Driving neuroplasticity with nerve stimulation and modified CIT

描述（由申请人提供）：中风是最具破坏性和最普遍的疾病之一，但在急性期限制组织损伤数量的努力令人失望，这突出了在神经损伤发生后需要有效的治疗干预。脑卒中康复研究的一个主要目标是利用大脑在神经损伤发生后的重组能力，从而最终导致功能的成功恢复。来自动物和人类模型的数据表明，感觉输入在运动输出中起重要作用，可能是通过影响皮质可塑性来实现的。然而，尽管迄今为止取得了进展，但对于周围神经刺激形式的感觉输入可以成功地与体育训练相结合的程度知之甚少。约束诱导疗法（CIT）是一种新型的功能运动强化训练方法，在脑卒中康复领域取得了可喜的成果。CIT包括用吊带或手套约束未受影响的手臂，结合受影响侧的高强度任务导向治疗，每天6小时，持续2周。这项初步研究将评估持续外周神经刺激与功能性运动训练相结合以改善手部运动功能的有效性。功能性运动训练遵循与CIT相同的原则，但每天的训练时间将缩短为每天4小时，因此在本提案中pi将其称为修改后的CIT。本研究的初步数据表明，外周神经刺激导致正常受试者皮层运动兴奋性增加。此外，慢性脑卒中患者的学习和使用依赖性可塑性可通过单次2小时的周围神经刺激得到显著增强。本研究的目的是验证在CIT前接受上肢周围神经刺激的脑卒中患者（干预组）与接受下肢周围神经刺激和CIT的脑卒中患者（对照组）相比，手部运动功能有改善的假设。运动功能改善的程度与经颅磁刺激测量的皮质运动图的增加有关。长期目标是：(a)最大限度地恢复中风后的手部运动功能；(b)确定这种干预对日常生活活动和生活质量的影响。

DESCRIPTION (provided by applicant): Stroke is one the most devastating and prevalent diseases, but efforts to limit the amount of tissue damaged in the acute phase have been disappointing, highlighting the need for effective therapeutic interventions after neurological damage has occurred. A major goal of the research in stroke rehabilitation is to harness the capacity of the brain to reorganize after neurological damage has occurred and thus ultimately lead to successful recovery of function. Data from animal and human models have suggested that sensory input plays an important role in motor output, possibly by influencing cortical plasticity. However, in spite of the advances to date, little is known about the extent to which sensory input in the form of peripheral nerve stimulation can be successfully combined to physical training. A new emerging approach called constraint induced therapy (CIT) is an intensive functional motor training and has produced promising results in the field of stroke rehabilitation. CIT involves restraining the unaffected arm with a sling or glove combined with intense task-oriented therapy of the affected side for six hours daily during 2 weeks. This pilot study will evaluate the effectiveness of sustained peripheral nerve stimulation coupled with functional motor training to improve hand motor function. While the functional motor training follows identical principles of CIT, the length of daily training will be shortened to 4 hours daily and thus the PIs will refer to it in this proposal as a modified CIT. Preliminary data for this study demonstrated that peripheral nerve stimulation results in increased cortical motor excitability in normal subjects. In addition, learning and use-dependent plasticity can be substantially enhanced by a single session of 2 hours of peripheral nerve stimulation in chronic stroke patients. The goal of this study is to test the hypothesis that stroke patients treated with upper extremity peripheral nerve stimulation preceding CIT (intervention group) will have improved hand motor function compared to a group receiving lower extremity peripheral nerve stimulation and CIT (control group). The PIs also expect that the degree of motor functional improvement will correlate with the increase of cortical motor map measured by transcranial magnetic stimulation. The long-range goals are: (a) to maximize the restoration of hand motor function after stroke and (b) to determine the impact of this intervention in activities of daily living and quality of life.