Priming with High-Frequency Trans-spinal Stimulation to Augment Locomotor Training Benefits in Spinal Cord Injury

项目摘要 脊髓损伤（SCI）严重损害站立和行走能力，严重影响日常生活 活动虽然运动训练可以部分改善这些缺陷， 然而，异常的肌肉活动和协调仍然存在。因此，运动训练本身并不能完全 优化神经元的可塑性，以加强连接大脑，脊髓和 本地电路因此，有效促进脊髓运动神经调节的治疗干预 因此，非常需要建立神经网络并加强受伤的人类脊髓的神经连接。 经皮脊髓（transspinal）刺激通过以下方式改变多个节段的运动神经元兴奋性： 使运动神经元更接近阈值，这是下行和局部输入功能的先决条件。 重要的是，是否同时治疗与经脊髓刺激和运动训练最大限度地提高运动 SCI后的恢复情况尚不清楚。本临床试验的目标是使用高频（30 Hz）经脊柱 刺激，以促进运动训练，并最终改善患有以下疾病的个体的站立和行走能力 慢性不完全性脊髓损伤（iSCI）。45名iSCI患者将接受40次体重训练- 通过高频经脊髓刺激进行支持性台阶训练。受试者将被随机分配至 在站立时（真实的或假的）或仰卧时（真实的）接受经脊髓刺激。目标1评估如何 iSCI患者高频经脊髓刺激引发运动训练改变皮质运动神经元 连接强度，如从腿部记录的运动诱发电位所示。目标2评估如何 在iSCI中用高频经脊髓刺激启动运动训练影响重组， 脊髓神经元回路的适当参与。最后，目标3评估了内部环境的改善 协调性和站立和行走的能力。这些结果将支持这一观点，即主音高频 经脊髓刺激通过姿势依赖性皮质脊髓神经元增强皮质-肌肉-神经元连接 神经可塑性此外，这些结果将表明适当的神经调节和促进脊髓 运动神经元网络我们预计，从这项机制性临床试验中获得的信息将 对临床实践影响很大。这是因为在现实世界的临床环境中， 刺激可以比侵入性硬膜外刺激更容易和更广泛地实施。此外，由 应用多种干预措施来加速运动恢复，我们采用的治疗方案， 代表了真正的临床方法。事实上，这种多方面的做法符合国家的优先事项， 康复卫生研究所。

PROJECT SUMMARY Spinal cord injury (SCI) greatly impairs standing and walking ability, which severely compromises daily living activities. While these deficits are partially improved by locomotor training, even after multiple training sessions, abnormal muscle activity and coordination still persist. Thus, locomotor training alone cannot fully optimize the neuronal plasticity required to strengthen the synapses connecting the brain, spinal cord, and local circuits. As such, treatment interventions that effectively promote neuromodulation of spinal locomotor networks and strengthen neural connectivity of the injured human spinal cord are greatly needed. Transcutaneous spinal cord (transspinal) stimulation alters motoneuron excitability over multiple segments by bringing motoneurons closer to threshold, a pre-requisite for functioning descending and local inputs. Importantly, whether concurrent treatment with transspinal stimulation and locomotor training maximizes motor recovery after SCI is unknown. The goal of this clinical trial is to use high frequency (30 Hz) transspinal stimulation to prime locomotor training and ultimately improve standing and walking ability in individuals with chronic incomplete SCI (iSCI). Forty-five individuals with iSCI will undergo 40 sessions of body weight- supported step training primed with high-frequency transspinal stimulation. Participants will be randomized to receive transspinal stimulation during standing (real or sham) or while supine (real). Aim 1 evaluates how priming locomotor training with high-frequency transspinal stimulation in iSCI alters corticomotoneuronal connectivity strength, as indicated by motor evoked potentials recorded from the legs. Aim 2 evaluates how priming locomotor training with high-frequency transspinal stimulation in iSCI affects reorganization and appropriate engagement of spinal neuronal circuits. Finally, Aim 3 evaluates improvement in intralimb coordination and the ability to stand and walk. These results will support the notion that tonic high-frequency transspinal stimulation strengthens corticomotoneuronal connectivity through posture-dependent corticospinal neuroplasticity. Additionally, these results will indicate appropriate neuromodulation and facilitation of spinal locomotor neuronal networks. We anticipate that the information gained from this mechanistic clinical trial will greatly impact clinical practice. This is because in real-world clinical settings, noninvasive transspinal stimulation can be more easily and widely implemented than invasive epidural stimulation. Additionally, by applying multiple interventions to accelerate motor recovery, we are employing a treatment regimen that represents a true clinical approach. Indeed, this multi-faceted approach meets the priorities of the National Institutes of Health for rehabilitation.