Department of Psychiatry and Neurosciences, Graduate School of Biomedical Sciences, Hiroshima University, Hiroshima, and Core Research for Evolutional Science and Technology (CREST), Japan Science and Technology Corporation, Seika
Hiroshima University Health Service Center, Hiroshima
Department of Psychiatry and Neurosciences, Graduate School of Biomedical Sciences, Hiroshima University, and CREST, Seika, Japan
Correspondence: Dr Shigeto Yamawaki, Department of Psychiatry and Neurosciences, Division of Frontier Medical Science, Programs for Biomedical Research, Graduate School of Biomedical Sciences, Hiroshima University, 1-2-3 Kasumi, Minami-ku, Hiroshima 734-8551, Japan.Tel: +81 82 257 5207; fax: +81 82 257 5209; e-mail: yamawaki{at}hiroshima-u.ac.jp
Funding detailed in Acknowledgement.
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ABSTRACT |
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Aims To detect gender differences in brain activation during processing of these words.
Method Functional magnetic resonance imaging was used to investigate 13 men and 13 women during an emotional decision task consisting of unpleasant words concerning body image and neutral words.
Results The left medial prefrontal cortex and hippocampus were activated only among men, and the left amygdala was activated only among women during the task; activation in the apical prefrontal region was significantly greater in men than in women.
Conclusions Our data suggest that the prefrontal region is responsible for the gender differences in the processing of words concerning body image, and may also be responsible for gender differences in susceptibility to eating disorders.
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INTRODUCTION |
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METHOD |
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Emotional decision task
We used the emotional decision task developed by Tabert et al
(2001), with some
modifications. The words used in the task were selected from the database of
Toglia & Battig (1978),
which includes 2854 words that have been rated on several items such as
familiarity and pleasantness, on a scale of 1 (very unfamiliar; very
unpleasant) to 7 (very familiar; very pleasant), with 4 as the mid-point. For
our study, 30 neutral words were selected from the database and translated
into Japanese. We also selected 30 highly unpleasant words concerning body
image, chosen from Japanese-language dictionaries and thesauri. The two groups
of words did not significantly differ with regard to word length (mean length
in Japanese letters: body image words 3.2, neutral words 3.1; P=0.575
by two-tailed, two-sample Students t-test). Our previous
validation study comparing women who had eating disorders with a control group
of healthy women showed that there was no significant difference in
familiarity between the two categories of words (eating disorder group mean
familiarity score: body image words 4.2; neutral words 4.1, P=0.727;
control group mean familiarity score: body image words 3.9, neutral words 4.1,
P=0.218, by two-tailed Wilcoxon single-rank test) and there was no
significant difference in the familiarity ratings of words concerning body
image between women with eating disorders and the control group
(P=0.365 by two-tailed Wilcoxon single-rank test), whereas there were
significant differences in pleasantness between the two categories of words
(mean pleasantness score in the eating disorder group: body image words 2.4,
neutral words 3.9, P=0.0002; mean pleasantness score in the control
group: body image words 3.0, neutral words 4.0, P=0.0001, by
two-tailed Wilcoxon single-rank test) and there were significant differences
in the ratings of pleasantness between the eating disorders group and the
control group (P=0.030 by two-tailed Wilcoxon single-rank test)
(Shirao et al,
2003b). Both lists of words contained nouns, verbs,
adjectives and adverbs.
The selected words were used to generate sets of unpleasant words concerning body image and sets of neutral words. Each word set comprised a unique combination of three words. The word sets were presented in six alternating blocks of two conditions (the task condition and the control condition) in three cycles (Fig. 1). During the task condition unpleasant word sets were presented, and during the control condition neutral word sets were presented. Each block began with a 3 s cue identifying the condition by displaying the word task or control. Five word sets were presented in each block. Each word set was shown for 4 s with a 1.4 s interstimulus interval (Fig. 1). The blood oxygen level-dependent (BOLD) response was recorded during three blocks of unpleasant words and three blocks of neutral words. During each interstimulus interval, a fixation cross placed centrally on the screen replaced the word set. Baseline functional magnetic resonance images were obtained during a 9 s period prior to the first block of trials, during which the individual viewed a centrally placed fixation cross. During each trial, the word set was projected to the centre of the persons field of view by a Super Video Graphics adapter computer-controlled projection system. The timing of presentation of word sets was controlled by Presentation Software Version 0.51 (Neurobehavioral Systems, Inc., San Francisco, CA, USA) and the word sets were presented in a randomised order. Immediately before functional magnetic resonance imaging (fMRI) scanning was begun, each participant was given ten practice trials (five unpleasant word sets and five neutral word sets). The words presented in the practice trials did not overlap with the experimental words.
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Participants were instructed to select the most unpleasant word from each set of unpleasant words based on their personal knowledge and experience, and for each set of neutral words, participants were instructed to select the word that they thought was the most neutral; they indicated their choice by pressing one of three buttons on a response pad in the MRI scanner.
Image acquisition and processing
The MRI scanner used was a Magnex Eclipse 1.5 T Power Drive 250 (Shimadzu
Medical Systems, Kyoto, Japan). A time-course series of 63 volumes was
acquired with T2*-weighted, gradient echo, echo
planar imaging (EPI) sequences. Each volume consisted of 28 slices, each 4.0
mm thick with no gap, encompassing the entire brain. The interval between two
successive acquisitions of the same image (time to repetition, TR) was 3000
ms, the time to echo (TE) was 55 ms and the flip angle was 90°. The field
of view was 256 mm and the matrix size 64 x 64, giving voxel dimensions
of 4.0 mm x 4.0 mm x 4.0 mm. After fMRI scanning, structural scans
were acquired using a T1-weighted gradient echo pulse
sequence (TR 12 ms, TE 4.5 ms, flip angle 20°, field of view 256 mm, voxel
dimensions 1.0 mm x 1.0 mm x 1.0 mm), to facilitate localisation
and co-registration of the functional data.
Image processing and statistical analysis were performed using Statistical Parametric Mapping (SPM) 99 software (Wellcome Department of Cognitive Neurology, London, UK) implemented in Matlab (Mathworks, Inc., Natick, MA, USA). The first two volumes of the fMRI run (pre-task period) were discarded because the magnetisation was unsteady, and the remaining 61 volumes were used for the statistical analysis. Images were corrected for motion and realigned with the first scan of the session, which served as the reference. The T1 anatomical images were co-registered to the first functional images in each individual and aligned to a standard stereotaxic space, using the Montreal Neurological Institute (MNI) T1 template in SPM99. The calculated non-linear transformation was applied to all functional images for spatial normalisation. Finally, the fMRI images were smoothed with a 12 mm full-width, half-maximum Gaussian filter.
Using group analysis according to a random effect model that allowed
inference to the general population
(Friston et al, 1999),
we first identified brain regions that showed a significantly greater response
to unpleasant word sets in comparison with the response to neutral word sets
among male and among female participants, as brain areas related to the
cognition of unpleasant word stimuli concerning body image in men and women,
respectively. We then took the data of 13 of the 15 women who had participated
in our previous study (Shirao et
al, 2003a) and directly compared the activation of
the entire brain in the male and female sub-samples using the two-sample
Students t-test. The resulting set of voxel values for each
contrast constituted an SPM{t} map. The SPM{t} maps were then interpreted by
referring to the probabilistic behaviour of Gaussian random fields. The data
were given an initial threshold at an uncorrected P < 0.001 at the
voxel level, and regions about which we had an a priori hypothesis
were reported at this threshold (Elliott
et al, 2000). For regions about which there was no clear
hypothesis, a more stringent threshold of P < 0.05 corrected at
the cluster level of multiple comparison was used. The x, y and
z coordinates provided by SPM, which were in MNI brain space, were
converted to the x, y and z coordinates in Talairach &
Tournouxs (TT) brain space
(Talairach & Tournoux,
1988) using the following formulae:
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Evaluation of pleasantness and familiarity of the word stimuli
Each participant was asked to rate the pleasantness and familiarity of all
the words presented in the tasks on a scale from 1 (very unfamiliar; very
unpleasant) to 7 (very familiar; very pleasant), immediately after scanning.
For this rating procedure the list of words was presented in randomised order
in a table format.
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RESULTS |
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Brain activation
In men there was significantly greater activation of the left hippocampus,
left superior temporal gyrus, left fusiform gyrus and left medial frontal
gyrus when the emotional decision task involved unpleasant words compared with
neutral words, whereas the women showed significantly greater activity of the
left parahippocampal gyrus including amygdala, left thalamus and right caudate
body in the same comparison (Table
1, Fig. 2).
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The two-sample Students t-test revealed that there was a significantly higher BOLD response in the left apical prefrontal region in men than in women during the unpleasant word task compared with neutral word task (Table 1, Fig. 3). No brain area showed significantly higher activation in women than in men during any of the tasks.
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Correlation between psychological data and brain activation
Among the 13 women participants, activation in the left apical prefrontal
area, which was significantly lower than that in men during the unpleasant
words task, was negatively correlated with the total EDI2 score
(Spearmans rank-order correlation analysis: correlational coefficient
-0.699, P=0.008). There was no correlation between any brain area
showing significant BOLD response and the EDI2 scores or the
pleasantness rating of the unpleasant words.
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DISCUSSION |
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Lack of amygdalar activation in men
Consistent with our hypothesis, the amygdala did not show significant
activation among men; however, the gender difference of the BOLD response in
the amygdala was not significant by two-sample Students
t-test.
The amygdala has been suggested by many studies to be strongly associated with stimuli signalling threat. Human lesion and imaging studies consistently indicate that the amygdala is concerned in fear conditioning (Morris et al, 1998), in the recognition of fearful facial expressions (Adolphs, 1999) and in the evocation of fearful emotional responses from direct stimulation (Halgren et al, 1978). The amygdala is also considered to be important in the detection of environmental threat (Scott et al, 1997), including verbal stimuli (Isenberg et al, 1999). Therefore, the lack of significant activation in the amygdala among men suggests that men may not process unpleasant words concerning body image as fearful information, whereas women seem to do so.
Medial prefrontal cortex and emotional processing
The significant activation in the medial part of the frontal gyrus
Brodmann areas (BAs) 9 and 10; medial prefrontal cortex was only
detected in men, and there was a significantly higher BOLD response in men
than in women in the left apical prefrontal region (BA 9) when performing the
unpleasant word task compared with the neutral word task by two-sample
Students t-test. These results were consistent with our
hypothesis. Many previous studies have suggested that the medial prefrontal
cortex might have a role generally in emotional processing. It is reported
that visual stimuli that evoke emotions, such as films or pictures, activated
the medial prefrontal cortex, and that recall of various emotions such as
happiness, sadness and disgust, and a mixture of these emotions, all
separately engaged this brain region (Lane
et al, 1997; Reiman
et al, 1997). Several more recent studies suggest that
when people turn their attention inwards to assess self-relevant attributes or
emotional awareness, activity increases in the medial prefrontal cortex
(Johnson et al, 2002;
Zysset et al, 2002).
The medial prefrontal cortex has connections to limbic structures, including
the amygdala, constituting an interaction zone between emotional processing
and cognitive processing (Drevets &
Raichle, 1998), and this region may have a role in modulating the
emotional response in the amygdala and other limbic structures. Limbic
structures, including the amygdala, are likely to respond to emotional stimuli
at a sensory or perceptual level (Reiman
et al, 1997), whereas the medial prefrontal cortex may be
involved in the cognitive aspects of emotional processing, such as attention
to emotion, appraisal or identification of emotion
(Drevets & Raichle, 1998). From this viewpoint, the gender differences detected in our study may
demonstrate differences of cognitive pattern in men and women. Our results
suggest the possibility that men processed the emotional decision task
including words concerning body image more cognitively rather than
emotionally, and activation in the medial prefrontal cortex was prominent; on
the other hand, women processed this task more emotionally rather than
cognitively, and the medial prefrontal cortex did not exhibit any significant
activation. Both men and women perceived the unpleasantness of the words
concerning body image to the same degree, according to their subjective
ratings, but the fMRI data suggest that their processes are different: women
are likely to use more intuitive processing whereas men use more rational
processing. This discrepancy between the genders in cognitive style related to
body image may contribute to the large gender difference in susceptibility to
eating disorders.
Another possible explanation of the different patterns of activation in the medial prefrontal cortex between men and women may be the difference in mens familiarity with the unpleasant word set compared with the neutral words. Although the ratings of familiarity were not different between men and women (P=0.133 by MannWhitney U test), there was a trend for male participants to be less familiar with the unpleasant words concerning body image than with the neutral words (P=0.054 by two-tailed Wilcoxon single-rank test). When processing unfamiliar words concerning body image, men might turn more attention inwards, and subsequently the BOLD response in the medial prefrontal cortex was higher than while processing neutral words.
Among women, correlational analysis revealed that the BOLD response in the left apical prefrontal region (BA 9), which was significantly lower in women than in men, was negatively correlated with total EDI2 scores; in other words women with higher EDI2 scores exhibited lower activity in this brain area. These results suggest the possibility that the apical prefrontal region might be involved in the pathophysiology of eating disorders.
Comparison with other neuroimaging studies
To our knowledge, two fMRI studies concerning body image distortion have
investigated the effects of pictorial body image stimuli in women with
anorexia nervosa and healthy controls
(Seeger et al, 2002; Wagner et al, 2003).
One study reported that patients with anorexia nervosa showed activation in
the right amygdala, right fusiform gyrus and brain-stem associated with
stimulation with their own body image whereas healthy controls showed
activation only in the fusiform gyrus
(Seeger et al, 2002),
and the other reported that patients with anorexia nervosa showed greater
activation in the prefrontal cortex and the inferior parietal lobule than did
controls (Wagner et al,
2003). The latter authors explain the discrepancy between these
results as a consequence of the design of the task. Many differences in the
experimental conditions between these studies and ours make it difficult to
compare the brain activation data, but a possible explanation of the
discrepancy between the study by Wagner et al
(2003) and our study is the
age of the participants: those in the former study were adolescents
(approximately 15 years old), whereas we recruited young adults (approximately
25 years old). An fMRI study which investigated the brain activation of adult
and adolescent men and women while processing emotional facial expressions
reported that the adult men and adolescents (both boys and girls) showed
significant activation in the bilateral orbitofrontal cortex and anterior
cingulate cortex in response to an angry face, whereas the adult women showed
significant activation in the left amygdala in addition to these brain areas
(McClure et al,
2004). These results suggest that the patterns of neural responses
to emotional stimuli may be different in adults and adolescents.
A positron emission tomography study of gender differences in brain activation patterns during recognition of emotional facial expressions revealed that greater amygdalar activation was observed in women and greater medial frontal activation was observed in men (Hall et al, 2004); these authors suggest that men might take a more analytic approach and might regulate their emotional reaction to the stimuli more than women. Although the categories of stimuli are different, these results support our findings.
Study limitations
Our study has some limitations. First, we did not administer a structured
interview when selecting the participants; however, they had no psychiatric or
neurological illness at the time of their participation, although we cannot
rule out its occurrence in the future. Second, participants were asked to rate
only the unpleasantness and familiarity of the words used. If we had also
asked about the fearfulness induced by the stimuli, we might have found gender
differences in subjective rating and the results with brain image data would
have been more clear-cut. Last, although our data suggest that there is
differential activation of the brains of men and women when processing
unpleasant words concerning body image, we cannot conclude whether these
results are specific to unpleasant stimuli concerning body image or would
apply to a wide range of unpleasant stimuli. Among women, a lower BOLD
response in the prefrontal region compared with men while processing
unpleasant words concerning body image exhibited a negative correlation with
the total EDI2 score, but it is unclear whether this brain region is
the focal area responsible for susceptibility to eating disorders.
In conclusion, our study revealed that the paralimbic area including the amygdala was activated only in women and that the left medial prefrontal cortex was activated only in men while performing the emotional decision task with unpleasant words concerning body image. These results suggest that gender differences in brain activation might explain the differences in the style of cognition towards unpleasant stimuli concerning body image. Further studies comparing people who have eating disorders with healthy controls and which include general unpleasant word stimuli to contrast with words specific to body image are needed to elucidate the neural substrate responsible for the onset of eating disorders.
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Clinical Implications and Limitations |
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LIMITATIONS
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ACKNOWLEDGMENTS |
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Received for publication March 4, 2004. Revision received August 10, 2004. Accepted for publication August 11, 2004.
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