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Mapping Continued Brain Growth and Gray Matter Density Reduction in Dorsal Frontal Cortex: Inverse Relationships during Postadolescent Brain Maturation
Open accessAbstract
Recent in vivo structural imaging studies have shown spatial and temporal patterns of brain maturation between childhood, adolescence, and young adulthood that are generally consistent with postmortem studies of cellular maturational events such as increased myelination and synaptic pruning. In this study, we conducted detailed spatial and temporal analyses of growth and gray matter density at the cortical surface of the brain in a group of 35 normally developing children, adolescents, and young adults. To accomplish this, we used high-resolution magnetic resonance imaging and novel computational image analysis techniques. For the first time, in this report we have mapped the continued postadolescent brain growth that occurs primarily in the dorsal aspects of the frontal lobe bilaterally and in the posterior temporo-occipital junction bilaterally. Notably, maps of the spatial distribution of postadolescent 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 executive cognitive functioning. Inverse relationships are not as robust in the posterior temporo-occipital junction where gray matter density reduction is much less prominent despite late brain growth in these regions between adolescence and adulthood. Overall brain growth is not significant between childhood and adolescence, but close spatial relationships between gray matter density reduction and brain growth are observed in the dorsal parietal and frontal cortex. These results suggest that progressive cellular maturational events, such as increased myelination, may play as prominent a role during the postadolescent years as regressive events, such as synaptic pruning, in determining the ultimate density of mature frontal lobe cortical gray matter.
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“Prior imaging studies show regional nonlinear changes in gray matter (GM) density during childhood and adolescence with prepubertal increase followed by postpubertal loss (11–14).”
From Dynamic mapping of human cortical development during childhood through early adulthood (2004) · cites this paper as [12]
In the citing paper
“A further MRI study of 35 normally developing children (7-11 years), adolescents (12-16 years) and young adults (23-30 years) demonstrated a sharp acceleration in the loss of grey matter between childhood and adolescence in the dorsal prefrontal cortex and the parietal cortex (Sowell et al., 2001).”
From Development of the adolescent brain: implications for executive function and social cognition (2006) · cites this paper as Sowell et al., 2001
In the citing paper
“The gradual decrease in grey matter density that occurs after puberty in certain brain regions has been attributed to post-pubescent synaptic pruning (Giedd et al., 1999a;Sowell et al., 2001;Gogtay et al., 2004).”
From Development of the adolescent brain: implications for executive function and social cognition (2006) · cites this paper as Sowell et al., 2001
In the citing paper
“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).”
From Development of the adolescent brain: implications for executive function and social cognition (2006) · cites this paper as Sowell et al., 2001
In the citing paper
“protracted maturation of the prefrontal cortex (PFC) and parietal regions”
From Adolescent risk taking, impulsivity, and brain development: Implications for prevention (2010) · cites this paper as Sowell, Thompson, Tessner, & Toga, 2001
In the citing paper
“Previous studies have shown that right frontal cortical thinning occurs prior to left frontal cortical thinning in children 5--11 years of age (Sowell et al. 2001).”
From Puberty influences medial temporal lobe and cortical gray matter maturation differently in boys than girls matched for sexual maturity (2011) · cites this paper as Sowell et al. 2001
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Differences in Brain Network Topology Based on Alcohol Use History in Adolescents
Kirse, H. A., Bahrami, M., Lyday, R. G., Simpson, S. L., Peterson-Sockwell, H., Burdette, J. H., & Laurienti, P. J. (2023) · Brain Sciences · doi:10.3390/brainsci13121676 · Cited by 5
Gut Microbiome, Neuroinflammation, and Fetal Alcohol Spectrum Disorders: Insights from Rodent Models
Busayli, A. M., Xu, W., Raffah, G. A., & Chen, G. (2025) · Biology · doi:10.3390/biology14060593 · Cited by 5
“These changes are particularly pronounced in prefrontal regions, which continue developing into adolescence and thus have extended vulnerability windows [83].”
Xie, K., Jin, Z., Jin, D., Zhang, J., & Li, L. (2022) · NeuroImage · doi:10.1016/j.neuroimage.2022.119483 · Cited by 6
“One possible mechanism is that the smaller gray matter structure (volume/density) reflects fine synaptic pruning and cortical myelination during adolescence and early adulthood (Gogtay et al., 2004; Kanai et al., 2011; MacDonald et al., 2006; Soto, et al., 2014; Sowell et al., 2001), potentially leading to increased f…”
BackgroundPersistent Cranial Defects After Endoscopic Sagittal Synostosis Surgery
Wu, R. T., & Menard, R. M. (2022) · Journal of Craniofacial Surgery · doi:10.1097/scs.0000000000009044 · Cited by 5
High-resolution imaging in studies of alcohol effect on prenatal development
Mbolle, A. M., Thapa, S., Bukiya, A. N., & Jiang, H. (2023) · Advances in Drug and Alcohol Research · doi:10.3389/adar.2023.10790 · Cited by 5
Kiss, O., Goldstone, A., de Zambotti, M., Yüksel, D., Hasler, B. P., Franzen, P. L., Brown, S. A., Bellis, M. D. D., Nagel, B. J., Nooner, K. B., et al. (2023) · SLEEP · doi:10.1093/sleep/zsad113 · Cited by 5
Kiss, O., Qu, Z., Müller‐Oehring, E. M., Baker, F. C., & Mirzasoleiman, B. (2023) · Journal of Affective Disorders · doi:10.1016/j.jad.2023.10.158 · Cited by 6
“While many cortical synapses are eliminated (Gogtay et al., 2004; Huttenlocher and Dabholkar, 1997; Pfefferbaum et al., 1994; Sowell et al., 2001), there is an increase in white matter volume enhancing both the quantity and quality of connections among disparate brain components throughout…”
BackgroundStructural Brain Magnetic Resonance Imaging of Typically Developing Children and Adolescents
Giedd, J. N., Raznahan, A., Lee, N., Weddle, C., Liverpool, M., Stockman, M., Wells, E. M., CLASEN, L. S., Blumenthal, J. D., Lenroot, R., et al. (2011) · Cambridge University Press eBooks · doi:10.1017/cbo9781139042819.004 · Cited by 5
Sentencing of Adolescent Offenders in Victoria: A Review of Empirical Evidence and Practice
Chu, C. M., & Ogloff, J. R. P. (2011) · Psychiatry Psychology and Law · doi:10.1080/13218719.2011.565716 · Cited by 5
“However, studies have indicated that significant differences in decision-making capacities and brain development do exist between late adolescence and young adulthood (e.g., Gardner & Steinberg, 2005; Modecki, 2008; Sowell et al., 2001).”
BackgroundGuimarães, R. M., Schaufelberger, M. S., Santos, L. C., Duran, F., Menezes, P. R., Scazufca, M., Gouvea, M. T. V., & Busatto, G. F. (2012) · Brazilian Journal of Medical and Biological Research · doi:10.1590/s0100-879x2012007500046 · Cited by 5
“The most affected areas are thought to be the frontal lobe, the neocortex of the temporal lobe and the insula (3,7,11,12).”
BackgroundLei, H. C., Sang, N., Du, X., Qiu, J., Wei, D., & Chen, X. (2015) · 中国科学通报：英文版 · doi:10.1007/s11434-015-0910-0 · Cited by 5
“Therefore, we thought that the negative correlation between rGMV of PCC/PreCu and alerting scores might be related to the synaptic pruning and myelination observed during brain maturation that decreases gray matter volume [49–53].”
BackgroundBarlaam, F., Fortin, C., Vaugoyeau, M., Schmitz, C., & Assaiante, C. (2018) · Journal of Neurophysiology · doi:10.1152/jn.00637.2017 · Cited by 6
“…assessed by MRI studies encompass a reduction of cortical gray volume, due to synaptic pruning, and an enhancement of white matter density, due to axonal myelinization, during development (Gogtay et al. 2004; Paus 2005; Paus et al. 1999, 2001; Shaw et al. 2008; Sowell et al. 2001, 2002, 2003).”
BackgroundMeyer, E., Morawa, E., Nacak, Y., Rösch, J., Doerfler, A., Forster, C., & Erim, Y. (2020) · Frontiers in Psychiatry · doi:10.3389/fpsyt.2020.497100 · Cited by 5
“The underlying, wellregulated cellular maturational processes (36) might be disturbed by adverse childhood experiences and result in normative deviation in gray matter volume (see (37)).”
BackgroundParental Autonomy and Relatedness Support
Froiland, J. M. (2020) · Cambridge University Press eBooks · doi:10.1017/9781108235532.016 · Cited by 6
The Academic Support Index: A Tool for Contextualizing Student Data
Stevens, D. (2020) · Cambridge University Press eBooks · doi:10.1017/9781108235532.009 · Cited by 5
The Evolution of Human Brain and Body Growth Patterns
Bogin, B. A. (2007) · Evolution of Nervous Systems · doi:10.1016/b0-12-370878-8/00027-6 · Cited by 5
Desarrollo del sistema nervioso humano. Perspectiva general del estadio prenatal hasta 2013
Domínguez, P. R. (2016) · Revista Internacional de Psicología · doi:10.33670/18181023.v15i01.172 · Cited by 7
Development of Perceptual Inhibition in Adolescents—A Critical Period?
Introzzi, I. M., Richard’s, M. M., Aydmune, Y. S., Zamora, E. V., Stelzer, F., Coni, A. G., López-Ramón, M. F., & Navarro‐Pardo, E. (2021) · Symmetry · doi:10.3390/sym13030457 · Cited by 6
“As has been argued, if it is found a retrogression in performance in EF tasks, it is likely that this phenomenon can be explained by the excess of synaptogenesis that occur prior to the activation of the synaptic pruning mechanism that occurs after puberty [47,53,54].”
BackgroundIn the twilight zone: adolescent capacity in the criminal justice arena
Sarkar, S. P. (2011) · Advances in Psychiatric Treatment · doi:10.1192/apt.bp.108.006254 · Cited by 5
Brain Development and Executive Functioning
Knapp, K., & Morton, J. B. (2013) · Cited by 5
Working with the Campus Community
Siggins, L. D. (2010) · Wiley eBooks · doi:10.1002/9780470686836.ch8 · Cited by 5
Identifying and Serving Gifted and Talented Students
Olszewski‐Kubilius, P., Worrell, F. C., & Subotnik, R. F. (2020) · Cambridge University Press eBooks · doi:10.1017/9781108235532.034 · Cited by 4
Cornet, L. J. M., van der Laan, P. H., Nijman, H. L. I., Tollenaar, N., & de Kogel, C. H. (2016) · Criminal Justice and Behavior · doi:10.1177/0093854816643732 · Cited by 4
ADHD College Coaching: Potential Adverse Events
Parker, D. R., Sleeper-Triplett, J., Field, S. L., & Sawilowsky, S. S. (2018) · The ADHD Report · doi:10.1521/adhd.2018.26.2.10 · Cited by 4
Andrade, M. Â., & Raposo, A. (2020) · Journal of Experimental Child Psychology · doi:10.1016/j.jecp.2020.105044 · Cited by 6
Gallagher, V. T., Murthy, P., Stocks, J. K., Vesci, B., Mjaanes, J., Chen, Y. J., Breiter, H. C., LaBella, C. R., Herrold, A. A., & Reilly, J. L. (2021) · Neurotrauma Reports · doi:10.1089/neur.2021.0030 · Cited by 4
“develop throughout adolescence and into early adulthood.(10,11) Neuroimaging studies assessing subconcussive events”
BackgroundA Holistic Performance Measurement System For Entrepreneurship Education
Green, J. A., & Johnston, G. (2020) · ASEE Annual Conference & Exposition · doi:10.18260/1-2--3671 · Cited by 4
“The frontal lobe is the last part of the brain to develop, which means that even as people become fully capable in other areas, 18 to 22 year-olds cannot reason as well as older adults since maturation, particularly in the frontal lobes, has been shown to correlate with measures of cognitive functioning.(54)”
BackgroundAytemür, A., Lee, K.-H., & Levita, L. (2021) · Neuropsychologia · doi:10.1016/j.neuropsychologia.2021.107908 · Cited by 6
Goldner, J. S. (2009) · Loyola eCommons (Loyola University of Chicago) · Cited by 4
Metadata
- Authors
- Sowell, E. R., Thompson, P. M., Tessner, K. D., & Toga, A. W.
- Affiliations
- University of California, Los Angeles (US)
- Venue
- The Journal of Neuroscience
- Publisher
- Society for Neuroscience
- Published
- 2001-11-15
- Volume
- 21
- Issue
- 22
- Pages
- 8819-8829
- ISSN
- 0270-6474 (ISSN-L)
- 1529-2401
- PMC
- PMC6762261
- OpenAlex
- W2095621691
- Cited by
- 983
- References
- 34
- Citations by year
- 2026: 12 · 2025: 19 · 2024: 24 · 2023: 24 · 2022: 27 · 2021: 34 · 2020: 78 · 2019: 52 · 2018: 35 · 2017: 28 · 2016: 37 · 2015: 51 · 2014: 45 · 2013: 67 · 2012: 50
- FWCI
- 10.83
- Type
- journal article
- Language
- en
- Open access
- hybrid
- doi.org
- Licence
- Locations
- Journal of Neuroscience (publishedVersion, cc-by-nc-sa)
- PubMed Central (publishedVersion)
- PubMed (publishedVersion)
- Funders
- National Science Foundation (9601356)
- National Institutes of Health (5t32mh016381-20)
- National Institute of Mental Health (K01 MH 01733, 5-T32-MH16381, K01MH001733, P20 MH/DA52176)
- National Institute of Neurological Disorders and Stroke (NS38753, R01NS038753)
- National Center for Research Resources (P41RR013642, RR 13642, P41 RR13642)
- Topics
- Life Sciences › Neuroscience › Cognitive Neuroscience › Neural and Behavioral Psychology Studies
- Life Sciences › Neuroscience › Cognitive Neuroscience › Functional Brain Connectivity Studies
- Health Sciences › Medicine › Radiology, Nuclear Medicine and Imaging › Advanced Neuroimaging Techniques and Applications
- Keywords
- brain maturation, myelination, synaptic pruning, parietal cortex, executive function, developmental neuroimaging, children, adolescents and young adults
- MeSH terms
- Adolescent, Adult, Aging, Brain, Brain Mapping, Cell Count, Child, Female, Frontal Lobe, Humans, Image Processing, Computer-Assisted, Magnetic Resonance Imaging, Male, Occipital Lobe, Temporal Lobe
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