Differences in resting state functional networks in HIV infected and uninfected children at age 7 years
Master Thesis
2015
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University of Cape Town
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Although early administration of highly active antiretroviral therapy (HAART) in infants provides the brain some protection against HIV damage, few studies have examined the long-term effects of HIV infection and HAART on neurodevelopment, and none have measured their impact on functional brain networks in young children. We use resting state functional magnetic resonance imaging (RS-fMRI) to explore differences in functional connectivity (FC) in HIV infected children stable on HAART and in HIV uninfected children. The 9 resting state networks (RSNs) identified using independent component analysis (ICA) included the visual lingual gyrus, visual occipital gyrus, salience, dorsal attention, auditory, motor, executive control, posterior default mode network (pDMN) and default mode network (DMN) . No significant group level differences were found in any RSNs using ICA. However, seed-based correlation analysis ( SCA ) revealed two regions where uninfected children had a higher FC compared to infected children (p < 0. 05 corrected for multiple comparison); specifically, between a seed in the left cingulate gyrus of the DMN and the left middle frontal gyrus, and between a seed in the right middle frontal gyrus of the executive control network and the right supramarginal gyrus. Consistent with our findings, previous RS-fMRI studies in HIV infected adults have reported reduced connectivity compared to uninfected adults in numerous DMN regions and executive control network. However, in contrast to the adult literature, in which a number of areas within the networks have been implicated, we only observed a focal effect in each of the two RSNs. Given that some of the RSNs are still undergoing major developments at age 7 years (i.e . time of scan for the children), the reduced FC may represent delayed network maturation within the infected cohort , with potential effects on cognitive functioning, information processing and memory recall abilities . Furthermore, positive associations were found between the clinical CD4/CD8 at time of enrollment and two regions within the dorsal attention and auditory networks. These results were independent of treatment arm and suggest that reduced FC in these networks at age 7 years are a result of poor immune function in early infancy (6-8 weeks of age), supporting the notion of in itiating ART immediately in HIV infected infants.
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Toich, J. 2015. Differences in resting state functional networks in HIV infected and uninfected children at age 7 years. University of Cape Town.