Selective increase in posterior corpus callosum thickness between the age of 4 and 11 years

Abstract

Establishing an efficient functional and structural connectivity between the two cerebral hemispheres is an important developmental task during childhood, and alterations in this development have accordingly been linked to a series of neurodevelopmental and pediatric disorders. The corpus callosum, the major white-matter structure connecting the hemispheres, has been shown to increase in size throughout the three first decades of life. However, behavioral studies indicate that adult-like performance levels of functional hemispheric interaction are already reached during middle and late childhood. Thus, here we specifically examine the structural development of the corpus callosum during the functionally relevant time period by for the first time (a) selectively addressing prospective childhood development and (b) analyzing a sample in which also younger children are well represented. Corpus callosum anatomy was assessed from 732 T1-weighted MRI datasets acquired from 428 children (213 boys, 215 girls) aged of 4.1 and 10.9 years, of which 304 were scanned at two time points. Regional callosal thickness was determined from an outline-based segmentation of the mid-sagittal cross-sectional surface area. Linear-mixed model analyses revealed a significant increase in thickness with age (effect size: up to 15% explained variance) equivalent to a growth in callosal thickness of up to 0.19 mm per year in the posterior corpus callosum. The age effect was found to be stronger in posterior segments (i.e., splenium) than in other callosal subregions. Also, the age effect was found to be comparable between boys and girls, and was detected irrespective of whether developmental or individual differences in overall brain size where accounted for or not. Our results demonstrate a selective increase in posterior corpus-callosum thickness during middle and late childhood. Since axons crossing the midline in the splenium mainly connect occipital and parietal cortices, the accentuated posterior growth might reflect the onset of a posterior-to-anterior moving maturation wave in cortical development known to take place in the same time period.

Introduction

The establishment and optimization of functional and structural connectivity between the two cerebral hemispheres can be seen as an important developmental task during childhood. Congenital failure to develop inter-hemispheric axons, as e.g. in cases of partial or complete agenesis of the corpus callosum, is associated with delayed and hampered interhemispheric integration (e.g., Bayard et al., 2004, Ocklenburg et al., 2015) and slowing of executive processing (Marco et al., 2012). Also, alterations during maturation of the corpus callosum have been linked to pediatric disorders or developmental disabilities, including attention/hyperactivity disorder (e.g., Gilliam et al., 2011, Dramsdahl et al., 2012) and dyslexia (e.g., von Plessen et al., 2002). These observations related to an altered callosal development also emphasize the importance of gaining a better understanding of the typical development of the corpus callosum during childhood. Thus, the aim of the present study was to examine the macrostructural development of the corpus callosum, with particular focus on middle to late childhood (4 to 11 years). This age period is of special relevance since a series of behavioral studies indicates substantial changes in functional inter-hemispheric interaction (Banich and Brown, 2000). The quality of bimanual motor coordination (Marion et al., 2003) and hemispheric-visuomotor integration (Chicoine et al., 2000), interhemispheric-transfer time (Brizzolara et al., 1994, Hagelthorn et al., 2000), magnitude of the bilateral visual field advantage (Banich et al., 2000, Hagelthorn et al., 2000), interhemispheric integration of auditory information (Westerhausen et al., 2010), as well as the incidence of mirror movements (Mayston et al., 1999) have been demonstrated to reach adult-like performance levels in this age period.

Although the corpus callosum is known to rapidly grow in size especially in the first two to three years of life (Clarke et al., 1989, Garel et al., 2011, Rakic and Yakovlev, 1968) the results of a series of important developmental structural magnetic resonance imaging (sMRI) studies indicate that the midsagittal corpus callosum increases during childhood and adolescence (e.g., Chavarria et al., 2014, De Bellis et al., 2001, Ganjavi et al., 2011, Giedd et al., 1999, Giedd et al., 1996, Keshavan et al., 2002, Lenroot et al., 2007, Luders et al., 2010b, Rauch and Jinkins, 1994, Thompson et al., 2000) and also well into the third decade of life (Prendergast et al., 2015, Pujol et al., 1993). From this, one might assume that the corpus callosum also grows within the above defined age period of interest. However, to fully evaluate these previous findings, the age distribution of the analyzed samples needs to be considered. In all previous studies that included participants from the respective age period the group of youngest children (below the age of 5 years) was not represented well, and rather represented only a small proportion of the study sample. All previous studies also included a substantial amount of adolescents and young adult participants (upper age ranging from late teens to late twenties). As a result, the statistical results were representative mostly for older children, adolescents, and partly young adults. For example, although showing a continuous increase in corpus callosum thickness during childhood and adolescence, Luders et al., 2010a, Luders et al., 2010b found statistically significant differences only when the youngest age group (5- to 6-year-olds) was compared with the oldest age group (17- to 18-year-olds).

The aim of the present mixed cross-sectional and longitudinal study was to, for the first time, (a) selectively address middle to late childhood development (4 to 11 years) without additionally including older participants, and (b) utilize an appropriate sample size also for younger children. Since previous studies have reported a pronounced thickness increase in posterior than anterior parts of the corpus callosum in combined childhood and adolescence samples (Giedd et al., 1996, Luders et al., 2010b), the present study also tests whether these regional differences are observable in children as well. Furthermore, the present study aims to examine corpus callosum development under consideration of the participant's sex as well as of the relation to the parallel growth in total brain volume. More specifically, two previous studies found sex differences in the developmental trajectories of the corpus callosum, with boys showing a faster increase as compared to girls when analyzing a combined childhood and adolescence sample (De Bellis et al., 2001, Luders et al., 2010b). However, it can be speculated that the observed sex differences in corpus callosum might be driven mainly by the adolescent subsample. Recent studies show that especially during adolescence sex differences in the brain anatomy are formed, likely driven by the hormonal changes during puberty (e.g., Ahmed et al., 2008, Bramen et al., 2011, Paus et al., 2010). Following this reasoning, developmental sex differences during childhood could be expected to be small, if present at all. Also, childhood and adolescence are characterized by an ongoing increase in overall brain size (De Bellis et al., 2001, Lenroot et al., 2007) and brain maturation (Ostby et al., 2009, Tamnes et al., 2010a). In the adult brain, corpus callosum size is positively related to measures of brain volume (Bermudez and Zatorre, 2001, Jancke et al., 1997) and the growth in corpus callosum might be seen secondary to the overall volumetric brain increase during childhood. However, since earlier studies indicate that childhood growth of the corpus callosum is stronger than it would be expected from growth in brain size (Rauch and Jinkins, 1994), it is predicted that even after considering brain size, an increase in callosal size should be observed during childhood in the present study.