Project Summary ADHD has long been believed to include brain-based pathophysiology, but the newest approaches to describing atypical brain organization in ADHD are thus far limited to cross-sectional studies. The current project aims at the crucial question of the neurobiological correlates of change in ADHD during adolescence. In adolescence, ADHD outcomes begin to diverge in important ways that are poorly explained. Understanding the neurobiological basis of those clinical changes would provide a major step forward in clinical understanding. At the same time, in adolescence the dynamics of functional brain development are non-linear and distinct from those processes in childhood, suggesting a deeper focus on that age period. Building on a conceptual framework that integrates cognitive and emotional circuitries in the brain, the present study has the following principal objectives. First, it seeks to discover how distinct types of brain organization within the ADHD population predict in ADHD course during adolescence. Second, it seeks to track variations in the development of cross-network brain organization within the ADHD population in relation to divergent clinical development during the adolescent period. Third, it seeks to evaluate prospects for developmental brain-based ?neurotypes? in ADHD. The significance of this effort lies both in its unprecedented ability to characterize ADHD neurobiology over time with methods of brain characterization that have not been examined in ADHD longitudinally in this way before, and in its effort to move brain imaging into the realm of clinical prediction using a longitudinal design. The project is innovative in regard to implementing network and topology features of brain analysis in a multi-wave design, identifying brain-based typologies of ADHD (neurobiological heterogeneity), and linking these to clinical course. The approach entails tracking of an already developed cohort of 376 children in a cross-lagged longitudinal design, enabling characterization of development from age 7-19 years. Brain organization will be operationalized with diffusion tensor imaging and resting state functional connectivity, while standard structural metrics will also be available. Youth will be characterized annually in relation to clinical symptoms, comorbidity, impairment, cognitive functioning, reward discounting, and emotion regulation and functioning. Analytic approaches will span brain circuit, network, and topological measurements using novel graph theoretical analyses to characterize brain systems. Clinical typologies will be evaluated using community detection procedures and more standard mixture model analysis of brain features. Latent class trajectory models will be used to explore distinct developmental types of ADHD if they exist. The Aims directly match key priorities of the NIMH strategic plan. If successful, the project hopes to break the impasse facing the field with regard to clinical utility of the growing grasp of atypical brain physiology in ADHD. All raw and processed/cleaned data are being made available to the field for exploration to maximize the utility of this one of a kind cohort.