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

靶向经颅直流电刺激联合双手训练治疗脑瘫患儿

• 批准号: 10460461
• 负责人: Kathleen Margaret Friel
• 金额: $ 64.96万
• 依托单位: WINIFRED MASTERSON BURKE MED RES INST
• 依托单位国家: 美国
• 财政年份: 2014
• 资助国家: 美国
• 起止时间: 2014-09-26 至 2025-08-31
• 项目状态: 未结题
• 来源: https://reporter.nih.gov/project-details/10460461
• 关键词: Activities of Daily Living; Adoption; Adult; Affect; Anodes; Area; Brain; Cerebral Palsy; Child; Childhood; Clinical; Contralateral; Corticospinal Tracts; Data; Development; Effectiveness; Family; Financial cost; Funding; Future; Goals; Hand; Hand functions; Handedness; Heterogeneity; Hour; Impairment; Individual; Ipsilateral; Lead; Maps; Measures; Methods; Motor; Motor Cortex; Movement; Movement Disorders; Muscle; Neuronal Plasticity; Outcome; Pathway interactions; Pediatric Brain Injury; Physical Rehabilitation; Physiologic pulse; Physiology; Randomized; Randomized Clinical Trials; Rehabilitation therapy; Research; Resources; Side; Spastic Cerebral Palsy; Stroke; Testing; Time; Training; Transcranial magnetic stimulation; Treatment Cost; Treatment Efficacy; Upper Extremity; Work; base; constraint induced movement therapy; cost; dosage; effective intervention; efficacious treatment; evidence base; hemisphere damage; improved; innovation; low socioeconomic status; motor control; motor impairment; nervous system disorder; noninvasive brain stimulation; novel; personalized approach; personalized intervention; relating to nervous system; response; skills

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.

项目总结/摘要 单侧痉挛性脑性瘫痪（USCP）的特点是运动障碍，特别是上肢 (UE)身体一侧的损伤。尽管在改善UE康复方面取得了进展， 即使是最好的治疗方法也不能完全改善UE损伤，成本高昂，并且需要 大量的时间。因此，迫切需要优化UE疗法的有效性和成本。 我们的长期目标是制定基于证据的策略，以改善USCP儿童的运动。 发育中大脑的早期损伤可导致直接皮质脊髓束（CST）的重新布线 投射支配UE功能。在许多患有USCP的儿童中， 受损的半球，而不是同侧（同侧）CST通路控制受影响的运动 UE的以前，这种类型的重组被认为是适应不良的，对治疗没有反应。 然而，在本R 01的第一个资助期内，我们确定UE治疗疗效不依赖于 CST偏侧性。重要的是，我们发现包含CST连接的半球与受影响的手 在强化治疗后出现了神经可塑性变化尽管如此，大脑中的这种异质性 连通性意味着“一刀切”的康复办法不太可能适用。所以我们的 下一个目标是利用这些发现，使用个性化的方法来获得相同或更大的变化 通过使用经颅直流电增强神经可塑性变化来使用剂量的一部分 刺激（tDCS）。我们的初步结果表明，tDCS提高UE训练的有效性，只有当它是 针对用单脉冲经颅磁刺激（TMS）确定的个体的CST偏侧性。 此次更新的总体目标是通过以下方式纵向扩展我们在之前的R 01中学到的知识： 确定如何以tDCS为最佳目标，以提高USCP儿童UE训练的有效性。我们 中心假设是，双手训练（BT）结合tDCS蒙太奇针对半球， 与BT加假刺激相比，CST与受损UE肌肉的连接将改善UE功能。 我们将通过进行随机临床试验（RCT）来测试这一点，以确定靶向药物的疗效。 tDCS/BT改善UE功能以及tDCS/BT与运动皮层生理学之间的相互作用 USCP患儿。我们的工作假设是，接受靶向阳极tDCS的儿童将显示 手部功能和运动皮层生理学的最强有力的变化。协同效应的测定 tDCS和BT的组合可以大大减少改善UE所需的康复时间和成本。 功能拟议的工作是创新的，因为它可能会增加治疗的可及性，特别是对 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。