Motor Control Deficits in Parkinson's Disease

帕金森病的运动控制缺陷

• 批准号: 7563312
• 负责人: Howard Poizner
• 金额: $ 33.8万
• 依托单位: UNIVERSITY OF CALIFORNIA, SAN DIEGO
• 依托单位国家: 美国
• 财政年份: 1997
• 资助国家: 美国
• 起止时间: 1997-07-01 至 2012-06-30
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/7563312
• 关键词: Affective; Area; Basal Ganglia; Behavior; Behavioral; Body Surface; Carbon; Classification; Complex; Data; Deep Brain Stimulation; Disease; Dopamine; Dopaminergic Agents; Electrodes; Environment; Feedback; Functional disorder; Grant; Hand; Impairment; Implanted Electrodes; Knowledge; Learning; Limb structure; Literature; Location; Maps; Mechanics; Medical; Modality; Motor; Movement; Operative Surgical Procedures; Outcome; Output; Parkinson Disease; Patients; Performance; Pharmaceutical Preparations; Pharmacotherapy; Play; Prior Therapy; Process; Proprioception; Quality of life; Relative (related person); Replacement Therapy; Robot; Role; Scheme; Sensory; Signal Transduction; Speed; Structure of subthalamic nucleus; System; Technology; Testing; Therapeutic; Touch sensation; Upper arm; Vision; Visual; deep brain stimulator; design; functional restoration; grasp; implantation; improved; motor control; motor learning; novel; public health relevance; research study; retinal rods; sensory integration; skills; virtual; virtual reality; visual feedback; visual motor

DESCRIPTION (provided by applicant): 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, preliminary data indicate, are not normalized with dopamine (DA) replacement therapy. The present proposal presents seven experiments that are designed to confirm and extend this 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, PD patients will be tested 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. Subjects are required 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, subjects' abilities to reconfigure their sensorimotor coordinations will be challenged. The final 2 experiments challenge subjects 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, a more systematic assessment of motor control in PD and its benefit by treatment can be obtained. The proposed approach 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. PUBLIC HEALTH RELEVANCE: A major question in the treatment of Parkinson's disease is the degree to which different therapies can ameliorate the range of dysfunctions that are a product of the disorder. Surgical implantation of deep brain stimulators, especially those targeted to the subthalamic nucleus, is an increasingly important modality for treatment and restoring function and quality of life in Parkinson's disease. The proposed studies will compare which deficits in sensorimotor control and learning deep brain stimulation therapy versus dopaminergic replacement therapy can reverse and which they cannot, and thus should fill an important gap in the literature that can inform treatment decisions.

描述(申请人提供)：了解帕金森氏病(PD)的功能障碍范围，以及它们可被药物或电生理治疗逆转的程度，既可以增加我们对PD治疗的理解，也有助于阐明基底节-皮质回路在运动控制中的关键功能。我们以前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，初步数据表明，多巴胺(DA)替代疗法并不能使这些过程正常化。本文提出了七个实验，旨在证实和扩展这一假说，并研究丘脑底核脑深部刺激(STN DBS)和DA替代疗法在多大程度上能够补救感觉运动控制、协调和学习方面的缺陷。为了对比这些疗法在相同患者中的效果，帕金森病患者将在接受手术植入电极之前接受DA替代治疗，并在手术后接受和停止脑深部刺激(和停止药物治疗)。前4个实验考察了视觉和本体感觉信息的整合，这可能是帕金森病中特别缺乏的。受试者将在不同的视觉反馈条件下，通过机械臂达到以视觉或运动方式呈现的3D目标。下一个实验引入了受试者学习在虚拟环境中移动的要求，作为建立准确获取目标所必需的新的感觉运动协调的先决条件。受试者被要求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。通过将运动与正常的感觉对应分离，受试者重新调整其感觉运动协调的能力将受到挑战。最后两个实验挑战受试者，要求他们将不同的马达动作整合成一个复杂的马达序列，并能够在这样的动作中补偿机械扰动。通过检查一系列的行为，并要求协调运动行为，利用不同的感觉信息来指导行为，学习新的感觉-运动对应关系，可以获得对帕金森病运动控制及其治疗益处的更系统的评估。提出的使用3D沉浸式虚拟现实和机器人引导的3D到达等当代技术来检查内科和外科治疗改善PD功能障碍的程度的方法是独一无二的。公共卫生相关性：帕金森氏症治疗中的一个主要问题是，不同的治疗方法可以在多大程度上改善作为该疾病产物的一系列功能障碍。脑深部刺激器的外科植入，尤其是针对丘脑底核的刺激器，在帕金森病的治疗和恢复功能和生活质量方面正变得越来越重要。拟议的研究将比较感觉运动控制和学习深部脑刺激疗法与多巴胺能替代疗法中哪些缺陷可以逆转，哪些不能逆转，从而填补可以为治疗决策提供信息的文献中的一个重要空白。