In recent years, research in Tourette Syndrome has focused on investigations designed to identify either neurochemical imbalances or specific anatomical localization in order to explain the production of tics and other symptoms of this disorder. Numerous neurotransmitter systems have been implicated, especially an imbalance of the neurotransmitter domapine (DA). A DA receptor hypersensitivity hypothesis has been proposed based primarily on studies of CSF monoamine metabolites. Efforts at neuranatomic localization of this defect have centered on the basal ganglia, but as yet no direct substantiating evidence has emerged. In these experiments, we plan to evaluate a specific cortical area, the supplementary motor area (SMA), in the pathogenesis of TS. While its existence has been known for more than three decades, only recently has the SMA’s role in the cortical organization of movement been appreciated. This cortical area has anatomic, physiologic and biochemical features which make it a prime pathophysiologic candidate in the production of the motor and behavioral symptoms of TS. For example, the SMA is capable of producing complex movement synergies and vocalizations in man and experimental animals. In addition, the SMA receives major afferents from other cortical motor areas, as well as areas associated with complex and affective behaviors such as prefrontal cortex, cingulate cortex, and the amygdaloid complex. The SMA has recently been shown to receive the bulk of basal ganglia influences. The SMA’s efferents, in addition to projection to the precentral motor cortex, include direct pathways to the spinal cord and brainstem reticulospinal system. Thus, connections place the SMA in an ideal position to mediate the direct expression of the movement-related components and the obsessional, affectively laden aspects of TS. In this study, we plan to evaluate the motor effects of dopaminergic denervation of the SMA in experimental animals, and to evaluate secondary receptor hypersensitivity by administration of DA-like drugs to these animals. These experiments may provide important insights into the role of the SMA and mesocortical DA projections in the production of involuntary movements such as those seen in TS. Thomas M. Lock, M.D. Johns Hopkins School of Medicine, Kennedy Institute for Handicapped Children, Baltimore, MD Award: $15,000 Tourette Association of America Inc. – Research Grant Award 1986
Role of the Supplementary Motor Area in Tourette Syndrome
Grant Type
Basic
Grant Year
1986
Institution Location
MD
Institution Organization Name
Johns Hopkins
Investigators Name
Lock, Thomas, MD