Transcranial Direct Current Stimulation and Robotic Training in Chronic Stroke

描述（由申请人提供）：运动技能训练和经颅直流电刺激（tDCS）分别被证明可以改变人类皮层的兴奋性和增强运动功能。它们的组合对增强中风患者的运动恢复很有吸引力，这是一个目前在全球范围内进行大量研究的领域。我们之前曾提出，经颅直流电刺激（tDCS）作为物理神经康复的补充治疗工具的成功可能取决于对两种技术相互作用的情况以及随后的行为结果的更精确的了解。为了验证这一点，我们使用常规参数（极性，位置，强度和持续时间）应用tDCS，但在偏瘫患者的受影响肌肉中，与简单的机器人运动练习任务相关的应用时间进行了操作。我们展示了时间的深远影响。我们表明，根据应用程序的时间，tDCS对一个练习会话的性能改进的影响是不同的。仅20分钟的机器人视觉运动训练，导致运动速度的优先增加而不损失准确性。在任何时间应用tDCS都可以消除这种效果，但在训练前应用tDCS时，这种效果被平滑度的改善所取代。运动流畅性与运动学习的高级阶段相关，并与临床功能量表高度相关。我们首次证明了tDCS应用的时机具有功能意义，在训练之前应用tDCS对自愿行为有益，tDCS效应可能不仅仅是训练效应的加法，而是可能改变训练效应的性质。我们在一项随机对照临床试验中单独报道，单独进行上肢机器人训练超过12周可以改善慢性中风患者的临床功能。基于我们对tDCS和机器人训练的研究结果，我们假设同样的重复机器人训练，但在tDCS之前，会比单独的机器人训练产生更大的持续和功能变化。在拟议的训练研究中，66名稳定的慢性卒中患者将在机器人上肢训练之前随机接受假或真tDCS，并将在3个变化水平上进行评估：(i)临床，（ii）运动学和（iii）神经生理学。我们将确定临床功能是否可以通过tdcs -机器人训练、运动的精确运动学方面和功能改善基础的皮质生理变化来改善和维持。

DESCRIPTION (provided by applicant): Motor skill training and transcranial direct current stimulation (tDCS) have separately been shown to alter cortical excitability and enhance motor function in humans. Their combination is appealing for augmenting motor recovery in stroke patients, and this is an area presently under heavy investigation globally. We had previously proposed that the success of transcranial direct current stimulation (tDCS) as a complementary therapeutic tool in physical neurorehabilitation may be contingent upon a more precise knowledge of the circumstances under which the two techniques interact, and the subsequent behavioral outcome. To test this we applied tDCS with conventional parameters (polarity, location, intensity and duration), but manipulated the timing of application in relation to a simple robotic motor practice task, in affected muscles of hemiplegic patients. We showed a profound effect of timing. We showed that performance improvement over one session of practice was differentially affected by tDCS depending on the timing of application. 20 mins of robotic visuomotor training only, led to a preferential increase in movement speed without a loss of accuracy. tDCS applied at any of the timings obliterated this effect, yet when tDCS was applied before training, the effect was substituted for an improvement in smoothness. Movement smoothness is associated with more advanced stages of motor learning and has high correlation with functional clinical scales. We showed for the first time that the timing of tDCS application has functional significance, that tDCS applied prior to training can be beneficial for voluntary behavior, and that tDCS effects may not simply be additive to training effects, but may change the nature of the training effect. We have separately reported in a randomized-controlled clinical trial, that upperlimb robotic training alone over 12 weeks can improve clinical function of chronic stroke patients. Based on our results with tDCS and robotic training, we hypothesize that the same repeated sessions of robotic training, but preceded by tDCS, would lead to a sustained and functional change greater than robotic training alone. In the proposed training study, 66 stable chronic stroke patients will be randomized to receive sham or real tDCS prior to robotic upperlimb training, and will be assessed at 3 levels of change: (i) clinical, (ii) kinematic, and (iii) neurophysiologic. We will determine if clinical function can be improved and sustained with tDCS-robotic training, the precise kinematic aspects of movement, and cortical physiology changes that underlie functional improvements. 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. We suggest that Transcranial Direct Current Stimulation (tDCS) delivered prior to robotic motor training will improve clinical function when performed over 12 weeks of training. We propose to test cortical neurophysiology and kinematic changes in relation to improved clinical function to report the specific aspects of movement control that are enhanced, and the underlying brain plasticity. This will help understand the physiological and behavioral aspects of this emerging rehabilitation strategy, and may be useful to guide clinical trials for optimizing motor recovery in stroke, and ultimately to have broader application to other neurological disorders.