Intra-DMN and DMN-striatal RSFC was comparable between PWH and HIV-negative controls.

PCC–hippocampus connectivity was associated to better working memory in PWH.

Education and DMN RSFC both contribute to working memory in PWH.

Previous studies demonstrated a link between disrupted resting-state functional connectivity (RSFC) in the Default Mode Network (DMN) and cognitive impairment in people with HIV (PWH). Rs-fMRI studies to date have not investigated DMN connectivity with other brain regions that are typically implicated in HIV (i.e., striatum), and how this is related to cognition. We hypothesized that intra-DMN RSFC and DMN-striatal RSFC will be significantly different between PWH and HIV-negative controls (HC), and that these alterations are associated with cognition.

We used the posterior cingulate cortex (PCC) as the main node of the DMN and calculated its RSFC to other DMN regions for intra-DMN RSFC and to striatum. We performed an Analysis of Covariance to examine group differences in RSFC between PWH and HC. We conducted linear regression modelling to test the association of cognitive performance and RSFC in PWH.

There were no statistically significant differences between PWH and HC in PCC-ROI RSFC. However, in PWH, we found that higher education and greater RSFC of PCC- right hippocampus were associated with better performance in working memory (p = 0.0007 and 0.03).

Our results suggest that altered intra-DMN RSFC may contribute to cognitive dysfunction observed in PWH.

NeuroHIV

Resting-state fMRI

DMN connectivity

Neurocognitive impairment

© 2025 The Author(s). Published by Elsevier B.V.