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

摘要 经皮(TSS)和硬膜外脊髓刺激(ESS)都是电生理技术，具有 被用来研究外源性电刺激与脊髓感觉运动网络的相互作用 在运动任务期间，将下行运动信号与来自外围设备的传入输入相结合 站着、走着。最近，使用这些刺激方式中的每一种进行的试点阶段临床试验 展示了先前因脊髓损伤(SCI)而丧失的运动功能的恢复。然而， 对TSS或ESS与康复训练的反应所发生的脊髓网络相互作用尚未得到证实 刻画和直接比较。因此，当务之急是(1)了解患者的神经生理特征。 个人参与者全面，从而勾勒出基本机制和(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-增强站立。我们将比较直接泛函 以及TSS和ESS在相同参与者中的神经生理学效应(目标1)。我们假设 由于调制兴奋性水平相似，ESS和TSS将在站立时产生类似的电机输出 感觉运动网络。然后，我们将比较站立训练的即时效果和延迟效果 结合TSS与ESS(目标2)。我们假设TSS-和ESS-的联合培训将导致 在类似的功能增益中。我们还预测，在TSS或TSS站立训练后休息一个月后 ESS，脊髓和棘上感觉运动网络的兴奋性和反应性将不同于 基线水平和假。这项研究的完成将确定无创和有创的疗效 脊髓损伤后改善功能的脊髓神经调节方法，影响研究和临床 社区。此外，它将阐明脊髓神经调节的潜在机制，使 我们自己和其他人来完善和改进刺激方案，以最大限度地恢复功能。

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.