Novel Strategies to Enhance Motor Function After Stroke

 描述（由申请人提供）：轻偏瘫（身体一侧的手臂和腿部失去运动控制和力量）是中风后最常见的问题，是成人残疾的主要原因。大多数力量和控制力的恢复发生在中风后的前3个月。随后的恢复主要是学习用剩余能力进行补偿的结果。动物模型表明，早期恢复是中风区域周围上调的修复过程（可塑性增强）和训练方案之间相互作用的结果。关于人类中风恢复的早期研究很少。在这个建议中，我们将使用两种主要方法来确定中风后前3个月与接下来的6个月相比大脑状态的区别。第一种方法使用非侵入性脑刺激方法来测试假设，即与中风后的后期和年龄匹配的对照组相比，人类大脑在中风后的前3个月内具有更高的兴奋性和可塑性。第二种方法检验了这样一个假设，即与随后的几个月相比，患者在中风后的前3个月对运动训练的反应更大。也就是说，中风后早期的患者可能是特别好的学习者。我们的两个假设的时间窗口的可塑性提高和训练的反应性增加的构象将有重要意义的未来创新的神经康复。首先，如果能够检测到任何特定患者的可塑性增强状态，那么它就可以用来设计一种算法来规划康复计划。例如，如果高度可塑性仍然存在，那么将强调损伤的康复，而不是教授依赖于备用能力的补偿策略。如果可塑性被认为已经恢复到正常水平，那么补偿将被强调。其次，具有增强的可塑性的测定将允许评估试图延长、增强或重新打开恢复的这个关键时间窗口的药理学和其他方法。

 DESCRIPTION (provided by applicant): Hemiparesis (loss of motor control and strength in the arm and leg on one side of the body) is the most common problem after stroke, the leading cause of adult disability. Most recovery of strength and control occurs in the first 3 months post stroke. Subsequent recovery is mainly the result of learning to compensate with residual capacities. Animal models suggest that the early recovery occurs as the result of interactions between up-regulated repair processes around the region of the stroke (heightened plasticity) and training regimens. There has been very little study of the early period of stroke recovery in humans. In this proposal we will use two principal approaches to determine what distinguishes the state of the brain in the first 3 months after stroke compared to the next 6 months. The first approach uses non-invasive brain stimulation methods to test the hypothesis that the human brain has heightened excitability and plasticity in the first 3 months after stroke compared both to later after stroke and to age-matched controls. The second approach tests the hypothesis that patients are more responsive to motor training in the first 3 months after stroke compared to subsequent months. That is to say, patients early after stroke may be particularly good learners. Conformation of our two hypotheses about a time window of heightened plasticity and increased responsiveness to training will have important implications for future innovations in neuro-rehabilitation. First, if it is possible to detect the state of heightened plasticity in any given atient then it could be used to devise an algorithm for how to plan rehabilitation. For example, if heightened plasticity were still present then rehabilitation of impairment would be emphasized rather than teaching compensatory strategies that rely on spared capacities. If plasticity were seen to have returned to normal levels then compensation would be emphasized. Second, having assays of heightened plasticity will allow assessment of pharmacological and other approaches that attempt to prolong, augment or re-open this critical time window of recovery.