Increased Functional Connectivity Characterises the Prodromal Phase of the Migraine Cycle

IntroductionEpisodic migraine is reflected by cyclic changes in behaviour and cortical processing. We aimed to identify how Functional connectivities change over the entire migraine cycle. MethodsBy using longitudinal neuroimaging and a whole-brain connectivity 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. ResultsWe Found that Functional connectivities linearly increased over the interictal interval. In the prodromal phase, we observed the strongest connections between the anterior agranular insula and the posterior orbitofrontal cortex with sensory, motor, and cingulate areas. The strengths of the connections dropped during the headache. Peak connectivity during the prodromal phase and its collapse during the headache can be regarded as a mechanism of normalising cortical processing. ConclusionsThe strongest connections during the ictal phase of the migraine cycle may contribute to the variety of symptoms of migraine attacks including headache, sensory hypersensitivity, and autonomous symptoms. We speculate about a malfunction at the molecular level in agranular frontal and insular regions, which needs to be addressed in subsequent studies. Article highlightsO_LIWe investigated functional connectivities over an entire migraine cycle. C_LIO_LIWe found cycle-related connectivity changes for two proximate agranular regions. C_LIO_LIThe prodromal increase and the collapse of connectivity during the headache may reflect normalising cortical processing. C_LI