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 新兴的研究表明，慢性中风引起的运动障碍表现出依赖于 升高脑干介导的单胺能驱动。可以解释的是，下降单胺的增加是 据信增加脊髓运动神经元的兴奋性，从而（1）产生痉挛和（2）放大弥漫性 负责屈曲协同表达的命令。虽然调节这种下降 单胺能驱动在影响这两种损伤方面产生巨大潜力， 这些方法被证明是不充分的，需要漫长的滴定时间表，并引起难以负担的副作用。因此，在本发明中， 我提出了新的应用经皮电眼三叉神经刺激（TNS）。这 非侵入性刺激已经显示出减弱单胺的全身性测量， 调节单胺能脑干区域如蓝斑。这种非侵入性地减少 单胺代表了显著改善中风引起的运动损伤的可能性。 为了研究这一潜力，拟议项目的目标是阐明TNS对（1）上层 肢体脊髓运动神经元兴奋性和（2）屈曲协同表达。高度 这两个目标都将采用量化指标。脊髓运动神经元兴奋性将通过 紧张性振动反射和深腱反射以及屈曲协同表达将用精确的机器人测量来量化。 上肢工作区的测量。这些措施将在真实的 或假TNS刺激条件，其中刺激诱导的度量变化在条件之间进行比较 和针对系统性单胺（唾液α-淀粉酶）的定量度量。前期工作突出了 委员会认为建议的措施是可行的，并支持所提出的理据。具体而言，初步努力已 显示慢性轻偏瘫中风患者在TNS期间运动障碍减少。 这项研究的结果将有助于了解单胺能神经递质的功能作用。 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， 促进神经康复范例发展的实质性努力。具体而言，通过 TNS的应用在这里详细介绍，该项目将提供初步证据的神经调节探针与 改变单胺能驱动和减少慢性中风引起的运动损伤的潜力。这将提供 了解单胺能对上肢运动神经元兴奋性和屈曲的贡献程度 协同表达和它们对单胺能驱动变化敏感性。