Brain structural and functional changes during menstrual migraine: Relationships with pain

Menstrual migraine (MM) is a special type of migraine associated with the ovarian cycle, which imposes a marked burden on female patients. However, the pathogenesis of MM is not completely understood. We investigated gray matter volume (GMV) and functional connectivity (FC) alterations in patients with MM to explore whether there are changes in resting-state FC (rsFC) in brain regions with structural GMV abnormalities and investigated their relevance to pain and concomitant symptoms.Seventy-five patients with MM and 54 female healthy controls underwent functional magnetic resonance imaging and examination. The patients completed a patient's headache diary, which included the frequency of migraine attacks, a visual analog scale for pain, a self-rating anxiety scale, and a self-rating depression scale. We used voxel-based morphometry (VBM) to examine the GMV differences between the MM and healthy control groups. The identified brain areas were selected as seeds to assess functional changes in the MM group. Correlation analysis between the altered VBM/rsFC and clinical outcomes was performed.Compared with healthy controls, patients with MM showed decreased GMV in the right anterior cingulum cortex (ACC) and increased GMV in the right superior parietal cortex. Pearson's correlation analysis illustrated that only GMV in the right ACC was associated with visual analogue scale pain scores in the MM group. RsFC with the ACC as the seed showed that patients with MM exhibited increased FC between the ACC and the left inferior temporal gyrus, bilateral angular gyrus, and right precuneus. Correlation analysis showed that the change in FC between the right ACC and the right precuneus was positively correlated with headache frequency, and the change in FC between the right ACC and the right angular gyrus was positively correlated with the depression score.Our results suggested that the ACC may be an important biomarker in MM, and its structural and functional impairments are significantly associated with the severity of pain and pain-related impairment of emotion in patients with MM. These findings demonstrated that headache-associated structural and functional abnormalities in the ACC may can provide integrative evidence on the physiological mechanisms of MM.