Morphological Changes of Frontal Areas in Male Individuals With HIV: A Deformation-Based Morphometry Analysis

Abstract

Objective: Previous studies on HIV-infected (HIV+) individuals have revealed brain structural alterations underlying HIV-associated neurocognitive disorders. Most studies have adopted the widely used voxel-based morphological analysis of T1-weighted images or tracked-based analysis of diffusion tensor images. In this study, we investigated the HIV-related morphological changes using the deformation-based morphometry (DBM) analysis of T1-weighted images, which is another useful tool with high regional sensitivity.

Materials and methods: A total of 157 HIV+ (34.7 ± 8.5 years old) and 110 age-matched HIV-uninfected (HIV-) (33.7 ± 10.1 years old) men were recruited. All participants underwent neurocognitive assessments and brain scans, including high-resolution structural imaging and resting-state functional imaging. Structural alterations in HIV+ individuals were analyzed using DBM. Functional brain networks connected to the deformed regions were further investigated in a seed-based connectivity analysis. The correlations between imaging and cognitive or clinical measures were examined.

Results: The DBM analysis revealed decreased values (i.e., tissue atrophy) in the bilateral frontal regions in the HIV+ group, including bilateral superior frontal gyrus, left middle frontal gyrus, and their neighboring white matter tract, superior corona radiata. The functional connectivity between the right superior frontal gyrus and the right inferior temporal region was enhanced in the HIV+ group, the connectivity strength of which was significantly correlated with the global deficit scores (r = 0.214, P = 0.034), and deficits in learning (r = 0.246, P = 0.014) and recall (r = 0.218, P = 0.031). Increased DBM indexes (i.e., tissue enlargement) of the right cerebellum were also observed in the HIV+ group.

Conclusion: The current study revealed both gray and white matter volume changes in frontal regions and cerebellum in HIV+ individuals using DBM, complementing previous voxel-based morphological studies. Structural alterations were not limited to the local regions but were accompanied by disrupted functional connectivity between them and other relevant regions. Disruptions in neural networks were associated with cognitive performance, which may be related to HIV-associated neurocognitive disorders.

Keywords: HIV; MRI; cognitive assessment; deformation-based morphometry; functional connectivity.

Figure 1

Group differences in deformation-based morphometry (DBM) indexes between HIV infected (HIV+) and HIV uninfected (HIV-) group. (A) Bilateral superior and left middle frontal regions showed decreased DBM indexes (i.e., tissue atrophy) in the HIV+ group (voxel-level uncorrected P < 0.001, cluster level P < 0.05, FWE corrected). (B) Right cerebellum showed increased DBM indexes (i.e., tissue enlargement) in the HIV+ group (voxel-level uncorrected P < 0.001, cluster level P < 0.05, FWE corrected). The colors indicate the t-statistics.

Figure 2

Functional alterations of the deformed brain region in the HIV+ group. Functional connection between the deformed right superior frontal region (in green color) and the right inferior temporal gyrus (in red color) was significantly increased in the HIV+ group (voxel-level uncorrected P < 0.005, cluster level P < 0.05, FWE corrected).

Figure 3

Correlations between brain alterations and cognitive performances in the HIV+ group. (A) The functional connection (FC) strength between the deformed right superior frontal gyrus (rSFG) and the right inferior temporal gyrus (rITG) was positively correlated with global deficit scores (r = 0.214, P = 0.034). (B) The FC strength between the deformed rSFG and rITG was positively correlated with the deficit score of learning (r = 0.246, P = 0.014). (C) The FC strength between the deformed rSFG and rITG was positively correlated with the deficit score of recall (r = 0.218, P = 0.031).