Abstract
Purpose:Neuroimaging elucidations have shown structural and functional brain alterations in HIV-infected (HIV+) individuals when compared to HIV-negative (HIV–) controls. However, HIV− groups used in previous studies were not specifically considered for sexual orientation, which also affects the brain structures and functions. The current study aimed to characterize the brain alterations associated with HIV infection while controlling for sexual orientation.Methods:Forty-three HIV+ and 40 HIV– homosexual men (HoM) were recruited and underwent resting-state MRI scanning. Group differences in gray matter volume (GMV) were assessed using a voxel-based morphometry analysis. Brain regions with the altered GMV in the HIV+ HoM group were then taken as regions of interest in a seed-based analysis to identify altered functional connectivity. Furthermore, the amplitude of low-frequency fluctuation (ALFF) and regional homogeneity values were compared between the two groups to evaluate the HIV-associated functional abnormalities in local brain regions.Results:HIV+ HoM showed significantly increased GMV in the bilateral parahippocampal gyrus and amygdala, and decreased GMV in the right inferior cerebellum, compared with the HIV– HoM. The brain regions with increased GMV were hyper-connected with the left superior cerebellum, right lingual gyrus, and left precuneus in the HIV+ HoM. Moreover, the ALFF values of the right fusiform gyrus, and left parahippocampal gyrus were increased in the HIV+ HoM. The regional homogeneity values of the right anterior cingulate and paracingulate gyri, and left superior cerebellum were decreased in the HIV+ HoM.Conclusion:When the study population was restricted to HoM, HIV+ individuals exhibited structural alterations in the limbic system and cerebellum, and functional abnormalities in the limbic, cerebellum, and visual network. These findings complement the existing knowledge on the HIV-associated neurocognitive impairment from the previous neuroimaging studies by controlling for the potential confounding factor, sexual orientation. Future studies on brain alternations with the exclusion of related factors like sexual orientation are needed to understand the impact of HIV infection on neurocognitive function more accurately.
Highlights
Even with the success of combination antiretroviral therapy, various neurological complications caused by the infiltration of the human immunodeficiency virus (HIV) in the central nervous system (CNS) [1], especially HIV-associated neurocognitive disorder [2], remain a heavy disease burden
The cluster with increased GMV in the parahippocampal gyrus and amygdala found in the voxel-based morphometry (VBM) analysis was used as the seed in the seed-based functional connectivity analysis of Resting-state functional MRI (rs-fMRI) data
As we studied a relatively young cohort compared to previous studies, we speculated that the increased GMV of the parahippocampal gyrus may have been related to the early compensation of brain functions due to the brain parenchymal lesions induced by HIV infection
Summary
Even with the success of combination antiretroviral therapy (cART), various neurological complications caused by the infiltration of the human immunodeficiency virus (HIV) in the central nervous system (CNS) [1], especially HIV-associated neurocognitive disorder [2], remain a heavy disease burden. Resting-state functional MRI (rs-fMRI) studies revealed that HIV+ individuals had certain attenuation in brain intra- and internetwork connections, especially in the default mode, salience, and executive control networks, which might underlie the reported cognitive impairments [11, 12]. These studies were inconsistent in regional distribution and effect sizes of brain abnormalities, and their conclusions cannot be generalized to the whole HIV+ cohort. The inconsistencies in neuroimaging studies of HIV infection might be caused by multiple confounding factors, including age, sex, and substance use. Many other factors have not been taken into account
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