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

通过高频经脊柱刺激增强脊髓损伤的运动训练效果

• 批准号: 10187619
• 负责人: NOAM Y. HAREL
• 金额: $ 54.62万
• 依托单位: COLLEGE OF STATEN ISLAND
• 依托单位国家: 美国
• 财政年份: 2020
• 资助国家: 美国
• 起止时间: 2020-06-09 至 2025-04-30
• 项目状态: 未结题
• 来源: https://reporter.nih.gov/project-details/10187619
• 关键词: Activities of Daily Living; Address; Affect; Body Weight; Brain; Chronic; Clinical; Clinical Trials; Complex; Electromyography; Equilibrium; Frequencies; Goals; H-Reflex; Human; Hyperreflexia; Impairment; Individual; Intervention; Knowledge; Leg; Limb structure; Locomotor training; Mental Depression; Motor; Motor Evoked Potentials; Motor Neurons; Muscle; Neuronal Plasticity; Neurons; Participant; Pattern; Persons; Physiological; Posture; Randomized; Recovery; Reflex action; Rehabilitation therapy; Soleus Muscle; Spinal; Spinal Cord; Spinal cord injury; Step training; Supination; Supine Position; Synapses; Testing; Therapeutic Intervention; Training; Treatment Protocols; United States National Institutes of Health; Walking; Work; base; clinical practice; functional gain; improved; injured; motor recovery; neuronal circuitry; neurophysiology; neuroregulation; relating to nervous system; sensory input; spinal reflex; standard of care

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.

项目概要 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。虽然这些缺陷可以通过运动训练得到部分改善，即使经过多次训练 训练期间，异常的肌肉活动和协调性仍然存在。因此，单靠运动训练并不能完全 优化加强连接大脑、脊髓和神经的突触所需的神经元可塑性 本地电路。因此，有效促进脊髓运动神经调节的治疗干预 非常需要网络和加强受损人类脊髓的神经连接。 经皮脊髓（经脊柱）刺激通过以下方式改变多个节段的运动神经元兴奋性 使运动神经元接近阈值，这是发挥下行和局部输入功能的先决条件。 重要的是，同时进行经脊柱刺激和运动训练治疗是否可以最大限度地提高运动能力 SCI 后的恢复情况未知。该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提高患有此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 次体重测量 支持以高频经脊柱刺激为基础的步进训练。参与者将被随机分配到 在站立（真实或假）或仰卧（真实）时接受经脊柱刺激。目标 1 评估如何 在 iSCI 中用高频经脊柱刺激启动运动训练会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 中用高频经脊柱刺激启动运动训练会影响重组和 脊髓神经元回路的适当参与。最后，目标 3 评估肢体内的改善 协调性以及站立和行走的能力。这些结果将支持高频补品的观点 经脊柱刺激通过姿势依赖性皮质脊髓增强皮质运动神经元连接 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柱 运动神经元网络。我们预计从这一机械临床试验中获得的信息将 极大地影响临床实践。这是因为在现实世界的临床环境中，无创经脊柱 与侵入性硬膜外刺激相比，刺激可以更容易、更广泛地实施。此外，通过 采用多种干预措施来加速运动恢复，我们采用的治疗方案是 代表了真正的临床方法。事实上，这种多方面的方法符合国家的优先事项 健康康复研究所。