Cortical network dysfunction in migraine: linking genes, metabolism and clinical disability

Migraine is a multifactorial neurovascular disorder that involves both genetic predisposition and environmental influences. Despite extensive research, the precise mechanisms through which genetic factors contribute to brain dysfunction and vulnerability in migraine remain unclear.

This study included 139 migraine patients and 65 healthy controls. We constructed a Morphometric Inverse Divergence (MIND) network based on regional morphometric measurements to explore the relationship between brain structural alterations, cognitive function, metabolic distribution, and gene expression profiles. The MIND network was further used to predict individual functional disability in migraine.

Transcriptomic analysis identified 124 genes involved in synaptic signaling and neurotransmitter transport, primarily expressed in endothelial cells, oligodendrocytes, and excitatory/inhibitory neurons. Metabolic dysregulation explained 5.61% of the variance, with the oxygen-glucose index (OGI) as the primary driver. Migraine patients showed significant disruptions in MIND networks associated with language, cingulo-opercular, and somatomotor systems, which were correlated with cognitive domains (e.g., memory, pain, language) and predictive of functional disability (r = 0.23, P_perm​ = 0.015).

This study reveals a novel link between macroscopic brain structural abnormalities and microscopic transcriptional patterns in migraine. These findings enhance our understanding of migraine neurobiology and offer potential therapeutic targets for future interventions.