Over the past few decades much has been learned about the nature of Tourette Syndrome (TS). This includes an increased understanding about the clinical manifestations, which include not only tics, but also associated behavioral difficulties—the most common being Attention Deficit Hyperactivity Disorder and Obsessive-Compulsive behaviors. Family studies have also led to a much better understanding about the inheritance of TS. Despite these valuable advances, the basic brain basis of TS that causes tic symptoms remains somewhat elusive. A variety of circumstantial evidence implicates specific brain systems in TS; in particular, deep brain structures, referred to as the basal ganglia, as well as interconnected regions of the frontal lobes. These basal ganglia-frontal circuits (often referred to as frontal-striatal circuits) are known to be important in the control of movement. Damage to these circuits has been linked to a number of other movement disorders including Huntington’s disease and Parkinson’s disease. While most investigators believe that these frontal-striatal circuits are important in causing tics, direct evidence of this causal relationship is lacking. Recent advances in techniques that image activity within the nervous system provide a novel and valuable opportunity to investigate the brain regions involved in the generation of tics, as well as answer other questions that will provide new insights into the neurologic basis of TS. In this study, we will use functional Magnetic Resonance Imaging (fMRI) in children with TS to investigate those regions associated with the generation of tics. We will also use fMRI to examine brain activity associated with tasks previously observed to be impaired in TS; tasks for which frontal-striatal circuits play an important role. These include preparing complex motor responses (e.g., sequential finger tapping) and inhibiting a behavioral response (e.g., stopping oneself from responding). The study will provide further information about the brain regions involved in the causing of tics, something that is still not fully understood. It will also provide insight into differences in regional brain function in children with TS. Both these findings should lead to a greater understanding about the neurologic basis of TS. Stewart H. Mostofsky, M.D., Assist. Prof. Dept. of Neurology, Kennedy Krieger Institute, Johns Hopkins School of Medicine, Baltimore, MD Award: $70,611 Tourette Association of America Inc. – Research Grant Award 2002-2003