Abnormalities in resting-state functional connectivity in early human immunodeficiency virus infection

Abstract

Limited information is available concerning changes that occur in the brain early in human immunodeficiency virus (HIV) infection. This investigation evaluated resting-state functional connectivity, which is based on correlations of spontaneous blood oxygen level-dependent functional magnetic resonance imaging (fMRI) oscillations between brain regions, in 15 subjects within the first year of HIV infection and in 15 age-matched controls. Resting-state fMRI data for each session were concatenated in time across subjects to create a single 4D dataset and decomposed into 36 independent component analysis (ICA) using Multivariate Exploratory Linear Optimized Decomposition into Independent Components. ICA components were back-reconstructed for each subject's 4D data to estimate subject-specific spatial maps using the dual-regression technique. Comparison of spatial maps between HIV and controls revealed significant differences in the lateral occipital cortex (LOC) network. Reduced coactivation in left inferior parietal cortex within the LOC network was identified in the HIV subjects. Connectivity strength within this region correlated with performance on tasks involving visual-motor coordination (Grooved Pegboard and Rey Figure Copy) in the HIV group. The findings indicate prominent changes in resting-state functional connectivity of visual networks early in HIV infection. This network may sustain injury in association with the intense viremia and brain viral invasion before immune defenses can contain viral replication. Resting-state functional connectivity may have utility as a noninvasive neuroimaging biomarker for central nervous system impairment in early HIV infection.

FIG. 1.

Eight group independent component analysis component maps from 30 subjects: (A) primary visual, (B) lateral occipital cortex (LOC), (C) auditory, (D) sensory-motor, (E) the “default mode” network (DMN), (F) executive control, and (G, H) two right- and left-lateralized fronto-parietal networks. All images have been coregistered into the space of MNI template. The coordinates refer to millimeter distances from the anterior commissure and images are shown in radiological convention. Z value of ∼3 is used for thresholding the component maps.

FIG. 2.

Group main effect for (A) Control and (B) HIV subjects. (C) Comparison between Control and HIV (Control > HIV). Color bar indicates p values after multiple comparison correction using threshold-free cluster enhancement and thresholded between 0 and 0.05. All images have been coregistered into the space of MNI template. The coordinates refer to millimeter distances from the anterior commissure and images are shown in radiological convention. HIV, human immunodeficiency virus.

FIG. 3.

The box plot of average beta-values within regions exhibiting statistical group differences (Control > HIV, regions shown in Fig. 2C) for HIV and Control. Color images available online at www.liebertonline.com/brain

FIG. 4.

Top row: in the HIV group, (A) a significant negative correlation between Grooved Pegboard (GP) dominant scores and functional connectivity strength and (B) a significant positive correlation between Rey Figure Copy performance and functional connectivity strength. Bottom row: in Control subjects these relationships were not significant (C, D). All p values were false discovery rate corrected. Color images available online at www.liebertonline.com/brain