Non-invasive stimulation for improving motor function in spinal cord injury

无创刺激改善脊髓损伤的运动功能

• 批准号: 8705562
• 负责人: Dylan James Edwards
• 金额: $ 23.19万
• 依托单位: WINIFRED MASTERSON BURKE MED RES INST
• 依托单位国家: 美国
• 财政年份: 2013
• 资助国家: 美国
• 起止时间: 2013-08-01 至 2015-07-31
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/8705562
• 关键词: Accounting; Affect; Animal Model; Behavioral; Brain; Chronic; Clinical; Corticospinal Tracts; Electromyography; Fiber; Future; H-Reflex; Human; Injury; Intervention; Leg; Lower Extremity; Magnetism; Measures; Methods; Motor; Motor Cortex; Motor Neurons; Motor Skills; Muscle; Muscle Contraction; Nervous System Trauma; Outcome Measure; Paraplegia; Patients; Performance; Peripheral; Physical therapy; Physiologic pulse; Pilot Projects; Placebo Effect; Placebos; Plastics; Posterior Tibial Nerves; Protocols documentation; Publishing; Recovery; Regulation; Rehabilitation therapy; Residual state; Rest; Sampling; Sensory; Soleus Muscle; Spinal; Spinal Cord; Spinal cord injury; Spinal cord injury patients; Stimulus; Surface; Techniques; Testing; Time; Training; Work; base; conditioning; improved; improved functioning; motor function improvement; nervous system disorder; neuroregulation; paired stimuli; post intervention; public health relevance; restoration; therapy design

DESCRIPTION (provided by applicant): Neuromodulation using non-invasive stimulation techniques in humans is one of the most promising advances in treatment of neurological damage. While extensive work has been done in developing these techniques for therapy targeting the brain, there has been little emphasis on targeting spinal cord directly. We recently a developed a human repetitive stimulation paradigm to target spinal cord that is safe, effective, well tolerated, and results in lasting spinal excitability enhancement. In a small pilot study we showed that this spinal excitability modulation could be replicated in affected lower limb muscles of chronic spinal cord injury patients. Objective: In the present study we aim to: (1) determine if spinal excitability is raised following spinal associative stimulation (SAS) in a larger sample of SCI patients with lower limb paralysis, (2) examine the time-course of after effects, and (3) establish the functional consequences by measuring the change in voluntary motor activation associated with raised spinal excitability, assessed by the presence of background EMG during attempted muscle contraction. Methods: Since our prior work showed that the excitability modulation is contingent upon the paired technique, and not placebo or peripheral stimulation alone, we will provide the real stimulation paradigm in 30 chronic incomplete SCI patients, using a within subjects, pre-post intervention design. The principal outcome measure will be H-reflex threshold as per our previous work in healthy subjects. We will secondarily examine how the effect changes over time by repeating the baseline measures at 0, 15 and 30 minutes post intervention. We additionally be recording surface EMG during attempted maximal voluntary contractions at each of the time points. We expect that spinal excitability will be raised for at least 15 minutes post intervention, and that voluntary activation may be enhanced in association with heightened excitability. Results/Conclusions: If, as predicted, we establish conclusively that our method termed spinal associative stimulation is effective in SCI patients, this could profoundly influence the field of non-invasive stimulation, and open up the potential for a range of techniques for spinal cord targeting, including down-regulating excitability in the presence of spasticity. Significance: Spinal associative stimulation is the first paired non-invasive technique based on known timing-dependent interactions in spinal networks, to modulate spinal excitability. Further, it is one few techniques in humans, ever developed targeting spinal cord, including invasive stimulation.

描述（由申请人提供）：在人体中使用无创刺激技术进行神经调节是治疗神经损伤方面最有前途的进展之一。虽然在开发这些针对大脑的治疗技术方面已经做了大量的工作，但很少强调直接针对脊髓。我们最近开发了一种针对脊髓的人类重复刺激范例，该范例安全、有效、耐受性良好，并导致持久的脊髓兴奋性增强。在一个小型的初步研究中，我们发现这种脊髓兴奋性调制可以在慢性脊髓损伤患者的下肢肌肉中复制。目的：本研究的目的是：（1）确定是否 脊髓兴奋性在伴有下肢瘫痪的SCI患者的较大样本中在脊髓联合刺激（SAS）后升高，（2）检查后效的时间过程，和（3）通过测量与升高的脊髓兴奋性相关的自主运动激活的变化来建立功能后果，通过在尝试肌肉收缩期间存在背景EMG来评估。研究方法：由于我们先前的工作表明，兴奋性调制是视配对技术，而不是安慰剂或外周刺激单独，我们将提供真实的刺激范例在30例慢性不完全性SCI患者，使用受试者内，前后干预设计。根据我们之前在健康受试者中的工作，主要结局指标将是H反射阈值。我们将通过在干预后0、15和30分钟重复基线测量，再次检查效果如何随时间变化。我们还记录了在每个时间点尝试最大自主收缩时的表面肌电图。我们预计，脊髓兴奋性将提高至少15分钟后干预，自愿激活可能会增强与兴奋性提高。结果/结论：如果，正如预测的那样，我们最终确定， 我们的称为脊髓联合刺激的方法在SCI患者中是有效的，这可以深刻地影响非侵入性刺激的领域，并为脊髓靶向的一系列技术打开潜力，包括在痉挛状态存在时下调兴奋性。重要性：脊髓联合刺激是第一个成对的非侵入性技术的基础上，已知的时间依赖性相互作用的脊髓网络，以调节脊髓兴奋性。此外，它是人类中少数几种针对脊髓开发的技术，包括侵入性刺激。