Abstract
Over the last decade, non-invasive, high-resolution magnetic resonance imaging has allowed investigating normal brain development. However, much is still not known in this context, especially with regard to regional differences in brain morphology between genders. We conducted a large-scale study utilizing fully automated analysis-approaches, using high-resolution MR-imaging data from 200 normal children and aimed at providing reference data for future neuroimaging studies. Global and local aspects of normal development of gray and white matter volume were investigated as a function of age and gender while covarying for known nuisance variables. Global developmental patterns were apparent in both gray and white matter, with gray matter decreasing and white matter increasing significantly with age. Gray matter loss was most pronounced in the parietal lobes and least in the cingulate and in posterior temporal regions. White matter volume gains with age were almost uniform, with an accentuation of the pyramidal tract. Gender influences were detectable for both gray and white matter. Voxel-based analyses confirmed significant differences in brain morphology between genders, like a larger amygdala in boys or a larger caudate in girls. We could demonstrate profound influences of both age and gender on normal brain morphology, confirming and extending earlier studies. The knowledge of such influence allows for the consideration of age- and gender-effects in future pediatric neuroimaging studies and advances our understanding of normal and abnormal brain development.
Similar content being viewed by others
References
Amunts K, Schlaug G, Schleicher A, Steinmetz H, Dabringhaus A, Roland PE, Zilles K (1996) Asymmetry in the human motor cortex and handedness. Neuroimage 4:216–222
Ashburner J, Friston KJ (1997) Multimodal image coregistration and partitioning—a unified framework. Neuroimage 6:209–217
Ashburner J, Friston KJ (1999) Nonlinear spatial normalization using basis functions. Hum Brain Mapp 7:254–266
Ashburner J, Friston KJ (2000) Voxel-based morphometry—the methods. Neuroimage 11:805–821
Ball WS Jr, Dunn RS (1997) Computed tomography and magnetic resonance imaging. In: Ball WS Jr (ed) Pediatric neuroradiology, 1st edn. Lippincott Raven, Philadelphia, pp 17–35
Barkovich AJ (2000) Normal development of the neonatal and infant brain, skull, and spine. In: Barkovich AJ (ed) Pediatric neuroimaging, 3rd edn. Williams & Wilkins, Philadelphia, pp 13–69
Binder JR (2000) Functional MRI of the language system. In: Moonen CTW, Bandettini PA (eds) Functional MRI. Springer, Berlin Heidelberg New York, pp 407–419
Bourgeois JP (2001) Synaptogenesis in the neocortex of the newborn: the ultimate frontier for individuation? In: Nelson CA, Luciana M (eds) Handbook of developmental cognitive neuroscience, 1st edn. MIT Press, Cambridge, pp 23–34
Burgund ED, Kang HC, Kelly JE, Buckner RL, Snyder AZ, Petersen SE, Schlaggar BL (2002) The feasibility of a common stereotactic space for children and adults in fMRI studies of development. Neuroimage 17:184–200
Cameron JL (2001) Effects of sex hormones on brain development. In: Nelson CA, Luciana M (eds) Handbook of developmental cognitive neuroscience, 1st edn. MIT, Press Cambridge, pp 59–78
Carrow-Woolfolk E (1996) Oral and written language scales: written expression scale manual. American Guidance Service, Circle Pines
Casey BJ, Giedd JN, Thomas KM (2000) Structural and functional brain development and its relation to cognitive development. Biol Psychol 54:241–257
Castellanos FX, Lee PP, Sharp W, Jeffries NO, Greenstein DK, Clasen LS, Blumenthal JD, James RS, Ebens CL, Walter JM, Zijdenbos A, Evans AC, Giedd JN, Rapoport JL (2002) Developmental trajectories of brain volume abnormalities in children and adolescents with attention-deficit/hyperactivity disorder. JAMA 288:1740–1748
Caviness VS, Kennedy DN, Richelme C, Rademacher J, Filipek PA (1996) The human brain age 7–11 years: a volumetric analysis based on magnetic resonance images. Cereb Cortex 6:726–736
Chard DT, Parker GJ, Griffin CM, Thompson AJ, Miller DH (2002) The reproducibility and sensitivity of brain tissue volume measurements derived from an SPM-based segmentation methodology. J Magn Reson Imaging 15:259–267
Courchesne E, Plante E (1996) Measurement and analysis issues in neurodevelopmental magnetic resonance imaging. In: Thatcher RW, Lyon GR, Rumsey J, Krasnegor N (eds) Developmental neuroimaging: mapping the development of brain and behavior, 1st edn. Academic, San Diego, pp 43–49
Courchesne E, Chisum HJ, Townsend J, Cowles A, Covington J, Egaas B, Harwood M, Hinds S, Press GA (2000) Normal brain development and aging: quantitative analysis at in vivo MR imaging in healthy volunteers. Radiology 216:672–682
De Bellis MD, Keshavan MS, Beers SR, Hall J, Frustaci K, Masalehdan A, Noll J, Boring AM (2001) Sex differences in brain maturation during childhood and adolescence. Cereb Cortex 11:552–557
Durston S, Hulshoff Pol HE, Casey BJ, Giedd JN, Buitelaar JK, van Engeland H (2001) Anatomical MRI of the developing human brain: what have we learned? J Am Acad Child Adolesc Psychiatry 40:1012–1020
Eliez S, Reiss AL (2000) MRI neuroimaging of childhood psychiatric disorders: a selective review. J Child Psychol Psychiatry 41:679–694
Evans AC, Brain Development Cooperative Group (2006) The NIH MRI study of normal brain development. Neuroimage 30(1):184–202
Friston KJ, Holmes AP, Worsley KJ, Poline JP, Frith CD, Frackowiak RSJ (1995) Statistical parametric maps in functional imaging: a general linear approach. Hum Brain Mapp 2:189–210
Genovese CR, Lazar NA, Nichols T (2002) Thresholding of statistical maps in functional neuroimaging using the false discovery rate. Neuroimage 15:870–878
Giedd JN, Snell JW, Lange N, Rajapakse JC, Casey BJ, Kozuch PL, Vaituzis AC, Vauss YC, Hamburger SD, Kaysen D, Rapoport JL (1996) Quantitative magnetic resonance imaging of human brain development: ages 4–18. Cereb Cortex 6:551–560
Giedd JN, Blumenthal J, Jeffries NO, Castellanos FX, Liu H, Zijdenbos A, Paus T, Evans AC, Rapoport JL (1999) Brain development during childhood and adolescence: a longitudinal MRI study. Nat Neurosci 2:861–863
Gogtay N, Giedd J, Rapoport JL (2002) Brain development in healthy, hyperactive, and psychotic children. Arch Neurol 59:1244–1248
Gogtay N, Giedd JN, Lusk L, Hayashi KM, Greenstein D, Vaituzis AC, Nugent TFR, Herman DH, Clasen LS, Toga AW, Rapoport JL, Thompson PM (2004) Dynamic mapping of human cortical development during childhood through early adulthood. Proc Natl Acad Sci USA 101:8174–8179
Good CD, Johnsrude I, Ashburner J, Henson RN, Friston KJ, Frackowiak RS (2001) Cerebral asymmetry and the effects of sex and handedness on brain structure: a voxel-based morphometric analysis of 465 normal adult human brains. Neuroimage 14:685–700
Harasty J, Double KL, Halliday GM, Kril JJ, McRitchie DA (1997) Language-associated cortical regions are proportionally larger in the female brain. Arch Neurol 54:171–176
Holland SK, Plante E, Weber Byars A, Strawsburg RH, Schmithorst VJ, Ball WS Jr (2001) Normal fMRI brain activation patterns in children performing a verb generation task. Neuroimage 14:837–843
Huttenlocher PR (1990) Morphometric study of human cerebral cortex development. Neuropsychologia 28:517–527
Lange N, Giedd JN, Castellanos FX, Vaituzis AC, Rapoport JL (1997) Variability of human brain structure size: ages 4–20 years. Psychiatry Res 4:1–12
Patwardhan AJ, Brown WE, Bender BG, Linden MG, Eliez S, Reiss AL (2002) Reduced size of the amygdala in individuals with 47, XXY and 47, XXX karyotypes. Am J Med Genet 114:93–98
Paus T, Zijdenbos A, Worsley K, Collins DL, Blumenthal J, Giedd JN, Rapoport JL, Evans AC (1999) Structural maturation of neural pathways in children and adolescents: in vivo study. Science 283:1908–1911
Pfefferbaum A, Mathalon DH, Sullivan EV, Rawles JM, Zipursky RB, Lim KO (1994) A quantitative magnetic resonance imaging study of changes in brain morphology from infancy to late adulthood. Arch Neurol 51:874–887
Pfluger T, Weil S, Weis S, Vollmar C, Heiss D, Egger J, Scheck R, Hahn K (1999) Normative volumetric data of the developing hippocampus in children based on magnetic resonance imaging. Epilepsia 40:414–423
Plante E, Schmithorst VJ, Holland SK, Byars AW (2006) Sex differences in the activation of language cortex during childhood. Neuropsychologia 44:1210–1221
Reiss AL, Abrams MT, Singer HS, Ross JL, Denckla MB (1996) Brain development, gender and IQ in children. A volumetric imaging study. Brain 119:1763–1774
Rivkin MJ (2000) Developmental neuroimaging of children using magnetic resonance techniques. Ment Retard Dev Disabil Res Rev 6:68–80
Rorden C, Brett M (2000) Stereotaxic display of brain lesions. Behav Neurol 12:191–200
Sampaio RC, Truwitt CL (2001) Myelination in the developing brain. In: Nelson CA, Luciana M (eds) Handbook of developmental cognitive neuroscience. MIT Press, Cambridge, pp 35–44
Schmithorst VJ, Wilke M, Dardzinski BJ, Holland SK (2002) Correlation of white matter diffusivity and anisotropy with age during childhood and adolescence: a cross-sectional diffusion-tensor MR imaging study. Radiology 222:212–218
Schmithorst VJ, Holland SK, Plante E (2006) Cognitive modules utilized for narrative comprehension in children: a functional magnetic resonance imaging study. Neuroimage 29:254–266
Sowell ER, Peterson BS, Thompson PM, Welcome SE, Henkenius AL, Toga AW (2003) Mapping cortical change across the human life span. Nat Neurosci 6:309–315
Sowell ER, Thompson PM, Holmes CJ, Batth R, Jernigan TL, Toga AW (1999) Localizing age-related changes in brain structure between childhood and adolescence using statistical parametric mapping. Neuroimage 9:587–597
Staudt M, Schropp C, Staudt F, Obletter N, Bise K, Breit A, Weinmann HM (1994) MRI assessment of myelination: an age standardization. Pediatr Radiol 24:122–127
Thompson PM, Cannon TD, Narr KL, van Erp T, Poutanen VP, Huttunen M, Lonnqvist J, Standertskjold-Nordenstam CG, Kaprio J, Khaledy M, Dail R, Zoumalan CI, Toga AW (2001) Genetic influences on brain structure. Nat Neurosci 4:1253–1258
Ugurbil K, Garwood M, Ellermann J, Hendrich K, Hinke R, Hu X, Kim SG, Menon R, Merkle H, Ogawa S (1993) Imaging at high magnetic fields: initial experiences at 4 T. Magn Reson Q 9:259–277
Wechsler D (1989) Manual for the Wechsler preschool and primary scale of intelligence, rev. The Psychological Corporation, San Antonio
Wechsler D (1991) Manual for the Wechsler intelligence scale for children, 3rd edn. The Psychological Corporation, San Antonio
Wechsler D (1997) Manual for the Wechsler adult intelligence scale-III. The Psychological Corporation, New York
White T, O’Leary D, Magnotta V, Arndt S, Flaum M, Andreasen NC (2001) Anatomic and functional variability: the effects of filter size in group fMRI data analysis. Neuroimage 13:577–588
Wilke M, Kaufmann C, Grabner A, Pütz B, Wetter TC, Auer DP (2001) Gray matter-changes and correlates of disease severity in schizophrenia: a statistical parametric mapping study. Neuroimage 13:814–824
Wilke M, Schmithorst VJ, Holland SK (2002) Assessment of spatial normalization of whole-brain MR-images in children. Hum Brain Mapp 17:48–60
Wilke M, Schmithorst VJ, Holland SK (2003a) Normative pediatric brain data for spatial normalization and segmentation differs from standard adult data. Magn Res Med 50:749–757
Wilke M, Sohn JH, Weber Byars AM, Holland SK (2003b) Bright spots: correlations of gray matter volume with IQ in a normal pediatric population. Neuroimage 20:202–215
Wright IC, Ellison ZR, Sharma T, Friston KJ, Murray RM, McGuire PK (1999) Mapping of grey matter changes in schizophrenia. Schizophr Res 35:1–14
Acknowledgments
We would like to thank Anna W. Byars, PhD, and Richard H. Strawsburg, MD, for performing the neuropsychological testing and the neurological examination. We also thank William S. Ball, Jr., MD, for reading the anatomical scans for structural abnormalities. Finally, our gratitude belongs to the large number of subjects and families: without their enthusiastic participation, this study would not have been possible. This work was funded in part by a grant from the National Institutes of Child Health and Human Development, RO1-HD38578-01.
Author information
Authors and Affiliations
Corresponding author
Rights and permissions
About this article
Cite this article
Wilke, M., Krägeloh-Mann, I. & Holland, S.K. Global and local development of gray and white matter volume in normal children and adolescents. Exp Brain Res 178, 296–307 (2007). https://doi.org/10.1007/s00221-006-0732-z
Received:
Accepted:
Published:
Issue Date:
DOI: https://doi.org/10.1007/s00221-006-0732-z