Motor Control Deficits in Parkinson's Disease

描述(由申请人提供)：我们在当前资助期的发现使我们假设帕金森病(PD)患者的一个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获得中发挥着重要作用，此外，我们的初步数据与一般观察结果一致，即这些过程可能对当前的治疗方式相对耐受。加深我们对这一缺陷的理解，研究它对运动学习的影响，并研究多巴胺能疗法逆转这一缺陷的能力是本提案的指导目标。目前的提案提出了三个实验，旨在证实和扩展我们的假设，并调查多巴胺能疗法能够在多大程度上补救这些缺陷。前两个实验(具体目标1和2)介绍了受试者学习在虚拟环境中移动的要求，作为建立准确获得目标所必需的新的感觉-运动协调的先决条件。我们要求受试者掌握在他们手臂的表观(虚拟)和真实(恰当地发出信号)位置之间造成差异的扭曲，并将由此产生的学习推广到这个环境中未经训练的区域。通过将动作与他们正常的感觉对应分离，我们将挑战受试者重新配置他们感觉运动协调的能力。第三个实验(具体目标3)挑战患者，要求他们整合不同的运动动作，以便通过补偿躯干辅助伸展过程中躯干的机械扰动来获得视觉呈现的真实目标。我们将以前开发的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结合在一起。我们不仅将检查受试者的准确性，还将检查他们在不同条件和类型的强加扭曲下的运动路径、时间和结构，以衡量帕金森病患者在停药和接受多巴胺治疗时的表现和学习。通过对比帕金森病患者接受和不接受多巴胺能治疗前后的表现和能力与可比的正常人，我们既可以获得如何克服帕金森病功能障碍的线索，也可以深入了解基底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.