Transcranial Direct Current Stimulation and Motor Training in Chronic Stroke

描述（由申请人提供）：中风后，专注于特定任务的运动康复训练比单独的自发恢复有更好的功能结果，但残余残疾仍然是一个突出的问题。目前，人们对使用脑电刺激来促进运动恢复有了新的兴趣。其基本原理是基于支持与电生理变化相关的短期行为变化的证据。如果补充脑刺激是产生更强大的和有临床意义的结果，那么就需要更好地理解应用参数。我们在8名慢性中风患者中发现，在机器人手腕训练之前进行的阳极tDCS可以显著提高受影响手臂的皮质兴奋性，同时减少皮质内抑制，并在短短6次训练中导致手腕功能的临床有意义的改善。这些结果表明，tDCS和随意感觉运动皮层激活可以共存，不受干扰，并可能导致运动记忆获得增强。这些结果也提出了关于tDCS应用与机器人训练的时间关系的关键问题。已知tDCS引起的运动皮层兴奋性变化是由刺激期间和刺激后的不同机制引起的，因此可能与自愿网络激活有不同的相互作用，这取决于刺激何时传递。操纵这种联合治疗顺序的行为和电生理后果以前没有被测试过。我们假设，如果tDCS直接先于治疗，tDCS联合物理治疗在促进脑卒中后皮质可塑性和帮助运动功能恢复方面比单独治疗更有效。我们计划使用公认的经颅磁刺激测量皮层兴奋性，以及一种新的抽搐扭矩测量和运动控制测量，来测试在不同时间进行的tDCS对慢性卒中患者既定运动编码范式的影响。我们预测，突触可塑性的后效应的阳极tDCS在M1，将加强运动模式的编码。本建议代表了一种理解新兴卒中康复治疗机制的创新方法，因此与当前R21 FOA的目标直接相关。公共卫生相关性：中风幸存者往往会留下残余的运动功能障碍，尽管有最好的治疗方法，但会导致巨大的个人、社会和经济成本。使用非侵入性脑刺激来增强慢性中风运动训练的效果是一项新兴技术，但其机制和最佳参数尚不清楚。我们的发现将有助于指导优化中风患者运动恢复的临床试验，并可能最终在其他神经系统疾病中有更广泛的应用。

DESCRIPTION (provided by applicant): Following stroke, focused task-specific training for motor rehabilitation leads to superior functional outcomes compared to spontaneous recovery alone, yet residual disability remains a prominent issue. There is presently a resurgence of interest in the use of electric brain stimulation to facilitate motor recovery. The rationale is based on evidence supporting short-term behavioral changes correlated with and electrophysiological changes. If supplementary brain stimulation is to produce more robust and clinically meaningful outcomes, then a better understanding of the application parameters is required. We showed in 8 chronic stroke patients, that anodal tDCS delivered prior to robotic wrist training can significantly raised cortical excitability to the affected arm, accompanied with reduced intracortical inhibition, and lead to clinically meaningful improvements in wrist function over as little as six sessions. These results suggest that tDCS and voluntary sensorimotor cortex activation can co-exist, without interference, and may lead to enhanced motor memory acquisition. These results also raise critical questions about the temporal relationship of tDCS application and robotic training. Changes in motor cortex excitability resulting from tDCS are known to result from separate mechanisms during, and after the stimulation period, thus may have differential interactions with voluntary network activation, depending on when stimulation is delivered. The behavioral and electrophysiological consequences of manipulating the order of this combined therapy have not been previously tested. We hypothesize that tDCS coupled with physical therapy, can be more effective than therapy alone in promoting cortical plasticity and aiding recovery of motor function after stroke, if tDCS directly precedes therapy. We plan to use accepted TMS measures of cortical excitability, together with a novel twitch torque measure and motor control measures, to test the effects of tDCS delivered at different times in relation to an established motor encoding paradigm in chronic stroke patients. We predict that synaptic plasticity after-effects of anodal tDCS in M1, will enhance encoding of a motor pattern. The present proposal represents an innovative approach to understanding mechanisms of emerging stroke rehabilitation therapies, and thus relates directly to the aims of the present R21 FOA. PUBLIC HEALTH RELEVANCE: Stroke survivors are often left with residual motor dysfunction which despite the best known care, results in substantial personal, social and economic cost. Using non-invasive brain stimulation to augment effects of motor training in chronic stroke is an emerging technique, yet the mechanisms and optimal parameters remain unclear. Our findings will be useful to guide clinical trials for optimizing motor recovery in stroke, and may ultimately have broader application to other neurological disorders.