No differences in subcortical volume between people with and without migraine: A REFORM study

To determine whether the volume of specific subcortical structures differ between people with migraine and healthy controls, and whether these volumes vary across distinct migraine subtypes and phases. Subcortical structures, including regions involved in pain processing and sensory integration, play a key role in migraine pathophysiology, yet studies on volumetric differences have shown conflicting results. This study uses a large cohort and robust imaging methods to clarify whether subcortical volumes differ in migraine.

In this cross-sectional study at the Danish Headache Center in Denmark, conducted between January 2020 and December 2023, adult participants with migraine and age- and sex-matched healthy controls underwent a single magnetic resonance imaging session at 3T. T1-weigthed scans were acquired to measure the volumes of subcortical structures using automated segmentation techniques. The structures analyzed included the thalamus, putamen, caudate nucleus, pallidum, nucleus accumbens, amygdala, and hippocampus.

Imaging data from 295 participants and 154 healthy controls were included in the final analyses. No significant differences were observed between participants with migraine and healthy controls in thalamic volume (migraine: 7243 ± 923 mm³ vs. healthy controls: 7350 ± 782 mm³; p = 0.774) or hippocampal volume (migraine: 4204 ± 398 mm³ vs. healthy controls: 4307 ± 446 mm³; p = 0.337). No differences were observed in any other subcortical structure. Likewise, different subgroup analyses revealed no volumetric differences in episodic versus chronic migraine, migraine with aura versus without aura, ictal versus headache free, or between each migraine subgroup and healthy controls (all p > 0.05 after multiple comparison correction).

In this large cross-sectional study, we found no evidence of subcortical volume differences between adults with migraine and healthy controls. Furthermore, no differences were found across migraine subtypes or phases. These findings indicate that subcortical volumetric measures are not suitable as imaging biomarkers of migraine. Future research should explore functional and metabolic alterations in subcortical structures to better understand the neurobiologic underpinnings of migraine.