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，意图和电动执行的发展是一种动态且高度的 源自大脑的分布式过程。预期的动作沿轴突超级传输 脊髓中智能电路的高速公路，将下降命令转化为协调模式 肌肉激活。尽管大脑用来驱动上部的控制策略有很多了解 肢体运动，对人类运动的中心控制知之甚少。此外，失败 在一个看似微不足道的处理循环中在大脑或外围的一个看似微不足道的处理循环中，并且通常会导致 引起短暂或永久定义运动控制的戏剧性后果。一个特别明显的 例如，脊髓损伤（SCI）导致的后果，在极端情况下， 使一个人完全无法与周围的世界互动。如此神经系统的伤害和 疾病在平民和退伍军人方面都有长期的健康，经济和社会后果 人口。尽管有最好的医疗治疗，但成千上万的人忍受了很长的时间 SCI的生活感应者的生活定义了极大的影响其生活质量。 该项目的具体目标是建立有关运动皮层（MI）如何控制的基本知识 自愿以及刻板印象，下肢运动，然后设计两个脑螺旋界面 利用完全植入的硬件系统，以及第一个同类端点脑机界面 下肢假肢。我们将研究各种非人类灵长类运动皮层的基本功能 后肢运动，包括在避免障碍期间被动行走，直接终点 在录制高保真神经群体数据和运动学的同时，控制坐着飞轮。最后，我们的 结果将在支持人类翻译的临床研究的背景下进行解释 脊柱损伤退伍军人的康复途径以及截肢者的神经假体途径。我们将 最终确定非人类灵长类运动皮层采用的策略以驱动和调整 运动过程中的后肢放置位置，我们将确定运动皮层活性是否在发生变化 在所谓的“自动”运动（例如在跑步机上行走）和自愿，高度精确的运动之间 运动（例如，飞轮上的端点控制）。 拟议的研究将与经过训练在仪器跑步机上行走的恒河猴合作，穿过公寓 走廊，在大型自然主义漫游空间内免费，并沿着2-控制踏板位置 尺寸飞轮。将动物植入a）两个硅微电极阵列中的动物，然后 包含运动计划信息的前前区域（PMD）； b）连接的可植入脉冲发生器 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。将在所有运动环境中评估动物 使用无线数据传输自定义的家庭式式笼子。我们将评估BSI的长期使用 恢复功能运动，并支持其他日常非人类灵长类动物活动。最后，我们会的 利用有关运动皮层在机车中的作用的知识以及我们以前的 开发脑脊柱界面，以部署完全植入人类翻译的脑脊柱界面 在VA内，以申请资深的运动康复。