Changing a reflex to improve locomotion

描述(由申请人提供)：不完全脊髓损伤(SCI)患者通常有严重残疾，即使在完成常规治疗后也是如此。脊髓损伤后常见的运动异常包括痉挛和自主肌肉控制能力弱。脊椎反射路径的改变导致了这些问题。在这个人群中，经常可以观察到夸大的伸展反射和异常的踝伸缩肌反射改变。正常情况下，脊柱反射是从站立到行走进行调节的，而在行走过程中，在步态周期的不同阶段之间，脊椎反射又被进一步调节。然而，在脊髓损伤后的个体中，比目鱼肌H反射在行走过程中的调制通常不存在或大大减弱(即，即使在H反射通常很小或不存在的早期站立或摆动阶段，反射幅度仍然很高)。脊髓反射可以通过操作性条件反射来改变。以前在大鼠和猴子身上的研究表明，成功的脊髓反射的可操作性条件反射不仅改变了受限制的反射路径，还改变了其他脊髓和脊髓上路径的活动。因此，有可能引导与学习相关的中枢神经系统的可塑性来改变脊髓反射通路的活性，从而改善运动障碍。本项目的目的是研究改变脊髓反射对慢性不完全性脊髓损伤后运动障碍的影响。在人类中，与大鼠相比，每天试验次数少得多的反射条件反射可以产生类似数量的反射变化。最近在大鼠身上的研究表明，比目鱼肌H反射操作性条件反射可以改变比目鱼肌在运动过程中的行为，并表明适当的条件反射可以改善不完全脊髓损伤后的运动能力。基于这些发现，该项目将检验两个假设。第一个假设是，在慢性不完全性脊髓损伤导致的痉挛反射亢进的受试者中，通过操作性下行条件反射降低比目鱼肌H反射可以改善运动能力。第二个假设是，在正常情况下没有H反射的适当运动阶段，通过应用向下条件反射程序，可以进一步改善运动能力。这些假说将通过对患有不完全性脊髓损伤的痉挛受试者应用比目鱼肌H反射下行条件来检验。在训练前后，我们将评估训练对运动性肌电活动、步态反射调节、步态运动学和行走速度的影响。我们还将评估这些影响的持久性。我们期望发现成功的H反射下行调节可以改善不完全性脊髓损伤后的运动恢复，并且这种改善将持续下去。该项目的成功完成将促进脊髓反射操作性调节作为一种新的治疗方法的发展，以改善脊髓损伤后个人运动功能的恢复。这种新的方法应该是对现有方法的补充，并增加有用功能的恢复。

DESCRIPTION (provided by applicant): People with incomplete spinal cord injury (SCI) often have substantial disabilities, even after completing conventional therapy. Common motor abnormalities after SCI include spasticity and weak voluntary muscle control. Altered spinal reflex pathways contribute to these problems. In this population, exaggerated stretch reflex and abnormal reflex modification of the ankle extensors are frequently observed. Normally, spinal reflexes are modulated from standing to walking, and during walking reflexes are further modulated between different phases of the gait cycle. However, in individuals after SCI, modulation of the soleus H-reflex during walking is often absent or greatly diminished (i.e., the reflex amplitude remains high even in the early stance or swing phase, where the H-reflex is normally very small or absent). Spinal reflexes can be changed through operant conditioning. Previous work in rats and monkeys shows that successful operant conditioning of a spinal reflex changes not only the reflex pathway that is conditioned but also the activity of other spinal and supraspinal pathways. Therefore, it may be possible to guide central nervous system plasticity associated with learning to change the activity of a spinal reflex pathway such that movement disabilities can be ameliorated. The goal of this project is to investigate the impact of changing a spinal reflex on impaired locomotion after chronic incomplete SCI in people. In humans, reflex conditioning with a far smaller number of trials per day than those used in rats can produce a comparable amount of reflex change. Recent work in rats shows that soleus H-reflex operant conditioning changes soleus behavior during locomotion, and indicates that appropriate conditioning can improve locomotion after incomplete SCI. Based on these findings, this project will test two hypotheses. The first hypothesis is that, in subjects with spastic hyperreflexia due to chronic incomplete SCI, decreasing the soleus H-reflex by operant down-conditioning can improve locomotion. The second hypothesis is that, locomotion can be further improved by applying down-conditioning procedures during appropriate phases of locomotion, when the H-reflex should normally be absent. These hypotheses will be tested by applying down-conditioning of the soleus H-reflex in spastic subjects with incomplete SCI. The impact of conditioning on the locomotor EMG activity, reflex modulation during gait, gait kinematics, and walking speed will be assessed, before and after conditioning. We will also assess the persistence of these effects. We expect to find that successful H-reflex down-conditioning can improve locomotion recovery after incomplete SCI and that this improvement will persist. Successful completion of this project will facilitate development of spinal reflex operant conditioning as a new, therapeutic approach to improving motor function recovery for individuals after SCI. This new method should complement existing methods and augment restoration of useful function.