HIV infection is linked with reduced error-related default mode network suppression and poorer medication management abilities

Brain activity linked with error processing has rarely been examined among persons living with HIV (PLWH) despite importance for monitoring and modifying behaviors that could lead to adverse health outcomes (e.g., medication non-adherence, drug use, risky sexual practices). Given that cannabis (CB) use is prevalent among PLWH and impacts error processing, we assessed the influence of HIV serostatus and chronic CB use on error-related brain activity while also considering associated implications for everyday functioning and clinically-relevant disease management behaviors. A sample of 109 participants, stratified into four groups by HIV and CB (HIV+/CB+, n  = 32; HIV+/CB−, n  = 27; HIV−/CB+, n  = 28; HIV−/CB−, n  = 22), underwent fMRI scanning while completing a modified Go/NoGo paradigm called the Error Awareness Task (EAT). Participants also completed a battery of well-validated instruments including a subjective report of everyday cognitive failures and an objective measure of medication management abilities. Across all participants, we observed expected error-related anterior insula (aI) activation which correlated with better task performance (i.e., less errors) and, among HIV− participants, fewer self-reported cognitive failures. Regarding awareness, greater insula activation as well as greater posterior cingulate cortex (PCC) deactivation were notably linked with aware (vs. unaware) errors. Regarding group effects, unlike HIV− participants, PLWH displayed a lack of error-related deactivation in two default mode network (DMN) regions (i.e., PCC, medial prefrontal cortex [mPFC]). No CB main or interaction effects were detected. Across all participants, reduced error-related PCC deactivation correlated with reduced medication management abilities and PCC deactivation mediated the effect of HIV on such abilities. More lifetime CB use was linked with reduced error-related mPFC deactivation among HIV− participants and poorer medication management across CB users. These results demonstrate that insufficient error-related DMN suppression linked with HIV infection, as well as chronic CB use among HIV− participants, has real-world consequences for medication management behaviors. We speculate that insufficient DMN suppression may reflect an inability to disengage task irrelevant mental operations, ultimately hindering error monitoring and behavior modification.