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

模拟人类皮层基底神经节动作调节网络的侵入性方法

• 批准号: 9356331
• 负责人: NADER POURATIAN
• 金额: $ 120.7万
• 依托单位: UNIVERSITY OF CALIFORNIA LOS ANGELES
• 依托单位国家: 美国
• 财政年份: 2016
• 资助国家: 美国
• 起止时间: 2016-09-30 至 2019-08-31
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/9356331
• 关键词: Address; Affect; Area; Basal Ganglia; Basic Science; Behavior; Behavioral; Biological; Brain; Brain region; Clinical; Communities; Computer Simulation; Conflict (Psychology); Data; Databases; Decision Making; Deep Brain Stimulation; Disease; Dorsal; Effectiveness; Electrocorticogram; Electrophysiology (science); Environment; Failure; Functional Magnetic Resonance Imaging; Gilles de la Tourette syndrome; Globus Pallidus; Human; Impairment; Implant; Impulsivity; Inferior frontal gyrus; Lesion; Liquid substance; Literature; Maps; Mediating; Microelectrodes; Modeling; Motor; Movement; Muscle; Nervous System Physiology; Obsessive-Compulsive Disorder; Operative Surgical Procedures; Output; Parkinson Disease; Pathway Analysis; Patients; Pattern; Recruitment Activity; Regulation; Research; Resolution; Rewards; Role; STN stimulation; Signal Transduction; Site; Specificity; Structure of subthalamic nucleus; Testing; Therapeutic; Time; frontal lobe; human data; implantation; improved; innovation; neural circuit; neurophysiology; neuropsychiatric disorder; neurorestoration; number theory; programs; relating to nervous system; response; sensory input; spatiotemporal; theories

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.

项目总结/摘要 行动启动和抑制是日常行为的关键部分，而这些行为的基础是行动 镇压这包括（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，直到可以做出适当的决定， (3)当环境快速变化时抑制响应，指示预先计划的响应必须 停止.文献表明，这三种功能是由不同的额基底神经节（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层和大脑皮层的变化。 皮层下区域具有足够的空间，时间和光谱分辨率，而受试者执行多个 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-BG 不同的额叶皮层区域与不同的BG区域进行因果联系。我们将测试这个 利用脑深部电刺激（DBS）手术的独特机会， 对于帕金森病，在3个动作抑制任务中获得多灶性皮质和BG记录 （自主节奏运动、Eriksen Flanker任务和停止信号）。我们将在多个尺度上记录-单 单位活动，局部场电位和功能磁共振成像-唯一的方法来获得时空数据足以测试 假说.在具体目标1中，我们的目标是证明空间，时间和光谱可分离 电路使用非常高的空间和时间精度的单位来调解不同类型的动作抑制 活动和局部场电位（LFPs）记录从丘脑底核（ESTA）和苍白球 内肌（GPi）和同时记录的3个皮层区域的丰富频谱皮层电图（ECoG） (pre-以及主运动、前辅助运动和右额下回）。在第二阶段，我们将 使用侵入性脑刺激来进一步表征这些额叶BG回路的可分离性。我们 假设DBS诱导的不同抑制任务中的损伤/改善模式与 额-BG网络募集相对于刺激部位的差异。我们将使用同步功能磁共振成像 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DBS如何在 在接受睡眠MR引导DBS的患者中，使用fMRI，不同的MRI病灶引起不同的脑网络 植入物.这些研究将指导术中刺激的侵入性神经生理记录， DBS手术。在具体目标3中，我们将采用动态生物学基础的行动计算模型 选择添加动作抑制功能。我们将把这个模型与电生理数据拟合， 评价几种行为抑制和选择的计算理论。影响广泛，包括 行动调节的基础科学，独立但平行的长距离人脑网络的作用， 动作调节，了解DBS如何差异调节动作抑制功能，并最终 用于调节人类在各种疾病中的行为的电路特定植入物。