Can spinal cord epidural stimulation increase the efficacy of midbrain excitation of locomotor circuits?

脊髓硬膜外刺激能否增加中脑运动回路兴奋的功效？

• 批准号: 10020796
• 负责人: James David Guest
• 金额: $ 19.19万
• 依托单位: UNIVERSITY OF MIAMI SCHOOL OF MEDICINE
• 依托单位国家: 美国
• 财政年份: 2019
• 资助国家: 美国
• 起止时间: 2019-09-30 至 2022-08-31
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/10020796
• 关键词: Acoustics; Address; Algorithms; Anesthesia procedures; Animals; Attitude; Automobile Driving; Axon; Biomedical Engineering; Bluetooth; Body Surface; Body Weight; Brain Stem; Chronic; Clinical; Communities; Coupled; Data; Deep Brain Stimulation; Devices; Dorsal; Electrodes; Electromyography; Equilibrium; Esthesia; Family suidae; Feedback; Fiber; Frequencies; Gait; Glutamates; Hip region structure; Histologic; Histology; Human; Impairment; Implant; Individual; Injury; Interneurons; Interruption; Intervention; Joints; Knee; Lead; Left; Light; Locomotion; Lumbar spinal cord structure; Lumbosacral Region; Maintenance; Measurement; Measures; Mediating; Medical; Midbrain structure; Miniature Swine; Mission; Modeling; Modification; Motion; Motor; Motor Neurons; Muscle; National Institute of Biomedical Imaging and Bioengineering; Neuronal Plasticity; Neurons; Outcome Measure; Output; Paralysed; Paraplegia; Parkinson Disease; Pathway interactions; Patients; Pattern; Pelvis; Performance; Physiologic pulse; Plant Roots; Postural adjustments; Posture; Process; Protocols documentation; Public Health; Quality of life; Randomized; Recovery; Rehabilitation therapy; Residual state; Safety; Sensory; Side; Signal Transduction; Site; Speed; Spinal; Spinal Cord; Spinal Cord Contusions; Spinal cord injury; Startle Reaction; Statistical Data Interpretation; Stimulus; Structure; Surface; Synapses; Techniques; Technology; Telemetry; Testing; Time; Tracer; Training; Translations; Unit of Measure; Urination; Variant; Walking; Weight; Weight-Bearing state; Wheelchairs; Width; base; clinically relevant; community setting; experimental study; fall risk; falls; foot; improved; kinematics; medical complication; motor control; multidisciplinary; neurological rehabilitation; neurophysiology; neuroregulation; painful neuropathy; primary outcome; repaired; response; reticulospinal tract; spinal tract

Project summary Spinal cord injury (SCI) interrupts motor control pathways between supraspinal and spinal sensorimotor networks. This disruption results in impairment of gait and sensation, chronic decreased quality of life (QOL), and numerous medical complications. In human studies of chronic SCI, lumbar electrical epidural stimulation (EES) based rehabilitation has allowed weight-bearing and unprecedented voluntary stepping in motor complete patients. These results establish that even severe complete SCIs have intact axons spared through the injury site. EES activates dorsal sensory roots to raise excitability of residual intact locomotor circuitry in the spinal cord. This allows otherwise silent descending inputs to become effective, permitting voluntary motion. Although impressive, ES based rehabilitation has not been adequate to restore balanced independent gait in the community setting. If applied during subacute rehabilitation, a period of increased neuroplasticity, this strategy may engender a greater level of permanent recovery. To address inadequate supraspinal drive we will use deep brain stimulation (DBS) of the mesencephalic locomotor region (MLR) to “overdrive” the stepping initiation center. We have previously developed protocols for MLR DBS and EES in a porcine contusion SCI model but have not combined them. In this project with 2:1 treatment:controls, we propose testing DBS and ES, together with developing a closed-loop perturbation and response protocol, to provide feedback driven stability and balance during weight supported stepping. In Aim 1, Yucatan minipigs with severe T9 SCI will be implanted with both MLR DBS and lumbar ES electrodes and undergo intensive rehabilitation for 3 months. In Aim 2 we test to what extent postural correction can be achieved by asymmetric modification of stimulus parameters in response to a posterior pelvic mounted inertial measurement unit coupled to a PID controller. Primary outcome measures include extent recovery of locomotion, time-walked testing, capacity to achieve unassisted weight support and structural plasticity of the reticulospinal tract. Measures will be acquired using state of the art kinematic analysis and telemetry-electromyography. In histological analysis after neuroanatomical tracing we determine if MLR- DBS causes axonal structural plasticity. Our aims align with the NIBIB mission statement by testing a multidisciplinary bioengineering approach in a clinically relevant and translational paraplegia model. ES and DBS technology has been applied in other clinical conditions including neuropathic pain and Parkinson’s disease. Thus, if successful, the translational path would be accelerated. The combined neuromodulation and rehabilitative intervention is relevant to public health, as it may fundamentally improve recovery from SCI and render subacute neurorehabilitation more effective allowing allow community-setting ambulation, supplanting wheelchair use and increasing QOL for individuals with SCI.

项目摘要 脊髓损伤（SCI）中断运动控制途径 网络。这种破坏会导致收集和感觉的损害，长期改善的生活质量（QOL）， 和许多医疗并发症。在慢性SCI的人类研究中，腰椎刺激 （EES）基于EES的康复允许重量和前所未有的自愿步进电动机完整 患者。这些结果表明，即使是严重的完整SCI也具有完整的轴突。 地点。 EES激活背部感觉根，以提高脊柱中残留完整运动电路的令人兴奋 绳索。这允许否则无声的下降输入变得有效，并允许自愿运动。虽然 令人印象深刻的基于ES的康复不足以恢复平衡的独立聚集 社区环境。如果在亚急性康复期间应用，神经可塑性增加时期，则该策略 可能会导致更大的永久恢复。为了解决不充分的脊柱上驱动器，我们将使用深度 Messencephalic运动区域（MLR）的脑刺激（DB），以“超速驱动”踏脚计划中心。 我们以前已经在猪挫伤科学模型中开发了MLR DB和EES的协议，但没有 将它们结合在一起。在2：1处理的项目中：对照组，我们提出了测试DB和ES，以及 开发闭环扰动和响应协议，以提供反馈驱动的稳定性和平衡 在体重支持的过程中。在AIM 1中，具有严重T9 SCI的尤卡坦小ii植物将与两者一起植入 MLR DBS和LUMBAR ES电极进行3个月的密集康复。在AIM 2中，我们测试什么 通过响应于A 后骨盆安装的惯性测量单元耦合到PID控制器。主要结果指标 包括运动的范围恢复，进行时间巡回的测试，实现无助的体重支持的能力和 网状脊髓区的结构可塑性。将使用最先进的运动学分析来获取措施 和遥测电视学。在神经解剖学跟踪后的组织学分析中，我们确定是否MLR- DBS引起轴突结构可塑性。我们的目标通过测试一个 临床相关和翻译的截瘫模型中的多学科生物工程方法。 ES和DBS 技术已应用于其他临床状况，包括神经性疼痛和帕金森氏病。 如果成功的话，翻译路径将被加速。联合神经调节和 康复干预措施与公共卫生有关，因为它可能从根本上改善SCI和 使亚急性神经康复更有效，允许社区设定的卧床 轮椅使用并增加了SCI个体的QOL。