Structural Covariance of Gray Matter Volume in HIV Vertically Infected Adolescents

Abstract

Human immunodeficiency virus (HIV) infection significantly affect neurodevelopmental and behavioral outcomes. We investigated whether alterations of gray matter organization and structural covariance networks with vertical HIV infection adolescents exist, by using the GAT toolbox. MRI data were analysed from 25 HIV vertically infected adolescents and 33 HIV-exposed-uninfected control participants. The gray matter volume (GMV) was calculated, and structural brain networks were reconstructed from gray matter co-variance. Gray matter losses were pronounced in anterior cingulate cortex (ACC), right pallidum, right occipital lobe, inferior parietal lobe, and bilateral cerebellum crus. The global brain network measures were not significantly different between the groups; however, the nodal alterations were most pronounced in frontal, temporal, basal ganglia, cerebellum, and temporal lobes. Brain hubs in the HIV-infected subjects increased in number and tended to shift to sensorimotor and temporal areas. In the HIV-infected subjects, decreased GMVs in ACC and bilateral cerebellum were related to lower Mini-Mental State Examination scores; the CD4 counts were positively related to the GMVs in ACC and sensorimotor areas. These findings suggest that focally reduced gray matter, disrupted nodal profiles of structural wirings, and a shift in hub distribution may represent neuroanatomical biomarkers of HIV infection on the developing brain.

Figure 1

Differences in GMV. The picture on the left side corresponds to the left hemisphere. (A) GMV changes occur in the region with MNI co-ordinates in the z direction between z = −27 to z = 25.5. (B) Sagittal bitmaps indicate the relative reduced GMV regions.

Figure 2

Correlation matrix and binary graph. HIV+ and HIV− groups’ correlation matrix; the strength of the connections is indicated by the color-bar. HIV+ and HIV− groups’ binary graph; the presence of a connection is indicated by the white-gray color. These matrices are graphs of the D_min (13%) threshold, where all nodes are fully connected in the two groups’ structural networks.

Figure 3

Changes in global network measurements and intergroup differences as a function of network density. HIV+ and HIV− networks’ normalized clustering (left top), normalized path length (left middle), and small-world index (left bottom). The intergroup differences and 95% confidence intervals in the normalized clustering (right top), normalized path length (right middle) and small-world index (right bottom). The difference is indicated by the red marker between the HIV− and HIV+ networks.

Figure 4

(A) Regions about the p_auc_MDeg compared the HIV+ group to the HIV− group. (B) Regions about the p_auc_MNodeBetw compared the HIV+ group to the HIV− group. (C) Regions about the p_auc_MClust compared the HIV+ group to the HIV− group. All regions survived following FDR correction (p < 0.05).

Figure 5

Network hubs. Green highlights hubs specific to HIV+ network; blue indicates hubs specific to HIV− network; red represents the common hubs in both groups.

Figure 6

Random failure and targeted attack analysis. The changes in the size of the remaining maximum component of the network as a function of the fraction of nodes that are randomly removed are depicted (left). By removing the nodes in a rank order of decreasing nodal betweenness centrality, the same procedure is used to analyze the network response to targeted attack (right).

Figure 7

Correlation results (after Bonferroni-corrected for multiple comparisons). ACC: anterior cingulate cortex.