Targeted transcranial direct current stimulation combined with bimanual training for children with cerebral palsy

项目摘要/摘要 单侧痉挛型脑性瘫痪(USCP)的特点是运动障碍，尤其是上肢 身体一侧的损伤。尽管在改善UE康复方面取得了很大进展 方法，即使是最好的治疗方法也不能完全改善UE的损害，成本高昂，需要 大量的时间。因此，迫切需要优化UE治疗的有效性和成本。 我们的长期目标是开发基于证据的策略，以改善USCP儿童的运动能力。 对发育中的大脑的早期损伤可能导致直接皮质脊髓束(Cst)的重新连接。 支配UE功能的投射。在许多患有USCP的儿童中，没有来自 受损的大脑半球，而是同侧(同侧)的CST通路控制受影响的运动 UE。以前，这种类型的重组被认为是不适应的，对治疗没有反应。 然而，在这个R01的第一个资助期，我们确定UE治疗的疗效独立于 CST偏侧性。重要的是，我们发现包含CST连接到患手的半球 对强化治疗的反应显示神经可塑性的改变。尽管如此，大脑的这种异质性 连通性意味着，一刀切的康复方法不太可能适用。因此，我们的 下一个目标是使用个性化的方法利用这些发现来实现相同或更大的更改 经颅直流电增强神经可塑性改变的一小部分剂量 刺激(Tdcs)。我们的初步结果表明，只有当它是 以单脉冲经颅磁刺激(TMS)确定的个人CST偏侧为目标。 此次更新的总体目标是垂直扩展在我们之前的R01中学到的内容 确定如何以TDC为最佳靶点，以提高USCP儿童UE训练的有效性。我们的 中心假设是双指甲训练(BT)与TDCS蒙太奇相结合，针对大脑半球 CST连接到受损的UE肌肉比BT加假刺激更能改善UE功能。 我们将通过进行随机临床试验(RCT)来测试这一点，以确定靶向治疗的疗效 Tdcs/Bt改善UE功能及其与运动皮质生理的相互作用 患有USCP的儿童。我们的工作假设是，接受靶向阳极tDCs治疗的儿童将表现出 手功能和运动皮质生理学的变化最强劲。协同效应的确定 TDC和BT的使用可以大大减少改善UE所需的恢复时间和成本 功能。拟议的工作具有创新性，因为它可以增加治疗的可及性，特别是 由于治疗费用的降低，为社会经济地位较低的家庭提供服务的中心。

PROJECT SUMMARY/ABSTRACT Unilateral spastic cerebral palsy (USCP) is characterized by movement deficits, particularly upper extremity (UE) impairments on one side of the body. Although strides have been made to improve UE rehabilitation approaches, even the best available therapies fail to fully ameliorate UE impairments, are costly, and require large amounts of time. Thus, there is an urgent need to optimize the effectiveness and cost of UE therapies. Our long-term goal is to develop evidence-based strategies to improve movement in children with USCP. Early damage to the developing brain can result in a re-wiring of the direct corticospinal tract (CST) projections innervating UE function. In many children with USCP, there are no CST connections from the damaged hemisphere, and instead ipsilateral (same-sided) CST pathways control movement of the affected UE. Previously, this type of reorganization was believed to be maladaptive and unresponsive to treatment. However, during the first funding period of this R01, we determined that UE therapy efficacy is independent of CST laterality. Importantly, we found that the hemisphere containing CST connectivity to the affected hand showed neuroplastic changes in response to intensive therapy. Nonetheless, this heterogeneity in the brain connectivity means it is unlikely that a one-size-fits-all rehabilitation approach will be suitable. Therefore, our next goal is to leverage these findings using an individualized approach to obtain the same or greater changes using a fraction of the dosage by enhancing the neuroplastic changes with transcranial direct current stimulation (tDCS). Our preliminary results show that tDCS enhances the efficacy of UE training only if it is targeted to an individual’s CST laterality determined with single-pulse transcranial magnetic stimulation (TMS). The overall objective for this renewal is to vertically extend what has been learned under our prior R01 by determining how to optimally target tDCS to enhance the efficacy of UE training in children with USCP. Our central hypothesis is that bimanual training (BT) combined with a tDCS montage targeting the hemisphere with CST connectivity to the impaired UE muscles will improve UE function more than BT plus sham stimulation. We will test this by conducting a randomized clinical trial (RCT) to determine the efficacy of targeted tDCS/BT for improving UE function and interactions between tDCS/BT and motor cortex physiology in children with USCP. Our working hypotheses are that children who receive targeted anodal tDCS will show the most robust changes in hand function and motor cortex physiology. Determination of the synergistic effects of tDCS and BT may substantially reduce the required rehabilitation time and cost necessary to improve UE function. The proposed work is innovative because it may increase accessibility of treatment, particularly for centers that serve families of lower socio-economic status, due to the reduced cost of therapy.