Cortical basal ganglia network dynamics during human gait control

项目摘要/摘要 该项目的长期目标是了解大脑皮质-基底节网络活动 与人类步态控制有关，并揭示了导致患者步态障碍的这一回路中的异常 患有帕金森氏症(PD)。人类步态是一项复杂的运动任务，需要两者灵活协调 大脑内的皮质和皮质下结构。然而，步态起始的神经编码，连续 有节奏的步行和步态适应在很大程度上是未知的，主要是由于方法学的限制。解码 步态的神经控制不仅对理解一种基本的人类行为很重要，而且也是 对于开发治疗帕金森病步态问题的新的神经调节范例具有重要意义。 我们建议通过捕捉同步局部场来研究人类步态控制的神经生理学。 10例帕金森病患者双侧运动皮质和苍白球内球电活动的研究 双向感应和刺激装置。我们计划破译大脑皮质和苍白球的神经活动 有效的和异常的步态启动、连续行走和步态修改是在不同的条件下进行的 除了实验室环境外，在自然环境中的药物状态和刺激周期。我们的 工作模型是连续步态是由有节奏的低频波动产生的--θ(4-8赫兹)，阿尔法 (8-12赫兹)和β振荡(13-30赫兹)，除周期性外，不需要太多的皮质输入 需要β去同步化去抑制运动皮质。步态时运动皮质受累更大 启动和步态适应，其中自上而下的皮质命令是改变基底节活动所必需的 以保持姿势平衡。我们推测，在帕金森病中，整个马达的β同步性增加 系统与无运动状态有关，步态损害是由这种过度的皮质苍白球引起的 同步和扰乱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启动(目标1)。 药物和刺激条件，持续运动(目标2)在实验室环境和 家庭环境，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)在实验室不同的用药和刺激条件下。这项研究的影响将 BE 1)使用大脑皮层和苍白球记录对人类步态进行首次慢性网络分析，2)调查 人类在自然环境中行走的大脑活动，以及3)提供一个概念性的框架 为了了解脊柱上网络控制步态的机制和步态损伤的病理生理学 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.