White matter microstructure correlates with mathematics but not word reading performance in 13-year-old children born very preterm and full-term

Abstract

Individuals born very preterm (VPT; <32 weeks' gestational age) are at increased risk of impaired mathematics and word reading performance, as well as widespread white matter microstructural alterations compared with individuals born full term (FT; ≥37 weeks' gestational age). To date, the link between academic performance and white matter microstructure is not well understood. This study aimed to investigate the associations between mathematics and reading performance with white matter microstructure in 114 VPT and 36 FT 13-year-old children. Additionally, we aimed to investigate whether the association of mathematics and reading performance with white matter microstructure in VPT children varied as a function of impairment. To do this, we used diffusion tensor imaging and advanced diffusion modelling techniques (Neurite Orientation Dispersion and Density Imaging and the Spherical Mean Technique), combined with a whole-brain analysis approach (Tract-Based Spatial Statistics). Mathematics performance across VPT and FT groups was positively associated with white matter microstructural measurements of fractional anisotropy and neurite density, and negatively associated with radial and mean diffusivities in widespread, bilateral regions. Furthermore, VPT children with a mathematics impairment (>1 standard deviation below FT mean) had significantly reduced neurite density compared with VPT children without an impairment. Reading performance was not significantly associated with any of the white matter microstructure parameters. Additionally, the associations between white matter microstructure and mathematics and reading performance did not differ significantly between VPT and FT groups. Our findings suggest that alterations in white matter microstructure, and more specifically lower neurite density, are associated with poorer mathematics performance in 13-year-old VPT and FT children. More research is required to understand the association between reading performance and white matter microstructure in 13-year-old children.

Diffusion magnetic resonance imaging assessment of regional white matter maturation in preterm neonates

“…WM NDI has previously been reported to increase with age in neonates [ 29 ], children [ 43 , 44 ] and adolescents [ 45 ], demonstrating that WM tracts undergo these changes beyond the neonatal period and throughout childhood. Greater NDI in childhood has been associated with better neurodevelopmental outcomes, IQ [ 18 , 31 ], visual motor integration [ 18 ], motor/behavioural/emotional scores [ 31 ], language [ 20 ] and maths [ 46 ].…”

The cingulum in very preterm infants relates to language and social-emotional impairment at 2 years of term-equivalent age

“…DTI is a noninvasive tool with a high sensitivity to changes in myelination, and axonal density and diameter, that can be used to investigate the pathophysiology underlying unfavorable neurodevelopmental alterations in the preterm brain ( Rogers et al, 2016 ). While previous reports of altered WM in preterm children have been obtained using univariate analytical methods with high exploratory power – e.g., region of interest (ROI)-based analysis ( Caldinelli et al, 2017 , Dodson et al, 2017 , Murray et al, 2016 ), tract-based spatial statistics (TBSS) ( Coker-Bolt et al, 2016 , Collins et al, 2019 , Hollund et al, 2018 , Jurcoane et al, 2016 , Murner-Lavanchy et al, 2018 ), and tensor-based morphometry (TBM) ( Rajagopalan et al, 2017 ) – these methods may be too conservative to detect subtle, spatially distributed differences because they require corrections for multiple comparisons to control the expected false discovery rate (FDR) ( Ecker et al, 2010b ). By contrast, a multivariate pattern analysis (MVPA) (e.g., support vector machine (SVM) and logistic regression models) accounts for interregional correlations and features increased sensitivity to abnormalities in neural systems ( Ecker et al, 2010 , Li et al, 2014 , Little and Beaulieu, 2019 , Schadl et al, 2018 ).…”

Maturation and interhemispheric asymmetry in neurite density and orientation dispersion in early childhood

“…These structural abnormalities have been associated with decreased IQ and visuomotor function in children born VPT (Kelly et al, 2016; Young et al, 2019), and greater symptoms of social impairment in individuals with ASD (Dimond 2019). These findings, alongside NDI-cognitive associations in healthy individuals (Chung et al, 2018; Collins et al, 2019; Huber et al, 2019; Merluzzi et al, 2016), suggest that neurite density plays an important role in cognitive function, likely mediated by influences on network connectivity. Age-related increases in NDI have been shown to be associated with increased structural network properties (Batalle et al, 2017) and greater functional network connectivity (Deligianni et al, 2016), which is believed to enable faster communication across brain regions in support of various cognitive processes (Zimmermann et al, 2018).…”

“…During early childhood, cognitive maturation is rapid, with developmental improvements in working memory (Burnett Heyes et al, 2012), math (Garon-Carrier et al, 2018), self-regulation (Montroy et al, 2016), reading (Ferretti et al, 2008), and attention (Breckenridge et al, 2013; Mullane et al, 2016), among other traits. Individual differences in axonal/neurite density have been linked to each of these cognitive traits (Chung et al, 2018; Collins et al, 2019; Genc et al, 2019; Huber et al, 2019; Kelly et al, 2016; Merluzzi et al, 2016), suggesting developmental increases in neurite density may contribute to cognitive-behavioral maturation in early childhood. Considering growth patterns in infancy and late childhood (Batalle et al, 2017; Dean et al, 2017; Jelescu et al, 2015), we interpret our NDI results to suggest maturation during early childhood in association fibers is becoming more rapid, commissural and projection fibers are approaching maturity, and maturation in limbic and frontal tracts remains modest.…”