Structural and functional brain network coupling across the lifespan

Neurodevelopmental disorders such as autism spectrum disorders (ASD) are common (~1% global prevalence) yet largely untreatable (1). The underlying pathophysiology of these disorders is not known, and diagnosis is typically delayed until childhood. Early clinical ASD biomarkers are not well established, with behavioural diagnoses taking place at ~18-24 months (2, 3), when affected children evidence developmental lag or regression versus typically-developing (TD) children (4).

Neurobiological alterations associated with these disorders include excitation-inhibition (E-I) imbalances (5), activity and cortical maturation (6) shifts and complex changes in brain connectivity (7). In addition to the influence of underlying genetics, recent studies suggest biological changes begin in the period surrounding birth. Furthermore, those born preterm (<37 weeks gestation) are considered to be at greater risk of neurodevelopmental disease. Consequently, the impact of altered neurodevelopment across the lifespan must be investigated from the perinatal period onwards. This necessitates studying not only functional connectivity (FC) of regions constituting resting-state networks (RSN) or the structural connectivity (SC) of white matter in isolation, but the development of both, and their coupling throughout the lifespan.

This project aims to characterise changes in network SC (from diffusion MRI), FC (from functional MRI) and their coupling across the lifespan. This will be performed for both TD and ASD groups where diagnoses are known (in the child-adult range). The overarching hypothesis is that across the lifespan, neurodevelopmental disease such as ASD will result atypical SC:FC coupling. Understanding longitudinal changes in structural-functional network coupling in ASD versus TD (including ASD sub-groups) may provide critical new insights into the etiology of ASD as a neurodevelopmental disease, with scope to yield a biomarker to identify individuals at risk in the perinatal period.