The neonatal brain: early connectome development and childhood cognition

Abstract

The human brain is a vastly complex system that develops rapidly during human gestation. Its developmental pace is unprecedented in any other period of human development. By the time of normal birth the brain's layout verges on the adult human brain. All major structures have come into place, including the white matter pathways. The brain’s white matter forms an intricate network of connections between gray matter regions. This macroscale brain network is referred to as the ‘connectome’. Recent years have witnessed a rapid surge of interest in connectomics to study early brain development. In this thesis, we contribute to this literature, advancing our understanding of early macroscale brain network development and how this process relates to brain function. Firstly, we explored early developmental processes of brain network formation. We identified a number of key attributes of connectome development during the earliest stages after its emergence, from approximately mid-gestation through the neonatal period. Early connectome wiring follows a primary-to-higher order, bottom-to-top, and central-to-peripheral sequence. Furthermore, the structural brain network matures before its functional counterpart and functional brain circuitry undergoes substantially more extensive remodeling than structural brain wiring. Given the complexity of the developmental processes unfolding during the critical timeframe of (late) pregnancy, they are susceptible to injurious events, including preterm birth. In this thesis, we also investigated the brain-behavior relationship following preterm birth. To this end, we related brain metrics measured in the neonatal brain to childhood cognitive functioning in preterm born children. We identified a set of potentially relevant imaging features that may be predictive of distinct developmental domains. White matter maturation measured at term equivalent age was related to performance IQ at early school age (age five years), while white matter volume correlated with processing speed at age five years. Smaller ventricle volumes were associated with better cognitive and motor performance in infancy and early childhood. Finally, we studied brain-behavior correlates in preterm twins and singletons and found no significant differences in brain volumes, cortical maturation and neurodevelopmental outcome in late infancy between the groups that were comparable in terms of gestational age and birth weight. Pre-eclampsia was associated with smaller brain volumes but did not affect cortical development in our study. Collectively, these findings are relevant to clinicians and researchers interested in the heritability of traits, and draw attention to the putative impact of the intrauterine environment to early brain development.