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

项目总结 脊髓损伤严重损害站立和行走能力，严重影响日常生活。 活动。虽然这些缺陷可以通过运动训练得到部分改善，即使在多次训练之后也是如此 然而，尽管仍有不正常的肌肉活动和协调，但这一现象仍然存在。因此，仅靠运动训练是不能完全 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措施 因此，迫切需要构建神经网络，加强人脊髓损伤后的神经连接。 经皮脊髓(经脊髓)刺激改变多节段运动神经元兴奋性 使运动神经元更接近阈值，这是功能下降和局部输入的先决条件。 重要的是，同时进行脊柱刺激和运动训练是否能最大限度地促进运动。 脊髓损伤后的恢复尚不清楚。这项临床试验的目标是使用高频(30赫兹)经脊髓 刺激主要的运动训练，并最终提高个人的站立和行走能力 慢性不完全性脊髓损伤。45名ISCI患者将接受40次体重测试- 支持步进训练，以高频经脊髓刺激为基础。参与者将被随机分配到 在站立时(真的或假的)或仰卧时(真的)接受脊柱刺激。目标1评估如何 ISCI患者高频经脊髓刺激启动运动训练改变皮质神经元区 连接强度，如从腿部记录的运动诱发电位所示。AIM 2评估如何 高频经脊髓刺激启动运动训练对ISCI患者重组和运动功能的影响 脊髓神经回路的适当接合。最后，目标3评估了Intralimb方面的改进 协调性和站立和行走的能力。这些结果将支持这样的观点，即主音高频 经脊髓刺激通过体位依赖的皮质脊髓加强皮质-神经-神经细胞的连接 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，从这项机械性临床试验中获得的信息将 极大地影响了临床实践。这是因为在现实世界的临床环境中，非侵入性经脊柱 刺激比有创性硬膜外刺激更容易、更广泛地实施。此外，由 应用多种干预措施加速运动恢复，我们正在采用一种治疗方案， 代表了一种真正的临床方法。事实上，这一多方面的方法符合国家和地区的优先事项 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.