Analysis of the Basal Ganglia Territories Involved in the Clinical Manifestation of TS by a Combined Anatomical, Pharmacological and Behavioral Study in Green Monkeys

Grant Type
Basic
Grant Year
2001-2002
Institution Location
Foreign
Institution Organization Name
Hopital de la Pitie-Salpetriere France
Investigators Name
Tremblay, Leon, PhD

Tourette Syndrome (TS) is primarily characterized by simple and complex motor and vocal tics, but obsessive-compulsive disorders and attention disturbance are also observed in TS. This pathology as a whole appears 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 participate not only in motor control, which has been well known for a long time, but also in 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 the clinical symptoms of TS. Our preliminary results indicate that it is possible to obtain a primate model of TS, since the broad behavioral repertoire of monkeys may allow the complex clinical symptoms of the disorder to be seen. Reversible and localized changes of neuronal activities will be induced in green monkeys using microinjection of pharmacological agents and correlated with behavioral changes. Spontaneous changes of behavior will be studied with monkeys performing conditioned tasks and free to move in cages. The analysis will be combined to an anatomical study using microinjection of axonal markers, which allow determination of the inputs and outputs (network) of the neuronal populations localized within the site where behavioral changes were observed. The first outcome of this study will be a better physiopathological explanation of TS. The induction of behavioral changes using different classes of drugs will allow us to provide a rational determination of the most appropriate and efficient pharmacological treatment. These behavioral changes related to dysfunction of well identified anatomical structures could represent an experimental model of human pathology which could be used in order to evaluate the potential efficiency of deep brain stimulation, a recently proposed treatment of TS. L̩on Tremblay, Ph.D., Chantal Fran̤ois, Ph.D. Hopital de la Salpetriere, Paris, France Award: $70,786 Tourette Association of America Inc. РResearch Grant Award 2001-2002