Brain connectivity in individuals with migraine resets during the headache phase: a whole-brain connectivity study.

Episodic migraine is reflected by cyclic changes in behavior and cortical processing. We aimed to identify how functional connectivity changes over the entire migraine cycle. By using longitudinal neuroimaging and a whole-brain connectivity analysis approach, we tested 12 episodic migraine patients across 82 functional MRI recordings during spontaneous migraine headaches with follow-up measurements over the pain-free interval without any external stimulation. We found that the functional connectivity 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 strength 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 normalizing cortical processing. We speculate about a malfunction at the molecular level in agranular frontal and insular regions, which needs to be addressed in subsequent studies.