Early predictors of white matter microstructure in the adult brain

The foundations for the brain’s structural organisation are laid already during prenatal life. External and internal signals interact to guide brain development in axonal growth, myelination and pruning, but also seem to programme long-term epigenetic effects which may only appear later in life. Altered neurodevelopment has been linked with psychiatric conditions and other states of compromised health. This work focuses on white matter, a brain structure that has received relatively little attention in research on typical and altered neurodevelopment. White matter constitutes about half of the human brain’s volume, and its axonal pathways provide conduction and modulation of signals across brain regions. The variation in the structural features of white matter in association with early-life factors, as well as interpretation of brain imaging findings is, however, far from resolved.

This work studies associations between prenatal factors and brain white matter structural features from childhood to early adulthood. White matter structural correlates of sex, prenatal maternal BMI and cigarette smoking are studied in five cohort samples from different countries. Statistical models are adjusted for important prenatal and later-life covariates. The structural features of main white matter tracts, including the corpus callosum (CC), are studied using mutually complementary metrics of multimodal brain magnetic resonance imaging (MRI).

The findings in the CC showed, first, a correlation between MRI relaxometry measures and small-calibre axons and second, sexual dimorphism in myelination in the midsagittal CC. Prenatal maternal BMI and cigarette smoking were observed to be associated with structural alterations of white matter tracts in adolescence and early adulthood, but with inconclusive replication across cohorts at different ages. These findings indicate that early-life factors are associated with alterations of white matter structure in offspring during the first decades of life, and thus pinpoint the importance of health support during pregnancy. The findings also emphasise the importance of considering the exposures as part of the wider socioeconomic environment.