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.

摘要 意义：暴露于窄带绿色光（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，并比暴露于 黑了由于许多偏头痛的特征归因于异常的皮质过度兴奋和反应性， 我们正在试图确定nbGL是否减弱皮层活动，如果是，在多大程度上，它在多大程度上不同， 从黑暗（已知有助于偏头痛）。鉴于疼痛和情绪变化是 偏头痛，我们将评估皮质活动，包括在翻译研究设计的功能连接。啮齿动物 模型将用于评估人类不可能的皮质兴奋性和反应性方面。如果成功 在揭示nbGL工作的皮质机制时，这项研究可以帮助验证这种非侵入性的使用， 无风险和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有着丰富的经验 （fNIRS）成像，技术开发和临床应用;我们的临床前研究团队 在偏头痛和先兆动物模型的直接皮层记录方面有丰富的经验。方法：使用fNIRS 偏头痛患者和健康受试者的脑电成像，以及初治和患病受试者的皮质电图（ECoG）记录 状态大鼠，我们建议（1）确定nbGL对感觉和情感皮层功能影响的机制基础 偏头痛发作期间和之间;（2）显示偏头痛发作期间疼痛/伤害性/情感反应的信号特异性 暴露于nbGL、无光（NL）和白色光（WL）;和（3）记录nbGL对皮质神经元关键特征的影响。 扩散性抑郁症--偏头痛相关的异常皮质事件之一。具体目标： 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。 对照组（Aim 1A）、发作间期（Aim 2A）和发作期（Aim 3A）偏头痛患者，以及首次发作（Aim 1B）和 疾病状态（目的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，我们将 观察基线时测量的fNIRS皮质信号和ECoG以及对感觉神经刺激的反应性 （B）由于发作间期状态反映了相对皮质的条件， 过度兴奋，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），并且ECoG测量将显示WL时更强的皮层活动功率， NL比nbGL;（c）即使在发作状态，这反映了3项研究中最高水平的皮质兴奋性 组中，nbGL将对通过fNIRS和ECoG测量的抑制皮质反应性具有更大的作用;以及（d） 暴露的持续时间将增强nbGL对皮层兴奋性和反应性的抑制作用，远远超过短暂的 exposure.团队：技术、临床和基础科学成员已经合作多年， 成功完成拟议的人类和大鼠研究所需的背景。