PALLIDAL PHYSIOLOGY IN HUMAN AND PRIMATE DYSTONIA

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DESCRIPTION (Adapted From The Applicant's Abstract): Dystonia is a movement disorder defined as a syndrome of sustained muscle contractions, causing twisting and repetitive movements, and abnormal postures. Its pathophysiology is poorly understood. Recently, attempts have been made to understand movement disorders in terms of alterations in a loop circuit involving, the cortex, basal ganglia and thalamus. The globus pallidus occupies a critical position in this circuit since it is the major output structure of the basal ganglia. Another movement disorder, Parkinson's disease, has been found to be associated with excessive and abnormally patterned pallidal activity. This finding has led to improved surgical treatments for Parkinson's disease by pallidal inactivation. In contrast to PD, a better understanding of dystonia has been hampered by a lack of data on the physiology of the basal ganglia in this condition, and by the lack of a well-characterized animal model of dystonia. Both problerns are addressed in this proposal. Single unit-recording in the external and internal pallidum is routinely performed for surgical navigation during the course of lesioning or electrode implantation into the globus pallidus. Spontaneous and movement-related discharges recorded during such surgeries will be analyzed. Similar recordings will be obtained in a primate model of focal arm dystonia, in which dystonia is generated by repetitive performance of a skilled motor task. The effect on motor performance of lesioning the globus pallidus in primate focal dystonia will be analyzed. The experiments will test the following hypotheses: 1.) Dystonia in humans is associated with abnormal neuronal discharge in the g1obus pallidus. 2.) Similar abnormalities of pallidal discharge are present in a primate model of dystonia. 3.) Inactivation of the globus pallidus in the primate model improves motor performance in the dystonic hand and prevents the induction of dystonia in normal primates. These experiments will confirm or refute existing theories of the pathophysiology of dystonia as well as provide theoretical support for the treatment of dystonia by pallidal surgery.