Altered activity within and between large-scale brain networks has been implicated across various neuropsychiatric conditions. However, patterns of network dysregulation associated with human immunodeficiency virus (HIV), and further impacted by cannabis (CB) use, remain to be delineated. We examined the impact of HIV and CB on resting-state functional connectivity (rsFC) between brain networks and associations with error awareness and error-related network responsivity. Participants (N = 106), stratified into four groups (HIV+/CB+, HIV+/CB−, HIV−/CB+, HIV−/CB−), underwent fMRI scanning while completing a resting-state scan and a modified Go/NoGo paradigm assessing brain responsivity to errors and explicit error awareness. We examined separate and interactive effects of HIV and CB on resource allocation indexes (RAIs), a measure quantifying rsFC strength between the default mode network (DMN), central executive network (CEN), and salience network (SN). We observed reduced RAIs among HIV+ (vs. HIV−) participants, which was driven by increased SN-DMN rsFC. No group differences were detected for SN-CEN rsFC. Increased SN-DMN rsFC correlated with diminished error awareness, but not with error-related network responsivity. These outcomes highlight altered network interactions among participants with HIV and suggest such rsFC dysregulation may persist during task performance, reflecting an inability to disengage irrelevant mental operations, ultimately hindering error processing.

One systems-level framework proposes that dysregulated brain network interactions may underlie neurocognitive aspects of addiction, neurodegeneration, and other neuropsychiatric conditions. Three specific networks have been highlighted: the default mode network (DMN), the central executive network (CEN), and the salience network (SN). To examine alterations linked with human immunodeficiency virus (HIV) and cannabis (CB) use across these three canonical brain networks, we utilized a composite network association index, previously used to assess drug-related effects on brain networks. This study provides a novel perspective on dysregulated DMN and SN rsFC among participants living with HIV and delineates potential implications for error-monitoring behavior.

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Competing Interests: The authors have declared that no competing interests exist.

Handling Editor: Andrew Zalesky

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