Brain substrates for cardiovascular stress physiology

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Project Summary/Abstract The candidate’s long-term goal is to become an independent investigator focused on the neurophysiological pathways that link psychological stress with cardiovascular disease (CVD). Individual differences in biological responses to acute psychological stress have been shown to predict risk for subclinical and clinical markers of CVD, indicating that variation in the stress response relates to measurable health outcomes. The proposed research and career development program will position the candidate to definitively address open and mechanistic questions on cardiovascular stress physiology with a multi-dimensional approach. The overall objective of the current project is to identify the ‘brain–cardiovascular’ pathways of metabolically excessive cardiovascular responses to stress. The central hypothesis is that metabolically excessive cardiovascular responses to stress are caused by increased brain activation in areas associated with cardiovascular and autonomic control. In extension, the candidate will test whether altering brain function via neuromodulation will regulate downstream cardiovascular responses. Proposed are two independent studies. In Aim 1, we will newly examine the relationship between metabolically excessive cardiovascular and neural responses using a cross-sectional approach. In Aim 2, we will measure stressor-evoked metabolic and cardiovascular responses before and after neuromodulation in an experimental approach. Participants will engage in a novel, non-invasive neuromodulation technique, transcranial infrared laser stimulation (TILS), known to alter the brain by increasing oxygenation, and will be compared to an established control. This research plan will help the candidate develop essential skills for career development including cardiovascular and metabolic testing, machine learning and cross-validation methods for functional magnetic resonance imaging analyses, and utilizing a neuromodulation technique, TILS. The proposed Mentored Research Scientist Development Award will provide 5 years of training through a combination of research, classroom experiences, and mentoring to further the candidate in preparation for scientific independence. Specifically, the candidate will gain expertise in measuring metabolic activity, advance her computational neuroimaging analysis skills, become proficient in experimentally manipulating brain function, and develop necessary statistical skills. The project brings together a mentoring team of experts in their respective areas to provide the candidate with the necessary skills to continue on the trajectory to make a transformative contribution to the field of Cardiovascular Behavioral Medicine. This project will provide vital information regarding the pathways between psychological stress and CVD risk while at the same time providing training and mentoring for the candidate’s further career.