Browsing by Author "Van Der Kouwe, Andre J. W."

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    Functional connectivity alterations between networks and associations with infant immune health within networks in HIV infected children on early treatment : a study at 7 years
    (Frontiers Media, 2018) Toich, Jadrana T. F.; Taylor, Paul A.; Holmes, Martha J.; Gohel, Suril; Cotton, Mark F.; Dobbels, Els; Laughton, Barbara; Little, Francesca; Van Der Kouwe, Andre J. W.; Biswal, Bharat; Meintjes, Ernesta M.
    ENGLISH ABSTRACT: Although HIV has been shown to impact brain connectivity in adults and youth, it is not yet known to what extent long-term early antiretroviral therapy (ART) may alter these effects, especially during rapid brain development in early childhood. Using both independent component analysis (ICA) and seed-based correlation analysis (SCA), we examine the effects of HIV infection in conjunction with early ART on resting state functional connectivity (FC) in 7 year old children. HIV infected (HIV+) children were from the Children with HIV Early Antiretroviral Therapy (CHER) trial and all initiated ART before 18 months; uninfected children were recruited from an interlinking vaccine trial. To better understand the effects of current and early immune health on the developing brain, we also investigated among HIV+ children the association of FC at 7 years with CD4 count and CD4%, both in infancy (6–8 weeks) and at scan. Although we found no differences within any ICA-generated resting state networks (RSNs) between HIV+ and uninfected children (27 HIV+, 18 uninfected), whole brain connectivity to seeds located at RSN connectivity peaks revealed several loci of FC differences, predominantly from seeds in midline regions (posterior cingulate cortex, paracentral lobule, cuneus, and anterior cingulate). Reduced long-range connectivity and increased short-range connectivity suggest developmental delay. Within the HIV+ children, clinical measures at age 7 years were not associated with FC values in any of the RSNs; however, poor immune health during infancy was associated with localized FC increases in the somatosensory, salience and basal ganglia networks. Together these findings suggest that HIV may affect brain development from its earliest stages and persist into childhood, despite early ART.
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    Perinatal HIV infection or exposure is associated with low N-acetylaspartate and glutamate in basal ganglia at age 9 but not 7 years
    (Frontiers Media, 2018) Robertson, Frances C.; Holmes, Martha J.; Cotton, Mark F.; Dobbels, Els; Little, Francesca; Laughton, Barbara; Van Der Kouwe, Andre J. W.; Meintjes, Ernesta M.
    ENGLISH ABSTRACT: Abnormalities of the basal ganglia are frequently seen in HIV-infected (HIV+) children despite antiretroviral treatment (ART) initiation during childhood. Assessment of metabolites associated with neuronal integrity or with glial proliferation can present a sensitive description of metabolic events underlying basal ganglia structural changes. We used magnetic resonance spectroscopy to examine differences in creatine, choline, N-acetylaspartate (NAA), glutamate, and myo-inositol between HIV+ children and HIV-unexposed controls, as well as between HIV-exposed uninfected (HEU) children and HIV-unexposed controls at age 7 and at age 9. No differences in metabolites relative to the HIV-unexposed control group were found at age 7. However, at 9 years, both HIV+ and HEU had lower NAA and glutamate than unexposed control children. HEU children also had lower creatine and choline than control children. At age 7, lower CD4/CD8 ratio at enrollment was associated with lower choline levels. At age 9 lower CD4/CD8 at enrollment was associated with lower myo-inositol. Low NAA and glutamate at age 9, but not 7, suggest that basal ganglia neurons may be particularly affected by perinatal HIV/ART and that neuronal damage may be ongoing despite early ART and viral suppression. Reduced basal ganglia metabolite levels in HEU children suggest an effect of HIV exposure on childhood brain development that merits further investigation using neuroimaging and neurocognitive testing.