Mapping Continued Brain Growth and Gray Matter Density Reduction in Dorsal Frontal Cortex: Inverse Relationships during Postadolescent Brain Maturation

“Using the methods described here, it is possible to find smaller regions of gray matter density gain and loss (or growth and shrinkage) within the same larger lobar regions typically measured in volumetric studies (Jernigan et al., 1991; Reiss et al., 1996; Giedd et al., 1999; Sowell et al., 2001b).”

“Future studies should also use diffusion tensor imaging (Pierpaoli et al., 1996) as an approach to disentangle increased white matter from synaptic loss, because increased myelination would increase the local diffusion anisotropy, whereas synaptic pruning should not increase the directional…”

“It may not be unreasonable to hypothesize that improved accuracy (i.e., improved cognitive task performance) may result from regressive changes such as synaptic pruning, given that unused or less efficient synaptic connections are being pruned away during this age range ( Huttenlocher, 1979 ).”

“MR images from each individual were processed with a series of manual and automated procedures that included the following steps: (1) automated linear transformation (Woods et al., 1993) of the images into a standard orientation with scaling to remove global differences in head size allowing assessment of local change…”

“…that is continuously deformed to fit a cortical surface tissue threshold intensity value (signal value that best differentiates cortical CSF on the outer surface of the brain from the underlying cortical gray matter) from the brain volume aligned in standard ICBM-305 space (Mazziotta et al., 1995).”

“Because the greatest changes in gray matter density occur in the dorsal frontal cortex between adolescence and adulthood (Sowell et al., 1999a), this was the region that we targeted in the permutation analyses (all gray matter brain tissue anterior to the central sulcus and superior to the axial…”

“As shown in Figure 5, between adolescence and adulthood, large, diffuse regions of shrinkage or decreased DFC are observed in frontal and parietal regions surrounding the frontal and temporal growth areas, probably resulting from large increases in cortical CSF known to occur more prominently between adolescence and a…”

“…cortical gray matter density has been observed primarily in the dorsal parietal and some frontal regions between childhood and adolescence (Sowell et al., 1999b) along with an increase in white matter density in the posterior limb of the internal capsule and arcuate fasciculus (Paus et al., 1999).”

“, 1996), increases in somal size, or perhaps even new cell generation (Gould et al., 1999).”

“Although we did not specifically screen patients for perinatal complications or prematurity, which can result in brain morphologic abnormalities (Peterson et al., 2000), it is unlikely that significant perinatal complications were present in our participants, given that they denied any significant history of neurologi…”

“Maturation, particularly in the frontal lobes, has been shown to correlate with measures of cognitive functioning ( Reiss et al., 1996; Sowell et al., 2001a).”

“, 1999a,b), revealing a pattern of maturational changes that is consistent with what would be expected given findings from postmortem studies of myelination (Yakovlev and Lecours, 1967; Benes et al., 1994) and synaptic pruning (Huttenlocher, 1979; Huttenlocher and de Courten, 1987).”

“Regressive (i.e., synaptic pruning) and progressive (i.e., myelination) cellular events are known to occur simultaneously in the brain during childhood, adolescence, and young adulthood, both of which could result in the appearance of gray matter density reduction or cortical thinning on MRI.”

“Because the greatest changes in gray matter density occur in the dorsal frontal cortex between adolescence and adulthood (Sowell et al., 1999a), this was the region that we targeted in the permutation analyses (all gray matter brain tissue anterior to the central sulcus and superior to the axial…”

“Increased gray matter density could result from increased synaptic density (Kleim et al., 1996), increases in somal size, or perhaps even new cell generation (Gould et al., 1999).”

“…had been studied with volumetric methods in which inferences could typically be made only at the gross lobar level and with voxel-based methods (Wright et al., 1995) in which relatively crude anatomical matching techniques had been used to create statistical maps of differences between age…”

“Given that the deformation maps (acquired during cortical surface matching) associate the same cortical anatomy in each subject, a local measurement of gray matter density (at each point over the surface of the brain) could be made for each subject in addition to the DFC measures and averaged across corresponding regi…”

“Although there is some evidence from in vivo volumetric studies to suggest that continued brain growth during the adolescent years occurs in dorsal brain regions (Jernigan et al., 1991), a detailed spatial mapping of brain growth has not yet been accomplished in vivo.”

“Our results of late brain growth in the dorsal frontal cortex are also consistent with what would be expected from the cognitive behavioral literature, which shows improved frontal lobe functioning during adolescence (Passler et al., 1985).”

“In a previous study, we saw evidence for increased sulcal asymmetry in the posterior sylvian fissure, which was related to increased gray matter density in the same region (Sowell et al., 2001c).”

“Animal studies have long shown increased dendritic arborization and cortical thickening as a result of enriched environmental experience (for review, see Diamond, 2001).”

“…cortical gray matter density reduction are highly consistent with maps of the spatial distribution of postadolescent brain growth, showing an inverse relationship between cortical gray matter density reduction and brain growth primarily in the superior frontal regions that control…”

“Each individual’s cortical surface was extracted using automated software (MacDonald et al., 1994) that creates a spherical mesh surface that is continuously deformed to fit a cortical surface tissue threshold intensity value (signal value that best differentiates cortical CSF on the outer surface…”

“Increased myelination would seem to necessarily result in a net brain volume increase, given that myelin consists of space-occupying glial cells (Friede, 1989).”

“tical plasticity (Schoop et al., 1997).”

“One such study of participants aged between 7 and 30 revealed that the loss of grey matter in the frontal cortex accelerated during adulthood between the early 20s and up to the age of 30 (Sowell et al., 2001).”

“…time 1 by manually selecting anatomical landmarks in both scans; (9) measuring cortical thickness in millimeters averaged within a 15 mm sphere attached to each cortical surface point; and (10) estimating relative local brain growth measured at each cortical surface point (Sowell et al., 2001b ).”