Migraine and the Hippocampus

The hippocampus is involved in pain processing, pain-related attention and anxiety, and stress response. The present review compiles the present knowledge of hippocampal volume, activity, and connectivity regarding migraine.

For hippocampal volume, a longitudinal study discovered decreased volume in newly diagnosed migraine patients after 1 year. Two cross-sectional studies suggested an adaptive increase of volume at low headache frequency and a maladaptive decrease of volume at higher headache frequency. Patients who carried a COMT Val homozygous were found to have larger hippocampi on both sides compared with healthy controls with the same polymorphism. For hippocampal activation, one study showed greater nociceptive activation in patients with migraine compared to healthy controls, with the activity correlated to headache frequency. Another study showed greater deactivation and higher functional connectivity linked to other pain-processing regions in low frequency compared to high-frequency migraineurs. At resting state, intraregional functional connectivity of hippocampus was demonstrated to be lower, and connectivity of the hippocampus with other brain regions was different in patients carrying specific genetic variants. For structural connectivity, two studies suggest a stronger connectivity between the hippocampus and other corticolimbic regions, and the altered connectivities are responsible for migraine-associated allodynia or placebo effect of migraine. Factors including headache frequency, accumulative number of migraine attacks, anxiety score, depression score, and genetic variants are related to hippocampal morphology and functional changes in people with migraine. Future studies should select participants precisely and appropriately control for genetic variants to investigate the complex relationship between the hippocampus and migraine.