Neural correlates of internalising and externalising problems in children born very preterm: a prospective longitudinal study
Creators: name: Gilchrist, Courtney
Publisher: name: RMIT University
Year: 2024
Subjects: classificationCode: 320903
subject: Central nervous system
classificationCode: 321302
subject: Infant and child health
classificationCode: 520202
subject: Behavioural neuroscience

description: Background: Although survival rates of the smallest and most vulnerable babies have improved across the past two decades with advances in neonatal intensive care, this has not been accompanied by improvements in long-term neurodevelopmental outcome. Various groups around the world report elevated risk for internalising problems in children born very preterm (&lt; 32 weeks’ gestation), ranging from subclinical symptoms to clinical diagnosis. Conversely, elevated risk of externalising problems in this population is primarily reported prior to adolescence but not beyond. A large body of work has used magnetic resonance imaging technology to characterise structural and functional brain development across the lifespan in individuals born very preterm, however few studies have leveraged this technology to understand the neural basis of internalising and externalising problems in these individuals. Limited studies in this area are primarily cross-sectional, providing a snapshot in time of how the brain relates to behaviour problems and psychopathology and many include just a narrow subset of structures or connections in their analyses. 

The overall objective of this thesis was to examine the neural correlates of internalising and externalising symptoms across childhood in typically developing individuals and individuals born very preterm using a series of advanced neuroimaging techniques. Separate studies investigated developmental trajectories of corticolimbic regions in very preterm children with and without an anxiety diagnosis at 13 years (Chapter 3) and how network organisation (Chapter 4) and microstructural and macrostructural features of white matter (Chapter 5) related to concurrent internalising and externalising problems at 7 and 13 years in individual born very preterm and full-term. 

Methods: Participants included in all studies were recruited as part of the Victorian Infant Brain Study cohort, a prospective longitudinal study consisting of children born very preterm (&lt; 30 weeks’ gestation) and full-term (37 – 42 weeks gestation). Participants had brain magnetic resonance imaging scans at term-equivalent age, 7 and 13 years. Whole-brain and corticolimbic region volumes were calculated based on parcellations from compatible neonatal and child atlases (Chapter 3). Network integration and segregation measures were calculated from structural connectomes generated at 7 and 13 years (Chapter 4). White matter microstructure and macrostructure measures were estimated with a fixel-based approach in relevant white matter tracts delineated with TractSeg at 7 and 13 years (Chapter 5). Anxiety diagnosis was assessed at 13 years using the Development and Well-Being Assessment. Internalising and externalising symptoms were assessed using the Strength and Difficulties Questionnaire parent-report at 7 and 13 years.

Results: Very preterm children diagnosed with an anxiety disorder at 13 years displayed slower volume growth in early childhood in two regions involved in regulating amygdala activation; the hippocampus and medial orbitofrontal cortex (Chapter 3). This was accompanied by slower growth in whole-brain measures and attenuated when factoring out the influence of total brain volume and familial social risk. Neural correlates of internalising and externalising problems were distinct across 7 and 13 years. Poorer integration of networks across the brain was related to greater internalising symptoms at 7 years but not later at 13 years, regardless of birth group (Chapter 4). In very preterm children, lower network integration at 7 years and higher network segregation at 13 years was related to greater externalising symptoms, but such associations were not evident in the full-term group. Consistent with findings of Chapter 4, lower fibre density, smaller fibre bundle cross-section and reduced overall capacity for information transfer across the brain were related to greater internalising symptoms at 7 years but not 13 years, irrespective of birth group (Chapter 5). Reductions in measures of white matter microstructure and macrostructure were also related to externalising symptoms in both groups at 7 years, and only full-term children at 13 years. 

Conclusion: Across three neuroimaging approaches, this work reveals that the way in which brain features relate to psychopathology changes across development and in fact appears to be more strongly related in early childhood Additionally, while some brain features correlate with internalising or externalising symptoms exclusively, others correlate across dimensions, suggesting some shared aetiology. Finally, brain features appear to relate to internalising symptoms similarly in very preterm and full-term children but differ across birth groups when assessing externalising symptoms. Together, there is hope that in characterising neural features related to psychopathology, this work puts the field one step closer towards incorporating neuroimaging techniques into clinical practice to inform which infants would benefit most from close monitoring and allocation of early intervention to support these individuals and their families.