PROJECT SUMMARY The current application aims to address racial/ethnic disparities in health experienced by African American young adults through the isolation of acute cognitive and affective mechanisms in the linkages between racial stigma, stress, and vulnerability to substance use. The extant literature provides critical observations of the link between self-reported racial discrimination and real- world risk behavior among African Americans. However, cognitive-neuroscience paradigms have been underutilized thus limiting our understanding of core cognitive and affective processes that underlie stress reactivity, recovery, and behavior in the immediate context of a racial stigma event—as well as factors that may amplify or mitigate acute effects. To address this need, we build on the cue reactivity and substance use literature to develop a racial-stigma, cue-focused task to drive event-related designs for assessing stigma-related change in brain systems involved in cue reactivity, executive function, and reward processing. This work has the potential to shed new light on (a) cognitive and affective processing of singular events of racial stigma (Aim 1) (b) how racial-stigma stress produces sustained changes in affective and regulatory processes (Aim 2) and (c) risk and resilience-promoting factors that moderate these processes (Aim 3). In the proposed K08 career development plan, the Candidate will undertake training to acquire core skills in cognitive-neuroscience approaches, based on electroencephalographic (EEG) event-related potential (ERP) measures, to assess underlying mechanisms of the stigma-stress-substance use pathway. These include conventional time- domain approaches (e.g. late positive potential; LPP), joint time-frequency EEG/ERP analysis of regional neural activation in amplitude (e.g. medial-frontal theta and centro-parietal delta), and how neurophysiological activity is coordinated into dynamic functional networks using time- frequency phase-synchrony approaches. Further, the Candidate will learn to utilize these approaches to index constructs that are consistent with emerging measurement domain frameworks, namely Research Domain Criteria (RDoC), which offer a heuristic for representing complex neurobiological systems. The RDoC constructs of focus are of key relevance to substance use and include negative valence and positive valence systems (affective) as well as cognitive control (regulatory). The utilization of cognitive-neuroscience measures and mapping to RDoC constructs will allow for the parsing of core cognitive and affective processes, enhance theoretical clarity and predictive utility of racial-adversity stress in the context of risk behavior, and ultimately provide more parsimonious intervention targets.