Migraine Attacks as a Result of Hypothalamic Loss of Control

To assess the natural trajectory of brain activity over the migraine cycle, we assessed (1) the cerebral perfusion and (2) the hypothalamic connectivity during spontaneous headache attacks with follow-up recordings towards the next migraine attack. Using pseudo-continuous arterial spin labelling and resting-state functional magnetic resonance imaging, 12 migraine patients were examined in 82 sessions. We detected cyclic changes of brain perfusion in the limbic circuit (insula, hippocampus, and nucleus accumbens), with the highest perfusion during headache attacks. In addition, we found an increase of hypothalamic connectivity to the limbic system over the interictal interval, then collapsing during the headache. Our data provide strong evidence for the predominant role of the hypothalamus as a zeitgeber for generating migraine attacks. Our findings suggest that migraine attacks are the result of the hypothalamus losing control over the limbic system.