Project Grant F32AA032966

NEUROPLASTICITY AS A MECHANISTIC LINK BETWEEN ADVERSITY AND ALCOHOL USE IN ADOLESCENCE - PROJECT SUMMARY/ABSTRACT: ADOLESCENCE IS AN IMPORTANT DEVELOPMENTAL WINDOW OF HEIGHTENED, EXPERIENCE-DEPENDENT NEUROPLASTICITY IN BRAIN REGIONS THAT ARE INVOLVED IN ESSENTIAL FUNCTIONS SUCH AS COGNITION. ADOLESCENCE IS ALSO A TIME WHEN RISKY DECISION-MAKING INCREASES, INCLUDING ALCOHOL AND OTHER SUBSTANCE USE, WHICH CAN HAVE HARMFUL AND LASTING EFFECTS ON THE DEVELOPING BRAIN. FURTHER, ADVERSE LIFE EXPERIENCES IN YOUTH CAN HAVE EFFECTS ON BOTH NEUROPLASTICITY AND ENGAGEMENT IN ALCOHOL USE. THE LINKS BETWEEN ADVERSE LIFE EXPERIENCES, NEURODEVELOPMENTAL TRAJECTORIES OF PLASTICITY, AND PROBLEMATIC ALCOHOL USE HAVE NOT YET BEEN WELL-DEFINED, THUS CLOUDING OUR MECHANISTIC UNDERSTANDING OF THESE POTENTIALLY INTERRELATED PROCESSES. THE PROPOSED PROJECT WILL LEVERAGE THE ADOLESCENT BRAIN COGNITIVE DEVELOPMENT STUDY TO CLARIFY THESE LINKS THROUGH THREE SPECIFIC AIMS. IN AIM 1, WE WILL EXPLORE WHETHER ADVERSE EXPERIENCES DURING ADOLESCENCE LEAD TO ALTERATIONS IN NEUROPLASTICITY IN COGNITIVE BRAIN REGIONS. WE WILL USE LATENT CHANGE SCORE MODELS TO EXAMINE WHETHER ADVERSE EXPERIENCES-MEASURED BY THE LIFE EVENTS SCALE (LES)-LEAD TO LATER REDUCTIONS IN PLASTICITY, AS INDICATED BY THE AMPLITUDE OF LOW-FREQUENCY FLUCTUATIONS (ALFF), A RESTING STATE FMRI-BASED MEASURE OF PLASTICITY. IN AIM 2, WE WILL TEASE APART THE DIRECTION OF IMPACT BETWEEN NEUROPLASTICITY AND ALCOHOL USE DURING ADOLESCENCE. SPECIFICALLY, WE WILL ASSESS IF INDIVIDUAL DIFFERENCES IN PLASTICITY LEAD TO ALCOHOL USE OR IF ALCOHOL USE IMPACTS PLASTICITY. WE WILL APPLY MULTILEVEL AND GROWTH CURVE MODELING TO ALCOHOL USE MEASURES FROM THE TIMELINE FOLLOW BACK (TLFB) SURVEY AND TO THE NEUROIMAGING MEASURE OF PLASTICITY (ALFF). IN AIM 3, WE WILL EXPLORE WHETHER THE LINKS BETWEEN ADVERSE LIFE EXPERIENCES DURING ADOLESCENCE AND ENGAGEMENT IN ALCOHOL USE ARE CAUSALLY MEDIATED BY NEUROPLASTICITY. WE WILL APPLY CAUSAL MEDIATION ANALYSES TO ADVERSITY DATA FROM THE LES, ALCOHOL USE DATA FROM THE TLFB, AND ALFF PLASTICITY DATA. FINDINGS FROM THIS PROJECT WILL INFORM A MECHANISTIC UNDERSTANDING OF THE IMPACTS OF EARLY ALCOHOL USE ON NEURODEVELOPMENT AND ON THE INFLUENCE OF BRAIN-ENVIRONMENT INTERACTIONS ON THE ETIOLOGY OF YOUTH ALCOHOL USE, THEREBY PROVIDING NOVEL AND SPECIFIC TARGETS FOR FUTURE INTERVENTIONS. THIS NIAAA F32 PROJECT IS HIGHLY FEASIBLE IN THE PROPOSED TIMELINE AND WELL-SUPPORTED BY THE MENTORSHIP TEAM (DRS. LINDSAY SQUEGLIA AND LOUISE MEWTON) AND INSTITUTION (MEDICAL UNIVERSITY OF SOUTH CAROLINA). THE PROPOSED PROJECT WILL PROVIDE ESSENTIAL TRAINING FOR THE CANDIDATE'S LONG-TERM CAREER DEVELOPMENT HEADING TOWARD AN INDEPENDENT RESEARCH CAREER FOCUSED ON APPLYING DEVELOPMENTAL NEUROSCIENCE METHODS TO THE STUDY OF ADOLESCENT ALCOHOL USE DISORDER (AUD). THIS STUDY WILL PROVIDE THE FIRST STEP TOWARD GENERATING HYPOTHESES FOR AN NIH K-AWARD GRANT AIMED AT TESTING MECHANISTICALLY SPECIFIC AND NEUROSCIENCE-INFORMED INTERVENTIONS FOR YOUTH AUD.