Improving mechanistic understanding of responsiveness to spinal cord stimulation after spinal cord injury

项目摘要/摘要 脊髓损伤(SCI)是一种毁灭性的事件，对一个人的健康、身体功能、成本(直接和 间接)和预期寿命。传统上认为，患有严重脊髓损伤、没有运动能力的人 功能低于损伤水平的人，将不能恢复其功能活动或 自愿步行。然而，脊髓刺激(Scs)已经成为一种具有挑战性的有前途的干预手段。 这一长期存在的假设。虽然脊髓刺激允许在严重的脊髓刺激后恢复自主运动 SCI，对于它是如何工作的，以及为什么一些人会做出反应，缺乏机械性的理解 比其他人都好。因此，这项提议的总体目标是应用神经成像生物标记物来生成 有关脊髓刺激(SCS)反应性的基本知识。 目的1：使用神经影像生物标志物了解硬膜外SCS的反应性 严重的脊髓损伤，在任意性运动和站立任务中。使用高分辨率磁共振成像进行前瞻性研究 设计中，申请人假设在手术植入前检测到的脊髓损伤的偏侧性将 在任何训练前预测同侧肢体肌肉对硬膜外SCS的反应性。 目的2：使用神经影像生物标志物了解经皮SCS的反应性 严重脊髓损伤的受试者，在任意性运动任务和感觉检查中。使用高- 在一项前瞻性设计中，申请者假设全部脊髓备用组织将预测 任何训练前和训练后双侧下肢肌肉对经皮SCS的反应性 在任何训练之前，脐带上的备用组织将预测轻触觉的恢复。 意义：成功完成这些目标将推进NIH/NICHD NCMRR目标：“加强 身体残障人士的健康、生产力、独立性和生活质量。一个重要的问题 在SCS领域，缺乏关于干预为什么有效的基础知识。神经影像学支持 解决这一问题的明显潜力。神经成像生物标记物不仅将提高对 对SCI后这种干预的反应性，但也将有助于推动使用SCS的个性化方法， 硬膜外SCS与经皮SCS的选择、SCS改善预后及鉴别 在以活动为基础的康复培训之前，谁可能以最佳方式作出反应。完成拟议的目标 将极有可能对SCS领域产生持续、强大的影响，为利用 MRI生物标志物用于指导SCS干预，最终改善SCI患者的临床治疗。

PROJECT SUMMARY / ABSTRACT Spinal cord injury (SCI) is a devastating event in terms of a person’s health, physical function, costs (direct and indirect), and life expectancy. It has been conventionally thought that individuals with severe SCIs, with no motor function below the level of injury, will not recover the ability to functionally move their lower extremities or voluntarily walk. However, spinal cord stimulation (SCS) has emerged as a promising intervention challenging this long-held assumption. While spinal cord stimulation allows for restored voluntary movement after severe SCI, there is a lack of mechanistic understanding regarding how it works and why some individuals respond better than others. Thus, the overall objective of this proposal is to apply neuroimaging biomarkers to generate fundamental knowledge regarding responsiveness to spinal cord stimulation (SCS). Aim 1: Use neuroimaging biomarkers to understand responsiveness to epidural SCS in participants with severe SCI, during volitional movement and standing tasks. Using high-resolution MRI in a prospective design, the applicant hypothesizes that the laterality of cord damage, detected prior to surgical implantation, will predict ipsilateral lower extremity muscle responsiveness to epidural SCS prior to any training. Aim 2: Use neuroimaging biomarkers to understand responsiveness to transcutaneous SCS in participants with severe SCI, during volitional movement tasks and sensory examination. Using high- resolution MRI in a prospective design, the applicant hypothesizes that total spinal cord spared tissue will predict bilateral lower extremity muscle responsiveness to transcutaneous SCS prior to any training, and that posterior cord spared tissue will predict light touch sensory recovery prior to any training. Significance: Successful completion of these Aims will advance the NIH/NICHD NCMRR aim: “to enhance the health, productivity, independence, and quality of life of people with physical disabilities.” One important problem in the field of SCS is a lack of foundational knowledge on why the intervention works. Neuroimaging holds pronounced potential to address this problem. Neuroimaging biomarkers will not only improve the understanding of responsiveness to this intervention after SCI, but will also help drive individualized approaches for using SCS, selection of epidural versus transcutaneous SCS, prognosis for improvement using SCS, and the identification of who is likely to optimally respond before activity-based recovery training. Completion of the proposed aims will lead to the high likelihood of sustained, powerful influence on the SCS field, laying a vital foundation for using MRI biomarkers to guide SCS intervention, ultimately improving the clinical management of persons with SCI.