As many as 20-30% of children manifest motor and/or vocal tics at some time in their life. Typically, these new-onset tics disappear within a few months. For other children, these tics represent the beginning of Tourette Syndrome (TS) or Chronic Tic Disorder (CTD). Given these epidemiological data, development of TS/CTD could be conceived as a two-step process: first tics appear, then they fail to remit. By the numbers, the failure to remit is the more abnormal step. Importantly, this step can be observed prospectively, minimizing the biases inherent in retrospective study designs. Equally important is that studies of tic persistence may identify entirely different causative factors than studies of established TS/CTD, where onset and persistence are confounded. This earliest phase of tic disorders may be a key to discovering etiology, prevention or treatment. Our project is the first-ever pathophysiological study of the “pre-Tourette” population (i.e., children with new-onset tics that will either persist or remit with time). With Drs. Kevin Black and Bradley Schlaggar, I will use carefully selected neuroimaging (functional connectivity MRI, volumetric structural MRI), neuropsychological, and clinical methods to examine children with recent-onset tics and follow them clinically through the one-year anniversary of tic onset. I will apply machine learning techniques, namely support vector machines (SVM), to predict whether or not a child with recent-onset tics will go on to develop TS/CTD, based on data collected when tics recently appear. Specifically, I will be able to use existing data to build a classifier that distinguishes children with diagnosed TS/CTD and neurotypical controls, and then use that classifier to make individual predictions regarding the children with recent-onset tics. I will also be able to interrogate the classifiers to identify features (e.g., functional connections, structural volumes) that drive the classification, pinpointing which features are better individual predictors of clinical outcome. Deanna Jacqelyn Greene, Ph.D. Washington University School of Medicine, St. Louis, MO Award: $40,000 (Fellowship – 2nd Year Funding) Tourette Association of America Inc. – Research Grant Award 2012-2013