Remote Ischemic Conditioning to Enhance Motor Learning and Corticospinal Excitability in Children with Unilateral Cerebral Palsy

远程缺血调理可增强单侧脑瘫儿童的运动学习和皮质脊髓兴奋性

• 批准号: 10669555
• 负责人: Swati Manoharrao Surkar
• 金额: $ 16.3万
• 依托单位: EAST CAROLINA UNIVERSITY
• 依托单位国家: 美国
• 财政年份: 2022
• 资助国家: 美国
• 起止时间: 2022-08-01 至 2025-07-31
• 项目状态: 未结题
• 来源: https://reporter.nih.gov/project-details/10669555
• 关键词: Acute; Affect; Age; Animal Model; Astrocytes; Behavior Therapy; Behavioral; Biostatistical Methods; Blood Pressure; Brain; Brain Injuries; Brain-Derived Neurotrophic Factor; Cerebral Palsy; Child; Childhood; Classification; Clinical; Clinical Trials; Disease; Dose; Effectiveness; Elderly; Enrollment; Equilibrium; Foundations; Future; Glutamates; Goals; Hand; Human; Impairment; Individual; Intervention; Ischemia; Knowledge; Knowledge acquisition; Learning Skill; Leg; Limb structure; Live Birth; Manuals; Methods; Motor; Motor Cortex; Motor Evoked Potentials; Motor Skills; Movement; Myocardium; Nature; Neurobiology; Neuronal Plasticity; Neurons; Organ; Outcome; Performance; Periodicity; Population; Process; Protocols documentation; Quality of life; Randomized, Controlled Trials; Recurrence; Rehabilitation Outcome; Rehabilitation therapy; Reperfusion Therapy; Research; Rest; Severities; Side; Speed; Stroke; System; Techniques; Technology; Time; Training; Transcranial magnetic stimulation; Translating; United States; Upper Extremity; Work; acute stroke; angiogenesis; arm; arm function; arm paresis; blind; cardioprotection; conditioning; cost; disability; effective intervention; efficacious intervention; functional improvement; functional outcomes; gamma-Aminobutyric Acid; improved; ischemic conditioning; motor learning; motor skill learning; neurogenesis; neuroimaging; neuroprotection; neuroregulation; noninvasive brain stimulation; novel; novel strategies; organ injury; phase 2 designs; phase II trial; post intervention; pre-clinical; pressure; rehabilitation strategy; remote delivery; repetitive task practice; skills; skills training; stroke model; young adult

PROJECT SUMMARY/ABSTRACT Unilateral cerebral palsy (UCP) is a leading cause of childhood disability. An early brain injury impairs the upper extremity function, bimanual coordination, and impacts the child's independence. The effectiveness of existing rehabilitation approaches to improve the paretic arm function is limited due to higher training doses, modest effect sizes, and poor retention of training effects. Thus, there is a critical need to find an effective priming agent that, when paired with motor (bimanual) skill training, will facilitate neurobiological processes to enhance the magnitude of training effects and improve functional capabilities of children with UCP. This proposal aims to determine the effects of a novel priming agent, remote ischemic conditioning (RIC), when paired with bimanual skill training to enhance bimanual skill learning and to augment skill dependent plasticity in children with UCP. Ischemic conditioning (IC) is a phenomenon of protecting the target organ from ischemia by directly exposing it to brief episodes of sublethal ischemia. RIC is a clinically feasible way of performing IC where episodes of ischemia and reperfusion are delivered with cyclic inflation and deflation of a blood pressure cuff on the arm or leg. Pre-clinical and preliminary clinical trials in humans show neuroprotective effects of RIC. Our prior work has shown that when paired with motor training, RIC enhances motor learning in healthy individuals. Based on these diversified benefits of RIC, our central hypothesis is that the multifactorial mechanisms of RIC can be harnessed as a priming agent to enhance motor learning and augment neuroplasticity in children with UCP. Our Specific Aims are: 1) to determine the effects of RIC + training on bimanual skill performance, and 2) to determine the effects of RIC + training on corticospinal randomized controlled trial, 30 children with UCP will first upper conditioning excitability undergo bimanual speed stack performance, functional extremity, and Transcranial Magnetic Stimulation assessments. Children will then undergo RIC/Sham plus training. in children with UCP. In this triple blind, We will deliver RIC/sham conditioning via cyclic inflation and deflation of a pressure cuff on the paretic arm using a standard protocol. Training will involve 5 days (15 trials/day) of bimanual speed stack training. Thechildren will perform the same baseline assessmentspost-intervention. We hypothesize that compared to sham conditioning + training, RIC + training will significantly enhance: 1) bimanual skill performance (decrease in movement time (sec) to complete bimanual speed stack task), 2) bimanual function (increase in the Assisting Hand Assessment scores), 3) cortical excitability in the ipsilesional primary motor cortex (M1) (larger amplitude of motor evoked potentials and lower resting or active motor thresholds), and 4) reduce motor cortex inhibition (reduced short-interval intracortical inhibition and increase in intracortical facilitation in ipsilesional M1). Our long-term goal is to develop effective interventions to improve function of children with UCP. Outcomes of this project will provide critical ingredients for designing Phase II trials that will determine the effects of RIC combined with intensive behavioral interventions to improve functional outcomes in children with UCP.

项目摘要/摘要 单侧脑性瘫痪(UCP)是儿童残疾的主要原因。早期脑损伤损害 上肢功能、双手协调，并影响孩子的独立性。的有效性。 现有的改善偏瘫手臂功能的康复方法由于训练剂量较高而受到限制， 效应大小适中，训练效果保持性差。因此，迫切需要找到一种有效的引爆方法 当与运动(双手)技能训练配对时，将促进神经生物学过程，以增强 训练效果的大小和改善UCP儿童的功能能力。这项建议旨在 确定一种新的启动剂，远程缺血条件(RIC)，当配对双曼纽尔时的效果 技能训练，以加强双指甲技能的学习，并增强技能依赖的可塑性的儿童。 缺血条件反射(IC)是一种直接保护靶器官免受缺血的现象 使其暴露在短暂的亚致命性缺血发作中。RIC是一种临床上可行的进行IC的方法 缺血和再灌注的发作伴随着血压袖带的周期性充气和放气。 手臂或腿。在人类的临床前和初步临床试验表明RIC具有神经保护作用。我们的 先前的研究表明，当与运动训练相结合时，RIC可以增强健康个体的运动学习。 基于RIC的这些不同益处，我们的中心假设是RIC的多因素机制 可作为启动剂用于增强儿童的运动学习和增强神经可塑性 UCP。我们的具体目标是：1)确定RIC+训练对双指甲技能表现的影响；2) RIC+训练对皮质脊髓功能的影响 随机对照试验，30例尿路感染患儿将首先 上端 调理 兴奋性 经历双手动速度堆栈性能、功能 四肢和经颅磁刺激评估。然后，儿童将经历RIC/Sham 外加培训。 在尿路感染的儿童中。在这三重盲目中， 我们将通过周期性的通货膨胀和压力的紧缩来提供RIC/虚假的条件作用 使用标准方案在偏瘫手臂上戴上手铐。训练将包括5天(15次/天)的双指甲速度 堆叠训练。这些孩子将进行相同的基线评估，而不是干预。我们假设 与假的条件反射+训练相比，RIC+训练会显著提高：1)双指甲技能表现 (完成双手速度堆叠任务的移动时间(秒)减少)，2)双手功能(增加 辅助手评估评分)，3)患侧初级运动皮质(M1)的皮质兴奋性(较大 运动诱发电位的幅度和较低的静息或活动运动阈值)，以及4)运动皮质减少 抑制(减少皮质内短间期抑制和增加同侧M1的皮质内促进)。 我们的长期目标是开发有效的干预措施来改善UCP儿童的功能。结果： 该项目将为设计第二阶段试验提供关键成分，以确定水稻的效果 结合强化行为干预改善UCP儿童的功能结局。

项目成果

Bimanual Movement Characteristics and Real-World Performance Following Hand-Arm Bimanual Intensive Therapy in Children with Unilateral Cerebral Palsy.

单侧脑瘫儿童手臂双手强化治疗后的双手运动特征和现实世界表现。

• DOI: 10.3390/bs13080681
• 发表时间: 2023-08-13
• 期刊: BEHAVIORAL SCIENCES
• 影响因子: 2.6
• 作者: Gardas, Shailesh S.;Lysaght, Christine;Mcmillan, Amy Gross;Kantak, Shailesh;Willson, John D.;Patterson, Charity G.;Surkar, Swati M.
• 通讯作者: Surkar, Swati M.

Remote ischaemic conditioning combined with bimanual task training to enhance bimanual skill learning and corticospinal excitability in children with unilateral cerebral palsy: a study protocol of a single centre, phase II randomised controlled trial.

• DOI: 10.1136/bmjopen-2023-076881
• 发表时间: 2023-09-28
• 期刊: BMJ open
• 影响因子: 2.9