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: 9917446
• 负责人: Kathleen Margaret Friel
• 金额: $ 70.95万
• 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/9917446
• 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; evidence base; hemisphere damage; improved; innovation; low socioeconomic status; motor control; motor impairment; nervous system disorder; 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.

项目概要/摘要 单侧痉挛性脑瘫 (USCP) 的特点是运动缺陷，尤其是上肢 (UE) 身体一侧的损伤。尽管在改善UE康复方面已经取得了长足进步 即使是最好的可用疗法也无法完全改善 UE 损伤，而且成本高昂，并且需要 大量的时间。因此，迫切需要优化 UE 治疗的有效性和成本。 我们的长期目标是制定基于证据的策略来改善 USCP 儿童的运动。 发育中大脑的早期损伤可能导致直接皮质脊髓束 (CST) 的重新布线 预测支配 UE 功能。在许多患有 USCP 的儿童中，没有与父母的 CST 连接。 受损的半球，而是同侧（同侧）CST 通路控制受影响的运动 UE。此前，这种类型的重组被认为是适应不良且对治疗无反应。 然而，在该 R01 的第一个资助期间，我们确定 UE 治疗效果独立于 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 显示出对强化治疗的反应的神经塑性变化。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方法不太可能适用。因此，我们的 下一个目标是使用个性化方法利用这些发现来获得相同或更大的变化 通过经颅直流电增强神经塑性变化，使用一小部分剂量 刺激（经颅直流电刺激）。我们的初步结果表明，只有在以下情况下，tDCS 才能增强 UE 训练的效果： 针对通过单脉冲经颅磁刺激 (TMS) 确定的个体 CST 偏侧性。 此次更新的总体目标是垂直扩展我们在之前的 R01 中学到的知识： 确定如何最佳地瞄准 tDCS，以提高 USCP 儿童 UE 训练的效果。我们的 中心假设是，双手训练 (BT) 与针对大脑半球的 tDCS 蒙太奇相结合 与 BT 加假刺激相比，CST 连接到受损的 UE 肌肉将更能改善 UE 功能。 我们将通过进行随机临床试验（RCT）来测试这一点，以确定靶向药物的功效 tDCS/BT 用于改善 UE 功能以及 tDCS/BT 与运动皮层生理学之间的相互作用 患有 USCP 的儿童。我们的工作假设是，接受靶向阳极 tDCS 的儿童将表现出 手部功能和运动皮层生理学最剧烈的变化。协同效应的测定 tDCS 和 BT 的结合可以大大减少改善 UE 所需的康复时间和成本 功能。拟议的工作具有创新性，因为它可以增加治疗的可及性，特别是对于 由于治疗费用降低，为社会经济地位较低的家庭提供服务的中心。