Triple network brain dynamics in chronic HIV disease associated with cognitive deficits

People with HIV (PWH) continue to experience elevated rates of neurocognitive impairment despite sustained viral suppression on combination antiretroviral therapy. While static resting-state functional connectivity studies have identified alterations in large-scale neural networks in PWH, less is known about how these networks dynamically fluctuate over time. This study utilized a hidden semi-Markov model (HSMM) approach to examine dynamic functional connectivity among the default mode network (DMN), executive control network (ECN), and salience network (SN) during resting-state functional magnetic resonance imaging in 125 PWH and 67 people without HIV (PWoH). Six distinct brain states were estimated, and occupancy time, dwell time, and transition probabilities were compared between PWH and PWoH. Group comparisons revealed that PWH spent significantly less total time in State 1, a highly activated network state characterized by strong ECN involvement and broad integration across the three networks relative to PWoH. No group differences were observed in dwell time or transition probabilities across states. Exploratory analyses indicated that occupancy time in State 1 was negatively associated with global cognition, and specifically in the domains of executive functioning and motor performance among PWH. Findings suggest that PWH demonstrate altered large-scale network dynamics characterized by reduced engagement of an integrated state and that alterations may be relevant to neurocognitive functioning. These results provide novel evidence that dynamic connectivity metrics may represent a sensitive neural marker of cognitive vulnerability in chronic HIV infection and highlight the utility of HSMM approaches in neuroHIV research.