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

项目总结/摘要 脊髓损伤（SCI）通常会破坏皮质脊髓驱动，导致肌肉的随意激活减弱， 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神经元的功能。 复苏然而，这种神经调节干预目前还不能用于不完全性痴呆患者。 SCI.例如，除了传统的物理治疗，最常见的治疗足下垂（弱 踝背屈）是踝足矫形器。这些标准 治疗的目的不是恢复皮质脊髓驱动，甚至可能进一步抑制它。操作性条件反射 刺激触发的EMG反应，它可以将有益的可塑性靶向产生肌电的通路。 或许，这份答卷能够填补这一空白。这个项目的首要假设是，增加 经颅磁刺激诱发的运动诱发电位（MEP） 调节可以改善靶肌肉的皮质脊髓激活，从而改善运动功能。 肌肉参与的功能。 在不完全性SCI患者中，胫骨前肌（TA）MEP通常较小，反映了皮质脊髓功能减退， 兴奋性这种TA的皮质脊髓激活减弱导致足下垂，这进一步损害了他们的步态 通过膝盖和臀部的补偿和适应不良链。因此，增加皮质脊髓的疗法 TA的兴奋性可以减少足下垂和其他相关问题，从而改善行走。最近 对TA MEP调节的小型研究表明，MEP上调可以增加皮质脊髓的 TA的兴奋性，可以改善慢性SCI患者的步态。在这些初步调查结果的基础上，该项目 试图描述TA MEP调节的生理机制和作用。 由于慢性不完全性SCI导致背屈弱的个体暴露于42个1小时的MEP会话（6 基线，随后是36次向上调节或36次对照会话）。基线前和第12、24、36次调节后 (or（1）描述TA MEP变化的皮质和皮质脊髓机制 由MEP上调、皮层MEP图、MEP募集曲线、短间隔皮层抑制产生， 测量颈髓MEP、H反射和F波;和（2）表征TA MEP向上的影响 运动功能调节，双侧运动EMG和运动学测量，10 m和6 min 进行行走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SCI患者的运动将阐明诱导和塑造的动态过程， 功能相关的CNS多部位可塑性，通过引导有针对性的可塑性。结果将有助于导航 MEP操作性条件反射的发展和临床转化，作为一种新的非侵入性治疗， 补充其他疗法，并进一步促进SCI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.