Gray matter correlates of migraine and gender effect: A meta-analysis of voxel-based morphometry studies

• Strong evidence of brain gray matter decrease occurred in migraine.
• GM loss in the right posterior insula, left PFC and ACC was identified.
• Higher female ratio in the patient sample correlated with GM loss in right DLPFC.

Background: An increasing number of neuroimaging studies have revealed gray matter (GM) anomalies of several brain regions by voxel-based morphometry (VBM) studies in migraineurs. However, not all the studies reported entirely consistent findings. Our aim is to investigate concurrence across VBM studies to help clarify the structural anomalies underpinning this condition. Methods: A systematic search of VBM studies of patients with migraine and healthy controls (HC) published in PubMed and Embase databases from January 2000 to March 2014 was conducted. A quantitative meta-analysis of whole-brain VBM studies in patients with migraine compared with HC was performed by means of anisotropic effect size version of signed differential mapping (AES-SDM) software package. Results: Nine studies comprising 222 patients with migraine and 230 HC subjects were included in the present study. Compared to HC subjects, the patients group showed consistent decreased GM in the posterior insular-opercular regions, the prefrontal cortex, and the anterior cingulate cortex. Results remained largely unchanged in the following jackknife sensitivity analyses. Meta-regression analysis showed that a higher percentage of females in the patient sample was associated with decreased GM in the right dorsolateral prefrontal cortex. Conclusions: This is the first quantitative whole-brain VBM meta-analysis in migraine showing strong evidence of brain GM anomalies within the pain-processing neural network. Further longitudinal investigations are needed to determine whether these structural anomalies are reversible with effective treatment on migraine.