Corticospinal control of spinal reflex plasticity

皮质脊髓对脊髓反射可塑性的控制

• 批准号: 10041767
• 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 2022-09-30
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/10041767
• 关键词: American; Automobile Driving; Brain; Brain Injuries; Chronic; Chronic Disease; Clinical; Clinical Trials; Complement; Contralateral; Data; Disease; Flexor; Goals; H-Reflex; Hand; Human; Hyperreflexia; Hyporeflexia; Impairment; Knowledge; Laboratories; Lead; 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; Sum; Testing; Therapeutic; Translating; Traumatic Brain Injury; Veterans; Walking; Work; abnormal reflex; animal data; arm; arm function; base; 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 改变大鼠、小鼠、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瞄准特定的反射途径。反射被引出，主题是 如果反射满足尺寸标准，则获得奖励。受试者学习改变皮质脊髓对 途径。这种控制逐渐改变脊髓通路本身，从而引发进一步有益的 其他地方的可塑性。在不完全性 SCI 患者中，比目鱼肌 H 反射的操作性条件反射增强 步行速度并减少跛行。改进持续存在；它们在人们的日常生活中是显而易见的。 {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，并且 只有 50-70% 的成功率。} 更好地了解驱动反射变化的皮质活动应该 导致更好的协议，提高反射调节的可靠性、幅度和速度，从而 提高其临床价值。该项目旨在识别反映以下情况的脑电图 (EEG) 特征： 关键的皮层活动，利用这些功能来改进反射调节协议，{并表明这 协议对患有慢性中风的退伍军人有效。}它有两个具体目标。 目标 1 将识别与手臂屈腕肌 H 反射大小相关的脑电图特征 Radiis (FCR) 并将这些功能合并到操作条件协议中。以人为本和 动物数据，我们预计最好的特征是对侧的感觉运动节律 (SMR) 幅度 H 反射激发前 1 秒内的感觉运动皮层 (SMC)。新协议将要求 该 EEG 特征满足 H 反射诱发之前的大小标准。我们预计这一新要求 将指导人们产生、最大化并维持皮质脊髓对身体的影响的适当变化 反射通路；从而提高 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。 {目标 2 将招募一年前因中风而导致手臂功能受损的退伍军人。一组将 使用增强方案进行 FCR H 反射下调；另一组将经历下行 使用标准协议进行调节。 （我们将下调这些退伍军人的 FCR H 反射，因为它 是临床上用于减少反射亢进和/或异常的下调方案 屈肌协同作用比中风时可能发生的那样。）因为增强的方案将指导患者产生， 最大化并保持皮质脊髓对反射途径的影响的适当变化，我们期望其 可靠性会更高，并且与标准相比，它会越来越快地降低 H 反射 协议。这一结果将验证针对慢性中风患者的增强方案。} 总之，该项目的目标是获得对新疗法的新机制理解并使用 这些知识可以改善治疗。 {通过识别反映皮质活动的脑电图特征 驱动 H 反射变化背后的脊柱可塑性，并表明该功能可用于增加 患有慢性中风的退伍军人的 H 反射变化的速度、幅度和可靠性，这项工作应该 增强脊髓反射调理的治疗价值和实用性。}如果成功，应该会导致 评估这种新的非侵入性疗法增强功能恢复能力的临床试验 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。 ！ ！