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的皮质兴奋性和增强运动功能。它们的结合是为了促进中风患者的运动恢复，这是目前全球正在大力研究的一个领域。我们先前提出，经颅直流电刺激(TDC)作为物理神经康复的补充治疗工具的成功可能取决于对这两种技术相互作用的环境以及随后的行为结果的更准确的了解。为了测试这一点，我们在偏瘫患者的受影响肌肉中应用了具有常规参数(极性、位置、强度和持续时间)的tDCS，但操纵了与简单的机器人运动练习任务相关的应用时间。我们表现出了对时机的深刻影响。我们发现，根据应用时间的不同，tdcs对一次练习的性能改善有不同的影响。只进行20分钟的机器人视觉运动训练，在不损失精确度的情况下优先提高运动速度。在任何时间点应用tdcs都会消除这种影响，但当tdcs在训练前应用时，这种效果会取代平顺性的改善。动作流畅性与运动学习的高级阶段有关，与功能性临床评分高度相关。本研究首次证明了tdcs应用的时机具有功能意义，tdcs在训练前应用对自愿行为是有益的，tdcs效应可能不是简单地增加训练效果，而是可能改变训练效果的性质。我们已经分别在一项随机对照临床试验中报道，仅上肢机器人训练超过12周就可以改善慢性中风患者的临床功能。根据我们对tDCS和机器人培训的结果，我们假设，相同的重复机器人培训课程，但在tDCS之前，将导致持续的和功能上的变化，比单独的机器人培训更大。在拟议的训练研究中，66名稳定的慢性中风患者将在机器人上肢训练之前随机接受假的或真实的tDC，并将在3个水平上进行评估：(I)临床、(Ii)运动学和(Iii)神经生理学。我们将确定是否可以通过tdcs-机器人训练、运动的精确运动学方面以及作为功能改善基础的皮质生理学变化来改善和维持临床功能。 公共卫生相关性：中风幸存者通常会留下残留的运动功能障碍，尽管众所周知的护理会导致大量的个人、社会和经济成本。我们认为，在机器人运动训练之前实施经颅直流电刺激(TDC)将改善超过12周的训练后的临床功能。我们建议测试与改善临床功能有关的皮质神经生理学和运动学变化，以报告增强的运动控制的特定方面，以及潜在的大脑可塑性。这将有助于理解这一新兴康复策略的生理和行为方面，并可能有助于指导临床试验，以优化中风的运动恢复，并最终在其他神经疾病中有更广泛的应用。

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.