Investigating the oscillation of sensory thresholds through the migraine cycle

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All sensory thresholds are dynamic during a migraine cycle, possibly driven by a genetically inherent periodic oscillation of the hypothalamo-thalamo-brainstem network. In general, sensory thresholds decrease during the interictal stage and reach a nadir during the headache pain attack, only to gradually recover afterwards. We aim to identify brain areas that decode such sensory thresholds changes in migraine patients with the ultimate goal to gain insight into the origin/generation of migraine attacks. In order to archive our goal we will conduct daily longitudinal measurements of sensory input at the threshold level towards a spontaneous migraine attack. Functional imaging will be done with a dedicated focus on brainstem and diencephalon areas using a brainstem optimized spinal imaging method. In order to capture spontaneous migraine attacks and at least two pre-attack days, we will scan patients with pure menstrually-related migraine and healthy female controls each day–always in the morning- for eight consecutive days. Thereby, the 7th day is calculated to be the start of menstruation and in migraine patients also the start of the migraine attack (± 1 day). Since migraine attacks in pure menstrual migraine only occur shortly before or during menstruation, this method allows to predict migraine attacks. Scanning patients and healthy controls equally towards the menstruation will allow to control menstruation as a confound. After determination of the individual pain threshold on each individual day inside the scanner, patients and healthy controls will be presented with a series of electrical inputs in the trigeminal area (ophthalmic division, on the forehead above the brow in exactly the stimulus intensity that has been determined to be the individual threshold of that specific day. Since 50% of the standardized input will be perceived as painful and 50% of the stimuli will not, data analysis will allow, using regression models and connectivity analysis, to determine the cycling neuronal excitability and alternating functional connectivity of limbic and brainstem areas that are the prerequisite to generate a migraine attack. Current literature suggests the following areas of the central nervous system to be candidates: Thalamus, Hypothalamus, Nucleus accumbens, periaqueductal gray (PAG), trigeminocervical complex (TCC), and rostral ventromedial medulla (RVM).