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).

项目概要/摘要 脑瘫 (CP) 由围产期脑损伤引起，是最常见和最昂贵的儿科疾病之一 在美国，神经系统疾病常常导致行动不便。我们广泛的实验工作 一直致力于开发治​​疗性步态训练方案，以改善患者的长期活动能力 患有 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，一些 青少年在治疗后活动能力有了很大改善，而其他人则明显没有反应。 这种反应变异性代表了治疗结果中的主要难题之一 患有 CP 的青少年。过去十年来，我们已经开始通过一系列有影响力的举措来解开这个结。 脑磁图 (MEG) 脑成像研究表明，患有 CP 的青少年 在规划腿部运动动作和感知体感时出现异常的感觉运动皮层振荡 反馈。我们关于步态治疗结果和感觉运动皮层神经影像学的初步工作 使我们在解决 RFA-HD-20-005 问题上处于领先地位，该文件要求“研究 了解对当前治疗有反应和无反应的潜在机制”。本质上， 我们将采用多模式方法来应对这一呼吁，该方法融合了我们在 MEG 脑成像、MRI 脊髓成像方面的专业知识 脊髓成像和脊髓间神经元回路评估以探测神经生理学 治疗性步态训练后被分类为有反应者和无反应者的青少年之间的差异。 本研究的具体目标将：（1）确定响应者和非响应者在 参与腿部运动动作的规划和执行的感觉运动皮层振荡的强度，(2) 确定响应者和非响应者在体感神经同步方面是否存在差异 刺激足部机械感受器后，皮层，以及（3）破译有反应者和无反应者 脊髓微观结构和电路动力学存在差异。简而言之，我们的研究设计包括 患有 CP 的青少年队列最初将接受 MEG 脑成像、MRI 脊髓成像、 脊髓间神经元回路的神经生理学测试和临床活动评估。后 完成基线测试后，青少年将接受我们的治疗性步态训练方案。之上 治疗计划完成后，青少年将重复在 基线。将青少年分为对治疗有反应者和无反应者 10 米步行速度测试中临床相关变化的标准。来自该项目的新数据 将为所观察到的不同流动性结果的潜在神经生理学起源提供无与伦比的见解 治疗后患有 CP 的青少年。这些见解将为未来的研究奠定基础，探索 使用基于神经科学的治疗方法，旨在突破特定的神经 无反应青少年可能面临的生理障碍（即运动计划、感官知觉）。