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; 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 偏头痛的标题及其两种符号的符号，并且比暴露更有效 黑暗的。由于许多偏头痛特征归因于皮质过度异常和反应性异常，所以 我们正在寻求确定NBGL是否会减弱皮质活动，如果是这样，它在何种程度上有所不同 来自黑暗（已知可帮助偏头痛标题）。鉴于痛苦和情绪改变是 偏头痛，我们将在翻译研究设计中评估包括功能连通性的皮质活动。啮齿动物 模型将用于评估人类不可能的皮质兴奋和反应性方面。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 无风险且负担得起的治疗方法是治疗偏头痛的替代/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具有丰富的经验 （FNIRS）成像，技术开发和临床设置的使用；我们的临床前研究团队有 在偏头痛和光环的动物模型中，具有直接皮质记录的丰富经验。方法：使用fnirs 偏头痛患者和健康受试者的成像以及幼稚和解散中的电视图（ECOG）记录 状态大鼠，我们建议（1）定义NBGL对感觉和情感皮质功能影响的机械基础 在偏头痛攻击期间和之间； （2）显示疼痛/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）； （3）记录NBGL对皮质关键特征的影响 扩散抑郁症 - 偏头痛相关的异常皮质事件之一。具体目的： 在AIMS 1-3中，我们将确定NBGL（与WL和NL相比）对在健康皮质中测得的FNIR的影响 控件（AIM 1A），充 疾病状态（AIMS 2B，3B）大鼠。假设：我们的假设是：（a）在健康的受试者和幼稚的大鼠中，我们将 观察到在基线时测得的FNIRS皮质信号和ECOG的显着差异以及对感觉的反应 在3个光条件下的每个条件下的每个条件下的刺激； （b）因为发作状态反映了相对皮质的条件 过度兴奋性，静息状态的FNIRS措施和诱发的疼痛将显示皮质区域的刺激较小 （S1，MPFC）在NBGL下，而不是在WL下，ECOG测量将显示WL和 NL比NBGL; （c）即使在ICTAL状态，这反映了3个研究中最高水平的皮质令人兴奋 组，NBGL将对通过FNIRS和ECOG衡量的抑制皮质反应性产生更大的影响。 （d） 暴露持续时间将增强抑制性NBGL对皮质兴奋性和反应性的影响，远远超出了短暂的 接触。团队：技术，临床和基础科学成员已经合作了很多年，并且 成功完成所提出的人类和大鼠研究的必要背景。