NEUROPHYSIOLOGY OF RESPONDERS AND NON-RESPONDERS WITH CEREBRAL PALSY

项目总结/摘要 脑性瘫痪（CP）是由围产期脑损伤引起的，是最普遍和最昂贵的儿科疾病之一。 在美国，神经系统疾病往往导致行动不便。我们广泛的实验工作 一直致力于开发一种治疗步态训练协议，将改善长期的流动性， 青少年CP尽管我们取得了重大突破，但很明显，在我们的调查中， 青少年在治疗后的活动能力有了很大的改善，而其他人则明显没有反应。 这种反应的变异性代表了治疗结果中的一个主要难题， 青少年CP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CP的青少年 在规划腿部运动动作和感知躯体感觉时， 反馈我们对步态治疗结果和感觉运动皮层神经成像的初步研究 使我们处于解决RFA-HD-20-005的领先地位，RFA-HD-20-005要求“研究 了解对当前治疗有反应和无反应的潜在机制”。从本质上讲， 我们将通过多模式方法来解决这一问题，该方法将我们在MEG脑成像、MRI脊髓成像、 脊髓成像和评估脊髓神经元间回路，以探测神经生理学 在治疗性步态训练后，将青少年分为应答者和非应答者。 本研究的具体目的是：（1）确定应答者和非应答者在以下方面是否存在差异： 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是否在躯体感觉内的神经同步中具有差异 皮质，在刺激足部机械感受器之后，以及（3）破译响应者和非响应者 在脊髓微结构和电路动力学上有差异。简而言之，我们的研究设计包括 CP青少年队列，最初将接受MEG脑成像，MRI脊髓成像， 脊髓神经元间回路的神经生理学测试和临床移动性评估。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。后 在完成治疗计划后，青少年将重复完成的相同评估， 基线。将青少年分为对治疗有反应者和无反应者将基于 10米步行速度试验中临床相关变化的标准。从这个项目中获得的新数据 将提供无与伦比的洞察力的潜在神经生理起源的各种流动性的结果， 治疗后的青少年CP。这些见解将为未来的研究奠定基础， 使用神经科学告知的治疗方法，旨在突破特定的神经系统， 无反应青少年可能面临的生理障碍（即，运动规划、感官知觉）。

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).