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

项目摘要/摘要 这项建议的总体目标是研究帕金森病患者大脑皮质网络活动的变化。 以及在DBS或左旋多巴治疗期间如何修改这些参数，以及运动体征的改善情况。 尽管多项研究检查了帕金森氏症患者基底节活动的变化 在这种状态下，对于皮质神经元的活动、功能、如何变化的研究很少，了解也很少 这些变化调节着运动体征的发育，或者它们在大脑深处的调节方式。 刺激(DBS)。在我们之前的提案中，我们在描述以下变化方面取得了重大进展 帕金森病患者辅助皮质和运动皮质(SMA和MC)的神经元活动 在STN或GPI DBS期间，使用MPTP猴帕金森病模型。目前的提议继续并扩大了范围 这项工作包括背外侧前额叶和背侧运动前皮质(DLPFC和PMD)， 已知的与基底节的解剖学联系，它与运动控制和 帕金森病运动体征的发生，但在帕金森病的非人类灵长类研究中基本上被忽略了 病理生理学。在这项建议中，我们将通过表征帕金森病患者的大脑皮质网络功能来研究帕金森病 帕金森病患者DLPFC、PMD、SMA和MC内和跨区神经元活动的变化 状态使用MPTP猴子模型的PD，检查DBS如何在内部和外部节段 苍白球(分别为GPI和GPE)和丘脑底核(STN)改变这种活动，以及 与左旋多巴的应用相比，与DBS相关的变化。我们会 使用Utah阵列同时记录DLPFC、PMD、SMA和MC中的细胞群 SMA中的DLPFC、PMD和MC，以及在静止和被动和主动运动期间的灰质设备 并比较以下情况下的结果：正常、帕金森病、帕金森病+DBS 不同部位(GPE、GPI和STN)和帕金森病+L-多巴(分别单独和合并DBS) 这三个站点)。我们将探讨GPE作为STN和GPI DBS的替代目标的作用 以前的研究表明，它对STN和GPI都有抑制作用。神经细胞的特征 活动性和连接性的变化将与帕金森氏症运动体征的发展相关，他们的 在DBS和L-多巴期间的改进，以及在计划、发起和执行动作方面的变化。

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.