Common and heritable components of white matter microstructure predict cognitive function at 1 and 2 y

Abstract

Previous studies indicate that the microstructure of individual white matter (WM) tracts is related to cognitive function. More recent studies indicate that the microstructure of individual tracts is highly correlated and that a property common across WM is related to overall cognitive function in adults. However, little is known about whether these common WM properties exist in early childhood development or how they are related to cognitive development. In this study, we used diffusion tensor imaging (DTI) to investigate common underlying factors in 12 fiber tracts, their relationship with cognitive function, and their heritability in a longitudinal sample of healthy children at birth (n = 535), 1 y (n = 322), and 2 y (n = 244) of age. Our data show that, in neonates, there is a highly significant correlation between major WM tracts that decreases from birth to 2 y of age. Over the same period, the factor structure increases in complexity, from one factor at birth to three factors at age 2 y, which explain 50% of variance. The identified common factors of DTI metrics in each age group are significantly correlated with general cognitive scores and predict cognitive ability in later childhood. These factors are moderately heritable. These findings illustrate the anatomical differentiation of WM fiber from birth to 2 y of age that correlate with cognitive development. Our results also suggest that the common factor approach is an informative way to study WM development and its relationship with cognition and is a useful approach for future imaging genetic studies.factor analysis | white matter | DTI | cognition | heritability I ndividual differences in white matter (WM) microstructure have been shown to be related to cognitive functions in adults (1, 2) and children (3-5). Diffusion tensor imaging (DTI) parameters in different WM regions or tracts are variably associated with processing speed, general intelligence, and higher-order cognitive abilities (1-5).To date, the majority of DTI studies of WM microstructure have analyzed each tract or WM region independently. However, more recent studies clearly demonstrate that fractional anisotropy (FA) and other DTI metrics of WM microstructure correlate highly across WM tracts and across a wide age range, including neonates, older children, and adults (6-8). Furthermore, studies indicate that a general factor derived by principal component analyses (PCA) describing common variance in FA across WM tracts is associated with information processing speed (9) as well as general intelligence (10), at least in older adults. In children ages 8 to 16 y, three principal components of FA have been identified; the one corresponding to the corpus callosum was significantly related to IQ (11).The identification of one or more common WM factors that influence variation in multiple WM tracts or regions is important for several reasons. Such factors could prove to be a good target for imaging genetic studies, as one would expect genetic variants influencing WM development and function ...

Imaging structural and functional brain development in early childhood

“…34,35 ; similarly, myelination increases more gradually after the second year 36,37 . The diffusion properties of white-matter tracts are highly correlated with each other at birth, but this correlation decreases with development as tracts mature and differentiate 38 .…”

“…Factors that describe common variation of FA, AD or RD across groups of white matter tracts are weakly related to cognitive development in an age-specific way; for example, a common factor of AD across 12 white matter tracts at birth is associated with cognitive development at age 1 year. 38 .…”

Pre‐natal brain development as a target for urban air pollution

“…Accordingly, experiments in mice exposed to diesel particles pre‐ and neo‐natally showed a reduction in the area of the corpus callosum (the largest white matter tract) and dilatation of the ventricles (indicating white matter damage). The area of the corpus callosum during weeks 28‐32 of gestation has been reported to predict post‐natal neurobehavioural impairment in children . Similarly, white matter tracts and microstructure at birth are suggested to predict general cognition in infancy .…”

“…There is consistent evidence that impaired placental function disrupts foetal neurodevelopment in animals and neurobehavioural development in children. Altered placental function is associated with the development of the corpus callosum in the foetal brain and with brain function in neonates and brain connectivity at one year of age . Experimentally reducing oxygen and nutrients during the last third of gestation in rabbits could result in poorer neurobehavioural performance and network diffusion early in life …”

Sex differences in associations between white matter microstructure and gonadal hormones in children and adolescents with prenatal alcohol exposure

“…Similarly, WM volumes and FA values increase steadily across adolescence, with boys exhibiting an overall steeper incline in volume compared to girls (Perrin et al, 2009), and these typical sex differences relating, in part, to gonadal hormone levels (Herting et al, 2012). Among typically developing individuals, positive associations are also observed between cognitive function and FA (Tamnes et al, 2010; Lee et al, 2017). Human DTI studies of adolescents with FASD have previously reported alterations in WM microstructure compared to controls, including regionally specific reduced FA and increased MD values (reviewed in (Wozniak and Muetzel, 2011)).…”