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

项目总结/摘要 这个建议的总体目标是检查帕金森病状态下皮层网络活动的变化 以及在DBS或左旋多巴给药期间这些是如何改变的，以及运动体征的改善。 虽然多项研究已经检查了帕金森病患者基底神经节活动的变化， 状态，很少有研究和了解皮质神经元活动，功能，如何改变， 这些变化介导了运动信号的发展，或者说它们是如何在大脑深部被调制的。 刺激（DBS）。在我们先前的提案中，我们在描述 在帕金森病条件下辅助和运动皮质（SMA和MC）中的神经元活动， 使用PD的MPTP猴模型在DBS或GPi DBS期间。目前的建议继续并扩大了 这项工作包括背外侧前额叶和背侧前运动皮层（DLPFC和PMd）， 已知的解剖连接到基底神经节，这是密切参与运动控制和在 帕金森病运动体征的发展，但在PD的非人灵长类动物研究中， 病理生理学在这个建议中，我们将通过表征帕金森病患者的大脑皮层， 帕金森病患者DLPFC、PMd、SMA和MC内和跨这些区域的神经元活动变化 状态使用MPTP猴模型的PD，检查如何DBS在内部和外部段的 苍白球（GPi和GPe，分别）和丘脑底核（ESTA）修改这一活动，以及如何 与DBS相关的变化与左旋多巴给药相关的变化相比。我们将 使用犹他州阵列同时记录DLPFC、PMd、SMA和MC中的细胞群。 DLPFC、PMd和MC，以及SMA中的灰质器械，在静息时以及被动和主动运动期间 并比较以下情况下的结果：正常、帕金森病、帕金森病+ DBS三种情况 不同部位（GPe、GPi和DBS）和帕金森综合征+左旋多巴（单独和与DBS联合， 三个网站）。我们将探讨GPe作为替代目标的作用，以取代GPi DBS和GPi DBS。 先前的研究表明其对P2P和GPi的抑制作用。神经元的特征 活动和连接的变化将与帕金森运动体征的发展相关， DBS和L-多巴期间的改善以及运动计划、启动和执行的变化。

PROJECT SUMMARY/ABSTRACT The overall goal of this proposal is to examine the changes in cortical network activity in the parkinsonian state and how these are modified during DBS or administration of levodopa and improvement in motor signs. Although multiple studies have examined the changes in basal ganglia activity that occur in the parkinsonian state, there are few studies and little understanding of the changes in cortical neuronal activity, function, how these changes mediate the development of motor signs, or how they are modulated during deep brain stimulation (DBS). In our previous proposal we have made significant strides in characterizing the changes in neuronal activity in the supplementary and motor cortices (SMA and MC) in the parkinsonian condition and during STN or GPi DBS using the MPTP monkey model of PD. The current proposal continues and broadens this work to include the dorsolateral prefrontal and dorsal premotor cortices (DLPFC and PMd), areas with known anatomical connections to the basal ganglia, which are intimately involved in motor control and in the development of parkinsonian motor signs but have been largely ignored in nonhuman primate studies of PD pathophysiology. In this proposal we will examine cortical network function in PD by characterizing the changes in neuronal activity that occur within and across the DLPFC, PMd, SMA and MC in the parkinsonian state using the MPTP monkey model of PD, examine how DBS in the internal and external segments of the globus pallidus (GPi and GPe, respectively) and subthalamic nucleus (STN) modify this activity, and how the changes associated with DBS compare to that which occurs with administration of levodopa. We will simultaneously record from populations of cells in the DLPFC, PMd, SMA and MC using Utah arrays in the DLPFC, PMd, and MC, and Gray Matter devices in the SMA, at rest and during passive and active movement and compare results across the following conditions: normal, parkinsonian, parkinsonian + DBS in three different sites (GPe, GPi and STN), and parkinsonism + L-dopa (alone and in combination with DBS in each of the three sites). We will explore the role of GPe as an alternative target to STN and GPi DBS given our previous studies demonstrating its suppressive effects on both STN and GPi. Characteristics of neuronal activity and connectivity changes will be correlated with the development of parkinsonian motor signs, their amelioration during DBS and L-dopa and to changes in the planning, initiation and execution of movement.