Principal Investigator: Prof Ernesta Meintjes

Neural Correlates of Fetal Alcohol Spectrum Disorder (FASD)

This work presents a long-standing collaboration with Profs Sandra and Joseph Jacobson from Wayne State University and Chris Molteno from UCT who have been conducting longitudinal research on FASD in Cape Town for more than a decade in a unique cohort of children whose mothers were recruited prospectively during pregnancy.

Our studies of number processing and working memory have shown that, while control children rely primarily on regions specialized for these functions, children with fetal alcohol syndrome (FAS) or partial FAS (PFAS) recruit a broader range of brain regions to perform the same tasks (Meintjes et al., 2010; Diwadkar et al., 2013). Increased alcohol exposure has also been found to be associated with greater regional contractions in the caudate and hippocampus (Joseph et al., 2012), and reduced cortical folding complexity, even among children with normal brain size (De Guio et al., 2013). Further, we have recently shown in a tensor-based morphometry (TBM) study that adjusting for brain size is not ideal in morphometric analyses and can hide important regional volumetric differences in disorders such as FASD, where reduced overall brain size is among the diagnostic criteria (Meintjes et al., 2014).

We have examined the different components of the eye-blink conditioning cerebellar circuit using a range of neuroimaging methods, and found differences that may mediate prenatal alcohol effects on a range of neurobehavioral endpoints, including eye-blink conditioning.

A new cohort of heavy drinking and methamphetamine abusing pregnant women is currently being recruited in order to (i) examine effects of prenatal alcohol (PAE) and methamphetamine (PME) exposure on the brain prior to the confounding influences of nutrition and environmental factors, and (ii) examine the protective role of maternal choline supplementation during pregnancy on the unborn fetus in heavy drinking mothers. Structural scans have revealed that increased maternal methamphetamine use (days/month) was strongly associated with bilateral reductions in caudate volumes. It was also shown using probabilistic tractography that parallel diffusivity was significantly related to the mother's frequency of heavy drinking.

Longitudinal Studies of the Effects of HIV and Different Antiretroviral Treatment (ART) Regimes on Brain Development in Children

To date, very little is known about the optimal age to initiate antiretroviral therapy (ART) in HIV-infected infants, whether treatment should be interrupted or continuous, the optimal time for interruption, and what the potential long-term effects of these different treatment options may be on brain development. Neuroimaging outcomes include metabolite levels in three regions (basal ganglia, midfrontal gray matter, and peritrigonal white matter), structural differences (volumetrics, morphology and cortical thickness), white matter integrity, and resting state connectivity. To date, all children have been scanned at age 5 years, and 95% of children have received neuroimaging at age 7 years.

Preliminary results have revealed striking differences between magnetic resonance spectroscopy (MRS) findings in HIV-exposed uninfected (HEU) and HIV-unexposed uninfected (HUU) children, providing convincing evidence of exposure-related differences in neurometabolism in young uninfected children. Due to successful programs for prevention of mother to child transmission (MTCT), large numbers of HEU babies are being born. In the Western Cape, rates of mother to child transmission (MTCT) have decreased to 2%. In view of recent changes to policy for treating HIV+ women during pregnancy, which have increased the exposure of the fetus and child to ART, it is vital to assess the effects of this increased exposure on the developing brain. Results thus far suggest that early brain damage may not be fully reversible, irrespective of timing of ART, providing further evidence for the potential benefit of earlier initiation of ART in infected infants.