Spinal reflex conditioning system for enhancing motor function recovery after incomplete spinal cord injury

项目摘要 由于慢性脊髓损伤（SCI）而导致痉挛的人可以从反射操作中受益 调节疗法，如母案申请中所述。经皮刺激 胫神经是我们正在实施的比目鱼肌H反射条件反射的重要组成部分， 产生因人而异的不适感。这种不适是最小的和可以忍受的 在大多数经历过它的人中。然而，在高达20%的人中， 刺激是不容易忍受的。因此，刺激程序无法执行 并且个体可以选择退出反射调节疗法。例如， 由于SCI引起的慢性疼痛或对经皮刺激过敏的个体， 更容易感受到皮肤表面刺激带来的不适。排除这些 来自潜在患者群体的个体并不理想，但迄今为止已被耐受， 因为刺激不适是一个长期存在的问题，并不是我们手术所独有的， 大多数候选患者选择接受操作性条件反射治疗， 体验它的好处。 我们最近有了一个意外的发现， 多电极配置可以减少患者的不适。通过结合可定制的 控制多电极刺激配置到我们的反射条件反射系统，我们建议 以降低刺激不适的发生率。这种刺激不适的减少将 扩大我们正在翻译的反射操作性条件反射疗法的候选患者群 投入临床使用，让更多的患者从中受益。 为了提高患者在刺激期间的舒适度，同时保持相同的有效性 在作为标准单电极刺激的H反射诱发中，我们提出了三个目标。要求1 将评估并最终确定针对刺激舒适性优化的刺激电极阵列设计， 可用性和有效性。我们将通过收集系列试验的反馈来实现这一目标 使用三种不同的电极设计迭代，对具有不同腿部尺寸的志愿者进行测试。目的 2将检查不同刺激电极的有效性、感知和舒适度 在没有神经系统疾病的志愿者中进行配置。这一目标将缩小参数 使募集最大化和使募集最小化 不适目标3将在神经系统疾病患者身上测试这些最佳配置。 这一目标将确认是否至少有一个多电极配置将产生更少的 比传统的单电极刺激更舒适。这一目标也将证实， 经历刺激不适的个体将 选择接受扩展操作性条件反射治疗。 拟议的行政补充将使我们能够利用意想不到的 有机会增加患者的舒适度与反射条件反射治疗，我们是 翻译到诊所这一进步应该会加强临床传播和采用 新系统，并扩大可以从中受益的患者人群。这些好处应该 大大提高了项目的最终实用价值，并与同行一致， 审查目标。

Project Summary People with spasticity due to chronic Spinal Cord Injury (SCI) can benefit from reflex operant conditioning therapy, as described in the parent application. Transcutaneous stimulation of the tibial nerve, an essential element of the soleus H-reflex conditioning we are implementing, can produce discomfort that varies from person to person. This discomfort is minimal and tolerable in most individuals who experience it. In up to 20% individuals, however, the discomfort from stimulation is not easily tolerable. As a result, the stimulation procedure cannot be administered and the individual may opt out of reflex conditioning therapy. For example, individuals with chronic pain due to SCI or individuals with hypersensitivity to transcutaneous stimulation can be more prone to experience discomfort from skin-surface stimulation. The exclusion of these individuals from the potential patient population is not ideal, but has been tolerated to date, because stimulation discomfort is a longstanding issue not unique to our procedures, and because the majority of candidate patients do elect to undergo operant conditioning therapy and experience its benefits. We recently made the unexpected discovery that surface stimulation with appropriately tuned multi-electrode configurations can reduce patient discomfort. By incorporating customizable control of multi-electrode stimulus configuration into our reflex conditioning system we propose to reduce the incidence of stimulation discomfort. This reduction of stimulation discomfort would expand the candidate patient base for the reflex operant conditioning therapy we are translating into clinical use, so that many more patients might benefit from it. In order to improve patient comfort during stimulation, while maintaining the same effectiveness in H-reflex elicitation as the standard single electrode stimulation, we propose three aims. Aim 1 will evaluate and finalize a stimulating electrode array design optimized for stimulation comfort, usability, and effectiveness. We will accomplish this aim by gathering feedback from serial trials on volunteers with various leg dimensions, using three different electrode design iterations. Aim 2 will examine the effectiveness, perception, and comfort level of different stimulation electrode configurations in volunteers with no neurological conditions. This aim will narrow the parameter space of potential electrode configurations which maximize recruitment and minimize discomfort. Aim 3 will test these optimal configurations on patients with neurological conditions. This aim will confirm whether at least one of the multi-electrode configurations will produce less discomfort than the conventional single-electrode stimulation. This aim will also confirm whether there is an increased probability that individuals who experience stimulation discomfort would elect to undergo extended operant conditioning therapy. The proposed administrative supplement will allow us to take advantage of the unanticipated opportunity to increase patient comfort involved with the reflex conditioning therapy that we are translating to the clinic. This advance should enhance clinical dissemination and adoption of the new system and expand the patient population that can benefit from it. These benefits should greatly increase the ultimate practical value of the project and are consistent with its peer- reviewed objectives.