Neurologists treating patients with movement disorders often encounter considerable heterogeneity of symptoms. While considerable progress has been made in the understanding of the pathophysiology and treatments of disorders such as Parkinson's Disease (PD), the varied presentations of this disease (e.g., tremor versus rigidity/bradykinesia) and how those clinical presentations are modulated by state of arousal remain poorly understood. The present proposal investigates the hypothesis that manifestations of movement disorders occurring at night reflect state-dependent alterations in the identical neural substrates also responsible for such clinical heterogeneity. The Parkinsonian condition provides an ideal opportunity to investigate this hypothesis since: 1) varying levels of cortically defined arousal in PD patients are commonly punctuated by specific forms of skeletomuscle activity; 2) neuronal output of the internal segment of the globus pallidus (GPi), whose dysfunction is central to models that account for manifestations of PD, target brainstem regions known to be important modulators of level of arousal; 3) the MPTP-primate model of Parkinsonism affords the unique opportunity to define the role of the GPi in electrophysiologically defined stares of activation. Ongoing human and animal protocols at Emory allow elucidation of the mechanisms underlying state-dependent motor control which we postulate to occur in PD. In humans, a recently initiate clinical trial assessing the efficacy of pallidotomy in affecting clinical features of Parkinson's Disease, such as tremor, rigidity, bradykinesia and dementia, presents a singularly unique opportunity to further understand nocturnal exacerbation of this disease. similarly, availability of primates subjected to experimentally-induced Parkinsonism through MPTP-injections will allow neurophysiologic, pharmacologic, and neuroanatomic understanding of how arousal state may modulate motor output form the GPi at the cellular level. The overall goal of this study is the elucidation of state-dependent motor control in neurologic illness via a coordinated effort of both clinical research and basic science.
Showing the most recent 10 out of 15 publications
