The Role of M1 Leg Area in Volitional and Stereotyped Control of the Lower Limb

M1 腿部区域在下肢意志和刻板控制中的作用

• 批准号: 10021472
• 负责人: David Allenson Borton
• 金额: --
• 依托单位: PROVIDENCE VA MEDICAL CENTER
• 依托单位国家: 美国
• 财政年份: 2018
• 资助国家: 美国
• 起止时间: 2018-11-01 至 2022-10-31
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/10021472
• 关键词: Address; Affect; Amputation; Amputees; Animals; Area; Attention; Automobile Driving; Award; Axon; Behavior; Behavioral; Brain; Breathing; Caring; Clinical Research; Custom; Data; Data Set; Development; Disabled Persons; Disease; Electric Stimulation; Electrocorticogram; Electromyography; Electronics; Failure; Follow-Up Studies; Future; Gait; Home environment; Hospital Costs; Human; Implant; Individual; Industry; Intention; Joints; Knowledge; Laboratories; Lead; Leg; Life; Limb Prosthesis; Limb structure; Location; Locomotion; Lower Extremity; Macaca; Macaca mulatta; Malignant Neoplasms; Mathematics; Medical; Methods; Microelectrodes; Military Personnel; Modality; Modeling; Motion; Motor; Motor Cortex; Movement; Muscle; Nervous System Trauma; Neurons; Neurostimulation procedures of spinal cord tissue; Palpable; Paraplegia; Pathway interactions; Pattern; Performance; Periodicity; Persons; Phase; Physiologic pulse; Play; Population; Positioning Attribute; Primates; Process; Prosthesis; Publishing; Quality of life; Rehabilitation therapy; Reporting; Robotics; Role; Rotation; Signal Transduction; Silicon; Spinal; Spinal Cord; Spinal Injuries; Spinal cord injury; Stereotyping; System; Technology; Therapeutic; Time; Training; Translations; Trauma; United States; Upper Extremity; Upper limb movement; Validation; Vascular Diseases; Vertebral column; Veterans; Volition; Walking; Wireless Technology; Work; base; brain machine interface; data exchange; design; feature extraction; first-in-human; flexibility; foot; health economics; human study; insight; instrument; kinematics; limb amputation; limb movement; locomotor tasks; mind control; motor control; motor rehabilitation; nervous system development; neural implant; neuroprosthesis; neurotechnology; nonhuman primate; operation; pre-clinical; relating to nervous system; sensor; social; spatiotemporal; tool; treadmill; two-dimensional

In the healthy nervous system, the development of intention and motor execution is a dynamic and highly distributed process that originates in the brain. The intended action is transmitted along the axonal super highway to smart circuits in the spinal cord that transform the descending command into coordinated patterns of muscle activation. While much is understood regarding the control strategies the brain uses to drive upper limb movements, relatively little is known about the central control of human locomotion. Further, failures of function in one seemingly insignificant processing loop in the brain or periphery can, and often does, lead to dramatic consequences that induce transient or permanent deficits in motor control. A particularly palpable example of this is the consequences resulting from spinal cord injury (SCI), which, in extreme cases, can render a person completely unable to interact with the world around them. Such nervous system injuries and disorders have long-term health, economic and social consequences in both the civilian and Veteran population. Despite the best available medical treatments, hundreds of thousands of individuals endure a long life post-SCI with sensorimotor deficits that dramatically affect their quality of life. The specific objective of this project is to build fundamental knowledge of how motor cortex (MI) controls voluntary, as well as stereotypic, lower limb movements, and then to design both a brain-spine interface leveraging a fully implanted hardware system, as well as a first of its kind end-point brain-machine interface for lower limb prosthetics. We will study the basic function of nonhuman primate motor cortices during a variety of hind limb movements, including passive walking on a treadmill, during obstacle avoidance, and direct endpoint control on a sitting flywheel while recording high-fidelity neural population data and kinematics. Finally, our results will be interpreted in the context of supporting a translational clinical study in humans to provide a new rehabilitation pathway for Veterans with spinal injury, as well as neuroprosthetic pathway for amputees. We will conclusively determine the strategies employed by nonhuman primate motor cortex to both drive and adjust hind limb placement during locomotion and we will determine if motor cortex activity consequently changes between so-called “automatic” movements (e.g. walking on a treadmill), and volitional, highly precise movements (e.g. end-point control on a flywheel). The proposed study will work with rhesus monkeys trained to walk on an instrumented treadmill, across a flat corridor, freely within a large naturalistic roaming space, as well as controlling the pedal location along a 2- dimensional flywheel. Animals will be implanted with a) two silicon microelectrode arrays in MI-leg, and premotor area (PMd) containing movement planning information; b) an implantable pulse generator connected to a custom epidural spinal cord stimulation microelectrode array; and c) electromyography sensors in key gait muscles of the lower limb. Animals will be evaluated across all locomotor contexts, as well as in their customized home-cage, using wireless data transmission. We will evaluate the long-term use of the BSI both to restore functional locomotion, and to support other daily nonhuman primate activities. Finally, we will leverage the knowledge gained about the motor cortex’s role in locomotion, as well as our previous development of a brain-spinal interface, to deploy a fully-implanted brain-spinal interface for human translation within the VA for application to veteran locomotor rehabilitation.

在健康的神经系统中，意图和运动执行的发展是动态的、高度的。 起源于大脑的分布式过程。预期的动作沿着轴突超传递 通往脊髓智能电路的高速公路，将下行命令转化为协调模式 的肌肉激活。虽然人们对大脑用来驱动上层的控制策略有很多了解。 对于肢体运动，人们对人类运动的中枢控制知之甚少。此外，失败 大脑或外周中看似微不足道的处理循环中的功能可以而且经常会导致 导致短暂或永久性运动控制缺陷的严重后果。一个特别明显的 脊髓损伤 (SCI) 造成的后果就是一个例子，在极端情况下， 使人完全无法与周围的世界互动。这样的神经系统损伤和 疾病对平民和退伍军人都会产生长期的健康、经济和社会后果 人口。尽管有最好的治疗方法，仍有数十万人忍受着长期的痛苦 脊髓损伤后的生活会出现感觉运动缺陷，严重影响他们的生活质量。 该项目的具体目标是建立运动皮层 (MI) 如何控制的基础知识 自愿的以及刻板的下肢运动，然后设计脑-脊柱界面 利用完全植入的硬件系统以及首个同类端点脑机接口 下肢假肢。我们将研究非人类灵长类动物运动皮层在各种过程中的基本功能 后肢运动，包括在跑步机上被动行走、避障期间和直接终点 控制坐式飞轮，同时记录高保真神经群体数据和运动学。最后，我们的 结果将在支持人类转化临床研究的背景下进行解释，以提供新的方法 脊柱损伤退伍军人的康复途径，以及截肢者的神经修复途径。我们将 最终确定非人类灵长类动物运动皮层驱动和调整所采用的策略 运动过程中后肢的放置，我们将确定运动皮层活动是否会因此改变 介于所谓的“自动”运动（例如在跑步机上行走）和意志性、高度精确的运动之间 运动（例如飞轮上的终点控制）。 拟议的研究将与经过训练的恒河猴一起在仪器跑步机上行走，穿过平坦的地面 走廊，在一个大的自然主义漫游空间内自由地移动，以及沿着 2- 控制踏板位置 立体飞轮。动物将在 MI 腿中植入 a) 两个硅微电极阵列，以及 运动前区（PMd）包含运动规划信息； b) 连接植入式脉冲发生器 定制硬膜外脊髓刺激微电极阵列； c) 关键步态中的肌电图传感器 下肢的肌肉。将在所有运动环境以及它们的运动环境中对动物进行评估 定制的家笼，采用无线数据传输。我们将评估 BSI 的长期使用 恢复功能性运动，并支持其他非人类灵长类动物的日常活动。最后，我们将 利用获得的关于运动皮层在运动中的作用的知识，以及我们之前的知识 开发脑-脊髓接口，部署完全植入的脑-脊髓接口用于人类翻译 在 VA 内应用于退伍军人运动康复。