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

在健康的神经系统中，意图和运动执行的发展是一个动态的、高度的过程。 源自大脑的分布式过程。预期的动作是沿着轴突超传导的 脊髓中智能电路的高速公路，将下行命令转换为协调模式 肌肉激活的过程。虽然我们对大脑用来驱动上层的控制策略有很多了解， 虽然我们对人类的肢体运动知之甚少，但对人类运动的中枢控制却知之甚少。此外，失败 在大脑或外围的一个看似微不足道的处理回路中， 戏剧性的后果，引起短暂或永久性的缺陷，在运动控制。一个特别明显的 这方面的例子是脊髓损伤（SCI）造成的后果，在极端情况下， 使人完全无法与周围的世界互动。这种神经系统损伤， 疾病对平民和退伍军人都有长期的健康、经济和社会后果。 人口尽管有最好的医疗手段，成千上万的人忍受着长期的痛苦。 生活后SCI与感觉运动缺陷，显着影响他们的生活质量。 这个项目的具体目标是建立运动皮层（MI）如何控制的基本知识 自愿的，以及刻板的，下肢运动，然后设计一个大脑-脊柱接口， 利用完全植入的硬件系统，以及首个此类端点脑机接口， 下肢假肢我们将研究非人类灵长类动物运动皮层在各种不同的运动过程中的基本功能。 后肢运动，包括在跑步机上被动行走、避障和直接终点 在记录高保真神经群体数据和运动学的同时，对坐着的飞轮进行控制。最后我们 结果将在支持人类转化临床研究的背景下进行解释， 脊髓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 结论性地确定非人类灵长类动物运动皮层在驱动和调整中所采用的策略 运动过程中后肢的位置，我们将确定运动皮层活动是否因此改变 在所谓的“自动”运动（例如在跑步机上行走）和意志之间，高度精确 运动（例如飞轮上的终点控制）。 这项拟议中的研究将对恒河猴进行训练，让它们在装有仪器的跑步机上行走， 走廊，自由地在一个大的自然漫游空间，以及控制踏板位置沿着2- 尺寸飞轮a）在MI-腿中植入两个硅微电极阵列，以及 运动前区（PMd），其包含运动规划信息; B）植入式脉冲发生器，其连接 定制的硬膜外脊髓刺激微电极阵列;以及c）关键步态中的肌电图传感器 下肢的肌肉动物将在所有运动环境中进行评估，以及在其 定制家居笼，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，并支持其他日常非人类灵长类活动。最后我们将 利用我们获得的关于运动皮层在运动中的作用的知识，以及我们以前的 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 用于退伍军人运动康复。

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.