Invasive Approach to Model Human Cortex-Basal Ganglia Action-Regulating Networks

项目摘要/摘要 行动的发起和抑制是日常行为的关键部分，而这些行为的基础是行动 压制。这包括(1)在从备选方案中选择一个动作时抑制竞争动作(2) 当出现冲突信息时抑制所有响应，直到可以做出正确的决定，并且 (3)当环境迅速变化时抑制响应，表明必须预先计划响应 停下来了。文献表明，这三种功能是由不同的额基底节(BG)支持的。 电路。然而，这方面的证据只是零碎的，因为很少有研究同时记录大脑皮质和 具有足够的空间、时间和光谱分辨率的皮质下区域，同时受试者执行多个 任务。我们假设，在选择、冲突和停止过程中的抑制涉及可分离的额叶-BG 回路--不同的额叶皮质区域与不同的BG区域进行因果联系。我们将对此进行测试 利用脑深部刺激(DBS)手术的独特机会进行全面假设 对于帕金森氏症，在3个动作抑制任务中获得多焦点皮质和BG记录 (自定步速移动、埃里克森侧翼任务和停止信号)。我们将跨多个比例进行录制-单个 单位活度、局部场势和功能磁共振成像-获得足以测试 假设。在具体目标1中，我们的目标是证明空间上、时间上和光谱上是可分离的 电路使用非常高的单位的空间和时间精度来调节不同类型的动作抑制 丘脑底核和苍白球记录的活动和局部场电位(LFP) 内侧(GPI)和同时记录的来自3个皮质区域的丰富频谱的皮层脑电(ECoG) (前运动和主运动、前辅助运动和右侧额下回)。在具体目标2中，我们将 使用侵入性脑刺激进一步表征这些额叶-BG环路的可分离性。我们 假设DBS引起的跨不同抑制任务的损害/改善模式与 在额叶-BG网络招募方面存在着相对于刺激部位的差异。我们将使用并发功能磁共振 使用DBS来评估DBS在不同任务中对大脑活动的不同影响。我们还将研究星展银行如何在 磁共振引导下睡眠DBS患者不同的STN病灶诱发不同的脑网络 植入物。这些研究将指导有创术中刺激的神经生理记录 星展银行的手术。在具体目标3中，我们将采用基于生物的动态计算行动模型 选择添加动作抑制功能。我们将把这个模型与电生理数据进行匹配 评估行动、保留和选择的几种计算理论。影响是广泛的，包括 行为调控的基础科学，作用是独立但平行的人脑远程网络 动作调节，了解DBS如何以不同方式调节动作抑制功能，并最终 用于调节人类在各种紊乱中的行为的特定电路植入物。

Project Summary/Abstract Action initiation and withholding are key parts of everyday behavior, and underlying these is action suppression. This includes (1) suppressing competing actions when selecting one action from alternatives (2) suppressing all responses when presented with conflicting information until a proper decision can be made and (3) suppressing a response when the environment rapidly changes indicating a pre-planned response must be stopped. The literature suggests that these three functions are supported by distinct fronto-basal ganglia (BG) circuits. Yet the evidence for this is only piecemeal as few studies simultaneously record from both cortical and subcortical regions with sufficient spatial, temporal, and spectral resolution while subjects perform multiple tasks. We hypothesize that suppression during selection, conflict and stopping involve dissociable fronto-BG circuits – that different frontal cortical regions causally communicate with different BG regions. We will test this over-arching hypothesis by taking advantage of the unique opportunity of deep brain stimulation (DBS) surgery for Parkinson’s disease, to obtain multi-focal cortical and BG recordings across 3 action suppression tasks (self-paced movement, Eriksen Flanker task, and stop signal). We will record across multiple scales – single unit activity, local field potentials, and fMRI - the only way to attain spatio-temporal data sufficient to test the hypothesis. In Specific Aim 1, we aim to demonstrate that spatially, temporally, and spectrally dissociable circuits mediate distinct types of action suppression using the very high spatial and temporal precision of unit activity and local field potentials (LFPs) recorded from the subthalamic nucleus (STN) and globus pallidus internus (GPi) and simultaneously recorded, spectrally rich electrocorticography (ECoG) from 3 cortical regions (pre- and primary motor, pre-supplementary motor, and right inferior frontal gyrus). In Specific Aim 2, we will use invasive brain stimulation to further characterize the separability of these fronto-BG circuits. We hypothesize that DBS-induced patterns of impairment/improvement across different suppression tasks relates to differences in fronto-BG network recruitment relative to the site of stimulation. We will use concurrent fMRI with DBS to evaluate disparate effects of DBS on brain activity across tasks. We will also examine how DBS at different STN foci evokes distinct brain networks using fMRI in patients undergoing asleep MR-guided DBS implants. These studies will guide invasive neurophysiological recordings with intraoperative stimulation during DBS surgery. In Specific Aim 3, we will adapt a dynamic biologically-grounded computational model of action choice to add an action suppression function. We will fit this model to the electrophysiological data and evaluate several computational theories of action withholding and choice. The impact is widespread, including the basic science of action regulation, the role of separate but parallel long-range human brain networks for action regulation, understanding how DBS differentially modulates action suppression functions, and ultimately for circuit-specific implants that modulate human action in various disorders.