Intrinsic network connectivity reflects the cyclic trajectory of migraine attacks

BACKGROUND: Episodic migraine is considered to be cyclic in nature, triggered by the hypothalamus. To assess the natural trajectory of intrinsic networks over an entire migraine cycle, we designed a longitudinal intra-individual study using functional magnetic resonance imaging (fMRI). METHODS: Intrinsic network connectivity was assessed for 12 migraineurs in 82 sessions including spontaneous, untriggered headache attacks and follow-up recordings towards the next attack. RESULTS: We found cyclic changes in the visual, auditory, and somatosensory networks, in limbic networks (e.g. thalamo-insular, parahippocampal), and in the salience network (anterior insula and dorsal anterior cingulate cortex). Connectivity changes also extended to further cortical networks, such as the central executive network, the default mode network, as well as subcortical networks. Almost all of these network connectivity changes followed the trajectory of a linear increase over the pain-free interval that peaked immediately prior to the headache, and “dropped” to the baseline level during the headache. These network alterations are associated with a number of cortical functions that may explain the variety of ictal and pre-ictal physiological and psychological migraine symptoms. CONCLUSION: Our results suggest that migraine disease is associated with widespread cyclic alterations of intrinsic networks that develop before the headache is initiated, i.e. during the interictal and premonitory phase. The increasing magnitude of connectivity within these networks towards the next attack may reflect an increasing effort to maintain network integrity.