Structural and functional changes of insula subregions in migraine without aura and their relationships with pain perception

Migraine is a highly prevalent and disabling neurological disorder characterized by abnormal encoding of pain perception, linked to structural and functional abnormalities in the insula. Insular subregions play critical but distinct roles in this process, however, the specific patterns and mechanisms remain elusive in migraineurs. In this study, voxel-based morphometry and seed-based functional connectivity (FC) were employed to investigate structural and functional alterations in insula subdivisions in 44 patients with migraine without aura (MWoA) compared with 51 matched healthy controls. Pain perception was evaluated using the intensity, frequency, and duration of migraine. Compared with healthy controls, patients exhibited(1) reduced gray matter volume in the bilateral dorsal anterior insula (dAI);(2) increased FC between the dAI/posterior insula and bilateral precuneus, the left dAI and left middle temporal gyrus, the left ventral AI and superior/middle frontal gyrus;(3) decreased FC between the left dAI and left middle frontal gyrus, left middle occipital gyrus and right pallidum. Moreover, the left dAI was correlated with the duration and frequency of migraine, the right dAI was correlated with the intensity and duration of migraine. Our results provide novel evidence in support of the insula abnormality hypothesis in migraine and highlight the pivotal role of alterations in the dAI in pain perception in migraineurs.