Our findings in the current grant period have led us to hypothesize that a major difficulty for patients with Parkinson disease (PD) is in assembling and using new sensorimotor mappings or coordinations. These process play a major role both in ongoing motor performance and in the acquisition of new skills, in addition, our preliminary data are consistent with a general observation that these processes may be relatively resistant to current therapeutic modalities. Furthering our understanding of this deficit, examining its impact on motor learning, and investigating the ability of dopaminergic therapy to reverse this deficit are the guiding aims of this proposal. The present proposal presents three experiments that are designed to confirm and extend our hypothesis and to investigate the degree to which dopaminergic therapy is able to remediate these deficits. The first two experiments (Specific Aims 1 and 2) introduce the requirement that subjects learn to move within a virtual environment as a prerequisite to establishing the new sensorimotor coordinations necessary for accurate target acquisition. We require subjects to master distortions which create discrepancies between the apparent (virtual) and real (proprioceptively signaled) location of their arms and to generalize the resulting learning to untrained regions of this environment. By dissociating movements from their normal sensory correspondences, we will challenge subjects' abilities to reconfigure their sensorimotor coordinations. The third experiment (Specific Aim 3) challenges patients by requiring them to integrate different motor acts in order to acquire visually-presented, real targets by compensating for a mechanical perturbation of the trunk during a trunk-assisted reach. We have integrated and coupled our previously developed system for analysis and display of three dimensional movements with our newly developed virtual reality environment. We will examine not only subjects' accuracy, but also the path, timing, and structure of their movements under different conditions and types of imposed distortions, in order to measure both performance and learning when PD patients are OFF versus ON dopaminergic therapy. By contrasting the performance and capacities of PD patients on and off dopaminergic therapy to that of comparable normals, we can both obtain clues as to how to overcome PD dysfunction and gain an insight into the key role of the basal ganglia in movement.
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