Corticospinal control of spinal reflex plasticity

皮质脊髓对脊髓反射可塑性的控制

• 批准号: 10670047
• 负责人: Jonathan Rickel Wolpaw
• 金额: --
• 依托单位: STRATTON VETERANS ADMIN MEDICAL CENTER
• 依托单位国家: 美国
• 财政年份: 2018
• 资助国家: 美国
• 起止时间: 2018-10-01 至 2023-09-30
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/10670047
• 关键词: American; Automobile Driving; Brain; Brain Injuries; Chronic; Chronic Disease; Clinical; Clinical Trials; Complement; Contralateral; Data; Disease; Electroencephalography; Flexor; Goals; H-Reflex; Hand; Human; Hyperreflexia; Hyporeflexia; Impairment; Knowledge; Laboratories; Learning; Locomotion; Methods; Monkeys; Motor; Multiple Sclerosis; Mus; Muscle; Neuromuscular Diseases; Operant Conditioning; Pathway interactions; Persons; Process; Protocols documentation; Rattus; Recovery; Recovery of Function; Reflex action; Rewards; Series; Soleus Muscle; Speed; Spinal; Spinal Cord; Spinal Cord Plasticity; Spinal cord injury; Stroke; Testing; Therapeutic; Translating; Traumatic Brain Injury; Vertebral column; Veterans; Walking; Work; abnormal reflex; animal data; arm; arm function; chronic stroke; conditioning; follow-up; functional restoration; grasp; human data; improved; nervous system disorder; novel therapeutics; recruit; spinal pathway; spinal reflex; synergism; walking speed

Spinal cord injury (SCI), traumatic brain injury, stroke, multiple sclerosis, and other chronic disorders produce abnormal reflexes that impair locomotion, reach-and-grasp, and other motor functions for millions of Americans, including many Veterans. New treatments are urgently needed. Operant conditioning protocols can change spinal reflexes in rats, mice, monkeys, and people. These protocols, which are non-invasive in humans, can target beneficial plasticity to a specific reflex pathway. The reflex is elicited and the subject is rewarded if the reflex satisfies a size criterion. The subject learns to modify corticospinal control over the pathway. This control gradually changes the spinal pathway itself, and thereby triggers further beneficial plasticity elsewhere. In people with incomplete SCI, operant conditioning of the soleus H-reflex increases walking speed and reduces limping. The improvements persist; they are apparent to people in their daily lives. {Reflex conditioning in people with SCI or stroke now requires 36 one-hr sessions over 12 weeks, and is successful in only 50-70%.} Better understanding of the cortical activity that drives the reflex change should lead to better protocols that increase the reliability, magnitude, and speed of reflex conditioning, and thereby enhance its clinical value. This project seeks to identify electroencephalographic (EEG) features that reflect the crucial cortical activity, to use these features to improve the reflex conditioning protocol, {and to show that this protocol is effective in Veterans with chronic stroke.} It has two specific aims. Aim 1 will identify EEG features that correlate will the size of the H-reflex in the arm muscle flexor carpi radialis (FCR) and incorporate these features into the operant conditioning protocol. Based on human and animal data, we expect that the best feature will be sensorimotor rhythm (SMR) amplitude over contralateral sensorimotor cortex (SMC) in the 1 sec immediately before H-reflex elicitation. The new protocol will require that this EEG feature satisfy a size criterion prior to H-reflex elicitation. We expect that this new requirement will guide the person to produce, maximize, and maintain appropriate change in corticospinal influence on the reflex pathway; it will thereby increase the reliability, magnitude, and speed of H-reflex change. We will develop and validate this new protocol through studies in Veterans without neurological disease. {Aim 2 will recruit Veterans with impaired arm function due to a stroke >1 yr earlier. One group will undergo FCR H-reflex down-conditioning with the enhanced protocol; another group will undergo down- conditioning with the standard protocol. (We will down-condition the FCR H-reflex in these Veterans because it is the down-conditioning protocol that would be used clinically to reduce the hyperreflexia and/or the abnormal flexor synergy than can occur with stroke.) Because the enhanced protocol will guide the person to produce, maximize, and maintain appropriate change in corticospinal influence on the reflex pathway, we expect that its reliability will be higher, and that it will decrease the H-reflex more and more rapidly, than the standard protocol. This result will validate the enhanced protocol for people with chronic stroke.} In sum, the goal of this project is to gain new mechanistic understanding of a novel therapy and to use this knowledge to improve the therapy. {By identifying an EEG feature that reflects the cortical activity that drives the spinal plasticity underlying H-reflex change, and by showing that the feature can be used to increase the rate, magnitude, and reliability of H-reflex change in Veterans with chronic stroke, this work should augment the therapeutic value and practicality of spinal reflex conditioning.} If it is successful, it should lead to clinical trials that evaluate the ability of this new non-invasive therapy to enhance functional recovery for Veterans with stroke, spinal cord or brain injury, multiple sclerosis, or other chronic neuromuscular disorders. ! !

脊髓损伤（SCI）、创伤性脑损伤、中风、多发性硬化症和其他慢性疾病 产生异常反射，损害数百万人的运动、伸手和抓握以及其他运动功能。 美国人，包括许多退伍军人。迫切需要新的治疗方法。操作性条件反射协议可以 改变老鼠猴子和人的脊髓反射。这些协议是非侵入性的， 人类可以将有益的可塑性靶向特定的反射途径。反射被激发，受试者 如果反射满足大小标准，则奖励。受试者学会修改皮质脊髓对大脑皮层的控制， 通路这种控制逐渐改变脊髓通路本身，从而触发进一步有益的 其他地方的可塑性在不完全SCI患者中，比目鱼肌H反射的操作性条件反射增加 步行速度和减少跛行。这些改善持续存在;它们在人们的日常生活中显而易见。 SCI或中风患者的反射调节现在需要在12周内进行36次一小时的训练， 只有50- 70%的人成功。更好地了解大脑皮层的活动，驱动反射的变化， 导致更好的协议，增加可靠性，幅度，和反射条件反射的速度，从而 提高其临床价值。该项目旨在确定反映脑电（EEG）的特征， 关键的皮层活动，使用这些功能来改善反射条件反射协议，{并表明，这 协议是有效的退伍军人与慢性中风。它有两个具体目标。 目的1将识别与手臂腕屈肌H反射大小相关的EEG特征 桡侧肌（FCR），并将这些功能纳入操作性条件反射协议。基于人类和 动物数据，我们预计最好的功能将是感觉运动节律（SMR）振幅超过对侧 感觉运动皮层（SMC）在1秒前立即H反射引发。新协议将要求 该EEG特征在H反射激发之前满足尺寸标准。我们希望这项新规定 将引导人产生，最大化，并保持适当的皮质脊髓影响的变化， 这将增加H反射变化的可靠性、幅度和速度。我们将开发 并通过对没有神经系统疾病的退伍军人的研究来验证这一新方案。 {Aim 2将招募由于中风>1年前手臂功能受损的退伍军人。一组将 用增强方案进行FCR H反射下调;另一组将进行下调- 用标准方案调节。(We会降低这些退伍军人的FCR H反射， 是将在临床上用于减少反射亢进和/或异常反射的降调节方案。 屈肌协同作用，而不是中风时发生的协同作用）。因为增强的协议将指导人生产， 最大化，并保持适当的变化，皮质脊髓的影响，反射途径，我们预计， 可靠性将更高，并且它将比标准更快地降低H反射 议定书这一结果将验证慢性中风患者的增强方案。 总之，本项目的目标是获得对新疗法的新机制理解，并使用 这些知识来改善治疗。{By识别反映皮层活动的EEG特征， 驱动H反射变化背后的脊髓可塑性，并通过显示该功能可用于增加 慢性卒中退伍军人H反射变化的速率、幅度和可靠性，这项工作应 增强脊髓反射调节的治疗价值和实用性。}如果成功的话， 临床试验，评估这种新的非侵入性治疗的能力，以促进功能恢复， 患有中风、脊髓或脑损伤、多发性硬化症或其他慢性神经肌肉疾病的退伍军人。! !