Spinal cord associative plasticity

脊髓关联可塑性

• 批准号: 10317823
• 负责人: Jason Brant Carmel
• 金额: $ 55.04万
• 依托单位: COLUMBIA UNIVERSITY HEALTH SCIENCES
• 依托单位国家: 美国
• 财政年份: 2021
• 资助国家: 美国
• 起止时间: 2021-09-10 至 2026-06-30
• 项目状态: 未结题
• 来源: https://reporter.nih.gov/project-details/10317823
• 关键词: Affect; Anatomy; Behavioral; Brain; Caliber; Cervical; Cervical spinal cord injury; Cervical spinal cord structure; Chronic; Clinical; Data; Disease; Electric Stimulation; Electrodes; Engineering; Evoked Potentials; Fingers; Forelimb; Goals; Hand; Hand functions; Hour; Human; Hyperreflexia; Hyporeflexia; Individual; Injury; Interruption; Joints; Knowledge; Learning; Magnetic Resonance Imaging; Measures; Mediating; Methods; Mission; Motor; Motor Cortex; Motor Evoked Potentials; Motor Pathways; Movement; Muscle; Muscle Tension; Nature; Neck; Nervous system structure; Neural Pathways; Neurostimulation procedures of spinal cord tissue; Operative Surgical Procedures; Paralysed; Participant; Patients; Physiology; Positioning Attribute; Public Health; Rattus; Reflex action; Research; Residual state; Sensory; Spinal; Spinal Cord; Spinal Cord Diseases; Spinal cord injury; Stimulus; Stroke; System; Techniques; Testing; Time; Training; Transcranial magnetic stimulation; Translating; Treatment Protocols; United States National Institutes of Health; Ventral Roots; arm; arm function; awake; dexterity; disability; efficacy trial; experience; experimental study; head-to-head comparison; improved; neural circuit; paired stimuli; preservation; recruit; relating to nervous system; response; sensorimotor system; spinal cord imaging; spinal nerve posterior root; spinal pathway; spinal reflex; transcutaneous stimulation; translation to humans

SUMMARY Experience leads to behavioral change through associative activity of neural circuits. Using this principle, paired stimulation has been used to selectively strengthen circuits. We propose to target the spinal cord for associative plasticity, exploiting strong interaction of descending motor connections and large diameter afferents, which mediate the senses of joint position and muscle tension. In rats and humans, sub-threshold cervical stimulation, which activates afferents, strongly augments motor cortex evoked muscle responses when timed to converge in the spinal cord. When pairing is performed repeatedly in rats, spinal cord associative plasticity (SCAP) is induced with a large and sustained increase in excitability. In rats with cervical spinal cord injury (SCI), 10 days of SCAP significantly improved forelimb function. We hypothesize that SCAP will strengthen spinal excitability, modulate reflexes, and increase pinch force in people with cervical SCI. Aim 1 tests the timing of pairing and the circuits mediating paired stimulation, key issues for proper targeting. Timing cortical and spinal stimulation to converge in the spinal cord, as opposed to cortex, is predicted to be strongest. We will use both non-invasive and invasive spinal cord stimulation. For non-invasive stimulation, we will combine transcutaneous stimulation over the neck with transcranial magnetic stimulation over cortex. For invasive stimulation, we will combine spinal epidural stimulation with transcranial electrical stimulation during clinically indicated surgery. Aim 2 tests the effects of SCAP to produce a lasting increase in spinal excitability, as measured by both cortical and spinal evoked potentials and pinch dynamometry. Controls will isolate the changes induced specifically through pairing. Finally, Aim 3 tests whether paired motor cortex and cervical spinal cord stimulation produces similar effects in people with the two most common causes of SCI, cervical myelopathy and traumatic SCI, as uninjured participants. Spinal excitability is predicted to increase, pinch force is expected to become stronger, and spinal reflexes are expected to diminish. The integrity of spinal pathways will be measured with both physiology and analysis of cervical MRI. Together, these studies will fill critical gaps about the nature of associative plasticity in the sensorimotor system and test a new strategy to strengthen residual connections after SCI. This strategy will be tested with both invasive and non-invasive stimulation, allowing direct comparison of these approaches for the first time. Thus, we intend to close gaps in our understanding of how paired stimulation of sensorimotor circuits should be targeted to the spinal cord and which residual circuits support the plasticity. This knowledge can optimize how we target electrical stimulation to induce SCAP. Multiple methods of motor cortex and cervical spinal cord stimulation have been proven to be safe, so these mechanistic studies can be translated quickly to efficacy trials.

概括 经验通过神经回路的联想活动导致行为改变。利用这个原理， 配对刺激已被用来选择性地加强电路。我们建议以脊髓为目标 关联可塑性，利用下降电机连接和大直径的强相互作用 传入神经，调节关节位置和肌肉张力的感觉。在大鼠和人类中，亚阈值 颈部刺激可激活传入神经，强烈增强运动皮层诱发的肌肉反应 定时汇聚于脊髓。当在大鼠中重复进行配对时，脊髓联想 可塑性（SCAP）是由兴奋性大幅持续增加引起的。在患有颈脊髓的大鼠中 损伤（SCI）后，10天的SCAP显着改善了前肢功能。我们假设 SCAP 将 增强脊髓兴奋性、调节反射并增加颈椎 SCI 患者的捏力。目标1 测试配对的时间和介导配对刺激的电路，这是正确定位的关键问题。定时 预计皮质和脊髓刺激集中在脊髓（而不是皮质）最强。 我们将使用非侵入性和侵入性脊髓刺激。对于非侵入性刺激，我们将 将颈部经皮刺激与皮质经颅磁刺激相结合。为了 侵入性刺激，我们将脊髓硬膜外刺激与经颅电刺激相结合 临床指征手术。目标 2 测试 SCAP 产生持久增加脊髓兴奋性的效果​​， 通过皮质和脊髓诱发电位以及捏测力测量来测量。控制将隔离 通过配对特别引起的变化。最后，Aim 3 测试运动皮层和颈椎是否配对 脊髓刺激对患有 SCI 两种最常见原因（颈椎病）的人产生类似的效果。 脊髓病和创伤性 SCI，与未受伤的参与者一样。脊髓兴奋性预计会增加，捏力 预计会变得更强，并且脊髓反射预计会减弱。脊髓通路的完整性 将通过生理学和颈部 MRI 分析进行测量。这些研究将共同​​填补关键空白 关于感觉运动系统中联想可塑性的本质并测试一种新的强化策略 SCI 后的残余连接。该策略将通过侵入性和非侵入性刺激进行测试， 首次允许直接比较这些方法。因此，我们打算缩小我们的差距 了解如何针对脊髓对感觉运动回路进行配对刺激，以及 哪些残余电路支持可塑性。这些知识可以优化我们针对电刺激的方式 诱导SCAP。运动皮层和颈脊髓刺激的多种方法已被证明是有效的 安全，因此这些机制研究可以快速转化为功效试验。