Abstract
Early brain development during the perinatal period establishes the skeleton for a lifetime of versatile and complex human functions and experiences. However, our current understanding of how variability in anatomy and circuitry formation in the developing brain relates to later emerging behaviours and abilities is limited. Specifically, neurodevelopment disorders, such as autism spectrum conditions, stem from alternations in typical neurodevelopmental processes, starting in-utero. The aetiology of these complex conditions is poorly understood and a consistent robust biomarker has not yet been confirmed. Moreover, to detect any deviations in brain development, our understanding of normative development should be first established. As such, our current capacity to predict future difficulties is very modest in most cases and is largely complicated by heterogeneity among individuals in brain structural features as well as in functioning. The ability to flag infants at greater likelihood for poor neurodevelopmental outcomes and intervene as early as possible would allow us to take advantage of increased brain plasticity in the first years of life, as well as inform us on the early neurodevelopmental processes underpinning these conditions.In this thesis, I first described structural brain maturation in-vivo as reflected by regional covariance of a variety of magnetic resonance properties relating to the shape and microstructure of the neonatal brain in a large cohort of healthy, term-born infants. I found rapid, dynamic changes in structural features of the cortex in the postnatal period, especially in primary and posterior regions, corresponding to developmental trajectories established from post-mortem and animal findings. Coordinated cortical maturation at birth was related to known functional cortical divisions and underlying cytoarchitecture. This cortical profile was also predictive of and associated with social-emotional and language capabilities at 18 months.
Next, I was interested in examining the effect of vulnerability for neurodevelopmental conditions on brain development at birth, and on behavioural outcomes in the second year of life. Specifically, I attempted to move beyond two-group designs that do not capture the spectrum of autism, or the spectrum of risk for autism, assuming an entity as an ‘average’ person with autism. Specifically, to quantify the likelihood for autism in infants with a family history of autism and infants without such a family history, I utilized a novel autism risk measurement combining genetic and environmental risk factors. I found that infants at greater likelihood for autism spectrum disorders showed difficulties or delays in cognitive, language and motor skills at 14 and 18 months. Also, I show that a greater likelihood for autism was associated with deviations from typical volumetric brain development. Specifically, by using normative modelling of volume development, I report that these infants showed both positive and negative deviations from the population mean, consolidating evidence for individual-specific early changes in anatomy among vulnerable infants.
This work promotes our understanding of typical structural brain development at birth, providing a normative template to detect deviations from typical trajectories. I show that behavioural functioning in the toddler period is reliant on the early maturation of cortical circuits. Further, this thesis attempted to improve our definitions of risk estimates for neurodevelopmental conditions by capturing the continuous nature of autism liability. Finally, my work supports an individualized assessment of brain phenotypes in autism, attending to the possibility of distinct neurobiological
underpinnings.
| Date of Award | 1 Aug 2022 |
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| Original language | English |
| Awarding Institution |
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| Supervisor | Jonathan O'Muircheartaigh (Supervisor) & Grainne McAlonan (Supervisor) |