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.

总结 经验通过神经回路的关联活动导致行为改变。利用这一原理， 配对刺激已用于选择性地加强电路。我们建议针对脊髓， 联想可塑性，利用下行运动连接和大直径的强相互作用， 传入神经，其调节关节位置和肌肉张力的感觉。在大鼠和人类中， 颈部刺激，激活传入神经，强烈增强运动皮层诱发的肌肉反应， 定时在脊髓中汇聚当在大鼠中重复进行配对时， 可塑性（SCAP）是通过兴奋性的大幅度和持续增加来诱导的。大鼠颈髓损伤 损伤（SCI），10天的SCAP显著改善前肢功能。我们假设SCAP将 增强脊髓兴奋性，调节反射，增加颈椎脊髓损伤患者的捏力。要求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 与皮层相反，会聚在脊髓中的皮层和脊髓刺激被预测为最强。 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 联合收割机将颈部的经皮刺激与皮层的经颅磁刺激相结合。为 侵入性刺激，我们将联合收割机脊髓硬膜外刺激与经颅电刺激相结合， 有临床指征的手术目的2测试SCAP产生脊髓兴奋性持久增加的作用， 如通过皮层和脊髓诱发电位和捏力测定法测量的。控件将隔离 特别是通过配对引起的变化。最后，目标3测试是否配对的运动皮层和颈椎 脊髓刺激在患有两种最常见的SCI原因的人中产生类似的效果， 脊髓病和创伤性SCI，作为未受伤的参与者。脊髓兴奋性预计会增加，挤压力 预计会变得更强，脊髓反射预计会减弱。脊髓通路的完整性 将通过生理学和颈椎MRI分析进行测量。总之，这些研究将填补关键空白 关于感觉运动系统中联想可塑性的本质，并测试一种新的策略， SCI后的残余连接。该策略将用侵入性和非侵入性刺激进行测试， 这是第一次对这些方法进行直接比较。因此，我们打算缩小我们 了解感觉运动回路的配对刺激应如何针对脊髓， 哪些残余回路支持可塑性。这些知识可以优化我们如何靶向电刺激 以诱导SCAP。运动皮层和颈脊髓刺激的多种方法已被证明是 安全，因此这些机制研究可以快速转化为功效试验。