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

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，与运动控制密切相关，在帕金森病（PD）运动体征的发展中起调解作用，并在脑深部刺激（DBS）期间改善运动功能。然而，这些皮质运动区域在PD的运动体征和病理生理发展中的作用仍然不明确。同样，丘脑下核（STN）和白球内段（GPi）的DBS对MC和SMA神经元活动的影响在很大程度上是未知的。迄今为止，只有少数研究在帕金森病动物中检查了MC和SMA的神经元活动变化，而在STN或GPi的DBS中进行这些研究的研究就更少了。目前的建议将描述MPTP猴PD模型的这些变化，以及在DBS （STN和GPi）中，在休息和被动和主动运动期间，MC和SMA发生的神经元活动变化。我们将确定在DBS期间检测到的特定神经元活动变化是否与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在慢性单侧刺激期间大脑两侧皮层活动的变化，并将其与动物同侧和对侧运动体征的同步变化联系起来。这项研究将为PD的病理生理学提供新的见解，为DBS期间运动症状改善的皮质机制提供更好的理解，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皮层活动的神经元模式与运动体征的发展和改善相对应，并为设计编程算法提供具体的理论基础，这些算法旨在修改皮层活动，以优化接受DBS治疗的PD患者的临床结果，并形成闭环编程方法可以开发的基础。

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.