Motor Control Deficits in Parkinson's Disease

描述（由申请人提供）：我们在当前资助期的研究结果使我们假设帕金森病（PD）患者的主要困难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新技能的习得中都起着重要作用，此外，我们的初步数据与一般观察一致，即这些过程可能相对抵抗当前的治疗方式。进一步了解这种缺陷，检查其对运动学习的影响，并研究多巴胺能治疗逆转这种缺陷的能力是本建议的指导目标。本提案提出了三个实验，旨在证实和扩展我们的假设，并调查多巴胺能治疗能够弥补这些缺陷的程度。前两个实验（具体目标1和2）要求受试者学习在虚拟环境中移动，这是建立准确目标获取所需的新感觉运动协调的先决条件。我们要求受试者掌握扭曲，这些扭曲会造成他们手臂的明显（虚拟）和真实（本体感觉信号）位置之间的差异，并将由此产生的学习推广到该环境的未经训练的区域。通过将运动从正常的感觉对应中分离出来，我们将挑战受试者重新配置感觉运动协调的能力。第三个实验（Specific Aim 3）要求患者整合不同的运动动作，通过补偿躯干在辅助伸展过程中的机械扰动来获得视觉上呈现的真实目标。我们已经将我们之前开发的用于分析和显示三维运动的系统与我们新开发的虚拟现实环境集成并耦合在一起。我们不仅会检查受试者的准确性，还会检查他们在不同条件和施加的扭曲类型下的运动路径、时间和结构，以衡量PD患者在关闭和打开多巴胺能治疗时的表现和学习。通过对比PD患者在多巴胺能治疗前后与正常人的表现和能力，我们既可以获得如何克服PD功能障碍的线索，也可以深入了解基底神经节在运动中的关键作用。

DESCRIPTION (provided by applicant): 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.