Abstract
Early brain development is sensitive to factors with the potential to cause deviations from typical developmental trajectories, such as preterm birth or genetic predisposition to autism. Such deviations can result in lasting effects, including an elevated likelihood of neurodevelopmental disorders. Significant advancements in high-quality functional magnetic resonance imaging now allow the in vivo study of the developing human brain with unprecedented detail. This progress has opened new avenues for examining both typical development and alterations in functional brain activity that may be linked to a higher likelihood of atypical neurodevelopment later in life. Despite these advancements, accurately identifying and characterizing the subtle brain changes that may indicate an increased likelihood of atypical development remains a key challenge. Metrics like functional degree centrality have proven sensitive to atypical neurodevelopmental profiles in adults with autism. Nonetheless, research in adults cannot disentangle primary mechanisms from secondary or compensatory effects. Furthermore, while altered temporal brain dynamics have been linked to neurodevelopmental conditions, limited knowledge exists regarding the early development of functional centrality and its dynamics. To address these issues, this thesis aims to improve our understanding of functional centrality topology and dynamics in typically developing infants and infants at increased likelihood of atypical neurodevelopmental outcomes.First, I characterized the development of centrality in term-born neonates and in infants with an increased likelihood of atypical neurodevelopment (infants born preterm), using a ‘static’ analysis approach. I found that postmenstrual age at scan is associated with a relative increase in functional centrality in the visual cortex and a relative decrease in the primary motor and auditory cortices. Preterm birth affects centrality largely in the same brain areas as typical maturation, with preterm-born infants showing higher relative centrality within the visual cortex and lower relative centrality in motor-related areas.
Next, I characterized dynamic centrality in term-born infants and infants with increased likelihood of atypical neurodevelopment (preterm-born infants and infants with a family history of autism) using a cofluctuation-based approach. I identified the main dynamic centrality states of the neonatal brain and demonstrated that as term-born infants grow older, they spend more time in a centrality brain state marked by high centrality in sensory-motor regions. Older infants at the time of scan also spend a higher proportion of time in a state characterized by high centrality in frontal-parietal regions. Compared to term-born neonates, preterm-born neonates spend less time in a state with high global centrality in the sensory-motor regions, but more time in a similar state with lower global centrality. Preterm-born infants also spend less time in states with high centrality in the frontal-parietal and parietal regions and more time in a state with overall low global centrality.
Finally, I proposed an atlas-based approach to explore how short-range and long-range functional connections contribute to the centrality patterns observed. Th analysis suggested that centrality in the neonatal brain may increasingly be driven by more integrated sensory-motor connectivity patterns as infants age. Conversely, preterm-born infants may exhibit less integrated sensory-motor processing. Both short-range connections within frontal and parietal regions, and long-range connections across the brain, appear important for the maturation of fronto-parietal centrality. I also explored relationships between centrality metrics and outcome at 18 months. Whilst effect sizes were small to moderate (no relationships survived multiple comparison correction), the associations present suggest potential functional brain centrality patterns in early life that may be associated with behavioural and emotional problems measured by the Child Behaviour Checklist in toddlerhood.
This thesis provides a detailed exploration of functional centrality within the neonatal brain, combining numerous approaches to better understand the patterns of centrality associated with typical and atypical development. This research offers new insights into early functional brain development and proposes novel approaches for analysing neonatal fMRI data. It underscores the importance of moving beyond traditional static methods and considering the dynamic interplay of functional connections, which shape the topology and dynamics of functional centrality in both typical and atypical development.
| Date of Award | 1 Jun 2024 |
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| Original language | English |
| Awarding Institution |
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| Supervisor | Grainne McAlonan (Supervisor) & Dafnis Batalle (Supervisor) |