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: 10643807
• 负责人: NOAM Y. HAREL
• 金额: $ 54.69万
• 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/10643807
• 关键词: Acceleration; Activities of Daily Living; Affect; Body Weight; Brain; Chronic; Clinical; Clinical Trials; Complex; Electromyography; Equilibrium; Force of Gravity; 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; Vertebral column; Walking; Work; clinical practice; effective intervention; functional gain; improved; injured; motor recovery; neural; neuronal circuitry; neurophysiology; neuroregulation; 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.

项目摘要 脊髓损伤（SCI）极大地损害了站立和步行能力，这严重损害了日常生活 活动。尽管这些缺陷通过运动训练可以部分改善，但即使经过多次训练 会议，异常的肌肉活动和协调仍然存在。因此，单独的运动训练不能完全 优化加强连接大脑，脊髓和 本地电路。因此，有效促进脊柱运动神经调节的治疗干预措施 非常需要网络并增强受伤的人脊髓的神经连通性。 经皮脊髓（经脊柱）刺激改变了多个片段的运动神经元兴奋性。 使运动神经元更接近阈值，阈值是功能下降和本地输入的先决条件。 重要的是，与跨脊柱刺激和运动训练的并发治疗是否可使运动最大化 SCI后的恢复未知。该临床试验的目的是使用高频（30 Hz）跨脊柱 刺激运动训练，并最终提高患者的站立和步行能力 慢性不完整SCI（ISCI）。 ISCI的45个人将进行40次体重 - 具有高频跨脊柱刺激的支持的步骤训练。参与者将被随机 在站立期间（实际或假）或仰卧（真实）接收跨脊柱刺激。 AIM 1评估如何 ISCI中具有高频跨脊柱刺激的启动运动训练改变了皮质瘤性神经元 连通性强度，如电动机从腿部记录的电势所表明的那样。 AIM 2评估如何 ISCI中具有高频跨脊柱刺激的启动运动训练会影响重组和 脊柱神经元电路的适当参与。最后，AIM 3评估INTALIMB的改善 协调和站立和行走的能力。这些结果将支持强调高频的观念 跨脊柱刺激通过姿势依赖性皮质脊髓增强皮质瘤性神经元连通性 神经可塑性。此外，这些结果将表明适当的神经调节和脊柱促进 运动神经元网络。我们预计从这项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中的临床环境中，无创跨脊髓 刺激比侵入性硬膜外刺激更容易和广泛地实现。另外，由 采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 代表一种真正的临床方法。确实，这种多方面的方法符合民族的优先事项 康复卫生研究院。

项目成果

Priming locomotor training with transspinal stimulation in people with spinal cord injury: study protocol of a randomized clinical trial.

对脊髓损伤患者进行经脊柱刺激启动运动训练：随机临床试验的研究方案。

• DOI: 10.21203/rs.3.rs-2527617/v1
• 发表时间: 2023
• 期刊: Research square
• 作者: Skiadopoulos,Andreas;Famodimu,GraceO;Solomon,ShammahK;Agrawal,Parul;Harel,NoamY;Knikou,Maria
• 通讯作者: Knikou,Maria

Adapting Human-Based Transcutaneous Spinal Cord Stimulation to Develop a Clinically Relevant Animal Model.

• DOI: 10.3390/jcm11072023
• 发表时间: 2022-04-05
• 期刊: Journal of clinical medicine
• 影响因子: 3.9
• 作者: Malloy DC;Knikou M;Côté MP
• 通讯作者: Côté MP

Brain and spinal cord paired stimulation coupled with locomotor training facilitates motor output in human spinal cord injury.

• DOI: 10.3389/fneur.2022.1000940
• 发表时间: 2022
• 期刊: Frontiers in neurology
• 影响因子: 3.4

Neurophysiological Changes After Paired Brain and Spinal Cord Stimulation Coupled With Locomotor Training in Human Spinal Cord Injury.

• DOI: 10.3389/fneur.2021.627975
• 发表时间: 2021
• 期刊: Frontiers in neurology
• 影响因子: 3.4
• 作者: Pulverenti TS;Zaaya M;Grabowski M;Grabowski E;Islam MA;Li J;Murray LM;Knikou M
• 通讯作者: Knikou M

Tapping Into the Human Spinal Locomotor Centres With Transspinal Stimulation.

通过跨脊柱刺激挖掘人类脊柱运动中心。

• DOI: 10.21203/rs.3.rs-3818499/v1
• 发表时间: 2024
• 期刊: Research square
• 作者: Skiadopoulos,Andreas;Knikou,Maria
• 通讯作者: Knikou,Maria