| dc.description.abstract | Despite advances in neonatal care leading to a dramatic reduction in mortality rates in recent decades, there have been comparatively modest improvements in neurodevelopmental outcomes for infants born with neonatal encephalopathy (NE), congenital heart disease (CHD), stroke, and preterm birth. The burden of the problem is significant, affecting a wide range of developmental domains including cognition, executive function, motor and language skills, and behavioural impairments. Hence, by using MRI, this PhD sought to examine the structure and function of the neonatal human brain to provide further insight into early neurodevelopment. It included three related experimental studies and one systematic review.
The first experimental study of this thesis investigated the relationship between 3 different MRI scoring systems (e.g. Barkovich, NICHD-NRN and Weeke) and neurodevelopmental outcome assessed using Bayley Scales of Infant and Toddler Development (Bayley-III) at 2 years of age in term-born infants with NE. Using multiple linear regression, we found a significant association between Barkovich, NICHD-NRN and Weeke scores and Bayley-III cognitive and motor scores. Only the Weeke scoring system was associated with Bayley-III language scores, suggesting more detailed scoring systems have higher predictive ability for outcome prediction. The second experimental study of this thesis used graph theory and network-based statistics (NBS) to assess global brain network topology and identify subnetworks of altered connectivity in infants with CHD prior to cardiac surgery. Using NBS we identified one subnetwork with reduced structural connectivity in infants with CHD involving basal ganglia, amygdala, hippocampus, cerebellum, vermis, and temporal and parieto-occipital lobe, primarily affecting core nodes and edges. The third study of this thesis involved a systematic review of resting-state functional MRI (rs-fMRI) studies to identify deviations in brain function due to early disruptions (e.g prematurity, neonatal insults) that were associated with motor and language outcomes in child- and adulthood. Evidence from this systematic review suggests a possible association between diaschisis and motor and language impairments in individuals after perinatal brain lesions. This result is demonstrated by altered intra- and inter-hemispheric connectivity and impaired lateralization of brain regions important for motor (primary motor cortex, parietal operculum, supplementary motor area, supramarginal gyrus, calcarine cortex, inferior parietal lobule) and language (inferior frontal gyrus, superior temporal gyrus, angular gyrus) functioning, as well as altered connectivity within and between RSNs of primary (sensorimotor, visual, auditory) and higher-order (cerebellum, frontoparietal, default-mode, salience, self-referential and attentional) functions. Finally, the fourth experimental study of this thesis assessed metastable neural dynamics using rs-fMRI data in healthy term-born infants from the developing human connectome project (HCP). We found that metastability of the thalamus and primary order networks were generally more mature than higher-order/associative networks, suggesting different developmental patterns of metastable neural dynamics between primary and higher-order functional systems. Overall, this thesis furthers our understanding of the link between the brain and behavioural changes in infants at risk of neurodevelopmental impairment and offers support for the use of neuroimaging biomarkers with the goal of improving outcomes in infants. | en |
