Understanding Circuit Dynamics in Parkinson's Disease using Real-Time Neural Control

使用实时神经控制了解帕金森病的电路动力学

• 批准号: 10703251
• 负责人: Joshua E Aman
• 金额: $ 18.56万
• 依托单位: UNIVERSITY OF MINNESOTA
• 依托单位国家: 美国
• 财政年份: 2021
• 资助国家: 美国
• 起止时间: 2021-09-17 至 2026-07-31
• 项目状态: 未结题
• 来源: https://reporter.nih.gov/project-details/10703251
• 关键词: Address; Affect; Basal Ganglia; Bradykinesia; Brain; Brain region; Computer Models; Data; Dedications; Deep Brain Stimulation; Development; Electric Stimulation; Electrocorticogram; Electrophysiology (science); Elements; Frequencies; Functional disorder; Generations; Globus Pallidus; Goals; Image; Implant; Incidence; Knowledge; Levodopa; Link; Location; Measures; Modeling; Motor; Motor Manifestations; Neurons; Parkinson Disease; Pathway interactions; Patients; Prefrontal Cortex; Process; Research; Resolution; Role; Severities; Structure of subthalamic nucleus; Techniques; Testing; Time; Work; catalyst; cohort; high resolution imaging; improved; insight; motor control; motor disorder; neural; neural circuit; neuroregulation; response; theories; time use; treatment optimization

ABSTRACT (CATALYST PROJECT) While much research has been dedicated to understanding the pathophysiology of Parkinson’s disease (PD), the neural circuit dynamics underlying the manifestation of motor signs remain to be determined. Current theories propose that the power and incidence of beta band (11-35 Hz) oscillations, synchronized throughout the basal ganglia thalamocortical (BGTC) circuit, are associated with the severity of motor signs. Although changes in bradykinesia and rigidity related to levodopa and deep brain stimulation (DBS) have been shown to correlate with the power of local field potential (LFP) oscillations in the subthalamic nucleus (STN), no study has deductively demonstrated their causal relationship. Clarifying whether this relationship is causal or epiphenomenon is critical to advance our understanding of PD pathophysiology. The goal of this Catalyst Project is to characterize the relationship of rigidity and bradykinesia with beta band oscillations and their propagation dynamics in the BGTC circuit. We will leverage a new neural control approach capable of suppressing or amplifying frequency-specific neural oscillations in real-time using DBS leads. This technique, referred to as evoked-interference closed-loop DBS (eiDBS), is based on the concept that electrical stimulation with precise amplitude and timing can evoke neural responses that modulate spontaneous neural activity via constructive or destructive interference. We will characterize how controlled suppression or amplification of beta band activity in the internal segment of the globus pallidus (GPi) or the STN via eiDBS relates to the severity of rigidity and bradykinesia in PD patients. We will also test the hypothesis that changes in the propagation of beta band oscillations (information flow) across the GPi, STN, motor (MC), premotor (PMC), and dorsolateral prefrontal (DLPFC) cortices will be better correlated with rigidity and bradykinesia than the amplitude of beta band oscillations alone (Aims 1,2). Furthermore, we will characterize the spectral, temporal, and spatial dynamics of neural responses in the BGTC circuit evoked by stimulation in the GPi and STN. By combining the evoked response (ER) data with high-resolution imaging and computational modeling, we will delineate how activation of distinct neuronal pathways in the GPi and STN influences ER dynamics, critical not only to optimize eiDBS, but also to provide insights into the mechanism(s) of action of DBS (Aim 3).

摘要（催化剂项目） 尽管很多研究都致力于了解帕金森氏病（PD）的病理生理学，但 电动标志表现的基础的神经回路动力学仍有待确定。当前理论 提出的β频段（11-35 Hz）振荡的功率和发生率，在整个基本的范围内同步 神经节丘脑皮层（BGTC）电路与运动符号的严重程度有关。虽然变化 与左旋多巴和深脑刺激有关 凭借丘脑下核（STN）中局部场电位（LFP）振荡的功能，没有研究 演绎地证明了他们的因果关系。澄清这种关系是因果关系还是 epiphenomenon对于促进我们对PD病理生理学的理解至关重要。该催化剂的目标 项目是为了表征刚性和铁趋化度的关系与β频段振荡和 它们在BGTC电路中的传播动力学。我们将利用一种新的神经控制方法 使用DBS Leads实时抑制或放大频率特异性神经振荡。这 技术，称为诱发干扰闭环DB（EIDB），是基于电气的概念 用精度放大器和时机刺激可以引起神经反应，从而调节自发神经 通过建设性或破坏性干扰活动。我们将表征如何受控抑制或 通过EIDBS的Globus Pallidus（GPI）或STN的内部段中β带活性的扩增 与PD患者的刚性和头肌障碍的严重程度有关。我们还将测试变化的假设 在GPI，STN，Motor（MC）的Beta频段振荡（信息流）的传播中 和背侧前额叶（DLPFC）皮质将与刚度和僵硬的关系更好 仅β带振荡的振幅（目标1,2）。此外，我们将表征光谱，暂时的 GPI和STN中刺激引起的BGTC电路中神经反应的空间动力学。经过 将诱发响应（ER）数据与高分辨率成像和计算建模相结合，我们将 描述GPI和STN中不同神经元途径的激活如何影响ER动态，而不是关键 仅仅是为了优化EIDB，还可以提供有关DBS作用机制的见解（AIM 3）。