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…”

“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.”

“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…”

“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 ).”

“Landmarks were defined according to a detailed anatomical protocol (Steinmetz et al., 1990; Leonard, 1996; Sowell et al., 2001; Hayashi et al., 2002) based on the Atlas of the Cerebral Sulci (Ono et al., 1990).”

“These mechanisms include neurogenesis [88,97], apoptosis [77], growth of axonal projections and axon sprouting [11,22,68], myelination [12,76,135], dendritic elaboration and retraction [43,72], synaptogenesis [14,15], and synapse elimination [6,38,52,72], often resulting in modiWcations of the gross morphology of the…”

“Losses in this area have been associated with devastating clinical syndromes such as schizophrenia (23).”

“According to some recent imaging studies (Sowell et al., 1999, 2001), that increase continues beyond adolescence into young adulthood.”

“This pattern of results is similar to those observed in cross-sectional and longitudinal data of normal brain maturation [4, 16 ], but the new methods enabled changes in cortical thickness to be assessed in millimeters for the first time.”

“Cross-sectional anatomical imaging studies of ADHD consistently point to involvement of the frontal lobes (Castellanos et al., 2002), parietal lobes (Sowell et al., 2003), basal ganglia (Castellanos and Giedd, 1994), corpus callosum (Giedd et al., 1994), and cerebellum (Berquin et al., 1998).”

“[20] Sowell ER, Thompson PM, Tessner KD, Toga AW.”

“Age-related changes in grey matter throughout normal adolescence are dynamic, with substantial thinning of cortical grey matter starting initially in primary areas and occurring later in the secondary cortices of the frontal and parietal lobes and finally in the temporal lobes (Giedd et al., 1999; Sowell et al., 2001;…”

“These criteria, along with interrater reliability measures, have been described previously (Sowell et al., 2001), and the written anatomical pro-”

“The dramatic growth of developmental neuroscience in the last decade has produced remarkable findings regarding brain development during childhood and adolescence (Giedd et al., 1999; Sowell, Thompson, Tessner, & Toga, 2001).”

“, 1999) might reflect a wave of synaptic proliferation at this time, while the gradual decrease in grey matter density that occurs in certain brain regions during adolescence has been attributed to synaptic pruning (Giedd et al., 1999; Gogtay et al., 2004; Sowell et al., 2001).”

“In general, loss of gray matter progresses from the back to the front of the brain with the frontal lobes among the last to show these structural changes [3,6].”

“At the same time, there is an increase in prefrontal cortex (PFC) and parietal cortex white matter (WM) density from puberty onset, throughout adolescence and into adulthood (Giedd et al., 1996; 1999; Reiss et al., 1996; Sowell et al., 2001; Barnea-Goraly et al., 2005; for more detailed reviews of structural developme…”

“…by guest on 29 Septem ber 2018 In contrast, gray matter volumes follow a nonlinear developmental trajectory whereby peak volumes are attained at approximately 10--12 years (Giedd et al. 1999), followed by a significant decline throughout adolescence and adulthood (Sowell et al. 2001, 2003).”

“Volumetric changes can be correlated with intelligence test and cognitive performance, most evident on tasks that rely heavily on the prefrontal cortex (Casey, Giedd, & Thomas, 2000; Shaw et al., 2006; Sowell et al., 2001; Sowell et al., 2004).”

“However, there are regional differences in the timing of this pattern (Giedd et al., 1999; Gogtay et al., 2004; Sowell et al., 2001).”

“2003), which also show decreases in cortical gray matter in the context of white matter development (Giedd, Blumenthal, Jeffries, Castellanos, et al. 1999; Sowell et al. 2001; Gogtay et al. 2004; Giorgio et al. 2009).”

“Human structural imaging studies have demonstrated a loss of gray matter during adolescence (Sowell et al., 1999, 2001), with gray-matter reductions in portions of the temporal lobe and cortical regions (dorsal PFC) occurring in late adolescence (Raznahan et al., 2011; Sowell et al., 1999, 2004).”

“…recent neurobiologic studies suggesting that the development of cognitive abilities appears to be related to structural and physiologic brain changes that occur during childhood and adolescence (Gomez-Perez et al., 2003; Sowell et al., 2001; Yurgelun-Todd et al., 2003; Yurgelun-Todd et al., 2002).”

“The extant literature indicates robust age-related cortical thinning in adolescence (Gennatas et al., 2017; Gogtay et al., 2004; Sotiras et al., 2017; Sowell et al., 2001, 2003, 2004; Tamnes et al., 2010; Vandekar et al., 2015).”

“…adolescence, as assessed by postmortem studies and structural imaging techniques (Giedd et al., 1999; Mukherjee et al., 2002; Paus et al., 2001; Sowell et al., 1999, 2001) and with reports of functional changes in PFC activation during performance of behavioral inhibition and working memory…”

“This loss continues during the transition from adolescence to young adulthood, especially in the dorsolateral prefrontal cortex (Giorgio et al., 2008; Sowell et al., 1999; Sowell et al., 2001).”

“2, panel 9), gray matter density (GMD; Good et al., 2001; Sowell et al., 1999a,b; Wright et al., 1995), or cortical pattern asymmetry (Sowell et al., 2002a,b,c; Thompson et al., 2001a,b).”

“These findings confirm those of a previous T1-weighted imaging study that reported significant brain growth between adolescence and adulthood, but very little growth between childhood and adolescence (Sowell et al., 2001).”

“Adapted from Giedd et al. (1999a, 1999b). gerated pattern of the normal brain development during adolescence and could reflect the lack of normal controls GM maturation (Schoop, Gardziella, & Muller, 1997; Sowell et al., 2001).”

“Overproduction and pruning has been more recently visualized with structural imaging studies (Giedd et al., 1999a; Giedd et al., 1996b; Giedd et al., 1996c; Sowell et al., 2002; Sowell et al., 2001; Sowell et al., 2004; Tau and Peterson, 2010).”

“…demonstrated that throughout the cerebral cortex there is a loss of gray matter during adolescence, with gray-matter reductions in portions of the temporal lobe and dorsolateral PFC occurring in late adolescence (Gogtay et al., 2004; Sowell et al., 2003; Sowell et al., 2001; Sowell et al., 2002).”

“2002), worse visuospatial and delayed verbal memory (Sowell et al. 2001), and slower reaction time (Spear 2000).”

“…a protracted period of postnatal structural development lasting into at least the third decade of life (Giedd et al., 1999; Gogtay et al., 2004; Sowell et al., 2001; Tsujimoto, 2008—see also Sowell et al., 2002 suggesting the cingulate cortex shows more rapid structural maturation relative to…”

“This reclassification from GM to WM would not necessarily entail changes in the number of synapses (Sowell et al, 2001).”

“An unresolved question is the degree to which the cortical GM reductions are driven by synaptic pruning versus myelination along the GM/WM border.(9) The volume of the caudate nucleus, a subcortical GM structure, also follows an inverted UYshaped developmental trajectory, with peaks similar to the frontal lobes with w…”

“Brain surface contraction is defined as the subvoxel-resolution distance between anatomically corresponding brain surface points of baseline and follow-up brain scans, the measure of which is an integrated part of Cortical Pattern Matching (Sowell et al., 2001).”

“These global figures are consistent with previous suggestions regarding postadolescent maturation in the association cortex (involving ongoing myelination and cortical pruning), followed by genuine atrophy at a later age [Sowell et al., 2001, 2003; Yakovlev and Lecours, 1967].”

“However, animal and human studies have shown this age to be a critical time for maturation of forebrain structure and function (Lewis and Akil 1997; Giedd et al. 1999; Benes et al. 2000; Lambe et al. 2000; Sowell et al. 2001).”

“In particular, gross morphological changes result from both increases in white matter by continued axonal myelination and changes in grey matter (Barnea-Goraly et al., 2005; Giedd et al., 1999; Paus et al., 1999; Reiss et al., 1996; Sowell et al., 2001).”

“Sowell et al. (2001) reported cortical thinning or gray matter density decrease in the frontal and parietal lobes in a similar age group.”

“…a forward-moving wave of maturation in which the frontal and temporal lobes had a more protracted period of development with peak volumes for these lobes occurring later in adolescence than for parietal and occipital lobes (Sowell et al., 1999, 2001; Gogtay et al., 2004; Gogtay and Thompson, 2010).”

“…indicating that gray matter thinning continues in association cortex across lobes indicates that cortical regions that support complex functional integration in each lobe develop last (Giedd et al., 1999; Gogtay et al., 2004; Paus et al., 1999; Sowell et al., 2001; Toga, Thompson, & Sowell, 2006).”

“Behavioral improvements in cognitive control coincide with synaptic pruning and increased myelination as well as experience-dependent synaptic strengthening (Sowell et al., 2001; Bjorklund, 2005; Dawson and Guare, 2010).”

“prior to left frontal cortical thinning in children 5--11 years of age (Sowell et al. 2001).”

“methods of morphological analysis to measure changes in cortical thickness with development.(39,55) One longitudinal study consisted of data from 45 children between the ages of 5 and 11 years who were scanned twice within a 2-year period.”

“grey matter density occurring in several areas of brain growth during the transitions between childhood, adolescence and adulthood (De Bellis et al., 2001; Sowell et al., 2001).”

“Human neuroimaging studies show corresponding patterns, in which gray matter volumes typically peak around 10e12 years of age (Giedd et al., 1999), with significant gray matter loss throughout adolescence and adulthood (Sowell et al., 2001, 2003).”

“At the same time, there is an increase in cortical white matter density from puberty, throughout adolescence and into adulthood (Giedd et al., 1996; 1999; Reiss et al., 1996; Sowell et al., 2001; Barnea-Goraly et al., 2005).”

“Structural imaging studies have similarly demonstrated prominent brain growth during this period rather than earlier in childhood (Sowell et al., 2001, 1999).”

“The subjects studied here (ALC and control subjects) are the same subjects examined in our earlier reports of callosal (Sowell et al., 2001a) and tissue density abnormalities (Sowell et al., 2001b).”

“Gray matter in the cerebral cortex shows a characteristic “rise and fall” pattern (Geidd et al., 1999; Sowell et al., 2001; Gogtay et al., 2004; Thompson et al., 2005; Hua et al., 2009), while white matter connecting gray matter areas increases steadily from birth to adulthood (Paus et al., 1999;…”

“Indeed, one of the startling findings from recent brain imaging studies is that the PFC may not fully develop until post-adolescence (Giedd, 2004; Sowell, Thompson, Tessner, & Toga, 2001 ).”

“1993), with a small increase occurring later at puberty (Durston et al. 2001; Sowell et al. 2001).”

“In conjunction with the behavioral development of executive functions, previous studies showed postadolescent structural development particularly of the frontal lobes (Giedd et al., 1999; Sowell et al., 1999, 2001).”

“Positive correlations between IQ and total frontal gray matter volume have been reported previously (Reiss et al., 1996; Sowell et al., 2001) but our findings suggest that the orbitofrontal and medial frontal regions may be particularly relevant.”

“Previous developmental studies have reported volumetric changes in brain structure associated with age and sex in pediatric populations of this age range (Sowell et al., 2001).”

“After this inflection point, there is steadily decreasing grey matter until early adulthood [26].”

“Myelination, which enables high-speed neural traffic, continues into the third and fourth decades, depending on the brain region (Allman and Hasenstaub 1999; Giedd et al. 1999; Sowell et al. 1999, 2001, 2002; Bartzokis et al. 2003).”

“growth in frontal and lateral temporal brain regions during the post-adolescent years (Sowell et al., 2001).”

“The initiation of gray matter loss in the frontal cortex during adolescence is considered a hormone-dependent process (Giedd et al., 1999; Gogtay et al., 2004; Peper et al, 2009; Sowell et al., 2001).”

“2004), with decreases in dorsal prefrontal cortical volume by late adolescence (Sowell et al. 2001).”