Decoding Global Networks Underlying Tourette Syndrome Subtypes Using PET and Electrophysiological Methodologies

Grant Type
Grant Year
Institution Location
Institution Organization Name
Korea Brain Research Institute
Investigators Name
McCairn, Kevin W, PhD

Clinically the symptoms of Tourette syndrome (TS) are complex; behaviors range from short myoclonic jerks to complex motor or vocal tics. We have developed a nonhuman primate (NHP) model of TS that utilizes GABAergic modulation, via the GABA antagonist bicuculline, which reliably induces several of the major symptom subtypes. Specifically, bicuculline targeted to the sensorimotor territory of the striatum (putamen) leads to repetitive myoclonic tics, while placement in the limbic territory (nucleus accumbens) induces persistent vocalizations. Using PET imaging, video, electromyographic, and local field potential (LFP) recordings, we have seen that simple myoclonic and vocal tics exhibit partly similar but largely distinct properties with respect to the emergence of pathological behavior and brain states. The aim of the study is two-fold: (1) to quantify the behavioral effects of limbic relative to sensorimotor network striatal disinhibition; and (2) to determine how differences in cortical and subcortical activity, as assessed through PET imaging, single unit and LFP recording differentiate abnormal behavioral profiles. Completion of the study will lead to the following novel contributions in the field of TS studies: 1. The investigation will provide the first detailed examination of the cortical/subcortical networks that drive pathological vocalizations and their temporal and spatial dynamics in NHP’s. 2. The use of PET imaging will allow the possibility of directly comparing the networks that are active/underactive in the NHP-TS model with those in TS patients. 3. A primary aim of this study, using global PET imaging and distributed electrophysiological recording, is to identify potential novel sites that could be used for surgical intervention Kevin W. McCairn, Ph.D., Masayuki Matsumoto, BSc, Ph.D., Masaki Isoda, BSc, M.D., Ph.D., and Takafumi Minamimoto, BSc, Ph.D. Korea Brain Research Institute, Daegu, Korea Award: $150,000 Tourette Association of America Inc. – Research Grant Award 2014-2015