Narrow band green light effects on cortical excitability and responsivity in migraine

窄带绿光对偏头痛皮质兴奋性和反应性的影响

• 批准号: 10675293
• 负责人: Rami Burstein
• 金额: $ 59.98万
• 依托单位: BETH ISRAEL DEACONESS MEDICAL CENTER
• 依托单位国家: 美国
• 财政年份: 2023
• 资助国家: 美国
• 起止时间: 2023-08-01 至 2028-07-31
• 项目状态: 未结题
• 来源: https://reporter.nih.gov/project-details/10675293
• 关键词: Acute; Affect; Affective; Amber; Anesthesia procedures; Animal Disease Models; Animal Model; Anxiety; Area; Attenuated; Auras; Aversive Stimulus; Basic Science; Brain; Characteristics; Clinical; Clinical Data; Clinical Research; Clinical Sciences; Cognitive; Color; Complex; Darkness; Data; Development; Disease; Electrocorticogram; Electrophysiology (science); Emotional; Event; Exposure to; Female; Frequencies; Goals; Headache; Hour; Human; Knowledge; Light; Measures; Medial; Methods; Migraine; Neurobiology; Neurons; Nociception; Outpatients; Pain; Patients; Persistent pain; Photophobia; Phototherapy; Property; Publishing; Rattus; Research; Research Design; Rest; Risk; Rodent Model; Sedation procedure; Sensory; Series; Signal Transduction; Somatosensory Cortex; Specificity; Spreading Cortical Depression; Stimulus; Symptoms; Testing; Therapeutic; Work; animal data; awake; experience; frontal lobe; functional near infrared spectroscopy; human subject; insight; light effects; male; member; migraine treatment; neural; novel; novel therapeutic intervention; pain perception; portability; pre-clinical research; preclinical study; response; sensory stimulus; side effect; spectroscopic imaging; translational study; trend

ABSTRACT Significance: Exposure to narrow band green light (nbGL) appears to reduce intensity, frequency, and duration of migraine headache and some of its most bothersome symptoms and does so more effectively than exposure to dark. Because many migraine characteristics are attributed to abnormal cortical hyperexcitability and responsivity, we are seeking to determine whether nbGL attenuates cortical activity, and if so to what extent, what extent it differs from dark (known to help migraine headache). Given that pain and emotional changes are major components of migraine, we will assess cortical activity including functional connectivity in a translational study design. A rodent model will be used to evaluate aspects of cortical excitability and responsivity not possible in humans. If successful in unraveling a cortical mechanism by which nbGL works, this study can help validate the use of this noninvasive, risk-free and affordable therapeutic approach as an alternative/additional method for the treatment of migraine. Preliminary data: Our clinical research team has extensive experience in functional near infrared spectroscopy (fNIRS) imaging, technical development and use in the clinical setup; and our pre-clinical research team has extensive experience in direct cortical recording in animal models of migraine and aura. Approach: Using fNIRS imaging in migraine patients and healthy subjects, and electrocorticography (ECoG) recording in naïve and diseased state rats, we propose to (1) define a mechanistic basis for nbGL effects on sensory and affective cortical functions during and in between migraine attacks; (2) show signal specificity of pain/nociceptive/affective responses during exposure to nbGL, no light (NL), and white light (WL); and (3) record nbGL effects on key characteristics of cortical spreading depression - one of the better-understood migraine-associated abnormal cortical event. Specific Aims: In Aims 1-3, we will determine effects of nbGL (compared to WL and NL) on fNIRS measured in cortices of healthy controls (aim 1A), interictal (Aim 2A) and ictal (Aim 3A) migraineurs, and ECoG recording in naïve (Aim 1B) and disease-state (Aims 2B, 3B) rats. Hypotheses: Our hypotheses are: (a) in healthy subjects and naïve rats we will observe significant differences in fNIRS cortical signals and ECoG measured at baseline and responsivity to sensory stimuli under each of the 3 light conditions; (b) because the interictal state reflects a condition of relative cortical hyperexcitability, fNIRS measures to resting state and evoked pain will show smaller excitation of cortical regions (S1, mPFC) under nbGL than under WL, and ECoG measures will show stronger cortical activity power at WL and NL than at nbGL; (c) even in the ictal state, which reflects the highest level of cortical excitability in the 3 study groups, nbGL will have a greater effect on inhibiting cortical responsivity as measured by fNIRS and ECoG; and (d) duration of exposure will enhance inhibitory nbGL effect on cortical excitability and responsivity, far beyond brief exposure. Team: The technical, clinical and basic science members have worked together for many years and have the necessary background to successfully complete the proposed human and rat studies.

抽象的 意义：暴露于窄带绿光 (nbGL) 似乎会降低强度、频率和持续时间 偏头痛及其一些最令人烦恼的症状，比接触更有效 因为许多偏头痛特征归因于皮质过度兴奋和反应性异常， 我们正在寻求确定 nbGL 是否会减弱皮质活动，如果是的话，减弱程度如何，差异有多大 鉴于疼痛和情绪变化是偏头痛的主要组成部分。 偏头痛，我们将评估皮质活动，包括转化研究设计中的功能连接。 如果成功，该模型将用于评估人类不可能实现的皮质兴奋性和反应性方面。 在揭示 nbGL 工作的皮质机制中，这项研究可以帮助验证这种非侵入性、 无风险且负担得起的治疗方法作为治疗偏头痛的替代/附加方法。 初步数据：我们的临床研究团队在功能性近红外光谱方面拥有丰富的经验 (fNIRS) 成像、技术开发和在临床设置中的使用；我们的临床前研究团队已经 在偏头痛和先兆动物模型中直接皮质记录方面拥有丰富的经验 方法：使用 fNIRS。 偏头痛患者和健康受试者的成像，以及幼稚和患病受试者的皮质电图 (ECoG) 记录 状态大鼠，我们建议（1）定义 nbGL 对感觉和情感皮层功能影响的机制基础 (2) 显示偏头痛发作期间和之间的疼痛/伤害感受/情感反应的信号特异性；(2) 显示偏头痛发作期间疼痛/伤害感受/情感反应的信号特异性； 暴露于 nbGL、无光 (NL) 和白光 (WL)；以及 (3) 记录 nbGL 对皮质关键特征的影响 扩散性抑郁症 - 更容易理解的与偏头痛相关的异常皮质事件之一。 在目标 1-3 中，我们将确定 nbGL（与 WL 和 NL 相比）对健康人皮质中测量的 fNIRS 的影响 控制（目标 1A）、发作间期（目标 2A）和发作期（目标 3A）偏头痛，以及幼稚（目标 1B）和 疾病状态（目标 2B、3B）大鼠 假设：我们的假设是：（a）在健康受试者和幼稚大鼠中我们会。 观察基线测量的 fNIRS 皮层信号和 ECoG 以及对感觉的反应性的显着差异 (b) 因为发作间期状态反映了相对皮质的状况 过度兴奋性、静息状态和诱发疼痛的 fNIRS 测量将显示皮质区域的较小兴奋 (S1, mPFC) 在 nbGL 下比在 WL 下，并且 ECoG 测量将显示 WL 和 WL 下更强的皮质活动能力 NL 高于 nbGL；(c) 即使在发作状态，这反映了 3 研究中皮质兴奋性的最高水平 根据 fNIRS 和 ECoG 测量，nbGL 对抑制皮质反应性具有更大的影响；(d) 暴露持续时间将增强 nbGL 对皮质兴奋性和反应性的抑制作用，远远超出短暂的范围 团队：技术、临床和基础科学成员共同工作多年，并拥有丰富的经验。 成功完成拟议的人类和大鼠研究的必要背景。