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com/locate/ynimg NeuroImage 32 (2006) 1299 1307

Men and women show distinct brain activations during imagery of sexual and emotional infidelity
Hidehiko Takahashi,a,b Masato Matsuura,c Noriaki Yahata,d Michihiko Koeda,e Tetsuya Suhara,a and Yoshiro Okubof,
a

Department of Molecular Neuroimaging, National Institute of Radiological Sciences, Japan Asai Hospital, Japan c Department of Life Sciences and Bio-informatics, Graduate School of Health Sciences, Tokyo Medical and Dental University, Japan d Department of Pharmacology, Nippon Medical School, Japan e Department of Bio-informatics, Medical Research Institute, Tokyo Medical and Dental University, Japan f Department of Neuropsychiatry, Nippon Medical School, 1-1-5, Sendagi, Bunkyo-ku, Tokyo, 113-8603, Japan
b

Received 26 January 2006; revised 22 April 2006; accepted 17 May 2006 Available online 7 July 2006 Jealousy-related behaviors such as intimate partner violence and morbid jealousy are more common in males. Principal questionnaire studies suggest that men and women have different modules to process cues of sexual and emotional infidelity. We aimed to elucidate the neural response to sentences depicting sexual and emotional infidelity in men and women using functional magnetic resonance imaging. Although there was no sex difference in the self-rating score of jealousy for sexual and emotional infidelity, men and women showed different brain activation patterns in response to the two types of infidelity. During jealous conditions, men demonstrated greater activation than women in the brain regions involved in sexual/aggressive behaviors such as the amygdala and hypothalamus. In contrast, women demonstrated greater activation in the posterior superior temporal sulcus. Our fMRI results are in favor of the notion that men and women have different neuropsychological modules to process sexual and emotional infidelity. Our findings might contribute to a better understanding of the neural basis of the jealousy-related behaviors predominantly observed in males. 2006 Elsevier Inc. All rights reserved.

Introduction There have been numerous neuroimaging studies on primary emotions (fear, disgust, happiness and sadness) that have led to a better understanding of the neuroanatomical correlates of emotions (Phan et al., 2002). In recent years, some efforts have been made to elucidate the neural basis of complex social emotions such as guilt, shame, embarrassment, and empathy (Berthoz et al., 2002; Shin et al., 2000; Singer et al., 2004; Takahashi et al., 2004). Still, neuroimaging studies investigating complex emotions are limited,
Corresponding author. Fax: +81 3 5814 6280. E-mail address: okubo-y@nms.ac.jp (Y. Okubo). Available online on ScienceDirect (www.sciencedirect.com). 1053-8119/$ - see front matter 2006 Elsevier Inc. All rights reserved. doi:10.1016/j.neuroimage.2006.05.049

and there has been no human study that investigated neural correlates associated with jealousy. Jealousy is a common human reaction generated by a threat to the loss of a valued relationship with another person due to a rival. Jealousy, however, becomes maladaptive when it causes distress in the jealous person or the target person and could be associated with some behavioral problems observed not only in a psychiatric setting but also in a general social environment (Kingham and Gordon, 2004). One of the most common forms of violence against women is that perpetrated by a husband or an intimate male partner (Wathen and MacMillan, 2003; Watts and Zimmerman, 2002). Intimate partner violence, often termed domestic violence, occurs in all countries, irrespective of social, economic, religious, or cultural group (World Health Organization, 2002). There are multiple risk factors for intimate partner violence, such as poverty, alcohol consumption, status of women, etc., and one of them is also partner's jealousy (Jewkes, 2002; Kingham and Gordon, 2004). Morbid jealousy is a condition of inappropriate or excessive jealousy together with unacceptable or extreme behavior based on a preoccupation with partner's unfaithfulness. It is more common in males (Kingham and Gordon, 2004). Study of the neural correlates associated with jealousy and their sex difference might contribute to a better understanding of the neural basis of the jealousy-related behaviors predominantly observed in males. A positron emission tomography (PET) study has investigated the neural correlates of sexual jealousy in male monkeys. In the study, dominant male monkeys were injected with [18F]fluorodeoxyglucose and scanned while visually confronted with an interaction between their female mate and a subordinate male. During the jealousy condition, the male monkey showed increased activation in the brain regions that have been implicated in negative emotions and social cognition such as the amygdala, insula, and superior temporal sulcus (STS) (Rilling et al., 2004).

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Some questionnaire studies have reported the sex differences in the nature of jealousy in different countries. Men tend to be more upset over partner's sexual unfaithfulness than women, and women tend to be more upset over partner's emotional unfaithfulness than men (Buller, 2005; Buss and Haselton, 2005). Based on this principal evidence, Buss et al. (1992) proposed an evolutionary hypothesis, namely that, over evolution, men and women have developed different modules to process the cue that triggers jealousy. In humans, fertilization occurs internally within women, and men could be uncertain of their paternity. If a man's mate is impregnated by another man, ancestral man might loose a chance to reproduce and run the risk of expending resources on another man's offspring. They argued that men are innately predisposed to having intense jealousy in response to cues of sexual infidelity. In contrast, women are always certain that they are the mothers of their offspring, but ancestral women are more concerned about emotional infidelity, because diversion of male's emotional commitment to another female and her children could entail the loss of parental resources and protection (Buss et al., 1992). Since jealousy is a complex emotion and is accompanied by different negative emotions (Parrott and Smith, 1993), it is not feasible to evaluate a pure form of jealousy and its neural correlates. We aimed to elucidate neural responses to sentences depicting sexual infidelity and emotional infidelity carrying jealousy content in men and women and their sex differences using functional magnetic resonance imaging (fMRI). We hypothesized that men and women would show distinct brain activations in response to sexual and emotional infidelity, specifically in the amygdala, insula, and STS, where the monkey study reported increased activity during jealousy condition. Methods Participants Eleven healthy heterosexual male university students (mean age 20.1 years, SD = 0.8) and 11 female students (mean age 21.4 years, SD = 1.5) including 3 couples (3 male and 3 female students) participated in this study. All subjects were Japanese and right-handed. Each student had not been married, and had been in an intimate relationship with a specific boyfriend/girlfriend. The average length of the intimate relationship was 14.8 months (SD = 10.6) for the males and 18.5 months (SD = 10.9) for the females. The students were free of any criteria for neuropsychiatric disorders based on unstructured psychiatric screening interviews. None of the participants were taking alcohol at the time, nor did they have a history of psychiatric disorder, significant physical illness, head injury, neurological disorder, or alcohol, or drug dependence. All participants underwent an MRI to rule out cerebral anatomic abnormalities. After complete explanation of the study, written informed consent was obtained from all participants, and the study was approved by the ethics committee of Asai Hospital. Materials Three types of short sentences were provided (neutral, sexual infidelity, and emotional infidelity). We defined sexual infidelity as a condition explicitly or implicitly indicating a sexual rela-

tionship or deep physical contact, and emotional infidelity as a condition indicating diversion of partner's emotional commitment to another boyfriend/girlfriend. Each sentence was written in Japanese and started with My girlfriend for male students and My boyfriend for female students. Sentences of sexual infidelity and emotional infidelity were expected to carry jealousy content and neutral sentences were expected to carry no prominent emotional content. In order to validate our expected results, we conducted an initial survey. We prepared 3035 sentences for each of 3 conditions (neutral, sexual infidelity, and emotional infidelity). Other healthy university students (22 males and 22 females, mean age 22.6 years, SD = 2.2 and 22.4 years SD = 1.9, respectively) than the subjects participating in this fMRI study were screened. They read each sentence and rated the intensity of jealousy they felt for each sentence using a 6-point analog scale (1 = none, 6 = extremely intense). Based on the initial survey, we selected 18 sentences for each of 3 conditions. The average of males and females for the mean ratings of jealousy for 18 neutral sentences was, respectively, 1.2 (SD = 0.3) and 1.2 (SD = 0.3), for 18 sentences of sexual infidelity 4.6 (SD = 1.4) and 4.6 (SD = 1.4), and for 18 sentences of emotional infidelity 4.3 (SD = 1.3) and 4.5 (SD = 1.2). Examples of the sentences are shown in Table 1. The sentences were projected via a computer and a telephoto lens onto a screen mounted on a head-coil. The subjects were instructed to read the sentences silently and were told to imagine the situations described in the sentences. After reading each sentence, the subjects were instructed to press a selection button with the right index finger, indicating that they had read and understood it. The experimental design consisted of 6 blocks for each of the 3 conditions (neutral, sexual infidelity and emotional infidelity) interleaved with 20-s rest periods. During the rest condition, participants viewed a crosshair pattern projected to the center of the screen. In each 24-s block, 3 different sentences of the same emotional class were presented for 8 s each. The order of presentation for the three conditions was randomized (Fig. 1). After the scan, the subjects read the sentences in the same order as presented during the scan, and they were asked to rate the sentences according to how they would feel if the scenario protagonist was their boyfriend/girlfriend. Since jealousy is a complex emotion and is accompanied by different negative emotions, the participants rated the intensity of jealousy and other basic emotions (anger, sadness, surprise, fear, disgust, and happiness) for each sentence using a 6-point analog scale. Image acquisition The images were acquired with a 1.5 T Signa system (General Electric, Milwaukee, WI). Functional images of 203 volumes were acquired with T2*-weighted gradient echo planar imaging sequences sensitive to the blood oxygenation level dependent (BOLD) contrast. Each volume consisted of 40 transaxial contiguous slices with a slice thickness of 3 mm to cover almost the whole brain (flip angle, 90; TE, 50 ms; TR, 4000 ms; matrix, 64 64; field of view, 24 24 cm). High-resolution, T1-weighted anatomic images were acquired for anatomic comparison (124 contiguous axial slices, 3D Spoiled-Grass sequence, slice thickness 1.5 mm, TE, 9 ms; TR, 22 ms; flip angle, 30; matrix, 256 192; field of view, 25 25 cm).

H. Takahashi et al. / NeuroImage 32 (2006) 12991307 Table 1 Examples of sentences Neutral My girlfriend stayed in a twin-bed room in a hotel with her female friend. My girlfriend wrote a new year's card to her female friend. My girlfriend spent a night in her female friend's room. My girlfriend meets her best female friend frequently. My girlfriend had her coat taken off by her female friend. My girlfriend telephones her parents on weekend. My girlfriend e-mailed to her mother yesterday. My girlfriend made a trip with her female friend. My girlfriend stayed in a double-bed room in a hotel with her ex-boyfriend. My girlfriend took a bath with another man. My girlfriend had her underwear taken off by another man. My girlfriend spent a night in her ex-boyfriend's room. My girlfriend kissed another man deeply. My girlfriend passionately embraced another man. My girlfriend took an overnight trip with another man. My girlfriend was naked with her ex-boyfriend in his bed. My girlfriend wrote a love letter to another man. My girlfriend had dinner with another man on my birthday. My girlfriend supplied another man with all the money she had saved. My girlfriend telephones her ex-boyfriend everyday. My girlfriend always talks with delight about her ex-boyfriend in front of me. My girlfriend e-mails to her ex-boyfriend every night. My girlfriend gave gorgeous birthday present to her ex-boyfriend. My girlfriend meets another man more frequently than me.

1301

Sexual infidelity

Emotional infidelity

Analysis of functional imaging data Data analysis was performed with statistical parametric mapping software package (SPM02) (Wellcome Department of

Cognitive Neurology, London, UK) running with MATLAB (Mathworks, Natick, MA). All volumes were realigned to the first volume of each session to correct for subject motion and were spatially normalized to the standard space defined by the Montreal Neurological Institute (MNI) template. After normalization, all scans had a resolution of 2 2 2 mm3. Functional images were spatially smoothed with a 3D isotropic Gaussian kernel (full width at half maximum of 8 mm). Low frequency noise was removed by applying a high-pass filter (cutoff period = 192 sec) to the fMRI time series at each voxel. A temporal smoothing function was applied to the fMRI time series to enhance the temporal signal-tonoise ratio. Significant hemodynamic changes for each condition were examined using the general linear model with boxcar functions convoluted with a hemodynamic response function. Statistical parametric maps for each contrast of t statistic were calculated on a voxel-by-voxel basis. The t values were then transformed to unit normal distribution, resulting in Z scores. To assess the specific condition effect, we used the contrasts of sexual infidelity minus neutral (SI-N) and emotional infidelity minus neutral (EI-N). A random effects model, which estimates the error variance for each condition across the subjects, was implemented for group analysis. This procedure provides a better generalization for the population from which data are obtained. The contrast images were obtained from single-subject analysis and were entered into the group analysis. A one-sample t test was applied to determine group activation for each effect. Significant activations were recognized at a height threshold of P < 0.0005, uncorrected (t > 4.59) and extent threshold of 3 contiguous voxels. We conducted regression analyses to demonstrate a more direct link between regional brain activities with subjective judgments of jealousy. Using the mean of ratings of jealousy for each subject as the covariate, regression analyses with the contrast (SI-N and EI-N) and the covariate were done at the second level (height threshold at P < 0.001, uncorrected, and extent threshold of 3 voxels) in male and female groups. The masks of SI-N and EI-N contrasts from one-sample t test (P < 0.005) were applied to confine the regions where significant activations were observed. Using the effect sizes, representing the percent signal change, in the insula and pSTS of the EI-N contrast at the peak coordinates uncovered by regression analyses, correlation coefficients between the degree of activation and rating of jealousy for emotional infidelity were calculated. To determine whether the correlation coefficients of men and women were significantly different, each correlation coefficient was converted into a Z score using Fisher's r-to-Z transformation, and the difference between Z scores of men and women was evaluated (Cohen and Cohen, 1983). We plotted the fMRI signal and ratings of jealousy for both gender groups. We tested for sex differences in the pattern of brain activation by subtracting the SI-N and EI-N contrasts of the females from the SI-N and EI-N contrasts of the males, respectively, and vice versa. Analysis of sex differences was

Fig. 1. Block design paradigm in the fMRI study. R = rest, N = neutral, SI = sexual infidelity, EI = emotional infidelity.

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H. Takahashi et al. / NeuroImage 32 (2006) 12991307 Table 3 Brain activations in sexual infidelity condition and emotional infidelity condition relative to neutral condition Brain region L/R Coordinates x Men SI-N Visual cortex Middle temporal gyrus Hippocampal regions Amygdala Claustrum Hypothalamus EI-N Visual cortex Frontal regions (med. FG, mid. FG, PCG) Cingulate cortex Insula Hippocampal regions Thalamus Caudate Hypothalamus Cerebellum Women SI-N Visual cortex Frontal regions (mid. FG) Thalamus Cerebellum EI-N Visual cortex Frontal regions (med. FG, mid. FG) pSTS (angular gyrus) Thalamus Globus pallidus Cerebellum y z Z score

performed with a two-sample t test. To exclude possible sex differences in brain activation during neutral conditions, we created masks of sex differences of the neutral minus rest contrast (threshold at P < 0.05, uncorrected). These masks were applied exclusively to the SI-N and EI-N contrasts in the sex differences analysis. Sex differences were recognized at a height threshold of P < 0.0005, uncorrected (t > 4.59) and extent threshold of 3 contiguous voxels. Results Self-rating As we predicted, neutral sentences elicited no prominent emotions in either male or female students. Group averages for mean ratings of jealousy, anger, sadness, surprise, disgust, fear, anxiety, and happiness for neutral sentences were within the range of 1.01.4 for both the male and female groups. Group averages for mean ratings of each emotion for sentences of sexual infidelity and for sentences of emotional infidelity are shown in Table 2. There were no sex differences in the ratings of jealousy, anger, sadness, surprise, and happiness for the two types of infidelity (t test, twotailed, P > 0.1 in each emotion). A t test revealed that men rated higher anxiety (t test, two-tailed, P = 0.04) and marginally higher fear (t test, two-tailed, P = 0.06) for sexual infidelity than women, and rated marginally higher disgust (t test, two-tailed, P = 0.08) for emotional infidelity than women. fMRI result In the male group, the SI-N condition produced activations in the visual cortex, middle temporal gyrus, amygdala, hippocampal regions, claustrum, and hypothalamus (Table 3 and Fig. 2a). The EI-N condition produced activations in the visual cortex, frontal regions (medial frontal gyrus, middle frontal gyrus, precentral gyrus), cingulate cortex, insula, hippocampal regions, thalamus, caudate, hypothalamus, and cerebellum (Table 3 and Fig. 2b). In the female group, the SI-N condition produced

L L L/R R L

4 44 28 22 30 0 8 40 18 42 32 4 12 8 10

76 78 22 2 12 14 90 8 10 4 28 26 2 14 64

2 10 18 14 8 10 10 48 38 12 4 6 18 12 30

4.1 4.25 4.6 3.75 3.86 3.68 4.37 4.59 3.56 4.65 3.98 4 3.35 3.51 3.67

L/R L/R L/R L/R L/R L R

R L L

28 44 8 6 16 48 44 6 12 16

92 6 2 38 92 4 66 30 2 82

16 50 0 6 14 50 34 0 2 22

3.69 3.56 4.04 3.85 4.2 4.29 4.25 4.73 3.56 5.46

L/R L L L/R L

Coordinates and Z score refer to the peak of each brain region. L = left; R = right; med. FG = medial frontal gyrus; mid. FG = middle frontal gyrus; PCG = precentral gyrus; pSTS = posterior superior temporal sulcus.

Table 2 The results of self-ratings of emotions accompanied by sexual and emotional infidelity Sexual infidelity Men Jealousy Anger Sadness Surprise Disgust Fear Anxiety Happiness 5.7 (0.4) P = 0.37 5.8 (0.3) P = 0.28 5.1 (1.5) P = 0.33 5.5 (1.1) P = 0.60 5.6 (1.1) P = 0.86 5.0 (1.7) P = 0.06 5.9 (0.1) P = 0.04 1.0 (0.0) Women 5.5 (0.8) 5.6 (0.5) 5.6 (0.7) 5.7 (0.4) 5.5 (0.6) 3.3 (2.2) 5.7 (0.4) 1.0 (0.0) Emotional infidelity Men 5.1 (0.5) P = 0.58 4.9 (0.5) P = 0.18 4.8 (1.1) P = 0.80 4.0 (1.3) P = 0.60 4.7 (1.0) P = 0.08 3.9 (1.9) P = 0.20 5.3 (1.0) P = 0.66 1.0 (0.0) Women 4.9 (0.8) 4.5 (0.8) 4.7 (0.8) 4.2 (0.9) 4.0 (0.9) 2.8 (2.1) 5.1 (1.0) 1.0 (0.0)

activations in the visual cortex, frontal regions (middle frontal gyrus), thalamus, and cerebellum (Table 3 and Fig. 2c). The EIN condition produced activations in the visual cortex, frontal regions (medial frontal gyrus, middle frontal gyrus), posterior STS (pSTS) (angular gyrus), thalamus, and cerebellum (Table 3 and Fig. 2d). In men, regression analysis revealed positive linear correlation between self-rating of jealousy for emotional infidelity and the degree of activation in the insula (x = 38, y = 6, z = 8; Z = 3.54) in EI-N contrast was observed (Figs. 3a and 4). In women, there were correlations between self-rating of jealousy for emotional infidelity and the degree of activation in the posterior STS (x = 46, y = 66, z = 34; Z = 3.69) and midbrain (x = 0, y = 24, z = 12; Z = 3.96) in EI-N contrast (Figs. 3b and 4). Since the ratings of jealousy for sexual infidelity were skewed to the ceiling for both genders, we did not use the results of regression analysis of the SI-N contrast. For men and women, correlation coefficients between the rating of jealousy and the degree of activation in the insula (x = 38, y = 6, z = 8) during EI-N condition were r = 0.88 (P < 0.001) and

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Fig. 2. Images showing brain activations in response to SI-N condition (a) and EI-N condition (b) in men, and SI-N condition (c) and EI-N condition (d) in women. (a) Significant activations in the amygdala, hypothalamus, and hippocampus are shown. (b) Significant activations in the insula, caudate, frontal regions, hypothalamus, and thalamus are shown. (c) Significant activation in the thalamus is shown. (d) Significant activations in the thalamus and posterior STS are shown. The bar shows the range of the t value. Within the images, L indicates left and R indicates right. Numbers in the bottom row indicate the coordinates of the Montreal Neurological Institute brain.

r = 0.03 (P = 0.94), and in the pSTS (x = 46, y = 66, z = 34) during EI-N condition were r = 0.07 (P = 0.83) and r = 0.88 (P < 0.001), respectively. The correlation coefficients of men and women were significantly different in these regions (P < 0.001). To assess regions commonly activated in both men and women, masks (threshold at P < 0.001, uncorrected) of the SI-N and EI-N contrasts of men were applied inclusively to the SI-N and EI-N contrasts of women, respectively. We observed a commonly activated area surviving a threshold of P < 0.001 uncorrected with an extent threshold of 3 contiguous voxels. Men and women in common recruited the visual cortex (x = 10, y = 64, z = 4; Z = 3.24) in response to the SI-N condition, and the visual cortex (x = 6, y = 86, z = 0; Z = 3.46) and thalamus (x = 4, y = 26, z = 4; Z = 3.85) in response to the EI-N condition. Sex difference analysis revealed that men showed greater activation than women in the amygdala for the SI-N contrast (Table 4 and Fig. 5a). Men showed greater activation than women in the frontal regions (precentral gyrus), insula, hippocampus, hypothalamus, and cerebellum for the EI-N contrast (Table 4 and Fig. 5b). Women demonstrated greater activation than men in the visual cortex and thalamus for the SI-N contrast (Table 4) as well as in the visual cortex, pSTS (angular gyrus), and thalamus for the EI-N contrast (Table 4 and Fig. 5c).

Discussion In this study, we found that men and women showed different brain activation patterns both in sexual infidelity and emotional infidelity conditions. The common regions activated in both sex groups were minimal. Men and women commonly recruited the visual cortex in response to sexual infidelity and the visual cortex and thalamus in response to emotional infidelity. Enhanced visual cortex activations by emotionally salient visual stimuli have been extensively reported (Phan et al., 2002, Takahashi et al., 2004). Emotionally salient stimuli have been suggested as modulating sensory processing in the visual cortex. Early visual cortex receives feedback projection from limbic structures (Emery and Amaral, 2000), and such pathway could act to enhance visual processing (Morris et al., 1998; Vuilleumier et al., 2001). With regard to behavioral data, our male and female students rated identical intensity of jealousy for both types of infidelity. This seems to contradict previous questionnaire studies showing a sex difference in jealousy. However, some factors have been reported to attenuate the sex difference. It was reported that there were no sex differences among men and women who had experienced actual infidelity (Berman and Frazier, 2005; Harris, 2002). The lack of sex difference might be in part attributable to the fact that

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H. Takahashi et al. / NeuroImage 32 (2006) 12991307 Table 4 Sex differences in brain activation during SI-N and EI-N conditions Brain region Menwomen SI-N Amygdala EI-N Frontal regions (PCG) Insula Hippocampus Hypothalamus Cerebellum Womenmen SI-N Visual cortex Thalamus EI-N Visual cortex pSTS (angular gyrus) Thalamus L/R Coordinates x y z Z score

R L L/R R

22 32 32 34 4 10

2 6 14 18 12 62

14 30 12 4 12 30

3.6 3.45 3.78 3.40 3.84 3.49

Fig. 3. Correlations between the self-ratings of jealousy for emotional infidelity and brain activations. (a) Correlations between self-rating of jealousy and the degree of activation in the insula in EI-N contrast of men. (b) Correlations between self-rating of jealousy and the degree of activation in the posterior STS in EI-N contrast of women.

there were possibly victims of infidelity among the subjects, although we did not ask them whether they had actually experienced infidelity. The explicit and implicit forms of infidelity presumably cause different psychological responses, and the victims of infidelity could be more sensitive, especially to implicit cues that predict sexual or emotional involvement, than those who had never experienced infidelity (Berman and Frazier, 2005). This inconsistency may also stem from the measurement method of behavioral data (Harris, 2003). A body of evidence supporting the sex difference in jealousy comes from self-report studies, in which participants were asked to choose which they would find more upsetting, a sexual infidelity or emotional infidelity. However,

R L R R L/R

30 10 28 52 4

94 4 92 62 28

16 2 14 34 2

4.39 3.99 3.61 3.49 3.85

Coordinates and Z score refer to the peak of each brain region. L = left; R = right; PCG = precentral gyrus; pSTS = posterior superior temporal sulcus.

several studies found no evidence of a sex-by-type of infidelity interaction, and both men and women rated higher jealousy for sexual infidelity than emotional infidelity when participants used

Fig. 4. Plots and regression lines of correlations between mean of rating of jealousy (1 = none, 6 = extremely intense) and the degree of activation in the brain regions. indicates male and indicates female. In men, there were correlations between mean of rating of jealousy for emotional infidelity and the degree of activation in the insula during EI-N condition (r = 0.88, P < 0.001). In women, there were positive correlations between mean of rating of jealousy for emotional infidelity and the degree of activation in the pSTS during EI-N condition (r = 0.88, P < 0.001).

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Fig. 5. Images showing sex differences in brain activations in response to SI-N and EI-N conditions. (a) Compared to women, greater activation in the amygdala in men was shown for SI-N contrast. (b) Compared to women, greater activations in the insula and hypothalamus in men were shown for EI-N contrast. (c) Compared to men, greater activation in the posterior STS in women was shown for EI-N contrast.

continuous rating scales as we did to estimate their jealousy over the two forms of infidelity (Harris, 2003). During the SI-N condition, males showed activation in the regions implicated in appraisal of sexual salience and reproductive behavior, such as the amygdala and hypothalamus (Sisk and Foster, 2004). During the EI-N condition, males did not demonstrate activation in the amygdala, but they did show activation in the insula along with the hippocampus and hypothalamus. Sex difference analysis revealed that males showed greater activation than females in the amygdala in response to sexual infidelity and greater activation in the insula, hippocampus, and hypothalamus in response to emotional infidelity. The amygdala and insula are the central nodes of processing basic negative emotions, fear and disgust, respectively (Calder et al., 2001; Craig, 2003; Phan et al., 2002; Wicker et al., 2003). Since males showed trends to rate higher fear for sexual infidelity and higher disgust for emotional infidelity than females, it is possible that sex differences of the fMRI results reflect the sex differences in the other basic emotions that characterize jealousy. However, we could not find any correlation between the self-ratings of fear and disgust and brain activations in these regions, and the ratings of jealousy were correlated with activation in the insula at least in the EI-N condition, perhaps implying some aspects of sex differences in the neural basis of jealousy-related behaviors. Previous fMRI studies reported that the amygdala and hypothalamus were more strongly activated in men than in women in response to sexually arousing stimuli (Karama et al., 2002; Hamann et al., 2004). Since emotional unfaithfulness could be accompanied by sexual unfaithfulness, activation in the hypothalamus in response to emotional infidelity might in part reflect a sexually arousing feature of emotional infidelity. Thus, greater hypothalamic activations elicited by emotional infidelity as well as greater amygdala activation elicited by sexual infidelity might

result from sexually arousing features of the sexual and emotional infidelity scenario. Lack of sex difference in hypothalamic activation during sexual infidelity might stem from subthreshold hypothalamic activation in women. In a monkey PET study, where it is not feasible to distinguish the type of infidelity, male monkeys showed increased activation in the amygdala, insula, and STS while viewing interaction between their female mate and another male monkey (Rilling et al., 2004). Furthermore, male monkeys showed increases in plasma testosterone during a situation provoking sexual jealousy (Rilling et al., 2004). Testosterone receptors in the brain exist mainly in the amygdala and hypothalamic regions that are involved in sexual/ aggressive behaviors (Fernandez-Guasti et al., 2000; Giammanco et al., 2005; Newman, 1999; Sisk and Foster, 2004). Testosterone increases vasopressin levels in the amygdala and hypothalamic regions, and vasopressin mediates partner-preference and pair bonding, especially in males (Young and Wang, 2004). In the monkey, vasopressinergic receptors were found in the amygdala and hypothalamus (Young et al., 1999), and vasopressin increases excitability of the amygdala (Huber et al., 2005). This means that hormonal transmissions might be responsible for increased activation in the amygdala and hypothalamus. Females showed activation in the cortical regions and thalamus during both infidelity conditions. In addition to these regions, females demonstrated activation in the pSTS during the emotional infidelity condition. The pSTS has been implicated in detection of intention, deception, trustworthiness of others (Calarge et al., 2003; Castelli et al., 2000; Winston et al., 2002), and violation of social norms (Greene et al., 2001; Heekeren et al., 2003; Moll et al., 2005; Takahashi et al., 2004). Sex difference analysis revealed that females showed greater activation than males in the pSTS for emotional infidelity. Regression analysis showed that the activation in the pSTS in the EI-N condition was correlated with the self-

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rating of jealousy. The ability to detect violations in social norms helps one to avoid or withdraw from relationships in which one is at risk of being cheated (DePrince, 2005). Considering the pSTS function, the greater activation elicited by emotional infidelity in females suggests that they are more sensitive to change of partner's mind. According to Buss's evolutionary hypothesis (1992), men and women have developed different modules to process the cue that triggers jealousy over evolution, that is, men are innately predisposed to have intense jealousy in response to cues of sexual infidelity, whereas women are more concerned about emotional infidelity (Buss et al., 1992). Since our self-rating results did not find sex difference in the rating of jealousy for the two types of infidelity, our data failed to fully support the Buss hypothesis. Nevertheless, sex differences in fMRI results at least support their view that men and women have different neuropsychological modules to process sexual and emotional infidelity. This study has some limitations. First, sexual infidelity might be accompanied by emotional infidelity and vice versa. For this reason, we carefully chose the situations, although we understand that it is not feasible to entirely dissociate sexual and emotional infidelity. This possible co-existence might account for the identical results of self-rating of jealousy in males and females. However, the overall higher ratings of different emotions including jealousy for sexual infidelity than emotional infidelity, which is consistent with previous questionnaire studies using a rating scale (Harris, 2003), and different distribution patterns of the self-ratings of jealousy for sexual and emotional infidelity tell us that our materials of sexual and emotional infidelity carried different aspects of infidelity. Second, females did not rate any emotions significantly higher than men for the two types of infidelity, although females showed greater activation in the fMRI results. This is linked to the general limitations of emotion studies, that fMRI results reveal something more that we could not learn by simple self-rating of emotions. These differences obtained in fMRI results might be manifested as real-life behaviors that we could not measure by simple rating methods. Third, we did not record behavioral data during scans. We aimed to measure automatic or implicit emotional processing, and cognitive demands such as explicit and elaborate evaluation of stimuli are known to attenuate automatic activation in subcortical areas such as the amygdala (Phan et al., 2002). Therefore, we acknowledge that this could be a general limitation of these kinds of emotional studies, but at the same time, this procedure could be advantageous for examining robust automatic emotional processing. Moreover, although we wanted the subjects to rate multiple emotions other than jealousy, it was not feasible to rate multiple emotions at one time during the scan. For these reasons, we delayed ratings until after the scan period. Finally, magnetic field inhomogeneities in the medial temporal regions, especially in close to airtissue interfaces, result in reduced signal-to-noise ratio of fMRI. Since sexual dimorphism of structural brain anatomy was reported in the medial temporal regions and hypothalamus (Giedd et al., 1997; Goldstein et al., 2001; Gur et al., 2002), sex differences in fMRI could be partly attributable to possible sexual dimorphism of cranial or brain structure in and around these regions. N.Y. and Y.O., blinded to the gender of the images, carefully inspected the quality of signal data in the medial temporal regions. They agreed that all individuals' data had good signal quality in the foci where the sex difference was observed.

In conclusion, we investigated the brain activations in response to sexual and emotional infidelity and demonstrated their sex differences. During jealousy situations, males demonstrated greater activation than females in several brain regions that are linked to sexual and aggressive behaviors. In contrast, females showed greater activation than males in the regions that are implicated in the detection of others' intention or violation of social norms. Since jealousy-related behaviors such as intimate partner violence in the general population and morbid jealousy in psychiatric settings are more common in males, we expect that our findings of sex differences in brain activation associated with sexual and emotional infidelity will contribute to broaden the knowledge concerning these behaviors. Acknowledgments The staff of the Section of Life Sciences and Bio-informatics, Graduate School of Medicine, Tokyo Medical and Dental University, is gratefully acknowledged. This study was supported by a consignment expense for the Molecular Imaging Program on Research Base for PET Diagnosis from the Ministry of Education, Culture, Sports, Science and Technology (MEXT), Japanese Government, a Grant-in-Aid for Scientific Research from the (MEXT) (15390438), a research grant for nervous and mental disorders (14B-3), and a Health and Labor Sciences Research Grant for Research on Psychiatric and Neurological Diseases and Mental Health (H15-KOKORO-003) from the Japanese Ministry of Health, Labor, and Welfare. References
Berman, M.I., Frazier, P.A., 2005. Relationship power and betrayal experience as predictors of reactions to infidelity. Pers. Soc. Psychol. Bull. 31, 16171627. Berthoz, S., Armony, J.L., Blair, R.J., Dolan, R.J., 2002. An fMRI study of intentional and unintentional (embarrassing) violations of social norms. Brain 125, 16961708. Buller, D.J., 2005. Evolutionary psychology: the emperor's new paradigm. Trends Cogn. Sci. 9, 277283. Buss, D.M., Haselton, M., 2005. The evolution of jealousy. Trends Cogn. Sci. 9, 506507. Buss, D.M., Larsen, R.J., Westen, D., Semmelroth, J., 1992. Sex differences in jealousy: evolution, physiology, and psychology. Psychol. Sci. 3, 251255. Calarge, C., Andreasen, N.C., O'Leary, D.S., 2003. Visualizing how one brain understands another: a PET study of theory of mind. Am. J. Psychiatry 160, 19541964. Calder, A.J., Lawrence, A.D., Young, A.W., 2001. Neuropsychology of fear and loathing. Nat. Rev., Neurosci. 2, 352363. Castelli, F., Happe, F., Frith, U., Frith, C., 2000. Movement and mind: a functional imaging study of perception and interpretation of complex intentional movement patterns. NeuroImage 12, 314325. Cohen, J., Cohen, P., 1983. Applied Multiple Regression/Correlation Analysis for the Behavioral Sciences, 2nd ed. Lawrence Erlbaum, Hillsdale, NJ. Craig, A.D., 2003. Interoception: the sense of the physiological condition of the body. Curr. Opin. Neurobiol. 13, 500505. DePrince, A.P., 2005. Social cognition and revictimization risk. J. Trauma Dissociation 6, 125141. Emery, N.J., Amaral, D.G., 2000. The role of the amygdala in primate social cognition. In: Lane, R.D., Nadel, L. (Eds.), Cognitive Neuroscience of Emotion. Oxford Univ. Press, New York, pp. 156191. Fernandez-Guasti, A., Kruijver, F.P., Fodor, M., Swaab, D.F., 2000. Sex

H. Takahashi et al. / NeuroImage 32 (2006) 12991307 differences in the distribution of androgen receptors in the human hypothalamus. J. Comp. Neurol. 425, 422435. Giammanco, M., Tabacchi, G., Giammanco, S., Di Majo, D., La Guardia, M., 2005. Testosterone and aggressiveness. Med. Sci. Monit. 11, RA136RA145. Giedd, J.N., Castellanos, F.X., Rajapakse, J.C., Vaituzis, A.C., Rapoport, J.L., 1997. Sexual dimorphism of the developing human brain. Prog. Neuro-Psychopharmacol. Biol. Psychiatry 21, 11851201. Goldstein, J.M., Seidman, L.J., Horton, N.J., Makris, N., Kennedy, D.N., Caviness Jr., V.S., Faraone, S.V., Tsuang, M.T., 2001. Normal sexual dimorphism of the adult human brain assessed by in vivo magnetic resonance imaging. Cereb. Cortex 11, 490497. Greene, J.D., Sommerville, R.B., Nystrom, L.E., Darley, J.M., Cohen, J.D., 2001. An fMRI investigation of emotional engagement in moral judgment. Science 293, 21052108. Gur, R.C., Gunning-Dixon, F., Bilker, W.B., Gur, R.E., 2002. Sex differences in temporo-limbic and frontal brain volumes of healthy adults. Cereb. Cortex 12, 9981003. Hamann, S., Herman, R.A., Nolan, C.L., Wallen, K., 2004. Men and women differ in amygdala response to visual sexual stimuli. Nat. Neurosci. 7, 411416. Harris, C.R., 2002. Sexual and romantic jealousy in heterosexual and homosexual adults. Psychol. Sci. 13, 712. Harris, C.R., 2003. A review of sex differences in sexual jealousy, including self-report data, psychophysiological responses, interpersonal violence, and morbid jealousy. Pers. Soc. Psychol. Rev. 7, 102128. Heekeren, H.R., Wartenburger, I., Schmidt, H., Schwintowski, H.P., Villringer, A., 2003. An fMRI study of simple ethical decision-making. NeuroReport 14, 12151219. Huber, D., Veinante, P., Stoop, R., 2005. Vasopressin and oxytocin excite distinct neuronal populations in the central amygdala. Science 308, 245248. Jewkes, R., 2002. Intimate partner violence: causes and prevention. Lancet 359, 14231429. Karama, S., Lecours, A.R., Leroux, J.M., Bourgouin, P., Beaudoin, G., Joubert, S., Beauregard, M., 2002. Areas of brain activation in males and females during viewing of erotic film excerpts. Hum. Brain Mapp. 16, 113. Kingham, M., Gordon, H., 2004. Aspects of morbid jealousy. Advan. Psychiatr. Treat. 10, 207215. Moll, J., Zahn, R., de Oliveira-Souza, R., Krueger, F., Grafman, J., 2005. Opinion: the neural basis of human moral cognition. Nat. Rev., Neurosci. 6, 799809. Morris, J.S., Friston, K.J., Buchel, C., Frith, C.D., Young, A.W., Calder, A.J., Dolan, R.J., 1998. A neuromodulatory role for the human

1307

amygdala in processing emotional facial expressions. Brain 121, 4757. Newman, S.W., 1999. The medial extended amygdala in male reproductive behavior. A node in the mammalian social behavior network. Ann. N. Y. Acad. Sci. 877, 242257. Parrott, W.G., Smith, R.H., 1993. Distinguishing the experiences of envy and jealousy. J. Pers. Soc. Psychol. 64, 906920. Phan, K.L., Wager, T., Taylor, S.F., Liberzon, I., 2002. Functional neuroanatomy of emotion: a meta-analysis of emotion activation studies in PET and fMRI. NeuroImage 16, 331348. Rilling, J.K., Winslow, J.T., Kilts, C.D., 2004. The neural correlates of mate competition in dominant male rhesus macaques. Biol. Psychiatry 56, 364375. Shin, L.M., Dougherty, D.D., Orr, S.P., Pitman, R.K., Lasko, M., Macklin, M.L., Alpert, N.M., Fischman, A.J., Rauch, S.L., 2000. Activation of anterior paralimbic structures during guilt-related script-driven imagery. Biol. Psychiatry 48, 4350. Singer, T., Seymour, B., O'Doherty, J., Kaube, H., Dolan, R.J., Frith, C.D., 2004. Empathy for pain involves the affective but not sensory components of pain. Science 303, 11571162. Sisk, C.L., Foster, D.L., 2004. The neural basis of puberty and adolescence. Nat. Neurosci. 7, 10401047. Takahashi, H., Yahata, N., Koeda, M., Matsuda, T., Asai, K., Okubo, Y., 2004. Brain activation associated with evaluative processes of guilt and embarrassment: an fMRI study. NeuroImage 23, 967974. Vuilleumier, P., Armony, J.L., Driver, J., Dolan, R.J., 2001. Effects of attention and emotion on face processing in the human brain: an eventrelated fMRI study. Neuron 30, 829841. Wathen, C.N., MacMillan, H.L., 2003. Interventions for violence against women: scientific review. JAMA 289, 589600. Watts, C., Zimmerman, C., 2002. Violence against women: global scope and magnitude. Lancet 359, 12321237. Wicker, B., Keysers, C., Plailly, J., Royet, J.P., Gallese, V., Rizzolatti, G., 2003. Both of us disgusted in My insula: the common neural basis of seeing and feeling disgust. Neuron 40, 655664. Winston, J.S., Strange, B.A., O'Doherty, J., Dolan, R.J., 2002. Automatic and intentional brain responses during evaluation of trustworthiness of faces. Nat. Neurosci. 5, 277283. World Health Organization, 2002. World Report on Violence and Health. World Health Organization, Geneva. Young, L.J., Wang, Z., 2004. The neurobiology of pair bonding. Nat. Neurosci. 7, 10481054. Young, L.J., Toloczko, D., Insel, T.R., 1999. Localization of vasopressin (V1a) receptor binding and mRNA in the rhesus monkey brain. J. Neuroendocrinol. 11, 291297.