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All content in this area was uploaded by Jiro Gyoba
Content may be subject to copyright.
Speci®c brain processing of facial expressions in
people with alexithymia: an H
2
15
O-PET study
Michiko Kano,
1,2,3
Shin Fukudo,
2,3
Jiro Gyoba,
4
Miyuki Kamachi,
5
Masaaki Tagawa,
1
Hideki Mochizuki,
1
Masatoshi Itoh,
6
Michio Hongo
7
and Kazuhiko Yanai
1
Departments of
1
Pharmacology,
2
Behavioral Medicine,
3
Psychosomatic Medicine, Tohoku University School of
Medicine,
4
Department of Psychology, Tohoku University,
Sendai,
5
ATR-International Human Information Science
Laboratories Department 2, Kyoto,
6
Cyclotron and
Radioisotope Center, Tohoku University and
7
Department
of Comprehensive Medicine, Tohoku University School of
Medicine, Sendai, Japan
Correspondence to: Professor Kazuhiko Yanai, MD, PhD,
Department of Pharmacology, Tohoku University School of
Medicine, 2-1 Seiryo-cho, Aoba-ku, Sendai 980-8575,
Japan
E-mail: yanai@mail.cc.tohoku.ac.jp
Summary
Alexithymia is a personal trait characterized by a
reduced ability to identify and describe one's own feel-
ings and is known to contribute to a variety of physical
and behavioural disorders. To elucidate the pathogen-
esis of stress-related disorders and the normal functions
of emotion, it is important to investigate the neurobiol-
ogy of alexithymia. Although several neurological mod-
els of alexithymia have been proposed, there is very
little direct evidence for the neural correlates of alex-
ithymia. Using PET, we studied brain activity in sub-
jects with alexithymia when viewing a range of
emotional face expressions. Twelve alexithymic and 12
non-alexithymic volunteers (all right-handed males)
were selected from 247 applicants on the basis of the
20-item Toronto Alexithymia Scale (TAS-20). Regional
cerebral blood ¯ow (rCBF) was measured with H
2
15
O-
PET while the subjects looked at angry, sad and happy
faces with varying emotional intensity, as well as neu-
tral faces. Brain response in the subjects with alexithy-
mia signi®cantly differed from that in the subjects
without alexithymia. The alexithymics exhibited lower
rCBF in the inferior and middle frontal cortex, orbito-
frontal cortex, inferior parietal cortex and occipital cor-
tex in the right hemisphere than the non-alexithymics.
Additionally, the alexithymics showed higher rCBF in
the superior frontal cortex, inferior parietal cortex and
cerebellum in the left hemisphere when compared with
the non-alexithymics. A covariance analysis revealed
that rCBF in the inferior and superior frontal cortex,
orbitofrontal cortex and parietal cortex in the right
hemisphere correlated negatively with individual TAS-
20 scores when viewing angry and sad facial expres-
sions, and that no rCBF correlated positively with TAS-
20 scores. Moreover, the anterior cingulate cortex and
insula were less activated in the alexithymics' response
to angry faces than their response to neutral faces.
These results suggest that people with alexithymia pro-
cess facial expressions differently from people without
alexithymia, and that this difference may account for
the disorder of affect regulation and consequent pecu-
liar behaviour in people with alexithymia.
Keywords: ACC, alexithymia, facial expression, lateralization, PET
Abbreviations: ACC = anterior cingulate cortex; fMRI = functional MRI; rCBF = regional cerebral blood ¯ow; SPM =
statistical parametric mapping; TAS-20 = 20-item Toronto Alexithymia Scale
Introduction
Alexithymia is a subclinical phenomenon characterized by
the following: reduced ability to identify and describe one's
feelings, dif®culty in distinguishing feelings from the bodily
sensations of emotional arousal and impaired symbolization,
along with a tendency to focus on external events rather than
inner experiences (Nemiah et al., 1976; Taylor, 1994; Taylor
et al., 1999). People with alexithymia tend to avoid internal
emotional con¯ict by relying on action to express emotion.
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They are socially conforming but humourless (Haviland et al.,
1996). This condition is considered a disorder of affect
regulation (Taylor et al., 1999).
Alexithymia has been reported as a typical personality
problem among patients with psychosomatic disorders
(Sifneos, 1973). Previous studies have reported a high rate
of alexithymia in patients with irritable bowel syndrome,
somatization, panic disorder, eating disorders, post-traumatic
stress disorders and substance abuse problems, suggesting
that alexithymia might have adverse effects on mental and
physical health (Taylor et al., 1991; Parker et al., 1993;
Taylor, 2000). Therefore, investigating the role of alexithy-
mia in the development of these disorders is of great interest.
It is especially important to study the brain activity of people
with alexithymia in order to elucidate the pathogenesis of
psychosomatic disorders and the normal functions of emotion.
There are several neurological models for alexithymia.
One of them, proposed by McLean (1949), postulates a
discommunication between the limbic and neocortical areas.
In this model the limbic system provides the physiological
sensation of emotions, while the neocortex offers the
symbolic representation of emotions. The second model
points to reduced interhemispheric communication evidenced
by split-brain patients being more alexithymic than the
controls (Hoppe and Bogen, 1977; TenHouten et al., 1986).
The third model involves dysfunction of the right hemisphere,
because highly alexithymic individuals, as well as patients
with right hemisphere lesion, show less accuracy in
recognizing facial expressions of emotions (Parker et al.,
1993; Mann et al., 1994; Lane et al., 1995), photographs of
emotional scenes and the emotional nuance of sentences
(Lane et al., 1995). The fourth model postulates a de®ciency
in the activation of the anterior cingulate cortex (ACC) during
emotional processing as a cause of alexithymia, suggesting
that people with alexithymia have a de®cit in the conscious
awareness of emotion (Lane et al., 1987). In addition, a PET
study revealed positive correlation between high scores on
the Level of Emotion Awareness Scale and increased activity
in the right ACC during emotional processing when watching
®lms or remembering personal experiences (Lane et al.,
1997). Recently, a functional MRI (fMRI) study showed that
alexithymia can be associated with deactivation and acti-
vation in ACC in response to highly negative emotional
stimuli and highly positive emotional stimuli, respectively
(Berthoz et al., 2002).
Many clinical reports and experimental studies have
supported the hypothesis that alexithymia might be associated
with variations in brain activity. However, most of these
studies have relied mainly on indirect methods to characterize
the brain functions of people with alexithymia. Even the
proposed dysfunction in ACC demonstrated by the fMRI
study might be insuf®cient to account for all of the features of
alexithymia. Therefore, the underlying neural structure of
people with alexithymia still remains to be elucidated.
Facial expressions are non-verbal communicative displays
that convey affective messages (King and Brothers, 1992).
Because previous studies have shown a correlation between
alexithymia and a lack of ability to recognize emotions in
photographs of facial expressions (Parker et al., 1993; Mann
et al., 1994; Lane et al., 1995, 2000), in the present study we
examined how the brain activity of people with alexithymia is
affected when they look at pictures of various facial
expressions, and compared the results with those of people
without alexithymia. Moreover, to clarify the effect of
valence (positive or negative) and emotional intensity (high
or low arousal), we adopted as stimuli four emotional
categories (anger, sadness, happiness and neutral) and a
range of three levels of emotional intensity (mild, moderate
and intense) for each emotional category. Using PET, direct
observation of the brain activity of subjects viewing facial
expressions is expected to elucidate the speci®c neural
structure in people with alexithymia. The question is whether
the neural variations in people with alexithymia correspond
with previous neurological models for alexithymia.
Material and methods
Subjects
Two hundred and forty-seven male volunteers were screened
for levels of alexithymia, using the 20-item Toronto
Alexithymia Scale (TAS-20), which is the most psychome-
trically valid measurement of alexithymia (Bagby et al.,
1994a, b). The TAS-20 is a self-report questionnaire with a
maximum score of 100 that measures participants' ability to
describe and identify feelings, and their tendency to exhibit
externally oriented thinking. Participants answer questions on
a ®ve-point scale indicating `strongly disagree' to `strongly
agree.' The Japanese version of the TAS-20 has been found to
be psychometrically valid (Fukunishi et al., 1997). The
averaged TAS-20 score of the 247 volunteers was 46.5 6 8.5
(mean 6 SD). Individuals with a TAS-20 total score of >61
were considered alexithymic, and those with a score of <51
were considered non-alexithymic (Taylor et al., 1999). In this
study, the PET subjects consisted of 12 alexithymic and 12
non-alexithymic subjects who were selected according to
these cut-off points (TAS-20 total score). The alexithymics
and non-alexithymic subjects were aged 23.2 6 2.4 and 22.8
6 1.7 years, respectively (mean 6 SD). All subjects were
evaluated as right-handed based on the Edinburgh inventory
(Old®eld, 1971). None of the subjects had a history of
psychiatric or neurological disorders, nor were any of them on
medication. Informed consent was obtained from all subjects
according to the Declaration of Helsinki, and all experiments
were performed in compliance with relevant laws and
institutional guidelines.
Facial expression images
Static images of Japanese models (expressers) in their 20s
were selected from the ATR (ATR International) face
database (Kamachi et al., 2001). This database is comprised
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of 60 males and 60 females showing basic facial expressions.
These faces had previously been rated on all expression
categories, making it possible to select models who were
good exmples of each of the required expressions. Four facial
expressionsÐanger, sadness, happiness and neutralityÐeach
expressed by 20 models (10 females and 10 males), were
selected and used as stimuli in the experiment. For each
emotional category and individual face used in this experi-
ment, a range of three levels of emotional intensity (33%
mild, 67% moderate, 100% intense) was produced by
computer graphic manipulation to enable the measurement
of various levels of emotional intensity. The 33 and 67%
emotional intensity faces were interpolations created using
computer morphing procedures (Kamachi et al., 2001). These
involved the shifting of the shape and the shading of the
neutral face (0%) towards the angry, happy or sad prototype
(100%).
Experimental task
In order to investigate implicit or automatic processing of
facial expressions under conditions free of bias and the
decision-making process, the subjects viewed static images of
emotional faces on a computer monitor screen and were
simply required to determine the gender of each face (male or
female) by pressing the left or right response button.
Attention to each face stimulus was required, but recognition
or categorization of the emotional expression was not
required during this task.
Several previous studies adopted this gender discrimin-
ation task as the ®rst step in examining implicit facial
expression processing (Morris et al., 1996; Phillips et al.,
1997; Sprengelmeyer et al., 1998; Blair et al., 1999; Critchley
et al., 2000a, b).
Experimental design
For each subject, 10 separate PET scans were required. The
scans consisted of one scan for the neutral facial expression,
three scans for anger (mild, moderate and intense), three
scans for sadness and three scans for happiness. During each
of the 10 PET scans, 20 photographs (10 females and 10
males) with the same emotional category and intensity of
emotional expression were presented, one at a time, on a
computer monitor screen. Each photograph was displayed for
3 s, followed by a 2 s interval. The order of emotional faces
presented was counterbalanced across the subjects.
Subject debrie®ng
Immediately after each scanning session, the subjects were
informed that all 20 individuals in the photographs had
displayed the same emotional category, and were asked to
recall and identify the emotions being expressed by the 20
individuals. They evaluated the intensity of anger, sadness,
happiness, disgust, fear and surprise on a 10-point scale. A
score of 10 corresponded to maximal intensity, while a score
of 1 corresponded to minimal intensity. The rating scores
were used to reveal differences between alexithymics and
non-alexithymics in their ability to accurately recognize the
emotions shown in facial expressions.
PET scan acquisition
Scans of the distribution of H
2
15
O were obtained using an
SET-2400W PET scanner (Shimadzu, Kyoto, Japan) operated
in high sensitivity 3D mode, with an average axial resolution
of 4.5 mm at maximum strength and sensitivity for a 20 cm
cylindrical phantom of 48.6 kcps/kBq/ml in the 3D mode
(Fujiwara et al., 1997). The subjects received ~5 mCi (185
MBq) of H
2
15
O intravenously through the antecubital vein for
each scan and engaged in the task during measurements of
regional cerebral blood ¯ow (rCBF). The task started 30 s
before the PET scan and ®nished 15 s after the end of the
scan.
Fig. 1 SPMs of a comparison of 12 alexithymic versus 12 non-
alexithymic subjects while viewing facial expressions. Each ®gure
depicts the brain areas where the rCBF was signi®cantly (P <
0.0001, uncorrected) lower in the alexithymics than in the non-
alexithymics while the subjects looked at (A) angry, (B) sad, (C)
happy and (D) neutral faces. The lower rCBF responses in the
alexithymic group were mainly lateralized in the neocortex of the
right hemisphere.
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PET data analysis
Statistical parametric mapping (SPM) software (SPM99;
Wellcome Department of Cognitive Neurology, London, UK)
was used for image realignment, normalization and smooth-
ing, and to create statistical maps of signi®cant rCBF changes
(Friston et al., 1995a, b). All rCBF images were stereo-
taxically normalized using nonlinear transformation into the
standard space of Talairach and Tournoux (1988). The
normalized images were smoothed using a 12 3 12 3 12 mm
Gaussian ®lter, and the values of rCBF were expressed as
ml/dl/min, adjusted using ANCOVA (analysis of covariance)
and scaled to a mean of 50. Group and covariate effects were
estimated according to the general linear model at each voxel.
To determine whether there are speci®c brain regions
correlated with alexithymia, we performed three types of
analysis. In all analyses, the estimates were compared using
linear compounds or contrasts, and the resulting set of voxel
values for each contrast constituted a parametric map of the
t-statistic. In the ®rst analysis, we compared rCBF changes
between alexithymics and non-alexithymics when they
looked at the same category of emotional faces (anger,
sadness or happiness). In order to maximize the sensitivity of
the analysis, mild, moderate and intense levels of emotional
intensity were combined in each emotional category. In the
second analysis, we performed a correlation analysis between
the rCBF changes combined in the three intensities of each
emotional category and the individual TAS-20 scores for all
24 subjects. The relationship between the relative rCBF
values at peak in each brain area and the TAS-20 scores was
evaluated by the Pearson's correlation method. Finally, the
third analysis was a conjunction analysis performed to assess
differences between alexithymic and non-alexithymic sub-
jects in cerebral regional activation in response to emotional
faces compared with neutral faces. Brain responses in the
three intensities of emotional expression were combined in
each emotional category. The conjunction analysis reveals
areas in the brain where there is a signi®cant main effect of
two contrasts (Price and Friston, 1997).
Results
TAS-20 scores
The TAS-20 scores were normally distributed with an
average of 46.5 6 8.5 (mean 6 SD). The means 6 SD for
TAS-20 scores between the alexithymic and the non-
alexithymic group were 64.2 6 3.6 (61±70) and 40.5 6 5.7
(31±49), respectively.
Behavioural data and subject debrie®ng
In the gender discrimination task, the alexithymics and non-
alexithymics correctly identi®ed 96% and 98% at the levels of
the images, respectively, and the task performance was not
signi®cantly different between the two groups.
The subjects, rating scores for stimuli indicated the degree
to which the subjects recognized each emotional category and
its intensity levels. For example, the rating score after the
subjects viewed 0 (neutral), 33, 67 and 100% of angry
expressions correlated highly with the original degree of
anger prototype in the morphed face (r = 0.59, P < 0.0001 in
Table 1 The coordinates and Z-scores for the brain areas where the rCBF responses were lower in the alexithymics than
in the non-alexithymics while the subjects viewed facial expressions
Area (BA) Angry Sad Happy
Side Z-score Talairach
coordinates
Z-score Talairach
coordinates
Z-score Talairach
coordinates
xyz xy z xyz
1 Orbitofrontal cortex (11) R 4.43 32 50 ±20 4.9 36 52 ±18 4.1 30 48 ±22
2 Middle frontal gyrus (9) R 4.78 44 2 42 4.53 44 0 42 5.5 44 0 44
3 Inferior parietal lobe (40) R 5.09 54 ±48 32 4.28 50 ±48 34 4.48 54 ±48 34
4 Cuneus (19) R 5.19 20 ±78 34 5.25 20 ±78 32 4.51 20 ±76 30
5 Cerebellum culmen R 4.44 20 ±52 ±22 4.23 16 ±52 ±26 5.2 18 ±52 ±24
6 Inferior frontal gyrus (44/45) R 5.47 62 16 12 5.75 62 18 10
7 Superior occipital gyrus (19) R 4.12 36 ±74 38 4.22 36 ±72 36
8 Lingual gyrus (19) L 4.2 ±20 ±58 0 4.28 ±18 ±54 0
9 Cerebellum tuber R 5.06 44 ±82 ±28 4.31 38 ±72 ±26
10 Superior temporal gyrus (40/42) R 5.52 70 ±18 24
11 Middle frontal gyrus (46) R 4.26 50 30 26
12 Postcentral gyrus (2) L 4.36 ±50 ±26 40
13 Fusiform gyrus (37) R 4.79 46 ±54 ±4
14 Middle occipital gyrus (19) R 4.65 40 ±94 10
15 Cerebellum L 4.12 ±8 ±80 ±38
16 Anterior cingulate gyrus (24) R 4.21 0 4 38
17 Inferior parietal cortex (40) R 4.41 72 ±22 ±26
18 Cuneus R 4.48 8 ±66 10
BA = Brodmann area; L = left; R = right.
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non-alexithymics, r = 0.68, P < 0.0001 in alexithymics).
Signi®cant correlations were similarly observed for sad
(r = 0.45, P < 0.002 in non-alexithymics, r = 0.41,
P < 0.004 in alexithymics) and happy (r = 0.67, P < 0.0001
in non-alexithymics, r = 0.77, P < 0.0001 in alexithymics)
expressions.
Unpaired t-tests showed that alexithymics signi®cantly
rated intense sad faces as disgust (t = 2.36, P < 0.03).
However, there were no signi®cant differences between the
alexithymics and the non-alexithymics in any other ratings.
Differences between alexithymics and
non-alexithymics
Areas of signi®cantly lower rCBF among the alexithymics
when compared with the non-alexithymics were mostly
localized in the neocortex of the right hemisphere
(P < 0.0001, uncorrected; Fig. 1). The coordinates and
Z-scores for these areas are given in Table 1. Lateralization
was commonly observed when viewing all three continua of
an emotional face. Areas where rCBF was lower in the
alexithymics than in the non-alexithymics were: the orbito-
frontal cortex, middle frontal gyrus, inferior parietal gyrus,
cuneus and cerebellum culmen of the right hemisphere. In
contrast, areas of higher rCBF in the alexithymics when
compared with the non-alexithymics were almost localized in
the neocortex of the left hemisphere (P < 0.0001, uncorrected;
Fig. 2). The coordinates and Z-scores for these areas are given
in Table 2. Lateralization was commonly observed in all
types of emotional faces. rCBF in the superior frontal cortex,
inferior parietal cortex and cerebellar lingual in the left
hemisphere was higher in the alexithymics regardless of the
emotional face used.
Differences between alexithymics and non-alexithymics in
response to each stimulus are listed in Tables 3 and 4
(P < 0.001, uncorrected). The less responsive areas in the
alexithymics were localized in the right hemisphere, while
the more responsive areas were mostly localized in the left
hemisphere. Differences between alexithymics and non-
alexithymics could frequently be identi®ed even at mild
levels of emotional intensity.
Correlation with individual TAS-20 scores
Most brain areas that negatively correlated with TAS-20
scores were localized in the right hemisphere (P < 0.05,
corrected; Fig. 3). The coordinates and Z-scores for these
areas are given in Table 5. Each brain area was observed
while the subject viewed angry and sad faces. On the other
hand, no signi®cant correlation was observed between rCBF
and TAS-20 scores when the subjects viewed happy and
neutral faces. Brain areas where the rCBF was lower in the
alexithymics than in the non-alexithymics also negatively
correlated with TAS-20 scores. No region in the brain
positively correlated with TAS-20 score.
Conjunction analysis
The coordinates and Z-scores of the conjunction analysis are
given in Table 6 (P < 0.001, uncorrected). Anger stimuli
(angry faces compared with neutral faces) induced less
activation in the alexithymics than in the non-alexithymics in
the bilateral insula, left precentral gyrus, right cingulate
cortex (Fig. 4), right superior temporal gyrus, left temporal
sub-gyrus, middle occipital gyrus and left cerebellum.
Sadness stimuli (sad faces compared with neutral faces)
were associated with reduced activation in the right insula,
left precentral cortex and left temporal sub-gyrus in the
alexithymics compared with the non-alexithymics. Happiness
stimuli (happy faces compared with neutral faces) were
related to less activation in the alexithymics than in the non-
alexithymics in the right medial frontal gyrus, right insula and
left precentral gyrus, left temporal sub-gyrus, corpus
callosum and left cerebellum culmen.
In contrast, anger stimuli induced a higher activation in the
alexithymics than in the non-alexithymics in the left temporal
sub-lobar (x = ±28, y = ±24, z = 22). Sadness and happiness
stimuli did not lead to high activation in any area of the brain
(data not shown).
Fig. 2 SPMs of a comparison of 12 alexithymic versus 12 non-
alexithymic subjects while viewing facial expressions. Each ®gure
depicts a signi®cantly (P < 0.0001, uncorrected) higher rCBF in
the alexithymics when compared with the non-alexithymics while
the subjects looked at (A) angry, (B) sad, (C) happy and (D)
neutral faces. The higher rCBF in the alexithymics was mainly
lateralized in the neocortex of the left hemisphere.
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Discussion
The present study clearly reveals differences in brain
response to facial expressions between people with and
without alexithymia. The salient results were as follows. (i)
Differences in brain response were mainly observed in the
cortex areas, but not in the subcortical regions. (ii) Brain
regions where rCBF was lower in the alexithymics than in the
non-alexithymics were localized in the right hemisphere,
while those where rCBF was higher in the alexithymics than
in the non-alexithymics were localized in the left hemisphere.
(iii) The ACC and insula were less activated in the
alexithymics in response to angry faces than neutral faces.
(iv) There were differences in response to stimuli depending
on the emotion shown, i.e. a negative correlation between
rCBF and TAS-20 scores was observed in the right
hemisphere when subjects were viewing the angry and sad
faces, but not the happy and neutral faces. (v) There was no
clear difference in the effect of emotional intensity (high or
low arousal) between people with and without alexithymia.
These results are consistent with the suggestion that
alexithymia is associated with a de®cit in the cognitive
comprehension of emotion (Reiman et al., 1997; Taylor,
Table 2 The coordinates and Z-scores for higher rCBF areas in the alexithymics when compared with the non-
alexithymics while the subjects looked at facial expressions
Area (BA) Angry Sad Happy
Side Z-score Talairach
coordinates
Z-score Talairach
coordinates
Z-score Talairach
coordinates
xyz xyz xyz
1 Superior frontal gyrus (10) L 5.6 ±18 68 16 4.34 ±16 68 14 5.16 ±18 68 16
2 Inferior parietal lobe (40) L 4.92 ±62 ±44 48 5.3 ±62 ±40 50 6.15 ±62 ±42 48
3 Cerebellar lingual L 5.48 ±4 ±46 ±12 5.18 ±4 ±46 ±12 4.84 ±4 ±44 ±10
4 Corpus callosum L/R 4.68 ±2 ±38 16 4.16 2 ±36 18
5 Middle occipital gyrus (19) L 5.35 ±48 ±86 4 4.49 ±50 ±82 0
6 Cerebellum L 4.37 ±60 ±50 ±26 4.26 ±58 ±50 ±26
7 Middle temporal gyrus (21) L 4.51 ±56 ±8 ±10 5.14 ±52 ±10 ±10
8 Corpus callosum R 4.29 16 ±14 30
9 Superior temporal gyrus (38) R 4.88 28 12 ±36
10 Thalamus L 4.15 ±18 ±32 8
11 Cerebellum tonsil L 4.77 ±28 ±36 ±32
12 Superior frontal gyrus (8) R 4.34 42 28 50
13 Insula L 4.29 ±42 10 10
14 Superior temporal gyrus (21) L 4.38 ±60 ±6 4
15 Superior parietal gyrus (7) L 4.21 ±46 ±66 52
16 Occipital gyrus L 4.27 ±22 ±92 30
BA = Brodmann area; L = left; R = right.
Table 3 The coordinates and Z-scores for the brain areas where the rCBF were lower in
the alexithymics than in the non-alexithymics while they viewed each facial stimulus
Area (BA) Side No. voxels Z-score Talairach coordinates
xy z
Mild anger
Inferior parietal gyrus (40) R 75 3.77 70 ±22 22
Middle frontal gyrus (9) R 100 3.76 48 30 30
Temporal sub-gyrus R 56 3.5 48 ±56 ±8
Moderate anger
Inferior frontal cortex (44) R 111 4.08 64 8 12
Mild sadness
Inferior frontal gyrus (40) R 20 3.6 64 10 10
Orbitofrontal cortex (11) R 20 3.41 36 60 ±16
Mild happiness
Cerebellum tuber R 29 3.31 40 ±76 ±26
BA = Brodmann area; R = right.
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2000). In addition, no difference between the alexithymics
and the non-alexithymics was observed in the limbic structure
(i.e. the amygdala, the hippocampal formation and hypotha-
lamus), which plays a central role in emotional responses to
simple perceptual aspects of stimuli. This ®nding is supported
by a recent fMRI study indicating that the limbic area is not
associated with alexithymia (Berthoz et al., 2002).
Previous studies have reported inhibition in the right
hemisphere and higher activation in the left hemisphere in
people with alexithymia. Accordingly, conjugate lateral eye
movements used as an index of hemisphere activation (Parker
et al., 1992) and right visual ®eld search of chimeric faces
(Berenbaum and Prince, 1994; Jessimer and Markham, 1997)
revealed left hemispheric dominance or right hemispheric
weakness among alexithymic subjects. The right hemisphere
contains essential emotional processing systems (Ross, 1981,
1984; Ross et al., 1994; Adolphs et al., 1996), and the right
inferior frontal cortex has been associated with comprehen-
sion and production of emotion in facial and vocal
expressions (Hornak et al., 1996). It has also been reported
that lesions in the right inferior parietal cortex correlate with
impaired recognition of emotion (Adolphs et al., 1996).
Moreover, lesions in the orbitofrontal cortex in the right
hemisphere are known to impair identi®cation of facial and
vocal expressions (Ross and Mesulam, 1979; Hornak et al.,
1996). The orbitofrontal cortex represents an important site
for capturing the emotional signi®cance of events, and is used
to guide behaviour through its rich interconnections with the
limbic and other cortices (Damasio, 1994; Barbas, 2000).
Dysfunction in these areas, as shown in the present study,
might account for the reduced ability to identify emotion and
consequent behavioural changes in people with alexithymia.
In contrast to the right hemisphere, the left hemisphere in
split-brain patients has been reported to show sharp improve-
ment in facial emotion discrimination when instructions are
changed slightly to emphasize verbal labels for the facial
expression (Stone et al., 1996). As the left hemisphere may be
superior in processing information analytically through the
language system, alexithymic subjects viewing facial expres-
sions might possibly activate functions in their left hemi-
sphere in compensation for the defect in the right hemisphere.
As suggested in previous reports, people with alexithymia
might rely on the cognitive processing style of the left
hemisphere over the right hemisphere (Cole and Bakan, 1985;
Hoppe, 1988). This hemisphericity might re¯ect a tendency
Table 4 The coordinates and Z-scores for the brain areas where the rCBF were higher in
the alexithymics than in the non-alexithymics while they viewed each facial stimulus
Area (BA) Side No. voxels Z-score Talairach coordinates
xyz
Mild anger
Middle occipital gyrus (19) L 75 3.77 70 ±22 22
Superior frontal gyrus (10) L 20 3.44 ±22 68 14
Intense anger
Inferior parietal lobe (40) L 21 3.33 ±60 ±46 50
Mild sadness
Inferior parietal lobe (40) L 33 3.62 ±62 ±42 50
Moderate sadness
Cerebellum culmen L 21 3.35 ±30 ±32 ±28
Mild happiness
Precentral gyrus (6) R 93 3.7 20 ±24 78
Moderate happiness
Inferior parietal lobe (40) L 107 4.47 ±60 ±44 52
Superior frontal gyrus (10) L 35 3.61 ±26 68 6
Intense happiness
Parietal sub-gyrus L 33 3.38 ±24 ±56 24
Neutral R 20 3.31 44 2 10
BA = Brodmann area; L = left; R = right.
Fig. 3 Brain activity was correlated negatively with TAS-20 scores
while the subjects looked at (A) angry and (B) sad faces. Areas of
signi®cant correlation (P < 0.05, corrected) are colour-scaled
according to the Z-scores (scale given in ®gure).
1480 M. Kano et al.
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to focus on external events and poor awareness of emotion in
people with alexithymia.
In the subjects' debrie®ng, the rating scores for the
emotional faces were similar between the subjects with and
without alexithymia. It has been shown that when rough
rating methods are used, alexithymics often accurately judge
affect-laden external stimuli (Roedema and Simons, 1999).
However, when using more targeted self-report measures,
such as having the subjects describe how the stimuli made
them feel, affective self-description is impoverished in
subjects with alexithymia (Wehmer et al., 1995; Roedema
and Simons, 1999). The peculiar brain activities in alex-
ithymics might produce almost the same output as those in
non-alexithymics. Consequently, people with alexithymia do
not deviate severely from the norm in their social interactions.
As anger was the most unpleasant and intense stimulus in
the emotional faces used in this study, the alexithymic
subjects showed less activation in the ACC and bilateral
insula in response to the anger component of the facial
expressions. The ACC has been associated with conscious
awareness of emotion (Lane et al., 1997), and increasing
intensity of the angry facial expressions has been associated
with enhanced activity in the ACC (Blair et al., 1999). It has
also been suggested that the ACC plays a crucial role in
assessing emotional arousal or the attentive components of
emotion, and that the insula, as well as the ACC, are activated
Table 5 The coordinates and Z-scores for areas of rCBF were negatively correlated with TAS-20 scores while the subjects
looked at facial expressions
Area (BA) Side Angry Sad
Z-score Talairach
coordinates
Z-score Talairach
coordinates
xyz xyz
1 Orbitofrontal cortex (11) R 5.57 28 54 ±22 5.21 34 54 ±22
2 Inferior frontal gyrus (44/45) R 4.64 64 18 10 5.71 64 22 10
3 Middle frontal gyrus (9) R 4.74 44 0 46 4.59 46 ±2 42
4 Middle temporal gyrus (21) L 5.62 ±44 ±54 8 5.17 ±38 ±52 10
5 Cuneus (19) R 4.85 20 ±76 32 4.63 20 ±76 30
6 Cerebellum tuber R 5.54 44 ±84 ±28
7 Superior temporal gyrus (40/42) R 4.81 68 ±24 24
8 Inferior parietal lobe (40) R 5.86 50 ±48 32
9 Fusiform gyrus (37) R 5.19 48 ±56 ±4
10 Precuneus (7) L 4.69 ±16 ±80 50
11 Middle frontal gyrus (6) R 5.16 48 2 62
BA = Brodmann area; L = left; R = right.
Table 6 The coordinates and Z-scores for areas where rCBF were lower in alexithymics than in non-alexithymics in
response to emotional faces compared with neutral faces
Area (BA) Angry Sad Happy
Side Z-score Talairach
coordinates
Z-score Talairach
coordinates
Z-score Talairach
coordinates
xyz xyz xyz
1 Insula R 3.8 42 2 10 3.7 44 0 20 3.66 42 2 10
2 Precentral gyrus (4) L 3.53 ±46 ±14 50 3.67 ±44 ±10 52 3.71 ±48 ±4 58
3 Temporal sub-lobar L 3.5 ±46 ±22 ±12 3.65 ±46 ±22 ±12 3.57 ±46 ±24 ±12
4 Cerebellum culmen L 4.13 ±30 ±38 ±20 3.96 ±26 ±38 ±24
5 Cingulate gyrus (32) R 3.74 14 6 48
6 Insula L 3.46 ±46 ±2 12
7 Superior temporal gyrus (42) R 4.71 70 ±26 14
8 Middle occipital gyrus (19) L 3.88 ±34 ±86 18
10 Cerebellum L 3.34 ±48 ±50 ±46
11 Corpus callosum L 3.62 ±10 ±16 24
12 Medial frontal gyrus (10) R 3.41 10 50 8
BA = Brodmann area; L = left; R = right.
Brain activity and facial expressions in alexithymia 1481
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by emotional recall/imagery and by emotional tasks with
cognitive demand (Phan et al., 2002). This led to the
assumption that emotional arousal might be insuf®cient in
people with alexithymia because of the de®cit in ACC
activity. Our results are partially in line with the ACC de®cit
model of alexithymia (Lane et al. 1997; Berthoz et al., 2002).
However, the ACC de®cit may not be the only structure to
account for alexithymia.
The difference in response depending on the emotion
shown, which was demonstrated in our correlation analysis,
might be associated with hemispheric specialization for
emotional valence. Indeed, the left hemisphere is considered
to be dominant for positive emotion and the right hemisphere
for negative emotion (Davidson and Tomarken, 1991;
Adolphs et al., 2001). Therefore, in alexithymic subjects,
negative emotion processing might be more impaired in the
right hemisphere.
In this study, the rating scores after each scan indicated that
subjects recognized the emotional signi®cance in facial
expressions even though they were not asked to categorize
the emotional expression in the task. However, the details of
how the subjects processed the stimuli in the implicit facial
expression processing task are still unclear. Further studies
more targeted to speci®c emotional processing might be
needed to reveal the details of brain activity in people with
alexithymia.
In summary, people with alexithymia showed lower
response in the right hemisphere and higher response in the
left hemisphere when viewing a range of facial expressions,
and less activation in the ACC, which is associated with
emotional arousal. These ®ndings may partly explain the
disorders that affect regulation and the consequent peculiar
behaviour associated with alexithymia.
Acknowledgements
We appreciate the technical assistance of M. Miyake,
Y. Ishikawa and S. Watanuki in the PET studies. This work
was supported by grants-in-aid from the Ministry of
Education, Science, Sports and Culture, and the Ministry of
Health and Welfare, Japan. This research was also supported
in part by the Telecommunications Advancement
Organization of Japan.
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Received August 21, 2002. Revised December 26, 2002.
Accepted January 15, 2003
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