Spinal Epidural Electrode Array to Facilitate Standing and Stepping After SCI

描述（由研究者提供）：基于多学科和多大学团队的共同努力，本研究项目将开发一种新颖、灵活、高密度的硬膜外脊髓刺激电极阵列技术。这项技术有可能显著改善严重脊髓损伤患者的姿势和运动恢复。高密度硬膜外电极阵列将使我们能够利用脊髓回路的两个关键特征，这对恢复姿势和运动至关重要。首先，脊髓回路将感觉信息解释并转导成依赖状态的运动活动。其次，运动网络是高度可塑性的，在训练过程中提供持续的感觉提示时，它会适应，从而使恢复发生。硬膜外刺激促进了这两个重要的过程，我们假设在脊髓损伤后，当下降运动控制丧失时，它将特别有益。由于感觉和运动处理发生在整个脊髓背侧，因此所提出的高密度电极阵列的分布式刺激能力将提供对运动网络中弥散分布的组成部分的全面访问。我们假设，当与运动训练相结合时，多部位硬膜外刺激将使脊髓损伤受试者的运动控制比以前可能的更精细和更强大。本研究计划由两个平行的轨道组成。第一个，也是主要的，重点是在一个完整的SCI大鼠模型中开发、测试和表征这些阵列。我们的初步动物实验已经证明，当用机器人装置定期训练后肢和在硬膜外单处或双处刺激脊髓时，可以成功地促进完全性脊髓损伤大鼠的行走恢复。在这个研究项目中，我们将设计、制造和测试一系列不同尺寸、电极数量和密度的电极阵列。我们将使用不同的设计组合在脊髓损伤大鼠身上测试这些高密度阵列，最终在一个实验中测试使用高密度刺激阵列和按需辅助机器人训练的联合疗法。第二个平行轨道将探索传统电极技术的使用，该技术在历史上主要用于抑制痉挛和背部疼痛，以促进严重脊髓损伤的人类受试者站立和行走。我们假设硬膜外刺激与特定任务运动训练的结合将使目前无法独立行走和站立的受伤个体恢复这些功能。我们的动物研究和人类研究的综合结果将为我们的团队接下来的工作做好准备，重点是将高密度阵列技术转化为人类临床研究。该提案将由加州大学（洛杉矶）、加州理工学院和路易斯维尔大学合作实施，并得到奥地利维也纳的临床医生、工程师和科学家专家团队的协助。公共卫生相关性：在这项提议中，我们将开发新的多电极阵列，它将通过手术放置在脊髓周围的结缔组织鞘上，可用于刺激脊髓的特定区域，以帮助脊髓损伤受试者恢复站立或行走的能力。这些电极阵列将帮助我们利用与站立和行走能力相关的脊髓神经回路的两个内置特征：1)解释复杂、动态的感觉信息；2)这些脊髓回路的使用依赖可塑性。我们假设脊髓刺激与站立或踏步训练相结合将使脊髓损伤患者恢复这些功能。

DESCRIPTION (provided by investigator): Based on the combined efforts of a multidisciplinary and multi-university team, this research program will develop a novel, flexible, high density electrode array technology for epidural spinal cord stimulation. This technology has the potential to significantly improve the recovery of posture and locomotion in individuals with a severe spinal cord injury. High density epidural electrode arrays will enable us to take advantage of two key features of spinal cord circuitry that are essential for rehabilitating posture and locomotion. First, the spinal circuitry interprets and transduces sensory information into state-dependent motor activity. Second, the locomotor network is highly plastic and adapts when provided with persistent sensory cues during training, thus enabling recovery to occur. Epidural stimulation facilitates both of these important processes and we hypothesize that it will be particularly beneficial after an SCI, when descending motor control is lost. Since sensory and motor processing occurs throughout the dorsal spinal cord, the distributed stimulation capability of the proposed high density electrode arrays will provide comprehensive access to the diffusely located components of the locomotor network. We hypothesize that, when combined with motor training, multi-site epidural stimulation will enable finer and more robust control of locomotion of SCI subjects than previously possible. This research program is composed of two parallel tracks. The first, and major, track focuses on developing, testing, and characterizing the arrays in a complete SCI rat model. Our preliminary animal experiments have demonstrated success in promoting recovery of stepping of complete spinal cord injured rats when the hindlimbs are trained regularly with robotic devices and when the spinal cord is stimulated epidurally at a single or at two sites. In this research program, we will design, fabricate, and test a series of electrode arrays that vary in size, electrode count, and density. We will test these high density arrays on SCI rats using various design combinations, culminating in an experiment that will test a combined therapy using a high density stimulating array coupled with assist-as-needed robotic training. A second parallel track will explore the use of conventional electrode technology, which historically has been used mainly for suppressing spasticity and back pain, to facilitate standing and stepping in human subjects with a severe spinal cord injury. We hypothesize that the combination of epidural stimulation with task specific motor training will enable individuals with an injury that presently precludes independent stepping and standing, to regain these functions. The combined results of our animal studies and human studies would prepare our team for subsequent work that focused on translating the high density array technologies to human clinical studies. This proposal will be conducted as a collaboration between the University of California (Los Angeles), Caltech, and the University of Louisville, with assistance from an expert team of clinicians, engineers, and scientists located in Vienna, Austria. PUBLIC HEALTH RELEVANCE: In this proposal we will develop new multielectrode arrays, which will be surgically placed on the connective tissue sheath surrounding the spinal cord, that can be used to stimulate specific regions of the spinal cord to help SCI subjects recover the ability to stand or step. These electrode arrays will help us take advantage of two built-in features of the spinal cord neural circuits that are associated with the ability to stand and step: 1) interpretation of complicated, dynamic sensory information and 2) use-dependent plasticity of these spinal circuits. We hypothesize that the combination of stimulation of the spinal cord and either stand or step training will allow individuals with a spinal cord injury to regain these functions.