| Sumario: | Problematic Use of the Internet (PUI) has been associated with functional alterations in the default mode network (DMN), which contains critical hubs in the entire brain network. Previous studies have predicted that hub disruption leads to widespread network alterations; however, whether DMN functional connectivity mediates the relationship between PUI and global network topology remains unclear. This study examined whether DMN connectivity mediates PUI-related brain network topology. Resting-state functional magnetic resonance imaging data were collected from 190 healthy participants aged 20–69 years. DMN functional connectivity was assessed using region of interest (ROI)-to-ROI analyses with the Generalized Problematic Internet Use Scale-2 (GPIUS-2) as the primary predictor, controlling for age, sex, and mean framewise displacement. Graph-theoretical analyses quantified whole-brain network properties, including the clustering coefficient (Cp), shortest path length (Lp), global efficiency (Eg), and local efficiency (Eloc). Mediation analyses were performed to determine whether DMN functional connectivity mediates the relationship between GPIUS-2 and each metric. The functional connectivity values of all 17 DMN cluster pairs showed negative partial correlations with PUI severity (p -FDR < 0.05). Mean DMN connectivity strongly predicted global network topology (|ρ| = 0.36–0.41, all p -FDR < 1 × 10−6). Mediation analyses revealed that DMN functional connectivity substantially mediated the relationship between PUI severity and each metric (indirect effects: all p -FDR < 0.001; all direct effects p > 0.49). Reduced DMN connectivity was associated with decreased Cp and Eloc, increased Eg, and decreased Lp, indicating a deviation from optimal small-world organization. DMN hub connectivity serves as a critical neurobiological pathway through which the PUI influences the whole-brain network organization. • DMN functional connectivity decreases with greater problematic use of the Internet. • DMN hub connectivity predicts whole-brain network topology. • DMN connectivity mediates the relationship between PUI and network topology.
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