VISUAL STIMULI ASSOCIATED WITH SWALLOWING ACTIVATE MIRROR...
Transcript of VISUAL STIMULI ASSOCIATED WITH SWALLOWING ACTIVATE MIRROR...
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CLINICAL DENTISTRY AND RESEARCH 2011; 35(3): 3-16
CorrespondenceYusuke Sanjo, DDS
Department of Oral Medicine, Oral and Maxillofacial Surgery,
Tokyo Dental College,5-11-13, Sugano, Ichikawa-city,
Chiba 272-8513, Japan
Phone: +81 47 3220151
Fax: +81 47 3248577 E-mail: [email protected]
Yusuke Sanjo, DDS Department of Oral Medicine, Oral and Maxillofacial Surgery,
Tokyo Dental College, Chiba, Japan
Yutaka Watanabe, DDS, PhD Department of Oral Medicine, Oral and Maxillofacial Surgery,
Tokyo Dental College, Chiba, Japan
Takashi Ushioda, DDSDepartment of Oral Medicine, Oral and Maxillofacial Surgery,
Tokyo Dental College, Chiba, Japan
Kazumichi Sato, DDS, PhDOral Cancer Center,
Tokyo Dental College, Chiba, Japan
Morio Tonogi, DDS, PhDDepartment of Oral Medicine, Oral and Maxillofacial Surgery,
Tokyo Dental College, Chiba, Japan
Shin-ichi Abe, DDS, PhDProfessor, Department of Anatomy,
Tokyo Dental College, Chiba, Japan
Gen-yuki Yamane, DDS, PhDProfessor, Department of Oral Medicine,
Oral and Maxillofacial Surgery,
Tokyo Dental College,Chiba, Japan
VISUAL STIMULI ASSOCIATED WITH SWALLOWING ACTIVATE MIRROR NEURONS: AN fMRI STUDY
ABSTRACT
Background and Aim: Human brain research in recent years
has demonstrated the existence of mirror neurons in Brodmann
areas (BA) 44, 6, and BA40. However, there has been almost
no previous research on swallowing and mirror neurons.
We have investigated the activity of mirror neurons during
swallowingrelated visual stimulation.
Subjects and Methods: Subjects were 15 healthy individuals
(6 male, 9 female; average age 27.3 years; right-handed). Brain
activity during the presentation of swallowing movements
was measured using 3T-fMRI. The swallowing movement
videos presented to subjects were conducted using 8 kinds
of stimuli videos, and 8 kind of control videos. fMRI signal
data were acquired based on the blood oxygenation level-
dependent (BOLD) effect to analyze differences between the
various swallowing videos and corresponding control videos by
MATLAB and Simulink Statistical Parametric Mapping 5 (SPM5).
Results: Activity in mirror neuron areas, was observed in
condition of water swallowing, fluoroscopic video, lateral
view (WXL) and chewing and swallowing, fluoroscopic video,
lateral view (CXL). The mirror neuron areas was lefthemisphere
dominant during the presentation of WXL and right-hemisphere
dominant during the presentation of CXL. Significantly stronger
activity was observed during WXL than during CXL.
Conclusion: This study was suggested that activity in the
mirror neuron areas has been observed in research on actual
swallowing. It was suggested that there were dominant
hemisphere like actual swallowing. Numerous studies have
been reported the application of mirror neurons to rehabilitation.
Therefore the use of videos shown in the study may have
applications in swallowing rehabilitation in the future.
Key words: Dysphagia, fMRI, Mirror neuron, Rehabilitation, Swallowing
Submitted for Publication: 10.12.2011
Accepted for Publication : 10.31.2011
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INTRODUCTION
Dysphagia may result in life-threatening conditions
such as inadequate nutrition, aspiration pneumonia, and
suffocation. Swallowing is a complex function involving
an intricate relationship between numerous muscles and
nerves, and there are currently few scientifically established
rehabilitation methods for its functional recovery.
We have focused on the mirror neuron system in order to
investigate new methods of rehabilitation for such patients.
Mirror neurons are described as neurons that activate in an
individual’s own nervous system as the result of observing
another’s movements, and were discovered in the F5 area of
monkeys’ brains.1-3 They have since also been demonstrated
in the PF area of monkeys’ brains.1, 3
Subsequently, numerous studies have revealed the
existence of mirror neurons in humans in areas corresponding
to those of monkey mirror neurons.1, 3 In addition, research
using the hand mirror neuron system has shown that the
presentation of healthy hand movements is an effective
method of rehabilitating the paralyzed hands of cerebral
infarction patients, suggesting that the presentation of
videos that activate mirror neurons may be effective in the
rehabilitation of motor function.4,5
Some work has already been done on oral movements6-8, but
previous research on mirror neurons and swallowing is the
only work to have suggested the existence of swallowing
mirror neurons.9 In the present study, we increased the
conditions imposed on the videos of swallowing movements
presented, and verified the existence of swallowing mirror
neurons. We also carried out a comparative investigation
of the differences between the left and right hemispheres
and in experimental conditions for the conditions under
which mirror neuron activity was observed. Further, we
investigated the possibility that the mirror neuron activity
seen during this study could be applied to a new method of
rehabilitation for swallowing.
MATERIALS AND METHODS
This study was conducted at the Advanced
Telecommunications Research (ATR) Brain Activity Imaging
Center with the approval of the Ethics Committee of Tokyo
Dental College (Protocol number: 78-A).
Subjects
Subjects were fifteen healthy individuals (age 20–34 years;
average age 27.3 years; 6 males, 9 females). On the day
of the experiment their understanding of the purpose of
the research was verified by means of an explanation in writing, possible risks were explained, and their consent to experimental participation obtained. All were assessed by the Edinburgh Inventory as right-handed.10 They also possessed sufficient visual acuity to perform the tasks.
Study design
The swallowing movement videos presented to subjects were conducted using 8 kinds of stimuli videos: 1) water swallowing, general video, frontal view (WGF); 2) water swallowing, fluoroscopic video, frontal view (WXF); 3) water swallowing, general video, lateral view (WGL); 4) Water swallowing, fluoroscopic video, lateral view (WXL); 5) chewing and swallowing, general video, frontal view (CGF); 6) chewing and swallowing, fluoroscopic video, frontal view (CXF); 7) chewing and swallowing, general video, lateral view (CGL); 8) chewing and swallowing, fluoroscopic video, lateral view (CXL), and 8 kind corresponding control videos consisted of 1000-piece mosaics of 1) - 8) videos; 9) mosaics of WGF; 10) mosaics of WGL; 11) mosaics of WXF; 12) mosaics of WXL; 13) mosaics of CGF; 14) mosaics of CGL; 15) mosaics of CXF; 16) mosaics of CXL. In the previous study, still control images were presented as the control condition.9 However, the possibility existed that they evoked an association with swallowing on the part of the subjects.11 Moreover, compared with the stimulus videos there was almost no movement on the screen, resulting in a difference in the amount of stimulus presented to the subjects, meaning that the appropriateness of these images as controls was questionable. We examined that actual swallowing for a control condition. However, by the preliminary experiment, the brain activity of swallowing that it was difficult to get the result that influence was correct greatly of the noise. Therefore, that way, we would not be able to extract mirror neuron activities with significance. For this reason, in the present study we produced mosaic videos corresponding to each stimulus condition and presented them to the subjects. The mosaic videos made it possible to match the amount of stimulus in the control videos with that of the stimulus videos. Stimulus presentation time was set at 6 seconds for videos of water swallowing condition 1) - 4) and 9) - 12), and 9 seconds for videos of chewing and swallowing condition 5) - 8) and 13) - 16), with a single swallow shown during that time (Figure 1).
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A block design was used for the stimulus presentation method, with videos 1) - 16) presented in four separate sessions: A) water swallowing frontal condition: 1), 2), 9), 10); B) water swallowing lateral condition: 3), 4), 11), 12); C) chewing and swallowing frontal condition: 5), 6), 13), 14), and D) chewing and swallowing lateral condition: 7), 8), 15), 16). In sessions A) and B), one block consisted of four consecutive presentations of a single video, after which a 12 seconds blank was inserted between each block, with the presentation of the four different types of video in the order given constituting one cycle. Three cycles were shown in each session. Experiments A) and B) consisted of 432 seconds of presentation in total, and were set to take a total of 144 scans (Figure 2-1).In sessions C) and D), one block consisted of three consecutive presentations of a single video, after which a 12 seconds rest was inserted between each block, with the presentation of the four different types of video in the order given constituting one cycle. Three cycles were shown in each session. Each session lasted 468 seconds, with a total of 156 scans taken (Figure 2-2). All videos were produced in MPEG1 format to enable their control by the presentation
software produced by NeuroBehavioral Systems, which provides precision control of stimulus presentation during fMRI experiments.Intervals of 2 minutes were provided between each session, and the order of presentation of sessions A), B), C), and D) was changed for each subject. This study design applied a previous study.9 Subjects lay supine during fMRI imaging experiments. A Victor DLA-G150CL monitor was used for swallowing videos, and images projected on the screen were displayed via a mirror fixed in place with a cranial coil. The subjects were not given any particular task during the experiment, but were instructed not to move their legs, head, mouth, or tongue while simply observing the visual stimuli. Hitachi Advanced Systems Corp. fMRI high-performance headphones were used to block out sound, and videos were shown with sound inside the fMRI equipment reduced to 20 dBSPL.
Device and imaging conditions
Both T1 and T2-weighted imaging (also called functional imaging or echo planar imaging [EPI]) were carried out with a fMRI instrument (3 Tesla Siemens MAGNETOM Trio, A Tim
Figure 1. Stimuli and corresponding control videos Stimulus presentation time was set at 6.0 s for WGF, WXF, WGL, WXL, and 9.0 s for CGF, CXF, CGL, CXL, with a single swallow shown during that time. These times were the same for the 1000-pieces mosaics videos. All videos were produced in MPEG1 format to enable their control by the presentation software produced by NeuroBehavioral Systems, which provides precision control of stimulus presentation during fMRI experiments. (W: water swallow, C: chewing and swallow, G: general video, X: fluoroscopic video, F: frontal, L: lateral)
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Figure 2-1. Sessions A) and B) In sessions, water swallowing frontal and water swallowing lateral, one block consisted of four consecutive presentations of a single video, after which a 12 s blank was inserted between each block, with the presentation of the four different types of video in the order given constituting one cycle. Three cycles were shown in each session. Experiments A and B consisted of 432 s (approx. 7.2 min) of presentation in total, and were set to take a total of 144 scans.
Figure 2-2. Sessions C) and D) In sessions, chewing and swallowing frontal and chewing and swallowing lateral, one block consisted of three consecutive presentations of a single video, after which a 12 s rest was inserted between each block, with the presentation of the four different types of video in the order given constituting one cycle. Three cycles were shown in each session. Each session lasted 468 s (approx.7.8 min), with a total of 156 scans taken. Intervals of 1-2 min were provided between each sessions.
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system) in the ATR-Brain Activity Imaging Center. The S/N ratio is high for 3T-MRI, enabling high resolution and shorter image acquisition times.12 Imaging was gradient EPI with
the following settings: repetition time (TR), 3 seconds;
Number of slices, 32; matrix size, 64×64 pixels; field of
view (FOV), 192×192 mm; TE, 49 ms; flip angle, 90°; 40
axial slices; plane resolution, 3×3 mm. 40 slices covering the
head were imaged at 123 scans per slice with a voxel size
of 2×2×4 mm and without a slice gap. The first 5 scans in
each session were not used in the analysis because of the
signal value was unstable immediately following the start
of imaging.
Date analysis methods
During these experiments, fMRI measurements were
synchronized with video presentations, and the fMRI signal
was observed on the basis of the blood oxygenation level-
dependent (BOLD) effect to analyze differences between
the various swallowing videos and corresponding control
videos. The “difference method” is a basic experimental
tool for fMRI, and block design is a suitable experimental
method for this. The difference method subtracts brain
activity under control conditions from that under stimulus
conditions, and is an appropriate experimental method for
isolating the brain activity under study.
All images were pre-processed using Statistical Parametric
Mapping 5 (SPM5) software. In SPM5, changes associated
with interactions of brain areas are not considered and,
based on the assumption that each brain area functions
independently, local results are examined statistically
for all pixels. In this study, the head position tended to
move during this long period of imaging. Any slip in head
position was corrected using three-dimensional translation
and rotation in SPM5, with brain imaging data adjusted
three-dimensionally to fit the initial data. Next, data were
normalized in accordance with the standard Montreal
Neurological Institute (MNI) brain. The averaged image was
constructed using the image in the corrected position, and
T2 and T1 structural images were adjusted and normalized
based on this position. Anatomically normalized brain
functional images were smoothed to meet the condition of
a Gaussian random field. Changes associated with activation
generally occur over several pixels and therefore smoothing
makes it easy to detect signal changes due to activation.
Smoothing was conducted using a Gaussian filter (full width
at half maximum (FWHM) = 6×6×8 mm). In this procedure,
signal values and counts are more normally distributed and
can be more effectively used in a statistical model. In fixed effect analysis, signal correlation was calculated using a box-car functional model with a blood flow response function to detect brain area showing statistically significant signal changes due to targeted activation. Furthermore, contrast images were constructed for each subject and a sample t test (a group analysis tool) was performed for these images to detect areas that displayed significant differences sequentially or between sessions. In examining brain activity across the subjects, a sample t test was conducted between brain activity distributions calculated for each subject, and areas with common significant brain activity were identified. As few activated areas were found at p<0.001 without correction of the significance level for multiple comparison, In analyzing the plural data using a random-effects model at p <0.001, z values of activated areas corresponded to 3.09 and higher, and areas showing this value were considered to be activated; these data are summarized (Table 1). The coordinate axes of the results were analyzed using SPM5, expressed as MNI coordinates, and converted into Talairach coordinates using MatLab. The Brodmann area and anatomical position were then estimated from the obtained coordinates in accordance with the Co-Planar Stereotaxic Atlas of the Human Brain (Talairach and Tournoux. 1988). Regions of interest (ROIs) analysis were also done for areas displaying significant activity during presentation of each stimulus. The amount of brain activity was quantified using the regression coefficient for each condition, and calculated it as contrast estimate. Wilcoxon signed rank test was performed that compared under different experimental conditions and between left and right hemispheres.
RESULTS
Brain activity under each condition
Figure 3 shows the MNI standard brain (left and right hemispheres) with brain activity areas obtained from group analysis shown in red. Table 1 shows the Talairach coordinates and Brodmann areas (BA) of brain activity for each condition. The activities for each condition are shown below.
a. Condition of WGF (Figure 3-1, Table1-1)
Activity was observed in BA18 (right hemisphere), regarded as the second visual cortex (V2); BA19 (both hemispheres),
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Figure 3. MNI standard brain with brain activity areas Montreal Neurological Institute (MNI) standard brain (left and right hemispheres) with brain activity areas obtained from group analysis shown in red. A determination of brain activity was made if the significance level of the comparison was p < 0.001 with no multiple comparison correction. (W: water swallow, C: chewing and swallow, G: general video, X: fluoroscopic video, F: frontal, L: rateral)
Brodman areaRight/Left
MNI coordinatesAnatomical position Z value
X Y Z
18 r 46 -80 0 Inferior occipitalis gyrus 3.48
l - - - - -
19 r 64 -72 -8 Middle occipitalis gyrus 4.34
l -54 -68 -4 Middle occipitalis gyrus 3.39
37 r 44 -64 -4 Inferior temporal gyrus 4.08
l -42 -64 2 Inferior temporal gyrus 3.39
Table 1. Talairach coordinates and Z-scores of the activated foci. Montreal Neurological Institute (MNI) coordinates and Brodmann areas (BA) of brain activity and Z value for each condition. A determination of brain activity was made if the significance level of the comparison was p<0.001 with no multiple comparison correction. Table 1-1. Condition of WGF
Table 1-2. Condition of WXF
Brodman areaRight/Left
MNI coordinatesAnatomical position Z value
X Y Z
r - - - - -
l - - - - -
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considered the visual association area (V3); and BA37 (both hemispheres), regarded as the fusiform gyrus.
b. Condition of WXF (Figure 3-2, Table1-2)
No significant activity was observed.
c. Condition of WGL (Figure 3-3, Table1-3)
Activity was observed in BA19 (both hemispheres) and BA37 (left hemisphere).
d. Condition of WXL (Figure 3-4, Table1-4)
As during the presentation of other conditions, activity was observed in BA18 (both hemispheres), 19 (both hemispheres), and BA37 (both hemispheres). In addition, activity was also observed bilaterally in BA44, 45, and BA46 in the frontal lobe; BA6 (both hemispheres), regarded as the premotor area; BA39 (left hemisphere), and BA40 (both hemispheres) in the parietal lobe; and BA7 (both hemispheres), regarded as the somatic sensation association area. This was the greatest amount of activity seen among the stimuli presented in this study.
e. Condition of CGF (Figure 3-5, Table1-5)
Activity was observed bilaterally in BA19 and BA37.
f. Condition of CXF (Figure 3-6, Table1-6)
In addition to BA18, 19, and BA37 (both hemispheres for all), activity was also observed in BA7 (both hemisphere).
g. Condition of CGL (Figure 3-7, Table1-7)
No significant activity was observed.
h. Condition of CXL (Figure 3-8, Table1-8)
As during the presentation of other conditions, bilateral activity was observed in BA18, 19 and BA37. In addition, activity was also observed in BA44 (right hemisphere) and BA45 (right hemisphere) in the frontal lobe and in BA40 (both hemispheres) in the parietal lobe. This was the
second greatest amount of activity seen among the stimuli presented in this study, after WXL. Activity in BA44, 6, or BA40, regarded as mirror neuron areas, was observed in condition of WXL and condition of CXL. Comparison of left and right hemisphere activity in BA44, BA6, and BA40 in condition of WXL (Figure 4)In BA40, significantly stronger activity was observed in the left hemisphere. More activity was observed in the left hemisphere for BA44 and in the right hemisphere for BA6, but these differences were not significant. Comparison of left and right hemisphere activity in BA44, BA6, and BA40 in condition of CXL (Figure 5)In BA44, significantly stronger activity was observed in the right hemisphere. More activity was also observed in the right hemisphere for BA40, but the difference was not significant. No significant activity was observed in BA6. Comparison of amount of activation in each area during condition of WXL and CXL (Figure 6)The amount of activity was significantly greater during WXL in BA44, 6, and BA40, bilaterally.
DISCUSSION
Comparison with other mirror neuron research
A large number of studies based on mirror neurons using, magnetoencephalography (MEG), positron emission tomography (PET), fMRI, and transcranial magnetic stimulation (TMS) has been published, and human mirror neuron areas have been demonstrated.6-9, 13-15 In studies investigating brain activity during the execution and perception of grasping movements by the human hand, and showed that areas BA44 and 40 are activated in both conditions. They emphasize that area BA44 and 6 in particular corresponds to area F5 (including F5c, F5p, and F5a) in monkeys, regarded as the site of mirror neurons.1,3 It
Table 1-3. Condition of WGL
Brodman area
Right/Left
MNI coordinatesAnatomical position Z value
X Y Z
19 r 48 -72 -10 Middle occipitalis gyrus 4.74
l -48 -74 -2 Middle occipitalis gyrus 3.09
37 r - - - - -
l -54 -72 8 Inferior temporal gyrus 3.18
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Brodman areaRight/Left
MNI coordinatesAnatomical position Z value
X Y Z
40 r 66 -22 26 Inferior parietal lobule 4.23
l -66 -26 28 Inferior parietal lobule 4.72
44 r 48 10 38 Inferior frontal gyrus 4.22
l -52 6 40 Inferior frontal gyrus 3.96
45 r 42 28 10 Inferior frontal gyrus 4.43
l -46 32 16 Inferior frontal gyrus 3.89
6 r 48 10 50 Middle frontal gyrus 4.72
l -40 0 54 Middle frontal gyrus 4.62
7 r 28 -60 50 Superior parietal lobule 5.20
l -26 -64 54 Superior parietal lobule 4.88
18 r 36 -78 14 Middle occipitalis gyrus 3.34
l -34 -86 14 Middle occipitalis gyrus 5.34
19 r 46 -70 -8 Middle occipitalis gyrus 5.45
l -52 -64 -8 Middle occipitalis gyrus 5.72
37 r 42 -58 -12 Inferior temporal gyrus 5.19
l -36 -54 -18 Inferior temporal gyrus 5.11
39 r - - - - -
l -34 -72 22 Middle temporal gyrus 5.01
46 r - - - - -
l -50 40 16 Inferior frontal gyrus 4.08
Table 1-4. Condition of WXL
Brodman areaRight/Left
MNI coordinatesAnatomical position Z value
X Y Z
19 r 44 -70 -4 Middle occipitalis gyrus 4.33
l -50 -70 -4 Middle occipitalis gyrus 4.08
37 r 54 -58 4 Middle temporal gyrus 4.02
l -46 -62 6 Middle temporal gyrus 4.11
Table 1-5. Condition of CGF
Brodman areaRight/Left
MNI coordinatesAnatomical position Z value
X Y Z
7 r 30 -54 54 Superior parietal lobule 3.50
l -30 -52 52 Superior parietal lobule 3.78
18 r 34 -84 6 Middle occipitalis gyrus 4.29
l -44 -86 4 Middle occipitalis gyrus 4.96
19 r 50 -68 -10 Middle occipitalis gyrus 5.27
l -50 -68 -6 Middle occipitalis gyrus 4.96
37 r 50 -70 2 Inferior temporal gyrus 5.05
l -50 -68 -6 Inferior temporal gyrus 5.20
Table 1-6. Condition of CXF
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Brodman areaRight/Left
MNI coordinatesAnatomical position Z value
X Y Z
r - - - - -
l - - - - -
Table 1-7. Condition of CGL
Brodman areaRight/Left
MNI coordinatesAnatomical position Z value
X Y Z
40 r 30 -38 42 Inferior parietal lobule 4.19
l -44 -38 32 Inferior parietal lobule 4.32
44 r 32 16 28 Inferior frontal gyrus 3.32
l - - - - -
45 r 34 20 20 Inferior frontal gyrus 4.20
l - - - - -
7 r 32 -54 66 Superior parietal lobule 4.81
l -38 52 58 Superior parietal lobule 3.77
18 r 32 86 6 Middle occipitalis gyrus 3.84
l -32 -86 2 Middle occipitalis gyrus 4.00
19 r 48 -68 -12 Middle occipitalis gyrus 6.23
l -48 -70 -4 Middle occipitalis gyrus 4.53
37 r 52 -58 0 Inferior temporal gyrus 5.06
l -50 -64 6 Inferior temporal gyrus 4.63
Table 1-8. Condition of CXL
Figure 4. Comparison of left and right hemisphere activity in BA44, BA6, and BA40 of WXL Contrast estimate of left and right hemisphere activity in BA44, 6, and BA40 of WXL, over 15 subjects. Error bars represent standard error of the mean (*p < 0.05) (R: right, L: left)
Contranst estimate
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Figure 5. Comparison of left and right hemisphere activity in BA44, BA6, and BA40 of CXL Contrast estimate of left and right hemisphere activity in BA44 and BA40 of CXL, over 15 subjects. Error bars represent standard error of the mean (**p<0.001)
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Figure 6. Comparison of amount of activation in each area during presentation of WXL and CXL Contrast estimate of WXL and CXL activity in BA44, 6, and BA40 of left and right hemisphere, over 15 subjects. Error bars represent standard error of the mean (*p<0.05, **p <0.001) (W: WXL, C: CXL)
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has also been reported that area PF in monkeys corresponds
to BA40 in the human. 3,16
In the present study, activity was observed in areas BA44, 6,
and 40 that included the area where activity was suggested
in the previous study, corresponding to the mirror neurons
above, in the two conditions of WXL and CXL. This suggests
the existence of swallowing mirror neurons that were
activated in response to the presentation of swallowing
movement videos. Our previous study, an fMRI investigation
of brain activity during the presentation of auditory and
visual stimuli associated with swallowing, is the only
published research to date on mirror neurons associated
with swallowing, and it suggested the activity of mirror
neurons during the presentation of visual stimuli.9 As there
has been little research on swallowing mirror neurons, at
present it is difficult to make comparisons.
Comparison with brain activity during actual swallowing
A large volume of research has been carried out on
actual swallowing by using fMRI, MEG, and PET, and the
elucidation of brain function during swallowing has been
highly successful.15, 17-20
In a meta-analysis of the results of seven studies on water
swallowing and five on saliva swallowing, involving a total
of 98 subjects, the active areas during water swallowing
were, in descending order of importance: BA4, 43, 44, and
40. During saliva swallowing they were: BA6, 32, 43, and 4.21
These results show that during actual swallowing, activity
was also observed in areas BA44, 6, and 40, which are
regarded as associated with mirror neurons. In light of the
results of the present study, the fact that they are active
during both actual swallowing and the observation of
swallowing suggests the existence of mirror neurons for
swallowing.
Laterality of activation associated with mirror neurons
As shown in Figures 4 and 5, activity in mirror neuron areas
was left-hemisphere dominant during the presentation
of WXL and right-hemisphere dominant during the
presentation of CXL.
According to fMRI research on brain activity during
observation of mouth opening and closing movements, the
right hemisphere was dominant during opening and closing
movements of the mouth in the absence of food, whereas
the left hemisphere was dominant during actual biting and
food-chewing movements.7 Research using MEG to monitor
brain activity during observation of a single movement to
open and close the mouth found that the left hemisphere
was dominant.8 When the results of the present study
are also taken into account, this suggests that the left
hemisphere may be dominant during the presentation of
voluntary movements such as biting food and swallowing
water, whereas the right hemisphere may be dominant
during the presentation of reflex movements such as simple
opening and closing of the mouth or rhythmical chewing.
Research involving actual swallowing has suggested that
the left hemisphere preferentially mediates voluntary
movement during the oral stage, whereas the right
hemisphere mediates reflex movement during the
pharyngeal and subsequent stages.22-24 These findings
suggest that voluntary movements during actual
swallowing are left-hemisphere dominant, whereas reflex
movements are right-hemisphere dominant. The results
of the present study indicate that in the two conditions
in which mirror neuron activity was suggested, the left
hemisphere was dominant during the presentation of
voluntary swallowing in WXL, whereas the right hemisphere
was dominant during the presentation of reflex swallowing
in CXL, demonstrating the same differentiation of function
found in actual swallowing movements. This suggests that
brain function differentiation is involved during both actual
swallowing and its observation.
Comparison of areas of activity associated with mirror
neurons during the presentation of WXL and CXL
As shown in Figure 6, significantly stronger activity was
observed during WXL than during CXL. These two conditions
differed in terms of whether water swallowing or chewing
and swallowing was shown.
During chewing and swallowing, although voluntary
movement is predominant at the start of chewing, the
subsequent rhythmical movement that starts during
chewing is believed to become mainly reflex movement as a
result of automaticity.25 Accordingly, conscious (voluntary)
observation was easier for water swallowing, suggesting
that this also contributed to the increased amount of brain
activity.
Reason for the observation of significant activity in regions
associated with mirror neurons during presentation of the
WXL and CXL conditions
The common factors between the WXL and CXL conditions
under which activity in mirror neuron areas was predominant
were the use of fluoroscopic video and lateral view.
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A comparison of general and fluoroscopic videos showed
that the main feature of general videos was that they
showed the elevation of the larynx. As described above,
however, the feature of fluoroscopic videos is that, unlike
general videos, they enable observers to obtain a large
amount of information by observing muscle and bone
movements. This is because they enable observation of
intra-oral phenomena associated with laryngeal elevation,
from the movement of the hyoid bone to inversion of the
epiglottis, elevation of the soft palate, and movement of
food by the tongue (especially the formation of a bolus by
chewing during chewing and swallowing and its passage
into the pharynx) until it passes through the esophagus. For
this reason, fluoroscopic videos evoked swallowing more
strongly than did general videos, and were suited to the
activation of mirror neuron areas.
A comparison of frontal and lateral views found that in
frontal view images there was a large amount of overlap
in the anatomical information described above between the
oral cavity and the pharynx, particularly under fluoroscopic
video conditions, with bolus movement also perceived as a
simple top-to-bottom movement from the oral cavity to the
esophagus. In lateral view, however, there was no overlap
of the anatomical information described above, and bolus
movement was perceived as an anatomically comprehensible
motion from the oral cavity to the pharynx and esophagus.
Accordingly, as for fluoroscopic videos, lateral views evoked
swallowing more strongly than did frontal views, and were
suited to the activation of mirror neuron areas.
Taking these points into account, the simultaneous
presentation of both factors in the form of fluoroscopic
videos in lateral view evoked a synergistic effect on activity
in mirror neuron areas, suggesting that an interaction effect
was involved.
Application to swallowing rehabilitation
Numerous reports have been published concerning the
application of mirror neurons to rehabilitation. Most
neurorehabilitation techniques rely on methods of inducing
plasticity in the motor cortex.26 Research on hand movement
in patients with long-term sequelae of cerebral infarction
with middle cerebral artery damage has shown that having
patients watch a video of a movement while they undergo
the same movement training increases effectiveness.
Further, the plasticity of the motor cortex has also been
demonstrated, showing that a combination of observation
and movement enables the easier formation of kinesthetic
memories.27-28 Studies of “mirror therapy,” which uses an
actual mirror, have also shown that tricking the vision into
believing that the hand on the paralyzed side is moving
activates movement areas on the damaged side, improving
hand and foot function in stroke patients.4-5 These results
have shown that changes in the plasticity of the motor
cortex and mirror neuron activity are associated with
functional recovery, and further use of the mirror mechanism
is regarded as an important element in promoting functional
recovery.29
Many of these rehabilitation techniques have been reported
for hand movement, for which the existence of mirror
neurons has been proven.4-5
In the hand rehabilitation which applied mirror neuron,
30 minutes of mirror therapy program a day consisting of
wrist and finger flexion and extraction movements or sham
therapy in addition to conventional stroke rehabilitation
program 5 days a week, 2 to 5 hours a day, for 4 weeks.
The effect of this program was shown.4,5 Therefore, it was
thought that observation and execution of swallowing of
30 minutes a day, 5 days a week, for 4 weeks were effective
for swallowing rehabilitation.
Cerebrovascular ascular damage has occurred in many
dysphagia patients, and it is possible that the introduction
of the experimental method described in this study may help
improve swallowing function by employing brain plasticity
resulting from mirror neuron activity. In the present study,
as the greatest mirror neuron activity was observed during
the presentation of WXL, this type of video may be the
most appropriate for activating mirror neurons associated
with swallowing.
The application of mirror therapy to swallowing will require
further investigation to take into account the fact that
effective types of video and stimulus intensity may vary
depending on the location and severity of damage in
patients.
CONCLUSION
In the same way as a previous study, this study suggests
the activity of mirror neurons during the observation of
videos of swallowing movements. The fact that activity
in the same brain areas has been observed in research on
actual swallowing provides indication of the existence of
swallowing mirror neurons. This study suggests that when
swallowing mirror neurons are active, in the same way as
15
ThE ACTIvITy OF MIrrOr nEurOnS FOr SwAllOwIng STIMulI
during actual swallowing, the left hemisphere is dominant
during observation of primarily voluntary movements and
the right hemisphere is dominant during the observation of
primarily reflex movements.
Numerous studies have been reported the application of
mirror neurons to rehabilitation, the use of videos shown in the study may have applications in swallowing rehabilitation in the future.
REFERENCES
1. Fabbri-Destro M, Rizzolatti G. Mirror neurons and mirror systems in monkeys and humans. Physiology (Bethesda). 2008; 23: 171-179.
2. Rizzolatti G, Craighero L. The mirror-neuron system. Annu Rev Neurosci 2004; 27: 169-192.
3. Rizzolatti G, Fabbri-Destro M, Cattaneo L. Mirror neurons and their clinical relevance. Nat Clin Pract Neurol 2009; 5: 24-34.
4. Altschuler EL, Wisdom SB, Stone L, Foster C, Galasko D, Llewellyn DM et al. Rehabilitation of hemiparesis after stroke with a mirror. Lancet 1999; 12; 353(9169): 2035-2036.
5. Yavuzer G, Selles R, Sezer N, Sutbeyaz S, Bussmann JB, Koseoglu F et al. Mirror therapy improves hand function in subacute stroke: a randomized controlled trial. Arch Phys Med Rehabil 2008; 89: 393-398.
6. Buccino G, Binkofski F, Fink GR, Fadiga L, Fogassi L, Gallese V et al. Action observation activates premotor and parietal areas in a somatotopic manner: an fMRI study. Eur J Neurosci 2001; 13: 400-404.
7. Buccino G, Binkofski F, Riggio L. The mirror neuron system and action recognition. Brain Lang 2004; 89: 370-376.
8. Shibukawa Y, Ishikawa T, Kato Y, Zhang ZK, Jiang T, Shintani M et al. Cerebral cortical dysfunction in patients with temporomandibular disorders in association with jaw movement observation. Pain 2007; 128: 180-188.
9. Kawai T, Watanabe Y, Tonogi M, Yamane GY, Abe S, Yamada Y et al. Visual and auditory stimuli associated with swallowing: an FMRI study. Bull Tokyo Dent Coll 2009; 50: 169-181.
10. Oldfield RC. The assessment and analysis of handedness: the Edinburgh inventory. Neuropsychologia 1971; 9: 97-113.
11. Umilta MA, Kohler E, Gallese V, Fogassi L, Fadiga L, Keysers C et al. I know what you are doing. a neurophysiological study. Neuron 2001; 19; 31:155-165.
12. Fukatsu H. 3T MR for clinical use: update. Magn Reson Med Sci 2003; 1; 2: 37-45.
13. Fadiga L, Craighero L, Buccino G, Rizzolatti G. Speech listening specifically modulates the excitability of tongue muscles: a TMS study. Eur J Neurosci 2002; 15: 399-402.
14. Filimon F, Nelson JD, Hagler DJ, Sereno MI. Human cortical representations for reaching: mirror neurons for execution, observation, and imagery. Neuroimage 2007; 1; 37: 1315-1328.
15. Harris ML, Julyan P, Kulkarni B, Gow D, Hobson A, Hastings D, et al. Mapping metabolic brain activation during human volitional swallowing: a positron emission tomography study using [18F] fluorodeoxyglucose. J Cereb Blood Flow Metab 2005; 25: 520-526.
16. Frey SH, Vinton D, Norlund R, Grafton ST. Cortical topography of human anterior intraparietal cortex active during visually guided grasping. Brain Res Cogn Brain Res 2005; 23: 397-405.
17. Abe S, Wantanabe Y, Shintani M, Tazaki M, Takahashi M, Yamane GY et al. Magnetoencephalographic study of the starting point of voluntary swallowing. Cranio 2003; 21: 46-49.
18. Martin R, Barr A, MacIntosh B, Smith R, Stevens T, Taves D et al. Cerebral cortical processing of swallowing in older adults. Exp Brain Res 2007; 176: 12-22.
19. Martin RE, Goodyear BG, Gati JS, Menon RS. Cerebral cortical representation of automatic and volitional swallowing in humans. J Neurophysiol 2001; 85: 938-350.
20. Watanabe Y, Abe S, Ishikawa T, Yamada Y, Yamane GY. Cortical regulation during the early stage of initiation of voluntary swallowing in humans. Dysphagia 2004; 19: 100-108.
21. Soros P, Inamoto Y, Martin RE. Functional brain imaging of swallowing: an activation likelihood estimation meta-analysis. Hum Brain Mapp 2009; 30: 2426-2439.
22. Dziewas R, Soros P, Ishii R, Chau W, Henningsen H, Ringelstein EB et al. Neuroimaging evidence for cortical involvement in the preparation and in the act of swallowing. Neuroimage 2003; 20: 135-144.
23. Daniels SK, Corey DM, Fraychinaud A, DePolo A, Foundas AL. Swallowing lateralization: the effects of modified dual-task interference. Dysphagia 2006; 21: 21-27.
24. Teismann IK, Dziewas R, Steinstraeter O, Pantev C. Time-dependent hemispheric shift of the cortical control of volitional swallowing. Hum Brain Mapp 2009; 30: 92-100.
25. Nakamura Y, Katakura N. Generation of masticatory rhythm in the brainstem. Neurosci Res 1995; 23: 1-19.
26. Dobkin BH. Training and exercise to drive poststroke recovery. Nat Clin Pract Neurol 2008; 4: 76-85.
16
CLINICAL DENTISTRY AND RESEARCH
27. Stefan K, Classen J, Celnik P, Cohen LG. Concurrent action observation modulates practice-induced motor memory formation. Eur J Neurosci 2008; 27: 730-738.
28. Stefan K, Cohen LG, Duque J, Mazzocchio R, Celnik P, Sawaki L et al. Formation of a motor memory by action observation. J Neurosci 2005; 12; 25: 9339-9346.
29. Moseley GL, Gallace A, Spence C. Is mirror therapy all it is cracked up to be? Current evidence and future directions. Pain 2008; 15; 138: 7-10.