Effect of preterm birth on white matter tracts and infant cognition

Abstract

Preterm birth (defined as birth before 37 weeks) is a leading cause of neurocognitive impairment in childhood, including difficulties in social cognition and executive function. Microstructural divergence from typical brain development in the preterm brain can be quantified using diffusion magnetic resonance imaging (dMRI) tractography during the neonatal period. The relationship between dMRI tractography metrics and later cognitive difficulties remains inconclusive. A general measure of white matter microstructure (gWM) offers a neural basis for cognitive processes in adults, however it remains unclear when gWM is first detectable in the developmental trajectory. Eye-tracking is a technique which assesses eye-gaze behaviour in response to visual stimuli, which permits inference about underlying cognitive processes, such as social cognition and executive function in infancy. The primary aims of this thesis were to test the hypotheses: dMRI tractography reveals significant differences in tract-average fractional anisotropy (FA) and mean diffusivity (MD) between preterm and term infants, and variance in tract-average FA and MD is shared across major tracts. Secondly, infants born preterm have altered social cognition and executive function compared to term born peers, assessed by eye-tracking and finally, neonatal MRI gWM is associated with cognitive function in infancy. Preterm (birth weight ≤ 1500g) and term infants (born ≥ 37 weeks’ post-menstrual age [PMA]) were recruited and underwent a MRI scan at term equivalent age (between 38 - 42 weeks’ PMA) and an eye-tracking assessment six to nine months later. Preterm infants were assessed at two years using the Bayley Scales of Infant and Toddler Development, Third Edition (BSID-III). dMRI tractography metrics were generated using probabilistic neighbourhood tractography (PNT) in eight pre-defined tracts-of-interest. Principal component analyses (PCA) were used to determine the correlations between the eight tracts-of-interest for four tract-averaged water diffusion parameters. dMRI metrics were compared to the eye-tracking performance and two year outcome data. Quantitative microstructural changes were identifiable within the preterm brain when compared to infants born at term. PCA revealed a single variable that accounts for nearly 50% of shared variance between tracts-of-interest, and all tracts showed positive loadings. Eye-tracking revealed group-wise differences in infant social cognition, attributable to preterm birth, but executive functions inferred from eye-tracking did not differ between groups. dMRI tractography metrics within the neonatal period did not relate to later outcome measures. This thesis shows that variance in dMRI parameters is substantially shared across white matter tracts of the developing brain and suggests that anatomical foundations of later intelligence are present by term equivalent age. Social cognition is altered by preterm birth, however social cognitive ability in infancy is independent of gWM.