Cerebral Cortex September 2007;17:2223--2234
doi:10.1093/cercor/bhl130
Advance Access publication December 5, 2006
Empathy and Judging Other’s Pain: An fMRI
Study of Alexithymia
Yoshiya Moriguchi1,2,3, Jean Decety4, Takashi Ohnishi2,
Motonari Maeda5, Takeyuki Mori2, Kiyotaka Nemoto2,
Hiroshi Matsuda3 and Gen Komaki1
Because awareness of emotional states in the self is a prerequisite
to recognizing such states in others, alexithymia (ALEX), difficulty
in identifying and expressing one’s own emotional states, should
involve impairment in empathy. Using functional magnetic resonance imaging (fMRI), we compared an ALEX group (n 5 16) and
a non-alexithymia (non-ALEX) group (n 5 14) for their regional
hemodynamic responses to the visual perception of pictures
depicting human hands and feet in painful situations. Subjective
pain ratings of the pictures and empathy-related psychological
scores were also compared between the 2 groups. The ALEX group
showed less cerebral activation in the left dorsolateral prefrontal
cortex (DLPFC), the dorsal pons, the cerebellum, and the left caudal
anterior cingulate cortex (ACC) within the pain matrix. The ALEX
group showed greater activation in the right insula and inferior
frontal gyrus. Furthermore, alexithymic participants scored lower
on the pain ratings and on the scores related to mature empathy. In
conclusion, the hypofunction in the DLPFC, brain stem, cerebellum,
and ACC and the lower pain-rating and empathy-related scores in
ALEX are related to cognitive impairments, particularly executive
and regulatory aspects, of emotional processing and support the
importance of self-awareness in empathy.
Keywords: anterior cingulate cortex, dorsolateral prefrontal cortex,
emotion regulation, empathy, self-awareness
Introduction
The construct of empathy refers to the ability to identify with
and vicariously share the feelings and thoughts of others. This
naturally occurring subjective experience of similarity between
the feelings of self and others is an important aspect of building
interpersonal relationships. However, there are several essential
aspects of empathy: 1) an affective response to another person,
which often, but not always, entails sharing that person’s
emotional state (affective component); 2) a cognitive capacity
to take the perspective of the other person (cognitive component); and 3) some regulatory mechanisms that keep track of
the origins of self and other feelings (Decety and Jackson 2004).
An integrative model of empathy was proposed by Preston and
de Waal (2002). This model draws on that the perception of
actions or emotions automatically activates the neural mechanisms that are responsible for the generation of those actions or
emotions. Such a system prompts the observer to resonate with
the emotional state of another individual, as a result of the
observer activating the motor representations and associated
The Author 2006. Published by Oxford University Press. All rights reserved.
For permissions, please e-mail: journals.permissions@oxfordjournals.org
autonomic and somatic responses that stem from the observed
target.
In support of this perception--action integrative model,
recent functional neuroimaging studies revealed shared neuronal substrates for empathy to the pain of others (Morrison et al.
2004; Singer et al. 2004; Botvinick et al. 2005; Jackson et al.
2005, 2006; Lamm et al. 2007; Saarela et al. 2006). These studies have indicated that watching others in painful situations
taps into the neural mechanisms that mediate the affective-motivational component of pain processing. Notably, the
anterior cingulate cortex (ACC) and anterior insula are similarly
activated by the experience of pain in the self and by the
observation of others in painful situations.
Self-awareness is a fundamental aspect of empathy because
the individual’s recognition of their own feelings is the basis for
identification with the feelings of others (Gallup 1998; Decety
and Jackson 2004). Individuals with alexithymia (ALEX) are
typically unable to identify, understand, or describe their own
emotions. Psychiatric and psychosomatic patients with ALEX
are unable to talk about feelings due to a lack of emotional selfawareness (Sifneos 1972, 1996). ALEX has been repeatedly
found in psychiatric disorders that have deficits in the recognition of feelings belonging to the self and identification with
others, such as autism and Asperger syndrome (Frith 2004; Hill
et al. 2004; Berthoz and Hill 2005), schizophrenia (Stanghellini
and Ricca 1995; Cedro et al. 2001), and borderline personality
disorder (Guttman and Laporte 2002). ALEX has also been
found in psychopathic personality disorder, where there is
a deficit in empathy (Haviland et al. 2004).
Although the concept of ALEX was originally used to describe
the characteristics of psychosomatic patients, recently it has
been used to refer to deficits in emotional functioning in
broader populations (Taylor et al. 1997; Taylor and Bagby
2004). Some researchers hypothesized that ALEX is associated
with brain abnormalities (Hoppe and Bogen 1977; Nemiah 1977;
Buchanan et al. 1980). Neuroimaging studies found that ALEX
may be associated with a higher level cognitive deficit in
estimating emotional inputs—in which the ACC plays a crucial
role—rather than a lack of neuronal response in structures
representing lower level processing of emotional stimuli
(Berthoz et al. 2002; Kano et al. 2003). ALEX has also been
found to be related to dysfunction in the posterior cingulate
cortex during various mental imagery conditions (Aleman 2005;
Mantani et al. 2005). Lane et al. (1997) stressed the core feature
of ALEX as a deficit in conscious awareness of emotions (e.g.,
Downloaded from https://academic.oup.com/cercor/article/17/9/2223/273662 by guest on 02 August 2022
1
Department of Psychosomatic Research, National Institute of
Mental Health, National Center of Neurology and Psychiatry,
Kodaira City, Tokyo 187-8553, Japan, 2Department of
Radiology, National Center Hospital for Mental, Nervous, and
Muscular Disorders, National Center of Neurology and
Psychiatry, Kodaira City, Tokyo 187-8553, Japan, 3Department
of Nuclear Medicine, Saitama Medical School Hospital, Irumagun, Saitama 350-0495, Japan, 4Department of Psychology, The
University of Chicago, Chicago, IL 60637, USA and 5Graduate
School of Art and Design, Joshibi University of Art and Design,
Sagamihara, Kanagawa 228-8538, Japan
Subjects
Three hundred and ten college students completed the 20-item Toronto
Alexithymia scale (TAS-20; Taylor et al. 2003). Individuals with high and
low TAS-20 total scores (n = 20, top quartile score > 60; n = 18, bottom
quartile score < 39) were selected in order to obtain a sample with as
large a variance on ALEX as possible. Thirty-seven students gave
informed written consent and participated in the experiment (Table
1). Participants were interviewed using the mini international neuropsychiatric interview (Sheehan et al. 1998). No subject had any history
of neurological, major medical, or psychiatric disorder. All participants
were right handed, as assessed by the Edinburgh handedness inventory
(Oldfield 1971). The participants were the same as reported in our
previous study about the association between ALEX and mentalizing
(Moriguchi et al. 2006). However, the present studies were conducted
in a completely different setting. In the present study, we focus only on
the analyses of the other’s pain perception paradigm.
The whole sample described above (n = 37) was divided into 2 groups
based on the cutoff scores on the TAS-20: ALEX (TAS > 60) and nonalexithymia (non-ALEX; TAS < 39) groups. The structured interview,
modified edition, of the Beth Israel hospital psychosomatic questionnaire (SIBIQ; Arimura et al. 2002) was used to further confirm the
presence or absence of ALEX. Four participants with high TAS-20 and
low SIBIQ scores, and 3 with low TAS-20 and high SIBIQ scores, were
discarded. Table 1 gives comparative information about the resulting
ALEX group (n = 16) and non-ALEX group (n = 14).
Methods and Materials
Note: F1 (factor 1), difficulty in identifying feeling; F2 (factor 2), difficulty in describing feeling; F3
(factor 3), externally oriented thinking; SD, standard deviation. The whole sample (n 5 37) is
introduced to analysis of main effect of painful picture tasks and correlation analysis between
neural activations and psychological measurements. Non-ALEX (n 5 14) and ALEX (n 5 16)
groups were obtained from this whole sample excluding the participants with discrepancy
between TAS-20 and SIBIQ scores (cf., Materials and Methods).
The study was approved by the local Ethics Committees (National
Center of Neurology and Psychiatry in Japan, National Institute of
Mental Health) and conducted in accordance with the Declaration of
Helsinki.
2224 fMRI Study of Alexithymia
d
Moriguchi et al.
Psychological Instruments
The TAS-20 (Taylor et al. 2003; the Japanese version by Komaki et al.
2003) is a 20-item self-administered questionnaire. The items are scored
on a 5-point scale from strongly disagree to strongly agree. The TAS-20
has a 3-factor structure. Factor 1 assesses difficulty in identifying
feelings. Factor 2 assesses difficulty in describing feelings. Factor 3
assesses externally oriented thinking.
The SIBIQ for ALEX (Arimura et al. 2002) is based on the Beth Israel
hospital psychosomatic questionnaire (Sriram et al. 1988), used mainly
with psychosomatic patients. The SIBIQ was developed for patients with
some physical or psychiatric symptoms, and they were asked to describe
how they perceived their own symptoms. For interviewing nonpatients
with no symptoms, we modified the SIBIQ by adding questions about
their feelings in response to bad/sad/difficult (negative) or happy/good/
satisfying (positive) events they had experienced. If they replied that
they had no equivalent life events, we added ‘‘if’’ questions in which they
were asked to imagine some situations that are generally supposed to
cause emotional responses (similar to the Alexithymia-provoked response questionnaire [Krystal et al. 1986]) and required them to answer
in terms of their own emotions. The testers rated these answers on the
scale of the SIBIQ. The SIBIQ was conducted by 2 medical doctors, who
were acquainted clinically with ALEX, and their 2 scores were averaged
for each subject. There is no standard cutoff point on the SIBIQ. We set
the thresholds as the top quartile of the SIBIQ scores (equivalent to
>47) as ‘‘high’’ SIBIQ and the lowest quartile ( <25) as ‘‘low’’ SIBIQ.
Table 1
Appearance of TAS-20 and SIBIQ scores in the 2 groups
Whole
Non-ALEX
ALEX
n (Male/female)
Age, mean (SD) (years)
37 (7/30)
20.4 (0.94)
14 (2/12)
20.8 (0.89)
16 (3/13)
20.2 (1.0)
TAS-20
Total
F1
F2
F3
SIBIQ total
Minimum--maximum, mean (SD)
26--74, 51.2 (16.5)
26--38, 34.1 (3.7)
7--32, 18.0 (8.1)
7--19, 10.6 (3.7)
5--25, 15.4 (6.2)
5--18, 9.6 (3.9)
9--30, 17.9 (5.1)
9--21, 13.9 (3.3)
18--70, 42.2 (16.7)
18--56, 31.5 (11.8)
61--74,
19--32,
15--24,
13--30,
25--70,
66.1
24.7
20.1
21.4
52.2
(4.5)
(3.9)
(2.4)
(4.0)
(14.1)
Downloaded from https://academic.oup.com/cercor/article/17/9/2223/273662 by guest on 02 August 2022
differentiating, symbolizing emotions, and appreciating complexity in the experience of self and other). Thus, ALEX refers to
an impairment in not only affective but also cognitive emotional
processing.
To our knowledge, the concept of ALEX itself does not
explicitly include deficits in empathy. However, the lack of
knowledge of their own emotional experiences should be
associated with a lack of empathy in alexithymics (e.g., Krystal
1979; see also levels of emotional awareness in Lane and
Schwartz 1987). Vorst and Bermond (2001) argued that an
important aspect of ALEX is ‘‘operative thinking’’ (i.e., preoccupation with ‘‘things’’ at the expense of object relations),
which covers many aspects of ALEX including the lack of
empathy.
The notion of ‘‘shared representations’’ between self and
other accounts for the functional computational properties that
emerge from the direct link between perception and action
(Decety and Sommerville 2003; Decety and Jackson 2004, 2006;
Sommerville and Decety 2006). Because empathy relies on
vicarious sharing of the feelings and thoughts of others, this
common representational network between the self and others
in conjunction with self--other awareness provides the basic
mechanism for empathy (Decety and Sommerville 2003; Decety
and Jackson 2004, 2006; Decety and Grèzes 2006). From this
perspective, we propose that ALEX (which is a deficit in
identifying emotional states in oneself) may be associated
with (or lead to) an impairment in empathy (connecting to
other’s emotional states). In line with this idea, some studies
demonstrated that individuals with ALEX show poor performance in identifying the emotional values of facial expressions
(e.g., Parker et al. 1993; Lane et al. 1996). Only a few studies,
however, have focused on the relationship between ALEX and
empathetic ability (Rastam et al. 1997; Guttman and Laporte
2002). Moreover, their results are not conclusive as to whether
a deficit in empathetic ability is an essential component of ALEX.
The purpose of the present study was to explore whether
individuals with ALEX have deficit in empathetic ability, and if
so, what aspect of empathy is impaired. We measured the
neurohemodynamic activity with functional magnetic resonance imaging (fMRI) in participants with ALEX as compared
with non-alexithymic controls, in potentially empathic situations involving both cognitive and affective aspect of painprocessing network (response to pictures depicting human
hands and feet in potentially painful situations and judging the
degree of pain in those situations; cf., Jackson et al. 2005). In
addition, we compared the scores assessing the empathyrelated abilities in the 2 groups. We hypothesized that the
ALEX group would score lower on pain- and empathy-related
scores and show different neural response in pain-related
regions demonstrated by previous neuroimaging studies about
pain processing, for example, the primary and secondary
somatosensory cortices, the posterior insula, the ACC, the
middle and anterior insula, thalamus, brain stem, and lateral
prefrontal cortex (for reviews, Davis 2000; Peyron et al. 2000;
Rainville 2002).
Picture Stimuli
The picture stimuli had been previously developed and validated by
Jackson et al. (2005) and were used with their permission. The picture
stimuli consisted of a series of digital color pictures that showed right
hands and right feet in painful and nonpainful situations, shot from
angles that facilitate a first-person perspective (i.e., no mental rotation of
the limb is required for the observer). All situations depicted familiar
events that can happen in everyday life. Various types of pain
(mechanical, thermal, and pressure) were represented. The target
persons in the pictures varied in gender and age (between 8 and 56
years), and their limbs and arms were smoothed in order to avoid any
influences of age and gender on judgments. For each painful situation,
there was a corresponding neutral picture, which involved the same
setting without any painful component. The 96 painful pictures used in
this study were selected from a larger sample, on the basis of the pain
intensity ratings of 20 independent subjects. All pictures were edited to
the same size and resolution (600 3 600 pixels).
Scanning Method and Procedure
Participants took part in one fMRI session. The session consisted of 26
blocks. The participants were asked to watch and assess the pictures
depicting right hands or feet in painful situations as a task condition (12
blocks) and right hands or feet in neutral situations as a control
condition (12 blocks). The baseline trials showed a static cross (2
blocks at the middle and end of the session). The order of conditions
was randomized within the session. No picture was presented more
than once throughout the whole experiment. Each task or control block
consisted of eight 4-s trials of the same condition. Each picture was
shown for 2 s, followed for 2 s by a modified faces pain-rating scale
(Wong and Baker 1988) that illustrated the 4-point Likert-type pain
scale (no pain [0], a little pain [1], moderate pain [2], and worst possible
pain [3]). In the baseline trials, subjects were asked to passively look at
the central cross for 4 s and were not shown the pain-rating scale. In the
task and control conditions, subjects were instructed to rate the
intensity of pain they thought the person in the picture would feel in
each situation. At the end of each task and control trial, they used a 4button response box under their right hand to select the rating (thumb
= 0, index = 1, middle finger = 2, and fourth finger = 3). The participants
were required to press the button in every trial in the task and the
control condition along the scale, thereby controlling for the motor
output involved in the rating process across the 2 conditions. Participants were provided with several training trials prior to the scanning
session in order to be acquainted with the rating scale and the task
within the allotted time. The pictures used in the training trials were
different from those used as stimuli for the fMRI measurements.
Data Acquisition and Analyses
Magnetic resonance imaging data were acquired on a 1.5-T Siemens
Magnetom Vision Plus System. Changes in blood oxygenation level-dependent T2*-weighted magnetic resonance (MR) signal (Ogawa et al.
1990) were measured using a gradient echo-planar imaging (EPI)
sequence (repetition time [TR] = 4000 ms, echo time [TE] = 40 ms,
field of view [FOV] = 220 mm, flip angle = 90 degree, 64 3 64 matrix, 40
slices per slab, slice thickness 3.0 mm, 0.3 mm gap, voxel size = 3.44 3
3.44 3 3.3 mm). For each scan session, a total of 213 EPI volume images
were acquired along the AC--PC plane. Structural MR images were
acquired with a magnetization-prepared rapid gradient echo sequence
(TE/TR, 4.4/11.4 ms; flip angle, 15 degree; acquisition matrix, 256 3 256;
1 NEX FOV, 31.5 cm; slice thickness, 1.23 mm). The first 5 volumes of
EPI images were discarded because of instability of magnetization;
therefore, we obtained 208 volumes of EPI for analysis.
The stimuli were projected onto a screen, ~50 cm from the subject’s
head. The participants viewed the screen through a mirror attached to
the head coil.
Image processing was carried out using Statistical Parametric Mapping software (SPM2, Wellcome Department of Imaging Neuroscience,
London, UK). The EPI images were realigned and coregistered to the
subjects’ T1-weighted MR images. Then the T1 images were transformed
to the anatomical space of a template brain whose space is based on the
MNI (Montreal Neurological Institute) stereotactic space. The parameters for the transformation were applied to the coregistered EPI
images. The normalized images were smoothed by a 6-mm full-width
half-maximum Gaussian kernel. A first fixed level of analysis was
computed subjectwise using the general linear model with hemodynamic response function modeled as a boxcar function whose length
covered the 8 successive pictures of the same type.
To test the hypotheses about regionally specific effects in the painful
picture condition, the estimates were compared by means of linear
contrasts for each epoch (painful picture epoch as task condition versus
neutral picture epoch as control). The resulting set of voxel values for
each contrast constituted a statistical parametric map (SPM) of the tstatistic SPM (t). Anatomic localization was presented as MNI coordinates, and to check the localization of the Brodmann area (BA), the
Talairach coordinates (Talairach and Tournoux 1988) were used. Firstlevel contrasts were introduced in a second-level random-effect analysis
(Friston et al. 1999) to allow for population inferences.
Main effects for watching painful pictures were computed using
1-sample tests for each ALEX (n = 16) and non-ALEX group (n = 14)
separately and subsequent conjunction analysis of both 1-sample tests to
show overlapping activations between 2 groups. The analyses were
done for each of the contrasts of interest, which yielded a SPM of the tstatistic (SPM [t]), subsequently transformed to the unit normal
distribution (SPM [Z]). A voxel and cluster level threshold of P < 0.05
corrected for multiple comparisons (false discovery rate; t = 2.26 for
non-ALEX group, 2.42 for ALEX group, 2.58 for conjunction analysis)
was used to identify other pain-related regions, compared against the
null hypothesis.
To compare the differences in neural activity between the ALEX
group (n = 16) and the non-ALEX group (n = 14), 2-sample tests were
Cerebral Cortex September 2007, V 17 N 9 2225
Downloaded from https://academic.oup.com/cercor/article/17/9/2223/273662 by guest on 02 August 2022
The emotional empathy scale (EES; Mehrabian and Epstein 1972;
Japanese version developed by Kato and Takagi 1980) is a selfadministered questionnaire that measures the ability of ‘‘emotional
empathy,’’ defined as an affective response to somebody else’s emotional
experience. Mehrabian and Epstein (1972) had made the items of EES
with expectation of multiple subscales of EES, but no subscales were
extracted, although the Japanese version was subdivided into 3
components (Kato and Takagi 1980) in the Japanese population as
follows: 1) Emotional warmth; a tender and compassionate attitude
toward other’s feelings. People with emotional warmth are impressionable in response to art, novel, and movies, as well as other’s sorrow and
distress, and sometimes participate in voluntary activities. 2) Emotional
chill; an apathetic and sometimes disfavoring attitude toward other’s
feeling like sorrow, distress, and joy etc. Such people always keep others
at a distance. 3) Emotional affectedness; a tendency to be easily
influenced by other’s feelings. It is almost the same as ‘‘emotional
contagion.’’
The interpersonal reactivity index (IRI; Davis 1983; Japanese version
developed by Aketa 1999) was another self-administered questionnaire
measuring the empathetic ability of the participants. The IRI consists of
4 scales, each measuring a distinct component of empathy: 1) empathic
concern, feeling emotional concern for others and 2) perspective
taking, cognitively taking the perspective of another, related to social
competence. The factors (1) and (2) were characterized as desirable
interpersonal styles. 3) fantasy, emotional identification with characters
in books, films, etc. and 4) personal distress, negative feelings in
response to the distress of others.
The stress coping inventory (SCI; Lazarus and Folkman 1984; Japanese
version developed by the Japanese Institute of Health Psychology 1996)
was used to investigate the participants’ character and coping style in
response to emotional stimuli. The SCI has 2 major factors: 1) cognitive
coping strategy and 2) emotional coping strategy. There are 8 subscales
on the SCI: 1) confrontational, 2) distancing, 3) self-controlling, 4)
seeking social support, 5) accepting responsibility, 6) escape--avoidance,
7) problem solving, and 8) positive reappraisal.
The Japanese version of these psychological scales (the TAS-20, EES,
IRI, and SCI) were the ones that have been translated into Japanese using
back-translation method, and the factor analyses of these Japanese
versions showed the same factor components as the original English
versions except for the EES. However, the concurrent validity and
reliability in each psychological measurement have been confirmed,
indicating that the Japanese version of each psychological test measures
the same aspects as the original one.
Results
Behavioral Measures
In the one sample, the individual ratings of painful pictures were
significantly higher than those of neutral control pictures
(paired t-test: mean [standard deviation (SD)] score of sum of
task pictures’ ratings in each subject; 34.2[3.6], control pictures’
ratings; 12.2[2.0], T = 343, P < 10–28). Table 2 compares the
scores for the pain ratings, IRI, EES, and the SCI between the
ALEX (n = 16) and the non-ALEX groups (n = 14). Alexithymic
participants showed lower pain ratings than non-alexithymics,
Table 2
Comparison of psychological measurements in the ALEX and non-ALEX groups
Mean (SD)
Pain ratings
IRI
Fantasy
Perspective taking
Empathic concern
Personal distress
EES
Warmth
Chill
Affectedness
SCI
Cognitive
Emotional
Problem solving
Confrontational
Seeking social support
Accepting responsibility
Self-controlling
Escape--avoidance
Distancing
Positive reappraisal
Non-ALEX (n 5 14)
ALEX (n 5 16)
23.8 (3.0)
21.0 (4.3)
2.08*
19.9
18.5
20.0
12.5
17.7
14.6
16.1
15.8
1.01
2.61*
2.48*
2.31*
(6.7)
(4.9)
(3.7)
(3.7)
(5.6)
(3.4)
(4.9)
(4.1)
T
58.0 (3.2)
29.3 (10.2)
21.0 (7.1)
49.2 (7.9)
35.6 (8.6)
22.0 (3.0)
3.93**
1.89
0.53
36.9 (12.4)
27.7 (8.1)
10.7 (4.7)
5.9 (2.1)
6.9 (3.8)
10.6 (3.8)
8.1 (3.9)
6.1 (2.6)
4.7 (2.9)
11.6 (4.0)
26.3 (10.7)
23.9 (7.4)
7.4 (4.0)
5.5 (2.5)
4.6 (3.7)
8.4 (4.4)
6.9 (3.4)
4.8 (1.7)
4.9 (2.1)
7.7 (4.1)
2.57*
1.30
2.11*
0.55
1.74
1.49
0.91
1.61
0.21
2.63*
Note: SD, standard deviation.
*P \ 0.05.
**P \ 0.001.
2226 fMRI Study of Alexithymia
d
Moriguchi et al.
indicating that they attributed lower levels of pain to the people
depicted in the painful situation pictures. They scored lower on
the IRI scales assessing ‘‘perspective taking’’ and ‘‘empathic
concern,’’ suggesting that they were less able to take the
perspective of another and had less empathy. On the EES,
alexithymics scored less on ‘‘warmth.’’ Alexithymics scored
lower on the SCI scales of ‘‘cognitive,’’ ‘‘problem solving,’’ and
‘‘positive reappraisal,’’ indicating that they were less likely to use
these approaches to manage emotional stimuli. On the other
hand, alexithymics had significantly higher ‘‘personal distress’’
scores on the IRI.
The fMRI Data
One-Sample Analyses and Conjunction Analysis
Tables 3--5 and Figures 1--3 give the results of 1-sample tests
(one for each group) throughout the whole brain related to
higher activations in response to the painful pictures than the
neutral pictures and conjunction analysis of both groups. Tables
3--5 give representative coordinates in pain-related regions; all
the coordinates are listed in Table 1 in the Supplementary
Materials. In each group and conjunction analysis, a similar
activity pattern was found. Significant signal changes were
detected in the dorsal ACC (Lt > Rt, BA 24/32), anterior insula
(Lt > Rt, BA 13), middle/inferior lateral prefrontal cortices (Lt >
Rt, BA 9/10/11/44--47), and postcentral/superior parietal cortices (Lt > Rt, BA 2; Rt > Lt, BA 1/2/3/5/7) adjacent to inferior
parietal lobule (BA 40), thalamus (Rt > Lt), brain stem (dorsal
pons/midbrain), and cerebellums (Rt > Lt). Additionally, activations were also found in the visual-related/fusiform areas/
uncus (BA 18/19/20), superior/middle frontal gyrus (BA 6), and
inferior frontal gyrus (BA 44/46). The only exception is that no
significant activity was found in the pons in the ALEX group in
contrast to high activity in this region in the non-ALEX group;
also there was no activation in the pons in the conjunction
analysis.
We calculated the correlation between neural activations in
response to painful pictures and the individual pain ratings in all
participants. Within the activated areas identified in the previous and present studies of perception of others in pain
network, we found positive correlations between the rating
scales and neural activities in the following areas: ROIs on the
right caudal ACC (BA 32, center [x, y, z] [mm] = [10, 28, 40], r =
0.44, P = 0.00312), sensory association cortex (BA 7 [(28, –68,
54), r = 0.59, P = 0.00006], BA 40 [(40, –50, 50), r = 0.63, P =
0.00002]), left lateral prefrontal cortex (BA 9, [–20, 52, 34], r =
0.41, P = 0.00587), right dorsal pons ([12, –34, –40], r = 0.52,
P = 0.00055), left thalamus ([–8, –12, 4], r = 0.40, P = 0.00769),
and right cerebellum ([18, –60, –16], r = 0.54, P = 0.00031).
Group Comparison Analysis
We compared the ALEX (n = 16) group with the non-ALEX (n =
14) group, examining group effects on neuronal activity in
response to painful pictures controlled with neutral pictures
(Table 6, Fig. 4). We found lower hemodynamic activity in the
ALEX group compared with non-ALEX group in the left
dorsolateral prefrontal cortex (DLPFC) (BA 8/9/10) in the
posterior lobes of cerebellar cortices, dorsal pons, left middle/
superior frontal gyrus (BA 6/8), and right middle temporal gyrus
(P < 0.001 uncorrected, k = 20). Although the ACC did not show
a significant difference with the chosen threshold, we found
Downloaded from https://academic.oup.com/cercor/article/17/9/2223/273662 by guest on 02 August 2022
used. The height and extent thresholds were set at Z = 3.09 (P < 0.001
uncorrected) and k = 20, respectively. For the areas with an a priori
pain-related hypothesis (derived from Singer et al. 2004; Jackson et al.
2005, 2006), we applied more lenient height and extent thresholds; Z =
2.6 (P < 0.005 uncorrected) and k = 20, respectively (adopted from Raij
et al. 2005) within the regions activated in the 1-sample group tests and
conjunction analysis to reduce the risk of false negatives. If the regions
with significant differences were included in an a priori pain matrix
confirmed by the previous studies (Peyron et al. 2000; Morrison et al.
2004; Singer et al. 2004; Jackson et al. 2005, 2006; Raij et al. 2005), we
confirmed them as group effects on pain-related activations. The a priori
regions were obtained from regions that had been emphasized as
important components and frequently reported in the literature, that is,
the primary and secondary somatosensory cortices, the posterior insula,
the caudal ACC, the middle and anterior insula, thalamus, brain stem, and
lateral prefrontal cortex (Davis 2000; Peyron et al. 2000). To further
clarify the characteristics of regions with group differences in the
a priori pain matrix, we made regions of interest (ROIs) consisted of 20
voxels centered on each peak coordinate found in the group comparisons in the present study and calculated individual mean contrast values
(task minus control) for each ROI using Marsbar software (http://
marsbar.sourceforge.net). The correlation coefficients between pain
ratings and neural responses within pain-related regions were calculated. (ROI corrected P < 0.05). The correlation coefficients between
these ROI mean contrast values and psychological measurement scores
were also calculated to investigate the features of the regions with
group differences.
Table 3
Coordinates and Z and T scores for the pain-related brain areas activated in response
to painful picture stimuli in a 1-sample test for the non-ALEX group
Table 4
Coordinates and Z and T scores for the pain-related brain areas activated in response
to painful picture stimuli in a 1-sample test for the ALEX group
Area
Area
ACC
Lt
Rt
Cerebellum
Lt anterior culmen
Rt posterior declive
DLPFC
Lt inferior frontal
Lt superior frontal
Rt inferior frontal
Rt middle frontal
Rt superior frontal
Insula
Lt anterior
Rt anterior/inferior frontal
Midbrain
Lt
Lt substantia nigra
Rt
Pons
Primary somatosensory cortex
Lt inferior parietal lobule
Lt postcentral gyrus
Rt postcentral gyrus
Secondary somatosensory cortex
Lt postcentral gyrus
Rt inferior parietal lobule
Rt postcentral gyrus
Thalamus
Lt/ventral lateral nucleus
Rt/ventral anterior nucleus
MNI x, y, z (mm)
T
Z
4.9
5.74
3.61
3.92
4.13***
4.63***
3.24**
3.47*
9.06
9.39
6.14****
6.26****
8.3
6.68
4.03
8.17
4.56
6.69
5.25
6.69
5.95
5.83
5.39
2.27
4.66
4.04
2.95
5.85****
5.12****
3.55*
5.8****
3.91***
5.13****
4.34***
5.13****
4.74*
4.68***
4.43*
2.16**
3.97***
3.55**
2.73**
24
32
24
32
10, 2, 52
8, 14, 48
8, 2, 36
12, 16, 42
—
—
32,
26,
9
10
45
46
9
10
11
9
10
9
45
11
46
47
10
54,
50,
56,
46,
42,
42,
44,
20,
34,
56,
56,
50,
54,
52,
24,
13
—
13
30, 16, 8
40, 10, 0
44, 24, 12
3.51
2.3
3.42
3.17*
2.18**
3.1*
—
—
—
—
0,
10,
6,
2,
32, 0
20, 16
18, 22
38, 42
5.87
4.06
2.74
5.37
4.7***
3.57*
2.56*
4.42***
40
3
1
5
2
40,
34,
60,
36,
52,
50,
36,
28,
46,
28,
58
48
42
58
44
8.06
5.03
8.72
5.47
9.54
5.75****
4.21*
6.01*
4.48*
6.32****
40
40
3/40
62,
68,
62,
20, 22
36, 36
20, 36
3.76
2.41
7.76
3.35*
2.28**
5.62****
—
—
14,
16,
14, 10
6, 12
5.72
4.54
4.62***
3.9***
34,
64,
10,
44,
14,
36,
36,
50,
54,
56,
56,
10,
10,
50,
32,
48,
72,
38
28
32
0
2
14
40
16
14
34
20
32
26
16
30
8
4
Note: Lt; left, Rt; right.
*P \ 0.05 false discovery rate (FDR) corrected in each ROI.
**P \ 0.05 FDR corrected (height threshold: t 5 2.26).
***P \ 0.001 FDR corrected (height threshold: t 5 4.28).
****P \ 0.05 family wise error (FWE) corrected (height threshold: t 5 6.39).
reduced activation for the ALEX group in the left ACC (BA 24/
32) when using a more lenient threshold (P < 0.005, k = 20)
within the a priori pain-related region. The ALEX group showed
stronger signal change compared with the non-ALEX group in
the right anterior insula (BA 13) and the inferior frontal gyrus
(BA 45) within a pain matrix and additionally bilateral ventral
anterior cingulate gyri, right superior frontal gyrus, and right
superior/middle temporal gyrus. ALEX group also showed
increased activity in the right posterior insula (BA 13) compared
with non-ALEX although activation in this area was not found in
the conjunction analysis. Correlation coefficients between the
hemodynamic activation in each ROI and the psychological
measurement scores are shown in Table 7 for the pain-related
regions found in the group comparison (i.e., right DLPFC [peak]
[x, y, z] = [–20, 56, 34]; left ACC [–12, 2, 52]; left dorsal pons [–2,
38, –42]; left cerebellum [–14, –64, –32]; right inferior frontal
gyrus [Rt IFG] [54, 22, 4]; right anterior insula [38, 14, 2]; and
ACC
Lt
Rt
Cerebellum
Lt posterior pyramis/vermis
Rt posterior uvula
DLPFC
Lt inferior frontal
Lt middle frontal
Rt inferior frontal
Rt middle frontal
Insula
Lt
Rt
Midbrain
Rt substantia nigra
Primary somatosensory cortex
Lt postcentral
Rt inferior parietal lobule
Rt postcentral
Secondary somatosensory cortex
Lt inferior parietal lobule
Lt postcentral gyrus
Rt postcentral gyrus
Thalamus
Lt
Rt
BA
MNI x, y, z (mm)
24
32
24
32
8/32
0, 6, 28
8, 24, 40
6, 24, 16
6, 8, 52
6, 16, 48
38
44
T
Z
4.05
4.96
2.62
4.93
4.98
3.6**
4.2***
2.5**
4.2***
4.2*
5.18
7.18
4.3***
5.4****
4.1
4.44
6.79
6.95
6.98
3.58
5.44
3.73
5.14
6.29
3.02
4.69
3.6*
3.8*
5.2****
5.3****
5.3*
3.2*
4.5***
3.3*
4.3***
4.9***
2.8*
4***
3.08
4.51
4.42
2.8**
3.9*
3.8*
4.61
3.9**
—
—
0,
12,
74,
74,
47
45
46
9
44
11
10
47
45
9
10
46
52,
58,
46,
56,
56,
46,
32,
56,
54,
56,
34,
38,
18, 6
20, 24
34, 12
8, 32
8, 20
52, 12
60, 10
22, 6
28, 6
8, 32
40, 24
28, 20
13
13
—
30, 26, 0
38, 6, 8
36, 20, 2
—
18,
18,
3
5
1
2
40
5
2
30,
42,
60,
68,
38,
34,
52,
38,
44,
28,
24,
34,
52,
28,
48
66
42
30
42
70
44
4.34
6.84
7.85
8.2
6.18
9.03
9.49
3.8*
5.2****
5.7*
5.8*
4.9*
6.1****
6.3*
40
40
3/40
68,
52,
62,
26, 30
26, 20
20, 38
8.27
3.57
8.08
5.8****
3.2*
5.8****
—
—
14,
8,
18, 10
26, 4
5.08
3.83
4.2***
3.4*
6
Note: Lt, left; Rt, right.
*P \ 0.05 false discovery rate (FDR) corrected in each ROI.
**P \ 0.05 FDR corrected (height threshold: t 5 2.42).
***P \ 0.001 FDR corrected (height threshold: t 5 4.53).
****P \ 0.05 family wise error (FWE) corrected (height threshold: t 5 6.39).
right posterior insula [38, –30, 18]). The DLPFC did not show any
significant correlations with the psychological scores. The left
dorsal ACC showed a significant positive correlation coefficient
with ‘‘self-controlling’’ on the SCI. The brain stem (dorsal pons)
showed a negative correlation with ‘‘personal distress’’ on the IRI
and a positive correlation with ‘‘cognitive’’ on the SCI. The left
cerebellum showed a positive correlation with ‘‘warmth’’ on the
EES and ‘‘problem solving’’ on the SCI. The right anterior insula
correlated positively with ‘‘affectedness’’ on the EES and negatively with ‘‘cognitive’’ and ‘‘problem solving’’ on the SCI. The
right posterior insula had positive correlation with ‘‘personal
distress’’ on the IRI and negative correlation with ‘‘cognitive,’’
‘‘seeking social support,’’ ‘‘accepting responsibility,’’ and ‘‘positive reappraisal.’’ The Rt IFG showed a negative correlation with
‘‘warmth’’ on the EES and ‘‘positive reappraisal’’ on the SCI.
Discussion
The results of the present experiment support previous neuroimaging studies of empathy for pain, showing selective
Cerebral Cortex September 2007, V 17 N 9 2227
Downloaded from https://academic.oup.com/cercor/article/17/9/2223/273662 by guest on 02 August 2022
Lt middle frontal
BA
Table 5
Coordinates and Z and T scores for the pain-related brain areas activated in response
to painful picture stimuli in conjunction analysis of 1-sample tests on both groups
Area
BA
ACC
Lt
24
32
8/32
Rt
Cerebellum
Lt posterior tonsil
DLPFC
Lt inferior frontal
Rt middle frontal
Insula
Lt
Midbrain
Lt midbrain
Lt substantia nigra
Primary somatosensory cortex
Lt postcentral
Rt inferior parietal lobule
Rt postcentral
Lt inferior parietal lobule
Secondary somatosensory cortex
Lt
Rt
Thalamus
Lt
Rt
0, 0, 40
8, 24, 40
2, 18, 48
40
T
Z
3.26
4.54
4.48
2.98**
3.9*
3.86*
3.48
3.15**
3.84
5.43
6.79
6.95
5.22
2.76
5.64
4.14
3.41*
4.45*
5.18*
5.25*
4.33*
2.58**
4.57**
3.63**
2.75
3.31
2.57**
3.02**
—
30,
36,
47
44
46
9
10
44
9
46
48,
56,
46,
56,
34,
54,
56,
42,
44, 12
8, 22
34, 12
8, 32
60, 8
8, 20
10, 32
28, 20
13
13
42, 2, 4
32, 16, 10
—
—
2,
14,
36,
22,
4
8
2.68
3.33
2.51**
3.03**
3
5
2
1
40
5
2
40
38,
42,
62,
60,
38,
38,
52,
54,
28,
46,
24,
28,
34,
48,
28,
32,
58
62
36
42
42
60
44
46
4.36
5.33
7.13
7.85
6.18
4.87
9.49
8.17
3.78*
4.39*
5.34*
5.66*
4.87*
4.11*
6.3**
5.8*
40
3/40
62,
62,
20, 22
20, 38
3.76
7.5
3.35*
5.51*
—
—
14,
4,
18, 10
32, 4
4.73
3.29
4.02**
3**
Downloaded from https://academic.oup.com/cercor/article/17/9/2223/273662 by guest on 02 August 2022
Lt middle frontal
Rt inferior frontal
MNI x, y, z (mm)
Note: Lt; left, Rt; right.
*P \ 0.05 false discovery rate (FDR) corrected in each ROI.
**P \ 0.05 FDR corrected (height threshold: t 5 2.58).
activation of the neural network mediating the perception of
other’s pain (Morrison et al. 2004; Singer et al. 2004; Botvinick
et al. 2005; Jackson et al. 2005, 2006; Lamm et al. 2007; Saarela
et al. 2006). Interestingly, individuals with ALEX rated the
painful stimuli as less painful than individuals without ALEX.
Furthermore, fMRI measures showed lower signal change in the
left lateral prefrontal cortex, left ACC, cerebellum, and dorsal
pons in the ALEX group than in the non-ALEX group in response
to viewing pictures of painful situations.
The behavioral measures revealed that the ALEX group
showed lower scores for pain ratings and on questionnaires
assessing empathetic qualities. This indicates that ALEX is
associated with not only difficulty in representing one’s own
emotional state but also the emotions of others. It is worth
noting that Guttman and Laporte (2002) reported behavioral
results very similar to ours: alexithymic participants had higher
levels of IRI personal distress and lower levels of perspective
taking and fantasy. Personal distress scale has clearly different
features from other scales on IRI: perspective taking and fantasy
were significant and positively related to empathic concern,
whereas a significant inverse relationship was found between
perspective taking and personal distress (Davis 1983). Personal
distress involves the experiences of another’s distress as if it
were one’s own due to incapability of distinguishing the self-other difference. It is generally considered as a primitive form of
empathic response in developmental science because the infant
2228 fMRI Study of Alexithymia
d
Moriguchi et al.
Figure 1. Brain images of the higher regional cerebral activation in response to the
other’s painful pictures compared with control pictures in the non-alexithymic sample.
The brain images illustrate the clusters with neural activities in response to the other’s
pain task (contrasted with no-pain control pictures) within pain-related regions using
1-sample tests for the non-ALEX group (n 5 14). The white circles on the brain images
indicate the notable clusters related to the pain network. The bar on the lower right
shows the range of t scores for SPM. The height threshold for illustrating the clusters
was P \ 0.05 corrected (false discovery rate). (a--e) sagittal view; (f) coronal view; (g,
h) axial view; (i) right side; (j) left side; (k) top. Ins, insula; Thal, thalamus; cACC, caudal
anterior cingulate cortex; S2, secondary sensory cortex; S1, primary sensory cortex.
imitates the emotional distress of another but without an
awareness of the other’s situation or condition (Eisenberg
2000; Decety 2007; Lamm et al. 2007). Davis (1996) noted
that personal distress as a mere reactive response to another’s
condition, rather than a direct representation of another’s
Downloaded from https://academic.oup.com/cercor/article/17/9/2223/273662 by guest on 02 August 2022
Figure 2. Brain images of the higher regional cerebral activation in response to the
other’s painful pictures compared with control pictures in the alexithymic sample. The
brain images illustrate the clusters with neural activities in response to the other’s pain
task (contrasted with no-pain control pictures) within pain-related regions using 1sample tests for the ALEX group (n 5 16). The white circles on the brain images
indicate the notable clusters related to the pain network. The bar on the lower right
shows the range of t scores for SPM. The height threshold for illustrating the clusters
was P \ 0.05 corrected (false discovery rate). (a--e) sagittal view; (f) coronal view; (g,
h) axial view; (i) right side; (j) left side; (k) top. Ins, insula; Thal, thalamus; cACC, caudal
anterior cingulate cortex; S2, secondary sensory cortex; S1, primary sensory cortex.
affect, characterized by a negative affective tone and selforiented thought processes. Such individuals experiencing
personal distress as a reaction to another’s distress tend to
feel more anxious and uncomfortable regardless of the state of
mind of the other. Personal distress scale is associated with high
Figure 3. Brain images of the higher regional cerebral activations in response to the
other’s painful pictures compared with control pictures in conjunction analysis of both
groups. The brain images illustrate the clusters with neural activities in response to the
other’s pain task (contrasted with no-pain control pictures) within pain-related regions
in conjunction analysis that shows overlapping areas using two 1-sample tests (ALEX
group [n 5 16] and non-ALEX group [n 5 14]). The white circles on the brain images
indicate the notable clusters related to the pain network. The bar on the lower right
shows the range of t scores for SPM. The height threshold for illustrating the clusters
was P \ 0.05 corrected (false discovery rate). (a--e) sagittal view; (f) coronal view; (g,
h) axial view; (i) left side; (j) right side; (k) top. Ins, insula; Thal, thalamus; cACC, caudal
anterior cingulate cortex; S2, secondary sensory cortex; S1, primary sensory cortex.
levels of social dysfunction, fearfulness, uncertainty, emotional
vulnerability, shyness, and social anxiety. High personal distress
was characterized by their concern with how others evaluate
them and with lowered concern for others (Davis 1983). Thus,
Cerebral Cortex September 2007, V 17 N 9 2229
Table 6
Coordinates and Z and T scores for the brain areas differently activated between
the ALEX and non-ALEX groups; group comparison using 2-sample tests
Area
BA
ALEX \ non-ALEX
Lt lateral prefrontal cortex
Cerebellum
Lt anterior dentate
Lt anterior culmen
Lt posterior declive
Rt posterior declive
Lt dorsal anterior cingulate gyrusa
Rt middle temporal gyrus
Lt superior frontal gyrus
Lt middle frontal gyrus
ALEX [ non-ALEX
Rt anterior insulaa
Rt posterior insula
Rt IFG
Rt ventral anterior cingulate
Rt superior frontal gyrus
Rt middle temporal gyrus
Rt superior temporal gyrus
Lt ventral anterior cingulate
9
9
8
20, 56, 34
12, 60, 32
12, 52, 44
—
—
—
—
—
—
—
—
—
24
24
38
8
6
14, 64,
18, 50,
10, 54,
4, 70,
6, 76,
22, 70,
32, 34,
22, 32,
2, 38,
12, 2, 52
14, 4, 56
32, 2, 32
20, 12, 46
32, 10, 58
13
13
40
45
24
9
21
21
22
—
38,
38,
48,
54,
6,
20,
62,
60,
62,
8,
32
24
28
20
28
28
40
36
42
14, 2
30, 18
24, 16
26, 6
26, 14
42, 34
6, 6
2, 8
26, 2
38, 4
T
Z
Cluster k
4.73
4.31
4.07
4.02
3.74
3.57
113
4.98
4.95
4.33
4.73
4.02
3.91
4.6
4.5
4.34
3.42
3.28
4.83
4.09
4.04
4.18
4.16
3.76
4.02
3.54
3.46
3.94
3.87
3.76
3.1
2.99
4.08
3.59
3.55
133
3.49
4.26
4.08
5.48
5.33
5.16
4.55
4.16
4.49
4.15
3.15
3.71
3.58
4.48
4.39
4.29
3.9
3.64
3.86
3.63
65
46
115
26
100
70
25
21
20
28
40
53
71
100
20
22
Note: Height and extent threshold: T 5 3.41(P 5 0.001 uncorrected) and k 5 20 voxels. Lt, left;
Rt, right.
a
T 5 2.76, (P 5 0.005 uncorrected) and k 5 20 voxels.
personal distress is regarded as a less mature aspect of empathy
and is related to impairments in cognitive aspects of empathy.
Higher levels of personal distress in alexithymics in the present
study indicate that ALEX may be related to immature forms of
empathy (Guttman and Laporte 2000, 2002). We also found
significantly lower scores in the ALEX group on the EES for
warmth and on the SCI for cognitive, ‘‘planful problem solving,’’
and positive reappraisal, reflecting their less cognitive strategies
on the occasion of coping with emotional stress. ALEX has been
found to be associated with low ‘‘emotional intelligence’’
(Fukunishi et al. 2001), which has a factor of empathy in terms
of recognizing and understanding emotions in others (Goleman
1995). Therefore, we consider that alexithymic individuals, who
have difficulty in identifying their own feelings, are also poor at
representing and evaluating other’s mental states, especially in
terms of their cognitive aspects.
The fMRI experiment showed that the main effect of watching painful stimuli was associated with activation in the
somatosensory (SI/SII), thalamus, ACC, anterior insula, cerebellum, lateral prefrontal cortex, and brain stem. Consistent with
previous neuroimaging studies, activation in these areas involved in empathy for pain was replicated, without physical
sensation of actual pain stimulation. Furthermore, we found
a relationship between the evaluation of painful pictures and
activation in the lateral prefrontal cortex, pons, cerebellum, and
right caudal ACC, as previously reported (Singer et al. 2004;
Jackson et al. 2005). In our study, sensory inputs and motor
outputs were controlled, so these activations derived from only
visual input and processing these stimuli, not sensory feedback
as a result of pressing the response buttons. It is possible that to
2230 fMRI Study of Alexithymia
d
Moriguchi et al.
Downloaded from https://academic.oup.com/cercor/article/17/9/2223/273662 by guest on 02 August 2022
Lt posterior cerebellar tonsil
Lt brain stem pons
MNI x, y, z(mm)
accurately estimate pain in others, participants might further
engage almost the whole pain matrix, not only the affective
component within the pain network, notably the rostral ACC
and anterior insula. Interestingly, a recent transcranial magnetic
stimulation study demonstrated the sensorimotor side of
empathy for pain by showing a reduction in excitability of hand
muscles during the observation of painful stimuli (Avenanti
et al. 2005). Together with our results, this points to the
implication of regions other than those implicated in the
affective component of empathy for pain.
The group comparison analyses indicated lower activation in
the left lateral prefrontal cortex, dorsal pons, cerebellum, and
ACC in the ALEX group as compared with the non-ALEX group.
These regions have been demonstrated to be activated in
association with the perception of other’s pain (Singer et al.
2004; Jackson et al. 2006; Lamm et al. 2007) and in other painrelated studies (Davis 2000; Peyron et al. 2000; Raij et al. 2005).
Reportedly, the interregional correlation of midbrain and
medial thalamic activity was reduced during high left DLPFC
activity (Lorenz et al. 2003). This indicates that the DLPFC
exerts active control of pain perception by modulating corticosubcortical and corticocortical pathways. Furthermore, the
locus of the region in the present study is close to that
activated by empathic and forgiveness tasks (Farrow et al.
2001), chronic facial pain contrasted with the pain-free
condition after thalamic stimulation (Kupers et al. 2000), and
rating the valence and intensity of affective pictures (Grimm
et al. 2005). In summary, the DLPFC was associated with
cognitive (especially executive and/or regulatory) processing
of visual stimuli. These results are consistent with the hypothesis proposed by Taylor and Bagby (2004) of a hypofunction of
the prefrontal cortex in individuals with ALEX, referring to the
neuroimaging study by Hariri et al. (2000). In addition, it has
been suggested that the DLPFC, reciprocally connected to
many other neocortical areas, including the ACC, as well as the
basal ganglia and the brain stem, regulates the functions that
utilize emotional feelings for a survival function like planning
and initiative. This includes the capacity to harmonize current
behavior with the demands of the environment. Hence, it
would be expected that selective lesions in this neural
network may result in alexithymic features (Bermond 1997).
Empathy requires emotional regulation (Eisenberg 2000;
Decety and Jackson 2006; Decety 2007), and the DLPFC is
key region implicated in this process (Ochsner and Gross
2005). It is thus logical to suggest that lateral prefrontal
hypoactivity in ALEX is associated with a deficit in cognitive
(particularly executive/regulating) function in empathizing and
evaluating other’s pain.
Moreover, the caudal ACC (cCZ [caudal cingulate zone]; Picard
and Strick 1996, posterior part of 24b9; Vogt and Peters 1981,
Vogt et al. 1996) showed less activation in alexithymics than in
non-alexithymics. TAS-20 total scores have been reported to be
correlated with the size of the normalized surface area of the
right ACC (Gundel et al. 2004). The ACC has been associated
with conscious awareness of emotion (Lane et al. 1997). The
locus of the ACC that was less activated in ALEX in our study
corresponds to the cognitive subdivision of the ACC that is
involved in second-order representation or awareness (Lane
2000; Berthoz et al. 2002). Alexithymic individuals have been
reported to show less activation in the ACC in response to the
emotionally laden (e.g., anger) components of facial expressions
(Kano et al. 2003). Interestingly, Vogt et al. (1996) argued that
Table 7
Correlation coefficients between the mean neural activity in ROIs found in group
comparisons for each psychological measurement
Lt DLPFC Lt cACC Pons
EES
Warmth
Chill
Affectedness
IRI
Fantasy
Perspective taking
Empathic concern
Personal distress
SCI
Cognitive
Emotional
Problem solving
Confrontational
Seeking social support
Accepting responsibility
Self-controlling
Escape--avoidance
Distancing
Positive reappraisal
Lt cerebellum Rt AI
Rt PI
Rt IFG
0.22
0.07
0.08
0.24
0.19
0.11
0.28
0.14
0.18
0.36*
0.23
0.1
0.12
0.14
0.36*
0.11
0.05
0.24
0.36*
0.02
0.21
0.27
0.17
0.2
0.15
0.14
0.14
0.07
0.05
0
0.06
0.19
0.44*
0.02
0.11
0.31
0.01
0.05
0.31
0.14
0.28
0.19
0.09
0.06
0.42*
0.12
0.14
0.19
0.07
0.15
0.07
0.16
0.02
0.09
0.1
0.07
0.05
0.15
0.11
0.24
0.18
0.17
0.12
0.04
0.26
0.35*
0.05
0.09
0.24
0.37*
0
0.3
0.12
0.14
0.26
0.15
0.03
0.16
0.29
0.3
0.04
0.37*
0.02
0.23
0.03
0.32
0.06
0.24
0.22
0.35*
0.2
0.36*
0.29
0.09
0.25
0.15
0.1
0.05
0.29
0.48*
0.32
0.26
0.11
0.37*
0.34*
0.28
0.19
0.12
0.53*
0.33
0.3
0.3
0.18
0.32
0.15
0.02
0.25
0.02
0.47*
Note: cACC, caudal anterior cingulate cortex; AI/PI, anterior/posterior insula; IFG, inferior frontal
gyrus; Lt, left; Rt, right.
Bold type *P \ 0.05.
different parts of cingulate cortex are engaged in different processing levels of nociceptive information and that area 24b9 is
involved in the controlling aspect of pain processing like response selection. A meta-analysis concluded that mid-ACC hemodynamic activations detected in the first-hand experience of
pain reflect the cognitive dimension of pain experience, including the awareness and response selection to pain stimuli
(Peyron et al. 2000). The location of the caudal ACC activation,
observed in group comparison analysis, is more posterior than
the rostral ACC region associated with affective reaction to
pain. Therefore, we suggest that ALEX may be related to some
impairment in the cognitive--motivational aspects of pain processing. It is important to note that the motivational dimension
of pain processing includes the selection and preparation of
movements of aversion (Morrison et al. 2004). Reportedly, activation in the mid-ACC is related to processes regarding pain in
self, such as somatic monitoring, negative stimulus evaluation,
and the selection of appropriate skeletomuscular movements of
aversion (Isomura and Takada 2004; Jackson et al. 2006).
Considering the participants with ALEX scored lower on pain
and empathy scales, they would not be concerned by other’s
pain, so there should be less need for them to prepare their own
organisms for a negative threatening experience. That might
result in the less activation in caudal ACC in alexithymics in the
present study. Interestingly, neural activities in this region had
a positive correlation with pain ratings, which alexithymic
participants estimated as lower. Activity in this region is
associated with self-control ability in response to painful picture
tasks. These results are fairly consistent with the ACC deficit
model of ALEX (Lane et al. 1997; Berthoz et al. 2002).
The dorsal pons and cerebellum were found to be less
activated in the ALEX group in the present study. Although
monoaminergic projections from the brain stem to the prefrontal cortex are well known (Porrino and Goldman-Rakic
1982), there are sizable and highly ordered inputs to the pons
from the DLPFCs, which are then relayed to the cerebellum
(Schmahmann and Pandya 1997). Hence, this area is an integral
node in the distributed cortical--subcortical neural circuitry
supporting cognitive operations (Schmahmann and Pandya
1995). In order to evaluate painful situations in others without
actually experiencing pain, people probably also rely on highorder cognitive functions to access minor changes in their
physical state as a tool for estimating the stimulus input.
Cerebellum abnormality is related to a broad range of psychiatric
Cerebral Cortex September 2007, V 17 N 9 2231
Downloaded from https://academic.oup.com/cercor/article/17/9/2223/273662 by guest on 02 August 2022
Figure 4. Brain images of the different regional cerebral activations between individuals with and without ALEX in response to the other’s painful picture task. The orthogonal views
of brain images illustrate the clusters with different neural activities in response to the other’s pain task (contrasted with no-pain control pictures) within pain-related regions. The
bar on the lower right shows the range of t scores for SPM. The height and extent threshold for illustrating were Z 5 2.6 (T 5 3.33), (P \ 0.005 uncorrected) and k 5 20,
respectively. (a) The figures for the notable clusters with less activation in the ALEX group compared with non-ALEX group. Peak MNI coordinates (x, y, z) 5 ( 20, 56, 34); cACC,
caudal anterior cingulate cortex ( 12, 2, 52); brain stem (dorsal pons) ( 2, 38, 42); and cerebellum ( 14, 64, 32). (b) The figures for the clusters with more activation in the
ALEX group than the non-ALEX group. AI, anterior insula (38, 14, 2); PI, posterior insula (38, 38, 18); and IFG, inferior frontal gyrus (54, 22, 4).
2232 fMRI Study of Alexithymia
d
Moriguchi et al.
Eisenberger et al. (2003) and Eisenberger Lieberman (2003,
2004) noted that the right ventral prefrontal cortex activation
(RVPFC [x = 42, y = 27, z = 11], near the Rt IFG in the present
study [x = 42, y = 27, z = 11]) was associated with less dorsal ACC
activation and less self-reported distress across participants,
suggesting that the RVPFC might serve a self-regulatory
suppressive function by disrupting the pain distress. One
possible interpretation is that the individuals with ALEX might
try to deny and suppress the negative emotional aspects of the
painful picture stimuli, resulting in their discreet evaluation
about pain in the task pictures. Relationship between ALEX and
a suppressive aspect of emotional processing remains to be
solved.
A limitation of our study is that multiple correlation analyses
were computed between hemodynamic ROI activation and
psychological measurements, which might induce a significant
result due to chance in each correlation analysis. However,
adopting a more conservative corrected alpha level could
increase false negative results. Although the present correlation
study is useful to check the features of hemodynamic activation
in each ROI in an exploratory way, one should acknowledge
that the present results are only suggestive values and need
further reconfirmations in future experiments. Another limitation is that the perception of pain in others with the use of
pictures of limbs does not account for the full construct of
empathy, but only part of it. According to several recent
neurocognitive models of empathy, this capacity includes
emotional contagion (that can lead to personal distress),
sympathy, cognitive empathy, helping behavior etc., which all
share aspects of their underlying process and cannot be totally
disentangled (Preston and de Waal 2002; Decety and Jackson
2004, 2006; Lawrence et al. 2006). Further studies are needed in
the future with the task to focus and discriminate each more
specific aspect of empathy. Moreover, it has not been concluded
whether the degree of ALEX does not influence thresholds for
experimentally induced pain (de Zwaan et al. 1996; Nyklicek
and Vingerhoets 2000; Jackson et al. 2002), so the results of the
group comparisons for empathy to pain in the present study
might be affected by actual tolerances for pain. Relationship
between pain perception and ALEX remains to be clarified.
In conclusion, the present study demonstrates that individuals with ALEX showed diminished pain ratings, less mature
empathy scores, and decreased neural activity associated with
cognitive empathy to other’s pain, notably in the lateral prefrontal and caudal anterior cingulate areas rather than in affective
components like the anterior insula. The pain-related areas like
the pons, ACC, and cerebellum showing decreased neural
activities in ALEX were associated with cognitive aspects of
empathy and coping style questionnaires. Empathy is comprised
of a number of components such as taking others’ perspectives
and emotional regulation (including identifying, describing, and
objectifying inner feelings) based on continuous self-awareness
(Decety and Jackson 2004, 2006). Any organism capable of selfrecognition would have an introspective awareness of its own
mental state and the ability to ascribe mental states to others
(Humphrey 1990). The emergence of a self-representation in
psychological development is crucial for the empathic process
(e.g., Lewis et al. 1989). Taken together with our results, the
impaired cognitive (particularly executive/regulatory) aspects
of empathy could be a part of the core deficit in ALEX, which
is associated with impaired emotional regulation and also
highlights the importance of self-awareness in empathy.
Downloaded from https://academic.oup.com/cercor/article/17/9/2223/273662 by guest on 02 August 2022
disorders (Konarski et al. 2005). Furthermore, in our study,
neural activity in the pons was associated with the cognitive
coping strategy scale and negatively correlated with personal
distress. Neural activation in the cerebellum correlated with
problem solving coping style, which suggests that the subtentorial structures may be engaged in cognitive control aspects
of empathy for other’s pain.
We found more activation in the anterior insula in the ALEX
group. The anterior insula, known to be closely connected to
the amygdala and ventral ACC, plays an important role in
responding to emotional stimuli as ‘‘ventral prelimbic’’ areas,
and these regions are often synchronized with each other
(Mayberg 1997). The prelimbic areas were found to be suppressed (or biased against) during cognitively demanding tasks
like a counting stroop task (Bush et al. 1998, 2000). Furthermore, reciprocal changes involving the prelimbic area and
prefrontal cortex were also found. Hemodynamic increases in
the prelimbic area and decreases in the prefrontal cortex were
reported in response to sadness, although these 2 areas
demonstrated the inverse correlation as a person recovered
from a depressive state (Mayberg et al. 1999). If an individual
engages less cognitive processing for the painful pictures, the
suppression of activation in the anterior insula would be
decreased. The ALEX group, which has more impairment in
cognitive aspects, may have had more activation in the anterior
insula compared with the non-alexithymics as a result of
decreased suppression. In contrast to our study, Kano et al.
(2003) found reduced activation in the anterior insula in
response to emotional faces. The reason for this discrepancy
might be that our study required participants to judge other’s
pain cognitively, whereas the paradigm used by Kano and
colleagues involved the passive observation of emotional stimuli,
less cognitively demanding. Thus, the present study might tap
into more cognitive processing than the study by Kano and
colleagues. Furthermore, the finding in the present study that
neural activity in the insula was associated with more personal
distress and emotional affectedness and less cognitive and less
problem solving coping styles supports these inferences.
ALEX group also showed increased neural activity in the right
posterior insula, although this region was not extracted by the
conjunction analysis. Craig (2003) noted that the dorsal
posterior insula involves the primary (not metarepresentational) interoceptive representation of the inputs of physiological condition from all tissues of the body, including pain,
temperature, itch, sensual touch, muscular and visceral sensations, vasomotor activity, hunger, thirst, and ‘‘air hunger.’’ Thus,
the posterior insula is related to lower level representation of
the physical state. Considering that neural activity in this region
positively correlated with the personal distress scale and
negatively with cognition-related stress coping scales, the result
of stronger activity in the posterior insula in the ALEX group
indicates that individuals with ALEX might be stuck in lower
level representation of one’s own physical state. Interestingly,
a recent neuroscience research, including intracranial electrophysiological stimulations in neurological patients, indicates
that distinct subregions of the insula contribute to different
aspects of empathy (Decety and Lamm 2006). The posterior
insula is associated with personal distress (self-oriented response), whereas the anterior insula is associated with empathy
(other oriented emotional responses).
In the present study, the neural activity in the Rt IFG (x = 54,
y = 22, z = 4) was stronger in ALEX group than non-ALEX group.
Supplementary Material
Supplementary material can be found at: http://www.cercor.
oxfordjournals.org/.
Notes
This study was supported by the Research Grant (17A-3, H17-kokoro007) for Nervous and Mental Disorders from the Ministry of Health,
Labor, and Welfare, Japan. Conflict of Interest: None declared.
Address correspondence to Yoshiya Moriguchi, Department of
Psychosomatic Research, National Institute of Mental Health, National
Center of Neurology and Psychiatry, 4-1-1, Ogawa-Higashi Cho, Kodaira
City, Tokyo 187-8551, Japan. Email: ymorigu@ncnp.go.jp.
Aketa H. 1999. Structure and measurement of empathy: Japanese version
of Davis’s Interpersonal Reactivity Index (IRI-J). Psychol Rep Sophia
Univ. 23:19--31.
Aleman A. 2005. Feelings you can’t imagine: towards a cognitive
neuroscience of alexithymia. Trends Cogn Sci. 9:553--555.
Arimura T, Komaki G, Murakami S, Tamagawa K, Nishikata H, Kawai K,
Nozaki T, Takii M, Kubo C. 2002. Development of the structured
interview by the modified edition of Beth Israel hospital psychosomatic questionnaire (SIBIQ) in Japanese edition to evaluate alexithymia. Jpn J Psychosom Med. 42:259--269.
Avenanti A, Bueti D, Galati G, Aglioti SM. 2005. Transcranial magnetic
stimulation highlights the sensorimotor side of empathy for pain. Nat
Neurosci. 8:955--960.
Bermond B. 1997. Brain and alexithymia. In: Vingerhoets AJM, van Bussel
FJ, Boelhouwer AJW, editors. The (non)expression of emotions in
health and disease. Tilburg (The Netherlands): Tilburg University
Press. p. 115--129.
Berthoz S, Artiges E, Van De Moortele PF, Poline JB, Rouquette S, Consoli
SM, Martinot JL. 2002. Effect of impaired recognition and expression
of emotions on frontocingulate cortices: an fMRI study of men with
alexithymia. Am J Psychiatry. 159:961--967.
Berthoz S, Hill EL. 2005. The validity of using self-reports to assess
emotion regulation abilities in adults with autism spectrum disorder.
Eur Psychiatry. 20:291--298.
Botvinick M, Jha AP, Bylsma LM, Fabian SA, Solomon PE, Prkachin KM.
2005. Viewing facial expressions of pain engages cortical areas
involved in the direct experience of pain. Neuroimage. 25:312--319.
Buchanan DC, Waterhouse GJ, West SC Jr. 1980. A proposed neurophysiological basis of alexithymia. Psychother Psychosom. 34:248--255.
Bush G, Luu P, Posner MI. 2000. Cognitive and emotional influences in
anterior cingulate cortex. Trends Cogn Sci. 4:215--222.
Bush G, Whalen PJ, Rosen BR, Jenike MA, McInerney SC, Rauch SL. 1998.
The counting Stroop: an interference task specialized for functional
neuroimaging—validation study with functional MRI. Hum Brain
Mapp. 6:270--282.
Cedro A, Kokoszka A, Popiel A, Narkiewicz-Jodko W. 2001. Alexithymia
in schizophrenia: an exploratory study. Psychol Rep. 89:95--98.
Craig AD. 2003. Interoception: the sense of the physiological condition
of the body. Curr Opin Neurobiol. 13(4):500--505.
Davis KD. 2000. Studies of pain using functional magnetic resonance
imaging. In: Casey KL, Bushnell MC, editors. Pain imaging (Progress
in pain research and management, Vol 18). Seattle (WA): IASP press.
p. 195--210.
Davis MH. 1983. Measuring individual differences in empathy: evidence
for a multidimensional approach. J Pers Soc Psychol. 44:113--126.
Davis MH. 1996. Empathy: a social psychological approach. Boulder
(CO): Westview Press.
de Zwaan M, Biener D, Bach M, Wiesnagrotzki S, Stacher G. 1996. Pain
sensitivity, alexithymia, and depression in patients with eating
disorders: are they related? J Psychosom Res. 41:65--70.
Decety J. 2007. A social cognitive neuroscience model of human empathy.
In: Harmon-Jones E, Winkielman P, editors. Fundamentals of social
neuroscience. New York: Guilford Publications. p. 9246--9270.
Decety J, Grèzes J. 2006. The power of simulation: imaging one’s own
and other’s behavior. Brain Res. 1079:4--14.
Cerebral Cortex September 2007, V 17 N 9 2233
Downloaded from https://academic.oup.com/cercor/article/17/9/2223/273662 by guest on 02 August 2022
References
Decety J, Jackson PL. 2004. The functional architecture of human
empathy. Behav Cogn Neurosci Rev. 3:71--100.
Decety J, Jackson PL. 2006. A social neuroscience perspective of
empathy. Curr Dir Psychol Sci. 15:54--58.
Decety J, Lamm C. 2006. Human empathy through the lens of social
neuroscience. Sci World J. 6:1146--1163.
Decety J, Sommerville JA. 2003. Shared representations between self and
other: a social cognitive neuroscience view. Trends Cogn Sci. 7:527--533.
Eisenberg N. 2000. Emotion, regulation, and moral development. Annu
Rev Psychol. 51:665--697.
Eisenberger NI, Lieberman MD. 2004. Why rejection hurts: a common
neural alarm system for physical and social pain. Trends Cogn Sci.
8:294--300.
Eisenberger NI, Lieberman MD, Williams KD. 2003. Does rejection hurt?
An FMRI study of social exclusion. Science. 302:290--292.
Farrow TF, Zheng Y, Wilkinson ID, Spence SA, Deakin JF, Tarrier N,
Griffiths PD, Woodruff PW. 2001. Investigating the functional
anatomy of empathy and forgiveness. Neuroreport. 12:2433--2438.
Friston KJ, Holmes AP, Worsley KJ. 1999. How many subjects constitute
a study? Neuroimage. 10:1--5.
Frith U. 2004. Emanuel Miller lecture: confusions and controversies
about Asperger syndrome. J Child Psychol Psychiatry. 45:672--686.
Fukunishi I, Wise TN, Sheridan M, Shimai S, Otake K, Utsuki N, Uchiyama
K. 2001. Association of emotional intelligence with alexithymic
characteristics. Psychol Rep. 89:651--658.
Gallup GG. 1998. Self-awareness and the evolution of social intelligence.
Behav Processes. 42:239--247.
Goleman D. 1995. Emotional intelligence: why it matters more than IQ.
New York: Bantam Books.
Grimm S, Schmidt CF, Bermpohl F, Heinzel A, Dahlem Y, Wyss M, Hell D,
Boesiger P, Boeker H, Northoff G. 2006. Segregated neural representation of distinct emotion dimensions in the prefrontal cortex—
an fMRI study. Neuroimage. 30(1):325--340.
Gundel H, Lopez-Sala A, Ceballos-Baumann AO, Deus J, Cardoner N,
Marten-Mittag B, Soriano-Mas C, Pujol J. 2004. Alexithymia correlates
with the size of the right anterior cingulate. Psychosom Med.
66:132--140.
Guttman H, Laporte L. 2002. Alexithymia, empathy, and psychological
symptoms in a family context. Compr Psychiatry. 43:448--455.
Guttman HA, Laporte L. 2000. Empathy in families of women with
borderline personality disorder, anorexia nervosa, and a control
group. Fam Process. 39:345--358.
Hariri AR, Bookheimer SY, Mazziotta JC. 2000. Modulating emotional
responses: effects of a neocortical network on the limbic system.
Neuroreport. 11:43--48.
Haviland MG, Sonne JL, Kowert PA. 2004. Alexithymia and psychopathy:
comparison and application of California Q-set prototypes. J Pers
Assess. 82:306--316.
Hill E, Berthoz S, Frith U. 2004. Brief report: cognitive processing of own
emotions in individuals with autistic spectrum disorder and in their
relatives. J Autism Dev Disord. 34:229--235.
Hoppe KD, Bogen JE. 1977. Alexithymia in twelve commissurotomized
patients. Psychother Psychosom. 28:148--155.
Humphrey N. 1990. The uses of consciousness In: Brockman J, editor.
Speculations: the reality club. New York: Prentice Hall. p. 67--84.
Isomura Y, Takada M. 2004. Neural mechanisms of versatile function in
primate anterior cingulate cortex. Rev Neurosci. 15:279--291.
Jackson PL, Brunet E, Meltzoff AN, Decety J. 2006. Empathy examined
through the neural mechanisms involved in imagining how I feel
versus how you feel pain. Neuropsychologia. 44(5):752--761.
Jackson PL, Meltzoff AN, Decety J. 2005. How do we perceive the pain of
others? A window into the neural processes involved in empathy.
Neuroimage. 24:771--779.
Jackson PL, Rainville P, Decety J. 2006. To what extent do we share the
pain of others? Insight from the neural bases of pain empathy. Pain.
125(1-2):5--9.
Jackson T, Nagasaka T, Fritch A, Gunderson J. 2002. Alexithymia is not
related to tolerance for cold pressor pain. Percept Mot Skills.
94:487--488.
Japanese Institute of Health Psychology. 1996. Lazarus type stress
coping inventory. Tokyo (Japan): Jitsumu Kyoiku Shuppan.
2234 fMRI Study of Alexithymia
d
Moriguchi et al.
Oldfield RC. 1971. The assessment and analysis of handedness: the
Edinburgh inventory. Neuropsychologia. 9:97--113.
Parker JD, Taylor GJ, Bagby RM. 1993. Alexithymia and the recognition
of facial expressions of emotion. Psychother Psychosom. 59:197--202.
Peyron R, Laurent B, Garcia-Larrea L. 2000. Functional imaging of brain
responses to pain. A review and meta-analysis (2000). Neurophysiol
Clin. 30:263--288.
Picard N, Strick PL. 1996. Motor areas of the medial wall: a review of
their location and functional activation. Cereb Cortex. 6:342--353.
Porrino LJ, Goldman-Rakic PS. 1982. Brainstem innervation of
prefrontal and anterior cingulate cortex in the rhesus monkey
revealed by retrograde transport of HRP. J Comp Neurol. 205:63--76.
Preston SD, de Waal FB. 2002. Empathy: its ultimate and proximate bases.
Behav Brain Sci. 25:1--20.
Raij TT, Numminen J, Narvanen S, Hiltunen J, Hari R. 2005. Brain
correlates of subjective reality of physically and psychologically
induced pain. Proc Natl Acad Sci USA. 102:2147--2151.
Rainville P. 2002. Brain mechanisms of pain affect and pain modulation.
Curr Opin Neurobiol. 12:195--204.
Rastam M, Gillberg C, Gillberg IC, Johansson M. 1997. Alexithymia in
anorexia nervosa: a controlled study using the 20-item Toronto
alexithymia scale. Acta Psychiatr Scand. 95:385--388.
Saarela MV, Hlushchuk Y, Williams AC, Schurmann M, Kalso E, Hari R.
2006. The compassionate brain: humans detect intensity of pain
from another’s face. Cereb Cortex. Advance Access published
February 22, 2006, doi:10.1093/cercor/bhj141.
Schmahmann JD, Pandya DN. 1995. Prefrontal cortex projections to the
basilar pons in rhesus monkey: implications for the cerebellar
contribution to higher function. Neurosci Lett. 199:175--178.
Schmahmann JD, Pandya DN. 1997. Anatomic organization of the basilar
pontine projections from prefrontal cortices in rhesus monkey. J
Neurosci. 17:438--458.
Sheehan DV, Lecrubier Y, Sheehan KH, Amorim P, Janavs J, Weiller E,
Hergueta T, Baker R, Dunbar GC. 1998. The mini-international
neuropsychiatric interview (M.I.N.I. the development and validation
of a structured diagnostic psychiatric interview for DSM-IV and
ICD-10. J Clin Psychiatry. 59(Suppl 20):22--33.
Sifneos PE. 1972. Short-term psychotherapy and emotional crisis.
Cambridge (MA): Harvard University Press.
Sifneos PE. 1996. Alexithymia: past and present. Am J Psychiatry.
153:137--142.
Singer T, Seymour B, O’Doherty J, Kaube H, Dolan RJ, Frith CD. 2004.
Empathy for pain involves the affective but not sensory components
of pain. Science. 303:1157--1162.
Sommerville JA, Decety J. 2006. Weaving the fabric of social interaction:
articulating developmental psychology and cognitive neuroscience.
Psychon Bull Rev. 13(2):179--200.
Sriram TG, Pratap L, Shanmugham V. 1988. Towards enhancing the
utility of Beth Israel hospital psychosomatic questionnaire. Psychother Psychosom. 49:205--211.
Stanghellini G, Ricca V. 1995. Alexithymia and schizophrenias. Psychopathology. 28:263--272.
Talairach J, Tournoux P. 1988. Co-planar stereotaxic atlas of the human
brain. New York: Thieme.
Taylor GJ, Bagby RM. 2004. New trends in alexithymia research.
Psychother Psychosom. 73:68--77.
Taylor GJ, Bagby RM, Parker JD. 2003. The 20-Item Toronto alexithymia
scale. IV. Reliability and factorial validity in different languages and
cultures. J Psychosom Res. 55:277--283.
Taylor GJ, Bagby RM, Parker JDA. 1997. Disorders of affect regulation:
alexithymia in medical and psychiatric illness. Cambridge (UK):
Cambridge University Press.
Vogt BA, Peters A. 1981. Form and distribution of neurons in rat cingulate
cortex: areas 32, 24, and 29. J Comp Neurol. 195(4):603--625.
Vogt BA, Derbyshire S, Jones AK. 1996. Pain processing in four regions of
human cingulate cortex localized with co-registered PET and MR
imaging. Eur J Neurosci. 8(7):1461--1473.
Vorst HCM, Bermond B. 2001. Validity and reliability of the BermondVorst alexithymia questionnaire. Pers Individ Dif. 30:413--434.
Wong DL, Baker CM. 1988. Pain in children: comparison of assessment
scales. Pediatr Nurs. 14:9--17.
Downloaded from https://academic.oup.com/cercor/article/17/9/2223/273662 by guest on 02 August 2022
Kano M, Fukudo S, Gyoba J, Kamachi M, Tagawa M, Mochizuki H, Itoh M,
Hongo M, Yanai K. 2003. Specific brain processing of facial
expressions in people with alexithymia: an H2 15O-PET study. Brain.
126:1474--1484.
Kato T, Takagi H. 1980. A trait of the emotional empathy in adolescence.
Stud Psychol Tsukuba Univ. 2:33--42.
Komaki G, Maeda M, Arimura T, Nakata A, Shinoda H, Ogata I, Shimura M,
Kawamura N, Kubo C. 2003. The reliability and factorial validity of
the Japanese version of the 20-item Toronto Alexithymia Scale.
J Psychosom Res. 55(2):143.
Konarski JZ, McIntyre RS, Grupp LA, Kennedy SH. 2005. Is the
cerebellum relevant in the circuitry of neuropsychiatric disorders?
J Psychiatry Neurosci. 30:178--186.
Krystal H. 1979. Alexithymia and psychotherapy. Am J Psychother. 33:17--31.
Krystal JH, Giller EL Jr, Cicchetti DV. 1986. Assessment of alexithymia in
posttraumatic stress disorder and somatic illness: introduction of
a reliable measure. Psychosom Med. 48:84--94.
Kupers RC, Gybels JM, Gjedde A. 2000. Positron emission tomography
study of a chronic pain patient successfully treated with somatosensory thalamic stimulation. Pain. 87:295--302.
Lamm C, Batson CD, Decety J. Forthcoming. The neural basis of human
empathy. Effects of perspective-taking and cognitive appraisal. J
Cogn Neurosci.
Lane RD. 2000. Neural correlates of conscious emotional experience. In:
Nadel L, editor. Cognitive neuroscience of emotion. Oxford: Oxford
University Press. p. 345--370.
Lane RD, Ahern GL, Schwartz GE, Kaszniak AW. 1997. Is alexithymia the
emotional equivalent of blindsight? Biol Psychiatry. 42:834--844.
Lane RD, Schwartz GE. 1987. Levels of emotional awareness: a cognitivedevelopmental theory and its application to psychopathology. Am
J Psychiatry. 144:133--143.
Lane RD, Sechrest L, Reidel R, Weldon V, Kaszniak A, Schwartz GE. 1996.
Impaired verbal and nonverbal emotion recognition in alexithymia.
Psychosom Med. 58:203--210.
Lawrence EJ, Shaw P, Giampietro VP, Surguladze S, Brammer MJ, David
AS. 2006. The role of ‘shared representations’ in social perception
and empathy: an fMRI study. Neuroimage. 29:1173--1184.
Lazarus RS, Folkman S. 1984. Stress, appraisal, and coping. New York:
Springer.
Lewis M, Sullivan MW, Stanger C, Weiss M. 1989. Self development and
self-conscious emotions. Child Dev. 60:146--156.
Lorenz J, Minoshima S, Casey KL. 2003. Keeping pain out of mind: the
role of the dorsolateral prefrontal cortex in pain modulation. Brain.
126:1079--1091.
Mantani T, Okamoto Y, Shirao N, Okada G, Yamawaki S. 2005. Reduced
activation of posterior cingulate cortex during imagery in subjects
with high degrees of alexithymia: a functional magnetic resonance
imaging study. Biol Psychiatry. 57:982--990.
Mayberg HS. 1997. Limbic-cortical dysregulation: a proposed model of
depression. J Neuropsychiatry Clin Neurosci. 9:471--481.
Mayberg HS, Liotti M, Brannan SK, McGinnis S, Mahurin RK, Jerabek PA,
Silva JA, Tekell JL, Martin CC, Lancaster JL, et al. 1999. Reciprocal
limbic-cortical function and negative mood: converging PET findings
in depression and normal sadness. Am J Psychiatry. 156:675--682.
Mehrabian A, Epstein N. 1972. A measure of emotional empathy. J Pers.
40:525--543.
Moriguchi Y, Ohnishi T, Lane RD, Maeda M, Mori T, Nemoto K, Matsuda H,
Komaki G. 2006. Impaired self-awareness and theory of mind: an fMRI
study of mentalizing in alexithymia. Neuroimage. 32(3):1472--1482.
Morrison I, Lloyd D, di Pellegrino G, Roberts N. 2004. Vicarious
responses to pain in anterior cingulate cortex: is empathy a multisensory issue? Cogn Affect Behav Neurosci. 4:270--278.
Nemiah JC. 1977. Alexithymia. theoretical considerations. Psychother
Psychosom. 28:199--206.
Nyklicek I, Vingerhoets AJ. 2000. Alexithymia is associated with low
tolerance to experimental painful stimulation. Pain. 85:471--475.
Ochsner KN, Gross JJ. 2005. The cognitive control of emotion. Trends
Cogn Sci. 9:242--249.
Ogawa S, Lee TM, Kay AR, Tank DW. 1990. Brain magnetic resonance
imaging with contrast dependent on blood oxygenation. Proc Natl
Acad Sci USA. 87:9868--9872.
Academia.edu no longer supports Internet Explorer.
To browse Academia.edu and the wider internet faster and more securely, please take a few seconds to upgrade your browser.
...Read more
Related Papers
Neuropsychologia, 2006
Download
PLoS One, 2007
Download
Neuroimage, 2005
Download
Journal of Neuroscience, 2010
Download
Social Cognitive and Affective Neuroscience, 2020
Download
Voces de guerrilleros y guerrilleras de la Liga Comunista 23 de Septiembre en la Sierra Tarahumara, 1973-1975. Cronología y algunas interpretaciones. , 2023
Download
Download
