Trigeminal Nerve Stimulation in Chronic Hemiparetic Stroke

三叉神经刺激治疗慢性偏瘫中风

基本信息

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
项目类别：
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

项目摘要

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.

项目概要新兴研究表明，慢性中风引起的运动障碍表现出对明确地，脑干介导的单胺能驱动力增加。据信可增加脊髓运动神经元的兴奋性，从而 (1) 产生痉挛状态并 (2) 放大弥漫性负责屈曲协同表达的命令。单胺能驱动在影响这两种损伤方面产生了巨大的潜力，目前的药理学事实证明，这些方法是不够的，需要漫长的滴定时间表，并会产生繁重的副作用。我提出了经皮眼科三叉神经电刺激（TNS）的新应用。非侵入性刺激已被证明可以减弱单胺的全身测量，并被认为调节单胺能脑干区域，例如蓝斑，以非侵入性方式减少这种能力。单胺代表了显着改善中风引起的运动障碍的可能性。为了研究这种潜力，拟议项目的目标是阐明 TNS 对 (1) 上层的影响慢性中风幸存者的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定量指标。强直振动反射、深腱反射和屈曲协同表达将通过精确的机器人进行量化这些措施将在实际操作之前、期间和之后进行。或假 TNS 刺激条件，比较条件之间的刺激引起的指标变化以及针对全身单胺（唾液 α-淀粉酶）的定量指标。具体而言，初步努力已证明了拟议措施的可行性并支持了所提出的理由。研究表明，慢性偏瘫中风患者在 TNS 期间运动障碍有所减少。这项研究的结果将有助于了解单胺能的功能作用这将加深我们对人类运动控制的理解，并可能具体来说，通过以下方式促进神经康复范式发展的实质性努力。这里详细介绍了 TNS 的应用，该项目将为神经调节探针提供初步证据改变单胺能驱动并减少慢性中风引起的运动障碍的潜力。深入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及其对单胺能驱动变化的敏感性。