Objectives To investigate the structural changes of hippocampus and amygdala and their relationships with migraine frequency and prognosis. Methods Hippocampus and amygdala volumes were measured by 3-T brain magnetic resonance imaging (MRI) in 31 controls and 122 migraine patients who were categorized into eight groups by headache frequency: group 1 (1-2 headache days/month), 2 (3-4), 3 (5-7), 4 (8-10), 5 (11-14), 6 (15-19), 7 (20-24), and 8 (25-30). Headache frequency was reassessed 2 years later and a frequency reduction ≥50% was regarded a good outcome. Results Hippocampus and amygdala volumes fluctuated in patient groups but did not differ from the controls. In migraine patients, the bilateral hippocampus volumes peaked in group 3. The volumes and headache frequencies correlated positively in groups 2-3 on bilateral sides (L: r = 0.44, p = 0.007; R: r = 0.35, p = 0.037), and negatively in groups 3-7 on the left side (5-24 days/month; L: r = -0.31, p = 0.004) and groups 3-8 on the right side ( r = -0.31, p = 0.002). The left amygdala volume also peaked in group 3, and correlated with headache frequency in groups 1-3 ( r = 0.34, p = 0.020) and groups 3-6 ( r = -0.30, p = 0.012). The volumetric changes of the right amygdala with headache frequency did not reach statistical significance. At 2-year follow-up, the right hippocampus volume was positively associated with a good migraine outcome after adjustment of headache frequency (OR 4.72, p = 0.024). Conclusions Hippocampus and amygdala display a structural plasticity linked to both headache frequency and clinical outcome of migraine.

Tension-type headache (TTH) and migraine are both common types of headaches. Despite distinct symptoms, TTH and migraine are highly comorbid and exhibit many clinical similarities. This study enrolled consecutive patients with TTH and age- and sex-matched patients with migraine and healthy controls to investigate whether TTH and migraine are similar in brain excitability change assessed by magnetoencephalography. Patients with TTH were excluded if they reported any headache features or associated symptoms of migraine. In response to paired-pulse electrical stimulations, the gating responses obtained from the contralateral primary somatosensory cortex differed between groups. The first response, which reflected the preactivation excitability, was smaller in the migraine group (29.54 ± 2.31 pAm) compared with the TTH group (79.76 ± 8.36, P < 0.001) and controls (59.95 ± 4.26, P = 0.006). The gating ratio (ie, the ratio of the second vs first response strength) was 0.76 ± 0.03 in controls, 0.88 ± 0.03 in the migraine group, 0.93 ± 0.03 in the TTH group, with a significant increase in TTH (P = 0.003 vs controls) suggesting central disinhibition. The area under the receiver operating characteristic curve of the first response strength in differentiating between TTH and migraine was 0.85 ± 0.44, indicating excellent discrimination. In conclusion, TTH and migraine are different clinical entities in view of somatosensory cortex excitability. The preactivation excitability assessed through somatosensory gating is a potential marker for differentiating between TTH and 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.