rTMS and Motor Learning Training to Promote Recovery from Hemiparesis

描述(申请人提供)：中风后瘫痪不仅源于中风后死亡神经元的丧失，也源于中风半球休眠神经元的丧失。存活神经元变得休眠(下调)的原因之一是非中风半球对它们施加了过度的大脑半球间抑制。神经康复的挑战是恢复中风半球中这些下调的神经元的兴奋性和自愿控制。抑制这种过度的大脑半球间抑制的来源可以通过称为重复经颅磁刺激(RTMS)的非侵入性方法来实现。在健康受试者中已经表明，低频rTMS的已知抑制作用可以通过在其之前进行6赫兹的启动刺激来增加和延长。在最近的一项安全性研究中，我们表明，一种应用于非卒中半球的6赫兹预置低频rTMS治疗是安全的。现在重要的是评估一系列这些治疗方法，以及是否可以通过将rTMS与运动学习训练相结合来提高它们的疗效。本研究的具体目的是确定6-Hz预置低频rTMS治疗非卒中半球并结合运动学习训练促进偏瘫手康复的5种治疗方法的疗效、机制和安全性。40名中风患者将被随机分配到四个治疗组中的一个。RTMS/Only组将收到20分钟。每天的rTMS。曲目/唯一组将获得20分钟的时间。每天的手指跟踪训练。RTMS/联合组将交替接受rTMS和Track治疗。RTMS/Sham组将收到20分钟。每天使用假电极的rTMS。假设如下：1)rTMS/联合组的手功能改善最大，2)rTMS/联合组在双脉冲TMS测试的皮质兴奋性和fMRI脑重组方面的改善最大，3)rTMS治疗是安全的。这项拟议的研究很重要，因为它解决了社会上长期残疾的最大原因-中风后偏瘫，而且它具有创新性，因为它应用了一种以前从未使用过的技术，即6赫兹启动的低频rTMS与运动学习训练相结合。这项研究的潜在影响是彻底改变康复，实现更高质量的中风生活。

DESCRIPTION (provided by applicant): Paralysis following stroke stems not only from the loss of neurons killed by the stroke but also from the loss of neurons lying dormant in the stroke hemisphere. One of the reasons viable neurons become dormant (down-regulated) is because of excessive interhemispheric inhibition imposed on them from the nonstroke hemisphere. The challenge in neurorehabilitation is to restore excitability and voluntary control of these down-regulated neurons in the stroke hemisphere. Suppression of the source of this excessive interhemispheric inhibition can be achieved with the noninvasive method called repetitive transcranial magnetic stimulation (rTMS). It has been shown in healthy subjects that the known depressant effects of low-frequency rTMS can be increased and prolonged by preceding it with 6-Hz priming stimulation. In a recent safety study, we showed that one treatment of 6-Hz primed low-frequency rTMS applied to the nonstroke hemisphere is safe. It is now important to evaluate a series of these treatments and whether their efficacy can be enhanced by combining the rTMS with motor learning training. The specific aims of this study are to determine the efficacy, mechanism, and safety of a series of 5 treatments of 6-Hz primed low- frequency rTMS applied to nonstroke hemisphere and combined with motor learning training to promote recovery of the paretic hand. Forty subjects with stroke will be randomly assigned to one of four treatment groups. The rTMS/only group will receive 20 min. of rTMS per day. The Track/only group will receive 20 min. of finger tracking training per day. The rTMS/combined group will receive alternating days of the rTMS and Track treatments. The rTMS/sham group will receive 20 min. of rTMS using a sham electrode each day. The hypotheses are: 1) the rTMS/combined group will show the greatest improvements in hand function, 2) the rTMS/combined group will show the greatest improvements in cortical excitability using paired-pulse TMS testing and in brain reorganization using fMRI, and 3) the rTMS treatment will be safe. The proposed research is important because it addresses the greatest cause of long-term disability in society, hemiparesis following stroke, and it is innovative because it applies a technique never used before, 6-Hz primed low-frequency rTMS combined with motor learning training. The potential impact of this research is a radical change to rehabilitation that accomplishes a higher quality of life in stroke.