Analysis of the Basal Ganglia Territories Involved in Different Clinical Manifestations of TS and Determination of potential Efficacy of Subthalamic Nucleus Stimulation in a New Monkey Model (2nd yr)

Grant Type
Basic
Grant Year
2002-2003
Institution Location
Foreign
Institution Organization Name
Hopital de la Pitie-Salpetriere France
Investigators Name
Tremblay, Leon, PhD

Tourette Syndrome (TS) is characterized by simple and complex motor and vocal tics and often by attention problems and obsessive-compulsive traits. These symptoms as a whole appear to be an association of motor, cognitive and affective disorders. It has been shown that behavioral abnormalities observed in this neurological condition are probably related to disturbances in frontal cortex and in sub-cortical structures such as the basal ganglia. These anatomical structures are involved not only with motor control (for example in Parkinson’s disease) but also in cognitive, attentional and motivational processes. Our goal is to investigate in primates the role of the basal ganglia and the implications of basal ganglia dysfunction in the expression of TS symptoms. During our first year grant, we have obtained a primate model of TS in which clinical symptoms of the disorder could be induced by microinjection of pharmacological agents in the external palladum. Complex behavioral changes were observed such as hyperactivity with attention deficit/compulsive behaviors. For the second year, microinjection of pharmacological agents will be performed in the striatum in order to try to induce motor tics, a hallmark symptom of TS. The complete clinical repertoire will thus be available in our primate model. We will then test the efficacy of high frequency stimulation of the subthalamic nucleus as a possible treatment of TS. This procedure has proved helpful in Parkinson’s disease, another condition caused by a disturbance of the basal ganglia. The first outcome of this study we hope for will be an improved understanding of TS based on an animal model. The second outcome will be an experimental preclinical evaluation of the efficacy and risks of subthalamic nucleus stimulation as a TS treatment. This may lead to a TS treatment for those who do not respond to any of the current medications available. Leon Tremblay, Ph.D., Jerome Yelnik, M.D., Ph.D., Hopital de la Pitie-Salpetriere, Paris, France Award: $73,693 (Second Year) Tourette Association of America Inc. – Research Grant Award 2002-2003