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Research report

The multiple dimensions of sustained attention

Tim Shallicea,b,*, Donald T. Stussc,d, Michael P. Alexandere,f,g,Terence W. Pictonc,d and Dena Derkzenc

aSISSA, Trieste, ItalybInstitute of Cognitive Neuroscience, University College London, UKcRotman Research Institute at Baycrest, Toronto, Ontario, CanadadUniversity of Toronto, Toronto, Ontario, CanadaeHarvard Medical School, Behavioral Neurology Unit, Beth Israel Deaconess Medical Center, Department of Neurology,

Boston, MA, United StatesfYouville Hospital, Cambridge, MA, United StatesgMemory Disorders Research Center, Boston University, Boston, MA, United States

a r t i c l e i n f o

Article history:

Received 6 November 2006

Reviewed 21 January 2007

Revised 2 April 2007

Accepted 5 April 2007

Action editor Carlo Umilta

Published online -

Keywords:

Prefrontal

Numerosity

Attention

Right dorsolateral

Superior Medial

* Corresponding author. Cognitive NeuroscieE-mail address: shallice@sissa.it (T. Shall

0010-9452/$ – see front matter ª 2007 Elsevidoi:10.1016/j.cortex.2007.04.002

Please cite this article in press as: Shallicj.cortex.2007.04.002

a b s t r a c t

Sustained counting (or temporal numerosity judgements) has been one of the key means of

investigating anterior attentional processes. Forty-three patients with localised lesions to

the frontal lobes were assessed on two tests of the ability to count the number (8–22) of

stimuli presented at either a slow (roughly one per 3 sec) or fast (roughly three per sec)

rate. Patients with lesions to the Superior Medial (SM) region (particularly Brodmann areas

24, 32, and 9) were impaired both in the Slow condition and also in the Fast condition,

where they underestimated the number of stimuli. Patients with Right Lateral (RL) lesions

(8, 45, and 46) also had difficulties in the Fast condition, especially when the number of tar-

gets was greater than 15. The results are considered from the perspectives of alternative

positions on anterior attentional processes developed by Posner & Petersen (1990) and by

Stuss et al., (1995). The most plausible interpretation is in terms of energising processes

which involve the SM frontal cortex and monitoring processes which involve the RL frontal

cortex.

ª 2007 Elsevier Masson Srl. All rights reserved.

1. Introduction for perception it may be narrowly focused on one part of space

Attention varies on a number of dimensions (see Evans, 1970).

It may be voluntarily or spontaneously drawn to an object, in

the latter case either under conscious control or not. Attention

may be oriented towards action, thought or perception. It may

be shared between activities or concentrated on one task, and

nce Sector, SISSA, 2-4 viaice).er Masson Srl. All rights

e T et al., The multiple d

or diffusely oriented towards a wide area.

To what extent do these different aspects of attention

involve the same or different neural mechanisms? Posner

and Petersen (1990), developing ideas from Posner (1978),

innovatively proposed the existence of three interacting neu-

ral systems of attention. The first was the orienting system

Beirut, 34014 Trieste, Italy.

reserved.

imensions of sustained attention, Cortex (2008), doi:10.1016/

c o r t e x x x x ( 2 0 0 8 ) 1 – 1 22

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which directed attention spatially to critical stimuli. A second

system was initially characterised in terms of response selec-

tion, for instance for focused attention in selection-for-action,

as in Stroop tasks, or when rapidly occurring signals have to be

responded to, as in serial reaction time paradigms. Later, this

second system became characterised as ‘executive attention’

(Posner and DiGirolamo, 1998; Fernandez-Duque and Posner,

2001). A third system was the ‘alertness’ system, which en-

sured the alert state necessary for carrying out tasks efficiently

when vigilance is needed because environmental stimulation

is low. Alerting can be ‘phasic’ as in increases in response to

a warning signal or ‘tonic’ as in decreases when low levels of

stimulation lead to problems in vigilance situations.

The three components of attention were initially charac-

terised as ‘systems’ with discrete localisations: orienting in

the parietal lobes, superior colliculi and pulvinar, response

selection in the anterior cingulate (ACG), and alertness in

the Right Lateral (RL) prefrontal region. In later formulations

(e.g., Fan et al., 2003, 2005) the components of attention were

described as ‘networks’ with broader localisations: orienting

became parieto-frontal, the response selection (or as it was

now called ‘executive’) network became more extensively me-

dial frontal than just ACG plus lateral prefrontal, and the alert-

ing network became right fronto-parietal (Fernandez-Duque

and Posner, 2001; Fan et al., 2003). It is unclear if these differ-

ent localisations are meant to be the evolution of the original

hypothesis or a distinct new hypothesis about localisations.

The most recent empirical evidence for three networks comes

from neuroimaging (Fan et al., 2005). The Attention Network

Test (ANT) contains three variables which are held to be inde-

pendently related to the functioning of the orienting, execu-

tive and alertness networks (Fan et al., 2002). The orienting

variable activated parietal sites as expected but also the fron-

tal eye fields. The executive control variable activated the ACG

but also several other brain areas. The alerting variable acti-

vated the thalamus and ‘‘anterior and posterior cortical sites’’

specifically right prefrontal.

That spatial orienting involves the inferior parietal lobes,

particularly on the right, is supported by both functional imag-

ing of normal subjects and lesion studies of the spatial neglect

syndrome (see e.g., Corbetta and Shulman, 2002; Mort et al.,

2003; Driver et al., 2004; but see also Karnath et al., 2001). How-

ever we have proposed an alternative method of characteriz-

ing more anteriorly located systems relevant to attention as

a cluster of processes. In our initial theoretical paper on this

topic (Stuss et al., 1995), we only suggested some possible

localisations of these attentional processes and noted the sim-

ilarities and differences of functional characterisation of the

systems with the Posner and Petersen proposals. In subse-

quent papers, we have defined some specific and consistent

anatomy for these processes. Two of these processes are crit-

ical in the present context and these correspond closely ana-

tomically to the localisations of Posner and Petersen’s

alerting and executive systems. One of our systems is held

to be ‘energising’; it is required for initiating and maintaining

preparation to respond and for sustaining the intention to re-

spond (Stuss et al., 2002b, 2005; Alexander et al., 2005) for any

action which is not highly over learned or which must occur at

a particular time. After any action schema has been activated

sufficiently to be selected for operation, its continuing

Please cite this article in press as: Shallice T et al., The multiple dj.cortex.2007.04.002

operation after its initiation requires energization. This ‘ener-

gising system’ may correspond to the ‘cognitive effort’ system

(Hockey, 1993) proposed within information-processing psy-

chology. Evidence that lesions of superior, medial frontal

structures including, but possibly not limited to the ACG, im-

pair ‘‘energising’’ processes is provided by the grossly slowed

performance of such patients in a variety of reaction time

tasks (Stuss et al., 2002b, 2005; Alexander et al., 2005). More-

over manipulations that slow reaction time in the normal sub-

ject show it even more in Superior Medial (SM) patients (Stuss

et al., 2005).

A second critical process we proposed to be that of the con-

trol of active monitoring or checking of the consequences of

one’s actions or of the state of the environment against the

goals of the task, so that compensatory action can be taken

if they deviate (see Shallice, 2006). We held this process to in-

volve predominantly the RL prefrontal cortex. From the per-

spective of the Posner–Petersen theory there is evidence

from both lesion studies and fMRI for a role of right prefrontal

structures in ‘‘alertness’’, from studies where vigilance is re-

quired because the rate of stimulus presentation is low (Pardo

et al., 1991; Wilkins et al., 1987; Rueckert and Grafman, 1996;

Paus et al., 1997; Fernandez-Duque and Posner, 2001; see

also Coull et al., 1996). A recent fMRI study of simple reaction

time to signals occurring at a rate of once every 3–5 sec again

demonstrated activation of a right fronto-parietal network

(Mottaghy et al., 2006); however in this case the anterior cingu-

late was viewed as having a central coordinating role for the

network, a point we will return to later. However, a failure in

vigilance tasks can also be explained on the Stuss et al. theory

as due to a problem in active monitoring. Moreover, lesions of

the RL, prefrontal cortex also lead to a number of other impair-

ments of attention and action that seem more compatible

with a disturbance in a second anterior attentional process

concerned with actively monitoring the appropriateness of

the on-going course-of-action. Thus, we have shown how le-

sions to this region lead to diminished sensitivity to distinc-

tions between targets and non-targets (Stuss et al., 2002b)

and to poor control of timing behaviour (Picton et al., 2006).

In addition we have shown that such lesions lead to problems

in the variable foreperiod reaction time paradigm in which the

time between a warning signal and the target stimulus varies

(Stuss et al., 2005; see also Vallesi et al., 2007 for confirmatory

TMS findings). Normal subjects show a speeding of the re-

sponse when the foreperiod is longer; RL patients show no

such effect. When the foreperiod is long, the patient is held

to fail to actively monitor during the foreperiod that no stim-

ulus has yet occurred and so does not increase preparation ap-

propriately for later-occurring stimuli: no analogous deficit

occurs if the foreperiod is fixed.

There is, in addition, evidence from functional imaging

that the RL prefrontal cortex is involved not only when in-

creasing alertness is required because the subject is in a vigi-

lance situation but also that it has a key role in active

monitoring in fully alert subjects, such as checking memory

judgements (e.g., Henson et al., 1999; Henson et al., 2000; see

Shallice, 2002, 2004 for discussion). In line with these findings

are analogous results in neuropsychological and TMS studies.

Patients with RL frontal lesions make excessive repeated re-

sponses in free recall of word lists (Stuss et al., 1994) and

imensions of sustained attention, Cortex (2008), doi:10.1016/

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many more capture errors in a concept attainment task

(Reverberi et al., 2005), both behaviours suggesting a lapse in

the monitoring of the suitability of on-going behaviour. More-

over, rTMS to RL prefrontal regions leads to subjects failing to

set criteria appropriately in memory recognition studies and

so to make many false positive errors (Rossi et al., 2001).

The models of Posner and Petersen and Stuss et al. have in

common that there are at least two anterior, attentional pro-

cesses involving SM and RL structures, but they differ in the

characterisation and localisation of the processes. To address

these unresolved issues, we returned to one of the critical ex-

perimental tasks: sustained counting of a string of clicks pre-

sented at a slow rate. In this task, there are at least two

procedures available for determining how many items have

been presented in a string. One is by estimation, which both

in monkeys and in humans seems to involve a fronto-parietal

system, which is predominantly right hemisphere based in

humans (Nieder et al., 2006; Piazza et al., 2006). The other is

counting, which involves individuation of each item in the

set, the assignment of an attentional index to each item and

then the use of phonological codes to keep a running total

(Gelman and Gallistel, 1978). In sustained counting paradigms

the optimal strategy is indeed to count, as estimation leads to

a higher error rate (Cordes et al., 2001).

In the sustained counting task the rate of stimuli is much

slower than the optimal rate for counting of one per second

and the number of clicks is well above that available from

any subitising process based on the contents of the immediate

present. The critical challenge of the sustained counting task

is then of maintaining accuracy when an essentially simple

task has to be performed at a much slower rate than optimal

for a time that is sufficiently long such that alertness may

wane. Thus we will argue is a task loading on vigilance, which

we operationally define as a task which is cognitively simple

and yet which shows deterioration over blocks in its perfor-

mance (see Sanders, 1998). Moreover, by contrasting perfor-

mance on the Slow condition with that on a Fast condition

where the rate of presentation is an order of magnitude faster,

a control task can be obtained which differs only in its atten-

tional requirements (vigilance or high-rate processing). A

model such as that of Posner and Petersen would predict dif-

ferent patterns of deficits in the two conditions.

The functional imaging data on sustained counting judge-

ments when alertness is stressed also tend to support a RL

prefrontal component. For instance, when subjects had to

count touches to the foot that occurred at a very slow (roughly

once every 20 sec) rate, there was increased activation of RL

prefrontal cortex (Pardo et al., 1991). However, Ortuno et al.

(2002) found no significant increase in activation of prefrontal

areas comparing a counting task at an easy one per sec rate to

an uncontrolled second task, namely simply listening to the

clicks.

Lesion studies also suggest a role for the right prefrontal

cortex in sustained counting. Wilkins et al. (1987) investigated

sustained counting with rates of either one or seven per sec.

The low rates are cognitively undemanding, so maintaining

vigilance (maintaining alertness in the terminology of Posner

and Petersen) appears to be the main process required for cor-

rect responding given a slow, long train (10–22 targets). When

the presentation rate was slow, there was a significantly

Please cite this article in press as: Shallice T et al., The multiple dj.cortex.2007.04.002

greater impairment for patients with anterior compared

with posterior lesions in the right hemisphere but not in the

left, but the result was not clear because the difference be-

tween the effects of left and right frontal lesions was not sig-

nificant. This result thus provides some support for the Posner

and Petersen position of a right frontal alerting system.

The two theoretical frameworks for the specification and

localisation of components of attention outlined above repre-

sent different ways of describing two distinct processes of

attention which are localised in the RL and SM prefrontal cor-

tex, but they differ in how the theories characterise the oper-

ations of the two brain regions and the predictions they make

concerning the sustained counting paradigm. First, as far as

the RL prefrontal cortex is concerned, any role of boosting

alertness as on the Posner–Petersen theory would predict

a deficit in the Slow condition rather than the Fast one. Active

monitoring, the Stuss et al. position, makes no such predic-

tion; monitoring is as relevant, if not more so, in highly de-

manding rapid tasks as in vigilance conditions. Thus the

Stuss et al. theory would see RL system as involved in both

the Fast and Slow conditions.

Second, as far as the SM structures are concerned, an ex-

ecutive role as in the Posner–Petersen account would see

them as being required more in the more demanding Fast

condition than in the Slow one. However, on the energising

function which is ascribed to these regions by the Stuss

et al. theory, they would be required in both the Slow and

the Fast conditions. Energising is held to be needed when

the rate of occurrence of stimuli differs from the optimal

one for the lower-level systems operating without top–

down control, namely unmodulated contention scheduling

(Norman and Shallice, 1986). This can be because the rate

of presentation is too low, leading to insufficient exogenously

induced arousal or because it is too high when the demand-

ing nature of the task also entails increased cognitive effort.

The present study in neurological patients of the effects of

lesions in different parts of prefrontal cortex on sustained

counting attempted to take advantage of some of the method-

ological lessons from earlier studies. To compare cognitively

demanding situations – rapid counting – to ones requiring vig-

ilance, there are two contrasting rates of presentation and

long trains of stimuli are compared to short ones. The slow

rate was set at one per 3 sec to increase the demand for main-

taining attention. This is a slower rate than the one per sec

one used in the previous study in view of the negative results

of others using that rate (Ortuno et al., 2002). The fast rate

(three per sec) is slower than the corresponding rate in the

earlier study (Wilkins et al., 1987) to allow higher accuracy.

The tasks were presented twice, with the two Slow condition

blocks following one another to check that that condition had

a vigilance component as planned; conditions which stress

vigilance lead to a decrement in performance over blocks

(Sanders, 1998). Moreover, longer strings are compared with

short strings as the former clearly loads more on any vigilance

component. Prior studies have not analysed error types so we

have expanded the assessment of errors to identify any sys-

tematic underestimation or bias in strategy.

To analyze the effects of lesion sites, we classified the le-

sions in much greater detail than the left versus right dichot-

omies of prior studies. The frontal lobes contain four major

imensions of sustained attention, Cortex (2008), doi:10.1016/

Table 2 – Means and SDs of the baselineneuropsychological test results for the four patientgroups and the controls

Group Mean (SD)

NART-Ra DSF DSB Token BNT JOLb BDI

LL 103 (9) 6 (1) 5 (2) 43 (2) 53 (4) 26 (3) 9 (8)

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regions based on differences in cortical and limbic connectiv-

ity; these functional subdivisions are readily identified for

analysis of lesions. We have demonstrated ample evidence

to support this approach (Stuss et al., 1995, 1998, 2002a).

When there is a significant effect for a large region, a second

analysis is made of the relative significance of individual ar-

chitectonic regions (Petrides and Pandya, 1994).

RL 113 (10) 6 (1) 5 (1) 44 (1) 57 (3) 25 (4) 11 (12)

IM 109 (6) 6 (1) 5 (1) 44 (1) 54 (9) 27 (2) 8 (9)

SM 108 (10) 7 (2) 5 (1) 43 (2) 52 (4) 24 (5) 8 (9)

CTL 112 (7) 7 (2) 6 (1) 42 (3) 56 (4) 28 (3) 6 (6)

a NART-R, National Adult Reading Test-Revised; DSF, Digit Span

Forward; DSB, Digit Span Backward; Token, Token Test; BNT,

Boston Naming Test; JOL, Judgement of Line Orientation; and BDI,

Beck Depression Inventory.

b JOL scores are corrected for age and gender.

2. Methods

2.1. Patients

Forty-three patients with a focal frontal lobe lesion with no ev-

idence of diffuse brain pathology were assessed in the post-

acute stage of recovery (range, 2–109 months post-onset,

M¼ 22 months) together with the same number of control

subjects (see Table 1). Aetiologies were all acute acquired dis-

orders: infarction, haemorrhage (including ruptured aneu-

rysms), trauma, and resection of a benign tumour. There

were 4/11 trauma patients in the left frontal group and 8/15

in the Inferior Medial (IM) group, the two groups that were

found to behave normally in the study. There were 3/11

such patients in the SM group and 0/6 in the RL group. Trauma

patients had no evidence of diffuse brain injury, as indicated

by imaging. Duration of coma was less than 1 h for six trauma

patients, less than 1 day in 3, 3–4 days in 3, and no information

was available on this point for the other three. The inclusion

of patients with varied aetiologies allows a greater variety of

lesion localisations within the frontal lobes, because different

aetiologies have predispositions for different regions (Stuss

et al., 1995). Moreover, the localisation of the lesion is more

relevant than the aetiology (Alexander et al., 2005; Elsass

and Hartelius, 1985; Stuss et al., 1994). The patient groups

did not differ significantly in age. To minimize possible con-

founds from other deficits, the patients had adequate compre-

hension, no clinically detectable neglect, and no other

significant neurological or psychiatric disorders. Intellectual

functioning was within the normal range (all IQ scores> 90:

patients – M¼ 108, standard deviation (SD)¼ 8.9; control –

M¼ 112, SD¼ 6.7) (see Table 2). None of the patients had any

impairment of motor control such as paresis, hypokinesia or

spasticity. The patients behaved normally on measures of ne-

glect (line bisection, and double simultaneous stimulation). As

a measure of premorbid intellectual ability, the National Adult

Table 1 – Means and SDs for age, years of education, andlesion size for the four patient groups and the controls(based on Table 3 of Alexander et al. (2005) where furtherinformation can be obtained on aetiology and lesionlocation for the neurological patients tested)

Group Sex Mean (SD)

M/F Age Years of education Lesion size (%)

LL 8/3 43 (12) 13 (2) 1.1 (.91)

RL 4/2 47 (12) 16 (2) 2.0 (1.48)

IM 9/6 45 (15) 14 (2) 2.1 (1.54)

SM 5/6 46 (17) 13 (2) 4.7 (3.7)

CTL 16/22 49 (16) 15 (2)

Please cite this article in press as: Shallice T et al., The multiple dj.cortex.2007.04.002

Reading Test-Revised (NART-R) was administered. Other neu-

ropsychological test measures included Digit Span Forward

(DSF) and Digit Span Backward (DSB), Token Test of language

comprehension, Boston Naming Test (BNT), and in addition

the Beck Depression Inventory (BDI) was used. There were

a number of minor but significant differences (see Alexander

et al., 2005), but all these involved in the Left Lateral (LL) group

which was not impaired on the measures to be reported.

2.2. Lesion anatomy

Based on previous research (Stuss et al., 1998, 2000, 2001),

the patients were assigned to one of four predefined anatom-

ical groups: LL frontal (n¼ 11); RL frontal (n¼ 6); IM (n¼ 15);

and SM (n¼ 11). All lesions were localised with a standard

template (Stuss et al., 2002a), adapted from the methods of

Damasio and Damasio (1989). Seven patients had pathology

extending to non-frontal structures. In all but one case (a

member of IM group with 35% non-frontal extension), the

non-frontal extension was less than 10% of the entire lesion

(range 3.3–8.1, mean¼ 6.1%; four RL, two SM). As will be

noted from the good performance for the IM group, the sin-

gle larger non-frontal extension does not bias the findings.

All the IM patients but two had bilateral lesions. The SM pa-

tients were more diverse; two unilateral left, five were uni-

lateral right and four were bilateral. The lateral groups

could include lateral subcortical lesions involving deep fron-

tal white matter and dorsal caudate (see Stuss et al., 1994 for

rationale). In patients with medial lesions, no IM patients

had a lesion that extended into the SM area, although the

converse was not true (see Stuss et al., 1998 for rationale).

In addition to the analysis based on the four standard ana-

tomical groups, we have evolved a more precise procedure for

mapping task-performance to lesion location (Stuss et al.,

2002a, 2005). First, we identified which particular brain regions

within the frontal lobes were damaged for each patient. This

was achieved by superimposing the scan of each patient on

a brain template based on the Petrides and Pandya (1994) ar-

chitectonic division (P&P areas) of the frontal lobes (see Stuss

et al., 2002a for a description). We also divided the anterior

cingulate into superior and inferior sections. Each of the 54

P&P areas (right and left) and five other regions (right and

left corpus callosum, right and left caudate, and septum) in

imensions of sustained attention, Cortex (2008), doi:10.1016/

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the frontal lobes was then used as an independent dummy

variable that identified the specific architectonic area, includ-

ing hemispheric laterality (e.g., right superior 32). If an individ-

ual patient’s lesion involved a defined architectonic region, it

was coded as 1 for damaged; if not, it was coded as 0. We could

then identify the areas that when damaged were related to

worse performance than normal.

2.3. Experimental procedure

The task involved counting or estimating the number of audi-

tory stimuli presented on a trial. Sets of between 8 and 22 au-

ditory stimuli were used. The auditory stimuli were brief

1000 Hz tones, each lasting 50 msec with rise and fall times

of 5 msec each. The interval between these stimuli was ran-

domly selected in the range 230–280 msec for the Fast condi-

tion and 2500–3500 msec for the Slow condition. The subject

was given feedback as to the accuracy of the count. Following

the practice trials, there were four blocks, each containing 10

trials. The first and fourth of these were at the fast rate and the

second and third were at the slow rate. Subjects were asked to

count the number of tones they heard. They were told that

there would be between 5 and 25 stimuli (so that the subject

would not be limited to the actual range of numbers being

counted). A Fast block lasted about 2 min and a Slow block

just less than 12 min.

Two different measures of the performance were used for

both the Fast and Slow conditions.

(a) Number Correct: the number of correct trials (when the

subject’s count was exactly equal to the actual number of

stimuli) out of 10. (This was the measure used by Wilkins

et al., 1987.)

(b) Signed Accuracy: the mean of the difference between the

number of tones counted by the subject and the actual

number of tones presented.

Measurements were separately obtained for the different

stimulus rates, the different (first and second) blocks of the

task, and for shorter (8–15) or longer (16–22) trains of stimuli.

Fig. 1 – The total Number Correct (out of 10) in the two

blocks of the Slow Count condition for the four patient

groups and the controls. LL stands for Left Lateral group, RL

for Right Lateral group, IM for Inferior Medial group, SM for

Superior Medial group and CTL for Control group.

2.4. Statistical evaluation

The main analysis of variance (ANOVA) design involved three

factors: block (whether the measurement was from the first

or second block of that presentation rate), length of similar

train [shorter (8–15) or longer (16–22)] and the patient group.

The measurements were compared across the subject groups

using two different ANOVA designs. Each patient group and

the Control group (CTL) were entered into a single ANOVA

with separate contrasts comparing each patient group to the

CTL group. If there was a difference for a particular group, a fur-

ther ANOVA was set up to see whether that patient group was

significantly different from the other patient groups combined.

If this effect was not significant, the original difference from

controls was only treated as significant if p< .0125, i.e., a Bon-

ferroni correction with n¼ 4 was applied. This two-stage anal-

ysis was set up first to demonstrate an abnormality and then to

indicate whether it was specific to a particular lesion location.

Please cite this article in press as: Shallice T et al., The multiple dj.cortex.2007.04.002

If there were significant effects on the initial ANOVAs, we

performed a finer anatomical analysis (see Alexander et al.,

2005; Stuss et al., 2005). For each Petrides & Pandya (P&P)

area in the frontal lobes, we identified all the patients who

had lesions in that area and, given there were at least three

such patients, compared their performance on a behavioural

measure (e.g., Number Correct) to all patients who had no

damage to that area using the Mann–Whitney. As the aim

was to be more specific anatomically about a lesion effect al-

ready established in the previous analysis, Bonferroni correc-

tions were not used. We considered all areas with a one-tailed

p< .05 as potentially involved in the processes that deter-

mined the measurement, and considered areas with a one-

tailed p< .01 to be critically involved.

3. Results

3.1. Overall analysis

The basic results for stimuli presented at the slow rate are

shown in Fig. 1 and for the fast rate in Fig. 2. An analysis of

the whole set of findings with five groups and three different

within-group factors (slow/fast; first/second block; and high/

low number) using the statistical procedure described above

was carried out on the mean Number Correct for each subject.

There was a main effect of speed of presentation, perfor-

mance on the slow rate being better than on fast rate

[F(1,76)¼ 31.70; p< .001] and also of the length of the stimulus

train [F(1,76)¼ 67.42; p< .001], performance on longer trains

being less often correct than on shorter trains. The effect of

longer and shorter trains is shown in Figs. 3 and 4. In addition,

one patient group, namely the SM, was impaired overall

[F(1,76)¼ 14.46; p< .001]. Two groups did significantly worse

than the others with the longer stimulus trains. The SM group

imensions of sustained attention, Cortex (2008), doi:10.1016/

Fig. 2 – The total Number Correct (out of 10) in the two

blocks of the Fast Count condition for the four patient

groups and the controls. LL stands for Left Lateral group, RL

for Right Lateral group, IM for Inferior Medial group, SM for

Superior Medial group and CTL for Control group.

Fig. 4 – The Number Correct for the low (<16) and high

number (>15) stimulus trains in the Fast Count condition

for the four patient groups and the controls. LL stands for

Left Lateral group, RL for Right Lateral group, IM for Inferior

Medial group, SM for Superior Medial group and CTL for

Control group.

c o r t e x x x x ( 2 0 0 8 ) 1 – 1 26

ARTICLE IN PRESS

showed a significant interaction with the length of the stimu-

lus train, being more impaired compared with the CTL group

with longer trains than with shorter ones [F(1,76)¼ 5.7;

p< .05]. A similar interaction was also shown by the RL group

[F(1,76)¼ 7.07; p< .01].

Most critically, there were a number of interactions with

the speed of presentation of the stimulus train. For the SM

group compared with controls, there was an interaction

with the length of stimulus train and speed of presentation

[F(1,76)¼ 9.81; p< .005)]. For the RL group compared with con-

trols there were interactions with the length of the stimulus

Fig. 3 – The Number Correct for low (<16) and high number

(>15) stimulus trains in the Slow Count condition for the

four patient groups and the controls. LL stands for Left

Lateral group, RL for Right Lateral group, IM for Inferior

Medial group, SM for Superior Medial group and CTL for

Control group.

Please cite this article in press as: Shallice T et al., The multiple dj.cortex.2007.04.002

train and speed of presentation [F(1,76)¼ 6.26; p< .02] and

with the presentation block and speed of presentation

[F(1,76)¼ 4.47; p< .05]. As two groups and two different vari-

ables are involved in complex interactions with the speed of

presentation, it is necessary to analyse the results of the

Slow and Fast conditions separately rather than rely on the

overall analysis.

3.2. The Slow condition

The performance of both the patients and controls was worse

on Slow Block 2 than on Slow Block 1 [F(1,76)¼ 7.76; p< .01]

(see Fig. 1). This supports the position that the Slow condition

is a vigilance task, defined by a greater processing demand

when stimuli need to be processed at a slower rate than is op-

timal. Strikingly, it was the SM group, rather than the RL

group, which performed significantly worse overall than

both the CTL group [F(1,76)¼ 20.80; p< .001] and the other le-

sion groups combined [F(1,41)¼ 11.54; p< .005]. Moreover, in

comparison with the CTL group, the SM group’s decline in per-

formance between Slow Block 1 and Slow Block 2 was partic-

ularly rapid [F(1,76)¼ 13.50; p< .001]. Thus it is the SM group

which is affected by the vigilance aspects of the task. On the

Signed Accuracy measure – whether the subject generally

over- or underestimated – there were no significant differ-

ences between any of the patient groups and the controls

(see Table 3).

Comparisons between trials for shorter trains of stimuli (8–

15) and longer trains (16–22) are shown in Fig. 3. There were no

significant effects of this variable. In particular, the SM group,

which showed a deficit in counting the overall number of

stimuli in this Slow condition, produced an almost identical

number of correct responses if the train was shorter or longer

(75% vs. 74%).

imensions of sustained attention, Cortex (2008), doi:10.1016/

Table 3 – Performance of the four patient groups and the control group on the Signed Accuracy measure

Fast Slow

Block 1 Block 2 Block 1 Block 2

Low High Low High Low High Low High

Mean (SD) LL �.23 (.68) �.91 (1.57) �.25 (.76) �.78 (1.59) .15 (.25) �.05 (.09) �.13 (.26) .05 (.25)

RL �.03 (.69) �.92 (1.24) .17 (.29) �.63 (.96) �.07 (.16) .07 (.21) .10 (.28) �.17 (.54)

IM �.18 (.50) �.57 (1.44) �.12 (.89) �.59 (1.68) .11 (.37) �.05 (.14) �.03 (.21) �.05 (.35)

SM �.24 (1.40) �1.55 (2.14) �.31 (.98) �1.86 (2.24) .00 (.36) �.15 (.38) .25 (.60) .05 (.61)

CTL �.06 (.73) �.50 (1.46) .01 (.42) �.42 (1.25) .01 (.06) �.02 (.18) .11 (.58) .00 (.39)

Positive values signify an overestimate and negative ones an underestimate. Low/high refers to the length of the stimulus train.

c o r t e x x x x ( 2 0 0 8 ) 1 – 1 2 7

ARTICLE IN PRESS

3.3. The Fast condition

There were a variety of effects involving two groups, the SM

and RL in the Fast condition. First there was an overall impair-

ment for one group, the SM one. The SM group was again sig-

nificantly worse than the CTL group when the groups were

compared on the Number Correct measure [F(1,76)¼ 6.75;

p< .02]. Second, unlike the Slow condition where performance

deteriorated going from Slow Block 1 to Slow Block 2, in the

Fast condition there was a learning effect; overall there was

a significant improvement in performance in going from Fast

Block 1 to Fast Block 2 for Number Correct [F(1,76)¼ 5.23; p< .0]

(see Fig. 2). This improvement in going from Fast Block 1 to

Fast Block 2 is especially marked in one group, the RL one,

for which there is a significantly greater improvement than

for both the CTL group [F(1,76)¼ 5.53; p< .05], and also for

the other lesion groups combined [F(1,41)¼ 5.25; p< .05]. This

is because the RL group is especially bad in the first block in

which the tones are presented at a fast rate. Post hoc analysis

also supported this finding: the RL group was significantly

worse than the CTL group on Fast Block 1 [F(1,76)¼ 4.93;

p< .05] but not on Fast Block 2.

Significant effects were also obtained for the Fast condition

with respect to the length of the stimulus train, unlike for the

Slow condition. Accuracy as measured by Number Correct was

much greater for shorter stimulus trains than for longer trains

[F(1,76)¼ 47.26; p< .001] (see Fig. 4). Significant interactions be-

tween the length of the stimulus train (short, long) and the pa-

tient group showed that in two groups, the decline with

increasing length of strings was particularly steep compared

with the CTL group: the RL group [F(1,76)¼ 9.54; p< .005] and

the SM group [F(1,76)¼ 10.72; p< .005]. Both the RL group and

the SM group also showed a steeper decline than the other

two lesion groups, namely LL and IM, when going from shorter

to longer stimulus trains [RL: F(1,30)¼ 9.12; p< .01; SM:

F(1,35)¼ 5.43; p< .05]. The RL group declined from 78% to 30%

correct for shorter trains compared with longer ones and the

SM group from 70% to 28%; by contrast the CTL group declined

only from 86% to 64% and the LL group only from 71% to 48%.

For Signed Accuracy the SM group significantly under-

estimated the count by comparison with the CTL group

[F(1,76)¼ 4.31; p< .05] (see Table 3). Also, the longer trains

were more greatly underestimated compared to the shorter

ones across all groups [F(1,76)¼ 12.35; p< .002]. Neither the pa-

tients nor the controls were able to keep up completely accu-

rately with the stimulus train. The effect was significantly

Please cite this article in press as: Shallice T et al., The multiple dj.cortex.2007.04.002

stronger for the SM group both with respect to the CTL group

[F(1,76)¼ 9.64; p< .005] and also compared with the other le-

sion groups combined [F(1,41)¼ 6.05; p< .02]. There was no

significant difference between the RL group and the CTL group

on this measure. Unlike the SM group the RL group did not

underestimate.

3.4. Lesion sizes and sites

In any neuropsychological group study patients inevitably dif-

fer in the size and specific locations of the lesions. This leads

to two different types of issue. First, could possible differences

in the size of the lesion across groups be the origin of the re-

sults obtained in the basic group analysis? Second, can one

be more specific about the location of any effect within the

two critical groups, the RL and the SM?

On the first of these questions, as shown in Table 1, the SM

group has overall the largest mean lesion size. Could the ef-

fects, and particularly those involving the SM group, be attrib-

utable to lesion size? We examined this possibility in two

different ways. First, we examined whether lesion size corre-

lated with performance within relevant patient groups, either

the ones in which there was an effect or in the other groups

combined. Second, we carried out an analysis of covariance

with log lesion size as the covariate for the intergroup compar-

isons which had produced significant effects in the basic

group analysis. As far as the Slow condition is concerned the

relevant Pearson correlation coefficients with lesion size are

negligible (SM: r¼�.04, p¼ .92; LL, RL and IM combined:

r¼�.07, p¼ .70). In addition, the analysis of covariance of

SM versus other lesion groups combined strongly corrobo-

rated the original result with a highly significant effect of

group [F(1,38)¼ 12.64; p¼ .001] and no effect of the covariate

[F(1,38)¼ 1.28; p¼ .26]. Moreover, the interaction of group

and block, which had been significant in the contrast between

the SM group and the controls was now also significant in the

contrast of the SM group compared with other lesion groups

combined [F(1,38)¼ 4.14; p¼ .04]. The performance of the SM

group declined more steeply from Block 1 to Block 2.

The results of the Fast condition also reproduced the

earlier effects. Again, the correlations within relevant

groups between lesion size and performance were negligible

(SM: r¼�.06, p¼ .86; RL: r¼�.06, p¼ .92; LL and IM: r¼ .04,

p¼ .87). In the basic groups analysis there had been an interac-

tion between the SM group and the LL and IM groups com-

bined with respect to train length and also for the RL group

imensions of sustained attention, Cortex (2008), doi:10.1016/

c o r t e x x x x ( 2 0 0 8 ) 1 – 1 28

ARTICLE IN PRESS

compared with the LL and IM groups combined. Analysis of

covariance with log lesion size as the covariate again pro-

duced similar significant interactions of group with stimulus

train length [SM vs. LL and IM: F(1,32)¼ 10.71, p¼ .005; RL vs.

LL and IM: F(1,27)¼ 9.65, p¼ .004]. Moreover the interaction

of group with block which had been found for the RL

group also replicated (RL vs. LL and IM: F(1,27)¼ 4.00, p¼ .02).

Again, the effects of the covariate were completely insignifi-

cant [RL vs. LL and IM: F(1,27)¼ .47, p¼ .50; SM vs. LL and IM:

F(1,32)¼ .35, p¼ .56]. The effects could not be attributed to

lesion size.

To examine whether the effects found in the basic groups

analysis could be made more anatomically specific, for each

prefrontal P&P area, we compared the performance of pa-

tients whose lesions affected the area with that of those pa-

tients where the lesion did not affect it. Effects are only

reported if the area was included in the lesions of at least

three patients. In the Slow condition we used Number Correct

as the critical measure on which to assess this finer grain

anatomy, since the measure had shown a significant effect

in the basic four-group analysis. In this condition there was

a large region for which the decreased accuracy effect was

significant at the .05 level; this involved both medial surfaces

(left 24s ( p< .01) and 9; right 24s ( p< .005), 32s ( p< .005), 9

( p< .001) and 10s) (see Fig. 5). These more precise anatomical

results specify the regions within the SM prefrontal lobes that

underlie the SM group impairment found in the basic analysis.

There were also trends for right areas 9/46 ( p< .06), 8Ad

Fig. 5 – Regions of prefrontal cortex (grey) where performance w

lesion affected the region compared with if it did not. A question

less) with lesions in the area to allow appropriate assessment

Please cite this article in press as: Shallice T et al., The multiple dj.cortex.2007.04.002

( p< .06) and 8Av ( p< .1) which are all on the border of the

SM and RL regions.

In the Fast condition no cortical areas were significant at

the .05 level for the Number Correct measure. Here the more

subtle anatomical analysis was less sensitive than the basic

four-group analysis (which had indicated dysfunction in the

SM and RL groups). There was a similar lack of effect when

considering the difference between first and second blocks

in the Fast condition. However the anatomically more specific

analysis produced striking effects in the Fast condition for the

comparison of the difference in performance between shorter

and longer stimulus trains. We examined these effects on

Number Correct in the Fast condition by subtracting perfor-

mance on the longer stimulus trains from that on the shorter

similar trains, and submitting these to our lesion analysis

based on P&P areas (see Fig. 6). Patients with lesions to two dif-

ferent surface regions both entirely involving the right medial

or lateral prefrontal cortex, gave a larger decline from shorter

to longer stimulus trains (at the .05 level) than patients where

the lesion did not affect the area: a region on the right medial

surface, involving areas 9, 32s and 24s and a region in the RL

region, anatomically separated from the first, involving area

46, area 8Av ( p< .01), and areas 6a and 6b ( p< .01), 44 and

45A. The four-group analysis had indicated a significantly in-

creased fall off in Number Correct with longer stimulus trains

for both the SM group and the RL group, and the more precise

localisations in the RL and right SM regions specify that find-

ing further.

as significantly worse in the Slow condition if the patient’s

mark indicates that there were insufficient patients (two or

of significance.

imensions of sustained attention, Cortex (2008), doi:10.1016/

Fig. 6 – Regions of prefrontal cortex (grey) where the deterioration in performance from low number targets to high number

targets in the Fast condition was significantly greater if the patient’s lesion affected that region compared with if it did not.

c o r t e x x x x ( 2 0 0 8 ) 1 – 1 2 9

ARTICLE IN PRESS

4. Discussion

Patients with lesions to certain regions of the frontal lobe have

significant difficulties in counting the number in a train of

auditory stimuli when stimuli are presented either at a slow

or at a fast rate. This was established in a group of patients

who showed no deficits on baseline neuropsychological tests

which do not stress executive functions, vigilance or rapid

responding. Although certain of the patients had traumatic le-

sions which could have created diffuse axonal injuries, these

were more common in the two groups in which the patients

behaved entirely normally in the counting tasks (LL 4/11; IM

8/15) by comparison with the two subgroups (RL 0/6; SM 3/15)

who showed no impairment. In addition, the use of four ana-

tomically distinct prefrontal groups enabled the critical effects

to be established not only by comparison with a CTL group of

healthy adult subjects but also by comparison between frontal

lobe groups, which is a tighter control procedure. Two differ-

ent types of analysis indicated that these effects could not be

attributed to differences in lesion size between groups.

More specifically, sustained counting judgements were im-

paired following lesions to the SM and to the RL prefrontal cor-

tex. Although this would be expected on the Posner and

Petersen model of the attentional system, the specific pattern

of deficits was different from that which would have been

predicted by their model and more similar to the predictions

from the Stuss et al. model.

Please cite this article in press as: Shallice T et al., The multiple dj.cortex.2007.04.002

The Slow condition is the one which paradigmatically

stresses the process of sustaining attention as required in vig-

ilance tasks which make few other cognitive demands. Pre-

sentation was at an approximately one per 3 sec rate so that

a stimulus train could last up to a minute. Accuracy was

high, but performance declined in all groups from Slow Block

1 to Slow Block 2. This is characteristic of a vigilance test and

confirms that the Slow condition was an appropriate instru-

ment to assess vigilance. Only the SM group was significantly

impaired, compared with both the CTL group and the other le-

sion groups; the group made 26% errors by comparison with

6% by the controls. That the SM group’s impairment is indeed

related to vigilance is shown by the way that this group had

a significantly greater decline in performance from Block 1

to Block 2 than did the CTL group. On both the earlier and re-

vised versions of the Posner and Petersen position this condi-

tion should stress the alertness network, which is related to

the RL frontal network, and is not the network involving

a key SM region – the anterior cingulate.

In the Fast condition, by contrast events must be

responded to at a very rapid rate. The Fast condition is not

the one which should require a Posner and Petersen RL frontal

alerting system. We used a rate of roughly three per sec rather

than the seven per sec rate used by Wilkins et al. There was

one major benefit of this modification. Control subjects (and

some of the frontal groups, e.g., the IM group) scored at

roughly 75% correct (much higher than in Wilkins et al., where

imensions of sustained attention, Cortex (2008), doi:10.1016/

c o r t e x x x x ( 2 0 0 8 ) 1 – 1 210

ARTICLE IN PRESS

nearly all estimates in this condition were incorrect). Inter-

preting accuracy is more revealing when there are no floor

effects. However, this condition remained the most demand-

ing. Subjects failed because they could not process the input

sufficiently rapidly. The condition was qualitatively very dif-

ferent from the vigilance-requiring Slow condition Thus, all

groups tended to underestimate in the Fast condition which

they did not do in the Slow condition. All groups improved

from Fast Block 1 to Fast Block 2, the opposite pattern to the

vigilance-type deterioration found in the Slow condition. In

addition, performance in the Fast condition was worse for lon-

ger than shorter strings in all groups, which was not the case

for the Slow condition.

Two groups had a particular problem in the Fast condition.

First there was the SM group again. They underestimated the

number presented significantly more than did the CTL group.

Moreover, with longer trains they showed deterioration in

performance significantly greater than that of the CTL group

or the two prefrontal groups unaffected on the basic group

analysis. Second, the RL group had a deficit when they were

presented with longer trains, with their decline in perfor-

mance of with longer trains being significantly greater than

that of the CTL group or of the two prefrontal groups who be-

haved like controls on the basic groups analysis. However, the

RL group did not underestimate significantly in this condition

unlike the SM group. Instead they just became generally less

accurate. In addition, they showed particularly poor perfor-

mance on Block 1, recovering to performing at a normal level

on Block 2.

The results of this experiment confirm that lesions of the

medial prefrontal cortex and of the RL frontal lobe impair per-

formance on sustained counting judgements, which fits the

localisations of the anterior attentional and vigilance subsys-

tems of the Posner–Petersen model. Their innovative proposal

that there are separable systems in the SM region, potentially

the anterior cingulate, and in the lateral right prefrontal cor-

tex which play differing attentional roles is strongly sup-

ported. However, the claimed properties of the two systems,

and particularly of the RL one, appear to need some modifica-

tion from the original proposal. What roles do these findings

suggest for these regions?

4.1. The medial region

In the basic four-group analyses, lesions in the SM region pro-

duced the widest range of deficits in the study. In a number of

reaction time studies we have found an impairment following

SM lesions (e g Stuss et al., 2002b, 2005; Alexander et al., 2005).

Moreover, in Stuss et al., (2005) we found that where concen-

tration demands are greater, for instance through having to

maintain the benefit of a warning stimulus for 3s rather than

1s, the slowing in reaction time occurring in patients with

SM lesions was considerably greater than for controls or other

frontal subgroups. Using the theoretical account developed by

Stuss et al. (1995), we argued that when the stimuli and/or the

motivational conditions are not optimal for responding,

lower-level systems need to be energised by a specific SM

prefrontal system. The position of Paus et al. (1997), that the

anterior cingulate is part of an arousal network, would make

a similar prediction. These positions are supported by the

Please cite this article in press as: Shallice T et al., The multiple dj.cortex.2007.04.002

current findings. Thus, patients with SM lesions underesti-

mate rapidly presented trains of stimuli, and perform rela-

tively worse with longer more demanding strings, frequently

being incorrect by two or more. The effect of counting longer

more demanding strings is particularly strong in patients

with right dorsal anterior cingulate and right area 9 lesions.

What is, however, suggested by the current results is that

this system comes into play not only when rapid rates of re-

sponses need to be produced, but also in more classic vigi-

lance situations, with low rates of input to be processed,

again as predicted by the Stuss et al. (1995) model. It also fits

with the perspective of Sturm and Willmes (2001) who have

argued that the abilities to respond rapidly and to be vigilant

both depend on a common alerting network. They assume

that the anterior cingulate exerts top–down control on this

network but also that it includes the lateral prefrontal cortex,

which we will argue shortly has a somewhat different role.

Further confirmatory evidence was provided by the findings

of Mottaghy et al. (2006) who required subjects to respond rap-

idly to stimuli occurring every 3–5 sec. Their structural equa-

tion modelling showed the right anterior cingulate to play

a central role in the processes involved in producing a re-

sponse but also showed that it was actively connected to the

right frontopolar cortex.

The specific P&P regions involved include the right medial

regions where lesions impair performance in the Fast condi-

tion but also most of the corresponding regions in the left me-

dial areas. Indeed this perspective fits with the idea that SM

structures, and in particular the anterior cingulate, should

be involved in increasing levels of energising or cognitive ef-

fort, and that this is just as relevant for vigilance situations

as for situations in which attention has to be focused so that

rapid or difficult responses can be produced.

There is one surprising result with respect to the SM re-

gions. At the slow rate SM patients do not perform any more

poorly with longer trains than with shorter ones. It appears

that in such an undemanding task what is critical is the tonic

level of energising. This deteriorates markedly in the second

slow block, a very similar effect to that we have found for

such patients in a task where they are required to tap at

a 1.5 sec rate; the SD of inter-tap intervals is completely nor-

mal for the first train of the 50 taps, but deteriorates dramati-

cally in the second such train (Picton et al., 2006). It would

appear in the present situation that once the string is well un-

derway, the self-stimulation of carrying out the task energises

them sufficiently to prevent further lapses.

4.2. The RL region

Patients with lesions in the RL region were impaired, but again

not in a pattern easily explained as defective alertness on the

original Posner and Petersen model. Their difficulty was with

the Fast condition rather than the Slow one, although it

should be noted that in the more detailed anatomical analyses

there is a trend for decrement in the Slow condition in three

RL regions. In addition, there was a significant effect of the

number of targets in the Fast condition; there is a considerably

greater impairment for high rather than low number targets.

From the more detailed anatomical analysis, the Fast condi-

tion requires a wide set of areas on the lateral prefrontal

imensions of sustained attention, Cortex (2008), doi:10.1016/

c o r t e x x x x ( 2 0 0 8 ) 1 – 1 2 11

ARTICLE IN PRESS

surface, basically not abutting the right medial regions; areas

6A, B, 8Av, 44, 45A and 46 are involved.

The localisation might suggest a possible working memory

problem, but the rate is too fast for subjects to sequentially

recognize the tone, remember the previous interim sum and

then augment it. Rather the subject must just count rapidly

and attempt to adjust the rate of counting to the occurrence

of the stimuli in the train.

Why might this set of RL regions be involved on the Stuss

et al. (1995) model? In other situations, such as serial reaction

time, RL patients can produce a long rapid sequence of re-

sponses as well as normal controls (Alexander et al., 2005).

However, as the numbers of the tones being counted increase

so the words being produced sub-vocally need to change from

mainly single syllable words such as ‘eight’ or ‘ten’ to two syl-

lable words such as ‘thirteen’ and ‘twenty’ and then to three

syllable ones such as ‘twenty-one’ and ‘twenty-two’. The sub-

ject must therefore increase the rate at which he or she pro-

duces syllables in order to keep counting synchronised with

the external train of clicks. In the current task a failure to

check the relative rates of the stimulus train against the sub-

vocal running estimate in inner speech in the high number

condition in order to recalibrate the rate of producing syllables

could indeed account for an impairment which manifested

itself only with higher number targets. Thus, for train lengths

up to 20 the average absolute error was .63; for train lengths

over 20 this rose to 2.05. In other situations we have found

that RL patients fail to monitor stimulus occurrence in order

to enhance their speed of response to upcoming stimuli (Stuss

et al., 2005; see also Vallesi et al., 2007). We therefore propose

that the RL lesions impair this checking of a possible discrep-

ancy between counting rate and the external rate of clicks and

so lead to the use of an inflexible maladaptive internal speech

rate. At the slow rate a count can occur in the ample time

before the next stimulus; there is no need to synchronise pre-

cisely the auditory stimuli and the counting rate.

It should be noted that in a recent study of this group (Picton

et al., 2006) on production of a 1.5 sec rate train of clicks, we

found that the RL group was affected in both externally timed

and internally timed tasks and therefore had problems adjust-

ing their response rate to both an external and internal clocks.

It was argued that this was due to a monitoring rather than

a clock problem. The critical regions were however only

a more ventral area rather than ventral and dorsal as involved

in the current study.

5. Conclusion

These findings extend our understanding of the role of pre-

frontal structures in three ways. They support Posner and

Petersen’s model that SM structures, including the anterior

cingulate, and the RL region play key roles in attention. How-

ever, Posner and Petersen’s proposal that the RL frontal region

is critical for low rates (vigilance) is not confirmed. Lesions in

SM structures impair both high and low rates because both

tasks require an attentional energising mechanism. We previ-

ously proposed that energising was centred in the anterior

cingulate (Stuss et al., 1995) and Paus et al. (1997) too has ar-

gued that the anterior cingulate is part of an arousal network

Please cite this article in press as: Shallice T et al., The multiple dj.cortex.2007.04.002

(see also Sturm and Willmes, 2001; Mottaghy et al., 2006). The

current results are largely compatible with these proposals al-

though lesions in a much larger portion of SM regions, partic-

ularly on the right, can affect energising.

The effect of lesions of the RL frontal lobe is more complex.

They do not impair the general alerting or energising func-

tions. Our findings suggest that RL lesions impair on-going

modulation of behaviour by reducing monitoring capacity

which we previously proposed to be controlled by systems

in the RL region (Stuss et al., 1995).

Acknowledgements

This study was funded by the Canadian Institutes of Health

Research, #MT-12853 and #MRC-GR-14974. M. Alexander is

partly supported by NIH (NS 26985), the Heart and Stroke

Foundation Centre for Stroke Recovery and the Louis and

Leah Posluns Centre for Stroke and Cognition at Baycrest.

T. Shallice is partly supported by a PRIN grant. D. Stuss is

the Reva James Leeds Chair in Neuroscience and Research

Leadership. T. Picton is the Anne and Max Tanenbaum Chair

in Cognitive Neuroscience. We are grateful to all of our staff

who have worked on these studies over the years, including

N. Arzumanian, S. Bisschop, B. Boucher, D. Floden, A. Savas

and particularly S. Gillingham for much assistance in the

preparation of the manuscript. We would also like to thank

D. Izukawa and M. Mountain for patient referral for research

participation.

r e f e r e n c e s

Alexander MP, Stuss DT, Shallice T, Picton TW, andGillingham SME. Impaired concentration in patients withfrontal damage: deficits from two anatomically distinct lesionsites. Neurology, 65: 572–579, 2005.

Corbetta M and Shulman GL. Control of goal-directed andstimulus-driven attention in the brain. Nature ReviewsNeuroscience, 3: 201–215, 2002.

Cordes S, Gelman R, Gallistel CR, and Whalen J. Variabilitysignatures distinguish verbal from nonverbal counting forboth large and small numbers. Psychonomic Bulletin & Review, 8:698–707, 2001.

Coull JT, Frith CD, Frackowiak RSJ, and Grasby PM. A fronto-parietal network for rapid information processing: a PET studyof sustained attention and working memory. Neuropsychologia,34: 1085–1095, 1996.

Damasio H and Damasio AR. Lesion Analysis in Neuropsychology.New York: Oxford University Press, 1989.

Driver J, Vuilleumier P, and Husain M. Spatial neglect andextinction. In Gazzaniga M (Ed), The New Cognitive NeurosciencesIII. Cambridge, MA: MIT Press, 2004: 589–606.

Elsass P and Hartelius H. Reaction time and brain disease:relations to location, etiology and progression of cerebraldysfunction. Acta Neurologica Scandinavica, 71: 11–19, 1985.

Evans CO. The Subject of Consciousness. London: George Allen andUnwin, 1970.

Fan J, Flombaum JI, Mccandliss BD, Thomas KM, and Posner MI.Cognitive and brain consequences of conflict. NeuroImage, 18:42–57, 2003.

imensions of sustained attention, Cortex (2008), doi:10.1016/

c o r t e x x x x ( 2 0 0 8 ) 1 – 1 212

ARTICLE IN PRESS

Fan J, McCandliss BD, Fossella J, Flombaum JI, and Posner MI. Theactivation of attentional networks. NeuroImage, 26: 471–479,2005.

Fan J, McCandliss BD, Sommer T, Raz A, and Posner MI. Testingthe efficiency and independence of attentional networks.Journal of Cognitive Neuroscience, 14: 340–347, 2002.

Fernandez-Duque D and Posner MI. Brain imaging of attentionalnetworks in normal and pathological states. Journal of Clinicaland Experimental Neuropsychology, 23: 74–93, 2001.

Gelman R and Gallistel CR. The Child’s Understanding of Number.Cambridge, MA: Harvard University Press, 1978.

Henson RNA, Rugg MD, Shallice T, and Dolan RJ. Confidence inrecognition memory for words: dissociating right prefrontalroles in episodic retrieval. Journal of Cognitive Neuroscience, 12:913–923, 2000.

Henson RNA, Rugg MD, Shallice T, Josephs O, and Dolan RJ.Recollection and familiarity in recognition memory: an event-related fMRI study. Journal of Neuroscience, 19: 3962–3972, 1999.

Hockey GRJ. Cognitive energetic control mechanisms in themanagement of work demands and psychological health. InBaddeley AD, and Weiskrantz L (Eds), Attention, Selection,Awareness and Control: a Tribute to Donald Broadbent. Oxford:Clarendon Press, 1993: 328–345.

Karnath HO, Ferber S, and Himmelbach M. Spatial awareness isa function of the temporal not the posterior parietal lobe.Nature, 411: 950–953, 2001.

Mort DJ, Malhotra P, Mannan SK, Rorden C, Pambakian A,Kennard C, and Husain M. The anatomy of visual neglect.Brain, 126: 1986–1997, 2003.

Mottaghy FM, Willmes K, Horwitz B, Muller H-W, Krause BJ, andSturm W. Systems level modeling of a neuronal networksubserving intrinsic alertness. NeuroImage, 29: 225–233, 2006.

Nieder A, Diester I, and Tudusciuc O. Temporal and spatialenumeration processes in the primate parietal cortex. Science,313: 1431–1435, 2006.

Norman DA and Shallice T. Attention to action: Willed andautomatic control of behaviour. In Davidson RJ, Schwartz GE,and Shapiro D (Eds), Consciousness and Self Regulation: Advancesin Research, vol. IV. New York: Plenum, 1986: 1–18 [Reprinted inGazzaniga MS (Ed), Cognitive Neuroscience: a Reader. Malden,MA: Blackwell, 2000].

Ortuno F, Ojeda N, Arbizu J, Lopez P, Marti-Climent JM, Penuelas I,and Cervera S. Sustained attention in a counting task: normalperformance and functional neuroanatomy. NeuroImage, 17:411–420, 2002.

Pardo JV, Fox PT, and Raichle ME. Localization of a human systemfor sustained attention by positron emission tomography.Nature, 349: 61–64, 1991.

Paus T, Zatorre RJ, Hofle N, Caramanos Z, Gotman J, Petrides M,and Evans AC. Time-related changes in neural systemsunderlying attention and arousal during the performance ofan auditory vigilance task. Journal of Cognitive Neuroscience, 9:392–408, 1997.

Petrides M and Pandya DN. Comparative architectonic analysis ofthe human and macaque frontal cortex. In Boller F, andGrafman J (Eds), Handbook of Neuropsychology, vol. 9.Amsterdam: Elsevier, 1994: 17–57.

Piazza M, Mechelli A, Price CJ, and Butterworth B. Exact andapproximate judgements of visual and auditory numerosity:an fMRI study. Brain Research, 1106: 111–122, 2006.

Picton TW, Stuss DT, Shallice T, Alexander MP, and Gillingham S.Keeping time: effects of focal frontal lesions. Neuropsychologia,44: 1195–1209, 2006.

Posner MI. Chronometric Explorations of Mind. Hillsdale, NJ:Erlbaum, 1978.

Posner MI and DiGirolamo GJ. Conflict, target detection, andcognitive control. In Parasuraman R (Ed), The Attentive Brain.Cambridge, MA: MIT Press, 1998: 401–423.

Please cite this article in press as: Shallice T et al., The multiple dj.cortex.2007.04.002

Posner MI and Petersen SE. The attention system of the humanbrain. Annual Review of Neuroscience, 13: 25–42, 1990.

Reverberi C, Lavaroni A, Gigli GL, Skrap M, and Shallice T. Specificimpairments of rule induction in different frontal lobesubgroups. Neuropsychologia, 43: 460–472, 2005.

Rossi S, Cappa SF, Babiloni C, Pasualetti P, Miniussi C, Carducci F,Babiloni F, and Rossini PM. Prefrontal cortex in long-termmemory: an ‘interference’ approach using magneticstimulation. Nature Neuroscience, 9: 948–952, 2001.

Rueckert L and Grafman J. Sustained attention deficits inpatients with right frontal lesions. Neuropsychologia, 34:953–963, 1996.

Sanders AF. Elements of human performance: reaction processes andhuman skill. Mahwah, NJ: Lawrence Erlbaum, 1998.

Shallice T. Fractionation of the supervisory system. In Stuss DT,and Knight RT (Eds), Principles of Frontal Lobe Function. NewYork: Oxford University Press, 2002: 261–277.

Shallice T. The fractionation of supervisory control. InGazzaniga MS (Ed), The Cognitive Neurosciences III. Cambridge,MA: MIT Press, 2004: 943–956.

Shallice T. Contrasting domains in the control of action: theroutine and the non-routine. In Johnson M, and Munakata Y(Eds), Attention and Performance XXI: Processes of Change in Brainand Cognitive Development. New York: Oxford University Press,2006: 3–29.

Sturm W and Willmes K. On the functional neuroanatomy ofintrinsic and phasic alertness. NeuroImage, 14: 76–84, 2001.

Stuss DT, Alexander MP, Floden D, Binns MA, Levine B,McIntosh AR, Rajah N, and Hevenor SJ. Fractionation andlocalization of distinct frontal lobe processes: Evidence fromfocal lesions in humans. In Stuss DT, and Knight RT (Eds),Principles of Frontal Lobe Function. New York: Oxford UniversityPress, 2002a: 392–407.

Stuss DT, Binns MA, Murphy KJ, and Alexander MP. Dissociationswithin the anterior attentional system: effects of taskcomplexity and irrelevant information on reaction time speedand accuracy. Neuropsychology, 16: 500–513, 2002b.

Stuss DT, Alexander MP, Hamer L, Palumbo C, Dempster R,Binns M, Levine B, and Izukawa D. The effects of focal anteriorand posterior brain lesions on verbal fluency. Journal of theInternational Neuropsychological Society, 4: 265–278, 1998.

Stuss DT, Alexander MP, Palumbo CL, Buckle L, Sayer L, andPogue J. Organizational strategies of patients with unilateral orbilateral frontal lobe injury in word list learning tasks.Neuropsychology, 8: 355–373, 1994.

Stuss DT, Alexander MP, Shallice T, Picton TW, Binns MA,MacDonald R, Borowiec A, and Katz DI. Multiple frontalsystems controlling response speed. Neuropsychologia, 43:396–417, 2005.

Stuss DT, Floden D, Alexander MP, Levine B, and Katz D. Stroopperformance in focal lesion patients: dissociation ofprocesses and frontal lobe lesion location. Neuropsychologia,39: 771–786, 2001.

Stuss DT, Levine B, Alexander MP, Hong J, Palumbo C, Hamer L,Murphy KJ, and Izukawa D. Wisconsin card sorting testperformance in patients with focal frontal and posteriorbrain damage: effects of lesion location and test structureon separable cognitive processes. Neuropsychologia, 38:388–402, 2000.

Stuss DT, Shallice T, Alexander MP, and Picton TW. Amultidisciplinary approach to anterior attentionalfunctions. Annals of the New York Academy of Sciences, 769:191–212, 1995.

Vallesi A, Shallice T, and Walsh V. Role of the prefrontal cortex inthe foreperiod effect: TMS evidence for dual mechanisms intemporal preparation. Cerebral Cortex, 17: 466–474, 2007.

Wilkins AJ, Shallice T, and McCarthy R. Frontal lesions andsustained attention. Neuropsychologia, 25: 359–365, 1987.

imensions of sustained attention, Cortex (2008), doi:10.1016/