The neonatal brain in Down Syndrome : white matter alterations and the relationship between brain volumes and childhood cognitive abilities

Ojinaga Alfageme, Olatz (2024) The neonatal brain in Down Syndrome : white matter alterations and the relationship between brain volumes and childhood cognitive abilities. PhD thesis, Birkbeck, University of London.

Abstract

Down Syndrome (DS) is the most common genetic cause of intellectual disability. This project is the first attempt to (1) determine associations between early structural brain imaging with subsequent neurodevelopmental outcomes in DS; and (2) explore white matter (WM) alterations in neonates with DS. Magnetic resonance imaging (MRI) was performed on neonates with DS and age- and sex-matched controls from 32 to 45 weeks postmenstrual age. WM microstructure alterations were explored with Tract-Based Spatial Statistics (TBSS) and Fixel-based Analysis (FBA) in a subsample of 10 neonates with DS and 39 typical developing (TD) controls. Planned and exploratory correlations were performed to analyse the relationship between neonatal brain volumes and cognitive outcome in infants with DS in an independent sample of 12 individuals with DS, who had neuropsychological assessments performed, between 6 months and 5 years of age. The diffusion data showed that all TBSS metrics (including fractional anisotropy and mean diffusivity) were reduced in the neonates with DS, relative to TD, in anterior WM tracts, corpus callosum and cerebral peduncles. FBA results showed statistically significant differences between DS and TD groups in WM organisation, but image registration was compromised by underlying volumetric difference between the groups and therefore the results were deemed unreliable. Regarding the structural data, there were no significant correlations between any of the brain tissue volumes and the outcome measures, but there were medium to large effect sizes (e.g., correlations between cortical grey matter and Mullen Receptive Language scores). However, there was a significant strong negative correlation between lateral ventricle volumes and Mullen Receptive Language Developmental quotient (DQ) scores (i.e., larger ventricle volumes relate to lower DQ 5 scores, or bigger delay). Overall, the research demonstrated that WM alterations in DS are present from early on in life, consistent with previous findings. However, it is too early to determine whether neonatal brain volumes might help predict measures of cognitive abilities in DS. Further research is needed to support these findings, to investigate whether other brain measures might be better predictors of outcomes (e.g., functional measures), and to understand the developmental mechanisms underlying the DS genotype-phenotype relationship across multiple levels of description.

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