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

在健康的神经系统中，意图和运动执行力的发展是一个动态的、高度的 起源于大脑的分布式过程。预期的动作沿着轴突超级传递 通向脊髓中将下行指令转换为协调模式的智能电路的高速公路 肌肉激活的结果。虽然关于大脑用来驱动上端的控制策略已经了解了很多 肢体运动，对人类运动的中枢控制知之甚少。此外，还存在以下问题 在大脑或外周一个看似微不足道的处理环路中的功能可以，而且通常确实会导致 导致暂时性或永久性运动控制缺陷的戏剧性后果。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，它可以 使一个人完全无法与周围的世界互动。这种神经系统损伤和 精神障碍对平民和退伍军人都有长期的健康、经济和社会后果。 人口。尽管有最好的治疗方法，但成千上万的人长期忍受着 有感觉运动缺陷的脊髓损伤后生活严重影响他们的生活质量。 这个项目的具体目标是建立运动皮质(MI)如何控制的基础知识 自愿的，以及刻板的，下肢运动，然后设计一个大脑-脊柱接口 利用完全植入的硬件系统，以及第一个此类终端脑机接口 腿部假肢。我们将研究非人灵长类运动皮质在各种不同的 后肢运动，包括在跑步机上被动行走，在避障期间和直接终点 在记录高保真神经种群数据和运动学的同时，控制坐着的飞轮。最后，我们的 结果将在支持人类转化性临床研究的背景下进行解释，以提供新的 脊柱损伤退伍军人的康复路径，以及截肢者的神经假体路径。我们会 最终确定非人灵长类运动皮质驱动和调整的策略 后肢在运动过程中的位置，我们将确定运动皮质活动是否因此而改变 在所谓的“自动”运动(如在跑步机上行走)和高度精确的意志运动之间 移动(例如，飞轮上的终点控制)。 这项拟议的研究将使用经过训练的恒河猴在仪表式跑步机上穿过公寓行走。 走廊，在一个大的自然漫游空间内自由，以及控制踏板位置沿2- 尺寸飞轮。动物将在MI腿中植入a)两个硅微电极阵列，以及 包含运动规划信息的前运动区(PMD)；b)连接的植入式脉冲发生器 到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 定制家笼，采用无线数据传输。我们将评估BSI的长期使用情况 以恢复功能性运动，并支持其他非人类灵长类日常活动。最后，我们会 利用所获得的关于运动皮质在运动中的作用的知识，以及我们以前 开发脑-脊髓接口，部署用于人工翻译的完全植入的脑-脊髓接口 在退伍军人管理局内适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.