Rehabilitation of corticospinal control of walking following stroke

描述（由申请人提供）： 目前用于中风后行走的康复方法不能充分恢复运动功能。例如，只有不到50%的中风引起的行走功能障碍患者能够在社区中恢复独立行走的能力。需要在康复方面取得新的突破，这将针对导致中风后个人行走功能差的运动障碍。功能恢复可以发生在响应受损脑回路的任务特异性神经可塑性。皮质脊髓束是神经可塑性的重要靶点，因为它在人类行走控制中起着重要作用。我们和其他人已经表明，与稳态行走相比，准确的步态调整（ACC）任务是激活皮质脊髓束的有效行为刺激。因此，我们建议使用ACC任务进行培训（例如，障碍物穿越/避免，准确的脚放置等）在诱发皮质脊髓神经可塑性和步行功能恢复方面可能上级稳态步行训练。大多数康复模式以前都集中在SS训练上。这在很大程度上是因为治疗师认为，当稳态行走的持续缺陷仍然存在时，进行ACC任务还为时过早。然而，这种推理可能适得其反，因为仅训练稳态行走可能不足以刺激受损皮质脊髓通路的神经可塑性。相反，ACC训练是专门设计来刺激皮质脊髓神经可塑性的。重要的是，由于AC训练的目标是一个中央机制，它的好处预计将在步行条件下推广。此外，预计它将使大多数卒中幸存者受益，这些幸存者至少具有激活皮质脊髓束的最小残余能力。ACC培训还提供了一个机会，练习类似于在家庭和社区环境中遇到的挑战的任务。因此，有很强的机制和实际的理由，行政协调会的培训。包括我们自己的飞行员训练干预在内的一些早期研究已经累积建立了令人兴奋的初步证据，表明行走功能通过ACC任务训练得到增强。然而，没有先前的研究已经专门设计和足够的权力，以确定在何种程度上“准确的步态修改”的成分是至关重要的步行功能的恢复。同样不清楚的是，ACC训练在多大程度上减少了导致行走功能差的神经损伤。这项研究的中心假设是，ACC训练将是上级的SS训练，增加步行功能和减少潜在的神经控制中风后轻偏瘫的成年人的轻瘫腿。每次干预将涉及12周的训练，每周3天（共36次），并将强调高强度，重复和 任务特异性评估将在干预前即刻、干预后即刻和3个月后的随访时进行。行走功能将在实验室和“真实的世界”中进行测量。神经损伤指标将包括肌间协调和皮质脊髓驱动的基于肌电图的指标。我们预计ACC训练的益处将证明更大规模的随机对照试验是合理的，以优化ACC训练的使用，包括与中风相关的时间，与其他治疗方法的结合，以及确定最有可能从这种方法中受益的个体。这项研究有望提高中风幸存者的行走功能，包括每年中风的15，000名退伍军人。

DESCRIPTION (provided by applicant): Current approaches for rehabilitation of walking following stroke do not sufficiently restore mobility function. For instance, fewer than 50% of individuals with stroke-induced walking dysfunction recover the ability to walk independently in the community. New breakthroughs in rehabilitation are needed that will target the motor impairments responsible for poor walking function in individuals post-stroke. Functional recovery can occur in response to task-specific neuroplasticity of damaged brain circuitry. The corticospinal tract is an important target for neuroplasticity because it plays an important role for control of walking in humans. We and others have shown that, compared to steady state walking, accurate gait modification (ACC) tasks are a potent behavioral stimulus for activating the corticospinal tract. Therefore, we propose that training with ACC tasks (e.g., obstacle crossing/avoidance, accurate foot placement, etc.) may be superior to training with steady state walking (SS) for eliciting corticospinal neuroplasticity and recovery of walking function. Most rehabilitation paradigms have previously focused on SS training. This is largely because therapists consider it premature to progress to ACC tasks when persistent deficits of steady state walking still remain. However, this reasoning might be counter-productive, because training only steady state walking may not sufficiently stimulate neuro- plasticity of the damaged corticospinal pathway. In contrast, ACC training is specifically designed to stimulate corticospinal neuroplasticity. Importantly, since AC training targets a central mechanism, its benefits are expected to generalize across walking conditions. Furthermore, it is expected to benefit most stroke survivors who possess at least a minimal residual capability to activate the corticospinal tract. ACC training also provides an opportunity to practice tasks that are analogous to challenges encountered in the home and community environments. Accordingly, there is strong mechanistic and practical rationale for ACC training. A number of earlier studies including our own pilot training intervention have cumulatively established exciting preliminary evidence showing that walking function is enhanced by training with ACC tasks. However, no prior study has been specifically designed and sufficiently powered to determine the extent to which the "accurate gait modification" ingredient is crucial for recovery of walking function. Also not known is the extent to which ACC training reduces the neural impairments underlying poor walking function. The central hypothesis of this study is that ACC training will be superior to SS training for increasing walkin function and for reducing underlying neural control of the paretic leg in adults with post-stroke hemiparesis. Each intervention will involve twelve weeks of training, 3 days per week (36 sessions total), and will emphasize the motor learning principles of high intensity, repetition and task-specificity. Assessments will be conducted immediately pre- intervention, immediately post-intervention and at a follow-up session 3 months later. Walking function will be measured in the lab and in the "real world". Neural impairment measures will include electromyography-based measures of inter-muscular coordination and corticospinal drive. We expect that the benefits of ACC training will justify larger randomized controlled trials to optimize the use of ACC training, including timing relative to stroke, combination with other therapeutic approaches, and identifying individuals who are most likely to benefit from this approach. This research is expected to enhance walking function in stroke survivors, including for the 15,000 Veterans who suffer a stroke each year.