Functional Connectivity in Virally Suppressed Patients with HIV-Associated Neurocognitive Disorder: A Resting-State Analysis

Abstract

Background and purpose: HIV-associated neurocognitive disorder still occurs despite virally suppressive combination antiretroviral therapy. In the pre-combination antiretroviral era and in patients without HIV suppression, HIV-associated neurocognitive disorder was caused by synaptodendritic injury resulting in impairment of neural networks, characterized by decreased attention, psychomotor slowing, and working memory deficits. Whether similar pathogenesis is true for HIV-associated neurocognitive disorder in the context of viral suppression is not clear. Resting-state fMRI has been shown to be efficient in detecting impaired neural networks in various neurologic illnesses. This pilot study aimed to assess resting-state functional connectivity of the brain in patients with active HIV-associated neurocognitive disorder in the context of HIV viral suppression in both blood and CSF.

Materials and methods: Eighteen patients with active HIV-associated neurocognitive disorder (recent diagnosis with progressing symptoms) on combination antiretroviral therapy with viral suppression in both blood and CSF and 9 demographically matched control subjects underwent resting-state functional MR imaging. The connectivity in the 6 known neural networks was assessed. To localize significant ROIs within the HIV and control group, we performed a seed-based correlation for each known resting-state network.

Results: There were significant group differences between the control and HIV-associated neurocognitive disorder groups in the salience (0.26 versus 0.14, t = 2.6978, df = 25, P = .0123) and executive networks (0.52 versus 0.32, t = 2.2372, df = 25, P = .034). The covariate analysis with neuropsychological scores yielded statistically significant correlations in all 6 studied functional networks, with the most conspicuous correlation in salience networks.

Conclusions: Active HIV-associated neurocognitive disorder in virally suppressed patients is associated with significantly decreased connectivity in the salience and executive networks, thereby making it potentially useful as a biomarker.

Fig 1.

Multiplanar and axial depictions of differences between patients with HIV and control subjects in Brodmann area 9 (executive networks) and Brodmann area 13 (salience networks). Positive values represent higher correlation, and negative values depict lower correlation in patients with HIV relative to control subjects. (All the resultant maps are cluster-corrected). A, Brodmann area 9: patients-controls. B, Brodmann area 13: patients-controls.

Fig 2.

A, Multiplanar depictions of group effect in subjects with HIV in the executive networks with the seed region in Brodmann area 9. Note large consistently activated voxels in the entire group, with activation in the dorsolateral frontal cortex and posterior inferoparietal regions and in the striatum. B, Multiplanar depictions of group effect in subjects with HIV in the executive networks with seed regions in Brodmann area 13. Large consistently activated voxels in the group with activation in the anterior insula, anterior cingulate, and thalamus.

Fig 3.

Salience networks. Difference in correlation of the salience network with neurocognitive score (NCS): (Correlation Value in NCS > Median) − (Correlation Value in NCS < median). Orange denotes areas showing larger correlation values in patients with larger neurocognitive values, while blue shows the opposite. Each of the maps is corrected with the cluster-correction approach.

Fig 4.

Covariate analysis with neurocognitive scores demonstrating surviving voxels in each of the 6 networks.