ABSTRACT Project 2 (Thomas Kamarck, PL) A neurobiological diathesis-stress model of CVD risk Psychosocial stress has been associated with risk for cardiovascular disease (CVD), and emerging evidence suggests that individuals may differ in their susceptibility to this stress-related risk. Project 2 will examine whether the activity of brain areas that coordinate autonomic and endocrine output to internal organs (called `visceral control areas') may help to explain some of these individual differences in stress susceptibility during daily life, and may also moderate the effects of psychosocial stress on preclinical CVD progression. Importantly, growing evidence indicates that physical activity (PA) modifies the influence of visceral control areas on peripheral physiology, and this influence may represent a source of resilience to reduce stress susceptibility. Accordingly, Project 2 also aims to test how individual differences in the functioning of visceral control areas may partly explain the association between PA and daily stress susceptibility effects. Specifically, we will follow 350 midlife and community dwelling adults over a 32-month period, collecting two one-week samples, at the beginning and at the end of this period. At each of these 2 points, we will assess daily psychosocial stressors using multiple momentary electronic diary reports and ambulatory blood pressure readings. We will use daily actigraphy to assess habitual PA, and we will collect biological markers of subclinical CVD. At baseline, all participants will complete a standardized battery of stressor tasks during fMRI. We will test whether individual differences in the functionality of visceral control areas (that is, differences stressor-evoked functional connectivity) predict corresponding differences in susceptibility to psychosocial stress in the natural environment. We hypothesize that people who exhibit greater stressor- evoked functional connectivity among visceral control areas will also exhibit a) larger blood pressure reactions to daily psychosocial stressors in the natural environment, and b) stronger associations between psychosocial stressor exposures and 32-month preclinical CVD progression. We further hypothesize that stressor-evoked functional connectivity will partly account for the effects of PA on daily stress-related blood pressure reactivity. The public health significance of this novel work is that understanding the role of particular brain circuits in stress susceptibility and CVD risk will help us to better measure and, potentially, to enhance stress resilience through more targeted intervention efforts.