Neurodevelopmental Abnormalities in the Indirect Basal Ganglia Pathway in Tourette Syndrome

Grant Type
Grant Year
Institution Location
Institution Organization Name
Yale Child Study Center
Investigators Name
Vaccarino, Flora, MD

Several lines of evidence suggest that Tourette Syndrome (TS) may result from a neurodevelopmental abnormality within the basal ganglia, a set of brain nuclei controlling motor and cognitive programs. We hypothesize that this developmental abnormality leads to a decrease in the activity of either the striato-pallidal connections or the subthalamic-pallidal connections within the indirect pathway. This decrease may result in a reduced output from the basal ganglia and a disinhibition of the thalamic-cortical circuitry in TS patients. In order to assess the nature of the developmental anomaly underlying TS, we are planning to carry out a quantitative morphometric study of the basal ganglia and associated regions in postmortem brain tissue of TS and control subjects using stereological methods. An initial step toward this objective is the creation of a “library” resource for both control and TS brain tissue sections suitable for stereological analysis as well as for other neuropathological assessments. The creation of such a centrally administered tissue resource is being supported by the TSA in conjunction with Dr. Cliff Saper of Harvard Medical School. Under this plan, we will perform stereological analysis of 10 normal control subjects using appropriately prepared tissue sections made available to us through this common tissue resource. The analysis of this control tissue will provide us with important information that will be invaluable for the future examination of tissue from TS patients. Data that we will be able to infer from these analyses include uniformity of section cutting techniques, optimal sampling methods, and between-subject variability. Thus, we may be able to build on these control studies in the future using tissue from TS brains. Our long term goal is to demonstrate whether TS brains exhibit a decrease in volume and cell number within one or more stations of the indirect pathway, and to correlate these changes with symptom severity. This information may provide important insights into the etiology and pathophysiology of TS, and may be used to generate further hypotheses regarding the developmental processes at fault in this syndrome. Flora M. Vaccarino, M.D. Yale University Child Study Center New Haven, CT Award: $40,000 Tourette Association of America Inc.- Research Grant Award 1998