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

摘要(催化剂项目) 虽然许多研究致力于了解帕金森氏病(PD)的病理生理学， 运动体征表现背后的神经回路动力学仍有待确定。当前的理论 提出了β频段(11-35赫兹)振荡的功率和入射频率，在整个基础上同步 丘脑皮质神经节(BGTC)回路，与运动体征的严重程度有关。尽管更改了 与左旋多巴和脑深部刺激(DBS)相关的运动迟缓和强直已被证明是相关的 关于丘脑底核(STN)局部场电位(LFP)振荡的威力，还没有研究 演绎地证明了它们之间的因果关系。澄清这种关系是因果关系还是 副反应是提高我们对帕金森病病理生理学认识的关键。此催化剂的目标是 项目是描述僵直和运动迟缓与β波段振荡和 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导联实时抑制或放大特定频率的神经振荡。这 这项技术被称为诱发干扰闭环式DBS(EiDBS)，是基于以下概念的 具有精确的幅度和时间的刺激可以唤起调节自发神经的神经反应 通过建设性或破坏性干预进行的活动。我们将描述如何控制压制或 利用eiDBS扩增苍白球(GPI)或STN内段的β带活性 与PD患者僵直和运动迟缓的严重程度有关。我们还将测试以下假设： 在通过GPI、STN、马达(MC)、前马达(PMC)、 而背外侧前额叶(DLPFC)皮质与强直和运动迟缓的相关性比 仅有β波段振荡的幅度(目标1，2)。此外，我们将描述光谱、时间、 刺激GPI和STN引起的BGTC环路神经反应的空间动力学。通过 将诱发反应(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中不同神经元通路的激活如何影响ER动力学，关键笔记 不仅是为了优化星展银行，也是为了深入了解星展银行的作用机制(S)(目标3)。

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).