See discussions, stats, and author profiles for this publication at: https://www.researchgate.

net/publication/51591449

Neural Substrates of Decision Making as Measured With the Iowa Gambling

Task in Men With Alexithymia

Article in Psychosomatic Medicine · August 2011

DOI: 10.1097/PSY.0b013e318223c7f8 · Source: PubMed

CITATIONS READS

34 428

3 authors, including:

Michiko Kano Shin Fukudo

Tohoku University Tohoku University
139 PUBLICATIONS 2,869 CITATIONS 450 PUBLICATIONS 11,592 CITATIONS

SEE PROFILE SEE PROFILE

All content following this page was uploaded by Michiko Kano on 20 December 2018.

The user has requested enhancement of the downloaded file.

Neural Substrates of Decision Making as Measured With the Iowa Gambling
Task in Men With Alexithymia
MICHIKO KANO, MD, PHD, MASATOSHI ITO, MD, PHD, AND SHIN FUKUDO, MD, PHD
Objective: Individuals with alexithymia have a reduced ability to use their feelings to guide their behavior appropriately in social
situations. To reveal the capacity to use emotional signals in alexithymia under conditions of uncertainty, this study investigates neural
substrates and performance on the Iowa Gambling Task (IGT), which was developed to assess decision making based on emotion-
guided evaluation. Methods: The participants were 10 men with alexithymia and 13 without. Alexithymia was assessed by the 20-item
Toronto Alexithymia Scale. Regional cerebral blood flow (rCBF) was measured by [15O]-H2O positron emission tomography during
four trials of the IGT and two visuomotor control tasks. Results: The participants with alexithymia failed to learn an advantageous
decision-making strategy, with performance differing significantly from the nonalexithymic group in the fourth IGT trial (p = .029).
Comparing performance between the IGT and the control tasks, both groups showed brain activation in the dorsolateral frontal
area, inferior frontal lobe, preYsupplementary motor area, inferior parietal lobe, fusiform gyrus, and cerebellum. Men with alexithymia
showed lower rCBF in the medial frontal area (Brodmann area [BA] 10) and higher rCBF in the caudate and occipital areas in the
first and second IGT trials, which are within a learning phase according to test performance data. All brain data were significant at
p e .001, uncorrected. Conclusions: BA10 activity may be associated with using internal signals accompanying affective evaluation of
the stimuli, which is crucial for successful decision making. Reduced BA10 activity in participants with alexithymia suggests that they
may not use an emotion-based biasing signal to lead to advantageous decision making. Key words: emotional regulation, alexithymia,
somatic marker, medial frontal cortex, decision making, neuroimaging.

BA = Brodmann area; IGT = Iowa Gambling Task; rCBF = regional
cerebral blood flow; STAI = Spielberger State-Trait Anxiety In-
ventory; TAS-20 = 20-item Toronto Alexithymia Scale; vmPFC =
ventromedial prefrontal cortex.
INTRODUCTION
valenced sentences, words, faces, and scenes. Compared with
controls, individuals with alexithymia recalled fewer responses
for emotional words but the same for neutral words (8). Brain
imaging studies using emotion-inducing images or the recall
of emotional events has shown that people with alexithymia
exhibit different activation of emotion-related brain regions
(9Y11) and impaired understanding of other people’s desires

A lexithymia is a personality trait derived from clinical ob-

servations of patients with psychosomatic illness (1) and
is considered a disorder of affect regulation (2). The salient
features of alexithymia include difficulty in recognizing and
verbalizing one’s feelings, difficulty in distinguishing feelings
from bodily sensations of emotional arousal, and an externally
oriented cognitive style (3). Alexithymia has been reported to
be a risk factor for a variety of medical and psychiatric disor-
ders, such as somatization, chronic pain, functional gastroin-
testinal disorders, eating disorders, substance use disorders,
anxiety, and depression (2,3). Moreover, alexithymia reduces
life satisfaction (4) and has also been prospectively associ-
ated with all-cause mortality (5). The prevalence of alexithymia
in healthy populations is reported to be approximately 8% to
10% (3); therefore, investigating the problems of affect regu-
lation in alexithymia may have important medical and social
implications.
Research has repeatedly shown impairment of affect regu-
lation in alexithymia. Lane et al. (6,7) reported that highly
alexithymic individuals perform poorly on a perception task
of recognizing basic emotions associated with emotionally
From the Behavioral Medicine (M.K., S.F.), Tohoku University Graduate
School of Medicine, and Cyclotron and Radioisotope Center (M.I.), Tohoku
University, Sendai, Japan.
Address correspondence and reprint requests to Shin Fukudo, MD, PhD,
Behavioral Medicine, Tohoku University Graduate School of Medicine, 2-1
Seiryo-cho, Aoba-ku, Sendai 980-8575, Japan. E-mail: sfukudo@med.
tohoku.ac.jp
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
(M.K.).
Received for publication July 13, 2010; revision received April 20, 2011.
DOI: 10.1097/PSY.0b013e318223c7f8
and intentions, in addition to reduced levels of empathy for
other people’s pain (12).
Each of the studies mentioned previously focused on one
stage of information processing in alexithymic individuals, that
is, either basic emotional or cognitive-emotional level. In ad-
dition to these difficulties in cognitive-emotional processing,
people with alexithymia have been thought to be unable to use
feelings to guide their behavior appropriately, which may lead
to difficulties in the social environment (2). In this research, we
investigate the ability to use emotional signals to guide their
behavior in social situations.
Bechara et al. (13) developed the Iowa Gambling Task (IGT)
to assess decision making in patient populations. The task
emphasizes the contribution of emotional processing to deci-
sion making. It requires the subject to learn the rewards and
punishments associated with four card decks to maximize
the earning of pretend money. High-risk decisions involve
the chance of great reward but also a high risk of loss (pun-
ishment). In contrast, low-risk decisions may lead to better
long-term payoff. The task requires the ability to distinguish
between high- and low-risk financial decisions, and learning
based on the experience of losses over time. Patients with bi-
lateral lesions in the ventromedial prefrontal cortex (vmPFC)
have shown impairment on the task; they remained unable
to develop affective reactions with appropriate affective judg-
ment (14Y16) and displayed poor decision making in everyday
life. Correspondingly, they showed poor IGT performance,
persistently selecting from the ‘‘risky’’ decks characterized
by large immediate rewards but larger long-term punishments
(14Y16). The role of vmPFC in decision making has been un-
derstood further by imaging studies in healthy subjects who

588 Psychosomatic Medicine 73:588Y597 (2011)

0033-3174/11/7307Y0588
Copyright * 2011 by the American Psychosomatic Society

Copyright © 2011 by the American Psychosomatic Society. Unauthorized reproduction of this article is prohibited.
BRAIN IMAGING OF GAMBLING TASK IN ALEXITHYMIA
show signal changes in the vmPFC while carrying out the IGT
trials (17Y19).
Such decision making as seen in the IGT presupposes the
theory of somatic markers, as developed by Damasio (20). This
theory argues that optimal decision making is not simply the
result of rationally, cognitively calculated categorization of
gains and losses but is also based on good or bad affective
reactions and emotionally guided evaluation. The decision-
making deficits found after vmPFC damage are due to an in-
ability to use emotion-based biasing signals generated from the
body (or ‘‘somatic markers’’) when appraising different re-
sponse options. The reasoning is influenced by crude biasing
signals arising from the neural machinery that underlies emo-
tion. Following Damasio (20), emotion is the representation
and regulation of the complex array of homeostatic changes
that occur in different levels of the brain and body in given
situations. When making decisions, a somatic marker arising
from the periphery or the central representation of the periphery
indicates our emotional reaction to a response option. For every
response option contemplated, a somatic state is generated,
including sensations from the viscera, internal milieu, and the
skeletal and smooth muscles. These somatic markers serve as
an indicator of the value of what is represented and also as a
booster signal for continued working memory and attention.
Particularly in situations of complexity and uncertainty, these
marker signals help to reduce the problem space to a tractable
size by marking response options with an ‘‘emotional’’ signal.
Only those options that are marked as promising are processed
in a full, cognitive fashion.
In this experiment, we aimed to investigate the strategy and
neural substrates for decision making in alexithymia while
performing the IGT. Because the defining feature of alexi-
thymia is disordered emotional regulation and difficulty in un-
derstanding bodily sensations associated with emotions, it is
expected that individuals with alexithymia cannot use emotion-
based biasing signals (i.e., somatic markers) in IGT trials and
that they exhibit brain activation different from controls dur-
ing IGT performance, particularly in the areas associated with
IGT processing.
MATERIALS AND METHODS
Subjects
Twenty-three healthy male volunteers (10 with alexithymia and 13 with-
out) participated in this study. All participants were right-handed and aged 18
to 26 years. Individuals with 20-item Toronto Alexithymia Scale (TAS-20)
scores greater than 61 (61Y73) were considered alexithymic, whereas those
with TAS-20 scores less than 51 (26Y46) were considered nonalexithymic,
according to published cut-off criteria (2). The Japanese version of the TAS-20
has previously been found to be psychometrically valid (21). In addition, in-
dividual trait score of the Spielberger State-Trait Anxiety Inventory (STAI)
(22) was used as a confounding factor in positron emission tomographic
(PET) analysis to remove variance from the TAS-20 due to self-reported neg-
ative affect, which tends to correlate positively with the TAS-20 (23), to ensure
its emotional processing deficit aspect. Individual TAS-20 score significantly
correlated with the trait score of STAI (r = 0.41, p G .05) by the Pearson
correlation method. Each participant underwent a basic evaluation that in-
cluded a medical history review to exclude individuals with organic dis-
eases. None of the volunteers had a history of psychiatric or neurological
disorders according to the Diagnostic and Statistical Manual of Mental
Psychosomatic Medicine 73:588Y597 (2011)
Copyright © 2011 by the American Psychosomatic Society. Unauthorized reproduction of this article is prohibited.
Disorders, Fourth Edition, Text Revision (24), and International Classification
of Diseases 10 (25) criteria. The subjects were given a description of the study
protocol, and their written informed consents were obtained. This study was
approved by the Ethics Committee of Tohoku University School of Medi-
cine and was performed in accordance with the policies of the Declaration
of Helsinki.
Decision-Making Task
The decision-making task is a computerized gambling card game that
tests the ability to choose between high gains with a risk for even higher
losses and low gains with a risk for smaller losses. The 100-item task is com-
pleted four times, and each run-through takes at least 2.5 minutes to com-
plete. The participants were instructed to accumulate as much (play) money
as possible by picking one card at a time from each of the four decks (A, B,
C, and D) until 100 cards were chosen. Once a card was selected, the mes-
sage ‘‘You get l5000’’ (or l10,000; equivalent to approximately US $50 or
$100) appeared immediately on the screen and remained for 1.5 seconds until
the subject was prompted to play again by the message, ‘‘Pick a card.’’ If a loss
was attached to the choice, a message lasting 1.5 seconds was added to the
screen (e.g., ‘‘You must pay l75,000’’; US $750). At the end of the 1.5 seconds,
the subject was prompted to make the next selection. The cumulative net
amount of money earned (i.e., the payout) was updated on the screen after each
card pick. The subjects continued to play until 100 cards were selected. The
scan started on average at 85 seconds after the task began, corresponding
to the completion of 34 cards or trials. During the 70-second scan, 28 trials were
completed, and 38 cards were completed after the PET scan ended. The sub-
jects continued to play until 100 cards were selected.
Task decks differed along two dimensions: immediate gain and risk of
penalties. The accumulated penalties were larger than the accumulated gains
in decks A and B (disadvantageous decks) and were smaller than the accu-
mulated gains in decks C and D (advantageous decks). The control task
was designed to replicate the decision-making task in all aspects except for
decision making and was similar in sensorimotor demands and in exposure
to gains and losses. The participants were instructed to pick cards from the
decks sequentially in the fixed order of A-B-C-D-A-B-C-D and so on.
Positron Emission Tomography
PET scans of the distribution of [15O]-H2O were obtained using an SET-
2400W PET scanner (Shimadzu, Kyoto, Japan) operated in the high-sensitivity
three-dimensional mode with average axial resolution of 4.5 mm at maximum
strength and sensitivity for a 20-cm cylindrical phantom of 48.6 kcps/kBq
permilliliter (26). PET sessions included seven 1-minute scans at 10-minute
intervals, each after the intravenous injection of approximately 5 mCi (185 MBq)
of [15O]-H2O to assess regional cerebral blood flow (rCBF). Before the PET
study, the subjects performed a 1-minute training task. The seven scans con-
sisted of four decision-making tasks, two control tasks, and one visual fixa-
tion task. The fixation task, used for quality control, was not part of the analysis.
The order of tasks was counterbalanced across subjects. The PET data were
obtained between April 2003 and September 2004.
Performance Data
Score on the IGT was defined as the number of choices from the advanta-
geous decks (C and D) minus the number of choices from the disadvanta-
geous decks (A and B) for 100 trials. This net score (decks [C + D] j decks
[A + B]) within each 25-choice time block enables the assessment of learn-
ing on the task.
Statistical Analysis
Statistical parametric mapping software (SPM2, Wellcome Department
of Cognitive Neurology, London, England, UK) was used for PET image
realignment, normalization, and smoothing and to create statistical maps of
significant rCBF changes (27). All rCBF images were stereotaxically nor-
malized into the standard space corresponding to the Montreal Neurological
Institute template. The normalized images were smoothed using a 12  12 
12-mm Gaussian filter. The contribution of each parameter of interest to
changes in rCBF was estimated by SPM2 according to the general linear
model at voxel level. The global cerebral blood flow effects were controlled
589
 M. KANO et al.
with analysis of covariance by participant, and the mean global value was TABLE 1. Iowa Gambling Task Performance of Alexithymic and
set to 50 mL/min per deciliter. Estimates were made using linear combina- Nonalexithymic Groups, Indicated by Net Score (Advantaged Decks
tions of contrasts, and the individual trait score on the STAI was covaried for [C + D] j Disadvantaged Decks [A + B])
the potentially confounding effects of negative emotion. The resulting set of
voxel values constituted a parametric map for each contrast. Nonalexithymic Group Alexithymic Group
To determine the regional brain activity associated with IGT perfor-
mance, activity during the two control tasks was subtracted from that during M SD M SD
the four IGT tasks in each group (alexithymic and nonalexithymic). A correla-
tion analysis was also performed between brain activity during the four IGT 1st
IGT tasks and individual TAS-20 scores for all 23 subjects. In addition, to 1Y25 j3.71 7.83 j1.70 6.90
detect differences in cerebral regional activation during the gambling task (GT) 26Y50 0.50 5.13 j1.30 4.42
compared with the control task between groups, GT-control contrast was sub- 51Y75 j1.50 6.02 0.70 10.69
tracted between groups (28). The eigenvariate values at the brain region where
76Y100 j0.93 10.25 3.70 12.07
the activity differed between groups were demonstrated with the volume of
interest function in SPM2, and the value was compared between two groups IGT 2nd
with the Student’s t test, using SPSS 18.0 (IBM, New York, NY). Voxel ac- 1Y25 j1.00 9.15 0.20 16.71
tivation was considered statistically significant at a threshold of p G .001 26Y50 3.29 8.30 3.60 14.02
(uncorrected), with an extent threshold of 20 voxels. However, to reduce false- 51Y75 j1.29 8.87 0.60 18.13
positive findings, we considered only those clusters reaching significance at
76Y100 j0.21 8.68 j0.20 15.50
the p corrected G .05 cluster level (correction for multiple comparisons) in
the main subtraction analysis. Repeated analysis of variance (ANOVA) was IGT 3rd
used to examine the effect of alexithymia on each of the four IGT tasks with 1Y25 2.71 8.11 j2.60 16.54
a two-level between-subjects variable (alexithymic and nonalexithymic) and 26Y50 5.50 8.31 j4.80 13.64
a within-subjects variable of the 25-choice time blocks on the IGT (four 51Y75 7.29 12.86 j6.00 13.96
levels), using SPSS 18.0.
76Y100 5.00 14.05 j5.00 15.17
RESULTS IGT 4tha
Performance Score of IGT 1Y25 10.14 13.21 j2.80 14.22
Each subject performed four IGT trials, and separate 26Y50 10.14 12.42 j8.80 16.29
PET scans were taken during each trial. The mean (standard 51Y75 8.71 16.41 j13.40 12.99
deviation) of the net score for each group (alexithymic and 76Y100 8.07 16.85 j7.40 17.61
nonalexithymic) across the four trials is presented in Table 1. a
p = .029, group by time-block interaction by repeated two-way analysis of
Repeated-measures ANOVA of net scores across the variance.
25-choice time blocks (four levels: 1Y25, 26Y50, 51Y75, and IGT = Iowa Gambling Task; M = mean; SD = standard deviation.
76Y100) by group showed significant interaction effects
(F(3,63) = 3.19, p = .029, partial G2 = 0.13) in the fourth GT.
trials (first, second, third, and fourth) against two control
There were no significant interaction effects in the first
tasks. The brain areas where rCBF was higher in individuals in
(F(3,63) = 0.78, p = .51, partial G2 = 0.03), second (F(3,63) =
the nonalexithymic group than the alexithymic group were
0.06, p = .9, partial G2 = 0.002), or third (F(3,63) = 0.75, p = .53,
the inferior temporal gyrus and the left medial frontal gyrus.
partial G2 = 0.03) GTs.
In contrast, the brain areas where rCBF was higher in indi-
Brain Activation viduals with alexithymia than those without were the right
Group Activation in IGT Versus Control Conditions cuneus and the lingual gyrus. Subtraction data of the rCBF in
Subtraction of the rCBF associated with the visuomotor the control conditions from that for each IGT condition are
control conditions (two scans) from that associated with the shown in Table 4 and Figure 3. In the first and second IGT
IGT (first, second, third, and fourth) conditions is represented conditions, individuals without alexithymia showed higher
in Table 2 and Figure 1. The nonalexithymic group showed brain activation in the left medial frontal gyrus than those
activation of areas in the middle frontal gyrus, orbitofrontal with alexithymia. There was no brain area where the rCBF
cortex (OFC), inferior parietal gyrus, insula, anterior cingulate was higher in the nonalexithymic group than in the alexithy-
gyrus, and cerebellum. The alexithymic group showed activation mic group in the third IGT. In the fourth IGT condition, the
of areas in the middle and inferior frontal gyrus, inferior parietal precuneus and the precentral gyrus were the brain areas where
gyrus, caudate, precuneus, fusiform gyrus, and cerebellum. rCBF was higher in the nonalexithymic group. In contrast,
the brain areas where the alexithymic participants showed higher
Correlation Between Brain Activation in IGT and
rCBF were the occipital lobe (V3), caudate, lingual gyrus, cin-
Alexithymia Score
gulate gyrus, superior temporal gyrus, and precentral gyrus in the
The TAS-20 score negatively correlated with rCBF in
first IGT condition; precuneus in the second IGT condition; and
the middle frontal gyrus (Brodmann area [BA] 10) with other
the fusiform gyrus in the third IGT condition. There was no brain
brain regions (Table 3 and Fig. 2).
area where rCBF was higher in the individuals with alexithymia
Comparison Between Groups that the nonalexithymic group in the fourth IGT condition.
Table 4 and Figure 2 show group comparisons between Figure 4 shows the subtraction of the average eigenvari-
participants with alexithymia and those without in the IGT ate values associated with the visuomotor control conditions

590 Psychosomatic Medicine 73:588Y597 (2011)

Copyright © 2011 by the American Psychosomatic Society. Unauthorized reproduction of this article is prohibited.
BRAIN IMAGING OF GAMBLING TASK IN ALEXITHYMIA
TABLE 2. Brain Regions With Significant Increases in Cerebral Blood Flow During Decision-Making Tasks in Alexithymic and Nonalexithymic Groups

Talairach-Tournoux Coordinate

Group, Contrast, and Brain Region (Brodmann Area) T Score k (Cluster Extent) X Y Z

IGT 1Y4 9 control (nonalexithymic group)

Inferior parietal lobule (40) 5.7 1714 44 j64 46
Dorsolateral prefrontal cortex (46) 5.66 1952 42 36 24
Cerebellum pyramis 5.3 1346 j16 j84 j28
Cerebellum tuber (left) 4.6 392 j52 j66 j32
Orbitofrontal cortex (47)/insula (13) 4.82 526 28 22 j4
Middle frontal gyrus (6) 4.8 486 40 6 54
Inferior temporal gyrus (20) 4.42 108 64 j28 j18
Cerebellum tuber (right) 4.4 786 54 j62 j38
Fusiform gyrus (19) 4.37 426 j40 j68 j14
Insula (13) 3.87 59 j24 20 j2
Cingulate gyrus (32) 3.67 145 8 32 28
IGT 1Y4 9 control (alexithymic group)
Medial frontal gyrus (10) 6.24 1092 40 60 2
Cerebellum 5.9 3009 j36 j66 j36
Precuneus (7) 5.62 532 12 j68 34
Fusiform gyrus (19) 4.87 448 38 j72 j16
Superior parietal lobe (7) 4.81 489 34 j72 44
Caudate 4.3 195 20 18 8
Inferior parietal lobe (40) 4.25 226 52 j50 46
Orbitofrontal cortex (47) 3.92 58 34 18 j8
Middle occipital gyrus (18) 3.78 33 j12 j98 14
Fusiform gyrus (37) 3.76 52 j54 j50 j20
Superior frontal gyrus (8) 3.52 22 28 28 54

T score indicates value for contrast in which rCBF during the IGT trials was greater than rCBF during control tasks. Significance level was set at p G .05, corrected for
false discovery rate for multiple comparisons. Cluster extent was set at 20.
IGT = Iowa Gambling Task; rCBF = regional cerebral blood flow.

from those associated with the IGT at the medial frontal gy-
rus (BA10) across the four IGT conditions between the two
groups. In the first and second IGTs, the value was signif-
icantly different between the two groups (p = .004 and
p = .003, respectively). No significant difference was detected
in the third (p = .06) or fourth (p = .16) IGT.
DISCUSSION
The neural substrate engaged in emotion-based decision
making differed in subjects with alexithymia compared with
those without alexithymia. In addition, individuals with alex-
ithymia showed lower task performance. Activity in the medial
frontal areaVwhere patients with lesions here show poor de-
cision makingVwas lower in the alexithymic group during the
first and second IGT trials. The IGT performance was signi-
ficantly worse in the alexithymic group than the nonalexithy-
mic group in the fourth IGT trial.
GT Versus Control Task
Decision-making tasks are embedded in the processes
that precede them (evaluation of stimuli) and those that fol-
low (response to outcomes). So, the IGT engages many brain
structures associated with emotional and motivational cod-
ing, working memory, conflict monitoring, and visual atten-
tion. Comparing all four IGT tasks to the control tasks, both
the nonalexithymic and alexithymic groups showed activa-
tion in the dorsolateral frontal area (BA46 and BA10), OFC
(BA47), preYsupplementary motor area (BA6 and BA8), infe-
rior parietal lobe (BA40), fusiform gyrus (BA19 and BA37),
and cerebellum, predominantly right lateralized. These areas
are consistent with previous neuroimaging studies of GTs
(18,19,29Y31). The emotional attributes of decision making
in tasks that involve rewards or risk taking may favor neural
processing in the right hemisphere (31). Neuropsychological
and PET studies indicate that IGT processing depends on
working memory functions associated with activity of the
dorsolateral PFC (15,16,29,32,33). The inferior frontal lobe
is the lateral part of the orbital area and was commonly acti-
vated in previous GT studies (30Y32) involved in flexible rep-
resentation of reinforcement of learning from reward and
punishment (30,31). The preYsupplementary motor area is
involved in planning motor responses under internal control
in complex tasks (34,35), and activation in BA8 and BA6
is associated with uncertainty and decision conflict (35,36).
Visual attentionYrelated areas such as the occipital, temporal,
and parietal cortices were often reported to be activated during

Psychosomatic Medicine 73:588Y597 (2011) 591

Copyright © 2011 by the American Psychosomatic Society. Unauthorized reproduction of this article is prohibited.
 M. KANO et al.

Figure 1. Brain images showing greater increase in cerebral blood flow during decision-making tasks in alexithymic and nonalexithymic individuals. Significance
level was set at p G .05, corrected. ACC = anterior cingulate cortex; DLPFC = dorsolateral prefrontal cortex; Fusiform = fusiform gyrus; INS = insular cortex; IPL =
inferior parietal lobule; MFG = middle frontal gyrus; OFC = orbitofrontal cortex; PCu = precuneus.

GTs, even if it is expected that mimicking visuomotor control

tasks may cancel the visual processing component of GTs. This
may be because of the fact that salient/arousing aspects of the TABLE 3. Brain Regions Where the Cerebral Blood Flow During
task will have a greater effect on visual attention (31). Although Decision-Making Tasks Negatively Correlated With
Individual TAS-20 Score
cerebellum function refers to movement control, the activities
may relate to error-based learning (37) and could be used to Talairach-Tournoux
improve performance during GTs (32). k Coordinate
In addition, men without alexithymia showed activation Group, Contrast, and Brain T (Cluster
Region (Brodmann Area) Score Extent) X Y Z
in the bilateral insula (BA13), cingulate gyrus (BA32), and
inferior temporal gyrus (BA20), which is the visual processing Cuneus (18) 4.88 930 j14 j70 16
area. The insula is thought to be one of the key regions for Posterior cingulate (30) 4.35 651 22 j56 10
successful IGT performance (38). The right anterior insula Fusiform gyrus (20) 4.15 93 j44 j12 j22
activation is related to explicit awareness of interoceptive sig- Middle temporal gyrus (37) 4.05 195 50 j62 6
nals (31) and may represent negative somatic states, includ- Middle frontal gyrus (10) 4 72 j8 62 0
ing those associated with risk taking and punishment (39). The Precuneus (7) 3.49 44 18 j72 36
left insula is reported to be activated mainly by positive and Superior temporal gyrus (38) 3.75 51 j26 18 j28
affiliative emotional feelings (40). The bilateral anterior insula Superior temporal gyrus (21) 3.66 47 38 2 j30
has been linked to response selection process accompanying Fusiform gyrus (20) 3.47 24 32 j38 j14
sensory perception (40). BA32 may relate to attention and Inferior occipital gyrus (18) 3.47 26 34 j82 j8
mediates response conflict in well-defined tasks where rules Cerebellum 3.4 15 2 j44 j2
are known (36). Meanwhile, individuals with alexithymia
demonstrated that caudate activationVwhich is also thought to T score indicates value for contrast in which rCBF during the IGT trials was
negatively correlated with TAS-20 scores. Significance level was set at p G .001,
be a part of a feedback loop critically involved in motor control, uncorrected. Cluster extent was set at 20.
cognition, and emotional processingVis often activated in GTs IGT = Iowa Gambling Task; rCBF = regional cerebral blood flow; TAS-20 =
(18,29,30,32). 20<item Toronto Alexithymia Scale.

592 Psychosomatic Medicine 73:588Y597 (2011)

Copyright © 2011 by the American Psychosomatic Society. Unauthorized reproduction of this article is prohibited.
BRAIN IMAGING OF GAMBLING TASK IN ALEXITHYMIA

Figure 2. Medial prefrontal cortex (BA10) was activated during the IGT trails more in nonalexithymic patients (A) rCBF was higher in BA10 in group comparison
between nonalexithymics and alexithymics in the IGT trials against two control tasks. (B) rCBF in BA10 was negatively correlated with individual TAS-20 scores of
23 subjects.

Comparison Between Subjects With and

Without Alexithymia TABLE 4. Brain Regions With a Significant Difference in Increase in
Cerebral Blood Flow During Decision-Making Tasks Compared With
Performance Data Control Tasks Between Alexithymic and Nonalexithymic Groups
Participants without alexithymia learned a strategy to choose
a good deck and gradually increase their net score, reaching Talairach-Tournoux
k Coordinate
around 10 by the fourth IGT trial. In contrast, those with Group, Contrast, and Brain T (Cluster
alexithymia failed to learn such an advantageous decision- Region (Brodmann Area) Score Extent) X Y Z
making strategy. The net average scores of the two groups
were almost the same during the first and second IGTs, but Nonalexithymic 9 alexithymic groups (IGT 1Y4)
diverged slightly in the third IGT, and showed a significant Inferior temporal gyrus (20) 3.7 55 j60 j38 j14
difference in the fourth IGT. These performance data suggest Medial frontal gyrus (10) 3.44 23 j10 66 6
that the first and second IGTs were probably the learning Alexithymic 9 nonalexithymic
groups (IGT 1Y4)
phases to find a winning strategy and involve a stage of brain
Precuneus (7) 4.03 115 12 j66 32
activity that processes complexity and uncertainty. In contrast,
Lingual gyrus (left) (19) 3.81 28 j22 j64 j6
it is possible that the third IGT, and certainly the fourth IGT,
Lingual gyrus (right) (19) 3.79 49 30 j76 j2
followed a learning period and likely do not involve guessing
Caudate 3.45 23 20 16 6
or searching for the correct strategy, but more likely involve just
Nonalexithymic 9 alexithymic groups (IGT 1)
a visuomotor process. Performance deterioration in latter tri-
Medial frontal gyrus (10) 3.51 44 j12 60 j4
als has often been observed in patient populations such as those
Alexithymic 9 nonalexithymic groups (IGT 1)
with vmPFC damage or a variety of psychiatric conditions
Occipital lobe (7) 4.2 165 10 j66 30
(41). Recently, an interesting article has reported the person-
Caudate 4.05 46 18 18 6
ality characteristics among healthy subjects who persisted in
Occipital lobe (19) 3.73 69 30 j76 j2
selecting from the risky deck B as the number of big losses
Cingulate gyrus (32) 3.61 35 18 14 36
increased. They were characterized as more deliberate, less
Superior temporal gyrus (38) 3.59 31 48 22 j26
self-consciousness, and with lower fantasy and aesthetics rat-
Precentral gyrus (6) 3.53 43 j40 j14 36
ings, but they were implicitly impulsive (42). These charac-
Nonalexithymic 9 alexithymic groups (IGT 2)
teristics reportedly overlap with alexithymia in regard to lower
Medial frontal gyrus (10) 3.37 18 j8 58 6
fantasy rating and external-oriented thinking (3). In addition,
Alexithymic 9 nonalexithymic groups (IGT 2)
Haviland and Reies (43) stated that the emphasized commu-
Precuneus (7) 3.38 26 14 j66 32
nication through action is extremely characteristic of alex-
Alexithymic 9 nonalexithymic groups (IGT 3)
ithymia. This impulsivity or action orientation during emotional
Fusiform gyrus (19) 3.44 26 j24 j66 j4
arousal might be associated with the risky choice and poor per-
Nonalexithymic 9
formance of IGT in individuals with alexithymia.
alexithymic groups (IGT 4)
Precuneus (left) (7) 3.87 67 j16 j68 52
Comparison Between Alexithymia and Nonalexithymia Precentral gyrus (4) 3.86 74 28 j28 56
During IGTs Precuneus (right) (7) 3.75 47 28 j74 24
Compared with men without alexithymia, neural activity in
T score indicates value for contrast in which rCBF during the IGT trials was
the medial frontal cortex (BA10) and inferior temporal gyrus greater than rCBF during control tasks. Significance level was set at p G .001,
(BA20) was lower during the IGT in subjects with alexithymia. uncorrected. Cluster extent was set at 20.
In contrast, activities in the visual processing area (BA7 and IGT = Iowa Gambling Task; rCBF = regional cerebral blood flow.

Psychosomatic Medicine 73:588Y597 (2011) 593

Copyright © 2011 by the American Psychosomatic Society. Unauthorized reproduction of this article is prohibited.
 M. KANO et al.

Figure 3. A, Change in mean difference indicated by net score (advantaged decks [C + D] j disadvantaged decks [A + B]) during the first, second, third, and fourth
IGT trials. Errors bars indicate standard error of the mean. * Significant interaction effect (p = .029) with repeated-measures ANOVA of net scores across 25-choice
time blocks (four levels: 1Y25, 26Y50, 51Y75, and 76Y100) by group (alexithymic and nonalexithymic). B, Brain regions with a significant difference in increase in
cerebral blood flow during the first, second, third, and fourth IGT trials compared with control tasks between nonalexithymic and alexithymic patients. B-1 shows the
brain areas where the rCBF is higher in nonalexithymic than alexithymic patients, and B-2 shows those where the rCBF is higher in alexithymic than nonalexithymic
group. Significance level was set at p G .001, uncorrected. Cluster extent was set at 20. a = medial frontal gyrus; b = medial frontal gyrus; c = no activation area;
d = precuneus; e = caudate, cingulate gyrus, and occipital lobe; f = precuneus; g = fusiform gyrus; h = no activation area. IGT = Iowa Gambling Task.

BA19) and caudate were higher in subjects with alexithymia Recent functional magnetic resonance imaging (fMRI) stud-
compared with those without. BA10 activity during the IGT ies have provided a functional role for BA10 in GTs. BA10 was
was also negatively correlated with individual TAS-20 score. found to be significantly correlated with task performance (net
The medial frontal cortex (BA10) is part of the key areas score) in risky versus safe decks decisions, suggesting that it is
needed for successful performance on the IGT (13). Damasio’s
classification of vmPFC includes the entirety of the medial
and aspects of the lateral OFC and overlaps with BAs 10, 11, 12
(medial aspects), lower 24, 25, and 32 (33). Observation of
patients with vmPFC lesions led to the original development
of the IGT (13). These patients fail to demonstrate appropriate
affective reactions and judgment, and display poor decision
making in everyday life. The role of the vmPFC in IGT pro-
cessing is to use emotion-based biasing signals generated from
the body (or somatic markers). The role of the medial frontal
cortex in the GT is thought to be the integration of reward-
related autonomic input. Studies of neurological patients sug-
gest that lesions in both the ventral and/or dorsal medial PFC Figure 4. Average eigenvariate values associated with visuomotor control con-
ditions from that associated with the IGT at the medial frontal gyrus (BA10) across
result in fairly specific neuropsychological impairments that the four IGT conditions between two groups. Error bars indicate standard errors.
would affect IGT performance (16,38). Significant difference from zero: * p G .005.

594 Psychosomatic Medicine 73:588Y597 (2011)

Copyright © 2011 by the American Psychosomatic Society. Unauthorized reproduction of this article is prohibited.
BRAIN IMAGING OF GAMBLING TASK IN ALEXITHYMIA
crucial for successful task performance (18). Neural activity in
the vmPFC during affective judgment of emotional pictures was
shown to be positively related to IGT performance, whereas the
amount of neuronal activity in the vmPFC seems to determine
our ability to make affective judgments, which in turn influences
our decision-making performance (44). Furthermore, activation
in this region may be associated with the development of an-
ticipatory arousal during risky decisions (31). The somatic
marker hypothesis suggests that the feedback of arousal, in
addition to generating feeling states, may bias social behavior
and decision making (20).
Another account of the role of medial BA10 in general
cognition suggests that it might be specialized for the explicit
processing of internal mental states or the introspective eval-
uation of one’s own thoughts and feelings (45). The anterior
PFC (medial BA10) is also suggested to be involved in epi-
sodic memory retrieval (45), especially in task structure re-
quiring the scheduled retrieval of multiple elements of a past
episode (46). In decision making, the anterior PFC is specif-
ically engaged when subjects suspend the execution of an
ongoing task associated with a priori largest future rewards to
explore a potentially more rewarding task (47). The function
may be an evolutionary adaptation to overcome the limita-
tions of more posterior prefrontal processes by enabling the
emergence of more flexible cognitive control of decision
making (48).
In the context of IGT-related processing, BA10 activity
may be associated with the use of internal signals accompa-
nying affective evaluation of the stimuli, which is crucial for
successful decision making. Compared with nonalexithymic
subjects, the BA10 area in those with alexithymia did not
function during the IGT, especially in the first and second
IGT trials, and even by the last IGT trial these subjects failed
to perform the task successfully. The difference of BA10 ac-
tivity in the learning phase indicates that subjects with alex-
ithymia could not use brain function related to emotion-based
biasing signals, which are described as somatic markers by
Damasio (20), in the learning phase of IGTs in which the sig-
nal should be most useful as an indicator leading to advanta-
geous decision making in situations of uncertainty. In a more
general cognitive aspect, subjects with alexithymia may not
be able to suspend persistent selection from risky decks char-
acterized by large immediate rewards but larger long-term
punishments because of the inability to access internal men-
tal states (own thought or feeling). Neither might they be able
to learn based on past episodes of loss. Consequently, they
may lose flexible cognitive control of decision making and end
up failing to choose the option of the largest expected future
rewards.
In contrast, men with alexithymia showed more brain ac-
tivity in the caudate, cingulate gyrus (BA32), precentral gyrus,
and occipital areas during the first IGT trial. These areas are
associated with motor control, attention, and visual processing
rather than emotion-based signal processing in the vmPFC
or insula during the IGT. Therefore, it is suggested that indi-
viduals with alexithymia use different strategies during IGT
Psychosomatic Medicine 73:588Y597 (2011)
Copyright © 2011 by the American Psychosomatic Society. Unauthorized reproduction of this article is prohibited.
performance in the learning phase, although the performance
results look the same. Particularly, the function of caudate is
to regulate or control impulsivity and disinhibition (48), and the
activity of it during decision making has been suggested to be
a maker of risk attitude (49). Individuals with alexithymia may
work on IGT impulsively rather than using emotional-based
signal. In the third and fourth IGT trials, after the learning
phase, there were no significant differences in the groups in
the medial frontal areas, and differences were only observed
in the visual processing areas. This may be because the trick
for advantageous decision making in IGT is clear for indi-
viduals without alexithymia, so they no longer need to use
medial frontal area function during the third and fourth IGT
trials. Tasks demanding neural activity in this period might
be less intense compared with what is required in the learn-
ing phase for the nonalexithymic group, so there is no dif-
ference in the core brain areas related to IGT performance.
However, differences were observed in the visual processing
areas in the fourth IGT task. Each group had almost made their
decision during the learning phase (A or B for the alexithy-
mic group and C or D for the nonalexithymic group), such that
the behavioral load might be equivalent. Consequently, the
imaging results across groups did not differ substantially in the
fourth trial.
Alexithymia Trait
GT impairment accompanying altered brain activities was
observed in association with personality traits, indicating that
alexithymia is an independent clinical condition.
The behavioral form of the IGT has been shown to be a
highly sensitive measure of impaired decision making in a va-
riety of neurological and psychiatric conditions characterized
by real world decision-making impairments, such as focal brain
damage, addiction, obsessive compulsive disorder, pathologi-
cal gambling, psychosis, bipolar disorder, attention deficit
hyperactivity disorder, eating disorder, and chronic pain (50).
Although around 20% of healthy adults perform disadvanta-
geously on the IGT, those that do so may in fact score high in
‘‘cognitive disinhibition,’’ defined as having a personality style
that leads to ‘‘myopia for the future,’’ which would explain their
pattern of IGT performance (51).
Concerning the overlapping characteristics between alex-
ithymia and patients with vmPFC who remain unable to de-
velop affective reactions with appropriate affective judgment
(6Y8,14Y16), the results of the present study may indicate that
emotion plays a necessary role in achieving successful perfor-
mance on the IGT even in nonclinical populations. In addition
to personality characteristics such as cognitive disinhibition
(48) or impulsiveness (42), which have been suggested to im-
pact on IGT performance, emotional dysregulation may un-
derlie the impairment seen on the IGT. Emotion-based biasing
signals may promote or inhibit impulsiveness during the IGT.
From the point of view of cognitive-developmental model
of emotional awareness (52), the problem of alexithymia has
been posited as deficient development in the cognitive mature
595

stage, which allows some rudimentary form of emotional
experiences like awareness of bodily sensations or action ten-
dency (52). We have demonstrated that subjects with alex-
ithymia were less aware of affective stimuli at the cognitive
level but highly aroused by affective stimuli at the physiolog-
ical level in our previous studies (10,53). The present study
provides further support for this phenomenon in alexithy-
mia. Reduced BA10 activity, which is the neural substrate to
appreciate complex emotion and enable flexible cognitive re-
gulation, and greater activity in the caudate associated with
impulsiveness or action orientation may indicate lack of the
function emotionally matured and the rudimentary form of
emotional response in individuals with alexithymia. With re-
gard to the relationship between emotions and physical dis-
eases, these neural substrates in individuals with alexithymia
are inconsistent with the unifying framework by Lane (52).
Limitations
The current study recruited only men because of reported
sex differences in IGT performance and brain activation
(18,48). Further studies should examine whether neural activity
related to alexithymia is different in women. Although the
results indicate significant differences in men with alexithy-
mia during IGT performance, the number of subjects in this
study was relatively small. This might limit the power to ob-
serve differences between groups and type II error remains a
possibility. Given the unbalanced sample size of 13 in the
nonalexithymic group and 10 in the alexithymic group, it
cannot be ruled out that the significant difference between the
groups was caused by a number effect. Furthermore, because
of the limited temporal and spatial resolution of PET meth-
odology compared with fMRI, we were not able to clarify re-
gional activation associated with temporally distinct elements
of IGT performance, such as responses during risky versus
advantageous decisions. In future studies, fMRI studies with
large numbers of subjects are expected to reveal further de-
tails of alexithymic features during IGT performance.
CONCLUSIONS
In this study, we examined performance and neural sub-
strates for an emotion-based decision-making task in alex-
ithymia. Subjects with alexithymia showed lower BA10 activity
during the uncertain learning phase and failed to achieve suc-
cessful IGT performance compared with subjects without
alexithymia. These results suggest that they might not use an
emotion-based biasing signal, which should be the most use-
ful indicator leading to advantageous decision making. This
study suggests that people with alexithymia may be unable to
use feelings to guide their behavior appropriately in addition to
being unable to recognize emotions, which supports previous
findings.
We would like to thank Hiroyuki Sasaki for programming the IGT,
and M. Miyake, Y. Ishikawa, and S. Watanuki for technical assistance
with the PET imaging studies.
596
Copyright © 2011 by the American Psychosomatic Society. Unauthorized reproduction of this article is prohibited.
M. KANO et al.
REFERENCES
1. Sifneos PE. The prevalence of ‘alexithymic’ characteristic mechanisms in
psychosomatic patients. Psychother Psychosom 1973;21:133Y6.
2. Taylor GJ. Recent developments in alexithymia theory and research. Can J
Psychiatry 2000;45:134Y42.
3. Taylor GJ, Bagby RM, Parker JDA. Disorder of Affect Regulation: Alex-
ithymia in Medical and Psychiatric Illness. New York: Cambridge Uni-
versity Press; 1997:29Y30.
4. Mattila AK, Poutanen O, Koivisto AM, Salokangas RK, Joukamaa M.
Alexithymia and life satisfaction in primary healthcare patients. Psycho-
somatics 2007;48:523Y9.
5. Kauhanen J, Kaplan GA, Cohen RD, Julkunen J, Salonen JT. Alexithymia
and risk of death in middle-aged men. J Psychosom Res 1996;41:541Y9.
6. Lane RD, Sechrest L, Reidel R, Weldon V, Kaszniak A, Schwartz GE.
Impaired verbal and nonverbal emotion recognition in alexithymia.
Psychosom Med 1996;58:203Y10.
7. Lane RD, Sechrest L, Riedel R, Shapiro DE, Kaszniak AW. Pervasive
emotion recognition deficit common to alexithymia and the repressive
coping style. Psychosom Med 2000;62:492Y501.
8. Luminet O, Vermeulen N, Demaret C, Taylor GJ, Bagby RM. Alexithymia
and levels of processing: evidence for an overall deficit in remembering
emotion words. J Res Pers 2006;40:713Y33.
9. Berthoz S, Artiges E, Van de Moortele PF, Poline JB, Rouquette S, Consoli
SM, Martinot JL. Effect of impaired recognition and expression of emo-
tions on frontocingulate cortices: an fMRI study of men with alexithymia.
Am J Psychiatry 2002;159:961Y7.
10. Kano M, Fukudo S, Gyoba J, Kamachi M, Tagawa M, Mochizuki H, Itoh M,
Hongo M, Yanai K. Specific brain processing of facial expressions in people
with alexithymia: an (H2O)-O-15-PET study. Brain 2003;126:1474Y84.
11. Mantani T, Okamoto Y, Shirao N, Okada G, Yamawaki S. Reduced acti-
vation of posterior cingulate cortex during imagery in subjects with high
degrees of alexithymia: a functional magnetic resonance imaging study.
Biol Psychiatry 2005;57:982Y90.
12. Moriguchi Y, Decety J, Ohnishi T, Maeda M, Mori T, Nemoto K, Matsuda
H, Komaki G. Empathy and judging other’s pain: an fMRI study of alex-
ithymia. Cerebral Cortex 2007;17:2223Y34.
13. Bechara A, Damasio AR, Damasio H, Anderson SW. Insensitivity to future
consequences following damage to human prefrontal cortex. Cognition
1994;50:7Y15.
14. Bolla KI, Eldreth DA, London ED, Kiehl KA, Mouratidis M, Contoreggi
C, Matochik JA, Kurian V, Cadet JL, Kimes AS, Funderburk FR, Ernst M.
Orbitofrontal cortex dysfunction in abstinent cocaine abusers performing a
decision-making task. Neuroimage 2003;19:1085Y94. Accessed March 1,
2003.
15. Clark L, Manes F, Nagui A, Sahakian BJ, Robbins TW. The contributions
of lesion laterality and lesion volume to decision-making impairment fol-
lowing frontal lobe damage. Neuropsychologia 2003;41:1474Y83.
16. Manes F, Sahakian B, Clark L, Rogers R, Antoun N, Aitken M, Robbins T.
Decision-making processes following damage to the prefrontal cortex.
Brain 2002;125:624Y39.
17. Fukui H, Murai T, Fukuyama H, Hayashi T, Hanakawa T. Functional ac-
tivity related to risk anticipation during performance of the Iowa Gambling
Task. Neuroimage 2005;24:253Y9.
18. Lawrence NS, Jollant F, O’Daly O, Zelaya F, Phillips ML. Distinct roles of
prefrontal cortical subregions in the Iowa Gambling Task. Cerebral Cortex
2009;19:1134Y43.
19. Li XR, Lu ZL, D’Argembeau A, Ng M, Becharal A. The Iowa Gambling
Task in fMRI images. Hum Brain Mapp 2010;31:410Y23.
20. Damásio AR. Descartes’ Error: Emotion, Reason, and the Human Brain.
New York: Putnam; 1994.
21. Komaki G, Maeda M, Arimura T, Nakata A, Shinoda H, Ogata I, Shimura
M, Kawamura N, Kubo C. The reliability and factorial validity of the
Japanese version of the 20-item Toronto Alexithymia Scale. J Psychosom
Res 2003;43:839Y46.
22. Speilberger CD, Gorsuch RL, Lushene RE. STAI Manual. Palo Alto, CA:
Consulting Psychologist Press; 1979.
23. Leising D, Grande T, Faber R. The Toronto Alexithymia Scale (TAS-20): a
measure of general psychological distress. J Res Pers 2009;43:707Y10.
24. American Psychiatric Association. Diagnostic and Statistical Manual of
Mental Disorders, 4th edition text revision. Arlington, VA: American Psy-
chiatric Publishing; 2000.
25. International Classification of Diseases. Available at: http://apps.who.int/
classifications/apps/icd/icd10online/.
Psychosomatic Medicine 73:588Y597 (2011)
BRAIN IMAGING OF GAMBLING TASK IN ALEXITHYMIA
26. Fujiwara T, Watanuki S, Yamamoto S, Miyake M, Seo S, Itoh M, Ishii K,
Orihara H, Fukuda H, Satoh T, Kitamura K, Tanaka K, Takahashi S. Per-
formance evaluation of a large axial field-of-view PET scanner: SET-
2400W. Ann Nucl Med 1997;11:307Y13.
27. Friston KJ, Holmes AP, Poline JB, Frith CD, Worsley KJ, Frackowiak RSJ.
Statistical maps in functional imaging: a general linear approach. Hum
Brain Mapp 1994;2:189Y210.
28. Price CJ, Friston KJ. Cognitive conjunction: a new approach to brain ac-
tivation experiments. Neuroimage 1997;5:261Y70.
29. Rogers RD, Owen AM, Middleton HC, Williams EJ, Pickard JD, Sahakian
BJ, Robbins TW. Choosing between small, likely rewards and large, un-
likely rewards activates inferior and orbital prefrontal cortex. J Neurosci
1999;19:9029Y38.
30. Rogers RD, Ramnani N, Mackay C, Wilson JL, Jezzard P, Carter CS, Smith
SM. Distinct portions of anterior cingulate cortex and medial prefrontal
cortex are activated by reward processing in separable phases of decision-
making cognition. Biol Psychiatry 2004;55:594Y602.
31. Critchley HD, Wiens S, Rotshtein P, Ohman A, Dolan RJ. Neural systems
supporting interoceptive awareness. Nat Neurosci 2004;7:189Y95.
32. Ernst M, Grant SJ, London ED, Contoreggi CS, Kimes AS, Spurgeon L.
Decision making in adolescents with behavior disorders and adults with
substance abuse. Am J Psychiatry 2003;160:33Y40.
33. Bechara A, Martin EM. Impaired decision making related to working
memory deficits in individuals with substance addictions. Neuropsychol-
ogy 2004;18:152Y62.
34. Vorobiev V, Govoni P, Rizzolatti G, Matelli M, Luppino G. Parcellation of
human mesial area 6: cytoarchitectonic evidence for three separate areas.
Eur J Neurosci 1998;10:2199Y203.
35. Ullsperger M, von Cramon DY. Error monitoring using external feedback:
specific roles of the habenular complex, the reward system, and the cin-
gulate motor area revealed by functional magnetic resonance imaging.
J Neurosci 2003;23:4308Y14.
36. Volz KG, Schubotz RI, von Cramon DY. Variants of uncertainty in decision-
making and their neural correlates. Brain Res Bull 2005;67:403Y12.
37. Doya K. Complementary roles of basal ganglia and cerebellum in learning
and motor control. Curr Opin Neurobiol 2000;10:732Y9.
38. Bechara A, Damasio H, Tranel D, Anderson SW. Dissociation of working
memory from decision making within the human prefrontal cortex. J
Neurosci 1998;18:428Y37.
39. Paulus MP, Rogalsky C, Simmons A, Feinstein JS, Stein MB. Increased
Psychosomatic Medicine 73:588Y597 (2011)
View publication stats Copyright © 2011 by the American Psychosomatic Society. Unauthorized reproduction of this article is prohibited.
activation in the right insula during risk-taking decision making is related
to harm avoidance and neuroticism. Neuroimage 2003;19:1439Y48.
40. Craig AD. How do you feelVnow? The anterior insula and human
awareness. Nat Rev Neurosci 2009;1:59Y70.
41. Buelow MT, Suhr JA. Construct validity of the Iowa Gambling Task.
Neuropsychol Rev 2009;19:102Y14.
42. Takano Y, Takahashi N, Tanaka D, Hironaka N. Big losses lead to irrational
decision-making in gambling situations: relationship between deliberation
and impulsivity. PLoS One 2010;5:2.
43. Haviland MG, Reise SP. A California Q-set alexithymia prototype and
its relationship to ego-control and ego-resiliency. J Psychosom Res 1996;
41:597Y608.
44. Northoff G, Grimm S, Boeker H, Schmidt C, Bermpohl F, Heinzel A, Hell
D, Boesiger P. Affective judgment and beneficial decision making: ven-
tromedial prefrontal activity correlates with performance in the Iowa
Gambling Task. Hum Brain Mapp 2006;27:572Y87.
45. Ramnani N, Owen AM. Anterior prefrontal cortex: insights into function
from anatomy and neuroimaging. Nat Rev Neurosci 2004;5:184Y94.
46. Koechlin E, Hyafil A. Anterior prefrontal function and the limits of human
decision-making. Science 2007;318:594Y8.
47. Daw ND, O’Doherty JP, Dayan P, Seymour B, Dolan RJ. Cortical substrates
for exploratory decisions in humans. Nature 2006;441:876Y9.
48. Newcombe VF, Outtrim JG, Chatfield DA, Manktelow A, Hutchinson PJ,
Coles JP, Williams GB, Sahakian BJ, Menon DK. Parcellating the neuro-
anatomical basis of impaired decision-making in traumatic brain injury.
Brain 2011;134:759Y68.
49. Hinvest NS, Elliott R, McKie S, Anderson IM. Neural correlates of choice
behavior related to impulsivity and venturesomeness [published online
ahead of print February 18, 2011]. Neuropsychologia 2011.
50. Dunn BD, Dalgleish T, Lawrence AD. The somatic marker hypothesis: a
critical evaluation. Neurosci Biobehav Rev 2006;30:239Y71.
51. Bolla KI, Eldreth DA, Matochik JA, Cadet JL. Sex-related differences
in a gambling task and its neurological correlates. Cerebral Cortex
2004;14:1226Y32.
52. Lane RD. Neural substrates of implicit and explicit emotional processes:
a unifying framework for psychosomatic medicine. Psychosom Med
2008;70:214Y31.
53. Kano M, Hamaguchi T, Itoh M, Yanai K, Fukudo S. Correlation between
alexithymia and hypersensitivity to visceral stimulation in human. Pain
2007;132:252Y63.
597