Neurodevelopment of exploration and alcohol problems in adolescence - PROJECT SUMMARY Exploring novel and unfamiliar foods, friend groups, and activities during adolescence critically shapes our preferences and personalities in adulthood. Conversely, for adolescents who engage in underage drinking, such novelty-seeking can be maladaptive and lead to the development of chronic alcohol use problems. Cross- sectional studies suggest that individuals become more strategic in their use of goal-directed exploration to optimize choice during the transition from adolescence to young adulthood. The core hypothesis of the proposed study is that the maturation of directed exploration is blunted or lagged in adolescents who experiment with alcohol and go on to develop increased alcohol use problems. Specifically, we will conduct an accelerated longitudinal fMRI study of N=135 participants (recruited at 13-21 years), merging clinical assays of alcohol use severity, computational modeling of novelty-driven exploration across multiple tasks, model-based decomposition of fMRI data at three longitudinal timepoints, and smartphone-based daily diary assessments to probe alcohol- and novelty-related decision making in vivo outside of the laboratory. In Aim 1 we will test the hypothesis that the normative maturation of novelty-driven exploration—i.e., expansion of strategic, goal- directed exploration to optimize choice—will be negatively modulated by increased alcohol use severity. Further, we will use longitudinal model-based fMRI to determine whether this expansion of directed exploration is driven by age-related increases in neural encoding of the latent value of exploring new options in frontoparietal (i.e., frontopolar cortex, dorsolateral prefrontal cortex, and intraparietal lobule) and motivational (i.e., striatum, amygdala, and orbitofrontal cortex) neural circuits. In Aim 2 we will contrast novelty-driven exploration to maximize gains versus minimize losses, hypothesizing that the presence of potential punishments should decrease exploratory behavior as individuals are motivated to avoid potential losses. Differentiation between reward- and punishment-evoked neural responses is blunted in adolescents with alcohol use problems, therefore we hypothesize that differential gating of novelty exploration across gain versus loss contexts will be diminished in adolescents with higher alcohol use severity. Lastly, in Aim 3 we will use daily diary prompts delivered via smartphone to determine the ecological relevance of our laboratory- based decision making assays for predicting real-world alcohol- and novelty-directed behaviors. This triangulation of computational phenotyping, neuroimaging, and ecologically-situated assessments has not been performed in existing studies, and could identify a new novelty-driven exploration dimension to be considered in future iterations of the Addictions Neuroclinical Assessment framework. In line with the Katz Early Stage Investigator mechanism—this computational developmental science approach will represent an innovative advance that will launch the PI in a new research direction: leveraging his skills and expertise in adolescent neuroimaging to focus on the development of decision making neurocircuitry and risk for alcohol use problems in adolescence.
