Increased Functional Connectivity Characterises the Prodromal Phase of the Migraine Cycle

Abstract

AbstractEpisodic migraine is reflected by cyclic changes in behaviour and cortical processing. In this study, we aimed to identify how functional connectivities change over the entire migraine cycle.By using longitudinal neuroimaging and a whole-brain analysis approach, we tested 12 episodic migraine patients across 82 fMRI recordings during spontaneous headache attacks, with follow-up measurements over the pain-free interval without any external stimulation.We focussed on two different trajectories with a linear increase of connectivity and a peak either during the prodromal phase or during the headache attack. We found cycle-related connectivity changes for the anterior insula and the posterior orbitofrontal cortex. Both regions showed the highest connections with sensory, motor, and cingulate areas in the prodromal phase. The connectivity between the hypothalamus and the locus coeruleus was strongest during the headache attack.The peak connectivity during the prodromal phase and its collapse during the headache can be regarded as a mechanism of normalising cortical processing. The increase of synchronicity of functional connections during the ictal phase of the migraine cycle may contribute to the variety of symptoms of migraine attacks, such as headache, hypersensitivity to sensory modalities, and autonomous symptoms. We speculate about a malfunction at the molecular level in agranular frontal and insular brain regions, which needs to be followed up upon in subsequent studies.Abbreviated SummaryEpisodic migraine is a cyclic disease. We investigated functional connectivities over an entire migraine cycle. We found cycle-related connectivity changes for two proximate agranular regions. The prodromal increase and the collapse of connectivity during the headache may reflect normalising cortical processing.