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Age-Related Effects and Sex Differences in Gray Matter Density, Volume, Mass, and Cortical Thickness from Childhood to Young Adulthood.
J Neurosci. 2017 05 17; 37(20):5065-5073.JN

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.

Authors+Show Affiliations

Brain Behavior Laboratory, Department of Psychiatry, and egenn@upenn.edu.Penn Image Computing and Science Laboratory, Department of Radiology, University of Pennsylvania, Philadelphia, Pennsylvania 19104, and.Brain Behavior Laboratory, Department of Psychiatry, and.Brain Behavior Laboratory, Department of Psychiatry, and.Brain Behavior Laboratory, Department of Psychiatry, and.Brain Behavior Laboratory, Department of Psychiatry, and.Center for Applied Genomics, Children's Hospital of Philadelphia, Philadelphia, Pennsylvania 19104.Brain Behavior Laboratory, Department of Psychiatry, and.Brain Behavior Laboratory, Department of Psychiatry, and.

Pub Type(s)

Journal Article
Research Support, N.I.H., Extramural
Research Support, Non-U.S. Gov't

Language

eng

PubMed ID

28432144

Citation

Gennatas, Efstathios D., et al. "Age-Related Effects and Sex Differences in Gray Matter Density, Volume, Mass, and Cortical Thickness From Childhood to Young Adulthood." The Journal of Neuroscience : the Official Journal of the Society for Neuroscience, vol. 37, no. 20, 2017, pp. 5065-5073.
Gennatas ED, Avants BB, Wolf DH, et al. Age-Related Effects and Sex Differences in Gray Matter Density, Volume, Mass, and Cortical Thickness from Childhood to Young Adulthood. J Neurosci. 2017;37(20):5065-5073.
Gennatas, E. D., Avants, B. B., Wolf, D. H., Satterthwaite, T. D., Ruparel, K., Ciric, R., Hakonarson, H., Gur, R. E., & Gur, R. C. (2017). Age-Related Effects and Sex Differences in Gray Matter Density, Volume, Mass, and Cortical Thickness from Childhood to Young Adulthood. The Journal of Neuroscience : the Official Journal of the Society for Neuroscience, 37(20), 5065-5073. https://doi.org/10.1523/JNEUROSCI.3550-16.2017
Gennatas ED, et al. Age-Related Effects and Sex Differences in Gray Matter Density, Volume, Mass, and Cortical Thickness From Childhood to Young Adulthood. J Neurosci. 2017 05 17;37(20):5065-5073. PubMed PMID: 28432144.
* Article titles in AMA citation format should be in sentence-case
TY - JOUR T1 - Age-Related Effects and Sex Differences in Gray Matter Density, Volume, Mass, and Cortical Thickness from Childhood to Young Adulthood. AU - Gennatas,Efstathios D, AU - Avants,Brian B, AU - Wolf,Daniel H, AU - Satterthwaite,Theodore D, AU - Ruparel,Kosha, AU - Ciric,Rastko, AU - Hakonarson,Hakon, AU - Gur,Raquel E, AU - Gur,Ruben C, Y1 - 2017/04/21/ PY - 2016/11/17/received PY - 2017/03/21/revised PY - 2017/04/12/accepted PY - 2017/4/23/pubmed PY - 2017/8/19/medline PY - 2017/4/23/entrez KW - MRI KW - T1-weighted imaging KW - brain structure KW - cortical thickness KW - gray matter density KW - gray matter volume SP - 5065 EP - 5073 JF - The Journal of neuroscience : the official journal of the Society for Neuroscience JO - J. Neurosci. VL - 37 IS - 20 N2 - 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. SN - 1529-2401 UR - https://wwww.unboundmedicine.com/medline/citation/28432144/Age_Related_Effects_and_Sex_Differences_in_Gray_Matter_Density_Volume_Mass_and_Cortical_Thickness_from_Childhood_to_Young_Adulthood_ L2 - http://www.jneurosci.org/cgi/pmidlookup?view=long&pmid=28432144 DB - PRIME DP - Unbound Medicine ER -