PROJECT SUMMARY / ABSTRACT During young adulthood, drinking dramatically increases, with binge-level drinking peaking at age 22 and nearly half of individuals reporting binge-level alcohol use2. Frequent binge alcohol use during the protracted neuromaturation spanning into the mid-20s may result in greater brain and cognitive effects than similar alcohol use in later adulthood. In response to RFA-AA-17-003, this application proposes a Research Project Site of the National Consortium on Alcohol and Neurodevelopment in Adolescence second phase (NCANDA-2) to determine the predictors and effects of heavy adolescent alcohol use in adolescence and young adulthood. To achieve this, the SRI site of NCANDA-2 will continue to follow a cohort of 169 San Francisco Bay Area (n=831 across all 5 sites) participants (ages 12-21 at baseline first visit) to acquire the necessary data to advance our understanding of adolescent development and the effects of alcohol use during adolescence on the adult brain. NCANDA-2 will use multimodal neuroimaging, cognitive testing, behavioral assessment, biospecimen collection, and multimodal assessments in the natural environment. The examination of alcohol consequences will focus on structural and functional maturation of brain areas that actively develop during adolescence and young adulthood, are involved in psychological regulation, respond to rewards, and appear vulnerable to neurotoxic effects of alcohol. In addition, the SRI will collaborate with the University of Pittsburgh NCANDA site to study sleep-related predictors and effects of alcohol use in a subgroup of adolescents. Behavioral and electrophysiological measures will be made on overnight visits, including electroencephalography, auditory evoked slow-wave potentials during sleep (K-complexes), and heart rate variability measures of autonomic function during sleep. Sleep-brain structural relationships will also be investigated. SRI will also collaborate with the UCSD site to collect the Stroop task in the fMRI environment to evaluate changes in the cognitive control system for youth who increase drinking versus those who do not. Sex differences in development, alcohol use patterns and history, impact of alcohol use on the brain, and sex- differentiating psychosocial factors (e.g., depression symptoms) will be considered in analyses. With the additional longitudinal data provided by this renewal, we will determine the effects of alcohol exposure on the developmental trajectory of the human brain, and identify preexisting psychobiological vulnerabilities and resiliencies that may alter adolescents' and young adults' risk for alcohol or other substance use disorder and other mental health and developmental outcomes.