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: 10268185
• 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 2023-10-31
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/10268185
• 关键词: Address; Affect; Amputation; Amputees; Animals; Area; Attention; Automobile Driving; Award; Axon; Behavior; Behavioral; Body mass index; 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; 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; 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; United States Department of Veterans Affairs; Upper Extremity; Upper limb movement; Validation; Vascular Diseases; Vertebral column; Veterans; Volition; Walking; 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 loss; limb movement; locomotor tasks; military operation; military veteran; mind control; motor control; motor rehabilitation; nervous system development; neural implant; neuroprosthesis; neurotechnology; nonhuman primate; pre-clinical; relating to nervous system; sensor; social; spatiotemporal; tool; treadmill; two-dimensional; wireless

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