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Down syndrome (DS) is the most common genetic cause of intellectual disability with a wide spectrum of neurodevelopmental outcomes. Magnetic resonance imaging (MRI) has been used to investigate differences in whole and/or regional brain volumes in DS from infancy to adulthood. However, to date, there have been relatively few in vivo neonatal brain imaging studies in DS, despite the presence of clearly identifiable characteristics at birth. Improved understanding of early brain development in DS is needed to assess phenotypic severity and identify appropriate time windows for early intervention. In this study, we used in vivo brain MRI to conduct a comprehensive volumetric phenotyping of the neonatal brain in DS. Using a robust cross-sectional reference sample of close to 500 preterm- to term-born control neonates, we have performed normative modelling and quantified volumetric deviation from the normative mean in 25 individual infants with DS [postmenstrual age at scan, median (range) = 40.57 (32.43 – 45.57) weeks], corrected for sex, age at scan and age from birth. We found that absolute whole brain volume was significantly reduced in neonates with DS (pFDR GRAPHICAL ABSTRACT

Features of brain asymmetry have been implicated in a broad range of cognitive processes ; however, their origins are still poorly understood. Here we investigated cortical asymmetries in 442 healthy term-born neonates using structural and functional magnetic resonance images from the Developing Human Connectome Project. Our results demonstrate that the neonatal cortex is markedly asymmetric in both structure and function. Cortical asymmetries observed in the term cohort were contextualized in two ways: by comparing them against cortical asymmetries observed in 103 preterm neonates scanned at term-equivalent age, and by comparing structural asymmetries against those observed in 1, 110 healthy young adults from the Human Connectome Project. While associations with preterm birth and biological sex were minimal, significant differences exist between birth and adulthood.

Brain functional dynamics have been linked to emotion and cognition in mature individuals, where alterations are associated with mental ill-health and neurodevelopmental conditions (such as autism spectrum disorder). Although reliable resting-state networks have been consistently identified in neonates, little is known about the early development of dynamic brain functional connectivity and whether it is linked to later neurodevelopmental outcomes in childhood. In this study we characterised dynamic functional connectivity in the first few weeks of postnatal life and evaluated whether early dynamic functional connectivity: i) changes with age in the neonatal period ii) is altered by preterm birth and iii) is associated with neurodevelopmental and behavioural outcomes at 18 months.Global brain dynamics in preterm-born infants were atypical when compared with term-born controls, and associated with atypical social, sensory, and repetitive behaviours measured by the Quantitative Checklist for Autism in Toddlers (Q-CHAT) scores at 18 months of age. On a modular scale, we identified six transient states of neonatal dynamic functional connectivity: three whole-brain synchronisation states and three regional synchrony states occupying occipital, sensory-motor, and frontal regions. Modular characteristics of these brain states were correlated with postmenstrual age and postnatal days at scan. Preterm-born infants had increased occurrence of frontal and occipital states. Higher neonatal sensory-motor synchronisation was associated with lower motor and language outcome scores at 18 months. Lower frequency of occurrence of whole-brain synchronisation states and higher frequency of occurrence of the sensory-motor state were associated with higher Q-CHAT scores at 18 months.Overall, we show that a dynamic landscape of brain connectivity is already established by the time of birth in the human brain. This landscape is altered by preterm birth and its profile is linked to neurodevelopmental outcomes in toddlerhood.

Formation of the functional connectome in early life underpins future learning and behavior. However, our understanding of how the functional organization of brain regions into interconnected hubs (centrality) matures in the early postnatal period is limited, especially in response to factors associated with adverse neurodevelopmental outcomes such as preterm birth. We characterized voxel-wise functional centrality (weighted degree) in 366 neonates from the Developing Human Connectome Project. We tested the hypothesis that functional centrality matures with age at scan in term-born babies and is disrupted by preterm birth. Finally, we asked whether neonatal functional centrality predicts general neurodevelopmental outcomes at 18 months. We report an age-related increase in functional centrality predominantly within visual regions and a decrease within the motor and auditory regions in term-born infants. Preterm-born infants scanned at term equivalent age had higher functional centrality predominantly within visual regions and lower measures in motor regions. Functional centrality was not related to outcome at 18 months old. Thus, preterm birth appears to affect functional centrality in regions undergoing substantial development during the perinatal period. Our work raises the question of whether these alterations are adaptive or disruptive and whether they predict neurodevelopmental characteristics that are more subtle or emerge later in life.

In the mature brain, structural and functional 'fingerprints' of brain connectivity can be used to identify the uniqueness of an individual. However, whether the characteristics that make a given brain distinguishable from others already exist at birth remains unknown. Here, we used neuroimaging data from the developing Human Connectome Project (dHCP) of preterm born neonates who were scanned twice during the perinatal period to assess the developing brain fingerprint. We found that 62% of the participants could be identified based on the congruence of the later structural connectome to the initial connectivity matrix derived from the earlier timepoint. In contrast, similarity between functional connectomes of the same subject at different time points was low. Only 10% of the participants showed greater self-similarity in comparison to self-to-other-similarity for the functional connectome. These results suggest that structural connectivity is more stable in early life and can represent a potential connectome fingerprint of the individual: a relatively stable structural connectome appears to support a changing functional connectome at a time when neonates must rapidly acquire new skills to adapt to their new environment. ispartof: DEVELOPMENTAL COGNITIVE NEUROSCIENCE vol:55 ispartof: location:Netherlands status: published