Evolution of Learned Nonuse in Stroke Hemiparesis

描述(申请人提供)：最近开发的一种治疗亚急性-慢性卒中后偏瘫的康复计划，强制诱导运动疗法(CI疗法)已被越来越多的人采用，由于其成功地从基础神经科学研究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，迄今已在全球范围内进行了300多项研究。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的情况下，改善瘫痪患者上肢在现实生活中的自发使用。中风后偏瘫肢体的减少使用，被称为习得性不使用(LNU)，被认为是由于反复无效的运动尝试而导致偏瘫肢体参与实际活动的行为抑制，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的LNU公式，而且许多慢性期CI治疗试验的结果表明，中风患者在治疗前就已经发展成LNU，但LNU假说到目前为止还没有在人类身上进行测试。拟议的两年研究将通过纵向评估急性偏瘫中风患者(N=66)在生活环境中自发使用瘫痪肢体的有效措施和实验室中的最大运动能力来解决这一知识差距。患者将在中风后7-10天接受评估，并在3个月后再次接受评估。不使用(定义为最大运动能力和同时自发的肢体使用之间的差异)被假设在此期间增加，这与学习机制一致。这项拟议的研究将前瞻性地确定不使用是否如LNU假说所预测的那样在这段时间间隔内显著增加。同时对协调性、灵巧性、触觉敏感度、握力、肢体张力、疼痛、抑郁、空间注意力和一般卒中损害进行临床评估，将确定这些因素是否调节LNU。脑部MRI弥散加权成像的急性缺血性损伤的程度，特别是皮质脊髓束脑过程的损伤程度，也将因其对LNU的贡献而被评估。这些发现将确定LNU的证据是否发生在急性-亚急性中风后阶段，以及它是否与临床或结构神经成像相关。这些发现将有助于更好地理解急性-亚急性偏瘫中风期间神经功能的连续纵向变化，这些变化与瘫痪肢体的运动有关，以及这些变化如何调节肢体的不使用。这些发现将被用于支持随后关于中风后LNU的流行病学和神经科学机制的扩展研究建议，这将对改善向中风幸存者提供神经康复服务具有重要意义。 与公共健康相关：这项提案将检验关于习得性不使用的起源的假设，习得性不使用是指在手臂仍有足够的运动能力进行日常生活活动的情况下，因中风而受损的手臂日常使用量的减少。不使用似乎通常发生在中风后，并已被发现在特定形式的运动疗法，特别是强制性诱导运动疗法(CI疗法)后显著和持久地改善。预计这项研究将提供试点数据，以帮助确定中风患者习得不使用的频率，以及哪些临床因素预测其发病，这反过来将有助于改进中风康复模型，该模型将在稍后更全面的资金提案中进一步测试。

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.