NEUROPHYSIOLOGY OF RESPONDERS AND NON-RESPONDERS WITH CEREBRAL PALSY

项目摘要/摘要 脑性瘫痪(CP)是围产期脑损伤的结果，是最常见和最昂贵的儿科疾病之一 美国的神经系统疾病，经常导致行动不便。我们广泛的实验工作 一直致力于开发一种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，但纵观我们的调查，显然有一些 青少年在接受治疗后，他们的行动能力有了很大的改善，而其他人显然是无反应的。 这种反应的可变性代表了治疗结果中的主要棘手问题之一 患有CP的青少年。在过去的十年里，我们已经开始通过一系列有影响力的 脑磁图(MEG)脑成像研究显示患有脑性瘫痪的青少年有 在规划腿部运动动作和感知躯体感觉时异常的感觉运动皮质振荡 反馈。我们关于步态治疗结果和感觉运动皮质神经成像的初步工作 已将我们定位为解决RFA-HD-20-005问题的前沿，该文件要求 了解应答者和非应答者对当前治疗的基本机制“。从本质上讲， 我们将通过多模式方法来解决这一问题，该方法融合了我们在脑磁图、MRI和脊柱成像方面的专业知识 脊髓成像和脊髓神经元间回路的评估以探测神经生理学 治疗步态训练后被归类为应答者和无应答者的青少年的差异。 这项研究的具体目的将：(1)确定应答者和非应答者在以下方面是否存在差异 参与规划和执行腿部运动动作的感觉运动皮质振荡的强度，(2) 确定应答者和非应答者在躯体感觉中的神经同步性是否存在差异 刺激足部机械感受器后的大脑皮层，以及(3)识别应答者和非应答者 在脊髓微结构和环路动力学方面有差异。简而言之，我们的研究设计包括一个 一组患有脑性瘫痪的青少年，最初将接受脑磁图、核磁共振脊髓成像、 脊髓神经元间回路的神经生理学测试和临床活动评估。之后 完成基线测试后，青少年将接受我们的治疗步态训练方案。vt.在.的基础上 在完成治疗计划后，这些青少年将重复在 基线。将青少年分为对治疗有反应和无反应的情况将基于 10米步行速度测试中临床相关改变的标准。从该项目派生的新数据 将提供无与伦比的洞察力，了解各种流动性结果的潜在神经生理来源 青春期CP患者治疗后。这些洞察力将为未来探索 使用神经科学知情的治疗方法，旨在突破特定的神经- 没有反应的青少年可能面临的生理障碍(即运动规划、感官感知)。

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).