Graph Theory Analysis of Topological Properties in White Matter Functional Networks of Adolescent Females with Primary Dysmenorrhea: A Resting-State fMRI Study
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Objectives Primary dysmenorrhea (PDM) is associated with functional reorganization in gray matter networks, but whether white matter functional networks exhibit similar topological alterations remains unknown. This study provides the first graph-theoretical analysis of white matter functional connectomes in adolescent PDM using resting-state functional magnetic resonance imaging (rs-fMRI). Methods This study enrolled 32 healthy controls (HC) and 30 patients with PDM, who underwent structural and rs-fMRI scans and clinical assessments.After rigorous preprocessing to minimize gray matter contamination, individual white matter functional networks were constructed using a 128-node group-level parcellation. Global topological properties --including normalized clustering coefficient (γ), normalized characteristic path length (λ), small-worldness (σ), clustering coefficient (Cp), characteristic path length (Lp), global efficiency (Eg), and local efficiency (Eloc)—were computed across a sparsity range of 0.10–0.30. Group comparisons were performed with age, BMI, and head motion as covariates. Correlations between significant network metrics and Self-Rating Anxiety Scale (SAS) / Self-Rating Depression Scale (SDS) scores were examined. Results Both groups exhibited small-world architecture in white matter functional networks. Compared with HCs, PDM patients showed significantly decreased γ (P = 0.013), σ (P = 0.015), and Eg (P = 0.031), along with significantly increased Lp (P = 0.025). No group differences were found in Cp, λ, or Eloc (all P > 0.05). Correlation analyses revealed that γ and σ were negatively correlated with both SAS and SDS scores (r = − 0.350 to − 0.280, all P < 0.05). Eg was negatively correlated with SAS (r = − 0.307, P = 0.015), while Lp was positively correlated with SAS (r = 0.308, P = 0.015). Conclusion This study provides the first evidence that PDM involves disrupted small-world topology, reduced global integration, and delayed information transfer specifically within white matter functional networks. The significant correlations between these network alterations and affective symptoms establish white matter functional connectome topology as a clinically relevant neurobiological marker for emotional comorbidities in PDM. These findings extend the current gray matter‑centric model of PDM and identify graph-theoretical metrics of white matter networks as potential targets for neuromodulation.