1. Increased Activation in Response to Male Faces in Areas Related to Reward During the Follicular Phase including the Orbitofrontal Cortex, Anterior Cingulate, Amygdala, and Hippocampus. Follicular (Faces-Fixation) - Luteal (Faces-Fixation) OFC ACC HIP ACC AMY -12,34,-7 -23,-9,-7 INTRODUCTION Women’s mate choice is believed to involve a complex process balancing the potential reward of a high quality masculine mate against the risks of low paternal care or sexually transmitted infection. Women’s preferences for men vary over the menstrual cycle in ways that may relate to this hypothesized conflict in reproductive priorities. The mechanisms by which hormones modulate females’ preferences for male traits are unknown. Recent fMRI studies show that women process monetary risk and reward as a function of their menstrual cycle phase (Dreher et al., 2007). Specifically, women demonstrate increased activation in brain areas related to reward and risk taking during the follicular versus luteal phase. It is unknown whether the reported cycle effects in response to monetary risk and reward may generalize to sexual reward and risk taking in women. In the current study, we investigated whether hormones might act centrally to mediate women’s risk and reward assessments of men as potential sexual partners. We predicted that women’s neural activation patterns in response to men would differ across the menstrual cycle and be related to men’s sexual risk. METHODS Subjects Eight self-identified heterosexual women between 23 and 28 years of age (mean±SD=26±1.85 years). Women were not currently in a committed relationship. None of the participants used hormonal contraceptives or any medications. Data Collection Participants attended two test sessions. In a counterbalanced order, women were tested during the follicular (cycle days 10-12) and luteal (21-23) phases of their menstrual cycle. While in the fMRI scanner (3 Tesla, Siemens), participants viewed photographs of male faces and houses (control stimuli). Male face stimuli were of 4 conditions that varied with masculinity and risk (Figure 1). Faces were masculinized (30%) and feminized (30%) using morphing software (Psychomorph, Rowland & Perrett). Risk was based on information provided about the men’s number of previous sexual partners and typical use of condoms (Janssen et al., in prep). While viewing each picture during scanning participants were asked to indicate with a button press how likely they would be to have sex with the man, or to rent the house, depicted (Figure 2). Participants were instructed to make their ratings based on a scenarios in which they were open to a sexual encounter (male faces) and moving (houses). Data Analysis fMRI data underwent motion correction, slice scan-time correction, spatial smoothing, and linear trend removal. They were co-registered to high-resolution structural volume and normalized into Talairach space. Activation to men’s faces and houses was compared across menstrual phases, partner risk, and masculinity using a Bonferroni correction for multiple comparisons (p<.05). DISCUSSION The findings suggest that women’s neural activation in response to men as potential sexual partners depends on phase of the menstrual cycle and sexual risk of the man. Women exhibited more neural activation in response to male faces when tested during the follicular phase in areas related to reward, even in the absence of cycle phase differences in subjective evaluations of women’s likelihood of sex. Women also showed increased activation in reward areas around ovulation in response to houses. This finding is consistent with previous literature (Dreher et al., 2007) using monetary reward and suggests that fluctuations in judgment and reward processing across the menstrual cycle may generalize across stimulus domains. Women’s viewing of high risk men was associated with decreased anterior cingulate and thalamic neural activation. The robust differences in brain activation in response to high and low risk men may be related to sexual decision making in women, especially around ovulation. Women did not respond differently to men based on levels of facial masculinity. This may be because explicit verbal descriptions of the men’s sexual risk may have taken priority over more subtle facial cues. Future studies should include women taking exogenous hormones and women who engage in high risk sexual behavior to see neural activation in those populations of women is different than that observed here. CONCLUSIONS The cyclic differences in central processing of male faces reported here may help to explain previously reported cyclic fluctuations in sexual behavior and partner preferences in women. ACKNOWLEDGEMENTS The authors thank Ryan Stevenson and Sun Ah Kim for assistance with programming and data analysis. we acknowledge the Indiana University Imaging Research facility and staff for the use and operation of the fMRI scanner. This work was supported by the NIH funded Common Themes in Reproductive Diversity training grant NICHHD-T32-HD-49339-0. REFERENCES Dreher, J., Schmidt, P.J., Kohn, P., Furman, D., Rubinow, D., & Berman, K.F. (2007). Menstrual cycle phase modulates reward-related neural function in women. PNAS, 104, 2465-2470. Janssen, E., Hahn, S.K., Rullo, J., & Sheya, A. (2007). In the heat of the moment: Individual differences in the effects of mood and sexual arousal on sexual decision making. Manuscript in preparation. Rowland, D.A, & Perrett, D.I. (1995). IEEE Comp Graphics & App., 15, 70-76. RESULTS MENSTRUAL CYCLE PHASE AND PARTNER RISK MODULATE PATTERNS OF NEURAL ACTIVATION IN WOMEN IN RESPONSE TO PHOTOS OF MALE FACES Heather A. Rupp 1,2, Thomas W. James 3, Ellen D. Ketterson 2, Dale R. Sengelaub 3, Erick Janssen 1,3, & Julia R. Heiman 1,3 1. The Kinsey Institute for Research in Sex, Gender, and Reproduction, Indiana University, Bloomington, IN, 47405 2. Department of Biology, Indiana University, Bloomington, Indiana 47405. 3. Department of Psychological and Brain Sciences, Indiana University, Bloomington, Indiana 47405. Usually 3 Subjects viewed eight runs each consisting of 35 pictures, 28 of male faces, 7 houses (session total 224 faces, 56 houses). Pictures were presented in a rapid event related design (TR=2 seconds) for four seconds with a variable ISI of 2, 4, or 6 seconds (mean 7.1 secs per trial, Figure 3). Figure 2 4 secs 2, 4, 6 secs Figure 3 ACC -9,32,-8-23,-35,3 -1,-8,44 OFC ACC Increased Activation in Response to Houses in Areas Related to Reward During the Follicular Phase including the Orbitofrontal Cortex, Anterior Cingulate, and Hippocampus. Follicular (Houses-Fixation) - Luteal (Houses-Fixation) ACC HIP Activation in Areas Related to Reward During the Follicular Phase Differed for Faces and Houses. Follicular (Faces-Fixation) - Luteal (Faces-Fixation) Follicular (Houses-Fixation) - Luteal (Houses-Fixation) OFC ACC HIP OFC Subjective evaluations of men did not differ by menstrual cycle phase or masculinity (mean±SD = 1.92±0.24). Women indicated a higher likelihood of engaging in sex with Lower Risk men (F 1,7 =112.03, p<.001; High, mean±SD = 1.46±0.25; Low, mean±SD = 2.27±0.35). No Difference in Activation in response to Masculinized compared to Feminized Male Faces (Masculine-Fixation) – (Feminine-Fixation) Less Activation in Response to High Risk Men in Areas Related to Risk Evaluation and Arousal including the Anterior Cingulate, Thalamus, and Hippocampus. (High Risk-Fixation) – (Lo Risk-Fixation) ACC THL ACC THL Decreased Activation to High Risk Men more evident during the follicular compared to luteal phase in the Anterior Cingulate, Midbrain and Thalamus. Follicular (HI-LO) - Luteal (HI-LO) Follicular (HO-LO) - Luteal (HI-LO) ACC MBN ACC THL High Risk Masculinized Feminized Low Risk Masculinized Feminized Figure 1 Rarely 11 Usually 3 Usually 3 Rarely 11