Network localization of regional intrinsic neural activity alterations in migraine and their neurochemical correlates

Background Migraine is a prevalent and disabling neurological disorder. Resting-state functional magnetic resonance imaging (rs-fMRI) studies have investigated regional intrinsic neural activity alterations in migraine but have often yielded inconsistent findings. Emerging network perspectives suggest that brain disorders may be better understood through disruptions in large-scale networks. Methods This systematic review included 31 rs-fMRI studies (1,238 migraine patients; 1,005 controls; 302 altered ALFF/ReHo coordinates) to clarify these discrepancies. Using functional connectivity network mapping (FCNM) with Human Connectome Project data (n = 1,093), we identified that heterogeneous regional intrinsic neural activity alterations in migraine converge onto common brain functional networks. Spatial relationships between the identified brain networks and the distribution of major neurotransmitter receptors/transporters were subsequently characterized using the Juspace toolbox. Results FCNM analysis revealed that heterogeneous regional intrinsic neural activity alterations reported in migraine studies mapped to common brain functional networks, particularly within visual, somatomotor, and attention systems. The FCNM-identified migraine network exhibited significant spatial correlations with normative distributions of metabotropic glutamate receptor 5 (mGluR5), 5-hydroxytryptamine receptor 2A (5-HT2A), and noradrenaline transporter (NAT). Conclusion These findings suggest that intrinsic neural dysfunctions in migraine map to large-scale networks with multi-neurochemical susceptibility. This framework suggests that heterogeneous regional intrinsic activity alterations in migraine are preferentially connected to visual, somatomotor, and attentional systems and are spatially aligned with normative neurochemical maps. These findings are hypothesis-generating and should not be interpreted as evidence of causality or patient-specific receptor alterations.