Cited by 302Advanced Neuroimaging Techniques and ApplicationsFunctional Brain Connectivity StudiesAdvanced MRI Techniques and Applications

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Age-Related Effects and Sex Differences in Gray Matter Density, Volume, Mass, and Cortical Thickness from Childhood to Young Adulthood

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Gennatas, Efstathios D., Avants, Brian B., Wolf, Daniel H., Satterthwaite, Theodore D., Ruparel, Kosha, Ciric, Rastko, Hakonarson, Hakon, Gur, Raquel E., Gur, Ruben C.·2017·The Journal of Neuroscience

DOI 10.1523/jneurosci.3550-16.2017PMC PMC5444192

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Abstract

Developmental structural neuroimaging studies in humans have long described decreases in gray matter volume (GMV) and cortical thickness (CT) during adolescence. Gray matter density (GMD), a measure often assumed to be highly related to volume, has not been systematically investigated in development. We used T1 imaging data collected on the Philadelphia Neurodevelopmental Cohort to study age-related effects and sex differences in four regional gray matter measures in 1189 youths ranging in age from 8 to 23 years. Custom T1 segmentation and a novel high-resolution gray matter parcellation were used to extract GMD, GMV, gray matter mass (GMM; defined as GMD × GMV), and CT from 1625 brain regions. Nonlinear models revealed that each modality exhibits unique age-related effects and sex differences. While GMV and CT generally decrease with age, GMD increases and shows the strongest age-related effects, while GMM shows a slight decline overall. Females have lower GMV but higher GMD than males throughout the brain. Our findings suggest that GMD is a prime phenotype for the assessment of brain development and likely cognition and that periadolescent gray matter loss may be less pronounced than previously thought. This work highlights the need for combined quantitative histological MRI studies. SIGNIFICANCE STATEMENT This study demonstrates that different MRI-derived gray matter measures show distinct age and sex effects and should not be considered equivalent but complementary. It is shown for the first time that gray matter density increases from childhood to young adulthood, in contrast with gray matter volume and cortical thickness, and that females, who are known to have lower gray matter volume than males, have higher density throughout the brain. A custom preprocessing pipeline and a novel high-resolution parcellation were created to analyze brain scans of 1189 youths collected as part of the Philadelphia Neurodevelopmental Cohort. A clear understanding of normal structural brain development is essential for the examination of brain–behavior relationships, the study of brain disease, and, ultimately, clinical applications of neuroimaging.

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Authors: Gennatas, E. D., Avants, B. B., Wolf, D. H., Satterthwaite, T. D., Ruparel, K., Ciric, R., Hakonarson, H., Gur, R. E., & Gur, R. C.
Affiliations: University of Pennsylvania (US)
Children's Hospital of Philadelphia (US)
ORCID: Gennatas, Efstathios D.
Avants, Brian B.
Wolf, Daniel H.
Satterthwaite, Theodore D.
Ruparel, Kosha
Hakonarson, Hakon
Gur, Raquel E.
Gur, Ruben C.
Venue: The Journal of Neuroscience
Publisher: Society for Neuroscience
Published: 2017-04-21
Volume: 37
Issue: 20
Pages: 5065-5073
ISSN: 0270-6474 (ISSN-L)
1529-2401
DOI: 10.1523/jneurosci.3550-16.2017
PMC: PMC5444192
OpenAlex: W2605712228
Cited by: 302
References: 37
Citations by year: 2026: 23 · 2025: 28 · 2024: 34 · 2023: 37 · 2022: 38 · 2021: 51 · 2020: 38 · 2019: 35 · 2018: 14 · 2017: 4
FWCI: 19.10
Type: journal article
Language: en
Open access: hybrid
doi.org
Licence: cc-by-nc-sa
creativecommons.org/licenses/by-nc-sa/4.0/ (vor, 210 d)
Locations: Journal of Neuroscience (publishedVersion, cc-by-nc-sa)
Europe PMC (PubMed Central) (publishedVersion)
PubMed Central (publishedVersion)
PubMed (publishedVersion)
Funders: National Institutes of Health (5r01mh107235-03, MH-089983, MH-096891, MH107235)
National Institute of Mental Health (RC2MH089983, P50MH096891, R01-MH-107235)
Topics: Health Sciences › Medicine › Radiology, Nuclear Medicine and Imaging › Advanced Neuroimaging Techniques and Applications
Life Sciences › Neuroscience › Cognitive Neuroscience › Functional Brain Connectivity Studies
Health Sciences › Medicine › Radiology, Nuclear Medicine and Imaging › Advanced MRI Techniques and Applications
Keywords: gray matter density, gray matter volume, cortical thickness, brain development, sex differences, age-related changes, adolescence, Philadelphia Neurodevelopmental Cohort, structural MRI
MeSH terms: Adolescent, Aging, Brain, Child, Female, Humans, Magnetic Resonance Imaging, Male, Organ Size, Sensitivity and Specificity, Sex Characteristics, Reproducibility of Results, Young Adult, Connectome, Gray Matter

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Age-Related Effects and Sex Differences in Gray Matter Density, Volume, Mass, and Cortical Thickness from Childhood to Young Adulthood

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