The National Institutes of Health (NIH) Magnetic Resonance Imaging (MRI) Study of Normal Brain Development is a landmark study in which structural and metabolic brain development and behavior are followed longitudinally from birth to young adulthood in a population-based sample of healthy children. The neuropsychological assessment protocol for children aged 6 to 18 years is described and normative data are presented for participants in that age range (N = 385). For many measures, raw score performance improved steeply from 6 to 10 years, decelerating during adolescence. Sex differences were documented for Block Design (male advantage), CVLT, Pegboard and Coding (female advantage). Household income predicted IQ and achievement, as well as externalizing problems and social competence, but not the other cognitive or behavioral measures. Performance of this healthy sample was generally better than published norms. This linked imaging-clinical/behavioral database will be an invaluable public resource for researchers for many years to come.

Recent findings from developmental neuroimaging studies suggest that the enhancement of cognitive processes during development may be the result of a fine-tuning of the structural and functional organization of brain with maturation. However, the details regarding the developmental trajectory of large-scale structural brain networks are not yet understood. Here, we used graph theory to examine developmental changes in the organization of structural brain networks in 203 normally growing children and adolescents. Structural brain networks were constructed using interregional correlations in cortical thickness for 4 age groups (early childhood: 4.8-8.4 year; late childhood: 8.5-11.3 year; early adolescence: 11.4-14.7 year; late adolescence: 14.8-18.3 year). Late childhood showed prominent changes in topological properties, specifically a significant reduction in local efficiency, modularity, and increased global efficiency, suggesting a shift of topological organization toward a more random configuration. An increase in number and span of distribution of connector hubs was found in this age group. Finally, inter-regional connectivity analysis and graph-theoretic measures indicated early maturation of primary sensorimotor regions and protracted development of higher order association and paralimbic regions. Our finding reveals a time window of plasticity occurring during late childhood which may accommodate crucial changes during puberty and the new developmental tasks that an adolescent faces.

The relationship between anxious/depressed traits and neuromaturation remains largely unstudied. Characterizing this relationship during healthy neurodevelopment is critical to understanding processes associated with the emergence of child/adolescent onset mood/anxiety disorders. In this study, mixed-effects models were used to determine longitudinal cortical thickness correlates of Child Behavior Checklist (CBCL) and Young Adult Self Report Anxious/Depressed scores in healthy children. Analyses included 341 subjects from 4.9 to 22.3 year-old with repeated MRI at up to 3 time points, at 2-year intervals (586 MRI scans). There was a significant "CBCL Anxious/Depressed by Age" interaction on cortical thickness in the right ventromedial prefrontal cortex (vmPFC), including the medial orbito-frontal, gyrus rectus, and subgenual anterior cingulate areas. Anxious/Depressed scores were negatively associated with thickness at younger ages (<9 years), but positively associated with thickness at older ages (15-22 years), with the shift in polarity occurring around age 12. This was secondary to a slower rate of vmPFC cortical thinning in subjects with higher scores. In young adults (18-22 years), Anxious/Depressed scores were also positively associated with precuneus/posterior cingulate cortical thickness. Potential neurobiological mechanisms underlying this maturation pattern are proposed. These results demonstrate the dynamic impact of age on relations between vmPFC and negative affect in the developing brain.

Using a population-based sampling strategy, the National Institutes of Health (NIH) Magnetic Resonance Imaging Study of Normal Brain Development compiled a longitudinal normative reference database of neuroimaging and correlated clinical/behavioral data from a demographically representative sample of healthy children and adolescents aged newborn through early adulthood. The present paper reports brain volume data for 325 children, ages 4.5-18 years, from the first cross-sectional time point. Measures included volumes of whole-brain gray matter (GM) and white matter (WM), left and right lateral ventricles, frontal, temporal, parietal and occipital lobe GM and WM, subcortical GM (thalamus, caudate, putamen, and globus pallidus), cerebellum, and brainstem. Associations with cross-sectional age, sex, family income, parental education, and body mass index (BMI) were evaluated. Key observations are: 1) age-related decreases in lobar GM most prominent in parietal and occipital cortex; 2) age-related increases in lobar WM, greatest in occipital, followed by the temporal lobe; 3) age-related trajectories predominantly curvilinear in females, but linear in males; and 4) small systematic associations of brain tissue volumes with BMI but not with IQ, family income, or parental education. These findings constitute a normative reference on regional brain volumes in children and adolescents.