Abstract
BACKGROUND: HIV-associated neurocognitive disorders (HAND) are common complications in HIV-infected individuals, and working memory impairment is one of the core features. Although combination antiretroviral therapy (cART) has reduced the incidence of severe HAND, mild HAND remains prevalent. This study aims to explore the functional brain characteristics related to working memory in HIV-infected individuals with different cognitive states using resting-state and task-based functional magnetic resonance imaging (fMRI), and to identify candidate imaging markers for early diagnosis and inform future intervention targeting. METHODS: Fifty-nine HIV-infected individuals (30 with cognitive integrity [CI], 29 with asymptomatic neurocognitive impairment [ANI]) and 37 healthy controls (HC) were enrolled. Resting-state and task-based fMRI were acquired. Task-fMRI was performed using a spatial working memory task to analyze brain activation, functional connectivity (FC), and reconfiguration efficiency of FC from rest to task. FC networks were constructed as ROI-ROI Pearson correlation matrices (Fisher z-transformed) and significant group differences were identified using network-based statistics. Pearson and Spearman correlation analyses were used to explore the relationships between reconfiguration efficiency and clinical/cognitive variables. RESULTS: HC showed better task performance than both HIV groups, and ANI exhibited the poorest accuracy. Compared with CI, ANI had significantly lower neurocognitive domain T-scores in memory, attention/working memory, and abstraction/executive function. In task-fMRI analyses, ANI showed decreased activation in the bilateral orbital middle frontal gyri and the left middle temporal gyrus, alongside increased activation in the left cerebellum crus I relative to CI. Whole-brain analyses demonstrated widespread FC increases in both HIV groups at rest and during the task compared with HC. Reconfiguration efficiency differed across groups and showed stage-related associations with immune and cognitive measures. CONCLUSIONS: Cognitive impairment in virally suppressed HIV is accompanied by altered working-memory network engagement, with greater cortico-cerebellar involvement in ANI. While static whole-brain FC showed widespread increases but limited CI-ANI separation under stringent correction, altered rest-to-task FC reconfiguration efficiency was associated with immune indices and neurocognitive/behavioral performance, suggesting that this cross-state metric may serve as a candidate marker for HAND phenotyping and risk stratification.