Widely characterized as a frontostriatal disorder, Tourette syndrome (TS) is believed to involve abnormalities in brain structures that are important for cognitive control: prefrontal cortex (PFC) and the striatum. These behavioral and brain abnormalities are thought to result from abnormal dopaminergic (DA) functioning in TS. Specifically, increased levels of DA lead to an imbalance of DA in frontostriatal pathways that are necessary for the control of thought and action. This study aims to investigate the effects of TS on DA-linked processes, such as response inhibition, reward processing, and feedback-based learning. In this study, we will compare performance of children with TS to healthy, age-matched controls, ages 7-12, on two variants of a Stop Signal task. During this measure of response inhibition, participants initiate ongoing actions (i.e. pressing a button as fast as possible) in response to a repeated cue, but must inhibit that action (i.e. stop themselves from pressing the button) in response to an occasional stop-signal. By using two variants of this Stop Signal Task, we hope to selectively engage two discrete inhibitory pathways. The proposed hyperdirect pathway from the prefrontal cortex (PFC) to the subthalamic nuclei is believed to remain relatively unaffected by increased DA, while activity in the indirect pathway via the basal ganglia is suppressed by the increase. In addition to motor control, striatal dopamine is known to play a major role in reward processing and feedback learning. Recent work indicates that fluctuations in dopaminergic activity in TS represent phasic rather than tonic increases. However, it remains unclear whether these TS-related phasic increases interfere with the dopaminergic reward signal. Thus, we will examine the consequences of altered dopaminergic transmission on performance during a reversal learning task that requires updating behavior on the basis of both positive and negative feedback. Silvia A. Bunge, Ph.D., Elysa Marco, Ph.D., Sarah Munro, B.S. University of California, Berkeley, CA Award: $75,000 Commentary: Tourette syndrome is thought to be caused by increased levels of dopamine, a brain chemical that is not only critical for movement control but which is also involved in learning and generating a sense of reward. This study examines inhibition and reward sensitivity in children with Tourette syndrome. We will use an imaging technique (functional Magnetic Resonance Imaging or fMRI) to understand how Tourette syndrome and deliberate suppression of tics affects the functioning of brain regions associated with movement control and learning. This award is funded by Alisa Yaffa and Ken McElvain Tourette Association of America Inc. – Research Grant Award 2010-2011