Neonatal brain dynamic functional connectivity: impact of preterm birth and association with early childhood neurodevelopment

Brain functional dynamics have been linked to emotion and cognition in mature individuals, where alterations are associated with mental ill-health and neurodevelopmental conditions (such as autism spectrum disorder). Although reliable resting-state networks have been consistently identified in neonates, little is known about the early development of dynamic brain functional connectivity and whether it is linked to later neurodevelopmental outcomes in childhood. In this study we characterised dynamic functional connectivity in the first few weeks of postnatal life and evaluated whether early dynamic functional connectivity: i) changes with age in the neonatal period ii) is altered by preterm birth and iii) is associated with neurodevelopmental and behavioural outcomes at 18 months. Global brain dynamics in preterm-born infants were atypical when compared with term-born controls, and associated with atypical social, sensory, and repetitive behaviours measured by the Quantitative Checklist for Autism in Toddlers (Q-CHAT) scores at 18 months of age. On a modular scale, we identified six transient states of neonatal dynamic functional connectivity: three whole-brain synchronisation states and three regional synchrony states occupying occipital, sensory-motor, and frontal regions. Modular characteristics of these brain states were correlated with postmenstrual age and postnatal days at scan. Preterm-born infants had increased occurrence of frontal and occipital states. Higher neonatal sensory-motor synchronisation was associated with lower motor and language outcome scores at 18 months. Lower frequency of occurrence of whole-brain synchronisation states and higher frequency of occurrence of the sensory-motor state were associated with higher Q-CHAT scores at 18 months. Overall, we show that a dynamic landscape of brain connectivity is already established by the time of birth in the human brain. This landscape is altered by preterm birth and its profile is linked to neurodevelopmental outcomes in toddlerhood.