Structural Co-Variance Patterns in Migraine: A Cross-Sectional Study Exploring the Role of the Hippocampus

Objective: To interrogate hippocampal morphology and structural co-variance patterns in migraine patients and to investigate whether structural co-variance patterns relate to migraine disease characteristics. Background: Migraine is associated with structural alterations in widespread cortical and subcortical regions associated with the sensory, cognitive, and affective components of pain processing. Recent studies have shown that migraine patients have differences in hippocampal structure and function relative to healthy control subjects, but whether hippocampal structure relates to disease characteristics including frequency of attacks, years lived with migraine and symptoms of allodynia remains unknown. Furthermore, this study investigated hippocampal volume co-variance patterns in migraineurs, an indirect measure of brain network connectivity. Here, we explore differences in hippocampal volume and structural co-variance patterns in migraine patients relative to healthy controls and examine whether these hippocampal measures relate to migraine disease burden. Methods: This study included 61 migraine patients and 57 healthy control subjects (healthy controls: median age = 34.0, IQR = 19.0; migraine patients: median age = 35.0, IQR = 17.5; P =.65). Regional brain volumes were automatically calculated using FreeSurfer version 5.3. Symptoms of allodynia were determined using the Allodynia Symptom Checklist 12 (ASC-12). Structural co-variance patterns were interrogated using pairwise correlations and group differences in correlation strength were estimated using Euclidian distance. A stepwise regression was used to investigate the relationship between structural co-variance patterns with migraine burden. Results: Migraine patients had less left hippocampal volume (healthy controls: left hippocampal volume = 4276.8 mm³, SD = 425.3 mm³, migraine patients: left hippocampal volume = 4089.5 mm³, SD = 453.9 mm³, P =.02) and less total (right plus left) hippocampal volume (healthy controls: total hippocampal volume= 8690.8 mm³, SD = 855.1 mm³; migraine patients: total hippocampal volume = 8341.8 mm³, SD = 917.9 mm³; P =.03) compared to healthy controls. Migraineurs had stronger structural covariance between the hippocampi and cortico-limbic regions in the frontal lobe (inferior opercular gyrus), temporal lobe (planum temporale, amygdala), parietal lobe (angular gyrus, precuneus), and the cerebellar white matter. Results of a stepwise regression showed that hippocampal volumes and the interactions between hippocampal volumes with the volumes of other cortico-limbic regions associate with migraine-related allodynia but not with headache frequency or years lived with migraine. Conclusion: Migraineurs have less hippocampal volume and stronger hippocampal-cortico-limbic connectivity compared to healthy controls. Hippocampal volumes and measures of hippocampal volume connectivity with other cortico-limbic network regions associate with symptoms of allodynia.