Neural Correlates of Mentalizing Altered in Childhood Trauma and Cocaine Use Disorder

Background Childhood trauma is highly prevalent among individuals with cocaine use disorder (iCUD), and both entail social cognition deficits, including impaired mentalizing (social inference) capacity. Here we sought to examine the neuro-circuits underlying these associations using task-based neuroimaging. We hypothesized that childhood trauma and CUD would show altered brain activation of the mentalizing network, related to deficits in real-world social capacities. Methods Participants (45 iCUD and 34 healthy controls (HC), with high/low trauma) performed the validated Why/How fMRI task, probing Why versus How photographed naturalistic behaviors are performed. Whole-brain analyses used a Why > How contrast at the first level, followed by group comparisons at the second level, with cluster-level family-wise error correction (p _FWE < .05). Social functioning and clinical measures were obtained using validated self-report instruments. Results Mentalizing task behavior outcomes were worse in iCUD than HC (F _(1,75)  = 4.45, p < .05), with no effect of trauma severity on accuracy. A significant interaction was observed in the precuneus, with greater BOLD responses in iCUD-low than HC-low, and lower responses in iCUD-high than HC-high. High-trauma individuals showed increased frontal pole activation, correlating positively with mentalizing accuracy (r ₍₃₉₎  > = .24, p < .05) and social anxiety (r ₍₇₉₎  = .29, p = .01), and negatively with resilience (r ₍₃₉₎ <= − .37, p < .001). Conclusion Greater frontal activation in high-trauma individuals may support task accuracy but is linked to poorer real-world social functioning. Additionally, the link between CUD diagnosis and precuneus activity depends on trauma severity, offering neural insights into how trauma history may influence CUD and social function.