Altering Activation Patterns in the Distal Upper Extremity After Stroke

描述（由申请人提供）：拟议研究的目的是探索一种新方法对瘫痪患者运动控制康复的潜在治疗益处 中风幸存者的上肢远端。这种多模态治疗将用于减少不必要的神经肌肉过度兴奋的药理学试剂的施用与专注于扩大肌肉激活工作空间的探索的训练范例相结合。在我们以前的研究中，我们已经观察到在手部产生适当的肌肉激活模式方面存在显着的缺陷。运动神经元过度兴奋，特别是长手指屈肌，是显而易见的，因为是一个减少的能力，适当地调节激活模式，根据任务。拟议的研究将直接解决这些复杂问题。因此，我们将追求以下目标：目标1：确定抗肾上腺素能药物在降低卒中后过度兴奋方面优于常规药物的程度，而不影响自主激活或警觉性。盐酸替扎尼定是一种临床使用的抗痉挛药物，已被证明可以有效降低运动神经元的过度兴奋性，可能是通过去甲肾上腺素能途径，但会引起严重的副作用，包括嗜睡。在初步研究中，我们确定了一种有前途的替代药物，抗肾上腺素能药物盐酸赛庚啶，它能够减少过度兴奋，而不减少单剂量的自愿力量。我们将比较替扎尼定和赛庚啶在慢性剂量下的作用。我们假设：赛庚啶比替扎尼定更有效地减少不需要的过度兴奋而不降低强度或增加嗜睡。 目的2：评估使用单胺能药物与上肢训练相结合的多模式干预的有效性。我们预期，将在目标1中发现有效的单胺能药物联合给药以减少屈肌过度兴奋，并进行集中训练以改变肌肉激活模式，将有助于康复。将比较两种不同的训练技术，一种直接关注通过定制的计算机游戏进行肌肉激活模式的训练，另一种利用新的职业治疗训练方案。我们假设：药物与训练的联合治疗将导致比单独给药或治疗性训练更大的功能改善。此外，我们假设：对于接受多模式训练的组，运动控制的改善对于那些用肌电图控制的计算机游戏进行训练的组将更大。 拟议的研究的目的是建立新的技术，最大限度地恢复瘫痪上肢中风后的运动功能，特别是在个人更严重的远端损害。本研究的结果将对脑卒中康复的临床实践有直接的意义。

DESCRIPTION (provided by applicant): The goal of the proposed study is to explore the potential therapeutic benefit of a novel approach to rehabilitation of motor control of the paretic distal upper limb in stroke survivors. This multimodality treatment combines administration of a pharmacological agent for reducing unwanted neuromuscular hyperexcitability with a training paradigm focused on expanding exploration of the muscle activation workspace. In our previous research, we have observed striking deficits in the generation of proper muscle activation patterns in the hand. Motoneuronal hyperexcitability, especially of the long finger-flexors, is readily apparent, as is a diminished capacity to appropriately modulate activation patterns according to task. The proposed study would directly address these complications. Accordingly, we will pursue the following aims: Aim 1: Determine the extent to which anti-serotonergic agents outperform conventional medications in reducing hyperexcitability post-stroke without impacting voluntary activation or alertness. Tizanidine hydrochloride, a clinically administered anti-spasticity medication, has been shown to effectively reduce motoneuron hyperexcitability, presumably through noradrenergic pathways, but causes serious side effects including somnolence. In preliminary studies we identified a promising alternative drug, the anti-serotonergic agent cyproheptadine hydrochloride, which was able to reduce hyperexcitability without reducing voluntary strength for single doses. We will compare the effects of tizanidine and cyproheptadine at chronic dosages. We hypothesize that: cyproheptadine will be more effective than tizanidine in reducing unwanted hyperexcitability without diminishing strength or increasing somnolence. Aim 2: Assess the efficacy of using a multimodality intervention combining monoaminergic agents with upper extremity training. We anticipate that combining administration of the monoaminergic drug found effective in Aim 1 to reduce flexor hyperexcitability with focused training to alter muscle activation patterns will facilitate rehabilitation. Two different training techniques will be compared, one focusing directly on the training of muscle activation patterns through a custom computer game and the other utilizing a novel occupational therapy training protocol. We hypothesize that: the combined therapy of the drug with the training will lead to greater functional improvement over either drug administration or therapeutic training alone. Further, we hypothesize that: for the groups receiving multimodal training, improvements in motor control, will be greater for those training with the electromyographically controlled computer games. The proposed study is aimed at contributing to the establishment of new techniques for maximizing recovery of motor function of the paretic upper limb post-stroke, especially in individuals with more severe distal impairment. The results of this study will have immediate import for clinical practice for stroke rehabilitation.