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: 9103227
• 负责人: Jerrold L Vitek
• 金额: $ 49.43万
• 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 2018-06-30
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/9103227
• 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; 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; motor symptom; neuronal patterning; nonhuman primate; programs; receptive field; reduce symptoms; somatosensory; symptomatic improvement

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）和补充运动区域（SMA）是与运动控制密切涉及的皮层皮质皮层和皮质皮层网络的组件，用于调解帕金森氏病（PD）运动迹象的发展，以及在深脑刺激过程中运动功能的改善（DBS）。然而，这些皮质运动区域在PD的运动体征和病理生理学发展中的作用仍然不明确。同样，DBS在丘脑下核（STN）和Globus Pallidus（GPI）对MC和SMA中神经元活性的影响在很大程度上尚不清楚。迄今为止，帕金森氏动物中只有少数研究检查了MC和SMA的神经元活动变化，而在STN或GPI中DBS进行了这些研究的较少研究。当前的建议将在PD的MPTP猴子模型中表征这些变化，以及在DBS（STN和GPI）（在被动和主动运动过程中）在DBS（STN和GPI）期间MC和SMA中发生的那些神经元活性变化。我们将确定特定的神经元活性的变化是否与DBS期间检测到的运动症状的改善相关。此外，在慢性单侧刺激期间，我们将使用慢性植入的微阵列来评估大脑每一侧的皮质活性的变化，这将它们与动物的同侧和对侧边的运动迹象的一致变化相关。这项研究将提供有关PD病理生理学的新见解，为DBS期间运动症状改善的基础的皮质机制提供了更深入的了解，并研究了基于单侧刺激过程中同侧运动体征改善的皮质机制。这项研究的结果将使我们能够确定哪些皮质活动的神经元模式对应于运动迹象的发展和改进，并为设计用于设计皮质活动的编程算法提供了特定的理由，以优化用DBS处理的PD患者的临床结果，并在哪些封闭循环编程中形成基础，可以开发出封闭的循环方法。