Larry Cahill’s research while affiliated with University of California, Irvine and other places

The issue of sex influences on the brain is rapidly moving center stage, driven by abundant results proving that subject sex can and regularly does alter, negate, and even reverse neuroscientific findings and conclusions down to the molecular level and thus can no longer be justifiably marginalized or ignored.

Sex role orientation, i.e., a person's masculinity or femininity, influences cognitive and emotional performance, like biological sex. While it is now widely accepted that sex differences are modulated by the hormonal status of female participants (menstrual cycle, hormonal contraceptive use), the question, whether hormonal status and sex hormones also modulate participants sex role orientation has hardly been addressed previously. The present study assessed sex role orientation and hormonal status as well as sex hormone levels in three samples of participants from two different cultures (Northern American, Middle European). Menstrual cycle phase did not affect participant's masculinity or femininity, but had a significant impact on reference group. While women in their follicular phase (low levels of female sex hormones) determined their masculinity and femininity in reference to men, women in their luteal phase (high levels of female sex hormones) determined their masculinity and femininity in reference to women. Hormonal contraceptive users rated themselves as significantly more feminine and less masculine than naturally cycling women. Furthermore, the impact of biological sex on the factorial structure of sex role orientation as well as the relationship of estrogen to masculinity/femininity was modulated by culture. We conclude that culture and sex hormones interactively affect sex role orientation and hormonal status of participants should be controlled for when assessing masculinity and/or femininity.

Oral contraceptive pills (OCs), which are used to prevent pregnancy by the majority of women in the United States, contain steroid hormones that may affect the brain's structure and function. In this investigation, we tested the hypothesis that OC use is associated with differences in brain structure using a hypothesis-driven, surface-based approach. In 90 women, (44 OC users, 46 naturally-cycling women), we compared the cortical thickness of brain regions that participate in the salience network and the default mode network, as well as the volume of subcortical regions in these networks. We found that OC use was associated with significantly lower cortical thickness measurements in the lateral orbitofrontal cortex and the posterior cingulate cortex. These regions are believed to be important for responding to rewards and evaluating internal states/incoming stimuli, respectively. Further investigations are needed to determine if cortical thinning in these regions are associated with behavioral changes, and also to identify whether OC use is causally or only indirectly related to these changes in brain morphology. Hum Brain Mapp, 2015. © 2015 Wiley Periodicals, Inc. © 2015 Wiley Periodicals, Inc.

The amygdala is a highly interconnected region of the brain that is critically important to emotional processing and affective networks. Previous studies have shown that the response of the amygdala to emotionally-arousing stimuli can be modulated by sex hormones. Because oral contraceptive pills dramatically lower circulating sex hormone levels with potent analogs of those hormones, we performed a functional magnetic resonance imaging experiment to measure amygdala reactivity in response to emotional stimuli in women using oral contraceptives, and compared their amygdala reactivity to that of naturally-cycling women. Here, we show that women who use oral contraceptive pills have significantly decreased bilateral amygdala reactivity in response to negatively-valenced, emotionally arousing stimuli compared to naturally-cycling women. We suggest that by modulating amygdala reactivity, oral contraceptive pills may influence behaviors that have previously been shown to be amygdala-dependent - in particular, emotional memory. © The Author (2015). Published by Oxford University Press. For Permissions, please email: journals.permissions@oup.com.

Sex differences in attentional selection of global and local components of stimuli have been hypothesized to underlie sex differences in cognitive strategy choice. A Navon figure paradigm was employed in 32 men, 41 naturally cycling women (22 follicular, 19 luteal) and 19 users of oral contraceptives (OC) containing first to third generation progestins in their active pill phase. Participants were first asked to detect targets at any level (divided attention) and then at either the global or local level only (focused attention). In the focused attention condition, luteal women showed reduced global advantage (i.e. faster responses to global vs. local targets) compared to men, follicular women and OC users. Accordingly, global advantage during the focused attention condition related significantly positively to testosterone levels and significantly negatively to progesterone, but not estradiol levels in a multiple regression model including all naturally cycling women and men. Interference (i.e. delayed rejection of stimuli displaying targets at the non-attended level) was significantly enhanced in OC users as compared to naturally cycling women and related positively to testosterone levels in all naturally cycling women and men. Remarkably, when analyzed separately for each group, the relationship of testosterone to global advantage and interference was reversed in women during their luteal phase as opposed to men and women during their follicular phase. As global processing is lateralized to the right and local processing to the left hemisphere, we speculate that these effects stem from a testosterone-mediated enhancement of right-hemisphere functioning as well as progesterone-mediated inter-hemispheric decoupling. (249 words).

Sex differences in emotional memory have received increasing interest over the past decade. However, to date, no work has explored how a postlearning stressor might modulate the influence of sex hormone status on memory for gist and peripheral detail in an emotional versus neutral context. Here, we tested 3 predictions. First, compared with naturally cycling (NC) women in the luteal phase, women on hormonal contraception (HC) would have significantly blunted hypothalamic-pituitary-adrenal reactivity to physical stress. Second, postlearning stress would enhance detail and gist memory from an emotional story in NC women, and finally, postlearning stress would not affect emotional memory for details or gist in HC women. Healthy NC and HC women viewed a brief, narrated story containing neutral or emotionally arousing elements. Immediately after, cold pressor stress (CPS) or a control procedure was administered. One week later, participants received a surprise free recall test for story elements. NC women exhibited significantly greater cortisol increases to CPS compared with HC women. NC women who viewed the emotional story and were administered CPS recalled the most peripheral details overall and more gist from the emotional compared with the neutral story. In HC women, however, the postlearning cortisol release did not affect memory for gist or peripheral details from the emotional or neutral story in any way. Additionally, NC and HC women performed similarly on measures of attention and arousal. These findings suggest that in women, postlearning stress differentially affects memory for emotional information depending on their hormonal contraceptive status. (PsycINFO Database Record (c) 2014 APA, all rights reserved).