Elucidating spinal sensorimotor network components that underlie recovery of motor functions via lumbosacral epidural electrical stimulation in humans with spinal cord injury

阐明脊髓损伤患者通过腰骶硬膜外电刺激恢复运动功能的脊髓感觉运动网络组成部分

• 批准号: 10466810
• 负责人: Peter Jonas Grahn
• 金额: $ 62.32万
• 依托单位: MAYO CLINIC ROCHESTER
• 依托单位国家: 美国
• 财政年份: 2020
• 资助国家: 美国
• 起止时间: 2020-08-15 至 2025-07-31
• 项目状态: 未结题
• 来源: https://reporter.nih.gov/project-details/10466810
• 关键词: 3-Dimensional; Address; Affect; Algorithms; Animals; Bilateral; Biomechanics; Brain; Characteristics; Chronic; Clinical Trials; Computer Analysis; Computer Models; Data; Dorsal; Dura Mater; Electric Stimulation; Electrodes; Electromyography; Electrophysiology (science); FDA approved; Failure; Frequencies; Human; Implant; Injury; Ipsilateral; Knowledge; Location; Motion; Motor; Motor Activity; Motor output; Neural Pathways; Nociception; Outcome; Output; Pain; Pain management; Paralysed; Paraplegia; Participant; Pathologic; Performance; Peripheral Nervous System; Pharmacology; Physiologic pulse; Physiological; Physiology; Plant Roots; Property; Proprioception; Protocols documentation; Reaction; Recovery; Recovery of Function; Rehabilitation therapy; Reporting; Research; Role; Sensory; Severities; Signal Transduction; Site; Skin; Spinal; Spinal Cord; Spinal Cord Column; Spinal cord injury; Stimulus; Structure; Supination; Surface; System; Task Performances; Testing; Thoracic spinal cord structure; Trauma; United States Food and Drug Administration; Walking; Weight-Bearing state; Width; Work; base; clinical trial participant; computer studies; design; dorsal column; effective therapy; functional gain; functional restoration; healing; implantation; improved; loss of function; man; motor function recovery; motor recovery; motor rehabilitation; neuromuscular; neuromuscular activity; painful neuropathy; response; spinal nerve posterior root; spinal reflex; success; tool; translational potential

PROJECT SUMMARY / ABSTRACT Trauma to the spinal cord disrupts neural pathways that convey signals between the brain and spinal sensorimotor networks (SSN) that reside below the injury site, resulting in chronic paralysis. There is currently no cure for spinal cord injury (SCI); however, recent studies involving a small number of humans with SCI have shown that paralyzed functions can be restored by electrically stimulating the dorsal surface of the lumbosacral spinal cord. Last year, our team reported the use of lumbosacral epidural stimulation (ES) with intense rehabilitation enabled recovery of independent standing and stepping by a man with complete paralysis due to a mid-thoracic SCI that occurred several years prior. The stimulation systems that are implanted in humans with SCI were originally developed, and subsequently approved by the U.S. Food and Drug Administration, for use in humans to treat intractable neuropathic pain. The mechanism of action through which ES alleviates pain is thought to involve inhibition of pathologic signals transmitted through the dorsal sensory roots and ascending dorsal columns of the spinal cord. Contrary to pain treatment, computational modeling and electrophysiological studies indicate ES enables motor functions after SCI via excitation of dorsal root signaling to downstream SSNs. Assuming appropriate parameters of ES (e.g., pulse frequency, pulse width, pulse amplitude, location on the dura mater) are applied, SSNs are capable of producing robust motor outputs that result in functions such as weight bearing standing and/or walking. However, currently available scientific evidence does not explain how ES interacts with nearby spinal structures to produce functional gains in humans with chronic paralysis. To address this gap in knowledge, we will temporarily implant spinal electrodes in 32 humans with lower extremity paralysis to stimulate the dorsal sensory roots and/or dorsal surface of the spinal cord during 10 days of rehabilitation. Dorsal root stimulation (DRS) and ES waveforms will be independently-controlled to inhibit and/or activate nearby structures. Each stimulus pulse will be synchronized to electrophysiologic recordings of downstream neuromuscular activity in order to characterize SSN activity in response to DRS and/or ES stimulation. We hypothesize unilateral DRS during motor-enabling ES will result in ipsilateral suppression of SSN outputs. We further hypothesize that bilateral DRS alone will enable motor functions that are similar to those generated by ES. To investigate the role of rehabilitation during stimulation-enabled motor recovery, we hypothesize that stimulation-enabled motor performance will improve significantly across 10 motor rehabilitation sessions with DRS/ES. Completion of this work will generate new information on the interactions that occur during SSN facilitation via spinal stimulation. This information will be used to develop algorithms that correlate stimulation waveform properties to neuromuscular recordings and motor performance metrics in order to identify stimulation settings that facilitate optimal performance of stimulation-enabled motor function in humans with SCI.

项目总结/摘要 脊髓损伤会破坏大脑和脊髓之间传递信号的神经通路 感觉运动网络（SSN）位于损伤部位下方，导致慢性瘫痪。目前 脊髓损伤（SCI）无法治愈;然而，最近的研究涉及少数SCI患者， 表明瘫痪的功能可以通过电刺激腰骶背表面来恢复 脊髓去年，我们的团队报告了使用腰骶部硬膜外刺激（ES）， 康复使一名完全瘫痪的男子能够恢复独立站立和行走， 几年前发生的胸中部脊髓损伤植入人体的刺激系统 SCI最初是由美国食品和药物管理局开发的，随后被批准用于 用于治疗顽固性神经性疼痛ES减轻疼痛的作用机制是 被认为涉及抑制通过背侧感觉根和上行传导的病理信号 脊髓的背柱。与疼痛治疗相反，计算建模和电生理学 研究表明，ES通过激发背根信号传导至下游SSNs而使SCI后的运动功能得以实现。 假设ES的适当参数（例如，脉冲频率、脉冲宽度、脉冲幅度、 硬脑膜），SSN能够产生鲁棒的运动输出，从而产生诸如 负重站立和/或行走。然而，现有的科学证据并不能解释为什么 ES与附近的脊柱结构相互作用，为慢性瘫痪患者带来功能改善。到 为了弥补这一知识空白，我们将在32名下肢瘫痪的人中暂时植入脊柱电极， 麻痹以刺激脊髓的背侧感觉根和/或背侧表面， 康复活动.将独立控制背根刺激（DRS）和ES波形，以抑制和/或 激活附近的结构。每个刺激脉冲将与电生理记录同步， 下游神经肌肉活动，以便表征响应于DRS和/或ES的SSN活动 刺激.我们假设在运动使能ES期间单侧DRS将导致同侧SSN抑制 产出我们进一步假设，双侧DRS单独将使运动功能类似于那些 由ES生成。为了研究康复在刺激激活的运动恢复过程中的作用，我们 假设在10种运动康复中，刺激激活运动表现将显著改善 与DRS/ES的会话。这项工作的完成将产生关于所发生的相互作用的新信息 在通过脊髓刺激的SSN易化过程中。这些信息将用于开发算法， 刺激波形特性与神经肌肉记录和运动性能指标的关系， 刺激设置，促进SCI患者刺激激活的运动功能的最佳表现。