Browsing by Author "Robertson, Frances C."

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    Longitudinal increases of brain metabolite levels in 5-10 year old children
    (Public Library of Science, 2017) Holmes, Martha J.; Robertson, Frances C.; Little, Francesca; Randall, Steven R.; Cotton, Mark F.; Van der Kouwe, Andre J. W.; Laughton, Barbara; Meintjes, Ernesta M.
    Longitudinal magnetic resonance imaging (MRI) and diffusion tensor imaging (DTI) studies reveal significant changes in brain structure and structural networks that occur together with cognitive and behavioral maturation in childhood. However, the underlying cellular changes accompanying brain maturation are less understood. Examining regional agerelated changes in metabolite levels provides insight into the physiology of neurodevelopment. Magnetic resonance spectroscopy (MRS) measures localize brain metabolism. The majority of neuroimaging studies of healthy development are from the developed world. In a longitudinal MRS study of 64 South African children aged 5 to 10 years old (29 female; 29 HIV exposed, uninfected), we examined the age-related trajectories of creatine (Cr +PCr), N-acetyl-aspartate (NAA), the combined NAA+N-acetyl-aspartyl-glutamate (NAAG), choline (GPC+PCh), glutamate (Glu) and the combined Glu+glutamine (Glu +Gln) in voxels within gray and white matter, as well as subcortically in the basal ganglia (BG). In frontal gray matter, we found age-related increases in Cr+PCr, NAA, NAA+NAAG and Glu+Gln levels pointing to synaptic activity likely related to learning. In the BG we observed increased levels of Glu, Glu+Gln and NAA+NAAG with age that point to subcortical synaptic reorganization. In white matter, we found increased levels of Cr+PCr, NAA, NAA+NAAG, Glu and Glu+Gln with age, implicating these metabolites in ongoing myelination. We observed no sex-age or HIV exposure-age interactions, indicating that physiological changes are independent of sex during this time period. The metabolite trajectories presented, therefore, provide a critical benchmark of normal cellular growth for a low socioeconomic pediatric population in the developing world against which pathology and abnormal development may be compared.
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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.