Selective increase in posterior corpus callosum thickness between the age of 4 and 11 years
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.
Section snippets
Participants
Participants were recruited via the Norwegian Mother and Child Cohort Study (MoBa) conducted by the Norwegian Institute of Public Health, which aimed to obtain a representative sample for the Norwegian population (Magnus et al., 2006). For the present study, MoBa participants living in greater Oslo and Trondheim area were invited to participate in the present magnetic resonance imaging (MRI) study. The resulting study sample consisted of 428 children (213 boys, 215 girls) of which 124 underwent
Analysis of regional callosal thickness
Not accounting for differences in TIV, a significant positive effect of Age was found in the splenium of the corpus callosum (all ω2 > 0.05; see Fig. 2, upper right panel). The strongest association was located in segment 59 in the splenium (β = 0.19; t727 = 6.57, p < 0.0001, ω2 = 0.15) indicative of a fitted average growth of 0.19 mm per year (see Fig. 3). Post-hoc inter-regional comparisons revealed that the slope for the effect of Age on thickness was significantly steeper in the posterior segments
Discussion
A significant and selective increase in thickness of the splenium of the corpus callosum between the age of 4 and 10 years was demonstrated by for the first time utilizing a large sample in which also younger children are well represented. Although also the total midsagittal area of the corpus callosum was found to increase in this age period, the regional thickness analysis indicates that this overall effect is mainly driven by segments located in the posterior corpus callosum. The callosal
Acknowledgements
This research was supported by grants from the Norwegian Research Council (K.B.W. and A.M.F.), as well as by the Department of Psychology, University of Oslo.
References (71)
- et al.
Sexual dimorphism in the corpus callosum: methodological considerations in MRI morphometry
NeuroImage
(2001) - et al.
Sex differences in the human corpus callosum: myth or reality?
Neurosci. Biobehav. Rev.
(1997) - et al.
Is interhemispheric transfer time related to age? A developmental study
Behav. Brain Res.
(1994) - et al.
Puberty in the corpus callosum
Neuroscience
(2014) - et al.
Exploration of scanning effects in multi-site structural MRI studies
J. Neurosci. Methods
(2014) - et al.
Adults with attention-deficit/hyperactivity disorder — a diffusion-tensor imaging study of the corpus callosum
Psychiatry Res. Neuroimaging
(2012) - et al.
A quantitative MRI study of the corpus callosum in children and adolescents
Dev. Brain Res.
(1996) - et al.
Developmental trajectories of the corpus callosum in attention-deficit/hyperactivity disorder
Biol. Psychiatry
(2011) - et al.
Effects of handedness and sex on the morphology of the corpus callosum: a study with brain magnetic resonance imaging
Brain Cogn.
(1991) - et al.
Reliability in multi-site structural MRI studies: effects of gradient non-linearity correction on phantom and human data
NeuroImage
(2006)
Development of the corpus callosum in childhood, adolescence and early adulthood
Life Sci.
Changes in white matter microstructure in the developing brain-A longitudinal diffusion tensor imaging study of children from 4 to 11 years of age
NeuroImage
Microstructural maturation of the human brain from childhood to adulthood
NeuroImage
Sexual dimorphism of brain developmental trajectories during childhood and adolescence
NeuroImage
When more is less: associations between corpus callosum size and handedness lateralization
NeuroImage
Why size matters: differences in brain volume account for apparent sex differences in callosal anatomy: the sexual dimorphism of the corpus callosum
NeuroImage
Accurate automatic estimation of total intracranial volume: a nuisance variable with less nuisance
NeuroImage
Sexual dimorphism in the adolescent brain: role of testosterone and androgen receptor in global and local volumes of grey and white matter
Horm. Behav.
Analysis of cross-sectional area measurements of the corpus callosum adjusted for brain size in male and female subjects from childhood to adulthood
Behav. Brain Res.
Voxel based versus region of interest analysis in diffusion tensor imaging of neurodevelopment
NeuroImage
Dysmyelination revealed through MRI as increased radial (but unchanged axial) diffusion of water
NeuroImage
Neuroanatomical correlates of executive functions in children and adolescents: a magnetic resonance imaging (MRI) study of cortical thickness
Neuropsychologia
Less developed corpus callosum in dyslexic subjects–a structural MRI study
Neuropsychologia
Corpus callosum size and shape in individuals with current and past depression
J. Affect. Disord.
Effects of handedness and gender on macro- and microstructure of the corpus callosum and its subregions: a combined high-resolution and diffusion-tensor MRI study
Cogn. Brain Res.
Interhemispheric transfer time and structural properties of the corpus callosum
Neurosci. Lett.
A critical re-examination of sexual dimorphism in the corpus callosum microstructure
NeuroImage
Pubertal hormones modulate the addition of new cells to sexually dimorphic brain regions
Nat. Neurosci.
Organizing principles of human cortical development-thickness and area from 4 to 30 years: insights from comparative primate neuroanatomy
Cereb. Cortex
A life-span perspective on interaction between the cerebral hemispheres
Dev. Neuropsychol.
Interhemispheric interaction during childhood: I. Neurologically intact children
Dev. Neuropsychol.
Inter- and intra-hemispheric processing of visual event-related potentials in the absence of the corpus callosum
J. Cogn. Neurosci.
Puberty influences medial temporal lobe and cortical gray matter maturation differently in boys than girls matched for sexual maturity
Cereb. Cortex
Absence of interhemispheric transfer of unilateral visuomotor learning in young children and individuals with agenesis of the corpus callosum
Dev. Neuropsychol.
Forms and measures of adult and developing human corpus callosum: is there sexual dimorphism?
J. Comp. Neurol.
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2021, Neuroscience ResearchCitation Excerpt :The segmentation was followed by a rigid-body co-registration (i.e., preserving size and shape of the corpus callosum) of the resulting images to the respective T1-template to achieve a non-tilted midsagittal plane. The structure of the corpus callosum was then automatically identified on the individual midsagittal white-matter maps of each individual and visually inspected, using the same routines previously described for human data (Westerhausen et al., 2016). That is, manual correction were applied where necessary using in house graphical user interface programmed in Matlab (MathWorks Inc.
Dump the “dimorphism”: Comprehensive synthesis of human brain studies reveals few male-female differences beyond size
2021, Neuroscience and Biobehavioral ReviewsCitation Excerpt :Over the past three decades many studies have assessed male/female difference in the corpus callosum during fetal and childhood development, most using sample sizes too small to detect the modest effect sizes cited above. Nonetheless, the fact that 9 out of 13 studies of fetuses and children (Suppl. Table 2B) find no significant male/female difference, and the two largest of these studies (Achiron et al., 2001; Westerhausen et al., 2016) reported opposite findings, does not support this claim. As direct evidence against the pruning hypothesis, one study actually measured fetal amniotic testosterone levels and found no correlation with corpus callosum area in boys at ages 8–11 (Chura et al., 2010).
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2020, CortexCitation Excerpt :For the actual measurement, the midline was resampled into 60 equidistant points, which then served as measurement points. The number of 60 measurement points represents a compromise between the previously used 29 to 100 points (Clarke et al., 1989; Luders et al., 2006) as it provides a sufficiently high density of sampling points to capture the structure of corpus callosum (Westerhausen et al., 2016). In a final preprocessing step, as the present analysis aims to examine the proportionality of the corpus callosum relative to brain size across the lifespan, the raw 60 segment thickness estimates were related to the forebrain volume (see section 2.3).