Harnessing Neuroplasticity of Postural Sensorimotor Networks Using Non-Invasive Spinal Neuromodulation to Maximize Functional Recovery After Spinal Cord Injury

利用姿势感觉运动网络的神经可塑性，使用非侵入性脊髓神经调节最大限度地提高脊髓损伤后的功能恢复

• 批准号: 10298841
• 负责人: Dimitry Sayenko
• 金额: $ 65.76万
• 依托单位: METHODIST HOSPITAL RESEARCH INSTITUTE
• 依托单位国家: 美国
• 财政年份: 2021
• 资助国家: 美国
• 起止时间: 2021-12-01 至 2027-08-31
• 项目状态: 未结题
• 来源: https://reporter.nih.gov/project-details/10298841
• 关键词: Address; Autonomic nervous system; Biological Markers; Biometry; Bladder; Body Weight; Cardiovascular system; Clinical; Clinical Research; Clinical Trials; Communities; Data; Development; Effectiveness; Electrophysiology (science); Environment; Functional Magnetic Resonance Imaging; Goals; Human; Individual; Injury; Intervention; Leg; Light; Lower Extremity; Measurement; Measures; Methodist Church; Methods; Modality; Modeling; Motor; Motor output; Movement; Muscle; Musculoskeletal Equilibrium; Nature; Nerve Regeneration; Nervous System Physiology; Neural Pathways; Neuronal Plasticity; Neurosciences; Neurostimulation procedures of spinal cord tissue; Outcome; Paralysed; Participant; Patient Selection; Patients; Performance; Personal Satisfaction; Phase; Physiological; Population; Positioning Attribute; Posture; Pre-Clinical Model; Protocols documentation; Recovery; Recovery of Function; Regimen; Rehabilitation therapy; Research; Research Institute; Research Methodology; Resources; Rest; Rogaine; Severities; Signal Transduction; Site; Spinal; Spinal Cord; Spinal cord injury; Stimulus; Techniques; Therapeutic; Training; Transcutaneous Electric Nerve Stimulation; Volition; Weight-Bearing state; Work; base; brain magnetic resonance imaging; clinical application; combinatorial; cost; cost effective; functional gain; functional improvement; functional outcomes; improved; improved functioning; individual response; minimally invasive; motor rehabilitation; multidisciplinary; neural network; neuroimaging; neurophysiology; neuroregulation; neurosurgery; potential biomarker; relating to nervous system; relative effectiveness; response; restoration; spinal nerve posterior root

ABSTRACT Transcutaneous (TSS) and epidural spinal stimulation (ESS) are both electrophysiological techniques that have been used to investigate the interactions between exogenous electrical stimuli and spinal sensorimotor networks that integrate descending motor signals with afferent inputs from the periphery during motor tasks such as standing and stepping. Recently, pilot phase clinical trials using each of these stimulation modalities have demonstrated restoration of motor functions that were previously lost due to spinal cord injury (SCI). However, the spinal network interactions that occur in response to TSS or ESS with rehabilitation training have yet to be characterized and directly compared. Thus, it is imperative to (1) understand the neurophysiological profiles of individual participants comprehensively, thereby delineating the underlying mechanisms and (2) establish the relative effectiveness of TSS versus ESS in regaining motor function. Our central hypothesis is that ESS and TSS will promote similar levels of stimulation-augmented standing. We will compare the immediate functional and neurophysiological effects of TSS versus ESS in the same participants (Aim 1). We hypothesize that ESS and TSS will generate comparable motor output during standing due to similar level of modulated excitability of sensorimotor networks. Then, we will compare immediate and delayed effects of standing training combined with TSS versus ESS (Aim 2). We hypothesize that both TSS- and ESS-combined trainings will result in similar functional gain. We further predict that after one month of rest following standing training with TSS or ESS, the excitability and responsiveness of spinal and supraspinal sensorimotor networks will differ from baseline levels and Sham. Completion of this study will establish the efficacy of both non-invasive and invasive spinal neuromodulatory approaches to improve functions after SCI, impacting both research and clinical communities. Further, it will shed light on the underlying mechanisms of spinal neuromodulation, allowing ourselves and others to refine and improve stimulation protocols to maximize functional recovery.

抽象的 经皮（TSS）和硬膜外脊柱刺激（ESS）都是具有电生理技术 用于研究外源性电刺激与脊柱感觉运动网络之间的相互作用 在电机任务期间，将下降的电机信号与外围的传入输入相结合 站立和踩踏。最近，使用每种刺激方式的试验阶段临床试验具有 证明了由于脊髓损伤（SCI）而丢失的运动功能的恢复。然而， 响应TSS或与康复培训的ESS发生的脊柱网络相互作用尚未 表征并直接比较。因此，必须（1）了解 全面参与者，从而描述了基本机制，（2）建立 TSS与ESS在恢复运动功能方面的相对有效性。我们的中心假设是Ess和 TSS将促进类似水平的刺激仪。我们将比较直接的功能 在同一参与者中，TSS与ESS的神经生理效应（AIM 1）。我们假设这一点 由于调制的兴奋性水平相似，ESS和TSS将在站立期间产生可比的电动机输出 感觉运动网络。然后，我们将比较站立训练的直接和延迟影响 结合TSS与ESS（AIM 2）。我们假设TSS和ESS兼有的培训将导致 在类似的功能增益中。我们进一步预测，经过TSS的站立培训或 ESS，脊柱和脊柱上感觉运动网络的兴奋性和反应性将与 基线水平和假。这项研究的完成将确定非侵入性和侵入性的功效 SCI后改善功能的脊柱神经调节方法，影响研究和临床 社区。此外，它将阐明脊柱神经调节的潜在机制 我们自己和他人可以完善和改善刺激方案，以最大程度地恢复功能恢复。