Cortical basal ganglia network dynamics during human gait control

人类步态控制过程中的皮质基底神经节网络动力学

• 批准号: 10567272
• 负责人: Doris Du Wang
• 金额: $ 40.66万
• 依托单位: UNIVERSITY OF CALIFORNIA, SAN FRANCISCO
• 依托单位国家: 美国
• 财政年份: 2023
• 资助国家: 美国
• 起止时间: 2023-01-15 至 2027-12-31
• 项目状态: 未结题
• 来源: https://reporter.nih.gov/project-details/10567272
• 关键词: Accelerometer; Address; Affect; Basal Ganglia; Behavior; Bilateral; Brain; Brain Stem; Chronic; Complex; Coupling; Cues; Data; Deep Brain Stimulation; Devices; Disinhibition; Dopamine; Electrodes; Electroencephalography; Environment; Feedback; Freezing; Frequencies; Functional disorder; Gait; Gait abnormality; Globus Pallidus; Goals; Home; Human; Impairment; Implant; Knowledge; Laboratories; Leg; Length; Limb structure; Locomotion; Measurement; Methodology; Methods; Modeling; Modification; Motion; Motor; Motor Cortex; Musculoskeletal Equilibrium; Output; Parkinson Disease; Pathway Analysis; Patients; Periodicals; Periodicity; Pharmaceutical Preparations; Phase; Positioning Attribute; Postural adjustments; Posture; Resolution; Role; Scalp structure; Signal Transduction; Stream; Structure; Structure of subthalamic nucleus; System; Testing; Therapeutic; Variant; Visual; Walking; flexibility; kinematics; neural; neural network; neurophysiology; neuroregulation; novel; recruit; sensory feedback; theories; wearable sensor technology; wireless

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.

项目概要/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，并揭示导致患者步态障碍的回路异常 帕金森病 (PD) 人类步态是一项复杂的运动任务，需要两者的灵活协调。 大脑内的皮质和皮质下结构然而，步态启动的神经编码是连续的。 由于解码方法的限制，有节奏的行走和步态适应在很大程度上是未知的。 步态的神经控制不仅对于理解人类的基本行为很重要，而且 对于开发新的神经调节范例来治疗帕金森病的步态问题非常重要。 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 植入 10 名 PD 患者双侧运动皮质和内苍白球 (GPi) 的电位 我们计划解码皮质和苍白球神经活动。 是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 除实验室环境外，自然环境中的药物状态和刺激周期。 工作模型是连续步态是由有节奏的低频波动产生的——theta (4-8Hz)、alpha (8-12Hz) 和 GPi 中的 β 振荡 (13-30Hz)，除了周期性的之外不需要太多的皮质输入 步态过程中，去抑制运动皮层所需的β去同步作用更大。 启动和步态适应，其中自上而下的皮质命令对于改变基底神经节活动是必要的 我们推测，在 PD 中，整个运动的 β 同步性增加。 系统与运动状态相关，步态障碍是由这种过度的皮质苍白球引起的 同步并破坏正常步态所需的动态和瞬态同步。 为了检验这一假设，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） 在实验室环境和实验室环境中的药物和刺激条件、连续运动（目标 2） 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 实验室中不同药物和刺激条件下的任务（目标 3）将对本研究产生影响。 1) 使用皮质和苍白球记录对人类步态进行首次慢性网络分析，2) 调查 在自然环境中行走的人脑活动，以及 3）提供概念框架 用于了解脊髓上网络控制步态的机制和步态障碍的病理生理学 在PD。