Neuroimaging studies have identified ongoing neural tissue development throughout adolescence and early adulthood. Increases in myelination and white matter (WM) integrity along with decreases in gray matter (GM) cortical thickness (e.g., pruning) are thought to strengthen synaptic connections and allow for efficient communication between brain regions. Adolescents are at increased risk for engaging in substance use behaviors, and problematic use often begins to peak during this developmental time period. The relationship between WM microstructural integrity and GM cortical thickness is only beginning to be explored in adolescent populations, with cross sectional studies showing relationships between substance misuse and both macrostructural and microstructural neural tissue status. Research has shown a large neurobiological component to risk taking behaviors during adolescence, however the link between the biological underpinnings of risky behaviors has not been clearly defined. It is possible that indices of WM integrity and GM cortical thickness used in conjunction will help us understand the predictive validity of two commonly used structural imaging measurements, particularly their utility in predicting future adolescent substance use. Therefore, this study will utilize diffusion tensor imaging (DTI) and structural magnetic resonance imaging (sMRI) to examine the influence of WM integrity and GM cortical thickness on real world risk taking behaviors such as drug and alcohol use, measured over a 36-month interval in adolescents ages 16-18 at baseline. If empirical support exists for WM integrity and GM cortical thickness as predictors of substance use behaviors, these measures may be used to help identify teens at risk for substance use disorders. PUBLIC HEALTH RELEVANCE: Understanding the brain features behind adolescent substance use will aid clinical assessment and help in design of prevention and intervention programs and strategies that limit risk taking opportunity and construct healthier outlets for teenagers. In the future, multi-domain risk taking assessment (e.g., brain imaging, personality) may be used to identify and guide high-risk teenagers, which could advantageously reduce disease transmission and costs to the healthcare and criminal justice system overall.