Mapping abnormal subcortical neurodevelopment in a cohort of Thai children with HIV

Abstract

Alterations in subcortical brain structures have been reported in adults with HIV and, to a lesser extent, pediatric cohorts. The extent of longitudinal structural abnormalities in children with perinatal HIV infection (PaHIV) remains unclear. We modeled subcortical morphometry from whole brain structural magnetic resonance imaging (1.5 T) scans of 43 Thai children with PaHIV (baseline age = 11.09±2.36 years) and 50 HIV− children (11.26±2.80 years) using volumetric and surface-based shape analyses. The PaHIV sample were randomized to initiate combination antiretroviral treatment (cART) when CD4 counts were 15–24% (immediate: n = 22) or when CD4 < 15% (deferred: n = 21). Follow-up scans were acquired approximately 52 weeks after baseline. Volumetric and shape descriptors capturing local thickness and surface area dilation were defined for the bilateral accumbens, amygdala, putamen, pallidum, thalamus, caudate, and hippocampus. Regression models adjusting for clinical and demographic variables examined between and within group differences in morphometry associated with HIV. We assessed whether baseline CD4 count and cART status or timing associated with brain maturation within the PaHIV group. All models were adjusted for multiple comparisons using the false discovery rate. A pallidal subregion was significantly thinner in children with PaHIV. Regional thickness, surface area, and volume of the pallidum was associated with CD4 count in children with PaHIV. Longitudinal morphometry was not associated with HIV or cART status or timing, however, the trajectory of the left pallidum volume was positively associated with baseline CD4 count. Our findings corroborate reports in adult cohorts demonstrating a high predilection for HIV-mediated abnormalities in the basal ganglia, but suggest the effect of stable PaHIV infection on morphological aspects of brain development may be subtle.

Neural encoding and functional interactions underlying pantomimed movements

“…Irrespective of the possible interpretations, our data highlighted the pivotal role of temporo-frontal bidirectional interactions for the performance of meaningful pantomimed movements. Further studies are needed to better understand the interactions within the tool network underlying this type of movements, unveiling also the possible role of homologous regions within the right hemisphere, as hinted by a recent investigation (see Watson et al 2019 ).…”

Normal structural brain development in adolescents treated for perinatally acquired HIV: a longitudinal imaging study

“…Up to now, only two other longitudinal studies have investigated brain development in PHIV-positive children transitioning into adulthood [ 15 , 16 ]. Both studies were limited by a follow-up time of only one year, as well as by the fact that they investigated brain development from a limited perspective, primarily focusing on either subcortical structures using 1.5T MRI [ 15 ] or solely performing region of interest analysis, studying grey matter and cortical thickness development [ 16 ]. Nonetheless, in line with the results of our findings, the effect of HIV on brain morphology was suggested to be subtle.…”

Effects of perinatal HIV-infection on the cortical thickness and subcortical gray matter volumes in young adulthood

“…The association between a low CD4 T-cell count and reduced subcortical regional volumes may indicate that prolonged immunosuppression could play and additional role in CNS damage, explaining the better brain development of well controlled patients. In line with this, Wade et al [ 18 ] described increased rates of volume growth in determined subcortical areas in children with higher CD4 counts and similarly, Cohen et al [ 3 ] published that longer time with low CD4 T-cell counts was associated with a lower total GM volume.…”

“…Commonly, within the PHIV population the alterations found in brain structure have been usually related to a poor immunovirological status and to the lack of an effective antiretroviral treatment. [ 9 , 14 , 17 , 18 ]…”

“…Secondly, we tested the hypothesis that a worse immunovirological status will be associated with smaller volumes of the BG since it has been reported to be particularly impacted. [ 11 , 12 , 14 , 16 – 18 ]…”