Correlation between white matter microstructure and executive functions suggests early developmental influence on long fibre tracts in preterm born adolescents

Abstract

Main objectivesExecutive functions are frequently a weakness in children born preterm. We examined associations of executive functions and general cognitive abilities with brain structure in preterm born adolescents who were born with appropriate weight for gestational age and who have no radiological signs of preterm brain injury on neuroimaging.MethodsThe Stockholm Neonatal Project (SNP) is a longitudinal, population-based study of children born preterm (<36 weeks of gestation) with very low birth weight (<1501g) between 1988–1993. At age 18 years (mean 18 years, SD 2 weeks) 134 preterm born and 94 full term participants underwent psychological assessment (general intelligence, executive function measures). Of these, 71 preterm and 63 full term participants underwent Magnetic Resonance Imaging (MRI) at mean 15.2 years (range 12–18 years), including 3D T1-weighted images for volumetric analyses and Diffusion Tensor Imaging (DTI) for assessment of white matter microstructure. Group comparisons of regional grey and white matter volumes and fractional anisotropy (FA, as a measure of white matter microstructure) and, within each group, correlation analyses of cognitive measures with MRI metrics were carried out.ResultsSignificant differences in grey and white matter regional volumes and widespread differences in FA were seen between the two groups. No significant correlations were found between cognitive measures and brain volumes in any group after correction for multiple comparisons. However, there were significant correlations between FA in projection fibres and long association fibres, linking frontal, temporal, parietal, and occipital lobes, and measures of executive function and general cognitive abilities in the preterm born adolescents, but not in the term born adolescents.Overall significance of the studyIn persons born preterm, in the absence of perinatal brain injury on visual inspection of MRI, widespread alterations in regional brain tissue volumes and microstructure are present in adolescence/young adulthood. Importantly, these alterations in WM tracts are correlated with measures of executive function and general cognitive abilities. Our findings suggest that disturbance of neural pathways, rather than changes in regional brain volumes, are involved in the impaired cognitive functions.

Neurocognitive reorganization between crystallized intelligence, fluid intelligence and white matter microstructure in two age-heterogeneous developmental cohorts

“…We observed multiple, partially independent contributions of specific tracts to individual differences in gc and gf. The clearest associations were observed for the anterior thalamic radiations, cingulum, forceps major, forceps minor, and superior longitudinal fasciculus, all of which have been implicated to play a role in cognitive functioning in childhood and adolescence Navas-Sánchez et al, 2014;Peters et al, 2014;Tamnes et al, 2010;Urger et al, 2015;Vollmer et al, 2017). However, except for the superior longitudinal fasciculus, these tracts were not significant in NKI Rockland sample.…”

Children with a very low birthweight showed poorer reading skills at eight years of age but caught up in most areas by the age of 10

“…Deficits in executive function have been identified in school‐age children born very preterm and these have involved goal‐directed behaviour, self‐regulation of emotions and working memory. Population‐based studies of children born preterm without radiological signs of perinatal brain injury have showed that alterations in regional brain tissue and microstructure in adolescence were associated with measures of executive functions and cognitive abilities .…”

Disruptions to the cerebellar GABAergic system in juvenile guinea pigs following preterm birth

“…Specifically, for moderate-late ex-preterm children many cohort studies have identified a 1-2 fold increased risk for requiring special education or repeating a grade at ages 5-10 (Huddy et al, 2001;van Baar et al, 2009;Morse et al, 2009;Gurka et al, 2010). The development of these disorders and school-related difficulties can manifest in moderate-late expreterm children who had no gross neuroanatomical injury in the newborn period (Vicari et al, 2004;Vollmer et al, 2017); thus, absence of significant injury is not necessarily an indicator of later neurodevelopmental function and wellbeing. The posterior lobe of the cerebellum is interconnected with the prefrontal cortex, association cortices, and the limbic system, which allows for its involvement in higher executive functioning (Stoodley and Schmahmann, 2010;Stoodley, 2012).…”

“…Decreases in the white matter volumes of regions often impacted by preterm birth, such as the hippocampus and cerebellum (Rees and Inder, 2005;Rees et al, 2008;Volpe, 2003), are suggested to play a key role in the defects in neurodevelopment and behaviour following preterm birth (Counsell et al, 2003). In cases of moderate-late preterm birth, often the type of neuroanatomical injury is a subtle and diffuse delay in myelination compared to more marked decreases in brain volume seen in those born at lesser gestational ages (Vollmer et al, 2017;Volpe, 2003) when large-scale increases in brain structures are occurring. The cerebellum and hippocampus are particularly vulnerable to damage and developmental delay following preterm birth as they each continue to mature throughout late gestation (Rees and Inder, 2005;Rees et al, 2008;Rivkin, 1997;Volpe, 2008;Arnold and Trojanowski, 1996), and this trajectory of maturation is inevitably altered following preterm birth.…”