Structural gray matter abnormalities in migraine relate to headache lateralization, but not aura

Background: The hallmark of migraine aura (MA) is transient cortical dysfunction but it is not known if MA is associated with structural cortical or subcortical changes. To determine the relation between MA and structural gray matter abnormalities, we studied a unique sample of 20 patients with frequent side-locked MA, i.e. visual aura consistently occurring in the same hemifield. Methods: We applied a highly sensitive within-patient design to assess anatomical differences with both voxel-based morphometry and surface-based morphometry on a whole-hemisphere level and for specific anatomical regions of interest. Within-subject comparisons were made with regard to aura symptoms (N = 20 vs 20) and with regard to headache (N = 13 vs 13). Results: We found no differences in gray matter structure with regard to aura symptoms in MA patients. Comparing the typical migraine headache side of the patients to the contralateral side revealed a difference in cortical thickness in the inferior frontal gyrus (mean difference 0.12 mm, p = 0.036). Conclusion: MA per se is associated with abnormal function but not with lateralized abnormalities of gray matter structure. Alteration of the inferior frontal cortex suggests structural reorganization of pain inhibitory circuits in response to the repeated intense nociceptive input due to the headache attacks.