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...

We used magnetic resonance imaging and cortical matching algorithms to map gray matter density (GMD) in 176 normal individuals ranging in age from 7 to 87 years. We found a significant, nonlinear decline in GMD with age, which was most rapid between 7 and about 60 years, over dorsal frontal and parietal association cortices on both the lateral and interhemispheric surfaces. Age effects were inverted in the left posterior temporal region, where GMD gain continued up to age 30 and then rapidly declined. The trajectory of maturational and aging effects varied considerably over the cortex. Visual, auditory and limbic cortices, which are known to myelinate early, showed a more linear pattern of aging than the frontal and parietal neocortices, which continue myelination into adulthood. Our findings also indicate that the posterior temporal cortices, primarily in the left hemisphere, which typically support language functions, have a more protracted course of maturation than any other cortical region.

Recent advances in magnetic resonance imaging (MRI) technology now allow the tracing of developmental changes in the brains of children. We applied computer-matching algorithms and new techniques for measuring cortical thickness (in millimeters) to the structural MRI images of 45 children scanned twice (2 yr apart) between the ages 5 and 11. Changes in brain size were also assessed, showing local brain growth progressing at a rate of ϳ0.4 -1.5 mm per year, most prominently in frontal and occipital regions. Estimated cortical thickness ranged from 1.5 mm in occipital regions to 5.5 mm in dorsomedial frontal cortex. Gray matter thinning coupled with cortical expansion was highly significant in right frontal and bilateral parieto-occipital regions. Significant thickening was restricted to left inferior frontal (Broca's area) and bilateral posterior perisylvian (Wernicke's area on the left) regions. In the left hemisphere, gray matter thickness was correlated with changing cognitive abilities. For the first time, developmental changes in gray matter thickness, brain size, and structure-function relationships have been traced within the same individuals studied longitudinally during a time of rapid cognitive development.

Structural imaging based on magnetic resonance is an integral part of the clinical assessment of patients with suspected Alzheimer dementia. Prospective data on the natural history of change in structural markers from preclinical to overt stages of Alzheimer disease are radically changing how the disease is conceptualized, and will influence its future diagnosis and treatment. Atrophy of medial temporal structures is now considered to be a valid diagnostic marker at the mild cognitive impairment stage. Structural imaging is also included in diagnostic criteria for the most prevalent non-Alzheimer dementias, reflecting its value in differential diagnosis. In addition, rates of whole-brain and hippocampal atrophy are sensitive markers of neurodegeneration, and are increasingly used as outcome measures in trials of potentially disease-modifying therapies. Large multicenter studies are currently investigating the value of other imaging and nonimaging markers as adjuncts to clinical assessment in diagnosis and monitoring of progression. The utility of structural imaging and other markers will be increased by standardization of acquisition and analysis methods, and by development of robust algorithms for automated assessment.

Human total brain size is consistently reported to be ~8-10% larger in males, although consensus on regionally-specific differences is weak. Here, in the largest longitudinal pediatric neuroimaging study reported to date (829 scans from 387 subjects, ages 3 to 27 years), we demonstrate the importance of examining size-by-age trajectories of brain development rather than group averages across broad age ranges when assessing sexual dimorphism. Using magnetic resonance imaging (MRI) we found robust male/female differences in the shapes of trajectories with total cerebral volume peaking at age 10.5 in females and 14.5 in males. White matter increases throughout this 24 year period with males having a steeper rate of increase during adolescence. Both cortical and subcortical gray matter trajectories follow an inverted U shaped path with peak sizes 1 to 2 years earlier in females. These sexually dimorphic trajectories confirm the importance of longitudinal data in studies of brain development and underline the need to consider sex matching in studies of brain development.