It is well established that older adults display marked impairments in the heat loss responses of sweating and skin blood flow relative to young adults which can exacerbate body heat storage by compromising whole-body heat loss (evaporative + dry heat exchange). Similarly, young women display reductions in whole-body heat loss relative to young men during exercise in dry heat. As such, it is possible that the age-related decline in whole-body heat loss will be greater among women relative to men. To examine whether the age-related decline in whole-body heat loss would be greater in women relative to men during exercise in dry heat, and whether this response would be more pronounced with a greater elevation in the level of heat stress, whole-body heat loss (evaporative ± dry heat exchange) was evaluated in 80 individuals (46 men, 34 women) aged between 18-70 years. Participants completed an incremental exercise model involving three, 30-min bouts of semi-recumbent cycling at fixed rates of metabolic heat production (150, 200, 250 W/m2), each separated by a 15-min recovery period in hot-dry conditions (40˚C, ~15% relative humidity). Whole-body heat loss was measured using direct calorimetry whereas metabolic heat production was measured using indirect calorimetry. Whole-body heat loss declined with age (across men and women) during moderate- and vigorous-intensity exercise by 4.2 and 6.6 W/m2 (both P < 0.050), respectively, however, these relationships were not modified by sex (both P > 0.050). Nonetheless, whole-body heat loss was lower in women relative to men during moderate- and vigorous-intensity exercise by 8.4 and 12.1 W/m2 (both P < 0.05), respectively. Therefore, the results of this thesis demonstrate that the age-related decline in whole-body heat loss is not dependent on sex.

Thesis advisor: John P. Christianson / Stress is a risk factor for neuropsychiatric disorders such as post-traumatic stress disorder and depression, yet not all individuals who are exposed to stress develop such disorders. Several factors influence susceptibility versus resilience to the effects of stress, including coping strategy biological sex. A growing body of research in humans has demonstrated that active coping strategies – defined as using available resources to problem solve – are positively correlated with resilience. In rodents, resilience to a potent acute stressor can be achieved through active coping, such as controlling the termination of a stressor, but only in males. During controllable stress males engage a stress mitigating pathway between the prelimbic (PL) and dorsal raphe nucleus (DRN), but this pathway isn’t engaged by control in females or when stress is uncontrollable in both sexes. Thus, neural activity within the ventromedial prefrontal cortex (vmPFC) is a critical determinant of stressor-induced anxiety. The mechanism that engage vmPFC excitability are not well understood. Therefore, the goals of the dissertation were 1) determine if eCBs in the PL promote neuronal excitability and behavioral resilience 2) test if ES and IS result in differential activation PL afferents, and will specifically test if ES results in greater activation PL-inputs from action-outcome associated regions, while IS leads to greater engagement of stress/fear inputs to the PL, and 3) identify network-wide patterns of activation and test the hypothesis that the stress and action-outcome networks are differentially activated as a function of stressor controllability and/or sex. We’ve demonstrated that augmenting eCBs in the PL increased excitability through a CB1 and GABA receptor dependent mechanism and was sufficient to block the stress induced decrease in social exploration. Regarding goal 2, PL inputs from the orbitofrontal cortex and DRN were activated in response to stress per se, but were not sensitive to stressor controllability and did not differ between males and females. PL afferents from the basolateral amygdala and mediodorsally thalamus were not sensitive to stress. Lastly, we quantified Fos expression in response to controllable and uncontrollable stress in male and female rats in 24 brain regions associated with stress, action-outcome learning, and showing sex differences in response to stress. Using interregional correlations, we found differences in functional connectivity as a function of stressor controllability and sex when considering all 24 regions and when considering only stress associated regions. Females showed greater overall functional connectivity compared with males, and IS resulted in greater overall connectivity than ES. We also reveal potentially important nodes in functional connectivity networks using centrality measures to identify network hubs. The findings of this research emphasize the need to study differences between males and females across all realms of neuroscience, particularly in relation to disorders of stress and anxiety. / Thesis (PhD) — Boston College, 2019. / Submitted to: Boston College. Graduate School of Arts and Sciences. / Discipline: Psychology.

Early life adversity (ELA) is a prevalent experience in young populations worldwide and can come in many forms, including limited access to resources as in many low socio-economic status households. ELA in humans has been linked to a variety of negative psychiatric outcomes including increased risk for psychiatric disorders such as schizophrenia, major depressive disorder (MDD), post-traumatic stress disorder (PTSD) and substance use disorder (SUD). One characteristic that these disorders share is a disruption in motivational processes. Motivation is largely regulated by the mesocorticolimbic dopamine (DA) system but is also modulated by other brain regions including the medial preoptic area (mPOA) and is crucial for processing of natural rewards such as sexual reproduction. This circuitry is sensitive to estrogenic and androgenic signaling in both males and females. Interestingly, estrogens and androgens can be modulated by the experience of ELA, pointing to gonadal hormones as a potential mediator for the impact of ELA on motivation and risk for psychiatric disorders. In the first set of experiments presented here, we characterize the limited bedding and nesting model (LBN) of early life adversity in rodents, in which rat dams and their pups are housed in a limited resource environment from postnatal day (PND) 2 through 9. LBN dams exhibited less self-care behaviors and more pup-directed behaviors, including grooming and nursing, compared to control dams. This type of maternal care is not characteristic of healthy rat dam behavior and may represent a compensatory mechanism to combat the lack of resources. However, LBN-raised pups still exhibit developmental alterations, notably a decrease in body weight that persisted into adulthood and an increase in adult plasma estradiol levels specifically in males. We build on these findings in the second set of experiments, which explores whether changes in development and gonadal hormones may also impact male reproductive behavior. We found that LBN males have a shorter latency to engage in sex behaviors at earlier timepoints in the sex assay compared to controls, suggesting an enhancement in the acquisition of this repertoire of behaviors. This enhancement in behavior was accompanied by highly sex-specific changes in gene transcription in the mPOA which underlies reproductive behaviors. The identification of genes and signaling pathways that are altered by LBN in the male mPOA lays the groundwork for future studies investigating the mechanisms by which ELA alters reproductive behaviors and underlying motivational processes. / Psychology

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Thesis advisor: Scott D. Slotnick / Sex differences exist in both brain anatomy and neurochemistry (Cahill, 2006). Many differences have been identified in brain regions associated with long-term memory including the dorsolateral prefrontal cortex, hippocampus, and visual processing regions (Andreano & Cahill, 2009). There is, however, a paucity of research investigating whether and how these differences translate into differences in functional activity. Part 1 investigated sex differences in the patterns of functional activity in the brain during spatial long-term memory, item memory, memory confidence, and false memory. In addition, a meta-analysis was conducted to identify whether there were consistent sex differences in the brain across different long-term memory types. Part 2 determined whether there were sex differences in the patterns of functional connectivity in the brain during spatial long-term memory. Specifically, differences in functional connectivity between the hippocampus and the rest of the brain in addition to the thalamus and the rest of the brain were investigated. Finally, Part 3 investigated whether the observed differences in the patterns of activity (identified in Chapter 1) had sufficient information to classify the sex of individual participants. The results of Part 3 argue against the popular notion that the average female brain and average male brain are not significantly different (Joel et al., 2015). More broadly, the studies presented in this dissertation argue against the widespread practice of collapsing across sex in cognitive neuroscience. / Thesis (PhD) — Boston College, 2021. / Submitted to: Boston College. Graduate School of Arts and Sciences. / Discipline: Psychology.