Altered locus coeruleus functional connectivity in migraine without aura based on resting-state functional magnetic resonance imaging

Background: Accumulating evidence indicates that the locus coeruleus (LC) plays a pivotal role in pain modulation and related network dysfunction in migraine. This study aimed to examine functional connectivity (FC) between the LC and other brain regions in patients with migraine without aura (MwoA) compared with healthy controls (HCs). Methods: A total of 55 patients with MwoA and 50 age-, sex-, and education-matched HCs underwent resting-state functional magnetic resonance imaging (fMRI). Seed-to-voxel whole-brain FC analysis was performed using the bilateral LC as seed regions. Different clinical and neuropsychological assessments are included. Pearson correlation analysis was used to determine the relationships between altered FC and clinical variables, and receiver operating characteristic (ROC) analysis was further performed to evaluate the discriminatory performance of significant FC measures. Results: Compared with HCs, patients with MwoA exhibited increased FC between the left LC and the right superior temporal gyrus (STG)/left cerebellar posterior lobe (CPL), as well as between the right LC and the left STG/left inferior occipital gyrus (IOG) (p < 0.05). Decreased FC was observed between the bilateral LC and the right superior frontal gyrus (SFG) (p < 0.05). Positive correlations were identified between disease duration and FC of the left LC–right STG connection (p = 0.012, r = 0.341), and between SDS scores and FC of the right LC–left IOG connection (p = 0.011, r = 0.344). ROC analysis demonstrated that FC between the right LC and right SFG had the best discriminatory performance (sensitivity 81.82%, specificity 68.00%). Conclusions: Patients with MwoA exhibited altered LC-related resting-state FC involving brain regions associated with pain processing, sensory integration, and emotional regulation. By separately characterizing the whole-brain connectivity patterns of the bilateral LC, this study extends previous LC-related imaging findings in migraine and provides a more refined description of LC-centered network dysfunction in MwoA.

Migraine without aura; Resting-state functional magnetic resonance imaging; Functional connectivity; Locus coeruleus

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