Dynamic mapping of human cortical development during childhood through early adulthood

Abstract

We report the dynamic anatomical sequence of human cortical gray matter development between the age of 4 -21 years using quantitative four-dimensional maps and time-lapse sequences. Thirteen healthy children for whom anatomic brain MRI scans were obtained every 2 years, for 8 -10 years, were studied. By using models of the cortical surface and sulcal landmarks and a statistical model for gray matter density, human cortical development could be visualized across the age range in a spatiotemporally detailed time-lapse sequence. The resulting time-lapse ''movies'' reveal that (i) higher-order association cortices mature only after lower-order somatosensory and visual cortices, the functions of which they integrate, are developed, and (ii) phylogenetically older brain areas mature earlier than newer ones. Direct comparison with normal cortical development may help understanding of some neurodevelopmental disorders such as childhood-onset schizophrenia or autism.H uman brain development is structurally and functionally a nonlinear process (1-3), and understanding normal brain maturation is essential for understanding neurodevelopmental disorders (4, 5). The heteromodal nature of cognitive brain development is evident from studies of neurocognitive performance (6, 7), functional imaging (functional MRI or positronemission tomography) (8-10), and electroencephalogram coherence studies (1, 2, 10). Prior imaging studies show regional nonlinear changes in gray matter (GM) density during childhood and adolescence with prepubertal increase followed by postpubertal loss (11)(12)(13)(14). The GM density on MRI is an indirect measure of a complex architecture of glia, vasculature, and neurons with dendritic and synaptic processes. Studies of GM maturation show a loss in cortical GM density over time (15,16), which temporally correlates with postmortem findings of increased synaptic pruning during adolescence and early adulthood (17-19). Here we present a study of cortical GM development in children and adolescents by using a brain-mapping technique and a prospectively studied sample of 13 healthy children (4-21 years old), who were scanned with MRI every 2 years for 8-10 years. Because the scans were obtained repeatedly on the same subjects over time, statistical extrapolation of points in between scans enabled construction of an animated time-lapse sequence (''movie'') of pediatric brain development. We hypothesized that GM development in childhood through early adulthood would be nonlinear as described before and would progress in a localized, region-specific manner coinciding with the functional maturation. We also predicted that the regions associated with more primary functions (e.g., primary motor cortex) would develop earlier compared with the regions that are involved with more complex and integrative tasks (e.g., temporal lobe).The result is a dynamic map of GM maturation in the pre-and postpubertal period. Our results, while highlighting the remarkable heterogeneity, show that the cortical GM development appears to f...

The effect of COMT Val158Met and DRD2 C957T polymorphisms on executive function and the impact of early life stress

“…Although the decreased D2 receptor binding (CC genotype) has been associated with poorer performance on timed attention tests in previous studies (Slagter et al., 2012; Yang et al., 2004), the main effect of genotype in our study emerged in two‐way ANCOVA with childhood trauma category as another fixed factor, showing that CC homozygotes who have experienced childhood trauma perform more poorly on a sustained attention test, compared to those who have not experienced childhood adversity. The effect of early life stress on cognitive outcomes has been repeatedly demonstrated in earlier studies (Bos et al., 2009; Colvert et al., 2008), and it is to be expected due to the long maturation period of the PFC (Gogtay & Thompson, 2010; Gogtay et al., 2004) and high concentration of glucocorticoid receptors and dopaminergic projections in the PFC (Pani et al., 2000). However, it should be noted that the genotype–early life stress interaction was only found in the RVP test.…”

“…Furthermore, the PFC appears to be particularly susceptible to early life stress. This susceptibility may be due to its high density of glucocorticoid receptors and dopaminergic projections (Pani, Porcella, & Gessa, 2000), and the fact that it is one of the last brain regions to reach maturity (Gogtay & Thompson, 2010; Gogtay et al., 2004). In support of this, deficits in functions mediated by PFC and cortico‐striatal networks, such as attention, working memory and other executive functions, have also been reported in individuals who have experienced childhood trauma (Bos, Fox, Zeanah, & Nelson, 2009; Colvert et al., 2008).…”

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“…Such large-scale genomic data combined with the high density of information provided by a contectome database will be transformative. By combining the information in these databases we can now begin to explore the genomic determinants of neuronal network topology, network myelination (by combining our techniques with diffusivity, magnetization transfer or T1 relaxation measurements (Barnea-Goraly et al, 2005;Gogtay et al, 2004;Xydis et al, 2006)), network information flow and functional interaction (using EEG and MEG).…”

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“…Despite extensive and ongoing research, clinicians still struggle with PCS prognosis, with no reliable process for distinguishing between those that will develop PCS and those that will not. Maturational brain changes that typify childhood and adolescent development,4, 5, 6 along with significant sex differences in neurological organization and function,7, 8, 9 likely contribute to the heterogeneity in injury outcomes and some of the difficulty associated with determining prognosis. To date, a majority of the animal and human studies that examine mTBI and RmTBI have focused on adult males,10 creating a void in the literature with respect to the female brain and the role of maturation.…”