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

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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.