Altered intrinsic neural timescales in cocaine use disorder

Cocaine use disorder (CUD) is a major public health challenge, but its neurodynamic and molecular mechanisms remain unclear despite evidence of structural and functional abnormalities. This study mapped whole-brain intrinsic neural timescales (INTs), reflecting temporal integration of neural activity, using resting-state functional magnetic resonance imaging in 44 CUD patients and 44 healthy controls. In the primary analysis with global signal regression (GSR), CUD showed increased network-level INTs in the visual, somatomotor, dorsal attention, frontoparietal control, and default mode networks compared with HC. In the sensitivity analysis without GSR, the visual and somatomotor network differences remained significant. Within the CUD group, regional and network-level INT variation was associated with individual differences in flanker-task performance, despite the absence of significant between-group differences in behavioral performance. Notably, the spatial distribution of INT differences was associated with normative maps of gamma-aminobutyric acid type A receptors and the noradrenaline transporter. Atlas-based models showed modest discrimination and limited validation, while outcome-informed cluster-based models yielded higher but exploratory estimates. Importantly, classification performance in a mixed-source evaluation sample was close to chance, indicating limited generalizability. Together, these findings reveal widespread alterations in intrinsic neural timescales in CUD and highlight the relevance of spatiotemporal brain organization to addiction.