Subregion-specific insular dysconnectivity in internet gaming disorder: From macroscale network abnormalities to transcriptomic and cellular substrates

The insular cortex is a pivotal hub for interoception and salience processing, yet subregion-specific circuit abnormalities in Internet Gaming Disorder (IGD) and their molecular correlates remain unclear. Using resting-state fMRI data from 71 IGD patients and 80 healthy controls, we conducted seed-based functional connectivity (FC) analyses across six bilateral insular subregions and applied Allen Human Brain Atlas (AHBA)-based imaging transcriptomics to characterize associated gene-expression patterns. IGD patients showed increased FC between the bilateral dorsal anterior insula (dAI) and paracingulate gyrus, reduced FC between the left dAI and frontal pole, and decreased FC between the bilateral posterior insula and postcentral gyrus. These findings suggest altered salience-network coordination with default-mode and executive-control systems, together with disrupted somatosensory-interoceptive integration. Right dAI-paracingulate FC was positively associated with symptom severity, suggesting clinical relevance of this circuit. Transcriptomic decoding revealed non-random spatial correspondence between right dAI FC abnormalities and AHBA gene-expression profiles. Associated genes were enriched in two molecular contexts: neuronal signal transmission and metabolic homeostasis (Corr⁺), and neurodevelopment and structural plasticity (Corr^-). They further showed enrichment in neuronal and glial cell-type signatures, with the highest overlap ratios during three key developmental windows: early infancy, adolescence, and young adulthood. These findings reveal dissociable, subregion-specific insular circuit abnormalities in IGD, provide a multi-scale mechanistic account linking macroscale dysconnectivity to molecular and cellular substrates, consistent with and extending the triple network model in the context of behavioral addiction, and provide circuit-to-cellular candidate targets for intervention.