Project Summary Racism is one of the most urgent and broadly impactful crises in contemporary society, increasing an array of adverse health outcomes including mortality in Black Americans, yet neuroscientists and psychologists have heretofore shied away from directly examining personal experiences with racism and their consequences on the brain, mind, and body. Such investigation is essential because it will allow us to better characterize mechanistic pathways linking experiences with racism to health disparities and to devise potential strategies for addressing such disparities. Repeated exposures to racism likely trigger and amplify a cascade of stress-related brain and physiological responses that are known to mediate elevated risk for adverse health outcomes. In this project, we will examine several elements of this mechanistic cascade. We aim to apply validated scientific paradigms in novel ways to examine brain, physiological, and psychological responses to the recollection of specific personal experiences with racism – compared to other types of life experiences – among people who identify as Black or African American. We will also use prospective smartphone-based ecological momentary assessment (EMA) methods to measure the frequency and severity of experiences with racism as they occur in daily life in real time, and we will associate these measures with brain, physiological, and health outcomes. We will examine the relationship between brain/physiological responses to racism and health outcomes and functioning measures – such as psychological distress, cardiovascular disease risk, cellular aging (telomere length), hair cortisol, coping, emotion regulation, and social support – and determine whether brain and physiological responses mediate the relationship between extent of racism exposure and health outcomes. The proposed investigation represents an innovative paradigm shift, in which racism is treated like other pathophysiological processes that affect health. We have assembled an interdisciplinary team with expertise in areas including neuroimaging, trauma, biomarkers of stress, physiological perspectives on health disparities, ecological momentary assessment, emotion regulation, and the empirical study of anti-Black racism, yielding a collaborative effort that is unique and synergistic. It is an approach with potential to transform the way that neuroscientists and psychologists conceptualize and study racism, helping to overcome some of the obstacles that have prevented previous scientific investigation of personal experiences with racism. Among our central aims is to increase the representation of a minoritized participant population that has been historically undersampled in NIH-funded research, and to promote the training and career advancement of underrepresented research trainees, consistent with NIH goals.