Characterization of Physiological Changes Induced Through MEP Conditioning in People with SCI

项目摘要/摘要 脊髓损伤(SCI)通常扰乱皮质脊髓驱动，导致肌肉和 运动控制受损。因此，进一步改善皮质脊髓功能的干预可以增强运动能力。 恢复。然而，这种神经调节干预目前还不适用于不完全的患者。 SCI。例如，除了常规的物理疗法外，最常见的治疗足下垂(虚弱)的方法 踝关节背屈)，在这一人群中经常损害步态，是一种脚踝矫形器。这些标准 治疗的目的不是恢复皮质脊髓动力，甚至可能进一步抑制它。操作性条件反射 刺激触发的肌电反应，它可以将有益的可塑性靶向产生 应对措施或许能够填补这一空白。这个项目的首要假设是，增加 操作员经颅磁刺激诱发的运动诱发电位 条件反射可以改善目标肌肉的皮质脊髓激活，从而改善运动 该肌肉参与的功能。 在不完全性脊髓损伤患者中，胫前肌MEP通常较小，反映皮质脊髓减少。 兴奋性。这削弱了TA的皮质脊髓激活，导致脚下垂，从而进一步损害他们的步态 通过膝盖和臀部的一系列补偿和适应不良。因此，一种增加皮质脊髓激素的疗法 TA的兴奋性可能会减少脚下垂和其他相关问题，从而改善步行。近期 对TA MEP条件反射的小规模研究表明，MEP上条件反射可以增加皮质脊髓 对TA的兴奋性，并能改善慢性脊髓损伤患者的步态。在这些初步发现的基础上，该项目 旨在描述TA MEP条件反射的生理机制和作用。 由于慢性不完全性脊髓损伤而导致背屈能力较弱的个体接受42次1小时的MEP训练(6 基线，然后是36次向上调节或36次对照)。基线前和12、24、36次条件反射后 (或对照)会议，(1)描述TA MEP变化的皮质和皮质脊髓机制 MEP上调产生，皮层MEP图，MEP募集曲线，短间期皮质抑制， 测量颈髓MEP、H反射和F波；以及(2)表征TA MEP UP的影响。 调节运动功能，双侧运动肌电和运动学测量，10米和6分钟 进行步行测试和运动反射测试。 确定MEP条件反射如何诱导皮质和皮质脊髓可塑性以及这种可塑性如何变化 不完全性脊髓损伤患者的运动将阐明诱导和塑造的动态过程 通过引导靶向可塑性实现与功能相关的中枢神经系统多部位可塑性。搜索结果将有助于导航 MEP操作性条件反射的发展和临床翻译，作为一种新的非侵入性治疗，可能 补充其他疗法，进一步促进脊髓损伤或其他疾病患者的康复。

Project Summary / Abstract Spinal cord injury (SCI) often disrupts corticospinal drive, resulting in weak voluntary activation of muscles and impaired motor control. Thus, an intervention that further improves corticospinal function could enhance motor recovery. However, such neuromodulatory interventions are not currently available to people with incomplete SCI. For example, other than conventional physical therapy, the most common treatment for foot drop (weak ankle dorsiflexion), which often impairs gait in this population, is an ankle foot orthosis. These standard treatments do not aim to restore corticospinal drive and may even depress it further. Operant conditioning of a stimulus-triggered EMG response, which can target beneficial plasticity to the pathway that produces the response may be able to fill this gap. The overarching hypothesis of this project is that increasing the size of the motor evoked potential (MEP) elicited by transcranial magnetic stimulation through operant conditioning can improve corticospinal activation of the targeted muscle and thereby improve motor function in which that muscle participates. In people with incomplete SCI, the tibialis anterior (TA) MEP is often small, reflecting reduced corticospinal excitability. This weakened corticospinal activation of TA contributes to foot drop, which further impairs their gait through a chain of compensation and maladaptation at knee and hip. Thus, a therapy that increases corticospinal excitability for TA may reduce foot drop and other associated problems, and thereby improve walking. Recent small studies of TA MEP conditioning suggest that MEP up-conditioning can increase the corticospinal excitability for TA and can improve gait in people with chronic SCI. Building upon those initial findings, this project seeks to characterize the physiological mechanisms and effects of TA MEP conditioning. Individuals with weak dorsiflexion due to chronic incomplete SCI are exposed to 42 1-hr MEP sessions (6 baseline followed by 36 up-conditioning or 36 control sessions). Before baseline and after 12, 24, 36 conditioning (or control) sessions, (1) to characterize the cortical and corticospinal mechanisms of the TA MEP changes produced by MEP up-conditioning, cortical MEP map, MEP recruitment curve, short-interval cortical inhibition, cervicomedullary MEP, H-reflex, and F-wave are measured; and (2) to characterize the impact of TA MEP up- conditioning on locomotor function, bilateral locomotor EMG and kinematics measurements, 10-m and 6-min walking tests, and locomotor reflex testing are performed. Determining how MEP conditioning induces cortical and corticospinal plasticity and how such plasticity changes locomotion in people with incomplete SCI will illuminate the dynamic process of inducing and shaping functionally-relevant CNS multi-site plasticity through guiding targeted plasticity. The results will help to navigate development and clinical translation of MEP operant conditioning, as a novel non-invasive therapy that may complement other therapies and further enhance recovery in people with SCI or other disorders.