Evolution of Learned Nonuse in Stroke Hemiparesis

描述（由申请人提供）：最近开发的亚急性慢性卒中后偏瘫康复计划，约束诱导运动疗法（CI疗法）已被越来越多地采用，迄今为止已在全球300多项研究中进行了调查，因为它成功地转化为基础神经科学研究，并在许多随机对照临床试验中证明了其有效性。该疗法的主要价值是在肢体有足够的运动能力来完成日常生活任务时，改善麻痹性上肢在现实生活中的自发使用。中风后麻痹肢体的使用减少，被称为习得性不使用（LNU），假设是由于麻痹肢体参与现实世界活动的行为抑制，因为它反复无效的运动尝试，同时受到影响较小的上肢的有效补偿。然而，尽管基础神经科学研究通过详细的观察支持了偏瘫动物模型中LNU的形成，并且许多慢性CI治疗试验的结果表明，中风患者在治疗前就已经发生了LNU，但迄今为止，LNU假说尚未在人类中得到验证。拟议的为期2年的研究将通过纵向评估急性偏瘫性卒中患者（N = 66）在生活环境中自发麻痹肢体使用和实验室最大运动能力的验证措施来解决这一知识差距。患者将在中风后7-10天和3个月时再次进行评估。不使用（定义为最大运动能力和同时自发肢体使用之间的差异）被假设在此期间增加，与学习机制一致。拟议的研究将前瞻性地确定不使用是否在这段时间间隔内显着增加，正如LNU假设所预测的那样。同时对协调性、灵巧性、触觉敏感性、握力、肢体张力、疼痛、抑郁、空间注意和一般卒中损害的临床评估将确定这些因素是否调节LNU。脑MRI弥散加权成像的急性缺血性损伤程度，特别是皮质脊髓束脑过程的损伤程度，也将评估其对LNU的贡献。研究结果将确定LNU的证据是否发生在脑卒中后急性-亚急性期，以及是否与临床或结构神经影像学相关。该研究结果将有助于提高对急性-亚急性偏瘫中风期间与麻痹肢体运动相关的神经功能的连续纵向变化的理解，以及这些变化如何调节肢体不使用。该研究结果将用于支持后续关于脑卒中后LNU的流行病学和神经科学机制的扩展研究建议，这将对改善脑卒中幸存者的神经康复服务具有重要意义。

DESCRIPTION (provided by applicant): A recently developed rehabilitation program for subacute-chronic post-stroke hemiparesis, Constraint-Induced Movement therapy (CI therapy), has become increasingly adopted, and has been investigated worldwide in over 300 studies to date, due to its successful translation from basic neuroscience research studies and its demonstrated efficacy in numerous randomized controlled clinical trials. The therapy's principal value is for improving the spontaneous use of the paretic upper extremity in the real-life setting when the limb has sufficient movement ability to complete daily living tasks. The reduced use of the paretic limb post-stroke, termed learned nonuse (LNU), is hypothesized to result from the behavioral suppression of the paretic limb's participation in real-world activities due to its repeated ineffectual movement attempts and simultaneously effective compensation by the less-affected upper extremity. However, although basic neuroscience research has supported the LNU formulation in animal models of hemiparesis through detailed observations, and outcomes from numerous CI therapy trials in the chronic phase have suggested that stroke patients had developed LNU before treatment, the LNU hypothesis thus far has not been tested in humans. The proposed 2 year research will address this knowledge gap by longitudinally evaluating acutely hemiparetic stroke patients (N = 66) on validated measures of spontaneous paretic limb use in the life setting and maximal movement ability in the laboratory. Patients will be evaluated at 7-10 days post-stroke and again at 3 months. Nonuse (defined as the difference between maximal movement ability and simultaneous spontaneous limb use) is hypothesized to increase during this period, consistent with a learning mechanism. The proposed research will prospectively determine whether nonuse significantly increases over this time interval, as predicted by the LNU hypothesis. Concurrent clinical evaluations of coordination, dexterity, tactile sensitivity, grip strength, limb tone, pain, depression, spatial attention, and general stroke impairment will determine whether these factors modulate LNU. The extent of acute ischemic injury on Diffusion-Weighted Imaging on brain MRI, and in particular the extent of injury to the cerebral course of the corticospinal tract, will also be evaluated for their contribution to LNU. The findings will determine whether evidence for LNU occurs in the acute-subacute poststroke phase and whether it has clinical or structural neuroimaging correlates. The findings will help to improve understanding the sequential longitudinal changes of neurologic functions during acute-subacute hemiparetic stroke that relate to movement of the paretic limb and how these may modulate limb nonuse. The findings will be used to support subsequent extended research proposals on the epidemiology and neuroscientific mechanisms of LNU after stroke, which will be important for improving the delivery of neurologic rehabilitation to stroke survivors. PUBLIC HEALTH RELEVANCE: This proposal will test hypotheses concerning the origin of learned nonuse, which is the reduction in the amount of daily use by the arm that has been impaired by stroke, when the arm nonetheless has sufficient movement ability to perform daily living activities. Nonuse appears to commonly occur after stroke and has been found to significantly and enduringly improve after specific forms of movement therapy, particularly Constraint-Induced Movement therapy (CI therapy). The research is expected to provide pilot data to help determine how frequently learned nonuse occurs in stroke and what clinical factors predict its onset, which in turn would help to improve models for stroke rehabilitation that will be tested further in later, more comprehensive funding proposals.