White matter integrity and cognitive performance in school-age children: A population-based neuroimaging study

Highlights

• Sample consists of a large population-based neuroimaging cohort of children.

• White matter microstructure is associated with non-verbal intelligence.

• Visospatial ability is associated with white matter integrity, independent of IQ.

• Structure–function associations are similar in boys and girls.

Abstract

Child and adolescent brain development are typically accompanied by marked improvements in a wide range of cognitive abilities. However, limited information is available surrounding the role of white matter in shaping cognitive abilities in children. The current study examined associations between white matter microstructure and cognitive performance in a large sample (n = 778) of 6- to 10-year-old children. Results show white matter microstructure is related to non-verbal intelligence and to visuospatial ability, independent of age. Specificity was demonstrated, as white matter associations with visuospatial ability were independent of general intellectual ability. Associations between white matter integrity and cognition were similar in boys and girls. In summary, results demonstrate white matter structure–function associations are present in children, independent of age and broader cognitive abilities. The presence of such associations in the general population is informative for studies examining child psychopathology

Introduction

Magnetic resonance imaging (MRI) studies demonstrate significant neurodevelopmental changes throughout childhood and adolescence, into young-adulthood. These neurodevelopmental changes occur concurrently with observed improvements in a wide range of cognitive abilities. White matter development, including myelination, continues throughout childhood and adolescence and is thought to play a key role in cognitive function. As distant brain regions become more efficiently interconnected, it is expected that the ability to utilize and manipulate information also becomes more efficient. The role of white matter in shaping cognitive abilities has been previously explored, however the literature in children, especially studies with large sample sizes, remains limited. Furthermore, while such structure–function associations seem intuitive, current in vivo neurobiological measures of the brain do not always demonstrate a straightforward link with neuropsychological performance, especially in the absence of severe neurological or psychiatric symptoms.

White matter maturational effects have been studied in vivo for over a decade using morphological information (i.e., volume, density) and, more recently, using measures of microstructural integrity (Lenroot and Giedd, 2006, Schmithorst and Yuan, 2010). Diffusion tensor imaging (DTI) is a non-invasive technique that provides such microstructural information related to white matter status (Basser et al., 1994). White matter integrity is inferred from DTI based on its ability to measure patterns of water diffusion in the brain. The water diffusion profile in white matter is distinct from that of gray matter due to the myelin sheath, axonal arrangement and packing, and axonal diameter (Beaulieu, 2002). Common parameters describing white matter integrity from DTI include fractional anisotropy (FA) and mean diffusivity (MD). Fractional anisotropy, ranging from 0 to 1, describes the degree of anisotropic diffusion, with 0 being completely isotropic (equal in all directions) and 1 being completely anisotropic (diffusion along only one axis). Mean diffusivity simply describes the average diffusion in all directions (Basser and Pierpaoli, 1996). Various cytoarchitectural features contribute to the diffusion signal by creating boundaries that impede or facilitate free water diffusion (e.g., axonal packing and myelin), and it has been shown that FA and MD (in addition to other scalar metrics) can contribute unique information (Beaulieu, 2002).

Beginning with morphological information from structural imaging, and more recently with DTI, white matter development in children and adolescents has been examined using both cross-sectional and longitudinal designs (Barnea-Goraly et al., 2005, Giedd et al., 1999, Giorgio et al., 2008, Lebel et al., 2008, Schmithorst et al., 2002, Schmithorst and Yuan, 2010). The majority of literature in children demonstrates that with age, both white matter volume and microstructural integrity increase. The precise determinant of these maturational effects has yet to be fully delineated, however the primary hypothesis suggests a combination of increases in myelination coupled with an optimized structural organization of axons (Paus, 2010). Interestingly, studies have demonstrated differential developmental trajectories in white matter between boys and girls (Erus et al., 2015, Simmonds et al., 2014), which may underlie some of the subtle cognitive differences (Maitland et al., 2000).

While studied to a lesser extent than white matter maturation, associations between white matter and cognitive performance have also been examined in children (Erus et al., 2015, Fryer et al., 2008, Johansen-Berg et al., 2007, Muetzel et al., 2008, Navas-Sanchez et al., 2014, Schmithorst et al., 2005). In an early study of roughly 50 children, 5 to 18 years old, Schmithorst et al. (2005) found positive associations between white matter microstructure (i.e., DTI metrics) and intelligence, irrespective of age and sex. A more recent study of 36 children and adolescents 11 to 15 years of age also showed a positive association between white matter microstructure and intelligence (Navas-Sanchez et al., 2014). These studies show IQ to be linked to white matter microstructure in multiple regions, including frontal, parietal and occipital lobes, and the corpus callosum. In general, available studies of white matter microstructure and cognitive ability demonstrate brain–behavior associations that suggest white matter integrity is linked to better cognitive performance.

The current study aims to describe associations between white matter microstructure and cognition across a wide range of neuropsychological domains in a large sample of 6- to 10-year-old children. We hypothesized age-independent associations between DTI measures and cognitive performance across all domains. Based on developmental literature, fractional anisotropy and axial diffusivity are hypothesized to associate positively with cognition, whereas mean diffusivity and radial diffusivity will associate negatively. Given substantial evidence for involvement of widespread brain regions in general intellectual ability (Jung and Haier, 2007), we hypothesize global associations across multiple white matter areas. For more specific cognitive functions, we also hypothesize involvement from multiple regions, but to a lesser extent than with general intelligence. As previous work has already demonstrated distinct patterns of white matter maturation in boys and girls, we also hypothesize differential structure–function associations in boys and girls, specifically in cognitive domains where differences in ability have been demonstrated (e.g., language and spatial ability).