reported in our previous study(Table 2 in Rainville Hofbauer et al 1999) We consid-ered that hypnosis-related changes in rCBF were repli-cated when a significant peak was observed within oneresel (Worsley et al 1992) of the peak sites reported inour previous study or when the peak sites were within asignificant cluster

Regression of rCBF on Self-Ratings of Relaxationand Absorption

Regression analyses were used to test the relationbetween ratings and rCBF (GLM) Subject- and stimu-lus-related effects were removed first (ANCOVA) andthe significance of the regression slope between thecovariate of interest and rCBF was estimated usingt tests Relaxation-specific and absorption-specific effectswere further tested using ANCOVAs to remove thevariance shared between absorption and relaxation(R2 = 42 p lt 001) The statistical criterion was setto t gt 258 (two-tailed uncorrected p lt 01) in the

directed searches restricted to the brainstem the thala-mus and the ACC (Table 1 Figure 2) Global searcheffects are significant ( p lt 05) based on peak (t valuegt 420) andor clusters analysis after a correction formultiple comparisons over the gray matter volume(uncorrected p lt 0001) (Table 2 Figure 3)

Thalamic Covariations

A covariation analysis was performed in which the rCBFmeasured in the thalamus was used as the covariate ofinterest after accounting for subject- and stimulus-related variance (ANCOVA see Tables 1 and 3) Becausewe were mainly interested in the relationship betweenthe activity in the thalamus and other absorption-relatedsites the threshold for statistical significance was set tot = 370 ( p = 05 uncorrected p lt 0008) based on thevolume defined by the sum of clusters of voxels showingsignificant absorption-specific effects (186 cm3 seeWorsley et al 1992)

Acknowledgments

We thank R Adolphs S Anderson A Bechara A R DamasioH Damasio Susan Lutgendorf J Parvizi and D Tranel fortheir comments on preliminary versions of the manuscriptPET analyses were performed using the software DOTdeveloped by Sylvain Milot and the MINC programs developedby Peter Neelin at the McConnell Brain Imaging Center of theMontreal Neurological Institute This study was supported bythe Medical Research Council (MRC) of Canada Dr Rainvillewas supported by the Medical Research Council of Canada andthe Human Frontier Science Program and Dr Hofbauer wassupported by the Fonds pour la recherche en sante du Quebecand the Royal Victoria Hospital Research Institute

Reprint requests should be sent to Pierre Rainville Faculte deMedecine dentaire Universite de Montreal CP 6128 SuccCentre-ville Montreal Qc H3C 3J7 Canada or via e-mailpierrerainvilleumontrealca

REFERENCES

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Badgaiyan R D amp Posner M I (1998) Mapping the cingulatecortex in response selection and monitoring Neuroimage7 255 ndash260

Balthazard C G amp Woody E Z (1992) The spectral analysisof hypnotic performance with respect to lsquolsquoabsorptionrsquorsquoInternational Journal of Clinical and ExperimentalHypnosis 40 21ndash43

Banyai E I amp Hilgard E R (1976) A comparison ofactive-alert hypnotic induction with traditional relaxationinduction Journal of Abnormal Psychology 85 218 ndash224

Blakemore S J amp Decety J (2001) From the perception ofaction to the understanding of intention Nature ReviewsNeuroscience 2 561 ndash567

Braun A R Balkin T J Wesenten N J Carson R EVarga M Baldwin P Selbie S Belenky G amp HerscovitchP (1997) Regional cerebral blood flow throughout the

Rainville et al 899

sleep ndashwake cycle An H2(15)O PET study Brain 1201173 ndash1197

Bush G Luu P amp Posner M I (2000) Cognitive andemotional influences in anterior cingulate cortex Trendsin Cognitive Sciences 4 215 ndash222

Chalmers D J (2000) What is a neural correlate ofconsciousness In T Metzinger (Ed) Neural correlatesof consciousness Empirical and conceptual questions(pp 17ndash39) Cambridge MIT Press

Coe W C amp Sarbin T R (1977) Hypnosis from thestandpoint of a contextualist Annals of the New YorkAcademy of Sciences 296 2ndash13

Cohen J D Botvinick M amp Carter C S (2000) Anteriorcingulate and prefrontal cortex Whorsquos in control NatureNeuroscience 3 421 ndash423

Collins D L Neelin P Peters T M amp Evans A C (1994)Automatic 3D intersubject registration of MR volumetric datain standardized Talairach space Journal of ComputerAssisted Tomography 18 192 ndash205

Coull J T Frackowiak R S amp Frith C D (1998) Monitoringfor target objects Activation of right frontal and parietalcortices with increasing time on task Neuropsychologia 361325 ndash1334

Coull J T amp Nobre A C (1998) Where and when to payattention The neural systems for directing attention tospatial locations and to time intervals as revealed by bothPET and fMRI Journal of Neuroscience 18 7426 ndash7435

Crawford H J (1994) Brain dynamics and hypnosisAttentional and disattentional processes InternationalJournal of Clinical and Experimental Hypnosis 42204 ndash232

Crawford H J amp Gruzelier J H (1992) A midstream view ofthe neuropsychophysiology of hypnosis Recent researchand future directions In E Fromm amp M R Nash (Eds)Contemporary hypnosis research (pp 227 ndash266) New YorkGuilford Press

Crawford H J Knebel T Kaplan L Vendemia J M C XieM Jamison S amp Pribram K H (1998) Hypnotic analgesia1 Somatosensory event-related potential changes to noxiousstimuli and 2 Transfer learning to reduce chronic low backpain International Journal of Clinical and ExperimentalHypnosis 46 92ndash132

Damasio A R (1999) The feeling of what happens Body andemotion and the making of consciousness New YorkHartcourt Brace

De Pascalis V Magurano M R amp Bellusci A (1999) Painperception somatosensory event-related potentials andskin conductance responses to painful stimuli in high midand low hypnotizable subjects Effects of differential painreduction strategies Pain 83 499 ndash508

Devinsky O Morrell M J amp Vogt B A (1995) Contributionsof anterior cingulate cortex to behaviour Brain 118279 ndash306

Fiset P Paus T Daloze T Plourde G Meuret PBonhomme V Hajj-Ali N Backman S B amp Evans A C(1999) Brain mechanisms of propofol-induced loss ofconsciousness in humans A positron emission tomographicstudy Journal of Neuroscience 19 5505 ndash5513

Friston K J Worsley K J Frackowiak R S J Mazziotta J Camp Evans A C (1994) Assessing the significance of focalactivation using their spatial extent Human Brain Mapping1 214ndash220

Gitelman D R Alpert N M Kosslyn S Daffner K ScintoL Thompson W amp Mesulam M M (1996) Functionalimaging of human right hemispheric activation forexploratory movements Annals of Neurology 39 174ndash179

Gitelman D R Nobre A C Parrish T B LaBar K S KimY H Meyer J R amp Mesulam M (1999) A large-scale

distributed network for covert spatial attention Furtheranatomical delineation based on stringent behavioural andcognitive controls Brain 122 1093 ndash1106

Gruzelier J (1998) A working model of the neurophysiologyof hypnosis A review of evidence Contemporary Hypnosis15 3ndash21

Henson R N A Rugg M D Shallice T amp Dolan R J (2000)Confidence in recognition memory for words Dissociatingright prefrontal roles in episodic retrieval Journal ofCognitive Neuroscience 12 913 ndash923

Henson R N A Rugg M D Shallice T Joseph O ampDolan R J (1999) Recollection and familiarity inrecognition memory An event-related functional magneticresonance imaging study Journal of Neuroscience 193962 ndash3972

Herscovitch P Markham J amp Raichle M E (1983) Brainblood flow measured with intravenous H2(15)O I Theoryand error analysis Journal of Nuclear Medicine 24782 ndash789

Hofbauer R K Rainville P Duncan G H amp Bushnell M C(2001) Cortical representation of the sensory dimension ofpain Journal of Neurophysiology 86 402 ndash411

Hofle N Paus T Reutens D Fiset P Gotman J EvansA C amp Jones B E (1997) Regional cerebral blood flowchanges as a function of delta and spindle activity duringslow wave sleep in humans Journal of Neuroscience 174800 ndash4808

Jeanmonod D Magnin M amp Morel A (1996) Low-thresholdcalcium spike bursts in the human thalamus Commonphysiopathology for sensory motor and limbic positivesymptoms Brain 119 363ndash375

Kajimura N Uchiyama M Takayama Y Uchida S Uema TKato M Sekimoto M Watanabe T Nakajima THorikoshi S Ogawa K Nishikawa M Hiroki M Kudo YMatsuda H Okawa M amp Takahashi K (1999) Activityof midbrain reticular formation and neocortex during theprogression of human non-rapid eye movement sleepJournal of Neuroscience 19 10065 ndash10073

Kawashima R OrsquoSullivan B T amp Roland P E (1995)Positron-emission tomography studies of cross-modalityinhibition in selective attentional tasks Closing the lsquolsquomindrsquoseyersquorsquo Proceedings of the National Academy of SciencesUSA 92 5969 ndash5972

Kim Y H Gitelman D R Nobre A C Parrish T BLaBar K S amp Mesulam M M (1999) The large-scaleneural network for spatial attention displays multifunctionaloverlap but differential asymmetry Neuroimage 9269 ndash277

Kinomura S Larsson J Gulyas B amp Roland P E (1996)Activation by attention of the human reticular formationand thalamic intralaminar nuclei Science 271 512ndash515

Kosslyn S M Thompson W L Costantini-Ferrando M FAlpert N M amp Spiegel D (2000) Hypnotic visual illusionalters color processing in the brain American Journal ofPsychiatry 157 1279 ndash1284

Laureys S Faymonville M E Luxen A Lamy M Franck Gamp Maquet P (2000) Restoration of thalamocorticalconnectivity after recovery from persistent vegetative stateLancet 355 1790ndash1791

Lou H C Kjaer T W Friberg L Wildschiodtz G Holm Samp Nowak M (1999) A 15OndashH2O PET study of meditationand the resting state of normal consciousness HumanBrain Mapping 7 98ndash105

Maquet P Degueldre C Delfiore G Aerts J Peters J MLuxen A amp Franck G (1997) Functional neuroanatomyof human slow wave sleep Journal of Neuroscience 172807 ndash2812

Maquet P Faymonville M E Degueldre C Delfiore G

900 Journal of Cognitive Neuroscience Volume 14 Number 6

Franck G Luxen A amp Lamy M (1999) Functionalneuroanatomy of hypnotic state Biological Psychiatry 45327 ndash333

Metzinger T (2000) The subjectivity of subjective experienceA representationalist analysis of the first-person perspectiveIn T Metzinger (Ed) Neural correlates of consciousnessEmprical and conceptual questions (pp 285 ndash306)Cambridge MIT Press

Nobre A C Sebestyen G N Gitelman D R MesulamM M Frackowiak R S amp Frith C D (1997) Functionallocalization of the system for visuospatial attention usingpositron emission tomography Brain 120 515 ndash533

Pardo J V Fox P T amp Raichle M E (1991) Localization of ahuman system for sustained attention by positron emissiontomography Nature 349 61ndash64

Paus T (2001) Primate anterior cingulate cortex Wheremotor control drive and cognition interface NatureReviews Neuroscience 2 417 ndash424

Paus T Koski L Caramanos Z amp Westbury C (1998)Regional differences in the effects of task difficulty andmotor output on blood flow response in the human anteriorcingulate cortex A review of 107 PET activation studiesNeuroReport 9 R37ndashR47

Paus T Zatorre R J Hofle N Caramanos Z Gotman JPetrides M amp Evans A C (1997) Time-related changesin neural systems underlying attention and arousal duringthe performance of an auditory vigilance task Journal ofCognitive Neuroscience 9 392ndash408

Peyron R Garcia-Larrea L Gregoire M C Costes NConvers P Lavenne F Mauguiere F Michel D ampLaurent B (1999) Haemodynamic brain responses to acutepain in humansmdashSensory and attentional networks Brain122 1765 ndash1779

Picard N amp Strick P L (1996) Motor areas of the medial wallA review of their location and functional activation CerebralCortex 6 342 ndash353

Portas C M Howseman A M Josephs O Turner R ampFrith C D (1998) A specific role for the thalamus inmediating the interaction of attention and arousal inhumans Journal of Neuroscience 18 8979 ndash8989

Posner M I amp Rothbart M K (1998) Attentionself-regulation and consciousness Philosophical

Transactions of the Royal Society of London Series BBiological Sciences 353 1915 ndash1927

Price D D (1996) Hypnotic analgesia Psychological andneural mechanisms In J Barber (Ed) Hypnosis andsuggestions in the treatment of pain (pp 67ndash84) NewYork Norton

Price D D amp Barrell J J (1980) An experiential approachwith quantitative methods A research paradigm Journal ofHumanistic Psychology 20 75ndash95

Rainville P Carrier B Hofbauer R K Bushnell M C ampDuncan G H (1999) Dissociation of pain sensory andaffective dimensions using hypnotic modulation Pain 82159 ndash171

Rainville P Duncan G H Price D D Carrier B ampBushnell M C (1997) Pain affect encoded in humananterior cingulate but not somatosensory cortex Science277 968 ndash971

Rainville P Hofbauer R K Paus T Duncan G H BushnellM C amp Price D D (1999) Cerebral mechanisms ofhypnotic induction and suggestion Journal of CognitiveNeuroscience 11 110ndash125

Ruby P amp Decety J (2001) Effect of subjective perspectivetaking during simulation of action A PET investigation ofagency Nature Neuroscience 4 546 ndash550

Steriade M amp McCarley R W (1990) Brainstem control ofwakefulness and sleep New York Plenum

Szechtman H Woody E Bowers K S amp Nahmias C(1998) Where the imaginal appears real A positronemission tomography study of auditory hallucinationsProceedings of the National Academy of Sciences USA95 1956 ndash1960

Talairach J amp Tournoux P (1988) Co-planar stereotaxicatlas of the human brain New York Thieme

Tellegen A amp Atkinson G (1974) Openness to absorbingand self-altering experiences (lsquolsquoabsorptionrsquorsquo) a trait relatedto hypnotic susceptibility Journal of Abnormal Psychology83 268 ndash277

Toma K Honda M Hanakawa T Okada T Fukuyama HIkeda A Nishizawa S Konishi J amp Shibasaki H (1999)Activities of the primary and supplementary motor areasincrease in preparation and execution of voluntary musclerelaxation An event-related fMRI study Journal ofNeuroscience 19 3527 ndash3534

Varela F J amp Shear J (1999) First-person methodologiesWhat why and how Journal of Consciousness Studies 61ndash14

Vingoe F J (1968) The development of a group alert-trancescale International Journal of Clinical and ExperimentalHypnosis 16 120 ndash132

Vingoe F J (1973) Comparison of the Harvard Group Scaleof Hypnotic Susceptibility Form A and the Group AlertTrance Scale in a university population InternationalJournal of Clinical and Experimental Hypnosis 21169 ndash179

Vogt B A amp Gabriel M (1993) Neurobiology of cingulatecortex and limbic thalamus A comprehensive handbookBoston Birkauser

Weitzenhoffer A M (1980) Hypnotic susceptibility revisitedAmerican Journal of Clinical Hypnosis 22 130 ndash146

Willoch F Rosen G Tolle T R Oslashye I Wester H J BernerN Schwaiger M amp Bartenstein P (2000) Phantom limbpain in the human brain Unravelling neural circuitries ofphantom limb pain sensations using positron emissiontomography Annals of Neurology 48 842 ndash849

Worsley K J Evans A C Marrett S amp Neelin P (1992)A three-dimensional statistical analysis for CBF activationstudies in human brain Journal of Cerebral Blood Flow andMetabolism 12 900 ndash918

Rainville et al 901

Page 10: Hypnosis Modulates Activity in Brain Structures Involved in the …pineda/COGS175/readings/Rain... · 2005. 2. 28. · Hypnosis Modulates Activity in Brain Structures Involved in

and attentional processes (ie increased attentionabsorption concurrent with decreased cortical arousalincreased relaxation) (Aston-Jones et al 1999) Theindirect nature of the rCBF measures and the relativelypoor resolution of the PET method require somecaution in evaluating the possible anatomo-functionalimplications of our results in the brainstem Howeverthe convergent findings observed in other brain imag-ing studies and the observations provided in animalstudies support the notion that ascending cholinergicand noradrenergic pathways may contribute differen-tially to the multiple dimensions of experience thatcharacterize hypnosis

The overall pattern of results found in the ACC likelyreflects the heterogeneity of functions associated withthis area (Devinsky Morrell amp Vogt 1995) The locationof the most posterior relaxation-related peak in the ACC(mACC) is consistent with our previous observationof ACC activation during hypnosis (Rainville Hofbaueret al 1999) This relaxation-related peak is only slightlyanterior to the motor area of the caudal ACC (Picard ampStrick 1996) and may be involved in the installment of arelaxed state (also see precentral area below) In con-trast a positive absorption-specific effect was observedin a more rostral region of the ACC (rACC) close to anegative relaxation-specific correlation (see Table 1)This area of the ACC has previously been involved inexecutive attention in the detection of errors and in themonitoring of conflict between competing cognitiveprocesses (Bush Luu amp Posner 2000 Cohen Botvinickamp Carter 2000 Badgaiyan amp Posner 1998 Posner ampRothbart 1998) A meta-analysis of PET studies inves-tigating cognitive functions further suggested that theincrease in activity within this sector of the ACC isrelated to the difficulty of the task performed (PausKoski Caramanos amp Westbury 1998) Our findings areconsistent with these propositions to the extent thatthe engagement of the cognitive and neurophysiologicalprocesses implied in each of those accounts may beaccompanied by a subjective experience of increasedmental absorption

The coordinated pattern of rCBF changes in thebrainstem the thalamus and the ACC may reflect theinterrelationships between the multiple components of anetwork (eg Paus et al 1997) herein shown to beassociated with the feeling of being lsquolsquomentally absorbedrsquorsquoThe precise location of the observed absorption-specificthalamic peak is consistent with an involvement of theintralaminar and medio-dorsal nuclei which have recip-rocal connections with the ACC (Vogt amp Gabriel 1993)The finding that the coordinated activity in the thalamusand the ACC is disrupted in persistent vegetative states isconsistent with the notion that these structures work intandem to regulate consciousness (Laureys et al 2000also see Jeanmonod Magnin amp Morel 1996) Further-more a functional interaction between arousal andattentional processes has been reported in the thalamus

where the putative attention-related activity associatedwith the performance of a simple visual discriminationtask was found to increase in states of low arousal (Portaset al 1998) This increase in thalamic activity wassuggested (1) to reflect a compensatory mechanism thatpermitted the maintenance of stable levels of perform-ance in states of low arousal and (2) to prevent thegeneralized thalamo-cortical synchronization that wouldlead to sleep Here the opposite effects of relaxation andabsorption on thalamic activity may reflect this compen-satory mechanism that maintains high levels of focusedattention in deeply relaxed subjects during hypnosisThis function may be critical not only in hypnosis butalso in other conditions of deep relaxation distinct fromboth sleep and normal wakefulness such as meditativestates (Lou et al 1999) Furthermore the coactivation ofthe ACC and the ponto-mesencephalic brainstem mayreflect the contribution of the ACC to the regulation ofattention-related activity in the locus coeruleus (Cohenet al 2000) The positive regression found with absorp-tion in the ponto-mesencephalic brainstem and themore robust regression observed in the thalamus andthe ACC after accounting for relaxation-related changes(absorption-specific Table 1) further substantiate thepossibility that brainstem and thalamic nuclei interactwith the ACC to regulate the interaction between atten-tion and cortical arousal Taken together these resultsare consistent with a contribution of brainstem nucleithe intralaminar and medio-dorsal nuclei of the thala-mus and the ACC to the changes in phenomenalexperience that characterize hypnotic states

Additional Relaxation- and Absorption-RelatedChanges in rCBF

Relaxation-Related Activity

We observed strong relaxation-related increases in rCBFin the precentral gyrus bilaterally and reciprocaldecreases in somatosensory areas (S1 S2 and insula)Precentral and premotor activation has been reportedduring hypnosis in an independent study (Maquet et al1999) and precentral rCBF was correlated with the rCBFmeasured at the ACC site of hypnosis-related activity inour previous study (see Appendix in Rainville Hofbaueret al 1999) Similar increases in activity in motor andpremotor areas have been associated with voluntarymuscular relaxation (Toma et al 1999) but the presentresults may reflect more than physical relaxation

All standard hypnotic procedures include instructionsfor relaxation However the specific contribution ofmuscular relaxation and decreased arousal to the pro-duction of hypnotic states is unclear as hypnotic phe-nomena have been produced during muscular exercise(Banyai amp Hilgard 1976) and with suggestions of active-alertness (Vingoe 1968 1973) Here the absence ofsignificant effect of hypnosis on heart rate indicates thatchanges in cerebral activity did not correlate with

896 Journal of Cognitive Neuroscience Volume 14 Number 6

changes in peripheral arousal and suggests that subjectswere already physically relaxed in the baseline controlcondition This implies that the hypnosis-inducedchanges in self-ratings of relaxation may not simplyreflect changes in lsquolsquoperipheralrsquorsquo arousal but may attestmore specifically of an increase in lsquolsquomentalrsquorsquo relaxationand a reduction in lsquolsquocorticalrsquorsquo arousal This is consistentwith Pricersquos experiential model of hypnosis (see Intro-duction) and with our previous study showing anincrease in slow (delta) EEG activity during hypnosis

Relaxation-related effects observed outside primarysomatomotor areas may partly reflect subjective feelingsof mental ease more closely In the subtraction analysishypnosis-related decreases were found in the rightlateral posterior parietal rCBF both here (x y z 40iexcl52 44) and in our previous study (x y z 46 iexcl50 42from Table 1 in Rainville Hofbauer et al 1999) Herethese changes were strongly but not specifically asso-ciated with relaxation (x y z 39 iexcl49 45 see Table 2Figure 3A) Furthermore after accounting for absorp-tion-related variance right prefrontal activity was neg-atively correlated with relaxation (Table 2) Thoseadditional changes in the right posterior parietal cortexand the right prefrontal cortices may contribute to thesubjective feelings of mental ease rather than or inaddition to physical relaxation

Fronto-Parietal Attention Networks

Absorption-related activity was widespread and bilateralin the prefrontal cortices but peaks were generallystronger in the right hemisphere Positive regressionpeaks were maximal in the ventrolateral frontal corticesover the inferior frontal gyrus and in the anterior insulaA positive absorption-related regression peak was alsosignificant in the right inferior parietal lobule Theseareas also displayed strong coactivation with absorption-related thalamic activity Very similar patterns of activa-tion have been associated with attentional processes intasks involving visual (eg Coull Frackowiak amp Frith1998) auditory (Paus et al 1997) and somatosensorystimuli (Peyron et al 1999) Notably the location of thepositive parietal peak observed here closely matches theactivation sites reported in those studies and the site ofcovariation with the right ventrolateral attention-relatedactivity reported in Paus et al (1997) suggesting theactivation of a similar network The coordinated absorp-tion-related activity observed here in the brainstem thethalamus the ACC the right inferior frontal gyrus andthe right inferior parietal lobule provides very strongevidence that mental absorption is an experiential cor-relate of the activation of the brainrsquos lsquolsquoexecutive atten-tional networkrsquorsquo and suggests that this system plays acritical role in the production of hypnotic states

Negative absorption-related regression peaks werealso found in both the right and left lateral parietalcortices and in the precuneus (see Table 2) These

effects were largely independent of thalamic activity asindicated by the absence of significant effects at theselocations in the covariation analysis (Table 3) The rightposterior parietal cortex has been suggested to con-stitute a vigilanceorientation system (Pardo Fox ampRaichle 1991) and hypnosis-related decreases in thisarea may reflect a relative disengagement towardexternal sources of stimulation Right and left posteriorparietal cortices at the precise sites of relaxation- andabsorption-related decrease in rCBF have been sug-gested to contribute to the monitoring of externalspace and time respectively (Gitelman et al 19961999 Kim et al 1999 Coull amp Nobre 1998 Nobreet al 1997) Although these functions were notdirectly assessed in this experiment the hypnoticinduction procedure includes specific instructions fordecreased orientation to and interest in irrelevantexternal sources of stimulation and previous observa-tions suggest that hypnotic relaxation and absorptionare precursors to some alterations in spatio-temporalorientation and monitoring (Price 1996) Thus wespeculate that those additional experiential changesmay be consequent to relaxation- and absorption-related decreases in posterior parietal activity

Relaxation- and Absorption-Related Effects onOccipital rCBF

The subtraction analysis confirmed the reliability of thehypnosis-related increase in occipital rCBF reported inour previous study (Rainville Hofbauer et al 1999) Wenow show that this effect was associated with the sub-jective experience of hypnotic relaxation (see Table 2relaxation-specific) Consistently our previous studydemonstrated a coupling between occipital increases inrCBF and increases in slow (delta) EEG activity duringhypnosis Similar increases in occipital rCBF andor slowEEG activity had been observed in another study onhypnosis (Maquet et al 1999) and in states of decreasedvigilance (Paus et al 1997) meditation (Lou et al 1999)and slow wave sleep (Kajimura et al 1999 Hofle et al1997) These effects are consistent with our previousproposition that hypnotic induction produces a globaldecrease in cross-modality suppression in unattendedsensory channels leading to a relative disinhibitionof cortical activity (see Paus et al 1997 KawashimaOrsquoSullivan amp Roland 1995)

In contrast negative correlations between rCBF andmental absorption were observed over both occipitallobes (Table 2 Figure 3B) Consistently occipital rCBFwas correlated negatively with thalamic rCBF at theabsorption-specific site (Table 3) These contrastingeffects imply that variations in occipital rCBF are asso-ciated with separate portions of the variance in relaxa-tion and absorption (Note that although absorptionand relaxation were significantly correlated the variancein absorption was largely independent of relaxation see

Rainville et al 897

Methods) For a given level of relaxation the increasein hypnotic absorption could reflect the concurrentengagement of the lsquolsquoexecutive attentional networkrsquorsquowhich exerts an opposite effect over brain areas sub-serving unattended sensory channels (ie a relativefacilitation of cross-modality suppression)

Hypnosis as a State of Consciousness

The representation of the body-self is central to theneurophenomenology of consciousness (Metzinger2000) In the Introduction we have proposed that theinduction of hypnosis produces global changes in sub-jective experience reflecting a modulation of basicaspects of the body-self representation Consistentlythe PET results indicate that hypnosis involves changesin activity within brain structures essential for the basicregulation of states of consciousness self-monitoringand self-regulation Furthermore changes in relaxationand absorption are precursors (although they may notbe essential) to other hypnosis-related effects such asthe diminished tendency to judge monitor and censorthe suspension of usual orientation toward time loca-tion andor sense of self and the experience of onersquosown response as automatic or extra-volitional (Price1996) These dimensions of experience also rely criticallyon self-representation and may depend at least partly oncerebral areas shown here to be involved in hypnosisAmong those changes the increased feeling of automa-ticity an altered feeling of agency may be the mostdistinctive aspect of hypnotic phenomenology (Weitzen-hoffer 1980) Interestingly the sense of agency hasrecently been suggested to involve areas that displayconsistent changes in activity during hypnosis such asthe right inferior parietal cortex the precuneus and thesomatosensory cortices (Blakemore amp Decety 2001Ruby amp Decety 2001) The modulation of activityobserved here within those areas is consistent withthe interpretation that hypnosis produces changes inself-representation construed as an essential element forconscious experience

Conclusion

The present study used self-ratings of subjective feelingsof mental relaxation and mental absorption to map brainareas involved in hypnosis We replicated previous find-ings and further demonstrated that hypnotic relaxationand absorption reflect changes in brain activity withinregions involved in the control of consciousness statesand in self-regulation such as the brainstem the thala-mus and the ACC The coordinated activity within thesestructures and other absorption-related areas such asthe ventrolateral frontal and right posterior parietalcortices has been previously shown to underlie theregulation of the content of consciousness throughmechanisms of executive attention We must recognize

that our findings are correlative in nature and arerelevant to hypnosis to the extent that mental relaxationand absorption are conceived as basic experientialdimensions that characterize hypnotic phenomenaWe further speculate that these changes in subjectiveexperience and brain activity may contribute to otherhypnosis-related effects such as the altered feeling ofagency experienced during hypnosis These findings areconsistent with the notion that hypnotic states areachieved through the modulation of activity within adistributed network of cerebral structures involved inthe regulation of consciousness states

METHODS

Subjects

Ten right-handed subjects (4 men 6 women) wereselected from a group of 22 volunteers as a part of astudy on the hypnotic modulation of pain (Hofbaueret al 2001) Hypnotic susceptibility was assessed usingthe SHSS-A administered between scans (range 111ndash1011 mean plusmn SD 69 plusmn28) The Ethics Committee ofthe Montreal Neurological Institute (MNI) approved allprocedures and subjects signed a consent form describ-ing the procedure and affirming their right to withdrawfrom the experiment without prejudice

Experimental Procedure

We report the results obtained in eight scans acquired ina restful baseline and hypnosis condition Hypnoticinduction started immediately after Scan 4 and wassustained in the remaining scans by repeating inductioninstructions between scans Instructions included sug-gestions for (1) increased physical and mental relaxa-tion (2) comfortable feeling of warmth heaviness anddrowsiness (3) sustained passive attention to theexperimenterrsquos voice and to the instructions and (4)decreased concern with and orientation to external andinternal (mental) sources of distraction No specificinstruction for visual imagery was included During allscans the subjectsrsquo eyes were closed and their left handwas immersed in warm or painfully hot water Pain-related activation and four additional scans performedwith suggestions for pain modulation are reported else-where (Hofbauer et al 2001)

Self-Ratings of Mental Relaxation and Absorption

After each scan subjects were instructed to rate (0ndash10)(1) their level of tensionndashrelaxation with lsquolsquo10 being themost relaxed and at ease you can bersquorsquo and (2) their levelof sustained focus of attention with lsquolsquo10 being the mostabsorbed and the largest amount of sustained focusedattention you can gatherrsquorsquo Ratings of relaxation andabsorption were transformed using the rank within sub-jects to (1) control for individual differences (2) prevent

898 Journal of Cognitive Neuroscience Volume 14 Number 6

scaling biases and (3) parallel the analysis of rCBF dataSubjects rated pain on separate scales (0ndash100) Hypno-sis-related increases in relaxation and absorption did notinteract with the stimulation condition (pain vs warmstimulation prsquos gt 10) neither relaxation nor absorptioncorrelated significantly with pain ratings (all prsquos gt 10)and pain was not altered by hypnosis alone [t(9) = 069p = 51]

PET Imaging Methods

rCBF was measured using the H215O bolus injection

method (10 millicuriesscan) without arterial blood sam-pling (Herscovitch Markham amp Raichle 1983) with ahigh-resolution PET scanner operated in 3-D acquisitionmode (Siemens ECAT HR+ 63 slices) Stimulus onsetwas simultaneous with bolus injection and 1-min acquis-ition scans started about 15 sec postinjection (interscaninterval of 12ndash15 min) Data from the first 40 sec ofacquisition were reconstructed and analyzed Each sub-ject also underwent a high-resolution anatomical MRI(160 1-mm sagittal slices acquired on a Philips 15-TGyroscan system) Each PET and MRI volume wasaligned and transformed using software developed atthe MNI to match the MNI standardized Talairach space(Collins Neelin Peters amp Evans 1994 Talairach ampTournoux 1988) PET volumes were smoothed (FWHM= 14 mm) and normalized to the average brain countPeak and cluster analyses were performed (FristonWorsley Frackowiak Mazziotta amp Evans 1994 WorsleyEvans Marrett amp Neelin 1992)

Reliability of Hypnosis-Related Effects

A first analysis was performed using the subtractionmethod (Hypnosis minus Baseline) to evaluate thereliability of the effects reported in our previous study(Table 2 in Rainville Hofbauer et al 1999) We consid-ered that hypnosis-related changes in rCBF were repli-cated when a significant peak was observed within oneresel (Worsley et al 1992) of the peak sites reported inour previous study or when the peak sites were within asignificant cluster

Regression of rCBF on Self-Ratings of Relaxationand Absorption

Regression analyses were used to test the relationbetween ratings and rCBF (GLM) Subject- and stimu-lus-related effects were removed first (ANCOVA) andthe significance of the regression slope between thecovariate of interest and rCBF was estimated usingt tests Relaxation-specific and absorption-specific effectswere further tested using ANCOVAs to remove thevariance shared between absorption and relaxation(R2 = 42 p lt 001) The statistical criterion was setto t gt 258 (two-tailed uncorrected p lt 01) in the

directed searches restricted to the brainstem the thala-mus and the ACC (Table 1 Figure 2) Global searcheffects are significant ( p lt 05) based on peak (t valuegt 420) andor clusters analysis after a correction formultiple comparisons over the gray matter volume(uncorrected p lt 0001) (Table 2 Figure 3)

Thalamic Covariations

A covariation analysis was performed in which the rCBFmeasured in the thalamus was used as the covariate ofinterest after accounting for subject- and stimulus-related variance (ANCOVA see Tables 1 and 3) Becausewe were mainly interested in the relationship betweenthe activity in the thalamus and other absorption-relatedsites the threshold for statistical significance was set tot = 370 ( p = 05 uncorrected p lt 0008) based on thevolume defined by the sum of clusters of voxels showingsignificant absorption-specific effects (186 cm3 seeWorsley et al 1992)

Acknowledgments

We thank R Adolphs S Anderson A Bechara A R DamasioH Damasio Susan Lutgendorf J Parvizi and D Tranel fortheir comments on preliminary versions of the manuscriptPET analyses were performed using the software DOTdeveloped by Sylvain Milot and the MINC programs developedby Peter Neelin at the McConnell Brain Imaging Center of theMontreal Neurological Institute This study was supported bythe Medical Research Council (MRC) of Canada Dr Rainvillewas supported by the Medical Research Council of Canada andthe Human Frontier Science Program and Dr Hofbauer wassupported by the Fonds pour la recherche en sante du Quebecand the Royal Victoria Hospital Research Institute

Reprint requests should be sent to Pierre Rainville Faculte deMedecine dentaire Universite de Montreal CP 6128 SuccCentre-ville Montreal Qc H3C 3J7 Canada or via e-mailpierrerainvilleumontrealca

REFERENCES

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Badgaiyan R D amp Posner M I (1998) Mapping the cingulatecortex in response selection and monitoring Neuroimage7 255 ndash260

Balthazard C G amp Woody E Z (1992) The spectral analysisof hypnotic performance with respect to lsquolsquoabsorptionrsquorsquoInternational Journal of Clinical and ExperimentalHypnosis 40 21ndash43

Banyai E I amp Hilgard E R (1976) A comparison ofactive-alert hypnotic induction with traditional relaxationinduction Journal of Abnormal Psychology 85 218 ndash224

Blakemore S J amp Decety J (2001) From the perception ofaction to the understanding of intention Nature ReviewsNeuroscience 2 561 ndash567

Braun A R Balkin T J Wesenten N J Carson R EVarga M Baldwin P Selbie S Belenky G amp HerscovitchP (1997) Regional cerebral blood flow throughout the

Rainville et al 899

sleep ndashwake cycle An H2(15)O PET study Brain 1201173 ndash1197

Bush G Luu P amp Posner M I (2000) Cognitive andemotional influences in anterior cingulate cortex Trendsin Cognitive Sciences 4 215 ndash222

Chalmers D J (2000) What is a neural correlate ofconsciousness In T Metzinger (Ed) Neural correlatesof consciousness Empirical and conceptual questions(pp 17ndash39) Cambridge MIT Press

Coe W C amp Sarbin T R (1977) Hypnosis from thestandpoint of a contextualist Annals of the New YorkAcademy of Sciences 296 2ndash13

Cohen J D Botvinick M amp Carter C S (2000) Anteriorcingulate and prefrontal cortex Whorsquos in control NatureNeuroscience 3 421 ndash423

Collins D L Neelin P Peters T M amp Evans A C (1994)Automatic 3D intersubject registration of MR volumetric datain standardized Talairach space Journal of ComputerAssisted Tomography 18 192 ndash205

Coull J T Frackowiak R S amp Frith C D (1998) Monitoringfor target objects Activation of right frontal and parietalcortices with increasing time on task Neuropsychologia 361325 ndash1334

Coull J T amp Nobre A C (1998) Where and when to payattention The neural systems for directing attention tospatial locations and to time intervals as revealed by bothPET and fMRI Journal of Neuroscience 18 7426 ndash7435

Crawford H J (1994) Brain dynamics and hypnosisAttentional and disattentional processes InternationalJournal of Clinical and Experimental Hypnosis 42204 ndash232

Crawford H J amp Gruzelier J H (1992) A midstream view ofthe neuropsychophysiology of hypnosis Recent researchand future directions In E Fromm amp M R Nash (Eds)Contemporary hypnosis research (pp 227 ndash266) New YorkGuilford Press

Crawford H J Knebel T Kaplan L Vendemia J M C XieM Jamison S amp Pribram K H (1998) Hypnotic analgesia1 Somatosensory event-related potential changes to noxiousstimuli and 2 Transfer learning to reduce chronic low backpain International Journal of Clinical and ExperimentalHypnosis 46 92ndash132

Damasio A R (1999) The feeling of what happens Body andemotion and the making of consciousness New YorkHartcourt Brace

De Pascalis V Magurano M R amp Bellusci A (1999) Painperception somatosensory event-related potentials andskin conductance responses to painful stimuli in high midand low hypnotizable subjects Effects of differential painreduction strategies Pain 83 499 ndash508

Devinsky O Morrell M J amp Vogt B A (1995) Contributionsof anterior cingulate cortex to behaviour Brain 118279 ndash306

Fiset P Paus T Daloze T Plourde G Meuret PBonhomme V Hajj-Ali N Backman S B amp Evans A C(1999) Brain mechanisms of propofol-induced loss ofconsciousness in humans A positron emission tomographicstudy Journal of Neuroscience 19 5505 ndash5513

Friston K J Worsley K J Frackowiak R S J Mazziotta J Camp Evans A C (1994) Assessing the significance of focalactivation using their spatial extent Human Brain Mapping1 214ndash220

Gitelman D R Alpert N M Kosslyn S Daffner K ScintoL Thompson W amp Mesulam M M (1996) Functionalimaging of human right hemispheric activation forexploratory movements Annals of Neurology 39 174ndash179

Gitelman D R Nobre A C Parrish T B LaBar K S KimY H Meyer J R amp Mesulam M (1999) A large-scale

distributed network for covert spatial attention Furtheranatomical delineation based on stringent behavioural andcognitive controls Brain 122 1093 ndash1106

Gruzelier J (1998) A working model of the neurophysiologyof hypnosis A review of evidence Contemporary Hypnosis15 3ndash21

Henson R N A Rugg M D Shallice T amp Dolan R J (2000)Confidence in recognition memory for words Dissociatingright prefrontal roles in episodic retrieval Journal ofCognitive Neuroscience 12 913 ndash923

Henson R N A Rugg M D Shallice T Joseph O ampDolan R J (1999) Recollection and familiarity inrecognition memory An event-related functional magneticresonance imaging study Journal of Neuroscience 193962 ndash3972

Herscovitch P Markham J amp Raichle M E (1983) Brainblood flow measured with intravenous H2(15)O I Theoryand error analysis Journal of Nuclear Medicine 24782 ndash789

Hofbauer R K Rainville P Duncan G H amp Bushnell M C(2001) Cortical representation of the sensory dimension ofpain Journal of Neurophysiology 86 402 ndash411

Hofle N Paus T Reutens D Fiset P Gotman J EvansA C amp Jones B E (1997) Regional cerebral blood flowchanges as a function of delta and spindle activity duringslow wave sleep in humans Journal of Neuroscience 174800 ndash4808

Jeanmonod D Magnin M amp Morel A (1996) Low-thresholdcalcium spike bursts in the human thalamus Commonphysiopathology for sensory motor and limbic positivesymptoms Brain 119 363ndash375

Kajimura N Uchiyama M Takayama Y Uchida S Uema TKato M Sekimoto M Watanabe T Nakajima THorikoshi S Ogawa K Nishikawa M Hiroki M Kudo YMatsuda H Okawa M amp Takahashi K (1999) Activityof midbrain reticular formation and neocortex during theprogression of human non-rapid eye movement sleepJournal of Neuroscience 19 10065 ndash10073

Kawashima R OrsquoSullivan B T amp Roland P E (1995)Positron-emission tomography studies of cross-modalityinhibition in selective attentional tasks Closing the lsquolsquomindrsquoseyersquorsquo Proceedings of the National Academy of SciencesUSA 92 5969 ndash5972

Kim Y H Gitelman D R Nobre A C Parrish T BLaBar K S amp Mesulam M M (1999) The large-scaleneural network for spatial attention displays multifunctionaloverlap but differential asymmetry Neuroimage 9269 ndash277

Kinomura S Larsson J Gulyas B amp Roland P E (1996)Activation by attention of the human reticular formationand thalamic intralaminar nuclei Science 271 512ndash515

Kosslyn S M Thompson W L Costantini-Ferrando M FAlpert N M amp Spiegel D (2000) Hypnotic visual illusionalters color processing in the brain American Journal ofPsychiatry 157 1279 ndash1284

Laureys S Faymonville M E Luxen A Lamy M Franck Gamp Maquet P (2000) Restoration of thalamocorticalconnectivity after recovery from persistent vegetative stateLancet 355 1790ndash1791

Lou H C Kjaer T W Friberg L Wildschiodtz G Holm Samp Nowak M (1999) A 15OndashH2O PET study of meditationand the resting state of normal consciousness HumanBrain Mapping 7 98ndash105

Maquet P Degueldre C Delfiore G Aerts J Peters J MLuxen A amp Franck G (1997) Functional neuroanatomyof human slow wave sleep Journal of Neuroscience 172807 ndash2812

Maquet P Faymonville M E Degueldre C Delfiore G

900 Journal of Cognitive Neuroscience Volume 14 Number 6

Franck G Luxen A amp Lamy M (1999) Functionalneuroanatomy of hypnotic state Biological Psychiatry 45327 ndash333

Metzinger T (2000) The subjectivity of subjective experienceA representationalist analysis of the first-person perspectiveIn T Metzinger (Ed) Neural correlates of consciousnessEmprical and conceptual questions (pp 285 ndash306)Cambridge MIT Press

Nobre A C Sebestyen G N Gitelman D R MesulamM M Frackowiak R S amp Frith C D (1997) Functionallocalization of the system for visuospatial attention usingpositron emission tomography Brain 120 515 ndash533

Pardo J V Fox P T amp Raichle M E (1991) Localization of ahuman system for sustained attention by positron emissiontomography Nature 349 61ndash64

Paus T (2001) Primate anterior cingulate cortex Wheremotor control drive and cognition interface NatureReviews Neuroscience 2 417 ndash424

Paus T Koski L Caramanos Z amp Westbury C (1998)Regional differences in the effects of task difficulty andmotor output on blood flow response in the human anteriorcingulate cortex A review of 107 PET activation studiesNeuroReport 9 R37ndashR47

Paus T Zatorre R J Hofle N Caramanos Z Gotman JPetrides M amp Evans A C (1997) Time-related changesin neural systems underlying attention and arousal duringthe performance of an auditory vigilance task Journal ofCognitive Neuroscience 9 392ndash408

Peyron R Garcia-Larrea L Gregoire M C Costes NConvers P Lavenne F Mauguiere F Michel D ampLaurent B (1999) Haemodynamic brain responses to acutepain in humansmdashSensory and attentional networks Brain122 1765 ndash1779

Picard N amp Strick P L (1996) Motor areas of the medial wallA review of their location and functional activation CerebralCortex 6 342 ndash353

Portas C M Howseman A M Josephs O Turner R ampFrith C D (1998) A specific role for the thalamus inmediating the interaction of attention and arousal inhumans Journal of Neuroscience 18 8979 ndash8989

Posner M I amp Rothbart M K (1998) Attentionself-regulation and consciousness Philosophical

Transactions of the Royal Society of London Series BBiological Sciences 353 1915 ndash1927

Price D D (1996) Hypnotic analgesia Psychological andneural mechanisms In J Barber (Ed) Hypnosis andsuggestions in the treatment of pain (pp 67ndash84) NewYork Norton

Price D D amp Barrell J J (1980) An experiential approachwith quantitative methods A research paradigm Journal ofHumanistic Psychology 20 75ndash95

Rainville P Carrier B Hofbauer R K Bushnell M C ampDuncan G H (1999) Dissociation of pain sensory andaffective dimensions using hypnotic modulation Pain 82159 ndash171

Rainville P Duncan G H Price D D Carrier B ampBushnell M C (1997) Pain affect encoded in humananterior cingulate but not somatosensory cortex Science277 968 ndash971

Rainville P Hofbauer R K Paus T Duncan G H BushnellM C amp Price D D (1999) Cerebral mechanisms ofhypnotic induction and suggestion Journal of CognitiveNeuroscience 11 110ndash125

Ruby P amp Decety J (2001) Effect of subjective perspectivetaking during simulation of action A PET investigation ofagency Nature Neuroscience 4 546 ndash550

Steriade M amp McCarley R W (1990) Brainstem control ofwakefulness and sleep New York Plenum

Szechtman H Woody E Bowers K S amp Nahmias C(1998) Where the imaginal appears real A positronemission tomography study of auditory hallucinationsProceedings of the National Academy of Sciences USA95 1956 ndash1960

Talairach J amp Tournoux P (1988) Co-planar stereotaxicatlas of the human brain New York Thieme

Tellegen A amp Atkinson G (1974) Openness to absorbingand self-altering experiences (lsquolsquoabsorptionrsquorsquo) a trait relatedto hypnotic susceptibility Journal of Abnormal Psychology83 268 ndash277

Toma K Honda M Hanakawa T Okada T Fukuyama HIkeda A Nishizawa S Konishi J amp Shibasaki H (1999)Activities of the primary and supplementary motor areasincrease in preparation and execution of voluntary musclerelaxation An event-related fMRI study Journal ofNeuroscience 19 3527 ndash3534

Varela F J amp Shear J (1999) First-person methodologiesWhat why and how Journal of Consciousness Studies 61ndash14

Vingoe F J (1968) The development of a group alert-trancescale International Journal of Clinical and ExperimentalHypnosis 16 120 ndash132

Vingoe F J (1973) Comparison of the Harvard Group Scaleof Hypnotic Susceptibility Form A and the Group AlertTrance Scale in a university population InternationalJournal of Clinical and Experimental Hypnosis 21169 ndash179

Vogt B A amp Gabriel M (1993) Neurobiology of cingulatecortex and limbic thalamus A comprehensive handbookBoston Birkauser

Weitzenhoffer A M (1980) Hypnotic susceptibility revisitedAmerican Journal of Clinical Hypnosis 22 130 ndash146

Willoch F Rosen G Tolle T R Oslashye I Wester H J BernerN Schwaiger M amp Bartenstein P (2000) Phantom limbpain in the human brain Unravelling neural circuitries ofphantom limb pain sensations using positron emissiontomography Annals of Neurology 48 842 ndash849

Worsley K J Evans A C Marrett S amp Neelin P (1992)A three-dimensional statistical analysis for CBF activationstudies in human brain Journal of Cerebral Blood Flow andMetabolism 12 900 ndash918

Rainville et al 901

Page 11: Hypnosis Modulates Activity in Brain Structures Involved in the …pineda/COGS175/readings/Rain... · 2005. 2. 28. · Hypnosis Modulates Activity in Brain Structures Involved in

changes in peripheral arousal and suggests that subjectswere already physically relaxed in the baseline controlcondition This implies that the hypnosis-inducedchanges in self-ratings of relaxation may not simplyreflect changes in lsquolsquoperipheralrsquorsquo arousal but may attestmore specifically of an increase in lsquolsquomentalrsquorsquo relaxationand a reduction in lsquolsquocorticalrsquorsquo arousal This is consistentwith Pricersquos experiential model of hypnosis (see Intro-duction) and with our previous study showing anincrease in slow (delta) EEG activity during hypnosis

Relaxation-related effects observed outside primarysomatomotor areas may partly reflect subjective feelingsof mental ease more closely In the subtraction analysishypnosis-related decreases were found in the rightlateral posterior parietal rCBF both here (x y z 40iexcl52 44) and in our previous study (x y z 46 iexcl50 42from Table 1 in Rainville Hofbauer et al 1999) Herethese changes were strongly but not specifically asso-ciated with relaxation (x y z 39 iexcl49 45 see Table 2Figure 3A) Furthermore after accounting for absorp-tion-related variance right prefrontal activity was neg-atively correlated with relaxation (Table 2) Thoseadditional changes in the right posterior parietal cortexand the right prefrontal cortices may contribute to thesubjective feelings of mental ease rather than or inaddition to physical relaxation

Fronto-Parietal Attention Networks

Absorption-related activity was widespread and bilateralin the prefrontal cortices but peaks were generallystronger in the right hemisphere Positive regressionpeaks were maximal in the ventrolateral frontal corticesover the inferior frontal gyrus and in the anterior insulaA positive absorption-related regression peak was alsosignificant in the right inferior parietal lobule Theseareas also displayed strong coactivation with absorption-related thalamic activity Very similar patterns of activa-tion have been associated with attentional processes intasks involving visual (eg Coull Frackowiak amp Frith1998) auditory (Paus et al 1997) and somatosensorystimuli (Peyron et al 1999) Notably the location of thepositive parietal peak observed here closely matches theactivation sites reported in those studies and the site ofcovariation with the right ventrolateral attention-relatedactivity reported in Paus et al (1997) suggesting theactivation of a similar network The coordinated absorp-tion-related activity observed here in the brainstem thethalamus the ACC the right inferior frontal gyrus andthe right inferior parietal lobule provides very strongevidence that mental absorption is an experiential cor-relate of the activation of the brainrsquos lsquolsquoexecutive atten-tional networkrsquorsquo and suggests that this system plays acritical role in the production of hypnotic states

Negative absorption-related regression peaks werealso found in both the right and left lateral parietalcortices and in the precuneus (see Table 2) These

effects were largely independent of thalamic activity asindicated by the absence of significant effects at theselocations in the covariation analysis (Table 3) The rightposterior parietal cortex has been suggested to con-stitute a vigilanceorientation system (Pardo Fox ampRaichle 1991) and hypnosis-related decreases in thisarea may reflect a relative disengagement towardexternal sources of stimulation Right and left posteriorparietal cortices at the precise sites of relaxation- andabsorption-related decrease in rCBF have been sug-gested to contribute to the monitoring of externalspace and time respectively (Gitelman et al 19961999 Kim et al 1999 Coull amp Nobre 1998 Nobreet al 1997) Although these functions were notdirectly assessed in this experiment the hypnoticinduction procedure includes specific instructions fordecreased orientation to and interest in irrelevantexternal sources of stimulation and previous observa-tions suggest that hypnotic relaxation and absorptionare precursors to some alterations in spatio-temporalorientation and monitoring (Price 1996) Thus wespeculate that those additional experiential changesmay be consequent to relaxation- and absorption-related decreases in posterior parietal activity

Relaxation- and Absorption-Related Effects onOccipital rCBF

The subtraction analysis confirmed the reliability of thehypnosis-related increase in occipital rCBF reported inour previous study (Rainville Hofbauer et al 1999) Wenow show that this effect was associated with the sub-jective experience of hypnotic relaxation (see Table 2relaxation-specific) Consistently our previous studydemonstrated a coupling between occipital increases inrCBF and increases in slow (delta) EEG activity duringhypnosis Similar increases in occipital rCBF andor slowEEG activity had been observed in another study onhypnosis (Maquet et al 1999) and in states of decreasedvigilance (Paus et al 1997) meditation (Lou et al 1999)and slow wave sleep (Kajimura et al 1999 Hofle et al1997) These effects are consistent with our previousproposition that hypnotic induction produces a globaldecrease in cross-modality suppression in unattendedsensory channels leading to a relative disinhibitionof cortical activity (see Paus et al 1997 KawashimaOrsquoSullivan amp Roland 1995)

In contrast negative correlations between rCBF andmental absorption were observed over both occipitallobes (Table 2 Figure 3B) Consistently occipital rCBFwas correlated negatively with thalamic rCBF at theabsorption-specific site (Table 3) These contrastingeffects imply that variations in occipital rCBF are asso-ciated with separate portions of the variance in relaxa-tion and absorption (Note that although absorptionand relaxation were significantly correlated the variancein absorption was largely independent of relaxation see

Rainville et al 897

Methods) For a given level of relaxation the increasein hypnotic absorption could reflect the concurrentengagement of the lsquolsquoexecutive attentional networkrsquorsquowhich exerts an opposite effect over brain areas sub-serving unattended sensory channels (ie a relativefacilitation of cross-modality suppression)

Hypnosis as a State of Consciousness

The representation of the body-self is central to theneurophenomenology of consciousness (Metzinger2000) In the Introduction we have proposed that theinduction of hypnosis produces global changes in sub-jective experience reflecting a modulation of basicaspects of the body-self representation Consistentlythe PET results indicate that hypnosis involves changesin activity within brain structures essential for the basicregulation of states of consciousness self-monitoringand self-regulation Furthermore changes in relaxationand absorption are precursors (although they may notbe essential) to other hypnosis-related effects such asthe diminished tendency to judge monitor and censorthe suspension of usual orientation toward time loca-tion andor sense of self and the experience of onersquosown response as automatic or extra-volitional (Price1996) These dimensions of experience also rely criticallyon self-representation and may depend at least partly oncerebral areas shown here to be involved in hypnosisAmong those changes the increased feeling of automa-ticity an altered feeling of agency may be the mostdistinctive aspect of hypnotic phenomenology (Weitzen-hoffer 1980) Interestingly the sense of agency hasrecently been suggested to involve areas that displayconsistent changes in activity during hypnosis such asthe right inferior parietal cortex the precuneus and thesomatosensory cortices (Blakemore amp Decety 2001Ruby amp Decety 2001) The modulation of activityobserved here within those areas is consistent withthe interpretation that hypnosis produces changes inself-representation construed as an essential element forconscious experience

Conclusion

The present study used self-ratings of subjective feelingsof mental relaxation and mental absorption to map brainareas involved in hypnosis We replicated previous find-ings and further demonstrated that hypnotic relaxationand absorption reflect changes in brain activity withinregions involved in the control of consciousness statesand in self-regulation such as the brainstem the thala-mus and the ACC The coordinated activity within thesestructures and other absorption-related areas such asthe ventrolateral frontal and right posterior parietalcortices has been previously shown to underlie theregulation of the content of consciousness throughmechanisms of executive attention We must recognize

that our findings are correlative in nature and arerelevant to hypnosis to the extent that mental relaxationand absorption are conceived as basic experientialdimensions that characterize hypnotic phenomenaWe further speculate that these changes in subjectiveexperience and brain activity may contribute to otherhypnosis-related effects such as the altered feeling ofagency experienced during hypnosis These findings areconsistent with the notion that hypnotic states areachieved through the modulation of activity within adistributed network of cerebral structures involved inthe regulation of consciousness states

METHODS

Subjects

Ten right-handed subjects (4 men 6 women) wereselected from a group of 22 volunteers as a part of astudy on the hypnotic modulation of pain (Hofbaueret al 2001) Hypnotic susceptibility was assessed usingthe SHSS-A administered between scans (range 111ndash1011 mean plusmn SD 69 plusmn28) The Ethics Committee ofthe Montreal Neurological Institute (MNI) approved allprocedures and subjects signed a consent form describ-ing the procedure and affirming their right to withdrawfrom the experiment without prejudice

Experimental Procedure

We report the results obtained in eight scans acquired ina restful baseline and hypnosis condition Hypnoticinduction started immediately after Scan 4 and wassustained in the remaining scans by repeating inductioninstructions between scans Instructions included sug-gestions for (1) increased physical and mental relaxa-tion (2) comfortable feeling of warmth heaviness anddrowsiness (3) sustained passive attention to theexperimenterrsquos voice and to the instructions and (4)decreased concern with and orientation to external andinternal (mental) sources of distraction No specificinstruction for visual imagery was included During allscans the subjectsrsquo eyes were closed and their left handwas immersed in warm or painfully hot water Pain-related activation and four additional scans performedwith suggestions for pain modulation are reported else-where (Hofbauer et al 2001)

Self-Ratings of Mental Relaxation and Absorption

After each scan subjects were instructed to rate (0ndash10)(1) their level of tensionndashrelaxation with lsquolsquo10 being themost relaxed and at ease you can bersquorsquo and (2) their levelof sustained focus of attention with lsquolsquo10 being the mostabsorbed and the largest amount of sustained focusedattention you can gatherrsquorsquo Ratings of relaxation andabsorption were transformed using the rank within sub-jects to (1) control for individual differences (2) prevent

898 Journal of Cognitive Neuroscience Volume 14 Number 6

scaling biases and (3) parallel the analysis of rCBF dataSubjects rated pain on separate scales (0ndash100) Hypno-sis-related increases in relaxation and absorption did notinteract with the stimulation condition (pain vs warmstimulation prsquos gt 10) neither relaxation nor absorptioncorrelated significantly with pain ratings (all prsquos gt 10)and pain was not altered by hypnosis alone [t(9) = 069p = 51]

PET Imaging Methods

rCBF was measured using the H215O bolus injection

method (10 millicuriesscan) without arterial blood sam-pling (Herscovitch Markham amp Raichle 1983) with ahigh-resolution PET scanner operated in 3-D acquisitionmode (Siemens ECAT HR+ 63 slices) Stimulus onsetwas simultaneous with bolus injection and 1-min acquis-ition scans started about 15 sec postinjection (interscaninterval of 12ndash15 min) Data from the first 40 sec ofacquisition were reconstructed and analyzed Each sub-ject also underwent a high-resolution anatomical MRI(160 1-mm sagittal slices acquired on a Philips 15-TGyroscan system) Each PET and MRI volume wasaligned and transformed using software developed atthe MNI to match the MNI standardized Talairach space(Collins Neelin Peters amp Evans 1994 Talairach ampTournoux 1988) PET volumes were smoothed (FWHM= 14 mm) and normalized to the average brain countPeak and cluster analyses were performed (FristonWorsley Frackowiak Mazziotta amp Evans 1994 WorsleyEvans Marrett amp Neelin 1992)

Reliability of Hypnosis-Related Effects

A first analysis was performed using the subtractionmethod (Hypnosis minus Baseline) to evaluate thereliability of the effects reported in our previous study(Table 2 in Rainville Hofbauer et al 1999) We consid-ered that hypnosis-related changes in rCBF were repli-cated when a significant peak was observed within oneresel (Worsley et al 1992) of the peak sites reported inour previous study or when the peak sites were within asignificant cluster

Regression of rCBF on Self-Ratings of Relaxationand Absorption

Regression analyses were used to test the relationbetween ratings and rCBF (GLM) Subject- and stimu-lus-related effects were removed first (ANCOVA) andthe significance of the regression slope between thecovariate of interest and rCBF was estimated usingt tests Relaxation-specific and absorption-specific effectswere further tested using ANCOVAs to remove thevariance shared between absorption and relaxation(R2 = 42 p lt 001) The statistical criterion was setto t gt 258 (two-tailed uncorrected p lt 01) in the

directed searches restricted to the brainstem the thala-mus and the ACC (Table 1 Figure 2) Global searcheffects are significant ( p lt 05) based on peak (t valuegt 420) andor clusters analysis after a correction formultiple comparisons over the gray matter volume(uncorrected p lt 0001) (Table 2 Figure 3)

Thalamic Covariations

A covariation analysis was performed in which the rCBFmeasured in the thalamus was used as the covariate ofinterest after accounting for subject- and stimulus-related variance (ANCOVA see Tables 1 and 3) Becausewe were mainly interested in the relationship betweenthe activity in the thalamus and other absorption-relatedsites the threshold for statistical significance was set tot = 370 ( p = 05 uncorrected p lt 0008) based on thevolume defined by the sum of clusters of voxels showingsignificant absorption-specific effects (186 cm3 seeWorsley et al 1992)

Acknowledgments

We thank R Adolphs S Anderson A Bechara A R DamasioH Damasio Susan Lutgendorf J Parvizi and D Tranel fortheir comments on preliminary versions of the manuscriptPET analyses were performed using the software DOTdeveloped by Sylvain Milot and the MINC programs developedby Peter Neelin at the McConnell Brain Imaging Center of theMontreal Neurological Institute This study was supported bythe Medical Research Council (MRC) of Canada Dr Rainvillewas supported by the Medical Research Council of Canada andthe Human Frontier Science Program and Dr Hofbauer wassupported by the Fonds pour la recherche en sante du Quebecand the Royal Victoria Hospital Research Institute

Reprint requests should be sent to Pierre Rainville Faculte deMedecine dentaire Universite de Montreal CP 6128 SuccCentre-ville Montreal Qc H3C 3J7 Canada or via e-mailpierrerainvilleumontrealca

REFERENCES

Aston-Jones G Rajkowski J amp Cohen J (1999) Role of locuscoeruleus in attention and behavioral flexibility BiologicalPsychiatry 46 1309 ndash1320

Badgaiyan R D amp Posner M I (1998) Mapping the cingulatecortex in response selection and monitoring Neuroimage7 255 ndash260

Balthazard C G amp Woody E Z (1992) The spectral analysisof hypnotic performance with respect to lsquolsquoabsorptionrsquorsquoInternational Journal of Clinical and ExperimentalHypnosis 40 21ndash43

Banyai E I amp Hilgard E R (1976) A comparison ofactive-alert hypnotic induction with traditional relaxationinduction Journal of Abnormal Psychology 85 218 ndash224

Blakemore S J amp Decety J (2001) From the perception ofaction to the understanding of intention Nature ReviewsNeuroscience 2 561 ndash567

Braun A R Balkin T J Wesenten N J Carson R EVarga M Baldwin P Selbie S Belenky G amp HerscovitchP (1997) Regional cerebral blood flow throughout the

Rainville et al 899

sleep ndashwake cycle An H2(15)O PET study Brain 1201173 ndash1197

Bush G Luu P amp Posner M I (2000) Cognitive andemotional influences in anterior cingulate cortex Trendsin Cognitive Sciences 4 215 ndash222

Chalmers D J (2000) What is a neural correlate ofconsciousness In T Metzinger (Ed) Neural correlatesof consciousness Empirical and conceptual questions(pp 17ndash39) Cambridge MIT Press

Coe W C amp Sarbin T R (1977) Hypnosis from thestandpoint of a contextualist Annals of the New YorkAcademy of Sciences 296 2ndash13

Cohen J D Botvinick M amp Carter C S (2000) Anteriorcingulate and prefrontal cortex Whorsquos in control NatureNeuroscience 3 421 ndash423

Collins D L Neelin P Peters T M amp Evans A C (1994)Automatic 3D intersubject registration of MR volumetric datain standardized Talairach space Journal of ComputerAssisted Tomography 18 192 ndash205

Coull J T Frackowiak R S amp Frith C D (1998) Monitoringfor target objects Activation of right frontal and parietalcortices with increasing time on task Neuropsychologia 361325 ndash1334

Coull J T amp Nobre A C (1998) Where and when to payattention The neural systems for directing attention tospatial locations and to time intervals as revealed by bothPET and fMRI Journal of Neuroscience 18 7426 ndash7435

Crawford H J (1994) Brain dynamics and hypnosisAttentional and disattentional processes InternationalJournal of Clinical and Experimental Hypnosis 42204 ndash232

Crawford H J amp Gruzelier J H (1992) A midstream view ofthe neuropsychophysiology of hypnosis Recent researchand future directions In E Fromm amp M R Nash (Eds)Contemporary hypnosis research (pp 227 ndash266) New YorkGuilford Press

Crawford H J Knebel T Kaplan L Vendemia J M C XieM Jamison S amp Pribram K H (1998) Hypnotic analgesia1 Somatosensory event-related potential changes to noxiousstimuli and 2 Transfer learning to reduce chronic low backpain International Journal of Clinical and ExperimentalHypnosis 46 92ndash132

Damasio A R (1999) The feeling of what happens Body andemotion and the making of consciousness New YorkHartcourt Brace

De Pascalis V Magurano M R amp Bellusci A (1999) Painperception somatosensory event-related potentials andskin conductance responses to painful stimuli in high midand low hypnotizable subjects Effects of differential painreduction strategies Pain 83 499 ndash508

Devinsky O Morrell M J amp Vogt B A (1995) Contributionsof anterior cingulate cortex to behaviour Brain 118279 ndash306

Fiset P Paus T Daloze T Plourde G Meuret PBonhomme V Hajj-Ali N Backman S B amp Evans A C(1999) Brain mechanisms of propofol-induced loss ofconsciousness in humans A positron emission tomographicstudy Journal of Neuroscience 19 5505 ndash5513

Friston K J Worsley K J Frackowiak R S J Mazziotta J Camp Evans A C (1994) Assessing the significance of focalactivation using their spatial extent Human Brain Mapping1 214ndash220

Gitelman D R Alpert N M Kosslyn S Daffner K ScintoL Thompson W amp Mesulam M M (1996) Functionalimaging of human right hemispheric activation forexploratory movements Annals of Neurology 39 174ndash179

Gitelman D R Nobre A C Parrish T B LaBar K S KimY H Meyer J R amp Mesulam M (1999) A large-scale

distributed network for covert spatial attention Furtheranatomical delineation based on stringent behavioural andcognitive controls Brain 122 1093 ndash1106

Gruzelier J (1998) A working model of the neurophysiologyof hypnosis A review of evidence Contemporary Hypnosis15 3ndash21

Henson R N A Rugg M D Shallice T amp Dolan R J (2000)Confidence in recognition memory for words Dissociatingright prefrontal roles in episodic retrieval Journal ofCognitive Neuroscience 12 913 ndash923

Henson R N A Rugg M D Shallice T Joseph O ampDolan R J (1999) Recollection and familiarity inrecognition memory An event-related functional magneticresonance imaging study Journal of Neuroscience 193962 ndash3972

Herscovitch P Markham J amp Raichle M E (1983) Brainblood flow measured with intravenous H2(15)O I Theoryand error analysis Journal of Nuclear Medicine 24782 ndash789

Hofbauer R K Rainville P Duncan G H amp Bushnell M C(2001) Cortical representation of the sensory dimension ofpain Journal of Neurophysiology 86 402 ndash411

Hofle N Paus T Reutens D Fiset P Gotman J EvansA C amp Jones B E (1997) Regional cerebral blood flowchanges as a function of delta and spindle activity duringslow wave sleep in humans Journal of Neuroscience 174800 ndash4808

Jeanmonod D Magnin M amp Morel A (1996) Low-thresholdcalcium spike bursts in the human thalamus Commonphysiopathology for sensory motor and limbic positivesymptoms Brain 119 363ndash375

Kajimura N Uchiyama M Takayama Y Uchida S Uema TKato M Sekimoto M Watanabe T Nakajima THorikoshi S Ogawa K Nishikawa M Hiroki M Kudo YMatsuda H Okawa M amp Takahashi K (1999) Activityof midbrain reticular formation and neocortex during theprogression of human non-rapid eye movement sleepJournal of Neuroscience 19 10065 ndash10073

Kawashima R OrsquoSullivan B T amp Roland P E (1995)Positron-emission tomography studies of cross-modalityinhibition in selective attentional tasks Closing the lsquolsquomindrsquoseyersquorsquo Proceedings of the National Academy of SciencesUSA 92 5969 ndash5972

Kim Y H Gitelman D R Nobre A C Parrish T BLaBar K S amp Mesulam M M (1999) The large-scaleneural network for spatial attention displays multifunctionaloverlap but differential asymmetry Neuroimage 9269 ndash277

Kinomura S Larsson J Gulyas B amp Roland P E (1996)Activation by attention of the human reticular formationand thalamic intralaminar nuclei Science 271 512ndash515

Kosslyn S M Thompson W L Costantini-Ferrando M FAlpert N M amp Spiegel D (2000) Hypnotic visual illusionalters color processing in the brain American Journal ofPsychiatry 157 1279 ndash1284

Laureys S Faymonville M E Luxen A Lamy M Franck Gamp Maquet P (2000) Restoration of thalamocorticalconnectivity after recovery from persistent vegetative stateLancet 355 1790ndash1791

Lou H C Kjaer T W Friberg L Wildschiodtz G Holm Samp Nowak M (1999) A 15OndashH2O PET study of meditationand the resting state of normal consciousness HumanBrain Mapping 7 98ndash105

Maquet P Degueldre C Delfiore G Aerts J Peters J MLuxen A amp Franck G (1997) Functional neuroanatomyof human slow wave sleep Journal of Neuroscience 172807 ndash2812

Maquet P Faymonville M E Degueldre C Delfiore G

900 Journal of Cognitive Neuroscience Volume 14 Number 6

Franck G Luxen A amp Lamy M (1999) Functionalneuroanatomy of hypnotic state Biological Psychiatry 45327 ndash333

Metzinger T (2000) The subjectivity of subjective experienceA representationalist analysis of the first-person perspectiveIn T Metzinger (Ed) Neural correlates of consciousnessEmprical and conceptual questions (pp 285 ndash306)Cambridge MIT Press

Nobre A C Sebestyen G N Gitelman D R MesulamM M Frackowiak R S amp Frith C D (1997) Functionallocalization of the system for visuospatial attention usingpositron emission tomography Brain 120 515 ndash533

Pardo J V Fox P T amp Raichle M E (1991) Localization of ahuman system for sustained attention by positron emissiontomography Nature 349 61ndash64

Paus T (2001) Primate anterior cingulate cortex Wheremotor control drive and cognition interface NatureReviews Neuroscience 2 417 ndash424

Paus T Koski L Caramanos Z amp Westbury C (1998)Regional differences in the effects of task difficulty andmotor output on blood flow response in the human anteriorcingulate cortex A review of 107 PET activation studiesNeuroReport 9 R37ndashR47

Paus T Zatorre R J Hofle N Caramanos Z Gotman JPetrides M amp Evans A C (1997) Time-related changesin neural systems underlying attention and arousal duringthe performance of an auditory vigilance task Journal ofCognitive Neuroscience 9 392ndash408

Peyron R Garcia-Larrea L Gregoire M C Costes NConvers P Lavenne F Mauguiere F Michel D ampLaurent B (1999) Haemodynamic brain responses to acutepain in humansmdashSensory and attentional networks Brain122 1765 ndash1779

Picard N amp Strick P L (1996) Motor areas of the medial wallA review of their location and functional activation CerebralCortex 6 342 ndash353

Portas C M Howseman A M Josephs O Turner R ampFrith C D (1998) A specific role for the thalamus inmediating the interaction of attention and arousal inhumans Journal of Neuroscience 18 8979 ndash8989

Posner M I amp Rothbart M K (1998) Attentionself-regulation and consciousness Philosophical

Transactions of the Royal Society of London Series BBiological Sciences 353 1915 ndash1927

Price D D (1996) Hypnotic analgesia Psychological andneural mechanisms In J Barber (Ed) Hypnosis andsuggestions in the treatment of pain (pp 67ndash84) NewYork Norton

Price D D amp Barrell J J (1980) An experiential approachwith quantitative methods A research paradigm Journal ofHumanistic Psychology 20 75ndash95

Rainville P Carrier B Hofbauer R K Bushnell M C ampDuncan G H (1999) Dissociation of pain sensory andaffective dimensions using hypnotic modulation Pain 82159 ndash171

Rainville P Duncan G H Price D D Carrier B ampBushnell M C (1997) Pain affect encoded in humananterior cingulate but not somatosensory cortex Science277 968 ndash971

Rainville P Hofbauer R K Paus T Duncan G H BushnellM C amp Price D D (1999) Cerebral mechanisms ofhypnotic induction and suggestion Journal of CognitiveNeuroscience 11 110ndash125

Ruby P amp Decety J (2001) Effect of subjective perspectivetaking during simulation of action A PET investigation ofagency Nature Neuroscience 4 546 ndash550

Steriade M amp McCarley R W (1990) Brainstem control ofwakefulness and sleep New York Plenum

Szechtman H Woody E Bowers K S amp Nahmias C(1998) Where the imaginal appears real A positronemission tomography study of auditory hallucinationsProceedings of the National Academy of Sciences USA95 1956 ndash1960

Talairach J amp Tournoux P (1988) Co-planar stereotaxicatlas of the human brain New York Thieme

Tellegen A amp Atkinson G (1974) Openness to absorbingand self-altering experiences (lsquolsquoabsorptionrsquorsquo) a trait relatedto hypnotic susceptibility Journal of Abnormal Psychology83 268 ndash277

Toma K Honda M Hanakawa T Okada T Fukuyama HIkeda A Nishizawa S Konishi J amp Shibasaki H (1999)Activities of the primary and supplementary motor areasincrease in preparation and execution of voluntary musclerelaxation An event-related fMRI study Journal ofNeuroscience 19 3527 ndash3534

Varela F J amp Shear J (1999) First-person methodologiesWhat why and how Journal of Consciousness Studies 61ndash14

Vingoe F J (1968) The development of a group alert-trancescale International Journal of Clinical and ExperimentalHypnosis 16 120 ndash132

Vingoe F J (1973) Comparison of the Harvard Group Scaleof Hypnotic Susceptibility Form A and the Group AlertTrance Scale in a university population InternationalJournal of Clinical and Experimental Hypnosis 21169 ndash179

Vogt B A amp Gabriel M (1993) Neurobiology of cingulatecortex and limbic thalamus A comprehensive handbookBoston Birkauser

Weitzenhoffer A M (1980) Hypnotic susceptibility revisitedAmerican Journal of Clinical Hypnosis 22 130 ndash146

Willoch F Rosen G Tolle T R Oslashye I Wester H J BernerN Schwaiger M amp Bartenstein P (2000) Phantom limbpain in the human brain Unravelling neural circuitries ofphantom limb pain sensations using positron emissiontomography Annals of Neurology 48 842 ndash849

Worsley K J Evans A C Marrett S amp Neelin P (1992)A three-dimensional statistical analysis for CBF activationstudies in human brain Journal of Cerebral Blood Flow andMetabolism 12 900 ndash918

Rainville et al 901

Page 12: Hypnosis Modulates Activity in Brain Structures Involved in the …pineda/COGS175/readings/Rain... · 2005. 2. 28. · Hypnosis Modulates Activity in Brain Structures Involved in

Methods) For a given level of relaxation the increasein hypnotic absorption could reflect the concurrentengagement of the lsquolsquoexecutive attentional networkrsquorsquowhich exerts an opposite effect over brain areas sub-serving unattended sensory channels (ie a relativefacilitation of cross-modality suppression)

Hypnosis as a State of Consciousness

The representation of the body-self is central to theneurophenomenology of consciousness (Metzinger2000) In the Introduction we have proposed that theinduction of hypnosis produces global changes in sub-jective experience reflecting a modulation of basicaspects of the body-self representation Consistentlythe PET results indicate that hypnosis involves changesin activity within brain structures essential for the basicregulation of states of consciousness self-monitoringand self-regulation Furthermore changes in relaxationand absorption are precursors (although they may notbe essential) to other hypnosis-related effects such asthe diminished tendency to judge monitor and censorthe suspension of usual orientation toward time loca-tion andor sense of self and the experience of onersquosown response as automatic or extra-volitional (Price1996) These dimensions of experience also rely criticallyon self-representation and may depend at least partly oncerebral areas shown here to be involved in hypnosisAmong those changes the increased feeling of automa-ticity an altered feeling of agency may be the mostdistinctive aspect of hypnotic phenomenology (Weitzen-hoffer 1980) Interestingly the sense of agency hasrecently been suggested to involve areas that displayconsistent changes in activity during hypnosis such asthe right inferior parietal cortex the precuneus and thesomatosensory cortices (Blakemore amp Decety 2001Ruby amp Decety 2001) The modulation of activityobserved here within those areas is consistent withthe interpretation that hypnosis produces changes inself-representation construed as an essential element forconscious experience

Conclusion

The present study used self-ratings of subjective feelingsof mental relaxation and mental absorption to map brainareas involved in hypnosis We replicated previous find-ings and further demonstrated that hypnotic relaxationand absorption reflect changes in brain activity withinregions involved in the control of consciousness statesand in self-regulation such as the brainstem the thala-mus and the ACC The coordinated activity within thesestructures and other absorption-related areas such asthe ventrolateral frontal and right posterior parietalcortices has been previously shown to underlie theregulation of the content of consciousness throughmechanisms of executive attention We must recognize

that our findings are correlative in nature and arerelevant to hypnosis to the extent that mental relaxationand absorption are conceived as basic experientialdimensions that characterize hypnotic phenomenaWe further speculate that these changes in subjectiveexperience and brain activity may contribute to otherhypnosis-related effects such as the altered feeling ofagency experienced during hypnosis These findings areconsistent with the notion that hypnotic states areachieved through the modulation of activity within adistributed network of cerebral structures involved inthe regulation of consciousness states

METHODS

Subjects

Ten right-handed subjects (4 men 6 women) wereselected from a group of 22 volunteers as a part of astudy on the hypnotic modulation of pain (Hofbaueret al 2001) Hypnotic susceptibility was assessed usingthe SHSS-A administered between scans (range 111ndash1011 mean plusmn SD 69 plusmn28) The Ethics Committee ofthe Montreal Neurological Institute (MNI) approved allprocedures and subjects signed a consent form describ-ing the procedure and affirming their right to withdrawfrom the experiment without prejudice

Experimental Procedure

We report the results obtained in eight scans acquired ina restful baseline and hypnosis condition Hypnoticinduction started immediately after Scan 4 and wassustained in the remaining scans by repeating inductioninstructions between scans Instructions included sug-gestions for (1) increased physical and mental relaxa-tion (2) comfortable feeling of warmth heaviness anddrowsiness (3) sustained passive attention to theexperimenterrsquos voice and to the instructions and (4)decreased concern with and orientation to external andinternal (mental) sources of distraction No specificinstruction for visual imagery was included During allscans the subjectsrsquo eyes were closed and their left handwas immersed in warm or painfully hot water Pain-related activation and four additional scans performedwith suggestions for pain modulation are reported else-where (Hofbauer et al 2001)

Self-Ratings of Mental Relaxation and Absorption

After each scan subjects were instructed to rate (0ndash10)(1) their level of tensionndashrelaxation with lsquolsquo10 being themost relaxed and at ease you can bersquorsquo and (2) their levelof sustained focus of attention with lsquolsquo10 being the mostabsorbed and the largest amount of sustained focusedattention you can gatherrsquorsquo Ratings of relaxation andabsorption were transformed using the rank within sub-jects to (1) control for individual differences (2) prevent

898 Journal of Cognitive Neuroscience Volume 14 Number 6

scaling biases and (3) parallel the analysis of rCBF dataSubjects rated pain on separate scales (0ndash100) Hypno-sis-related increases in relaxation and absorption did notinteract with the stimulation condition (pain vs warmstimulation prsquos gt 10) neither relaxation nor absorptioncorrelated significantly with pain ratings (all prsquos gt 10)and pain was not altered by hypnosis alone [t(9) = 069p = 51]

PET Imaging Methods

rCBF was measured using the H215O bolus injection

method (10 millicuriesscan) without arterial blood sam-pling (Herscovitch Markham amp Raichle 1983) with ahigh-resolution PET scanner operated in 3-D acquisitionmode (Siemens ECAT HR+ 63 slices) Stimulus onsetwas simultaneous with bolus injection and 1-min acquis-ition scans started about 15 sec postinjection (interscaninterval of 12ndash15 min) Data from the first 40 sec ofacquisition were reconstructed and analyzed Each sub-ject also underwent a high-resolution anatomical MRI(160 1-mm sagittal slices acquired on a Philips 15-TGyroscan system) Each PET and MRI volume wasaligned and transformed using software developed atthe MNI to match the MNI standardized Talairach space(Collins Neelin Peters amp Evans 1994 Talairach ampTournoux 1988) PET volumes were smoothed (FWHM= 14 mm) and normalized to the average brain countPeak and cluster analyses were performed (FristonWorsley Frackowiak Mazziotta amp Evans 1994 WorsleyEvans Marrett amp Neelin 1992)

Reliability of Hypnosis-Related Effects

A first analysis was performed using the subtractionmethod (Hypnosis minus Baseline) to evaluate thereliability of the effects reported in our previous study(Table 2 in Rainville Hofbauer et al 1999) We consid-ered that hypnosis-related changes in rCBF were repli-cated when a significant peak was observed within oneresel (Worsley et al 1992) of the peak sites reported inour previous study or when the peak sites were within asignificant cluster

Regression of rCBF on Self-Ratings of Relaxationand Absorption

Regression analyses were used to test the relationbetween ratings and rCBF (GLM) Subject- and stimu-lus-related effects were removed first (ANCOVA) andthe significance of the regression slope between thecovariate of interest and rCBF was estimated usingt tests Relaxation-specific and absorption-specific effectswere further tested using ANCOVAs to remove thevariance shared between absorption and relaxation(R2 = 42 p lt 001) The statistical criterion was setto t gt 258 (two-tailed uncorrected p lt 01) in the

directed searches restricted to the brainstem the thala-mus and the ACC (Table 1 Figure 2) Global searcheffects are significant ( p lt 05) based on peak (t valuegt 420) andor clusters analysis after a correction formultiple comparisons over the gray matter volume(uncorrected p lt 0001) (Table 2 Figure 3)

Thalamic Covariations

A covariation analysis was performed in which the rCBFmeasured in the thalamus was used as the covariate ofinterest after accounting for subject- and stimulus-related variance (ANCOVA see Tables 1 and 3) Becausewe were mainly interested in the relationship betweenthe activity in the thalamus and other absorption-relatedsites the threshold for statistical significance was set tot = 370 ( p = 05 uncorrected p lt 0008) based on thevolume defined by the sum of clusters of voxels showingsignificant absorption-specific effects (186 cm3 seeWorsley et al 1992)

Acknowledgments

We thank R Adolphs S Anderson A Bechara A R DamasioH Damasio Susan Lutgendorf J Parvizi and D Tranel fortheir comments on preliminary versions of the manuscriptPET analyses were performed using the software DOTdeveloped by Sylvain Milot and the MINC programs developedby Peter Neelin at the McConnell Brain Imaging Center of theMontreal Neurological Institute This study was supported bythe Medical Research Council (MRC) of Canada Dr Rainvillewas supported by the Medical Research Council of Canada andthe Human Frontier Science Program and Dr Hofbauer wassupported by the Fonds pour la recherche en sante du Quebecand the Royal Victoria Hospital Research Institute

Reprint requests should be sent to Pierre Rainville Faculte deMedecine dentaire Universite de Montreal CP 6128 SuccCentre-ville Montreal Qc H3C 3J7 Canada or via e-mailpierrerainvilleumontrealca

REFERENCES

Aston-Jones G Rajkowski J amp Cohen J (1999) Role of locuscoeruleus in attention and behavioral flexibility BiologicalPsychiatry 46 1309 ndash1320

Badgaiyan R D amp Posner M I (1998) Mapping the cingulatecortex in response selection and monitoring Neuroimage7 255 ndash260

Balthazard C G amp Woody E Z (1992) The spectral analysisof hypnotic performance with respect to lsquolsquoabsorptionrsquorsquoInternational Journal of Clinical and ExperimentalHypnosis 40 21ndash43

Banyai E I amp Hilgard E R (1976) A comparison ofactive-alert hypnotic induction with traditional relaxationinduction Journal of Abnormal Psychology 85 218 ndash224

Blakemore S J amp Decety J (2001) From the perception ofaction to the understanding of intention Nature ReviewsNeuroscience 2 561 ndash567

Braun A R Balkin T J Wesenten N J Carson R EVarga M Baldwin P Selbie S Belenky G amp HerscovitchP (1997) Regional cerebral blood flow throughout the

Rainville et al 899

sleep ndashwake cycle An H2(15)O PET study Brain 1201173 ndash1197

Bush G Luu P amp Posner M I (2000) Cognitive andemotional influences in anterior cingulate cortex Trendsin Cognitive Sciences 4 215 ndash222

Chalmers D J (2000) What is a neural correlate ofconsciousness In T Metzinger (Ed) Neural correlatesof consciousness Empirical and conceptual questions(pp 17ndash39) Cambridge MIT Press

Coe W C amp Sarbin T R (1977) Hypnosis from thestandpoint of a contextualist Annals of the New YorkAcademy of Sciences 296 2ndash13

Cohen J D Botvinick M amp Carter C S (2000) Anteriorcingulate and prefrontal cortex Whorsquos in control NatureNeuroscience 3 421 ndash423

Collins D L Neelin P Peters T M amp Evans A C (1994)Automatic 3D intersubject registration of MR volumetric datain standardized Talairach space Journal of ComputerAssisted Tomography 18 192 ndash205

Coull J T Frackowiak R S amp Frith C D (1998) Monitoringfor target objects Activation of right frontal and parietalcortices with increasing time on task Neuropsychologia 361325 ndash1334

Coull J T amp Nobre A C (1998) Where and when to payattention The neural systems for directing attention tospatial locations and to time intervals as revealed by bothPET and fMRI Journal of Neuroscience 18 7426 ndash7435

Crawford H J (1994) Brain dynamics and hypnosisAttentional and disattentional processes InternationalJournal of Clinical and Experimental Hypnosis 42204 ndash232

Crawford H J amp Gruzelier J H (1992) A midstream view ofthe neuropsychophysiology of hypnosis Recent researchand future directions In E Fromm amp M R Nash (Eds)Contemporary hypnosis research (pp 227 ndash266) New YorkGuilford Press

Crawford H J Knebel T Kaplan L Vendemia J M C XieM Jamison S amp Pribram K H (1998) Hypnotic analgesia1 Somatosensory event-related potential changes to noxiousstimuli and 2 Transfer learning to reduce chronic low backpain International Journal of Clinical and ExperimentalHypnosis 46 92ndash132

Damasio A R (1999) The feeling of what happens Body andemotion and the making of consciousness New YorkHartcourt Brace

De Pascalis V Magurano M R amp Bellusci A (1999) Painperception somatosensory event-related potentials andskin conductance responses to painful stimuli in high midand low hypnotizable subjects Effects of differential painreduction strategies Pain 83 499 ndash508

Devinsky O Morrell M J amp Vogt B A (1995) Contributionsof anterior cingulate cortex to behaviour Brain 118279 ndash306

Fiset P Paus T Daloze T Plourde G Meuret PBonhomme V Hajj-Ali N Backman S B amp Evans A C(1999) Brain mechanisms of propofol-induced loss ofconsciousness in humans A positron emission tomographicstudy Journal of Neuroscience 19 5505 ndash5513

Friston K J Worsley K J Frackowiak R S J Mazziotta J Camp Evans A C (1994) Assessing the significance of focalactivation using their spatial extent Human Brain Mapping1 214ndash220

Gitelman D R Alpert N M Kosslyn S Daffner K ScintoL Thompson W amp Mesulam M M (1996) Functionalimaging of human right hemispheric activation forexploratory movements Annals of Neurology 39 174ndash179

Gitelman D R Nobre A C Parrish T B LaBar K S KimY H Meyer J R amp Mesulam M (1999) A large-scale

distributed network for covert spatial attention Furtheranatomical delineation based on stringent behavioural andcognitive controls Brain 122 1093 ndash1106

Gruzelier J (1998) A working model of the neurophysiologyof hypnosis A review of evidence Contemporary Hypnosis15 3ndash21

Henson R N A Rugg M D Shallice T amp Dolan R J (2000)Confidence in recognition memory for words Dissociatingright prefrontal roles in episodic retrieval Journal ofCognitive Neuroscience 12 913 ndash923

Henson R N A Rugg M D Shallice T Joseph O ampDolan R J (1999) Recollection and familiarity inrecognition memory An event-related functional magneticresonance imaging study Journal of Neuroscience 193962 ndash3972

Herscovitch P Markham J amp Raichle M E (1983) Brainblood flow measured with intravenous H2(15)O I Theoryand error analysis Journal of Nuclear Medicine 24782 ndash789

Hofbauer R K Rainville P Duncan G H amp Bushnell M C(2001) Cortical representation of the sensory dimension ofpain Journal of Neurophysiology 86 402 ndash411

Hofle N Paus T Reutens D Fiset P Gotman J EvansA C amp Jones B E (1997) Regional cerebral blood flowchanges as a function of delta and spindle activity duringslow wave sleep in humans Journal of Neuroscience 174800 ndash4808

Jeanmonod D Magnin M amp Morel A (1996) Low-thresholdcalcium spike bursts in the human thalamus Commonphysiopathology for sensory motor and limbic positivesymptoms Brain 119 363ndash375

Kajimura N Uchiyama M Takayama Y Uchida S Uema TKato M Sekimoto M Watanabe T Nakajima THorikoshi S Ogawa K Nishikawa M Hiroki M Kudo YMatsuda H Okawa M amp Takahashi K (1999) Activityof midbrain reticular formation and neocortex during theprogression of human non-rapid eye movement sleepJournal of Neuroscience 19 10065 ndash10073

Kawashima R OrsquoSullivan B T amp Roland P E (1995)Positron-emission tomography studies of cross-modalityinhibition in selective attentional tasks Closing the lsquolsquomindrsquoseyersquorsquo Proceedings of the National Academy of SciencesUSA 92 5969 ndash5972

Kim Y H Gitelman D R Nobre A C Parrish T BLaBar K S amp Mesulam M M (1999) The large-scaleneural network for spatial attention displays multifunctionaloverlap but differential asymmetry Neuroimage 9269 ndash277

Kinomura S Larsson J Gulyas B amp Roland P E (1996)Activation by attention of the human reticular formationand thalamic intralaminar nuclei Science 271 512ndash515

Kosslyn S M Thompson W L Costantini-Ferrando M FAlpert N M amp Spiegel D (2000) Hypnotic visual illusionalters color processing in the brain American Journal ofPsychiatry 157 1279 ndash1284

Laureys S Faymonville M E Luxen A Lamy M Franck Gamp Maquet P (2000) Restoration of thalamocorticalconnectivity after recovery from persistent vegetative stateLancet 355 1790ndash1791

Lou H C Kjaer T W Friberg L Wildschiodtz G Holm Samp Nowak M (1999) A 15OndashH2O PET study of meditationand the resting state of normal consciousness HumanBrain Mapping 7 98ndash105

Maquet P Degueldre C Delfiore G Aerts J Peters J MLuxen A amp Franck G (1997) Functional neuroanatomyof human slow wave sleep Journal of Neuroscience 172807 ndash2812

Maquet P Faymonville M E Degueldre C Delfiore G

900 Journal of Cognitive Neuroscience Volume 14 Number 6

Franck G Luxen A amp Lamy M (1999) Functionalneuroanatomy of hypnotic state Biological Psychiatry 45327 ndash333

Metzinger T (2000) The subjectivity of subjective experienceA representationalist analysis of the first-person perspectiveIn T Metzinger (Ed) Neural correlates of consciousnessEmprical and conceptual questions (pp 285 ndash306)Cambridge MIT Press

Nobre A C Sebestyen G N Gitelman D R MesulamM M Frackowiak R S amp Frith C D (1997) Functionallocalization of the system for visuospatial attention usingpositron emission tomography Brain 120 515 ndash533

Pardo J V Fox P T amp Raichle M E (1991) Localization of ahuman system for sustained attention by positron emissiontomography Nature 349 61ndash64

Paus T (2001) Primate anterior cingulate cortex Wheremotor control drive and cognition interface NatureReviews Neuroscience 2 417 ndash424

Paus T Koski L Caramanos Z amp Westbury C (1998)Regional differences in the effects of task difficulty andmotor output on blood flow response in the human anteriorcingulate cortex A review of 107 PET activation studiesNeuroReport 9 R37ndashR47

Paus T Zatorre R J Hofle N Caramanos Z Gotman JPetrides M amp Evans A C (1997) Time-related changesin neural systems underlying attention and arousal duringthe performance of an auditory vigilance task Journal ofCognitive Neuroscience 9 392ndash408

Peyron R Garcia-Larrea L Gregoire M C Costes NConvers P Lavenne F Mauguiere F Michel D ampLaurent B (1999) Haemodynamic brain responses to acutepain in humansmdashSensory and attentional networks Brain122 1765 ndash1779

Picard N amp Strick P L (1996) Motor areas of the medial wallA review of their location and functional activation CerebralCortex 6 342 ndash353

Portas C M Howseman A M Josephs O Turner R ampFrith C D (1998) A specific role for the thalamus inmediating the interaction of attention and arousal inhumans Journal of Neuroscience 18 8979 ndash8989

Posner M I amp Rothbart M K (1998) Attentionself-regulation and consciousness Philosophical

Transactions of the Royal Society of London Series BBiological Sciences 353 1915 ndash1927

Price D D (1996) Hypnotic analgesia Psychological andneural mechanisms In J Barber (Ed) Hypnosis andsuggestions in the treatment of pain (pp 67ndash84) NewYork Norton

Price D D amp Barrell J J (1980) An experiential approachwith quantitative methods A research paradigm Journal ofHumanistic Psychology 20 75ndash95

Rainville P Carrier B Hofbauer R K Bushnell M C ampDuncan G H (1999) Dissociation of pain sensory andaffective dimensions using hypnotic modulation Pain 82159 ndash171

Rainville P Duncan G H Price D D Carrier B ampBushnell M C (1997) Pain affect encoded in humananterior cingulate but not somatosensory cortex Science277 968 ndash971

Rainville P Hofbauer R K Paus T Duncan G H BushnellM C amp Price D D (1999) Cerebral mechanisms ofhypnotic induction and suggestion Journal of CognitiveNeuroscience 11 110ndash125

Ruby P amp Decety J (2001) Effect of subjective perspectivetaking during simulation of action A PET investigation ofagency Nature Neuroscience 4 546 ndash550

Steriade M amp McCarley R W (1990) Brainstem control ofwakefulness and sleep New York Plenum

Szechtman H Woody E Bowers K S amp Nahmias C(1998) Where the imaginal appears real A positronemission tomography study of auditory hallucinationsProceedings of the National Academy of Sciences USA95 1956 ndash1960

Talairach J amp Tournoux P (1988) Co-planar stereotaxicatlas of the human brain New York Thieme

Tellegen A amp Atkinson G (1974) Openness to absorbingand self-altering experiences (lsquolsquoabsorptionrsquorsquo) a trait relatedto hypnotic susceptibility Journal of Abnormal Psychology83 268 ndash277

Toma K Honda M Hanakawa T Okada T Fukuyama HIkeda A Nishizawa S Konishi J amp Shibasaki H (1999)Activities of the primary and supplementary motor areasincrease in preparation and execution of voluntary musclerelaxation An event-related fMRI study Journal ofNeuroscience 19 3527 ndash3534

Varela F J amp Shear J (1999) First-person methodologiesWhat why and how Journal of Consciousness Studies 61ndash14

Vingoe F J (1968) The development of a group alert-trancescale International Journal of Clinical and ExperimentalHypnosis 16 120 ndash132

Vingoe F J (1973) Comparison of the Harvard Group Scaleof Hypnotic Susceptibility Form A and the Group AlertTrance Scale in a university population InternationalJournal of Clinical and Experimental Hypnosis 21169 ndash179

Vogt B A amp Gabriel M (1993) Neurobiology of cingulatecortex and limbic thalamus A comprehensive handbookBoston Birkauser

Weitzenhoffer A M (1980) Hypnotic susceptibility revisitedAmerican Journal of Clinical Hypnosis 22 130 ndash146

Willoch F Rosen G Tolle T R Oslashye I Wester H J BernerN Schwaiger M amp Bartenstein P (2000) Phantom limbpain in the human brain Unravelling neural circuitries ofphantom limb pain sensations using positron emissiontomography Annals of Neurology 48 842 ndash849

Worsley K J Evans A C Marrett S amp Neelin P (1992)A three-dimensional statistical analysis for CBF activationstudies in human brain Journal of Cerebral Blood Flow andMetabolism 12 900 ndash918

Rainville et al 901

Page 13: Hypnosis Modulates Activity in Brain Structures Involved in the …pineda/COGS175/readings/Rain... · 2005. 2. 28. · Hypnosis Modulates Activity in Brain Structures Involved in

scaling biases and (3) parallel the analysis of rCBF dataSubjects rated pain on separate scales (0ndash100) Hypno-sis-related increases in relaxation and absorption did notinteract with the stimulation condition (pain vs warmstimulation prsquos gt 10) neither relaxation nor absorptioncorrelated significantly with pain ratings (all prsquos gt 10)and pain was not altered by hypnosis alone [t(9) = 069p = 51]

PET Imaging Methods

rCBF was measured using the H215O bolus injection

method (10 millicuriesscan) without arterial blood sam-pling (Herscovitch Markham amp Raichle 1983) with ahigh-resolution PET scanner operated in 3-D acquisitionmode (Siemens ECAT HR+ 63 slices) Stimulus onsetwas simultaneous with bolus injection and 1-min acquis-ition scans started about 15 sec postinjection (interscaninterval of 12ndash15 min) Data from the first 40 sec ofacquisition were reconstructed and analyzed Each sub-ject also underwent a high-resolution anatomical MRI(160 1-mm sagittal slices acquired on a Philips 15-TGyroscan system) Each PET and MRI volume wasaligned and transformed using software developed atthe MNI to match the MNI standardized Talairach space(Collins Neelin Peters amp Evans 1994 Talairach ampTournoux 1988) PET volumes were smoothed (FWHM= 14 mm) and normalized to the average brain countPeak and cluster analyses were performed (FristonWorsley Frackowiak Mazziotta amp Evans 1994 WorsleyEvans Marrett amp Neelin 1992)

Reliability of Hypnosis-Related Effects

A first analysis was performed using the subtractionmethod (Hypnosis minus Baseline) to evaluate thereliability of the effects reported in our previous study(Table 2 in Rainville Hofbauer et al 1999) We consid-ered that hypnosis-related changes in rCBF were repli-cated when a significant peak was observed within oneresel (Worsley et al 1992) of the peak sites reported inour previous study or when the peak sites were within asignificant cluster

Regression of rCBF on Self-Ratings of Relaxationand Absorption

Regression analyses were used to test the relationbetween ratings and rCBF (GLM) Subject- and stimu-lus-related effects were removed first (ANCOVA) andthe significance of the regression slope between thecovariate of interest and rCBF was estimated usingt tests Relaxation-specific and absorption-specific effectswere further tested using ANCOVAs to remove thevariance shared between absorption and relaxation(R2 = 42 p lt 001) The statistical criterion was setto t gt 258 (two-tailed uncorrected p lt 01) in the

directed searches restricted to the brainstem the thala-mus and the ACC (Table 1 Figure 2) Global searcheffects are significant ( p lt 05) based on peak (t valuegt 420) andor clusters analysis after a correction formultiple comparisons over the gray matter volume(uncorrected p lt 0001) (Table 2 Figure 3)

Thalamic Covariations

A covariation analysis was performed in which the rCBFmeasured in the thalamus was used as the covariate ofinterest after accounting for subject- and stimulus-related variance (ANCOVA see Tables 1 and 3) Becausewe were mainly interested in the relationship betweenthe activity in the thalamus and other absorption-relatedsites the threshold for statistical significance was set tot = 370 ( p = 05 uncorrected p lt 0008) based on thevolume defined by the sum of clusters of voxels showingsignificant absorption-specific effects (186 cm3 seeWorsley et al 1992)

Acknowledgments

We thank R Adolphs S Anderson A Bechara A R DamasioH Damasio Susan Lutgendorf J Parvizi and D Tranel fortheir comments on preliminary versions of the manuscriptPET analyses were performed using the software DOTdeveloped by Sylvain Milot and the MINC programs developedby Peter Neelin at the McConnell Brain Imaging Center of theMontreal Neurological Institute This study was supported bythe Medical Research Council (MRC) of Canada Dr Rainvillewas supported by the Medical Research Council of Canada andthe Human Frontier Science Program and Dr Hofbauer wassupported by the Fonds pour la recherche en sante du Quebecand the Royal Victoria Hospital Research Institute

Reprint requests should be sent to Pierre Rainville Faculte deMedecine dentaire Universite de Montreal CP 6128 SuccCentre-ville Montreal Qc H3C 3J7 Canada or via e-mailpierrerainvilleumontrealca

REFERENCES

Aston-Jones G Rajkowski J amp Cohen J (1999) Role of locuscoeruleus in attention and behavioral flexibility BiologicalPsychiatry 46 1309 ndash1320

Badgaiyan R D amp Posner M I (1998) Mapping the cingulatecortex in response selection and monitoring Neuroimage7 255 ndash260

Balthazard C G amp Woody E Z (1992) The spectral analysisof hypnotic performance with respect to lsquolsquoabsorptionrsquorsquoInternational Journal of Clinical and ExperimentalHypnosis 40 21ndash43

Banyai E I amp Hilgard E R (1976) A comparison ofactive-alert hypnotic induction with traditional relaxationinduction Journal of Abnormal Psychology 85 218 ndash224

Blakemore S J amp Decety J (2001) From the perception ofaction to the understanding of intention Nature ReviewsNeuroscience 2 561 ndash567

Braun A R Balkin T J Wesenten N J Carson R EVarga M Baldwin P Selbie S Belenky G amp HerscovitchP (1997) Regional cerebral blood flow throughout the

Rainville et al 899

sleep ndashwake cycle An H2(15)O PET study Brain 1201173 ndash1197

Bush G Luu P amp Posner M I (2000) Cognitive andemotional influences in anterior cingulate cortex Trendsin Cognitive Sciences 4 215 ndash222

Chalmers D J (2000) What is a neural correlate ofconsciousness In T Metzinger (Ed) Neural correlatesof consciousness Empirical and conceptual questions(pp 17ndash39) Cambridge MIT Press

Coe W C amp Sarbin T R (1977) Hypnosis from thestandpoint of a contextualist Annals of the New YorkAcademy of Sciences 296 2ndash13

Cohen J D Botvinick M amp Carter C S (2000) Anteriorcingulate and prefrontal cortex Whorsquos in control NatureNeuroscience 3 421 ndash423

Collins D L Neelin P Peters T M amp Evans A C (1994)Automatic 3D intersubject registration of MR volumetric datain standardized Talairach space Journal of ComputerAssisted Tomography 18 192 ndash205

Coull J T Frackowiak R S amp Frith C D (1998) Monitoringfor target objects Activation of right frontal and parietalcortices with increasing time on task Neuropsychologia 361325 ndash1334

Coull J T amp Nobre A C (1998) Where and when to payattention The neural systems for directing attention tospatial locations and to time intervals as revealed by bothPET and fMRI Journal of Neuroscience 18 7426 ndash7435

Crawford H J (1994) Brain dynamics and hypnosisAttentional and disattentional processes InternationalJournal of Clinical and Experimental Hypnosis 42204 ndash232

Crawford H J amp Gruzelier J H (1992) A midstream view ofthe neuropsychophysiology of hypnosis Recent researchand future directions In E Fromm amp M R Nash (Eds)Contemporary hypnosis research (pp 227 ndash266) New YorkGuilford Press

Crawford H J Knebel T Kaplan L Vendemia J M C XieM Jamison S amp Pribram K H (1998) Hypnotic analgesia1 Somatosensory event-related potential changes to noxiousstimuli and 2 Transfer learning to reduce chronic low backpain International Journal of Clinical and ExperimentalHypnosis 46 92ndash132

Damasio A R (1999) The feeling of what happens Body andemotion and the making of consciousness New YorkHartcourt Brace

De Pascalis V Magurano M R amp Bellusci A (1999) Painperception somatosensory event-related potentials andskin conductance responses to painful stimuli in high midand low hypnotizable subjects Effects of differential painreduction strategies Pain 83 499 ndash508

Devinsky O Morrell M J amp Vogt B A (1995) Contributionsof anterior cingulate cortex to behaviour Brain 118279 ndash306

Fiset P Paus T Daloze T Plourde G Meuret PBonhomme V Hajj-Ali N Backman S B amp Evans A C(1999) Brain mechanisms of propofol-induced loss ofconsciousness in humans A positron emission tomographicstudy Journal of Neuroscience 19 5505 ndash5513

Friston K J Worsley K J Frackowiak R S J Mazziotta J Camp Evans A C (1994) Assessing the significance of focalactivation using their spatial extent Human Brain Mapping1 214ndash220

Gitelman D R Alpert N M Kosslyn S Daffner K ScintoL Thompson W amp Mesulam M M (1996) Functionalimaging of human right hemispheric activation forexploratory movements Annals of Neurology 39 174ndash179

Gitelman D R Nobre A C Parrish T B LaBar K S KimY H Meyer J R amp Mesulam M (1999) A large-scale

distributed network for covert spatial attention Furtheranatomical delineation based on stringent behavioural andcognitive controls Brain 122 1093 ndash1106

Gruzelier J (1998) A working model of the neurophysiologyof hypnosis A review of evidence Contemporary Hypnosis15 3ndash21

Henson R N A Rugg M D Shallice T amp Dolan R J (2000)Confidence in recognition memory for words Dissociatingright prefrontal roles in episodic retrieval Journal ofCognitive Neuroscience 12 913 ndash923

Henson R N A Rugg M D Shallice T Joseph O ampDolan R J (1999) Recollection and familiarity inrecognition memory An event-related functional magneticresonance imaging study Journal of Neuroscience 193962 ndash3972

Herscovitch P Markham J amp Raichle M E (1983) Brainblood flow measured with intravenous H2(15)O I Theoryand error analysis Journal of Nuclear Medicine 24782 ndash789

Hofbauer R K Rainville P Duncan G H amp Bushnell M C(2001) Cortical representation of the sensory dimension ofpain Journal of Neurophysiology 86 402 ndash411

Hofle N Paus T Reutens D Fiset P Gotman J EvansA C amp Jones B E (1997) Regional cerebral blood flowchanges as a function of delta and spindle activity duringslow wave sleep in humans Journal of Neuroscience 174800 ndash4808

Jeanmonod D Magnin M amp Morel A (1996) Low-thresholdcalcium spike bursts in the human thalamus Commonphysiopathology for sensory motor and limbic positivesymptoms Brain 119 363ndash375

Kajimura N Uchiyama M Takayama Y Uchida S Uema TKato M Sekimoto M Watanabe T Nakajima THorikoshi S Ogawa K Nishikawa M Hiroki M Kudo YMatsuda H Okawa M amp Takahashi K (1999) Activityof midbrain reticular formation and neocortex during theprogression of human non-rapid eye movement sleepJournal of Neuroscience 19 10065 ndash10073

Kawashima R OrsquoSullivan B T amp Roland P E (1995)Positron-emission tomography studies of cross-modalityinhibition in selective attentional tasks Closing the lsquolsquomindrsquoseyersquorsquo Proceedings of the National Academy of SciencesUSA 92 5969 ndash5972

Kim Y H Gitelman D R Nobre A C Parrish T BLaBar K S amp Mesulam M M (1999) The large-scaleneural network for spatial attention displays multifunctionaloverlap but differential asymmetry Neuroimage 9269 ndash277

Kinomura S Larsson J Gulyas B amp Roland P E (1996)Activation by attention of the human reticular formationand thalamic intralaminar nuclei Science 271 512ndash515

Kosslyn S M Thompson W L Costantini-Ferrando M FAlpert N M amp Spiegel D (2000) Hypnotic visual illusionalters color processing in the brain American Journal ofPsychiatry 157 1279 ndash1284

Laureys S Faymonville M E Luxen A Lamy M Franck Gamp Maquet P (2000) Restoration of thalamocorticalconnectivity after recovery from persistent vegetative stateLancet 355 1790ndash1791

Lou H C Kjaer T W Friberg L Wildschiodtz G Holm Samp Nowak M (1999) A 15OndashH2O PET study of meditationand the resting state of normal consciousness HumanBrain Mapping 7 98ndash105

Maquet P Degueldre C Delfiore G Aerts J Peters J MLuxen A amp Franck G (1997) Functional neuroanatomyof human slow wave sleep Journal of Neuroscience 172807 ndash2812

Maquet P Faymonville M E Degueldre C Delfiore G

900 Journal of Cognitive Neuroscience Volume 14 Number 6

Franck G Luxen A amp Lamy M (1999) Functionalneuroanatomy of hypnotic state Biological Psychiatry 45327 ndash333

Metzinger T (2000) The subjectivity of subjective experienceA representationalist analysis of the first-person perspectiveIn T Metzinger (Ed) Neural correlates of consciousnessEmprical and conceptual questions (pp 285 ndash306)Cambridge MIT Press

Nobre A C Sebestyen G N Gitelman D R MesulamM M Frackowiak R S amp Frith C D (1997) Functionallocalization of the system for visuospatial attention usingpositron emission tomography Brain 120 515 ndash533

Pardo J V Fox P T amp Raichle M E (1991) Localization of ahuman system for sustained attention by positron emissiontomography Nature 349 61ndash64

Paus T (2001) Primate anterior cingulate cortex Wheremotor control drive and cognition interface NatureReviews Neuroscience 2 417 ndash424

Paus T Koski L Caramanos Z amp Westbury C (1998)Regional differences in the effects of task difficulty andmotor output on blood flow response in the human anteriorcingulate cortex A review of 107 PET activation studiesNeuroReport 9 R37ndashR47

Paus T Zatorre R J Hofle N Caramanos Z Gotman JPetrides M amp Evans A C (1997) Time-related changesin neural systems underlying attention and arousal duringthe performance of an auditory vigilance task Journal ofCognitive Neuroscience 9 392ndash408

Peyron R Garcia-Larrea L Gregoire M C Costes NConvers P Lavenne F Mauguiere F Michel D ampLaurent B (1999) Haemodynamic brain responses to acutepain in humansmdashSensory and attentional networks Brain122 1765 ndash1779

Picard N amp Strick P L (1996) Motor areas of the medial wallA review of their location and functional activation CerebralCortex 6 342 ndash353

Portas C M Howseman A M Josephs O Turner R ampFrith C D (1998) A specific role for the thalamus inmediating the interaction of attention and arousal inhumans Journal of Neuroscience 18 8979 ndash8989

Posner M I amp Rothbart M K (1998) Attentionself-regulation and consciousness Philosophical

Transactions of the Royal Society of London Series BBiological Sciences 353 1915 ndash1927

Price D D (1996) Hypnotic analgesia Psychological andneural mechanisms In J Barber (Ed) Hypnosis andsuggestions in the treatment of pain (pp 67ndash84) NewYork Norton

Price D D amp Barrell J J (1980) An experiential approachwith quantitative methods A research paradigm Journal ofHumanistic Psychology 20 75ndash95

Rainville P Carrier B Hofbauer R K Bushnell M C ampDuncan G H (1999) Dissociation of pain sensory andaffective dimensions using hypnotic modulation Pain 82159 ndash171

Rainville P Duncan G H Price D D Carrier B ampBushnell M C (1997) Pain affect encoded in humananterior cingulate but not somatosensory cortex Science277 968 ndash971

Rainville P Hofbauer R K Paus T Duncan G H BushnellM C amp Price D D (1999) Cerebral mechanisms ofhypnotic induction and suggestion Journal of CognitiveNeuroscience 11 110ndash125

Ruby P amp Decety J (2001) Effect of subjective perspectivetaking during simulation of action A PET investigation ofagency Nature Neuroscience 4 546 ndash550

Steriade M amp McCarley R W (1990) Brainstem control ofwakefulness and sleep New York Plenum

Szechtman H Woody E Bowers K S amp Nahmias C(1998) Where the imaginal appears real A positronemission tomography study of auditory hallucinationsProceedings of the National Academy of Sciences USA95 1956 ndash1960

Talairach J amp Tournoux P (1988) Co-planar stereotaxicatlas of the human brain New York Thieme

Tellegen A amp Atkinson G (1974) Openness to absorbingand self-altering experiences (lsquolsquoabsorptionrsquorsquo) a trait relatedto hypnotic susceptibility Journal of Abnormal Psychology83 268 ndash277

Toma K Honda M Hanakawa T Okada T Fukuyama HIkeda A Nishizawa S Konishi J amp Shibasaki H (1999)Activities of the primary and supplementary motor areasincrease in preparation and execution of voluntary musclerelaxation An event-related fMRI study Journal ofNeuroscience 19 3527 ndash3534

Varela F J amp Shear J (1999) First-person methodologiesWhat why and how Journal of Consciousness Studies 61ndash14

Vingoe F J (1968) The development of a group alert-trancescale International Journal of Clinical and ExperimentalHypnosis 16 120 ndash132

Vingoe F J (1973) Comparison of the Harvard Group Scaleof Hypnotic Susceptibility Form A and the Group AlertTrance Scale in a university population InternationalJournal of Clinical and Experimental Hypnosis 21169 ndash179

Vogt B A amp Gabriel M (1993) Neurobiology of cingulatecortex and limbic thalamus A comprehensive handbookBoston Birkauser

Weitzenhoffer A M (1980) Hypnotic susceptibility revisitedAmerican Journal of Clinical Hypnosis 22 130 ndash146

Willoch F Rosen G Tolle T R Oslashye I Wester H J BernerN Schwaiger M amp Bartenstein P (2000) Phantom limbpain in the human brain Unravelling neural circuitries ofphantom limb pain sensations using positron emissiontomography Annals of Neurology 48 842 ndash849

Worsley K J Evans A C Marrett S amp Neelin P (1992)A three-dimensional statistical analysis for CBF activationstudies in human brain Journal of Cerebral Blood Flow andMetabolism 12 900 ndash918

Rainville et al 901

Page 14: Hypnosis Modulates Activity in Brain Structures Involved in the …pineda/COGS175/readings/Rain... · 2005. 2. 28. · Hypnosis Modulates Activity in Brain Structures Involved in

sleep ndashwake cycle An H2(15)O PET study Brain 1201173 ndash1197

Bush G Luu P amp Posner M I (2000) Cognitive andemotional influences in anterior cingulate cortex Trendsin Cognitive Sciences 4 215 ndash222

Chalmers D J (2000) What is a neural correlate ofconsciousness In T Metzinger (Ed) Neural correlatesof consciousness Empirical and conceptual questions(pp 17ndash39) Cambridge MIT Press

Coe W C amp Sarbin T R (1977) Hypnosis from thestandpoint of a contextualist Annals of the New YorkAcademy of Sciences 296 2ndash13

Cohen J D Botvinick M amp Carter C S (2000) Anteriorcingulate and prefrontal cortex Whorsquos in control NatureNeuroscience 3 421 ndash423

Collins D L Neelin P Peters T M amp Evans A C (1994)Automatic 3D intersubject registration of MR volumetric datain standardized Talairach space Journal of ComputerAssisted Tomography 18 192 ndash205

Coull J T Frackowiak R S amp Frith C D (1998) Monitoringfor target objects Activation of right frontal and parietalcortices with increasing time on task Neuropsychologia 361325 ndash1334

Coull J T amp Nobre A C (1998) Where and when to payattention The neural systems for directing attention tospatial locations and to time intervals as revealed by bothPET and fMRI Journal of Neuroscience 18 7426 ndash7435

Crawford H J (1994) Brain dynamics and hypnosisAttentional and disattentional processes InternationalJournal of Clinical and Experimental Hypnosis 42204 ndash232

Crawford H J amp Gruzelier J H (1992) A midstream view ofthe neuropsychophysiology of hypnosis Recent researchand future directions In E Fromm amp M R Nash (Eds)Contemporary hypnosis research (pp 227 ndash266) New YorkGuilford Press

Crawford H J Knebel T Kaplan L Vendemia J M C XieM Jamison S amp Pribram K H (1998) Hypnotic analgesia1 Somatosensory event-related potential changes to noxiousstimuli and 2 Transfer learning to reduce chronic low backpain International Journal of Clinical and ExperimentalHypnosis 46 92ndash132

Damasio A R (1999) The feeling of what happens Body andemotion and the making of consciousness New YorkHartcourt Brace

De Pascalis V Magurano M R amp Bellusci A (1999) Painperception somatosensory event-related potentials andskin conductance responses to painful stimuli in high midand low hypnotizable subjects Effects of differential painreduction strategies Pain 83 499 ndash508

Devinsky O Morrell M J amp Vogt B A (1995) Contributionsof anterior cingulate cortex to behaviour Brain 118279 ndash306

Fiset P Paus T Daloze T Plourde G Meuret PBonhomme V Hajj-Ali N Backman S B amp Evans A C(1999) Brain mechanisms of propofol-induced loss ofconsciousness in humans A positron emission tomographicstudy Journal of Neuroscience 19 5505 ndash5513

Friston K J Worsley K J Frackowiak R S J Mazziotta J Camp Evans A C (1994) Assessing the significance of focalactivation using their spatial extent Human Brain Mapping1 214ndash220

Gitelman D R Alpert N M Kosslyn S Daffner K ScintoL Thompson W amp Mesulam M M (1996) Functionalimaging of human right hemispheric activation forexploratory movements Annals of Neurology 39 174ndash179

Gitelman D R Nobre A C Parrish T B LaBar K S KimY H Meyer J R amp Mesulam M (1999) A large-scale

distributed network for covert spatial attention Furtheranatomical delineation based on stringent behavioural andcognitive controls Brain 122 1093 ndash1106

Gruzelier J (1998) A working model of the neurophysiologyof hypnosis A review of evidence Contemporary Hypnosis15 3ndash21

Henson R N A Rugg M D Shallice T amp Dolan R J (2000)Confidence in recognition memory for words Dissociatingright prefrontal roles in episodic retrieval Journal ofCognitive Neuroscience 12 913 ndash923

Henson R N A Rugg M D Shallice T Joseph O ampDolan R J (1999) Recollection and familiarity inrecognition memory An event-related functional magneticresonance imaging study Journal of Neuroscience 193962 ndash3972

Herscovitch P Markham J amp Raichle M E (1983) Brainblood flow measured with intravenous H2(15)O I Theoryand error analysis Journal of Nuclear Medicine 24782 ndash789

Hofbauer R K Rainville P Duncan G H amp Bushnell M C(2001) Cortical representation of the sensory dimension ofpain Journal of Neurophysiology 86 402 ndash411

Hofle N Paus T Reutens D Fiset P Gotman J EvansA C amp Jones B E (1997) Regional cerebral blood flowchanges as a function of delta and spindle activity duringslow wave sleep in humans Journal of Neuroscience 174800 ndash4808

Jeanmonod D Magnin M amp Morel A (1996) Low-thresholdcalcium spike bursts in the human thalamus Commonphysiopathology for sensory motor and limbic positivesymptoms Brain 119 363ndash375

Kajimura N Uchiyama M Takayama Y Uchida S Uema TKato M Sekimoto M Watanabe T Nakajima THorikoshi S Ogawa K Nishikawa M Hiroki M Kudo YMatsuda H Okawa M amp Takahashi K (1999) Activityof midbrain reticular formation and neocortex during theprogression of human non-rapid eye movement sleepJournal of Neuroscience 19 10065 ndash10073

Kawashima R OrsquoSullivan B T amp Roland P E (1995)Positron-emission tomography studies of cross-modalityinhibition in selective attentional tasks Closing the lsquolsquomindrsquoseyersquorsquo Proceedings of the National Academy of SciencesUSA 92 5969 ndash5972

Kim Y H Gitelman D R Nobre A C Parrish T BLaBar K S amp Mesulam M M (1999) The large-scaleneural network for spatial attention displays multifunctionaloverlap but differential asymmetry Neuroimage 9269 ndash277

Kinomura S Larsson J Gulyas B amp Roland P E (1996)Activation by attention of the human reticular formationand thalamic intralaminar nuclei Science 271 512ndash515

Kosslyn S M Thompson W L Costantini-Ferrando M FAlpert N M amp Spiegel D (2000) Hypnotic visual illusionalters color processing in the brain American Journal ofPsychiatry 157 1279 ndash1284

Laureys S Faymonville M E Luxen A Lamy M Franck Gamp Maquet P (2000) Restoration of thalamocorticalconnectivity after recovery from persistent vegetative stateLancet 355 1790ndash1791

Lou H C Kjaer T W Friberg L Wildschiodtz G Holm Samp Nowak M (1999) A 15OndashH2O PET study of meditationand the resting state of normal consciousness HumanBrain Mapping 7 98ndash105

Maquet P Degueldre C Delfiore G Aerts J Peters J MLuxen A amp Franck G (1997) Functional neuroanatomyof human slow wave sleep Journal of Neuroscience 172807 ndash2812

Maquet P Faymonville M E Degueldre C Delfiore G

900 Journal of Cognitive Neuroscience Volume 14 Number 6

Franck G Luxen A amp Lamy M (1999) Functionalneuroanatomy of hypnotic state Biological Psychiatry 45327 ndash333

Metzinger T (2000) The subjectivity of subjective experienceA representationalist analysis of the first-person perspectiveIn T Metzinger (Ed) Neural correlates of consciousnessEmprical and conceptual questions (pp 285 ndash306)Cambridge MIT Press

Nobre A C Sebestyen G N Gitelman D R MesulamM M Frackowiak R S amp Frith C D (1997) Functionallocalization of the system for visuospatial attention usingpositron emission tomography Brain 120 515 ndash533

Pardo J V Fox P T amp Raichle M E (1991) Localization of ahuman system for sustained attention by positron emissiontomography Nature 349 61ndash64

Paus T (2001) Primate anterior cingulate cortex Wheremotor control drive and cognition interface NatureReviews Neuroscience 2 417 ndash424

Paus T Koski L Caramanos Z amp Westbury C (1998)Regional differences in the effects of task difficulty andmotor output on blood flow response in the human anteriorcingulate cortex A review of 107 PET activation studiesNeuroReport 9 R37ndashR47

Paus T Zatorre R J Hofle N Caramanos Z Gotman JPetrides M amp Evans A C (1997) Time-related changesin neural systems underlying attention and arousal duringthe performance of an auditory vigilance task Journal ofCognitive Neuroscience 9 392ndash408

Peyron R Garcia-Larrea L Gregoire M C Costes NConvers P Lavenne F Mauguiere F Michel D ampLaurent B (1999) Haemodynamic brain responses to acutepain in humansmdashSensory and attentional networks Brain122 1765 ndash1779

Picard N amp Strick P L (1996) Motor areas of the medial wallA review of their location and functional activation CerebralCortex 6 342 ndash353

Portas C M Howseman A M Josephs O Turner R ampFrith C D (1998) A specific role for the thalamus inmediating the interaction of attention and arousal inhumans Journal of Neuroscience 18 8979 ndash8989

Posner M I amp Rothbart M K (1998) Attentionself-regulation and consciousness Philosophical

Transactions of the Royal Society of London Series BBiological Sciences 353 1915 ndash1927

Price D D (1996) Hypnotic analgesia Psychological andneural mechanisms In J Barber (Ed) Hypnosis andsuggestions in the treatment of pain (pp 67ndash84) NewYork Norton

Price D D amp Barrell J J (1980) An experiential approachwith quantitative methods A research paradigm Journal ofHumanistic Psychology 20 75ndash95

Rainville P Carrier B Hofbauer R K Bushnell M C ampDuncan G H (1999) Dissociation of pain sensory andaffective dimensions using hypnotic modulation Pain 82159 ndash171

Rainville P Duncan G H Price D D Carrier B ampBushnell M C (1997) Pain affect encoded in humananterior cingulate but not somatosensory cortex Science277 968 ndash971

Rainville P Hofbauer R K Paus T Duncan G H BushnellM C amp Price D D (1999) Cerebral mechanisms ofhypnotic induction and suggestion Journal of CognitiveNeuroscience 11 110ndash125

Ruby P amp Decety J (2001) Effect of subjective perspectivetaking during simulation of action A PET investigation ofagency Nature Neuroscience 4 546 ndash550

Steriade M amp McCarley R W (1990) Brainstem control ofwakefulness and sleep New York Plenum

Szechtman H Woody E Bowers K S amp Nahmias C(1998) Where the imaginal appears real A positronemission tomography study of auditory hallucinationsProceedings of the National Academy of Sciences USA95 1956 ndash1960

Talairach J amp Tournoux P (1988) Co-planar stereotaxicatlas of the human brain New York Thieme

Tellegen A amp Atkinson G (1974) Openness to absorbingand self-altering experiences (lsquolsquoabsorptionrsquorsquo) a trait relatedto hypnotic susceptibility Journal of Abnormal Psychology83 268 ndash277

Toma K Honda M Hanakawa T Okada T Fukuyama HIkeda A Nishizawa S Konishi J amp Shibasaki H (1999)Activities of the primary and supplementary motor areasincrease in preparation and execution of voluntary musclerelaxation An event-related fMRI study Journal ofNeuroscience 19 3527 ndash3534

Varela F J amp Shear J (1999) First-person methodologiesWhat why and how Journal of Consciousness Studies 61ndash14

Vingoe F J (1968) The development of a group alert-trancescale International Journal of Clinical and ExperimentalHypnosis 16 120 ndash132

Vingoe F J (1973) Comparison of the Harvard Group Scaleof Hypnotic Susceptibility Form A and the Group AlertTrance Scale in a university population InternationalJournal of Clinical and Experimental Hypnosis 21169 ndash179

Vogt B A amp Gabriel M (1993) Neurobiology of cingulatecortex and limbic thalamus A comprehensive handbookBoston Birkauser

Weitzenhoffer A M (1980) Hypnotic susceptibility revisitedAmerican Journal of Clinical Hypnosis 22 130 ndash146

Willoch F Rosen G Tolle T R Oslashye I Wester H J BernerN Schwaiger M amp Bartenstein P (2000) Phantom limbpain in the human brain Unravelling neural circuitries ofphantom limb pain sensations using positron emissiontomography Annals of Neurology 48 842 ndash849

Worsley K J Evans A C Marrett S amp Neelin P (1992)A three-dimensional statistical analysis for CBF activationstudies in human brain Journal of Cerebral Blood Flow andMetabolism 12 900 ndash918

Rainville et al 901

Page 15: Hypnosis Modulates Activity in Brain Structures Involved in the …pineda/COGS175/readings/Rain... · 2005. 2. 28. · Hypnosis Modulates Activity in Brain Structures Involved in

Franck G Luxen A amp Lamy M (1999) Functionalneuroanatomy of hypnotic state Biological Psychiatry 45327 ndash333

Metzinger T (2000) The subjectivity of subjective experienceA representationalist analysis of the first-person perspectiveIn T Metzinger (Ed) Neural correlates of consciousnessEmprical and conceptual questions (pp 285 ndash306)Cambridge MIT Press

Nobre A C Sebestyen G N Gitelman D R MesulamM M Frackowiak R S amp Frith C D (1997) Functionallocalization of the system for visuospatial attention usingpositron emission tomography Brain 120 515 ndash533

Pardo J V Fox P T amp Raichle M E (1991) Localization of ahuman system for sustained attention by positron emissiontomography Nature 349 61ndash64

Paus T (2001) Primate anterior cingulate cortex Wheremotor control drive and cognition interface NatureReviews Neuroscience 2 417 ndash424

Paus T Koski L Caramanos Z amp Westbury C (1998)Regional differences in the effects of task difficulty andmotor output on blood flow response in the human anteriorcingulate cortex A review of 107 PET activation studiesNeuroReport 9 R37ndashR47

Paus T Zatorre R J Hofle N Caramanos Z Gotman JPetrides M amp Evans A C (1997) Time-related changesin neural systems underlying attention and arousal duringthe performance of an auditory vigilance task Journal ofCognitive Neuroscience 9 392ndash408

Peyron R Garcia-Larrea L Gregoire M C Costes NConvers P Lavenne F Mauguiere F Michel D ampLaurent B (1999) Haemodynamic brain responses to acutepain in humansmdashSensory and attentional networks Brain122 1765 ndash1779

Picard N amp Strick P L (1996) Motor areas of the medial wallA review of their location and functional activation CerebralCortex 6 342 ndash353

Portas C M Howseman A M Josephs O Turner R ampFrith C D (1998) A specific role for the thalamus inmediating the interaction of attention and arousal inhumans Journal of Neuroscience 18 8979 ndash8989

Posner M I amp Rothbart M K (1998) Attentionself-regulation and consciousness Philosophical

Transactions of the Royal Society of London Series BBiological Sciences 353 1915 ndash1927

Price D D (1996) Hypnotic analgesia Psychological andneural mechanisms In J Barber (Ed) Hypnosis andsuggestions in the treatment of pain (pp 67ndash84) NewYork Norton

Price D D amp Barrell J J (1980) An experiential approachwith quantitative methods A research paradigm Journal ofHumanistic Psychology 20 75ndash95

Rainville P Carrier B Hofbauer R K Bushnell M C ampDuncan G H (1999) Dissociation of pain sensory andaffective dimensions using hypnotic modulation Pain 82159 ndash171

Rainville P Duncan G H Price D D Carrier B ampBushnell M C (1997) Pain affect encoded in humananterior cingulate but not somatosensory cortex Science277 968 ndash971

Rainville P Hofbauer R K Paus T Duncan G H BushnellM C amp Price D D (1999) Cerebral mechanisms ofhypnotic induction and suggestion Journal of CognitiveNeuroscience 11 110ndash125

Ruby P amp Decety J (2001) Effect of subjective perspectivetaking during simulation of action A PET investigation ofagency Nature Neuroscience 4 546 ndash550

Steriade M amp McCarley R W (1990) Brainstem control ofwakefulness and sleep New York Plenum

Szechtman H Woody E Bowers K S amp Nahmias C(1998) Where the imaginal appears real A positronemission tomography study of auditory hallucinationsProceedings of the National Academy of Sciences USA95 1956 ndash1960

Talairach J amp Tournoux P (1988) Co-planar stereotaxicatlas of the human brain New York Thieme

Tellegen A amp Atkinson G (1974) Openness to absorbingand self-altering experiences (lsquolsquoabsorptionrsquorsquo) a trait relatedto hypnotic susceptibility Journal of Abnormal Psychology83 268 ndash277

Toma K Honda M Hanakawa T Okada T Fukuyama HIkeda A Nishizawa S Konishi J amp Shibasaki H (1999)Activities of the primary and supplementary motor areasincrease in preparation and execution of voluntary musclerelaxation An event-related fMRI study Journal ofNeuroscience 19 3527 ndash3534

Varela F J amp Shear J (1999) First-person methodologiesWhat why and how Journal of Consciousness Studies 61ndash14

Vingoe F J (1968) The development of a group alert-trancescale International Journal of Clinical and ExperimentalHypnosis 16 120 ndash132

Vingoe F J (1973) Comparison of the Harvard Group Scaleof Hypnotic Susceptibility Form A and the Group AlertTrance Scale in a university population InternationalJournal of Clinical and Experimental Hypnosis 21169 ndash179

Vogt B A amp Gabriel M (1993) Neurobiology of cingulatecortex and limbic thalamus A comprehensive handbookBoston Birkauser

Weitzenhoffer A M (1980) Hypnotic susceptibility revisitedAmerican Journal of Clinical Hypnosis 22 130 ndash146

Willoch F Rosen G Tolle T R Oslashye I Wester H J BernerN Schwaiger M amp Bartenstein P (2000) Phantom limbpain in the human brain Unravelling neural circuitries ofphantom limb pain sensations using positron emissiontomography Annals of Neurology 48 842 ndash849

Worsley K J Evans A C Marrett S amp Neelin P (1992)A three-dimensional statistical analysis for CBF activationstudies in human brain Journal of Cerebral Blood Flow andMetabolism 12 900 ndash918

Rainville et al 901


Hypnosis Scripts - American School of Hypnosis · School of Hypnosis Instructors and affiliates. The materials in this manual were designed to be used by hypnosis professionals. They

Hypnosis Scripts - American School of Hypnosis · School of Hypnosis Instructors and affiliates. The materials in this manual were designed to be used by hypnosis professionals. They

Fast Hypnosis

Fast Hypnosis

HYPNOSIS - sasch.co.za

HYPNOSIS - sasch.co.za

Altering Consciousness Through Meditation and Hypnosis...of hypnosis. All forms of hypnosis may actually involve self-hypnosis. All forms of hypnosis may actually involve self-hypnosis.

Altering Consciousness Through Meditation and Hypnosis...of hypnosis. All forms of hypnosis may actually involve self-hypnosis. All forms of hypnosis may actually involve self-hypnosis.

Hypnosis - songee.co.nz · Hypnosis THE SECOND WELL TRUST presents ‘Hypnosis ’ A Teaching from Songee 10th August 2000 CONTENT PART ONE Crystal Light of Love Hypnosis Hypnosis

Hypnosis - songee.co.nz · Hypnosis THE SECOND WELL TRUST presents ‘Hypnosis ’ A Teaching from Songee 10th August 2000 CONTENT PART ONE Crystal Light of Love Hypnosis Hypnosis

Hypnosis: Bowel dysfunction Brigitte Collins, BSc, MSc, Diploma in Hypnosis.

Hypnosis: Bowel dysfunction Brigitte Collins, BSc, MSc, Diploma in Hypnosis.

Hypnosis overview

Hypnosis overview

Mp3 hypnosis hypnosis downloads and free hypnosis

Mp3 hypnosis hypnosis downloads and free hypnosis

41922287 Street Hypnosis Conversational Hypnosis Private Question and Answer Session

41922287 Street Hypnosis Conversational Hypnosis Private Question and Answer Session

Advanced Hypnosis - Law of Attraction Haven · PDF fileContents What is Hypnosis? Is Hypnosis a Mainstream Concept? How Does Hypnosis Work? Who Shouldn’t use Self-Hypnosis? What

Advanced Hypnosis - Law of Attraction Haven · PDF fileContents What is Hypnosis? Is Hypnosis a Mainstream Concept? How Does Hypnosis Work? Who Shouldn’t use Self-Hypnosis? What

Banff Hypnosis 2017 - Clinical Hypnosis

Banff Hypnosis 2017 - Clinical Hypnosis

Exercise & Altered States of Consciousness Michael Galindo - Hannah Kang Scott Garcia COGS175 - 5/30/2007.

Exercise & Altered States of Consciousness Michael Galindo - Hannah Kang Scott Garcia COGS175 - 5/30/2007.

An Explanation of Hypnosis, Self-Hypnosis & NLP (Neuro ...An Explanation of Hypnosis, Self-Hypnosis & NLP (Neuro Linguistic Programming) by A.E. Abedi Taoist-Books.com ... hypnosis

An Explanation of Hypnosis, Self-Hypnosis & NLP (Neuro ...An Explanation of Hypnosis, Self-Hypnosis & NLP (Neuro Linguistic Programming) by A.E. Abedi Taoist-Books.com ... hypnosis

INTRODUCTION - hypnosiseire.com · Clinical Hypnosis for Sexual Dysfunction Clinical Hypnosis for Pain & Suffering Clinical Hypnosis for Enhancing Academic Performance Clinical Hypnosis

INTRODUCTION - hypnosiseire.com · Clinical Hypnosis for Sexual Dysfunction Clinical Hypnosis for Pain & Suffering Clinical Hypnosis for Enhancing Academic Performance Clinical Hypnosis

Hypnosis - Sample Hypnosis Script - Building a Stress-Free Future

Hypnosis - Sample Hypnosis Script - Building a Stress-Free Future

Hetero Hypnosis

Hetero Hypnosis

XIX International Congress of Hypnosis · • Hypnosis and Speech Pathology 25 • Hypnosis with children and adolescents 26 5.2 Medical Hypnosis • Pain 28 • Anesthesia 30 •

XIX International Congress of Hypnosis · • Hypnosis and Speech Pathology 25 • Hypnosis with children and adolescents 26 5.2 Medical Hypnosis • Pain 28 • Anesthesia 30 •

Hypnosis in psychotherapy and hypnosis as psicotherapy

Hypnosis in psychotherapy and hypnosis as psicotherapy

Psilocybin and Consciousness Andy Alexander, Zane Andre Albert Anaya, Dan Lotz COGS175 Dr. Pineda March 12, 2008.

Psilocybin and Consciousness Andy Alexander, Zane Andre Albert Anaya, Dan Lotz COGS175 Dr. Pineda March 12, 2008.

Hypnosis Study

Hypnosis Study