This proposal is based on the hypothesis that Tourette Syndrome (TS) is, in part, a consequence of atypical development of executive control networks in the brain. The brain’s executive control systems are responsible for performing goal-directed tasks, and are thought to be anatomically separate from the brain’s moment-to-moment processing systems. Therefore, rather than focusing on the functioning of a particular brain region, or set of regions, to try and understand what is different in TS, the emphasis in this study will be on the composition of well-defined networks within the context of typical development. Consistent with this hypothesis, we have shown that in typically developing school-aged children, executive control networks have an immature configuration and that mature network architecture emerges through principles of segregation and integration. Preliminary findings resulting from the first year of funding from the TSA enabled us to show that adolescents with TS have delayed maturation of executive control networks when compared to adolescents who do not have TS and a preponderance of atypical connections in the fronto-parietal network. These findings prompted this second year proposal, which has two aims. The first aim is to determine whether the lag for development of network architecture persists into adulthood. The second aim is to determine whether introduction of anti-tic medication will alter network architecture. Building on the results from Year 1, we propose a design wherein adolescents with TS will be scanned immediately prior to starting anti-tic medication, and once again 2 months after initiation of medication. We hypothesize that anti-tic medications may reconfigure network architecture, providing a plausible mechanism for their clinical efficacy. Successful demonstration of TS-related aberrant network development using resting state fcMRI has the potential for providing significant insight into the developmental pathobiology of TS. Bradley L. Schlaggar, M.D., Ph.D. Washington University School of Medicine, St. Louis, MO Award: $74,765 (2nd Year) Tourette Association of America Inc. – Research Grant Award 2008-2009