Motor Control Deficits in Parkinson's Disease

了解帕金森病（PD）功能障碍的范围及其程度

Understanding the range of dysfunctions in Parkinson's disease (PD), and the degrees to which they are reversible by pharmacological or electrophysiological treatments, can both increase our understanding of PD therapies and help illuminate critical functions of basal ganglia-cortical circuits in the control of movement. Our previous findings 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 processes play a major role both in ongoing motor performance and in the acquisition of new skills, and, we are finding, are not normalized with dopamine (DA) replacement therapy. The present proposal presents seven experiments that are designed to confirm and extend our hypothesis and to investigate the degrees to which deep brain stimulation to the subthalamic nucleus (STN DBS) and DA replacement therapy are able to remediate deficits in sensorimotor control, coordination, and learning. To contrast the effects of these therapies in the same patients, we will test PD patients ON versus OFF DA replacement prior to their having surgically implanted electrodes, and again after surgery ON and OFF deep brain stimulation (and off medications). The first 4 experiments examine the integration of visual and proprioceptive information, which may be particularly deficient in PD. Subjects will reach to 3D targets presented either visually or kinesthetically with a robot arm under various conditions of visual feedback. The next experiment introduces 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 that create discrepancies between the apparent (virtual) and real (proprioceptively signaled) location of their arms. By dissociating movements from their normal sensory correspondences, we will challenge subjects' abilities to reconfigure their sensorimotor coordinations. The final 2 experiments challenge patients by requiring them to integrate different motor acts into a complex motor sequence and to be able to compensate for a mechanical perturbation during such an action. By examining a full range of behaviors, and requiring coordinated motor acts, utilization of variable sensory information to guide behavior, and the learning new sensorimotor correspondences, we can come to a more systematic assessment of motor control in PD and its benefit by treatment. We feel that the approach we take of using such contemporary technologies as 3D immersive virtual realities and robot-guided 3D reaching in examining the degree to which medical versus surgical therapies can ameliorate dysfunctions in PD is unique.