J Neurophysiol 93: 1020 –1034, 2005.
First published September 22, 2004; doi:10.1152/jn.00637.2004.
Dominance of the Right Hemisphere and Role of Area 2
in Human Kinesthesia
Eiichi Naito,1,2 Per E. Roland,1 Christian Grefkes,3 H. J. Choi,3 Simon Eickhoff,3 Stefan Geyer,3 Karl Zilles,3
and H. Henrik Ehrsson1,4
1
Division of Human Brain Research, Department of Neuroscience, Karolinska Institute, Stockholm, Sweden; 2Graduate School of Human
and Environmental Studies, Kyoto University, Kyoto, Japan; 3C. and O. Vogt Institute for Brain Research, University of Dusseldorf,
Germany; and 4Wellcome Department of Imaging Neuroscience, Institute of Neurology, London, United Kingdom
Submitted 23 June 2004; accepted in final form 11 September 2004
INTRODUCTION
Somatic perception of limb position or limb movement
depends to a large extent on the central processing of kinesthetic information originating from the receptors in muscles.
With eyes closed, vibration stimuli at ⬃80 Hz on the tendon of
a limb can elicit a kinesthetic illusory movement of the limb in
the absence of actual movements (Goodwin et al. 1972a,b;
Naito and Ehrsson 2001; Naito et al. 1999, 2002a,b). The
Address for reprint requests and other correspondence: E. Naito, Graduate
School of Human and Environmental Studies, Kyoto University, Sakyo-ku,
Kyoto 606 8501 Japan (E-mail: [email protected]).
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vibration stimuli mainly excite the muscle spindle afferents
signaling that the vibrated muscles are stretched although the
limb remains immobile (Burke et al. 1976; Collins and
Prochazka 1996; Gandevia 1985; Roll and Vedel 1982; Roll et
al. 1989). We have consistently demonstrated by positron
emission tomography (PET) and functional magnetic resonance imaging (fMRI) that the contralateral motor cortex (M1;
cytoarchitectonic areas 4a and 4p), primary somatosensory
cortex (SI), dorsal premotor cortex (PMD), supplementary
motor area (SMA), cingulate motor area (CMA) (Naito and
Ehrsson 2001; Naito et al. 1999, 2002a,b), and the ipsilateral
cerebellum (Naito et al. 2002a,b) are active during illusory
movements of arm or hand. In particular, M1 appears to be
primarily responsible for the kinesthetic processing of muscle
spindle input, and its activity is associated with the perception
of limb movements (Naito 2004; Naito et al. 2002b). The
general aim of the present study was to investigate the brain
regions, in addition to the motor areas described in the preceding text, which may be active during kinesthetic illusions. We
examine three specific hypotheses.
First, we examine the hypothesis that area 2 is involved in
kinesthetic illusions. A large number of studies in non-human
primates suggest that neurons in cytoarchitectonic area 2 respond to sensory input during passive or active limb movements (Burchfiel and Duffy 1972; Costanzo and Gardner 1981;
Gardner 1988; Gardner and Costanzo 1981; Iwamura 2000;
Iwamura and Tanaka 1996; Iwamura et al. 1993, 1994; Jennings et al. 1983; Mountcastle and Powell 1959; Pons et al.
1992; Salimi et al. 1999; Schwarz et al. 1973; Taoka et al.
1998, 2000; Wolpaw 1980). As there seem to be no obvious
anatomical differences between area 2 in monkeys and humans
(Zilles and Palomero-Gallagher 2001), one may expect that the
human area 2 would be involved in the processing of kinesthetic information. One possible reason for the apparent discrepancy between our imaging results and the non-human
primate literature is the differences in afferent input during
kinesthetic illusions and passive limb movement. During tendon vibration illusions, the muscle spindle afferent is the only
sensory source signaling limb movements (see references in
the preceding text), whereas during passive limb movements,
the brain receives multiple somatosensory inputs from muscle
receptors, joint receptors, and skin receptors (Burke et al. 1988;
Collins and Prochazka 1996; Hulliger et al. 1979). As neurons
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0022-3077/05 $8.00 Copyright © 2005 The American Physiological Society
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Naito, Eiichi, Per E. Roland, Christian Grefkes, H. J. Choi, Simon
Eickhoff, Stefan Geyer, Karl Zilles, and H. Henrik Ehrsson.
Dominance of the right hemisphere and role of area 2 in human
kinesthesia. J Neurophysiol 93: 1020 –1034, 2005. First published
September 22, 2004; doi:10.1152/jn.00637.2004. We have previously
shown that motor areas are engaged when subjects experience illusory
limb movements elicited by tendon vibration. However, traditionally
cytoarchitectonic area 2 is held responsible for kinesthesia. Here we
use functional magnetic resonance imaging and cytoarchitectural
mapping to examine whether area 2 is engaged in kinesthesia, whether
it is engaged bilaterally because area 2 in non-human primates has
strong callosal connections, which other areas are active members of
the network for kinesthesia, and if there is a dominance for the right
hemisphere in kinesthesia as has been suggested. Ten right-handed
blindfolded healthy subjects participated. The tendon of the extensor
carpi ulnaris muscles of the right or left hand was vibrated at 80 Hz,
which elicited illusory palmar flexion in an immobile hand (illusion).
As control we applied identical stimuli to the skin over the processus
styloideus ulnae, which did not elicit any illusions (vibration). We
found robust activations in cortical motor areas [areas 4a, 4p, 6; dorsal
premotor cortex (PMD) and bilateral supplementary motor area
(SMA)] and ipsilateral cerebellum during kinesthetic illusions (illusion-vibration). The illusions also activated contralateral area 2 and
right area 2 was active in common irrespective of illusions of right or
left hand. Right areas 44, 45, anterior part of intraparietal region (IP1)
and caudo-lateral part of parietal opercular region (OP1), cortex
rostral to PMD, anterior insula and superior temporal gyrus were also
activated in common during illusions of right or left hand. These
right-sided areas were significantly more activated than the corresponding areas in the left hemisphere. The present data, together with
our previous results, suggest that human kinesthesia is associated with
a network of active brain areas that consists of motor areas, cerebellum, and the right fronto-parietal areas including high-order somatosensory areas. Furthermore, our results provide evidence for a right
hemisphere dominance for perception of limb movement.
AREAS ACTIVE DURING ILLUSORY MOVEMENT OF RIGHT OR LEFT HAND
METHODS
Subjects
Ten right-handed (Oldfield 1971) male subjects (21–33 yr) with no
history of neurological or other disease participated in the study. All
subjects had given their informed consent and the Ethical Committee
of the Karolinska Hospital had approved the study. The fMRI experiment was carried out following the principles and guidelines of the
Declaration of Helsinki (1975).
fMRI measurement and tasks
A 1.5 T General Electric scanner with head-coil provided T1weighted anatomical images (3D-SPGR) and functional T2*weighted echoplanar images (64 ⫻ 64 matrix, 3.4 ⫻ 3.4 mm, TE ⫽
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60 ms). A functional image volume comprised 30 slices of 5-mm
thickness (with 0.4-mm interslice gap); this ensured that the whole
brain was within the field of view.
The subjects were blindfolded and their ears were plugged. They
rested comfortably in a supine position in the MR scanner. The
extended arms were oriented in a relaxed supine position parallel to
the trunk. The arms were supported proximal to the wrist. The hands
were completely relaxed in this position. During the experimental
conditions, the subjects were instructed to completely relax (and make
no movements) and to be aware of the sensation from the wrist.
We vibrated the tendon of wrist extensor muscles (the extensor
carpi ulnaris; ECU) to elicit an illusory palmar flexion of the wrist
(illusion). To control for the effect of the skin vibration, we applied
the identical stimuli to the skin over the processus styloideus ulnae,
which does not elicit any illusion (vibration). A rest condition where
the subjects relaxed completely was also included. We used a nonmagnetic vibrator that was driven by constant air pressure provided by
an air-compressor (Biltema Art. 17– 635, Linköping, Sweden). The
frequency was ⬃80 Hz. The vibration site was ⬃1 cm2. For each
subject, we performed six fMRI sessions: in three of these the right
wrist was vibrated alternating with three sessions in which the left
wrist was vibrated (e.g., left session, right session, left session, and so
forth). A total of 6 ⫻ 128 functional image volumes were collected for
each subject. In each session, there were six conditions. The subjects
were tested on illusion, vibration, and rest when right and left hands
were separated and also when right and left hands were in contact
palm to palm. The results from the latter three conditions have been
reported elsewhere (Naito et al. 2002b). Thus in the present paper, we
only describe the results from the conditions where right and left
hands were separated, i.e., illusion, vibration, and rest. Each condition
lasted for 32 s (8 functional images, TR ⫽ 4 s) and was repeated twice
during each session. The order of conditions was randomized according to a balanced schedule.
In the training session before fMRI, we selected 10 of 16 subjects,
who experienced vivid illusory palmar flexion (⬎20° wrist flexion)
(see METHODS sections in Naito and Ehrsson 2001; Naito et al.
2002a,b). An electromyogram (EMG) from the skin surface of the
vibrated ECU muscle showed slight increase of the activity. From the
flexor muscle (the flexor carpi ulnaris; FCU), we found that no EMG
activity was present during illusion. These EMG results confirmed
those in the previous study (Naito et al. 2002a). During the fMRI
scanning, we observed no overt hand movements in any of the
conditions. After the fMRI, all subjects reported that they vividly
experienced the sensation of a palmar flexion of the vibrated hand.
fMRI data analysis
The fMRI data were analyzed with the Statistical Parametric Mapping software [SPM99; http//:www.fil.ion.ucl.ac.uk/spm; Wellcome
Department of Cognitive Neurology, London, U.K. (Friston et al.
1995a,b)]. The functional images were realigned to correct for head
movements (Ashburner and Friston 1997), co-registered with each
subject’s anatomical MRI, and transformed (linear and nonlinear
transformations) into the reference system of Talaraich and Tournoux
(Ashburner and Friston 1997; Talaraich and Tournoux 1988), using
the Montreal Neurological Institute (MNI) reference brain (Naito et al.
2002b). The functional images were scaled to 100 to correct for global
changes in the MR signal to eliminate the effects of global changes in
the signal and were spatially smoothed with a 8-mm full width at
half-maximum (FWHM) isotropic Gaussian kernel and smoothed in
time by a 4-s FWHM Gaussian kernel. We fitted a linear regression
model (general linear model) to the pooled data from all subjects to
increase the sensitivity of the analysis (fixed effects model) (Naito et
al. 2002b). The validity of this approach, in terms of consistency of
effects across all subjects in the group, was confirmed by conducting
single-subject volume-of-interest (VOI) analyses (see further in the
following text). Each condition was modeled with a boxcar function
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in area 2 respond to input from cutaneous receptors (Costanzo
and Gardner 1980; Gardner 1988; Hyvärinen and Poranen
1978; Iwamura and Tanaka 1978; Iwamura et al. 1993, 1994;
Warren et al. 1986), area 2 may receive a greater amount of
somatosensory input during passive limb movement than during tendon vibration. Nevertheless, if human area 2 is genuinely involved in kinesthetic processing, we would expect to
detect area 2 activity during the kinesthetic illusions if we used
a sensitive imaging method.
If this is the case, it is important to know the functional
differences between M1 and area 2 during kinesthetic illusion.
This brings us to our second hypothesis that area 2 should be
active not only during illusion of the contralateral limb but also
during illusion of the ipsilateral limb, whereas M1 should be
active only during illusion of the contralateral limb (Naito and
Ehrsson 2001). Neurons in monkey’s area 2 are known to
respond to the afferent input not only from the contralateral
limbs but also from the ipsilateral limbs (Iwamura 2000;
Iwamura et al. 1994; Taoka et al. 1998, 2000). Thus we
predicted that area 2 would be active no matter whether
subjects experience illusions of the right or the left limb.
Our third hypothesis was that the right hemisphere would
have a dominant role in kinesthetic processing. It is a common
view in clinical neurology that the right hemisphere is specialized for bodily perception (Berlucchi and Aglioti 1997; Critchley 1953; Devinsky and D’Esposito 2004). This notion is based
on human lesion studies (e.g., Halligan et al. 1993; McGonigle
et al. 2002; Sellal et al. 1996). However, few imaging studies
of intact brains have been conducted to support this view.
Therefore we tested the hypothesis that the right hemisphere is
statistically more active than the left hemisphere when subjects
experience the illusory movements of the right or the left hand.
We utilized fMRI to measure the brain activity when subjects experienced an illusory palmar flexion of the wrist that
was elicited by the tendon vibration of the wrist extensor
muscles. We used fMRI rather than PET because fMRI allowed us to collect a significantly greater number of brain
scans per subject and hence provides a better statistical power
than PET to detect relatively weak but significant brain activities. Furthermore, we vibrated the tendon of the right or left
hand respectively in the same group of subjects. This allowed
us to directly investigate a possible lateralization of the activations during kinesthetic illusions. Finally, we used cytoarchitecturally defined areas from 10 postmortem human brains
to describe the topography of each area in a probabilistic
fashion.
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Testing of dominance of the right-sided regions that are
commonly active during illusions of right and left hands
The conjunction analysis showed that right-sided areas were active
in common during right illusions and left illusions (see RESULTS). This
could indicate lateralization of the right hemisphere for kinesthetic
processing during tendon vibration. However, to directly test if this
reflects a genuine dominance of the right hemisphere, one has to
compare the activities in the right areas with those in the corresponding areas in the left hemisphere. In other words, one has to test if the
right-sided areas are significantly more activated than the corresponding areas in the left hemisphere. We did this by flipping (a right-to-left
transformation in the x axis) the functional images from all scans of all
subjects (the smoothed and normalized images). The right and the left
hemispheres were reversed (flipped images). As just pointed out, this
method allowed us to directly compare an activity in a voxel in the
right hemisphere with the corresponding voxel in the left hemisphere.
We defined a new general linear model that included both the flipped
and the unflipped data. To test whether the blood oxygenation leveldependent (BOLD) signals of the right hemisphere during illusion of
the right hand were significantly greater than those registered in the
left hemisphere, we defined the contrast of [(right illusion–right
vibration) – (right flipped illusion–right flipped vibration)]. The contrast (right illusion–right vibration) was used as an inclusive mask to
exclude the areas that were not active during illusion of right hand
(P ⬍ 0.05, uncorrected). The corresponding contrasts were defined to
test the right-sided dominance during illusion of the left hand. For
these tests, we chose a threshold of P ⬍ 0.05 after a correction for
multiple comparisons in the right regions.
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Single-subject VOI analyses
FUNCTIONAL DIFFERENCES BETWEEN M1 AND AREA 2 DURING ILLUTo investigate functional
SIONS OF THE RIGHT AND LEFT HAND.
differences between M1 and area 2 during illusions of the right and
left hand, a post hoc single-subject analysis was done (see METHODS in
Naito et al. 2002b). When the right illusion was contrasted with the
right vibration, we found peak activities in the left M1 (⫺36, ⫺24, 51)
and in the left area 2 (⫺30, ⫺36, 60). When the left illusion was
contrasted with the left vibration, we found peak activities in the right
M1 (36, ⫺18, 51) and in the right area 2 (48, ⫺27, 51). Two peaks of
(⫺30, ⫺36, 60) and (48, ⫺27, 51) were located in the caudal part of
the postcentral gyrus in all subjects (of the anatomically standardized
T1-weighted MR image of each subject). Similarly, peaks of (⫺36,
⫺24, 51) and (36, ⫺18, 51) were located in the precentral gyrus in all
subjects.
We extracted the fMRI data from the four peaks of activities. We
then calculated the mean percent increase of BOLD signal for each
epoch of illusion compared with vibration conditions. The mean
activity was calculated from six functional images: we excluded the
first two functional images. This was done for all epochs on either
hand in each subject. The percent increase was calculated for each
epoch by using the following formula: (Mean in illusion –Mean in the
corresponding vibration) ⫻ 100 Mean in the corresponding vibration.
Finally, the mean value for each individual subject was calculated
from the six values from six epochs. The right- and left-hand conditions were separately treated. We performed a two-factorial ANOVA
[vibrated side (right or left) (2) ⫻ MI, area 2 (2) repeated measurement design] for the mean of individual subject (see Fig. 3). The
ANOVA was done separately for the right and the left hemisphere.
Dominance of right-sided areas during illusions of right and
left hand
To investigate activities in the regions that are commonly active
during illusions of the right and the left hand, another post hoc
single-subject analysis was done. We extracted the fMRI data from
eight peaks of clusters that were commonly active during illusions of
the right and the left hand (see Table 3 and Fig. 5). We calculated the
mean percent increase for each epoch of the illusion compared with
the rest condition. We also calculated the mean for each epoch of the
vibration compared with the rest condition.
The mean activity was calculated from six functional images: we
excluded the first two functional images. This was done for all epochs
on either hand in each subject. The percent increase was calculated for
each epoch by using the following formula: (Mean in illusion or
vibration –Mean in the corresponding rest) ⫻ 100 divided by Mean in
the corresponding rest.
Finally, the mean value for each individual subject was calculated
from the six values from six epochs. The right- and left-hand conditions were separately treated. We performed a two-factorial ANOVA
[vibrated side (right or left) (2) ⫻ illusion, vibration (2); repeated
measurement design] for the mean of each individual subject for each
peak (Fig. 5).
Anatomical definitions
We used cytoarchitecturally defined areas from 10 postmortem
brains to describe in a probabilistic way the topography of cytoarchitectonic areas 4a, 4p (Geyer et al. 1996; Schleicher et al. 1999), 2
(Grefkes et al. 2001), 6 [dorsal premotor cortex (PMD), and supplementary motor area (SMA)] (Geyer 2004; Geyer et al. 2002), 44 and
45 (Amunts et al. 1999), areas in the intraparietal sulcus region (IP1
and IP2) (Choi et al. 2002), and areas in the parietal opercular region
(OP1, OP2, OP3 and OP4) (Eickhoff et al. 2002) in the standard
anatomical space (Roland et al. 2001). The brains were corrected for
deformations attributable to histological processing and the images
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delayed by 4 s and convoluted with the standard SPM99 hemodynamic response function.
To identify the brain areas that are active during the kinesthetic
illusion we performed pair-wise contrasts of the conditions i.e.,
(illusion–vibration). To identify the areas that were active during
illusion of the right hand, we used the contrast of (right illusion–right
vibration). We used the contrast of (right illusion–right rest) as an
inclusive mask to exclude voxels that were not at all active during the
illusions as compared with the rest condition. This masking procedure
was done to remove voxels that only showed deactivation during
vibration. The threshold for the mask was set at the very liberal
threshold of P ⬍ 0.05, uncorrected so that no relevant areas were
excluded. For the left hand, we used the contrast of (left illusion–left
vibration). We also used the contrast of (left illusion–left rest) as an
inclusive mask (P ⬍ 0.05, uncorrected). We used a significant
threshold of P ⬍ 0.05 (t ⬎ 4.58) corrected for multiple comparisons
in the whole brain space.
To depict the areas that are commonly active during illusions of
right and left hand, we used the SPM99 conjunction analysis of [(right
illusion–right vibration) 艚 (left illusion–left vibration)]. Similarly to
identify the areas that are commonly active during skin vibration over
the bone, the conjunction analysis of [(right vibration–right rest) 艚
(left vibration–left rest)] was performed. This latter conjunction was
done so that we could determine whether the illusion conditions
activated quantitatively different areas from the vibration conditions.
For the conjunction analysis (Price and Friston 1997; Worsley and
Friston 2000), we used the same t threshold (4.58) for each of the two
contrasts because we only wanted to depict those voxels that were
significantly active during right illusions as well as left illusions. This
means that the threshold of the conjunction analysis corresponds to
P ⬍ 0.00000025 for two contrasts after a correction of the number of
multiple comparisons in the whole brain space. Because of this
conservative threshold in the conjunction analysis, one should bear in
mind that we do not report areas that showed a statistical trend for
activation during illusion of one hand and a significant activation
during the illusion of the other hand. Finally, we only report the
clusters whose sizes were ⬎10 voxels in this analysis.
AREAS ACTIVE DURING ILLUSORY MOVEMENT OF RIGHT OR LEFT HAND
RESULTS
All subjects verbally reported that they experienced vivid
illusions of wrist flexion in the illusion condition and no
illusion in the vibration condition during fMRI scanning. When
the tendon on the right wrist extensor muscles (the ECU) was
vibrated, all subjects felt the illusory flexion of the right wrist.
Similarly when the tendon on the left muscle was vibrated, all
subjects felt the illusion of the left wrist. They also reported
that there was no difference in vividness of illusory experience
between the right and left hand. No overt wrist movement was
observed in any of the experimental sessions.
Brain activation during kinesthetic illusion of right
hand movement
When right illusion was contrasted with right vibration, we
found significant activations in cortical motor areas, right
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parietal cortex, bilateral inferior frontal cortices, bilateral prefrontal cortices and right cerebellum (Fig. 1 and Table 1).
In the cortical motor areas, one cluster was located in the left
cytoarchitectonic areas 4a, 4p (M1), and 6 (PMD). This cluster
further extended rostrally into cortex rostal to area 6 (PMD)
and caudally into areas 3a, 3b, and 2. In this cluster, we found
three peaks of activation in areas 4p, 6 (PMD), and 2. The
second cluster was located in the bilateral medial walls of the
frontal lobes. We found three peaks in the left area 6 (SMA/
CMAc) and in the right CMAr and CMAc. The third cluster
was located in the right area 6 (PMD). The peak was located in
the border between area 6 (PMD) and cortex rostral to PMD.
In the right parietal cluster, we found three peaks of activation in areas 2, IP1, and OP1. The bilateral inferior frontal
clusters extended ventrally into the tip of superior temporal
gyrus (STG). In the right cluster, we found four peaks of
activation in areas 44, 45, STG, and anterior insula. In the left
cluster, we found a peak in STG.
Brain activation during kinesthetic illusion of lefthand movement
When left illusion was contrasted with left vibration, we
found significant activations in cortical motor areas, right
parietal cortices, right inferior frontal cortices, right putamen,
and left cerebellum (Fig. 2 and Table 2).
In the cortical motor areas, one cluster was located in the
right areas 4a, 4p, 6 (PMD). This cluster further extended
rostrally into cortex rostal to area 6 (PMD) and caudally into
areas 3a, 3b, 2, IP1, and OP1. In this cluster, we found peaks
of activation in areas 4a, 6 (PMD), 2, IP1, and OP1, respectively. The second cluster was located in the bilateral medial
walls of the frontal lobes. We found three peaks in the left area
6 (SMA/CMAc) and in the right area 6 (SMA/CMAc and
pre-SMA).
In the right inferior frontal cluster, we found peaks in areas
44 and 45 and in the STG. Right superior parietal cortex was
also activated.
Differences between right- and left-hand illusions
To identify areas that are specifically active during the
illusions of right hand movements we contrasted [(right illusion–right vibration) - (left illusion–left vibration)]. The left
M1 was significantly activated (⫺36, ⫺21, 51; area 4p; P ⬍
0.05 corrected for whole brain space). Similarly, the right M1
(36, ⫺18, 51; area 4a) was specifically activated during the
illusion of left hand movement [(left illusion–left vibration) (left illusion–left vibration)].
Activities in M1 and area 2 during illusions of right- or lefthand movement
Figure 3 shows the mean percent increase of the BOLD
signal in M1 and area 2 when illusion was compared with
vibration. The signal in M1 only increased when the subjects
experienced illusory movements of the contralateral hand,
whereas the signal in area 2 also increased when they experienced illusions of the ipsilateral hand as well (Fig. 3). A
two-factorial ANOVA [vibrated side (right or left) (2) ⫻ areas
(MI, area 2) (2); repeated measurement design] of the percent
increase in each area and hemisphere showed significant inter-
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were warped to the same standard anatomical format (Roland et al.
2001) by using the full-multigrid (FMG) method (Schormann and
Zilles 1998).
A population map was generated for each area (Roland and Zilles
1998). The population maps describe, for each voxel, how many
brains have a representation of one particular cytoarchitectonic area.
In the case of anatomically adjacent areas, the individual variation in
the location and extent of each cytoarchitectural area led to population
maps overlapping each other and thus to voxels representing more
than one area. In these cases, the voxel was allocated to the cytoarchitectural area with the highest number of postmortem brains associated with it (Roland and Zilles 1996a, 1998). For example, one
voxel can correspond to area 4a in 5 of the 10 brains and simultaneously to area 4p in 1 of 10 brains. This voxel was then assigned to
area 4a. The result was a probability map of the cytoarchitectural areas
(Roland et al. 2001).
At the “outer” border of a cytoarchitectural area (i.e., where the area
abutted on a cortical region for which microstructural data and thus a
population map was not available, e.g., anterior border of area 6
toward the prefrontal cortex), a threshold of 3 of 10 (30%) brains was
applied. This means that voxels with a representation of a given area
in n ⱖ 3 brains were assigned to this area, whereas voxels with a
representation of this area in n ⬍ 3 brains were discarded. This
criterion has been used before (see e.g., Bodegard et al. 2001; Naito
et al. 2002b). The result of this procedure is a probability map that
provides a working definition of each area’s most probable location in
the standard anatomical space (Roland et al. 2001). The probability
map was finally transformed into the MNI reference brain space
(Ashburner and Friston 1997). This procedure allowed us to relate the
locations of fMRI activation peaks to the cytoarchitectural probability
maps (Mohlberg et al. 2003: www.bic.mni.mcgill.ca/cytoarchitectonics/). This technique provided us with an observer-independent possibility to localize activations in the cytoarchitectonic areas. However,
some cautions are required when interpreting results. Because the
cytoarchitectural areas are probability maps, a voxel in the standard
space can correspond to more than one area, i.e., individual postmortem brains can have different areas located at this particular location.
Thus the anatomical localizations of activations in the cytoarchitectural areas should be considered as “probabilistic indicators.” For
further discussion of the technique of combining functional imaging
and cytoarchitectural mapping, see Bodegard et al. (2001), Ehrsson et
al. (2003), Mohlberg et al. (2003), Naito et al. (2002b); Roland et al.
(2001), Roland and Zilles (1998), and Young et al. (2004).
We adopted the definition of the functional areas of rostral cingulate motor area (CMAr) and caudal cingulate motor area (CMAc) in
the cortical motor system as defined by Roland and Zilles (1996b).
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action between these two factors [F(1,9) ⫽ 17.7, P ⬍ 0.005 for
the left hemisphere; F(1,9) ⫽ 6.8, P ⬍ 0.05 for the right
hemisphere]. This suggests that M1 participates only in the
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processing of kinesthetic illusions of the contralateral hand,
whereas area 2 is involved in the illusions of both right and left
hands.
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FIG. 1. Active regions during kinesthetic
illusion of right-hand movement. Right illusion was contrasted with right vibration
(P ⬍ 0.05 corrected). All clusters are displayed on an anatomical T1-weighted MRI
from a representative single subject. A: horizontal section z ⫽ ⫹58; B: z ⫽ ⫹51; C: z ⫽
⫹34; D: z ⫽ ⫹18; E: z ⫽ ⫹4; F: z ⫽ ⫺24.
Right hemisphere is shown to the right.
AREAS ACTIVE DURING ILLUSORY MOVEMENT OF RIGHT OR LEFT HAND
1. Significant activations when right illusion was
contrasted with right vibration
TABLE
Coordinates of
Peak
Areas
y
z
t-Value
⫺36
⫺30
⫺24
⫺36
51
60
8.35
5.89
⫺27
⫺9
57
5.72
⫺3
3
6
⫺3
15
⫺21
48
42
36
9.39
7.58
5.78
33
0
54
7.04
42
66
69
⫺36
⫺27
⫺24
54
33
21
8.66
8.63
7.75
185
458
56
324
525
51
57
57
36
18
15
21
24
⫺12
⫺3
24
⫺3
10.02
9.87
6.17
7.23
⫺57
45
⫺36
15
⫺36
12
51
48
⫺54
21
⫺6
6
18
⫺24
⫺3
8.64
9.27
6.19
5.49
5.55
109
118
22
13
11
Area IP1 is caudally located to area 2, lining the rostral part of the
intraparietal sulcus and also ventrally extending into supramarginal gyrus
(SMG). Area OP1 is located laterally in the parietal operculum (PO) and also
dorsally extending into SMG (see Fig. 4) and see also (Young et al. 2004).
Coordinates in Talairach and Tournoux (1988) as defined by the Montreal
Neurological Instiutute. The atlas of the human cerebellum is based on that of
Schmahmann et al. (2000). Anatomical naming of the activated areas is based
on coordinates of activation peaks. PMD, dorsal premotor cortex; SMA:
supplemenatry motor area, CMA: cingulate motor area, CMAr: rostral CMA,
CMAc: caudal CMA, STG: superior temporal gyrus, PFC: prefrontal cortex.
x/y indicates border between area x and area y.
Brain regions commonly active during illusions of right- and
left-hand movement
The results from the simple pair-wise contrasts presented in
the preceding text revealed that some areas appeared to be
activated in common during kinesthetic illusions of both rightand left-hand movement. Most notably, frontal and parietal
areas in the right hemisphere seem to be more strongly active
no matter when the subjects experienced illusions of right or
left hand. To verify these observations, we performed two
additional tests (see METHODS). First we used a conjunction
analysis to directly show, in the same statistical image, that the
same voxels were active during both right and left illusions.
Using the contrast (right illusion–right vibration) 艚 (left
illusion–left vibration), we found four clusters of active voxels
in the bilateral medial walls of the frontal lobes (SMA/CMAc),
the right area 6 (PMD), the right parietal cortex, and the right
inferior frontal cortex (Fig. 4 and Table 3). In the medial wall
cluster, we found peaks in bilateral area 6 (SMA/CMAc). In
the right PMD cluster, the peak was located in the border
between area 6 (PMD) and cortex rostal to PMD. In the right
parietal cortex, we found peaks in areas 2, IP1, and OP1.
J Neurophysiol • VOL
Finally, in the right inferior frontal cluster, we found peaks in
areas 44, 45, and STG. From these findings, it is evident that
the commonly active areas were predominantly located in the
right hemisphere.
In contrast, when we identified the brain areas that were
active in common during skin vibration over the right- and
left-sided bone (right vibration–right rest) 艚 (left vibration–left
rest), we only found activations in the bilateral parietal opercular regions (areas OP1 and OP4). It is noteworthy that none
of the regions that were active in common during illusions of
right- and left-hand movement was commonly activated during
vibration stimuli over the skin (minimum t value of 4.58 in the
conjunction analysis). This suggests that there are qualitative
differences in the activation patterns during kinesthetic illusions and during skin vibration with no illusions.
Dominance of the right-sided regions that are commonly
active during illusions of right- and left-hand movement
As described in the preceding text, we found activations in
the frontal and parietal areas that were active in common
during illusions of the right and left hand. This finding appears
to suggest a right-hemisphere dominance in the processing of
kinesthetic illusions. However, to statistically test this hypothesis, one has to directly compare the activities in the right-sided
areas with those in the corresponding areas in the left hemisphere. Therefore we compared the activities of the clusters in
the right hemisphere as detected by the conjunction analysis
with those of the corresponding regions in the left hemisphere
(see METHODS).
We found that when the subjects experienced illusory movements of the right hand, right area 6 (PMD)/cortex rostral to
PMD, area 45, IP1/OP1, and STG were significantly more
activated than the corresponding left regions (Table 4). In
contrast, right SMA and area 2 did not show significantly
stronger activity than the corresponding left regions during
illusions of right-hand movement. During illusions of the left
hand, right area 6 (PMD)/cortex rostral to PMD, 44, 4p, 2, IP1,
and STG were significantly more activated than the corresponding left regions. These results demonstrate a right-hemisphere dominance in the processing of kinesthetic illusions
elicited by the tendon vibration.
Single-subject analysis for a dominance of right-sided areas
during illusions of right- and left-hand movement
To investigate activities in those regions that are active in
common during illusions of right- and left-hand movement,
another post hoc single-subject analysis was done (see METHODS). One purpose of this analysis was to confirm that the
activities in the right-sided regions that were commonly active
during illusions of right- and left-hand movement were not
biased by the data from a few subjects. We tested if the mean
percent increase of the BOLD signal across subjects in the
illusion condition is greater than that in the vibration condition
(see METHODS). Another purpose was to test whether the levels
of activities in the right-sided areas differ between right and
left illusions.
Figure 5 shows that the mean percent increase of the BOLD
signal was greater in the illusion condition than in the vibration
condition in all commonly activated areas [main effect of
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Left areas 4a-4p-6-3a-3b-2 cluster
Area 4p
Area 2
Area 6 (PMD) extending cortex
rostral to PMD
Bilateral medial wall cluster
L area 6 (SMA/CMAc)
R CMAr
R CMAc
Right area 6 cluster
R PMD/cortex rostral to PMD
Right areas 2-IP1-OP1 cluster
Area 2
Areas IP1/OP1
Area OP1
Right areas 44–45-STG-insular
cluster
STG
Area 44
Area 45
Anterior insular
Left areas 44–45-STG cluster
STG
Right PFC
Left PFC
Right cerebellum lobe V
Left anterior insular
x
Cluster
Size
Voxels
1025
1026
NAITO ET AL.
tendon vibration in the ANOVA, see METHODS; left SMA/
CMAc: F(1,9) ⫽ 14.5, P ⬍ 0.005; right SMA/CMAc: P ⬍
0.025; right area 2: P ⫽ 0.11; right PMD/cortex rostral to
J Neurophysiol • VOL
PMD: P ⬍ 0.025; right IP1: P ⬍ 0.05; right area 45: P ⬍ 0.1;
right area 44: P ⬍ 0.025; right STG: P ⬍ 0.025]. In addition,
the left-hand stimulation activated right SMA/CMAc, area 2
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FIG. 2. Active regions during kinesthetic
illusion of left hand movement. Left illusion
was contrasted with left vibration (P ⬍ 0.05
corrected). A: horizontal section z ⫽ ⫹63; B:
z ⫽ ⫹55; C: z ⫽ ⫹34; D: z ⫽ ⫹18; E: z ⫽
⫹4; F: z ⫽ ⫺27. For other conventions, see
legend of Fig. 1.
AREAS ACTIVE DURING ILLUSORY MOVEMENT OF RIGHT OR LEFT HAND
TABLE 2. Significant activations when left illusion was contrasted
with left vibration
Coordinates of
Peak
Structures
x
y
z
558
9.78
6.39
6.32
5.94
5.67
5.15
Methodological considerations
295
9.18
6.65
5.87
306
7.62
7.36
6.42
150
7.92
5.74
5.21
107
7.22
6.22
4.99
5.72
limb (Fig. 3). This suggests functional differences in the
processing of kinesthetic signals between M1 and area 2.
Third, we found a dominance of the right hemisphere in
brain activation during kinesthetic illusions. Right area 6
(PMD)/cortex rostral to PMD, areas 44, 45, IP1, OP1, anterior
insula, and STG were all activated in common during illusions
of right and left hand (Fig. 4). These right-sided areas were
significantly more activated than the corresponding areas in the
left hemisphere (Table 4). This provides the first neurophysiological evidence for a dominant role of the right hemisphere
in human kinesthetic processing.
17
See Table 1.
and PMD/cortex rostral to PMD significantly more than the
right-hand stimulation [main effect of the vibrated side in the
ANOVA; SMA/CMAc: F(1,9) ⫽ 5.5, P ⬍ 0.05; area 2: P ⬍
0.025; PMD/cortex rostral to PMD: P ⬍ 0.005]. In contrast,
there were no significant differences between right- and lefthand stimulation in right IP1, areas 44 and 45, and STG (P ⬎
0.33 for all regions).
In the illusion and vibration conditions, we vibrated the skin
surface at two sites of the wrist. Because the size of skin area
that was contacted by the vibrator was identical (⬃1 cm2) and
we used the same frequency (80 Hz) of vibration stimuli,
similar sets of skin receptors would probably be recruited in
these two conditions (Naito and Ehrsson 2001). It is very
unlikely that the conspicuous differences in brain activations
observed during the illusion and vibration conditions were due
to the fact that we vibrated the different skin areas around the
wrist. The distance between the two stimulation areas was
small [3.6 ⫾ 0.5 (SD) cm], and therefore the cutaneous afferent
input should be very similar. The difference in activation
between these two conditions arose from the fact that the
tendon of the wrist extensor muscle was only vibrated in the
illusion condition. This tendon vibration is an optimal stimulus
to excite muscle spindle afferents and elicit kinesthetic illusions (Naito and Ehrsson 2001; Naito et al. 1999, 2002a,b; Roll
and Vedel 1982; Roll et al. 1989). In contrast, when we
vibrated the skin surface over the nearby bone, the subjects did
not experience any reliable illusions because the tendon was
not directly stimulated. Although muscle spindles are highly
DISCUSSION
We measured brain activities by fMRI when healthy human
subjects experienced kinesthetic illusory flexions of the right or
left wrist elicited by tendon vibration. There were three main
findings.
First, in the absence of actual limb movements, we found
robust activations in the contralateral cortical motor areas
[areas 4a and 4p (M1) and 6 (PMD)]. We also found strong
activity in bilateral medial area 6 (SMA/CMAc) and in the
ipsilateral anterior cerebellum. These results corroborate those
from our earlier studies that the motor system participates in
the processing of kinesthetic illusions (Naito 2004; Naito and
Ehrsson 2001; Naito et al. 1999, 2002a,b).
Second, as suggested by electrophysiological studies in
monkeys, cytoarchitectonic area 2, especially right area 2, was
also involved in the processing of kinesthetic signals in human
subjects. However, the engagement of area 2 in kinesthetic
illusions was different from that of M1 in a sense that M1 was
strictly active during illusions of the contralateral limb,
whereas area 2 was also active during illusions of the ipsilateral
J Neurophysiol • VOL
FIG. 3. Mean percent increase of the blood oxygenation level-dependent
(BOLD) signal in M1 and area 2 when illusion was compared with vibration
(single-subject analysis). The signal in M1 only increased when the subjects
experienced illusory movements of the contralateral hand, whereas the signal
in area 2 also increased when they experienced illusions of the ipsilateral hand
as well. Bars indicate SE.
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Right areas 4a-4p-6-3a-3b-2-IP1-OP1
cluster
Area 4a
36 ⫺18
51
Area 6 (PMD) extending cortex
rostral to PMD
27 ⫺18
63
Area IP1/OP1
57 ⫺33
33
Areas 2/IP1
63 ⫺27
42
Area 2
48 ⫺27
51
Area OP1
69 ⫺33
24
Bilateral medial wall cluster
R area 6 (SMA/CMAc)
6 ⫺3
51
L area 6 (SMA/CMAc)
⫺6 ⫺3
48
R area 6 (Pre-SMA)
9
15
60
Right areas 44–45-STG-insular
cluster
Areas 44/45
60
18
18
STG
51
24 ⫺15
Area 44
60
15
6
Left cerebellum cluster
Lobe V
⫺18 ⫺51 ⫺27
Lobe V
⫺27 ⫺42 ⫺39
Crús I
⫺27 ⫺66 ⫺33
Right putamen-insular cluster
Rostral
30 ⫺9
0
Caudal
27
9 ⫺3
Anterior insular
36
18
0
Right superior parietal
15 ⫺48
63
Cluster
Size
t-Value Voxels
1027
1028
NAITO ET AL.
J Neurophysiol • VOL
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FIG. 4. Active regions shared by illusions
of right- and left-hand movement. All clusters and cytoarchitectonic maps are displayed on an anatomical T1-weighted MRI
from a single subject. Right hemisphere is
shown to the right. Blue voxels indicate
cytoarchitectonic probability map of area 6.
Yellow voxels: area 2; orange voxels: area
IP1; dark blue voxels: IP2; green voxels:
area 45; white voxels: area 44; light yellow
voxels: area OP1; light blue voxels: area
OP4; light green voxels: area OP2; pink
voxels: area OP3. Superimposed clusters encircled by red voxels are the results of the
conjunction analysis (right illusion–right vibration) 艚 (left illusion–left vibration). We
employed the same t threshold of 4.58 as
used in the contrast of (illusion–vibration).
The bilateral medial area 6 (SMA/CMAc),
right cortex rostral to PMD (area 6), areas 2,
44 and 45, IP1, and OP1, anterior insula and
tip of STG were commonly activated. The
right hemisphere was predominantly activated no matter whether the subjects experienced illusions of the right or left hand.
AREAS ACTIVE DURING ILLUSORY MOVEMENT OF RIGHT OR LEFT HAND
TABLE
3. Common active areas during right illusion and
left illusion
Coordinates of
Peak
Structures
y
z
t-Value
3
⫺6
0
⫺3
51
48
7.93
6.65
39
63
57
⫺36
⫺27
⫺27
57
42
33
7.46
5.94
5.85
51
57
60
57
24
21
15
18
⫺15
24
6
⫺6
7.36
6.17
6.42
6.32
33
⫺3
54
6.57
176
134
207
42
See Table 1.
sensitive and some spindles in the hand would be activated by
the spread of the vibration from the bone to the surrounding
tissue, this spread was not strong enough to elicit any clear
illusions. In a previous study, we found that when we vibrated
the skin surface over the tendon, we never elicited any illusions
nor found any motor activations (10 and 220 Hz) unless we
used optimal vibration frequency (70 and 80 Hz) (Naito et al.
1999). Thus the present brain activations detected when illusion was contrasted with vibration is most likely to be associated with kinesthetic illusions elicited by afferent information
from muscle spindles excited by tendon vibration at an optimal
frequency (80 Hz). We did not measure the attention to the
stimuli in the different conditions. However, we think it is
unlikely that differences in attention could explain our results.
First, the subjects did not perform any active task, they were
just instructed to relax and be aware of the sensation form their
wrists. Second, the subjects were instructed to be aware of their
wrists both in the illusion and in the vibration conditions. This
suggests that the participants were attending slightly to the
stimulated hand in both conditions.
1994; Taoka et al. 1998, 2000). The bilateral involvement of
area 2 in the central processing of kinesthetic illusions is
different from the strictly contralateral engagement of M1 (Fig.
3). This difference implies that M1 and area 2 might participate
in different stages of neuronal processing of kinesthetic information and suggests that human area 2 is a high-order somatosensory area (Bodegard et al. 2001; Roland et al. 1998).
In addition, we found peaks of activation in areas IP1 and
OP1 in the right hemisphere when the subjects experienced
illusory wrist movements. Area IP1 is caudally located to area
2, lining the rostral part of the intraparietal sulcus and also
extending into supramarginal gyrus (SMG; Fig. 4B). Area OP1
is located laterally in the parietal operculum (PO; Fig. 4D) and
also extending into SMG (Fig. 4C) (see also Young et al.
2004). These areas are considered to be high-order somatosensory areas in humans in a sense that they are engaged in
somatosensory tasks but less somatotopically organized
(Young et al. 2004). Indeed, identical section in the right areas
IP1 and OP1 was commonly engaged in illusions of right- or
left-hand movements.
The precise homology between the cytoarchitectural areas of
the human and monkey inferior parietal lobe is still unknown
(Eidelberg and Galaburda 1984). In the present study, the
activation (areas IP1 and OP1) associated with kinesthetic
illusion was located in the lateralmost part of the inferior
parietal cortex (Fig. 4, Table 1). Similarly, the lateral and
posterior part of the monkey inferior parietal cortex (area
7b/PF) contains neurons that predominantly respond to somesthetic input (Hyvärinen 1981; Hyvärinen and Shelepin
1979). In fact, it has been suggested that the inferior parietal
cortex in monkeys (area 7b/PF) corresponds to the SMG in the
human brain (Passingham 1998). In the monkey brain, this
somaesthetic section of the inferior parietal cortex has ipsilateral cortical connections with areas 2, 4, 5, 45, PO (Hyvärinen
1982a,b; Neal et al. 1987, 1990b), ventral premotor cortex
(Ghosh and Gattera 1995; Godschalk et al. 1984; Neal et al.
1990a), SMA (Cavada and Goldman-Rakic 1989), and insular
cortex (Neal et al. 1987, 1990b 1990b). In our present study,
we observed activations in all these areas in conjunction with
TABLE 4. Comparing activation in the right hemisphere and the
left hemisphere (flip analysis)
Coordinates of
Peak
Cytoarchitectonic area 2 and parietal cortex
Area 2 was more strongly activated when the tendon was
vibrated over the skin (illusion) than when only the skin was
vibrated without directly involving the tendon (vibration; Fig.
5C). Hence, the activity in this area probably reflects the
processing of kinesthetic afferent input from muscle spindles.
This result fits well with results from earlier single-unit studies
in non-human primates that neurons in area 2 react to kinesthetic afferent input during passive limb movements (see references in the INTRODUCTION).
Area 2 was active during illusions of not only the contralateral but also the ipsilateral hand (Fig. 1, A and B) even though
the activity in area 2 was larger when the contralateral hand
was stimulated (Fig. 3). This finding is in good agreement with
findings in non-human primates that neurons in area 2 respond
to somatosensory afferent input from not only the contralateral
but also the ipsilateral limb (Iwamura 2000; Iwamura et al.
J Neurophysiol • VOL
Structures
Right illusion: unflipped vs
flipped
R STG
R cortex rostral to PMD/area 6
(PMD)
R area 45
R area IP1/OP1
Left illusion: unflipped vs flipped
R STG
R cortex rostral to PMD/area 6
(PMD)
R area 44
R area 4p
R area 2
R IP1
See Table 1.
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z
t-Value
Cluster
Size
Voxels
27
⫺15
6.87
91
36
57
63
3
24
⫺24
51
18
33
5.17
4.6
3.9
24
41
17
51
27
⫺12
3.86
12
33
57
36
48
60
3
15
⫺30
⫺24
⫺24
54
21
57
48
39
3.95
5.99
6.02
5.18
4.8
12
71
119
x
y
48
Downloaded from http://jn.physiology.org/ by 10.220.33.2 on June 17, 2017
Bilateral medial wall cluster
R area 6 (SMA/CMAc)
L area 6 (SMA/CMAc)
Right areas 2-IP1-OP1 cluster
Area 2
Area IP1
Areas IP1/OP1
Right areas 44–45-STG-insular
cluster
STG
Area 45
Area 44
STG/areas 44/45
Right area 6 (PMD)/cortex rostal
to PMD
x
Cluster
Size
Voxels
1029
1030
NAITO ET AL.
Frontal areas
Kinesthetic illusions activated the contralateral areas 4a, 4p,
and 6 (PMD), bilateral SMA (area 6), CMA, and pre-SMA
(area 6), and the ipsilateral cerebellum. The contralateral cluster extended into areas 3a and 3b, but we could not find any
significant peaks in these areas. The activity in M1 (areas 4a
and 4p) was strictly related to the illusions of the contralateral
hand (Fig. 3), whereas SMA and CMA were bilaterally engaged in illusions. The evidence that SMA and CMA participates in the kinesthetic processing of muscle spindle afferent
input fits with the finding that many neurons in the SMA and
CMA respond to proprioceptive input during joint rotation and
muscle stretch (Cadoret and Smith 1995). The bilateral activation pattern in these areas irrespective of illusions of right- or
left-hand movement (Fig. 4) is most probably due to interconnection between right and left SMA as has been well established by non-human primates studies showing that neurons in
two SMAs are strongly interconnected (Rouiller et al. 1994;
Tanji 1994).
One of the new observations in the present study was that
kinesthetic illusions activated the border between area 6
(PMD) and cortex rostral to PMD in the right hemisphere no
matter if the participants experienced illusions of right or left
hand (Fig. 4). In the present study, the blindfolded subjects
were instructed to be aware of the hand movements with no
intention of executing movement. When we sense limb movement, we are not only aware of the changes in joint angle, but
we also sense the changes of limb location in extrapersonal
space. We speculate that the activity in this area is related to
the somatic monitoring of positional changes of the limb in
extrapersonal space because this area is associated with spatialcognitive processes in primates (Boussaoud 2001; Picard and
Strick 2001).
In addition, we found a large active cluster that was located
in the inferior frontal cortex and that extended into the anterior
insula and superior temporal cortex. We know that lesions that
damage this region impair the normal perception of one’s own
body (Berlucchi and Aglioti 1997; Sellal et al. 1996), and thus
FIG. 5. Mean percent increase of the BOLD signal in the areas that were
active in common when illusion was compared with rest and vibration
compared with rest, respectively. Bars indicate SE.
J Neurophysiol • VOL
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activation in SMG (areas IP1 and OP1); this indicates that the
human SMG could be an important node in the network of
fronto-parietal sensorimotor-related areas that represent limb
movements.
The involvement of the right PO (area OP1) in kinesthetic
illusions is consistent with the early observation that the right
PO was activated during passive movements of the right arm
(Weiller et al. 1996). Although PO seems to be activated by a
wide range of somatosensory stimuli (Bodegard et al. 2000;
Ledberg et al. 1995; Naito et al. 1999; Roland et al. 1998), our
results indicate that the right PO is active when we sense limb
movements. Although the role of the right inferior parietal
areas in kinesthetic processing is still unclear, the present
results fit well with human brain lesion studies demonstrating
that damage to the right inferior parietal cortex impairs perception of one’s own body (Berlucchi and Aglioti 1997;
Damasio 1999; Hyvärinen 1982b; Sellal et al. 1996).
AREAS ACTIVE DURING ILLUSORY MOVEMENT OF RIGHT OR LEFT HAND
J Neurophysiol • VOL
Right hemispheric dominance for kinesthetic processing
An important observation was that right area 6 (PMD)/
cortex rostral to PMD, areas 44, 45, IP1, OP1, anterior insula,
and STG were statistically more activated than the corresponding regions in the left hemisphere no matter whether the
subjects experienced illusions of the right or left hand. Importantly, none of these right-sided areas was activated in common
when the skin surface over the nearby bone of right or left hand
was vibrated. Thus it is unlikely that the activity in these
right-sided areas reflects the somatosensory processing of skin
vibration or attention to somatosensory stimuli. Rather, the
activities in these right-sided areas seem to be related to the
processing of kinesthetic information, which is consistent with
the results from human brain lesion studies (Halligan et al.
1993; McGonigle et al. 2002; Sellal et al. 1996).
Claims of hemispheric dominance of brain functions have
rarely been statistically supported with the exception of language dominance in the left hemisphere (Binder et al. 1997;
Springer et al. 1999; Vikingstad et al. 2000; Wada and Rasmussen 1960). Here a hemispheric dominance for human
kinesthesia has been statistically demonstrated for the first time
in a neuroimaging experiment of intact brains, though a dominance of the right hemisphere for somatosensory functions has
been suggested (thermal pain: Coghill et al. 2001; tactile and
proprioception: Kawashima et al. 2002). The reason for this
right-sided dominance in right-handed subjects is unknown.
However, one may conjecturally suggest a developmental
arrangement of the functional organization of language and
body functions, permitting simultaneous use of language and
motoring of somatic functions (e.g., Chiron et al. 1997; Corballis et al. 2000; Geschwind and Galaburda 1985; Karnath
2001). This would give the brain a benefit of avoiding interference between language and somatic functions (Roland 2002;
Roland and Zilles 1998).
As stated, our results suggest that the right hemisphere is
specialized for the perception of one’s own body. Interestingly,
this conclusion fits well with the observation that patients that
undergo preoperative evaluation lose awareness and memory
of arm weakness during amytal inactivation of their right
hemisphere (Carpenter et al. 1995; Meador et al. 2000). During
such inactivation testing, these patients no longer feel the
weakness of their arm, they lose the ability to visually recognize the weak arm as their own, and they become poor in
pointing to different parts of their arm. Thus our results that, in
healthy subjects, perception of an illusory limb movement
engages a right-sided network of frontal and parietal areas,
provides a neurophysiological basis for these perceptual deficits in patients after inactivation of the right hemisphere.
GRANTS
This study was supported by the Axel and Margaret Ax:sson Johnsson’s
Foundation and the Swedish Medial Research Council (Project 9456-11A and
5925). E. Naito was supported by the grant-aids for the exchange of foreign
research for young scientists from the Ministry of Education, Culture, Sports,
Science, and Technology (MEXT) Japan. H. H. Ehrsson was supported by a
postdoctoral grant from the Human Frontier Science Programme.
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it is possible that the activity in these areas is related to
kinethetic perception. The inferior frontal peak was located in
the right-sided equivalent of Broca’s area (areas 44 and 45)
(Amunts et al. 1999). Previously, right areas 44 and 45 were
activated during motor imagery of the right hand (Binkofski et
al. 2000; Ehrsson et al. 2003) and when visually observing
hand actions (Buccino et al. 2001). Right area 44, together with
right PMv (ventral part of area 6), is also active during the
performance of skilled finger movements of the right hand
(Ehrsson et al. 2001). Thus right areas 44 and 45 appear to be
related both to kinesthetic and motor representations of hand
actions.
Activation in the anterior insular cortex is commonly observed during painful and unpleasant stimulation, and it has
been suggested that these regions contain a representation of
the physical condition of one’s body (Craig 2002). Finally, a
distinct peak of activity was found in the right tip of the STG
during illusions. The superior temporal gyrus is a multimodal
sensory area that receives somatosensory input (Jones and
Powell 1970; Seltzer and Pandya 1978), and human lesion
studies suggest that this region may be involved in functions
related to spatial awareness (Karnath et al. 2001).
How does the muscle spindle information reach the nonprimary frontal and parietal areas? In non-human primates neurons in M1 (Asanuma et al. 1980; Brinkman et al. 1985;
Colebatch et al. 1990; Fetz et al. 1980; Hore et al. 1976; Huerta
and Pons 1990; Lemon 1981; Lemon et al. 1976; Lemon and
Porter 1976; Lemon and Van Der Burg 1979; Porter and
Lemon 1993; Rosén and Asanuma 1972; Strick and Preston
1982; Wong et al. 1978), area 3a (Hore et al. 1976; Huerta and
Pons 1990; Iwamura et al. 1983; Philips et al. 1971; Schwarz
et al. 1973), and area 2 (Burchfiel and Duffy 1972; Costanzo
and Gardner 1981; Gardner and Costanzo 1981; Iwamura et al.
1993, 1994; Jennings et al. 1983; Mountcastle and Powell
1959; Schwarz et al. 1973) respond to muscle spindle afferent
input. It is well established that M1 is connected with cytoarchitectonic area 2 (Darian-Smith et al., 1993; Ghosh et al.
1987; Jones et al. 1978; Leichnetz 1986; Pons and Kaas 1986)
and with SMA and PMD (Darian-Smith et al. 1993; Godschalk
et al. 1984; Ghosh et al. 1987; Jones et al. 1978; Leichnetz
1986; Stepniewska et al. 1993). Area 2 is also connected with
SMA and PMD (Pons and Kaas 1986). The inferior parietal
cortex has ipsilateral connections with areas 2, 4, 45, PO
(Hyvärinen 1982a,b; Neal et al. 1987, 1990b), ventral premotor
cortex (Ghosh and Gattera 1995; Godschalk et al. 1984; Neal
et al. 1990a), SMA (Cavada and Goldman-Rakic 1989), and
the insular cortex (Neal et al. 1987, 1990b). In addition,
fronto-parietal opercular regions and insular cortex are connected with sensory-motor areas (Cipolloni and Pandya 1999;
Darian-Smith et al. 1993; Guldin et al. 1992; Preuss and
Goldman-Rakic 1989). This evidence suggests that also in
humans the kinesthetic information from muscle spindles is
spread from “primary” motor and sensory areas to “nonprimary” fronto-parietal association areas. However, it should be
stressed that future studies are needed to elucidate the exact
roles of these nonprimary areas in kinesthetic perception. So
far we only have conclusive evidence that activity in the
primary motor cortex reflect the perception of limb movement
per se (Naito 2004; Naito et al. 2002b).
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