Blunted modulation of hierarchical brain organization in opioid use disorder

Opioid use disorder (OUD) is associated with persistent catecholaminergic dysfunction, but its impact on large-scale cortical organization remains unclear. We used pharmacological resting-state fMRI and functional gradient mapping to test whether OUD alters catecholaminergic modulation of cortical hierarchy. Fifty-three individuals with OUD and 40 healthy controls underwent resting-state fMRI after placebo and methylphenidate. Under placebo, principal and secondary cortical gradients showed canonical organization with no group differences. In controls, methylphenidate compressed the dynamic range of the principal gradient while preserving its spatial topology, indicating state-dependent modulation of the unimodal-transmodal hierarchy. This response was attenuated in OUD and further reduced among participants receiving methadone or buprenorphine. Methylphenidate improved visual attention in controls but not OUD, and gradient modulation predicted attentional benefit only in controls. Gradient features also predicted years of opioid use. These findings identify blunted catecholaminergic modulation of cortical hierarchy as a clinically relevant systems-level feature of OUD.