Parkinson's Disease (PD) results from the degeneration of dopaminergic neurons in the substantia nigra, yet little is understood about how this loss results in the primary motor symptoms of the disease (rigidity, bradykinesia and tremor). Although a lesion placed in the globus pallidus can relieve rigidity tremor and/or drug-induced dyskinesia, the mechanism underlying this effect is also not understood. Furthermore, the role of the basal ganglia in the control of movement remains to be established. These facts underscore the need for directly studying basal ganglia function in PD patients. The surgical treatment of PD by pallidotomy provides an excellent, and largely unexploited, opportunity for achieving this goal. Our proposed work brings together recent developments in the fields of behavioral science, neurophysiology and clinical neurology to test the hypothesis that specific motor symptoms of PD are the result of specific changes in the spatiotemporal dynamics of the neural activity within the basal ganglia. These properties have received little attention in studies of the human globus pallidus. To establish this relationship, we propose the following specific aims: 1). to determine the severity of the constellation of Parkinsonian motor symptoms in individual patients using a battery of tests that are more quantitative than standard neurological rating scales; 2). to characterize the spatiotemporal dynamics of neural activity in the basal ganglia of individual PD patients who have undergone microelectrode-guided pallidotomy; 3). to determine the neuronal correlates, in the pallidum of the primary motor symptoms of PD by constructing a relational database of the results of the two components of the study. The results of the proposed work should lead to modifications of the current theories of the neural mechanisms underlying the motor symptoms of PD and guide others in their search for the cellular mechanisms which underlie the transformation of the normal striatum and globus pallidus following the loss of striatal dopamine.
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