Human Spinal Circuit Plasticity with Locomotor Training in SCI

描述（由申请人提供）： 目的-本研究旨在研究运动不完全性脊髓损伤（SCI）后与运动训练相关的人脊髓神经回路可塑性，并确定该可塑性与步态功能恢复程度之间的关系。研究计划-在拟议的研究中，我们将研究亚急性运动不完全性脊髓损伤的受试者之前，多次期间，和3个月后的机器人运动训练课程。我们将通过H反射测试评估脊髓反射回路的功能，并将其与地面步态的功能恢复进行比较。我们已经研究了在3个月的运动训练之前和之后的步行过程中比目鱼肌中的H反射，并且发现那些反射在恢复相对较大的地面步态速度的患者中减少或“正常化”，但是那些反射实际上在仅恢复较慢的地面步态速度的患者中增加。我们感兴趣的是确定这些患者反射变化的时间过程，并找出恢复更快的步态速度和更正常的反射的患者，如果他们只达到较慢的步态速度时，第一次经历反射亢进的相对增加。这表明我们应该训练那些恢复步态速度较慢的人更长时间。我们还建议同时研究其他腿部肌肉的H反射，以确定比目鱼肌H反射恢复模式是否适用于所有下肢肌肉。方法-一旦患者符合入选/排除标准并提供知情同意书，他们将适合并定向于机器人步态矫形器，Lokomat和该设备中的运动训练。在4个月的运动训练之前、期间每月和之后3个月，将通过步态恢复的临床测量对患者进行电生理评估。功能性步态测量将是在10米步行期间测量的速度，以及使用GAITRite系统记录步幅和站立宽度等参数的步进测量。电生理测试将采用一种新技术进行，以在多个下肢肌肉中同时产生H反射。对腰背根的刺激在所有腿部肌肉中产生这些“背根运动电位”，并且可以在运动训练期间的不同条件下在相同的时间点进行研究，作为步态测量。具体来说，我们将研究背根运动电位在两个不同的跑步机速度和两个不同的体重支持在Lokomat。一旦进行了基线电生理和功能步态测量，患者将在Lokomat中开始开始16周的运动训练。随着时间的推移，运动训练速度将增加，BWS将降低，这是患者可以耐受的。一旦训练开始，功能步态测量和电生理测试将每4周进行一次，错开两周。也就是说，在训练开始后2、6、10和14周，将重复功能性步态测量，并在4、8、12和16周，将进行电生理测量。一旦患者完成运动训练，他们将被要求在3个月后返回进行随访功能步态测量和电生理测试，以确定自训练以来这些功能步态测量和电生理测试是否随时间发生变化。

DESCRIPTION (provided by applicant): Objective - The proposed study is designed to investigate human spinal neural circuit plasticity associated with locomotor training following motor incomplete spinal cord injury (SCI) and determine the relationship between that plasticity and the extent of functional recovery of gait. Research Plan - In the proposed study we will study subjects with sub-acute motor incomplete SCI before, multiple times during, and 3 months following a course of robotic locomotor training. We will assess spinal reflex circuit functioning as measured by H reflex testing and compare that with functional recovery of over ground gait. We have studied H-reflexes in the soleus muscle during stepping before and after 3 months of locomotor training and found that those reflexes decrease or "normalize" in patients who recover relatively greater over ground gait speeds but that those reflexes actually increase in patients who only recover slower over ground gait speeds. We are interested in determining the time course of reflex changes in these patients and in finding out if patients who recover faster gait speeds and more normal reflexes first experience a relative increase in hypereflexia when they have only achieved slower gait speeds. This would indicate we should train those with slower recovered gait speeds for longer periods of time. We also propose to study H-reflexes simultaneously in other leg muscles to determine if the soleus H-reflex recovery pattern is common to all lower limb muscles or not. Methods - Once patients meet inclusion/exclusion criteria and provide informed consent, they will be fitted for and oriented to the robotic gait orthosis, the Lokomat, and locomotor training in that device. Before, monthly during and 3 months after 4 months of locomotor training, patients will be assessed electrophysiologically and by clinical measures of gait recovery. Functional gait measures will be speed, measured during a 10 meter walk, and stepping measurements using the GAITRite system to document parameters like stride length and stance width. Electrophysiological testing will be carried out with a new technique to generate simultaneous H reflexes in multiple lower limb muscles. Stimulation of the lumbar dorsal roots generates these "dorsal root motor potentials" in all leg muscles and can be studied under various conditions at the same time points during locomotor training as gait measures are taken. Specifically, we will study dorsal root motor potentials at two different treadmill speeds and at two different body weight supports in the Lokomat. Once baseline electrophysiological and functional gait measures have been taken, patients will begin 16 weeks of locomotor training in the Lokomat. Over time, the locomotor training speed will be increased and the BWS decreased as can be tolerated by the patient. Once training has begun, functional gait measurement and electrophysiological testing will occur every 4 weeks, staggered by two weeks. That is to say that at 2, 6, 10 and 14 weeks after training begins functional gait measures will be repeated and at 4, 8, 12 and 16 weeks, electrophysiological measures will be taken. Once patients have completed their locomotor training, they will be asked to return 3 months later for follow up functional gait measures and electrophysiological testing to determine whether those have changed over time since training.