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

描述（由申请人提供）：在人类中使用非侵入性刺激技术进行神经调节是神经损伤治疗中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模式，该模式安全、有效、耐受性好，并能持久地增强脊髓兴奋性。在一个小型的试点研究中，我们发现这种脊髓兴奋性调节可以在慢性脊髓损伤患者的下肢肌肉中复制。目的：在本研究中，我们旨在：(1)确定是否

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.