Neuronal Activity in MC and SMA during STN and GPi DBS in the Parkinsonian Monkey

帕金森猴 STN 和 GPi DBS 期间 MC 和 SMA 的神经元活动

• 批准号: 8690182
• 负责人: Jerrold L Vitek
• 金额: $ 51.62万
• 依托单位: UNIVERSITY OF MINNESOTA
• 依托单位国家: 美国
• 财政年份: 2012
• 资助国家: 美国
• 起止时间: 2012-07-15 至 2017-06-30
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/8690182
• 关键词: 1-Methyl-4-phenyl-1,2,3,6-tetrahydropyridine; Acute; Affect; Algorithms; Animals; Area; Bilateral; Bradykinesia; Brain; Brain region; Characteristics; Chronic; Clinical; Contralateral; Deep Brain Stimulation; Development; Diagnosis; Disease; Dyskinetic syndrome; Electric Stimulation; Evolution; FDA approved; Frequencies; Functional disorder; Globus Pallidus; Goals; Implant; Ipsilateral; Knowledge; Location; Longitudinal Studies; Mediation; Methods; Microelectrodes; Modeling; Monkeys; Motion; Motor; Motor Cortex; Movement; Movement Disorders; Neurons; Noise; Outcome; Parkinson Disease; Parkinsonian Disorders; Patients; Pattern; Performance; Pharmaceutical Preparations; Reaction Time; Relative (related person); Rest; Role; Severities; Side; Signal Transduction; Site; Specificity; Structure of subthalamic nucleus; Symptoms; System; Thalamic structure; Therapeutic; Work; advanced disease; base; design; implantable device; improved; insight; kinematics; motor control; neuronal patterning; nonhuman primate; programs; receptive field; somatosensory

DESCRIPTION (provided by applicant): The motor cortex (MC) and supplementary motor area (SMA) are components of a subcortical-cortical and cortical-cortical network intimately involved in motor control, in mediation of the development of motor signs in Parkinson's disease (PD), and the improvement in motor function during deep brain stimulation (DBS). Yet, the role of these cortical motor areas in the development of motor signs and pathophysiology of PD remains ill-defined. Similarly, the effects of DBS in the subthalamic nucleus (STN) and internal segment of the globus pallidus (GPi) on neuronal activity in the MC and SMA are largely unknown. To date, there are only a few studies in parkinsonian animals that have examined neuronal activity changes in the MC and SMA and fewer still that have performed these studies during DBS in the STN or GPi. The current proposal will characterize these changes in the MPTP monkey model of PD and those neuronal activity changes that occur in the MC and SMA during DBS (STN and GPi) both at rest and during passive and active movement. We will determine if specific neuronal activity changes correlate with improvements in motor symptoms detected during DBS. In addition, we will use chronically implanted microarrays to assess the changes in cortical activity on each side of the brain during chronic unilateral stimulation correlating them to coincident changes in motor signs on both the ipsilateral and contralateral sides of the animal. This study will provide new insights into the pathophysiology of PD, provide a greater understanding of the cortical mechanisms underlying the improvement in motor symptoms during DBS and investigate the cortical mechanisms that underlie improvement in ipsilateral motor signs during unilateral stimulation. Results from this study will allow us to beter determine which neuronal patterns of cortical activity correspond to the development of, and improvement in, motor signs and provide specific rationale for designing programming algorithms directed at modifying cortical activity to optimize clinical outcomes in PD patients treated with DBS and form the basis upon which closed loop programming methods could be developed.

描述（由申请人提供）：运动皮层（MC）和辅助运动区（SMA）是皮层下-皮层和皮层-皮层网络的组成部分，密切参与运动控制、调节帕金森病（PD）运动体征的发展以及深部脑刺激（DBS）期间运动功能的改善。然而，这些皮质运动区在帕金森病运动体征和病理生理学发展中的作用仍然不明确。同样，丘脑底核 (STN) 和苍白球内段 (GPi) 中的 DBS 对 MC 和 SMA 神经元活动的影响在很大程度上尚不清楚。迄今为止，只有少数针对帕金森病动物的研究检查了 MC 和 SMA 中的神经元活动变化，而在 DBS 期间对 STN 或 GPi 进行这些研究的研究则更少。目前的提案将描述 PD 的 MPTP 猴模型中的这些变化，以及在静息和被动和主动运动期间 DBS（STN 和 GPi）期间 MC 和 SMA 中发生的神经元活动变化。我们将确定特定的神经元活动变化是否与 DBS 期间检测到的运动症状的改善相关。此外，我们将使用长期植入的微阵列来评估慢性单侧刺激期间大脑两侧皮质活动的变化，将它们与动物同侧和对侧运动体征的一致变化相关联。这项研究将为 PD 的病理生理学提供新的见解，更好地了解 DBS 期间运动症状改善的皮质机制，并研究单侧刺激期间同侧运动症状改善的皮质机制。这项研究的结果将使我们能够更好地确定哪些皮质活动的神经元模式与运动体征的发展和改善相对应，并为设计旨在修改皮质活动的编程算法提供具体的原理，以优化接受 DBS 治疗的 PD 患者的临床结果，并构成开发闭环编程方法的基础。