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 通过药理学或电生理学治疗可逆，可以增加我们对PD的理解 治疗和帮助照亮运动控制中的基底神经节-皮质回路的关键功能。 我们之前的发现使我们假设帕金森患者的主要困难是 疾病（PD）的关键是组装和使用新的感觉运动映射或协调。这些 过程在持续的运动表现和获得新技能方面都起着重要作用，我们 多巴胺（DA）替代疗法不能使其正常化。本提案提出 七个实验，旨在证实和扩展我们的假设，并调查程度， 丘脑底核的脑深部刺激（DBS）和DA替代疗法能够 修复感觉运动控制、协调和学习方面的缺陷。为了对比这些 在相同患者中进行治疗时，我们将在PD患者接受DA替代治疗之前， 手术植入的电极，并再次手术后打开和关闭深部脑刺激（和关闭 药物）。前4个实验检查视觉和本体感受信息的整合， 可能特别缺乏PD。受试者将达到视觉上呈现的3D目标， 在各种视觉反馈条件下用机器人手臂进行动觉测试。下一个实验介绍 要求主体学习在虚拟环境中移动，作为建立 新的感觉运动协调是准确获取目标所必需的。我们要求受试者 在表观（虚拟的）和真实的（本体感受信号）之间产生差异的失真 他们的手臂的位置。通过将运动与它们的正常感觉对应分离，我们将 挑战受试者重新配置感觉运动协调的能力。最后两个实验 通过要求患者将不同的运动动作整合成复杂的运动序列来挑战患者， 能够补偿这种动作期间的机械扰动。通过检查全方位的 行为，并需要协调的运动行为，利用可变的感觉信息来指导行为， 和学习新的感觉运动对应，我们可以得出一个更系统的评估 PD的运动控制及其治疗益处。我们认为，我们采取的方法，使用这种 当代技术，如3D沉浸式虚拟现实和机器人引导的3D到达 检查药物与手术治疗在多大程度上可以改善PD患者的功能障碍 是独一无二的.

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.