DTI-based tractographic analysis of white matter alterations in HIV infected children

Madzime, Joanah

DTI-based tractographic analysis of white matter alterations in HIV infected children

Master Thesis

2019

Abstract

Despite early combination antiretroviral therapy (cART) administration, children born with human immunodeficiency virus (HIV) continue to demonstrate neurodevelopmental abnormalities. Often, there is a link between structural and functional abnormalities. Previously, we found HIV-associated changes in white matter and functional networks in a cohort of 7-year-old HIV infected (HIV+) children who intiatied early cART compared to uninfected controls. To explore possible relationships between these alterations, we used tractography to identify HIV-related abnormalities within structural connections located in functional resting state networks. Within HIV+ children (n=61), we identified white matter (WM) tracts with lower mean fractional anisotropy (FA) and/or higher mean diffusivity (MD) located in several functional networks, including the somatosensory, auditory, salience, default mode network (DMN), motor and basal ganglia networks compared to uninfected controls (n=46). Among the uninfected controls, children born to HIV+ mothers (exposed uninfected, HEU) (n=19) showed WM alterations (higher FA) compared to HIV unexposed uninfected children (HUU) (n=27) within tracts in the posterior DMN, visual (occipital lobe and lingual gyrus), salience and motor networks. The observed WM alterations in HIV+ children point to demyelination/dysmyelination within six networks. Four of these networks – the basal ganglia, default mode, salience and somatosensory – were all found to have altered functional connectivity in a previous study; therefore, these results point to damage or developmental delay in white matter may be related to or responsible for the HIV-associated functional abnormalities. The observed WM alterations in the HEU children suggest that even exposure to HIV and/or antiretroviral therapy (ART) also has long-term effects on axonal integrity in the developing brain.

Keywords

Neurosciences

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