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: 8571168
• 负责人: Dylan James Edwards
• 金额: $ 28.73万
• 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/8571168
• 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）：在人类中使用非侵入性刺激技术的神经调节是治疗神经系统损害的最有希望的进步之一。尽管在开发针对大脑的治疗技术方面已经做出了广泛的工作，但直接靶向脊髓几乎没有重点。我们最近开发了一种人类重复的刺激范式，以靶向安全，有效，耐受性的脊髓，并导致持久的脊柱兴奋性增强。在一项小型试点研究中，我们表明这种脊柱兴奋性调节可以在受影响的慢性脊髓损伤患者的下肢肌肉中复制。目的：在本研究中，我们的目标是：（1）确定是否是否 在脊柱缔合性刺激（SAS）之后，在下肢瘫痪的SCI样本样本中提高了脊柱兴奋性，（2）检查后效应的时间顺序，（3）通过测量与脊柱兴奋性的自愿运动的变化来确定功能后果，并通过在未尝试的肌肉固定过程中评估的脊柱兴奋性相关，并评估脊柱兴奋性。方法：由于我们先前的工作表明，兴奋性调节取决于配对技术，而不是仅安慰剂或外围刺激，因此我们将使用主体内部使用PES POST干预设计，在30名慢性不完整的SCI患者中提供实际刺激范式。根据我们以前在健康受试者中的工作，主要结果度量将为H反射阈值。其次，我们将通过在干预后0、15和30分钟重复基线测量来检查效果如何随时间变化。此外，在每个时间点尝试最大自愿收缩期间，我们还记录表面EMG。我们预计干预后至少15分钟会提高脊柱兴奋性，并且随着兴奋性的增强，自愿激活可能会增强。结果/结论：如果正如预测的，我们确定 我们称为脊柱缔合性刺激的方法对SCI患者有效，这可能会深刻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了潜力，包括在存在痉挛的情况下降低兴奋性。意义：脊柱缔合刺激是基于脊柱网络中已知的时机相互作用的第一个配对的非侵入性技术，可调节脊柱兴奋性。此外，它是人类中的几种技术，曾经开发出靶向脊髓，包括侵入性刺激。