Spinal Cord Associative Plasticity

脊髓关联可塑性

• 批准号: 10487487
• 负责人: Jason Brant Carmel
• 金额: $ 50.43万
• 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/10487487
• 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; Persons; 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