Abnormal functional integration and effective connectivity in striatal-cortical networks with neurotransmitter system...

Migraine without aura (MWoA) is linked to abnormal subcortical/cortical network activity and neurotransmitter dysregulation. However, the alteration of functional integration and the information flow between brain networks participated in pain sensory pathway and the patterns of neurotransmitter dysregulation during the interictal period remain unclear.

This cross-sectional study compared 53 interictal MWoA patients and 51 healthy controls using resting-state fMRI. Whole-brain functional integration (degree centrality, DC) and effective connectivity (EC) were analyzed. JuSpace toolbox mapped spatial correlation between functional alterations and neurotransmitter systems.

MWoA patients showed decreased DC in the left putamen and increased DC in the left angular gyrus. Altered EC from subcortical to cortical regions included pathways from the left putamen to right medial superior frontal gyrus, supramarginal gyrus, dorsolateral superior frontal gyrus, and postcentral gyrus, as well as bilateral caudate to left angular gyrus. Cortical-to-subcortical EC changes involved right dorsolateral superior frontal gyrus to left putamen and left angular gyrus to left caudate. EC from left putamen to right postcentral gyrus inversely correlated with headache frequency, while right caudate to left angular gyrus EC positively correlated with disease duration. Altered DC patterns spatially overlapped with serotonergic, dopaminergic, and glutamate pathways and correlated with quality-of-life impairments (MSQ scores).

MWoA involves disrupted functional integration and bidirectional subcortical-cortical connectivity during interictal periods, associated with headache severity and neurotransmitter system imbalances. These findings highlight network-level pathophysiology and neurochemical dysregulation underlying migraine.