NEUROPHYSIOLOGY OF RESPONDERS AND NON-RESPONDERS WITH CEREBRAL PALSY

脑瘫有反应者和无反应者的神经生理学

• 批准号: 10322310
• 负责人: Max J Kurz
• 金额: $ 35.57万
• 依托单位: FATHER FLANAGAN'S BOYS' HOME
• 依托单位国家: 美国
• 财政年份: 2020
• 资助国家: 美国
• 起止时间: 2020-06-01 至 2025-05-31
• 项目状态: 未结题
• 来源: https://reporter.nih.gov/project-details/10322310
• 关键词: NEUROPHYSIOLOGY; RESPONDERS; NON; CEREBRAL; PALSY

PROJECT SUMMARY/ABSTRACT Cerebral palsy (CP) results from a perinatal brain injury and is one of the most prevalent and costly pediatric neurologic conditions in the United States that often results in mobility deficits. Our extensive experimental work has been focused on developing a therapeutic gait training protocol that will improve the long-term mobility of adolescents with CP. Despite our major breakthroughs, it is apparent across our investigations that some adolescents have vast improvements in their mobility after treatment, while others are clearly non-responders. This response variability represents one of the major Gordian knots in the treatment outcomes seen in adolescents with CP. Over the past decade, we have begun to disentangle this knot through a series of influential magnetoencephalographic (MEG) brain imaging studies that have revealed that adolescents with CP have aberrant sensorimotor cortical oscillations while planning their leg motor actions and perceiving somatosensory feedback. Our preliminary work on the gait treatment outcomes and neuroimaging of the sensorimotor cortices has positioned us to be on the leading-edge for addressing RFA-HD-20-005, which requests “studies to understand the underlying mechanisms for responders and non-responders to current treatments”. Essentially, we will address this call with a multimodal approach that blends our expertise in MEG brain imaging, MRI spinal cord imaging, and assessments of the spinal cord interneuronal circuitry to probe the neurophysiological differences in adolescents that are classified as responders and non-responders after therapeutic gait training. The Specific Aims of this study will: (1) identify if responders and non-responders have differences in the strength of the sensorimotor cortical oscillations involved in the planning and execution of a leg motor action, (2) determine if responders and non-responders have differences in the neural synchrony within the somatosensory cortices, following stimulation of the foot mechanoreceptors, and (3) decipher if responders and non-responders have differences in the spinal cord microstructure and circuitry dynamics. Briefly, our study design consists of a cohort of adolescents with CP that will initially undergo MEG brain imaging, MRI spinal cord imaging, neurophysiological tests of the spinal cord interneuronal circuitry and clinical mobility assessments. After completing the baseline tests, the adolescents will undergo our therapeutic gait training protocol. Upon completion of the treatment program, the adolescents will repeat the same assessments that were completed at baseline. Separation of the adolescents into responders and non-responders to treatment will be based on the criteria for a clinically relevant change in the 10-meter walking speed test. The new data derived from this project will provide unparalleled insight on the potential neurophysiological origins of the diverse mobility outcomes seen in adolescents with CP after treatment. These insights will set-the-stage for future studies that will explore the use of neuroscience-informed therapeutic approaches that are directed at breaking through the specific neuro- physiological barriers that non-responding adolescents may face (i.e., motor planning, sensory perception).

项目摘要/摘要 脑瘫（CP）是由围产期脑损伤引起的，是最普遍，最昂贵的小儿之一 美国通常导致流动性的神经系统疾病定义。我们广泛的实验工作 一直专注于制定一种治疗性收集培训方案，该方案将提高长期流动性 具有CP的青少年。尽管我们取得了重大突破，但在我们的调查中很明显，有些 青少年在治疗后的活动能力大大改善，而其他人显然是无反应的。 这种响应的可变性代表了治疗结果中的主要戈尔德结之一。 具有CP的青少年。在过去的十年中，我们开始通过一系列影响力解散这一结 磁脑（MEG）脑成像研究表明，患有CP的青少年有 在计划腿部运动动作并感知体感时，感觉运动皮层振荡异常 反馈。我们在满足治疗结果和感觉运动皮质的神经影像学上的初步工作 已将我们定位为解决RFA-HD-20-005的领先地位，该问题要求“研究 了解响应者和对当前治疗的无反应者的潜在机制”。从本质上讲， 我们将采用一种多模式的方法来解决这个电话，该方法将我们在MEG脑成像的专业知识融合在一起 电线成像和脊髓间神经元电路的评估以探测神经生理学 在治疗后被归类为反应者和非反应者的青少年差异。 这项研究的具体目的将：（1）确定响应者和非反应者在 腿部运动动作计划和执行涉及的感觉运动皮质振荡的强度，（2） 确定响应者和非反应者在体感内的神经同步方面是否有差异 皮质刺激脚步机制受体，以及（3）解密的响应者和无反应者 脊髓微结构和电路动力学有差异。简而言之，我们的研究设计包括 与CP的青少年队列最初会进行MEG脑成像，MRI脊髓成像， 脊髓间神经元电路和临床迁移率评估的神经生理测试。后 完成基线测试，青少年将接受我们的治疗聚会培训方案。之上 完成治疗计划的完成，青少年将重复与在 基线。将青少年分离为反应者和无反应者将 10米步行速度测试中临床相关变化的标准。该项目得出的新数据 将提供对潜在潜在的潜在神经生理起源的无与伦比的见解，请参见 在治疗后CP的青少年中。这些见解将为以后的研究设定舞台，以探索 使用神经科学知识的治疗方法，旨在突破特定的神经 - 无反应的青少年可能面临的生理障碍（即运动计划，感官感知）。