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Recent advances in human neuroimaging research have revealed that white-matter connectivity can be described in terms of an integrated network, which is the basis of the human connectome. However, the developmental changes of this connectome in childhood are not well understood. This study made use of two independent longitudinal diffusion-weighted imaging data sets to characterize developmental changes in the connectome by estimating age-related changes in fractional anisotropy (FA) for reconstructed fibers (edges) between 68 cortical regions. The first sample included 237 diffusion-weighted scans of 146 typically developing children (4-13 years old, 74 females) derived from the Pediatric Longitudinal Imaging, Neurocognition, and Genetics (PLING) study. The second sample included 141 scans of 97 individuals (8-13 years old, 62 females) derived from the BrainTime project. In both data sets, we compared edges that had the most substantial age-related change in FA to edges that showed little change in FA. This allowed us to investigate if developmental changes in white matter reorganize network topology. We observed substantial increases in edges connecting peripheral and a set of highly connected hub regions, referred to as the rich club. Together with the observed topological differences between regions connecting to edges showing the smallest and largest changes in FA, this indicates that changes in white matter affect network organization, such that highly connected regions become even more strongly imbedded in the network. These findings suggest that an important process in brain development involves organizing patterns of inter-regional interactions. Hum Brain Mapp 39:157-170, 2018. © 2017 Wiley Periodicals, Inc.

This study investigates the relationship between variability in cortical surface area and thickness of the pars opercularis of the inferior frontal gyrus and motor-inhibitory performance on a stop-signal task in a longitudinal, typically developing cohort of children and adolescents. Linear mixed-effects models were used to investigate the hypotheses that (1) cortical thinning and (2) a relatively larger cortical surface area of the bilateral pars opercularis of the inferior frontal gyrus would predict better performance on the stop-signal task in a cohort of 110 children and adolescents 4-13 years of age, with one to four observations (totaling 232 observations). Cortical thickness of the bilateral opercular region was not related to inhibitory performance. However, independent of age, gender, and total cortical surface area, relatively larger cortical surface area of the bilateral opercular region of the inferior frontal gyrus was associated with better motor-inhibitory performance. Follow-up analyses showed a significant effect of surface area of the right pars opercularis, but no evidence for an effect of area of left pars opercularis, on motor-inhibitory performance. These findings are consistent with the previous work in adults showing that cortical morphology of the pars opercularis is related to inhibitory functioning. It also expands upon this literature by showing that, in contrast to earlier work highlighting the importance of cortical thickness of this region in adults, relative cortical surface area of the pars opercularis may be related to developing motor-inhibitory functions during childhood and adolescence. Relationships between cortical phenotypes and individual differences in behavioral measures may vary across the lifespan.

Anxiety is a risk factor for many adverse neuropsychiatric and socioeconomic outcomes, and has been linked to functional and structural changes in the ventromedial prefrontal cortex (VMPFC). However, the nature of these differences, as well as how they develop in children and adolescents, remains poorly understood. More effective interventions to minimize the negative consequences of anxiety require better understanding of its neurobiology in children. Recent research suggests that structural imaging studies may benefit from clearly delineating between cortical surface area and thickness when examining these associations, as these distinct cortical phenotypes are influenced by different cellular mechanisms and genetic factors. The present study examined relationships between cortical surface area and thickness of the VMPFC and a self-report measure of anxiety (SCARED-R) in 287 youths aged 7-20 years from the Pediatric Imaging, Neurocognition, and Genetics (PING) study. Age and gender interactions were examined for significant associations in order to test for developmental differences. Cortical surface area and thickness were also examined simultaneously to determine whether they contribute independently to the prediction of anxiety. Anxiety was negatively associated with relative cortical surface area of the VMPFC as well as with global cortical thickness, but these associations diminished with age. The two cortical phenotypes contributed additively to the prediction of anxiety. These findings suggest that higher anxiety in children may be characterized by both delayed expansion of the VMPFC and an altered trajectory of global cortical thinning. Further longitudinal studies will be needed to confirm these findings.

Based on the Huttenlocher lecture, this article describes the need for a more integrative scientific paradigm for addressing important questions raised by key observations made over 2 decades ago. Among these are the early descriptions by Huttenlocher of variability in synaptic density in cortex of postmortem brains of children of different ages and the almost simultaneous reports of cortical volume reductions on MR imaging in children and adolescents. In spite of much progress in developmental neurobiology, developmental cognitive neuroscience, and behavioral and imaging genetics, we still do not know how these early observations relate to each other. It is argued that large scale, collaborative research programs are needed to establish the associations between behavioral differences among children and imaging biomarkers, and to link the latter to cellular changes in the developing brain. Examples of progress and challenges remaining are illustrated with data from the Pediatric Imaging, Neurocognition, and Genetics Project (PING).

Based on the Huttenlocher lecture, this article describes the need for a more integrative scientific paradigm for addressing important questions raised by key observations made over 2 decades ago. Among these are the early descriptions by Huttenlocher of variability in synaptic density in cortex of postmortem brains of children of different ages and the almost simultaneous reports of cortical volume reductions on MR imaging in children and adolescents. In spite of much progress in developmental neurobiology, developmental cognitive neuroscience, and behavioral and imaging genetics, we still do not know how these early observations relate to each other. It is argued that large scale, collaborative research programs are needed to establish the associations between behavioral differences among children and imaging biomarkers, and to link the latter to cellular changes in the developing brain. Examples of progress and challenges remaining are illustrated with data from the Pediatric Imaging, Neurocognition, and Genetics Project (PING). [ABSTRACT FROM AUTHOR]