This project aims at shedding light on the neurophysiological basis of Tourette Syndrome (TS) by studying it in the context of a wider group of disorders. As evident from its high co-morbidity rate TS is related to other behavioral disorders such as obsessive compulsive disorder (OCD) and attention-deficit hyperactivity disorder (ADHD). Despite their different clinical manifestations, this group of disorders has been associated with a common neuronal pathway: the cortico-basal ganglia loop. Recently, a primate model demonstrated that localized injection of a pharmacological agent into one of the nuclei of this pathway, the external pallidum, enabled reproduction of stereotypy, hyperactivity and movement abnormality characteristic of these disorders. This finding suggests that these disorders may have a common neurophysiological basis. In this project we will utilize multi-electrode recording in the basal ganglia of primates following induction of behavioral symptoms. Neuronal activity and interaction within small neuronal networks will be characterized. Neuronal activity will be correlated with clinical and behavioral symptoms and compared to the neuronal activity of the animal when in its normal state. The same electrodes will be used to apply electrical stimulation and behavioral and clinical changes resulting from this altered neuronal activity will be assessed. Finally, the data acquired in the animal model will be compared with neurophysiological data acquired intra-operatively during deep brain stimulation (DBS) surgeries in TS patients (in collaboration with Dr. Paul Larson, Department of Neurosurgery, University of California, San Francisco). A better understanding the elusive neurophysiological basis of TS and the differences in information processing occurring in the cortico-basal ganglia pathway will enable objective assessment of existing treatments. Izhar Bar-Gad, Ph.D. Bar-Ilan University, Ramat-Gan, Israel Award: $75,000 Tourette Association of America Inc. – Research Grant Award 2006-2007