Neurophysiologic Correlates of Sensory Over-Responsivity in Tourette Syndrome

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Project Summary / Abstract Candidate: David Isaacs, MD, MPH is Assistant Professor in the Department of Neurology at Vanderbilt University Medical Center. During his faculty tenure, he has demonstrated enthusiasm and aptitude for patient- centered research, with emphasis on non-motor aspects of movement disorders. Notable early career highlights include founding Vanderbilt’s Adult Tourette Syndrome (TS) Clinic and co-directing Vanderbilt’s Tourette Association of America (TAA) Center of Excellence; securing multiple extra- and intra-mural grants, including the TAA Young Investigator Award to support research into sensory phenomena in TS; and serving as site principal investigator for industry-sponsored clinical trials in TS. He seeks to become a leading researcher in neurophysiologic mechanisms of non-motor symptoms in TS and other movement disorders. Research Project: TS affects 0.5-0.8% of school-aged children, one-third of whom suffer bothersome tics into adulthood. Tics are the defining feature of TS, but sensory symptoms are widespread. In particular, over 50% of children and 80% of adults with TS report sensory over-responsivity (SOR), defined as heightened awareness of and behavioral reactivity to sensory stimuli. SOR is an integral facet of the TS phenotype, but significant knowledge gaps surround its clinical significance and neurobiological underpinnings. This proposal seeks to clarify the mechanistic bases of SOR in TS (Aims 1 and 2) and to determine whether SOR is a risk marker for more severe clinical course in TS (Aim 3). To achieve Aims 1 and 2, Dr. Isaacs will use quantitative electroencephalography (EEG) and multi-modal autonomic measurement to assess neurophysiologic response to auditory and tactile stimuli in adults with TS. To achieve Aim 3, he will use validated rating scales to assess motor, sensory, and psychiatric symptoms in adolescents with TS at two time points: baseline and 2 years. Study results will deepen insight into TS pathophysiology and identify risk markers for more severe TS course. Career Development Plan and Goals: With guidance from his Scientific Steering Committee, Dr. Isaacs has created a curriculum incorporating formal coursework, workshops, conferences, and individualized training with mentors and collaborators to adequately prepare himself for independent research in the neurophysiologic basis of non-motor aspects of movement disorders. His short-term career goals are to develop proficiency in 1) measurement of sensory and neuropsychiatric symptoms; 2) event-related potentials and quantitative EEG methodology; and 3) psychophysiological techniques complementary to EEG. Environment: Vanderbilt University Medical Center is an optimal academic environment for nurturing Dr. Isaacs’ maturation into a fully-fledged independent researcher. The institution has an exceptional track record for fostering productive, independently funded, and internationally renowned clinician-scientists. The primary mission of Vanderbilt’s Clinical and Translational Science Award is provision of infrastructure for clinical research excellence, with an entire arm devoted to training and career development.