Changing a Reflex to Improve Locomotion

描述（由申请人提供）：不完全性脊髓损伤（SCI）患者通常有实质性残疾，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无力的随意肌控制。脊髓反射通路的改变导致了这些问题。在这个人群中，经常观察到过度的拉伸反射和踝关节伸肌的异常反射修饰。正常情况下，脊柱反射从站立到行走发生调节，在行走过程中，脊柱反射在步态周期的不同阶段进一步调节。然而，在脊髓损伤后的个体中，行走时比目鱼h反射的调节通常不存在或大大减弱（即，即使在站立或摆动的早期阶段，h反射通常很小或不存在，反射振幅仍然很高）。脊髓反射可以通过操作性条件反射而改变。先前对大鼠和猴子的研究表明，成功的操作性条件反射不仅改变了条件反射通路，还改变了其他脊髓和棘上通路的活动。因此，有可能引导与学习相关的中枢神经系统可塑性改变脊髓反射通路的活动，从而改善运动障碍。这个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受损的影响。在人类身上，每天进行的反射条件反射实验次数要比在老鼠身上进行的实验少得多，但也能产生相当数量的反射变化。最近在大鼠身上的研究表明，比目鱼h反射操作性条件反射改变了比目鱼在运动中的行为，表明适当的条件反射可以改善不完全性脊髓损伤后的运动。基于这些发现，该项目将测试两个假设。第一种假说认为，在慢性不完全性脊髓损伤引起的痉挛性反射高的受试者中，通过操作性下条件反射降低比目鱼h反射可以改善运动。第二个假设是，在运动的适当阶段，当h反射通常不存在时，通过下行条件反射程序可以进一步改善运动。这些假设将通过在不完全性脊髓损伤的痉挛受试者中应用比目鱼h反射的下调节来验证。将评估条件反射对运动肌电活动、步态反射调节、步态运动学和步行速度的影响。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条件反射作为一种新的治疗方法的发展，以改善脊髓损伤后个体的运动功能恢复。这种新方法应该补充现有的方法，增强有用功能的恢复。

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.