Cortical basal ganglia network dynamics during human gait control

项目总结/摘要 该项目的长期目标是了解皮质-基底神经节网络活动， 涉及人类步态控制，并揭示了在这一电路的异常，患者的步态障碍的基础 帕金森病（PD）人体步态是一项复杂的运动任务，需要两者的灵活协调 大脑皮层和皮层下结构。然而，神经编码步态启动，连续 有节奏的行走和步态适应在很大程度上是未知的，这主要是由于方法上的限制。解码 步态的神经控制不仅对理解基本的人类行为很重要，而且 这对于开发新的神经调节范例以治疗PD中的步态问题是重要的。 我们建议通过捕获同步局部场来研究人类步态控制的神经生理学 10名植入了 双向传感和刺激装置。我们计划解码大脑皮层和苍白球的神经活动， 在不同条件下，有效和异常步态启动、连续行走和步态修正的基础 药物状态和刺激周期在自然环境中除了实验室设置。我们 工作模型是由节律性低频波动-θ（4-8Hz）、α（10 - 10 Hz）、α（10 - 10 Hz）和α（10 - 10 Hz）产生连续步态。 （8- 12 Hz）和β振荡（13- 30 Hz），并且除了周期性的外，不需要太多的皮层输入 去抑制运动皮层所需的β去兴奋化。步态时运动皮质受累更大 启动和步态适应，其中自上而下的皮层命令是必要的，以修改基底神经节活动 保持姿势平衡我们的理论是，在帕金森病中，整个运动中增加的β同步性 系统与运动不能状态有关，步态障碍是由这种过度的皮质苍白球引起的。 同步和破坏正常步态所需的动态和瞬时同步。 为了验证这一假设，我们将在实验室环境中研究不同条件下的步态起始（目标1）。 药物和刺激条件下，在实验室环境中和 家庭设置，以捕捉自然环境中步态的动态变化，以及视觉引导的步态适应 任务（目标3）在不同的药物和刺激条件下，在实验室。这项研究的影响将 是1）使用皮层和苍白球记录执行人类步态的第一个慢性网络分析，2）研究 在自然环境中行走的人脑活动，以及3）提供一个概念框架 以了解步态的脊髓上网络控制机制和步态障碍的病理生理学 在警局

PROJECT SUMMARY/ ABSTRACT The long-term goal of this project is to understand the cortical-basal ganglia network activities that are involved with human gait control, and reveal the abnormalities in this circuit that underlie gait disorders in patients with Parkinson’s disease (PD). Human gait is a complex motor task that requires the flexible coordination of both cortical and subcortical structures within the brain. However, the neural encoding for gait initiation, continuous rhythmic walking, and gait adaptation is largely unknown due largely to methodological constraints. Decoding the neural control of gait is not only important for understanding a fundamental human behavior, but is also important for developing novel neuromodulation paradigms to treat gait problems in PD. We propose to study the neurophysiology of human gait control by capturing simultaneous local field potentials from bilateral motor cortex and globus pallidus interna (GPi) of ten PD patients implanted with bidirectional sensing and stimulating devices. We plan to decode the cortical and pallidal neural activities that underlie effective and abnormal gait initiation, continuous walking, and gait modification under different medication states and stimulation cycles in the naturalistic environment in addition to the laboratory setting. Our working model is that continuous gait is generated by rhythmic low frequency fluctuations—theta (4-8Hz), alpha (8-12Hz), and beta oscillations (13-30Hz) in the GPi and does not require much cortical input except periodic beta desynchronization required to disinhibit the motor cortex. Motor cortical involvement is greater during gait initiation and gait adaptation, where top-down cortical command is necessary to modify basal ganglia activities to maintain postural balance. We theorize that in PD, where increased beta synchrony throughout the motor system is associated with an akinetic state, gait impairments are caused by this excessive cortical-pallidal synchronization and disrupt the dynamic and transient synchronization required for normal gait. To test this hypothesis, we will study gait initiation (Aim 1) in the laboratory setting under different medication and stimulation conditions, continuous locomotion (Aim 2) both in the laboratory setting and in the home setting to capture dynamic changes of gait in the naturalistic setting, and a visually guided gait adaptation task (Aim 3) under different medication and stimulation conditions in the laboratory. The impact of this study will be 1) perform the first chronic network analysis of human gait using cortical and pallidal recordings, 2) investigate the human brain activities underlying walking in the natural environment, and 3) provide a conceptual framework for understanding the mechanism of supraspinal network control of gait and pathophysiology of gait impairments in PD.