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

项目摘要/摘要 脊髓损伤扰乱了大脑和脊髓之间传递信号的神经通路 位于损伤部位下方的感觉运动网络(SSN)，导致慢性瘫痪。目前有 无法治愈脊髓损伤(SCI)；然而，最近涉及一小部分患有SCI的人类的研究已经 结果表明，通过电刺激腰椎背侧表面可以恢复瘫痪的功能 脊髓。去年，我们的团队报告了使用腰骶硬膜外刺激(ES)的强烈 康复使一名完全瘫痪的男子能够恢复独立站立和行走，原因是 几年前发生的胸中段脊髓损伤。植入人类体内的刺激系统 SCI最初是开发的，后来得到了美国食品和药物管理局的批准，用于 用于治疗顽固性神经病理性疼痛。ES减轻疼痛的作用机制是 被认为涉及抑制通过背感觉根和上行传递的病理信号 脊髓背侧的柱状物。与疼痛治疗相反，计算建模和电生理 研究表明，ES通过刺激背根信号传递到下游SSN，使脊髓损伤后的运动功能得以发挥。 假设ES的适当参数(例如，脉冲频率、脉冲宽度、脉冲幅度、在 DURA MATER)，SSN能够产生坚固的电机输出，从而产生如下功能 负重站立和/或行走。然而，目前可用的科学证据并不能解释 ES与附近的脊柱结构相互作用，在患有慢性瘫痪的人类中产生功能收益。至 为了解决这一知识缺口，我们将在32名有下肢的人身上暂时植入脊髓电极 在10天内刺激脊髓背感觉根和/或背侧表面的瘫痪 康复。背根刺激(DRS)和ES波形将独立控制以抑制和/或 激活附近的建筑。每个刺激脉冲将与电生理记录同步 下游神经肌肉活性以表征SSN活性对DRS和/或ES的响应 刺激。我们假设在运动激活的ES过程中单侧DRS会导致同侧SSN的抑制 产出。我们进一步假设，仅双侧DRS就能使运动功能类似于 由ES生成。为了研究康复在刺激使能运动恢复中的作用，我们 假设刺激性运动表现将在10项运动康复中显著改善 与DRS/ES的会议。这项工作的完成将产生关于发生的相互作用的新信息 在通过脊髓刺激促进SSN的过程中。这些信息将被用来开发相关算法 神经肌肉记录和运动表现指标的刺激波形特性，以便识别 在患有脊髓损伤的人类中，促进刺激使能运动功能的最佳表现的刺激设置。

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.