Spinal Epidural Electrode Array to Facilitate Standing and Stepping After SCI

描述(由研究人员提供)：基于多学科和多大学团队的共同努力，该研究计划将开发一种用于硬膜外脊髓刺激的新颖、灵活、高密度的电极阵列技术。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，这两个特征对于恢复姿势和运动是必不可少的。首先，脊髓回路解释感觉信息，并将其转换为状态相关的运动活动。其次，运动网络是高度可塑性的，当在训练期间提供持续的感觉线索时，它会适应，从而使恢复得以发生。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，当下行运动失去控制时，硬膜外刺激将特别有益。由于感觉和运动处理发生在整个背侧脊髓，建议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分散分布的组件的全面访问。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能够比以前更精细和更稳健地控制运动。这项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脊髓损伤大鼠模型中开发、测试和表征阵列。我们的初步动物实验表明，当后肢有规律地使用机器人设备进行训练，并在单个或两个位置对脊髓进行硬膜外刺激时，成功地促进了完全性脊髓损伤大鼠的台阶恢复。在这项研究计划中，我们将设计、制造和测试一系列大小、电极数量和密度不同的电极阵列。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，最终将测试一种使用高密度刺激阵列和按需辅助机器人训练的组合疗法。第二个平行轨道将探索使用传统电极技术，这一技术历史上主要用于抑制痉挛和背部疼痛，以促进患有严重脊髓损伤的人类受试者的站立和行走。我们假设，硬膜外刺激和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损伤患者能够恢复这些功能。我们的动物研究和人体研究的综合结果将为我们的团队后续的工作做好准备，这些工作的重点是将高密度阵列技术转化为人类临床研究。这项提案将作为加州大学洛杉矶分校和路易斯维尔大学之间的合作项目，由位于奥地利维也纳的临床医生、工程师和科学家组成的专家团队提供协助。与公共卫生相关：在这项提案中，我们将开发新的多电极阵列，通过手术将其放置在脊髓周围的结缔组织鞘上，可以用来刺激脊髓的特定区域，帮助脊髓损伤患者恢复站立或行走的能力。这些电极阵列将帮助我们利用脊髓神经回路的两个内置特征，这两个特征与站立和行走的能力有关：1)解释复杂的、动态的感觉信息；2)这些脊髓回路依赖于使用的可塑性。我们假设，脊髓刺激和站立或台阶训练的结合将使脊髓损伤的个体恢复这些功能。

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.