The medial temporal hippocampal system exhibits high plasticity and is influenced by behavioral and socioenvironmental factors. Animal models have demonstrated the neuroplasticity of this system through environmental enrichment, exercise, and chronic stress. Human studies have replicated these findings, highlighting the positive impact of exercise and cardiorespiratory fitness, as well as the detrimental effect of chronic stress on brain structure. However, limited research has explored the differences between young and older adults in extrahippocampal regions of the medial temporal lobes. Additionally, the impact of psychosocial stressors such as perceived discrimination and moderating factors like sense of control on this brain system remains understudied. Furthermore, there is a lack of investigation into the neurobiological consequences of perceived discrimination as a significant psychosocial stressor on neurocognitive health. The goals of this dissertation project were to investigate the role of cardiorespiratory fitness and perceived discrimination on medial temporal hippocampal system neurocognitive integrity in humans. I had two hypotheses. First, higher cardiorespiratory fitness would correlate with higher extrahippocampal cortical thickness in young and older adults. Second, a greater number of experiences of perceived discrimination would correlate with reduced amygdala and anterior hippocampus volume in older adults. Two experiments were conducted to assess the impact of behavioral and socioenvironmental factors on medial temporal hippocampal system structure. In the first experiment, cross-sectional data were collected from two randomized clinical controlled trials (n = 100; 56 young adults and 44 older adults). In the second experiment data were collected from two pilot studies (n = 36). Finally, we discuss how the built and social environment, artificially created or modified areas where individuals live, work, or engage in recreational activities, can facilitate or impede behaviors that benefit brain health such as physical activity to increase cardiorespiratory fitness or social engagement. Experiment 1 used structural MRI and assessed cardiorespiratory fitness in sedentary young and older adults. The primary objective was to examine the relationship between cardiorespiratory fitness and entorhinal, parahippocampal, and perirhinal cortical thickness. The results indicated a positive association between cardiorespiratory fitness and cortical thickness in these regions, specifically in the left hemisphere of young adults. However, this relationship was not observed in older adults. Experiment 2 focused on the association between participants' perceived social discrimination experiences and amygdala and anterior hippocampus volume. Additionally, the moderating role of locus of control, a measure of self-efficacy, was examined. The findings revealed that higher levels of perceived social discrimination were associated with reduced amygdala and anterior hippocampus volume. Moreover, higher levels of locus of control attenuated the relationship between perceived social discrimination and these brain regions. The third project integrated the aforementioned ideas within the context of the built and social environment. The discussion centered around how systemic barriers within the environment can either support or hinder engagement in health-promoting behaviors like cardiorespiratory fitness. The importance of considering the built and social environment in clinical interventions was highlighted, with a focus on improving translation of research findings to benefit research participants. Factors such as safety, access to green spaces, and social connectedness were explored, particularly in relation to universal design and its potential to enhance healthy aging and accessibility while addressing systemic racism and structural barriers. These chapters provide evidence to inform policymakers, clinicians, and neuroscientists about the broader implications of clinical research in communities. By considering the impact of clinical interventions on the built and social environment, this work aims to promote health and well-being beyond laboratory settings.

An emerging framework, the Identity Pathology (IP) model, partially addresses persistent uncertainties about the primary causes of disparities in cardiovascular health (CVH) between black and white women and men through outlining how identity beliefs associated with social group membership lead to predictable differences in the health-damaging effects of discrimination exposure. Using data from the CARDIA cohort, this doctoral thesis seeks to: 1) propose a novel psychosocial characteristic, identity pathology, that drives the distribution of reported race and gender discrimination in health-relevant ways, 2) assess whether there are group differences in the effects of multiple versus single forms of discrimination on future CVH, and 3) assess variation between these groups in the relationships of reported racial and gender discrimination in a variety of daily life settings with future CVH. The IP framework suggests that beliefs about identity unique to each gendered race group influence the perception of discrimination and whether reported exposure will be associated with CVH. Simultaneous reports of racial and gender discrimination in multiple settings (compared with no discrimination) were negatively associated with future CVH only among white men. Further, the setting in which discrimination was reported appeared to be a significant indicator of whether experiencing multiple forms of discrimination negatively impacted CVH in each group. Our findings contribute to the literature through introducing a novel framework for assessing the effects of interpersonal discrimination. This work also provides preliminary evidence that compounded experiences of interpersonal racial and gender discrimination may not substantially contribute to poorer CVH among black women.