Reciprocal longitudinal associations between brain function and alcohol use trajectories in adolescents and young adults

PROJECT SUMMARY/ABSTRACT Alcohol use is a global health problem that often begins in adolescence/young adulthood. Despite extensive research efforts, effective preventative and treatment measures remain elusive. While bi-directional associations between alcohol use and brain function form the cornerstone of prominent neurobiological theories of addiction, the reciprocal relationship between alcohol use and brain function remains underexplored. This 5-year K99/R00 proposal is designed to address this fundamental gap in knowledge, through the novel application of cutting- edge techniques which overcome many of the limitations of between-subject cross-sectional designs, including low reliability and small effect sizes. It is hypothesized that neurocognitive mechanisms of decision making which underly elevated risk taking in adolescence (i.e., elevated reward processing relative to lower cognitive control) contribute to alcohol use initiation in adolescence, as well as escalation and maintenance in young adults, and that the consumption of alcohol in turn influences these same mechanisms, thereby promoting future use. Crucially, this proposal is designed to support the applicant’s transition to independence through: 1) technical training in advanced longitudinal and machine learning analysis, and the collection and analysis of precision functional mapping (PFM) data, 2) training in assessments of alcohol use behavior in young adults, and 3) professional and career development, including leadership and mentorship, grantsmanship, professional networking, publication, and scientific presentations. Aim 1 (K99) will assess prospective long-term associations between reward, cognitive control, and alcohol use in two large extant datasets of adolescents and young adults (IMAGEN: ages 14-22, N=2000; ABCD: ages 9-18, N=11,000). Analyses will use multivariate neural signatures of these processes, which are more reliable and sensitive to individual differences than regional estimates. Aims 2&3 (K99/R00) will collect the novel ALC-21 sample – a sample of college students who engage in heavy episodic drinking (N=24), who will be scanned repeatedly (8-10 scans each) over a semester, immediately following periods of elevated use (e.g., 21st birthday) and reduced use. The use of precision functional mapping (PFM) – studying an effect with large within-subject variation by acquiring large quantities of imaging data per subject – maximizes the neuroimaging signal, spatial resolution, and measurement reliability. PFM results in robust and reliable within-subject brain-behavior associations. A subset of the full sample (N=5) will be collected for Aim 2, and will be used to test the short-term effect of heavy episodic drinking on reward and cognitive control. The remainder of the sample will be collected during the R00 portion for Aim 3, which will assess bi- directional short-term associations between reward, cognitive control, and alcohol use. Together, these studies will provide fundamental insights into the reciprocal relationship between alcohol use and brain function, both over the long-term and in the short-term. Further, completing this training plan will prepare the applicant to lead an innovative research program as an independent investigator.