Alterations in local activity and whole-brain functional connectivity in human immunodeficiency virus-associated neurocognitive disorders: a resting-state functional magnetic resonance imaging study.

Background: Approximately half of human immunodeficiency virus (HIV) patients experience HIV-associated neurocognitive disorders (HAND); however, the neurophysiological mechanisms underlying HAND remain unclear. This study aimed to evaluate changes in functional brain activity patterns during the early stages of HIV infection by comparing local and global indicators using resting-state functional magnetic resonance imaging (rs-fMRI). Methods: A total of 165 people living with HIV (PLWH) but without neurocognitive disorders (PWND), 173 patients with asymptomatic neurocognitive impairment (ANI), and 100 matched healthy controls (HCs) were included in the study. A cross-sectional study of the participants was conducted. The metrics of functional segregation and integration were computed, using graph theory to explore differences across methodologies. Brain functional changes in the PWND and ANI groups were assessed, and correlations between the rs-fMRI metrics, clinical data, and cognitive function were examined. Results: As cognitive function declined, changes reflected by regional homogeneity (ReHo) were primarily observed in the default mode network (DMN). In the DMN and visual network (VIS), amplitude of low-frequency fluctuation (ALFF) decreases were mainly observed in the parieto-occipital lobes, while increases were mainly observed in the limbic network (LIM). Reductions in fractional ALFF (fALFF) were mainly observed in the somatomotor network (SMN) and LIM, while increases were observed in the DMN and LIM. Unlike local indicators, global functional connectivity (FC) significantly decreased in both the PWND and ANI groups compared to the HC group. The ANI group showed partial increases in FC compared to the PWND group, with major changes observed in the DMN, VIS, and LIM. Notably, FC between the right insula and right supramarginal gyrus decreased significantly following HIV infection, while FC between the right caudate nucleus and the left middle frontal gyrus declined further in the ANI group. Graph theory further confirmed the significance of the DMN, and revealed changes in the eigenvector centrality mapping (ECM) values of the frontoparietal network (FPN) and dorsal attention network (DAN). Conclusions: HIV patients exhibit complex changes in both local and global brain activity, regardless of cognitive impairment. Widespread abnormalities primarily involve the DMN, VIS, and LIM. Changes in FC along the fronto-striatal pathway may play a crucial role in the decline of cognitive function in individuals with HAND. Our findings provide new insights that may assist in the early detection of brain damage in the early stages of HIV infection. The use of multiple methodologies may offer a more comprehensive and effective approach, enabling the early detection of brain damage in HIV patients.