Trigeminal Nerve Stimulation in Chronic Hemiparetic Stroke

三叉神经刺激治疗慢性偏瘫中风

• 批准号: 10272422
• 负责人: James Andrew Beauchamp
• 金额: $ 4.25万
• 依托单位: NORTHWESTERN UNIVERSITY AT CHICAGO
• 依托单位国家: 美国
• 财政年份: 2020
• 资助国家: 美国
• 起止时间: 2020-12-01 至 2022-11-30
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/10272422
• 关键词: Affect; Area; Articular Range of Motion; Attenuated; Brain Stem; Chronic; Coupling; Dependence; Development; Diffuse; Disease; Elbow; Exhibits; Fingers; Functional disorder; Goals; Height; Human; Hyperactivity; Impairment; Individual; Joints; Limb structure; Measures; Mediating; Methods; Motor; Motor Neurons; Motor Pathways; Norepinephrine; Outcome; Output; Paresis; Pathway interactions; Pharmacology; Population; Predisposition; Quality of life; Reflex action; Rehabilitation therapy; Research; Robotics; Role; Salivary; Schedule; Serotonin; Shoulder; Spinal; Stimulus; Stroke; Tendon Reflex; Therapeutic; Titrations; Torque; Transcutaneous Electric Nerve Stimulation; Trigeminal nerve structure; Upper Extremity; Volition; Work; Wrist; alpha-amylase; attenuation; biceps brachii muscle; chronic stroke; hemiparetic stroke; improved; insight; locus ceruleus structure; monoamine; motor control; motor deficit; motor impairment; neurological rehabilitation; neuroregulation; noradrenergic; novel; post stroke; response; reticulospinal tract; side effect; spasticity; stretch reflex; stroke survivor; synergism; vibration

Project Summary Emerging research has suggested that chronic stroke induced motor impairments exhibit a dependence on heighted brainstem mediated monoaminergic drive. Explicitly, an increase in descending monoamines is believed to increase spinal motoneuron excitability and thus (1) generate spasticity and (2) amplify the diffuse commands that are responsible for flexion synergy expression. Though modulating this descending monoaminergic drive yields tremendous potential in affecting both impairments, current pharmacological approaches prove inadequate and require lengthy titration schedules and elicit burdensome side effects. Thus, I propose the novel application of transcutaneous electrical ophthalmic trigeminal nerve stimulation (TNS). This non-invasive stimulus has been shown to attenuate systemic measures of monoamines and is believed to modulate monoaminergic brainstem areas such as the locus coeruleus. Such an ability to non-invasively reduce monoamines represents the possibility for substantial improvements in stroke induced movement impairments. To investigate this potential, the goal of the proposed project is to elucidate the effects of TNS on (1) upper limb spinal motoneuron excitability and (2) flexion synergy expression in chronic stroke survivors. Highly quantitative metrics will be employed for both aims. Spinal motoneuron excitability will be quantified through the tonic vibration reflex and deep tendon reflex and flexion synergy expression will be quantified with precise robotic measures of upper extremity work area. These measures will be conducted before, during and after either a real or sham TNS stimulus condition, with stimulus induced changes in the metrics compared between conditions and against a quantitative metric of systemic monoamines (salivary α-amylase). Preliminary work has highlighted the feasibility of the proposed measures and supported the posited rationale. Specifically, initial efforts have shown a reduction of motor impairments during TNS in individuals with chronic hemiparetic stroke. Findings from this study will act to inform an understanding of the functional role of monoaminergic contributions to human motor control. This will deepen our understanding of human motor control and could facilitate substantive efforts in the development of neurorehabilitation paradigms. Specifically, through the application of TNS detailed here, this project will supply initial evidence for a neuromodulatory probe with the potential to alter monoaminergic drive and reduce chronic stroke induced motor impairments. This will provide insight into the magnitude of monoaminergic contributions to upper extremity motoneuron excitability and flexion synergy expression and their susceptibility to changes in monoaminergic drive.

项目摘要 新兴研究表明，慢性中风诱导的运动障碍表现出对 脑干介导的单胺能驱动。明确地，下降单胺的增加是 相信会增加脊柱运动神经元的兴奋性，因此（1）产生痉挛，（2）扩增分散 负责屈曲协同表达的命令。虽然调节这个下降 单胺能驱动在影响这两种损伤的情况下都具有巨大的潜力 方法证明是不足的，需要长时间的滴定时间表并引起燃烧的副作用。那， 我提出了经皮眼眼神经刺激（TNS）的新型应用。这 已证明非侵入性刺激会衰减单胺的全身度量，并被认为是 调节单胺能脑干区域，例如基因座二聚体。这种非侵入性降低的能力 单胺代表了中风诱导运动障碍的实质性改善的可能性。 为了研究这一潜力，拟议项目的目标是阐明TNS对（1）上部的影响 肢体脊柱运动神经元兴奋性和（2）慢性中风存活中的屈曲协同表达。高度 两个目标都将雇用定量指标。脊柱运动神经元令人兴奋 补品振动反射和深肌腱反射和屈曲协同表达将通过精确机器人定量 上肢工作区域的度量。这些措施将在实际，期间和之后进行 或假TNS刺激条件，刺激引起的条件之间的指标变化 并针对系统性单胺（唾液α-淀粉酶）的定量度量。初步工作已突出显示 提出的措施的可行性并支持受试者的理由。具体而言，最初的努力有 表明在慢性偏瘫中风的个体中，TNS期间运动障碍的减少。 这项研究的结果将采取行动，以了解对单胺能的功能作用的理解 对人类运动控制的贡献。这将加深我们对人类运动控制的理解，并且可以 促进神经康复范式发展的实质性努力。具体来说，通过 此处详细介绍的TNS的应用，该项目将提供有关神经调节探针的初始证据 改变单胺能驱动并减少慢性中风诱导运动障碍的潜力。这将提供 深入了解单胺能对上肢运动神经元的贡献的巨大贡献和屈曲 协同表达及其对单胺能驱动变化的敏感性。