Abstract

Despite extensive research on the neurobiology of addiction, little is known about how repeated drug use and withdrawal are related to social functioning impairments in humans, a highly social species. This obscures the broader societal impact of drug addiction and limits treatment efficacy. This study examined social cognitive impairment and its multi-brain neural underpinnings during socially interactive problem-solving in heroin use disorder (HUD), and further explored their co-occurrence with protracted withdrawal symptoms. Thirty-eight HUD pairs and thirty healthy control (HC) pairs completed a turn-based group problem-solving task. Functional near-infrared spectroscopy was employed during the whole task to simultaneously measure neural activity within individual brains and between interacting partners. Compared to the HC pairs, the HUD pairs demonstrated poorer individual and group problem-solving performance, as well as reduced perspective-taking behavior. Altered intra-brain neural signatures were observed, characterized by reduced activation in the right inferior frontal gyrus (rIFG) and left orbitofrontal cortex (lOFC), along with decreased functional connectivity strength in the right dorsolateral prefrontal cortex. Additionally, the rIFG-centred interpersonal neural synchronization (INS) was disrupted. Aberrant intra-brain signatures in lOFC and the consequent difficulties in establishing INS contribute to poorer group performance. These behavioral and neural deficits exhibited comorbidity with emotional and sleep-related withdrawal symptoms. This study advances our understanding of social cognitive deficits in drug addiction and provides a novel insights into their interpersonal basis. The findings have a translational impact on developing targeted treatment to restore social functioning for drug addiction and other psychiatric disorders. [Abstract copyright: Copyright © 2026. Published by Elsevier Inc.]