Altered regional cerebral blood flow and hypothalamic connectivity immediately prior to a migraine headache

Abstract

Background There is evidence of altered resting hypothalamic activity patterns and connectivity prior to a migraine, however it remains unknown if these changes are driven by changes in overall hypothalamic activity levels. If they are, it would corroborate the idea that changes in hypothalamic function result in alteration in brainstem pain processing sensitivity, which either triggers a migraine headache itself or allows an external trigger to initiate a migraine headache. We hypothesise that hypothalamic activity increases immediately prior to a migraine headache and this is accompanied by altered functional connectivity to pain processing sites in the brainstem. Methods In 34 migraineurs and 26 healthy controls, we collected a series comprising 108 pseudo-continuous arterial spin labelling images and 180 gradient-echo echo planar resting-state functional magnetic resonance volumes to measure resting regional cerebral blood flow and functional connectivity respectively. Images were pre-processed and analysed using custom SPM12 and Matlab software. Results Our results reflect that immediately prior to a migraine headache, resting regional cerebral blood flow decreases in the lateral hypothalamus. In addition, resting functional connectivity strength decreased between the lateral hypothalamus and important regions of the pain processing pathway, such as the midbrain periaqueductal gray, dorsal pons, rostral ventromedial medulla and cingulate cortex, only during this critical period before a migraine headache. Conclusion These data suggest altered hypothalamic function and connectivity in the period immediately prior to a migraine headache and supports the hypothesis that the hypothalamus is involved in migraine initiation.

Identifying New Antimigraine Targets: Lessons from Molecular Biology

“…A study by Schulte and May showed, upon daily imaging of a single migraine patient, that the hypothalamus was active during 24 h preceding the migraine attack [7]. The activity was coupled/connected to the brainstem (e.g., the trigeminal nucleus caudalis, TNC) during the ictal stage (see Glossary), and similar data on hypothalamic connectivity has been reported to occur prior to a migraine attack [8]. We speculate that changes in the TNC causes further activation, potentiation, or modification of the function in the trigeminal ganglion (TG), either by direct activation or by modulation of incoming sensory information.…”

Contextual experience modifies functional connectome indices of topological strength and efficiency

“…Undersampled Nyquist frequencies can alias into the measured fMRI signal and drive hypothalamic 'synchronous' activity in the presence of suppressed cortical connectivity strength. However, despite this possible non-neuronal mechanism there are studies that have observed a role for hypothalamic nuclei in functional connectivity in models of pain, in human studies of migraine headache, and in studies of obesity where increases in hypothalamic functional connectivity have been reported [62][63][64] .…”

Contextual experience modifies functional connectome indices of topological strength and organization

“…Nyquist frequencies can alias into the measured fMRI signal and drive hypothalamic 'synchronous' activity in the presence of suppressed cortical connectivity strength. However, despite this possible non-neuronal mechanism there are studies that have observed a role for hypothalamic nuclei in functional connectivity in models of pain, in human studies of migraine headache, and in studies of obesity where increases in hypothalamic functional connectivity have been reported (83)(84)(85).…”