Microstructural maturation of the human brain from childhood to adulthood
Introduction
Brain development is a complex process linked with behavioral, emotional, cognitive, and overall maturation that progresses throughout childhood, adolescence, and into adulthood. A thorough knowledge of structural brain development during adolescence is crucial for understanding the extensive cognitive and behavioral advances that occur during the same period, and for linking brain structure with brain function in both healthy and disease states. Postmortem studies can and have provided valuable insight into white matter development, demonstrating continued myelination of white matter tracts into the second and third decades of life (Yakovlev and Lecours, 1967, Benes, 1989). However, these studies are limited by the availability of young, previously healthy subjects.
Magnetic resonance imaging (MRI) is a powerful tool that has made it possible to investigate healthy brain development in vivo, demonstrating both global brain development, as well as more specific brain maturation. MRI has been used extensively to study brain and tissue volume changes, and has demonstrated that though total brain volume remains approximately constant after early childhood, the volume of the individual tissue components changes throughout the life span (Giedd et al., 1999, Good et al., 2001). Studies of cortical gray matter development have shown regional patterns of brain maturation, with distinct areas developing at different rates (Sowell et al., 2004, Lerch et al., 2006, Whitford et al., 2007).
Despite the fact that adolescence is considered a crucial period of brain rewiring, relatively little is known about the development of the white matter tracts that form this wiring or the deep gray matter structures that provide the relay stations. Previous studies using T1-weighted anatomical MRI have shown various brain white matter changes during adolescence, including an overall volume increase (Giedd et al., 1999), and increases of “white matter density” in the internal capsule and the left arcuate fasciculus (Paus et al., 1999). Diffusion tensor MRI (DTI) is a non-invasive tool that provides unique information about tissue microstructure, including indirect measures of myelination and axonal growth, and may be more sensitive than conventional imaging (Basser et al., 1994, Beaulieu, 2002, Le Bihan, 2003). DTI has demonstrated more widespread white matter and deep gray matter development with age during childhood and adolescence (Mukherjee et al., 2001, Schmithorst et al., 2002, Barnea-Goraly et al., 2005, Ben Bashat et al., 2005, Snook et al., 2005, Ashtari et al., 2007) than is observed on T1-weighted scans. However, previous DTI studies of adolescence were limited by small sample sizes (Morriss et al., 1999, Eluvathingal et al., 2007), limited brain regions analyzed (Ben Bashat et al., 2005, McLaughlin et al., 2007), narrow age ranges (Schneider et al., 2004, Snook et al., 2005), and/or assumptions of linear development (Schmithorst et al., 2002, Barnea-Goraly et al., 2005, Giorgio et al., 2008). Since nonlinear patterns of development have been shown in some cognitive abilities during adolescence (Kail, 1993, Luna et al., 2004), it is probable that DTI measures of specific brain white matter and deep gray matter structures may also deviate from a linear trajectory of development through adolescence.
Here, we use DTI to characterize the trajectory of microstructural brain development from childhood to adulthood, showing regionally specific changes in both timing and relative magnitude. We measured fractional anisotropy (FA), an indicator of white matter coherence and axonal organization, and mean diffusivity (MD), the average magnitude of water diffusion, to assess brain development in a large, age distributed sample. Subjects were 202 individuals ranging from 5 to 30 years, with no history of neurological/psychiatric disease or brain injury. Twenty distinct brain regions were analyzed, including major white matter tracts, subcortical white matter in gyri, and deep gray matter. Ten structures were examined using region-of-interest analysis, and ten structures were analyzed using diffusion tensor tractography, a novel method of virtually reconstructing and visualizing white matter tracts in vivo (Conturo et al., 1999, Jones et al., 1999, Mori et al., 1999, Basser et al., 2000). These two complementary methods provide a means of assessing three-dimensional white matter tracts, as well as structures such as deep gray matter and subcortical white matter in gyri, which cannot be examined using tractography.
Section snippets
Subjects
This study included 202 healthy subjects with no self-reported history of neurological or psychiatric disease or brain injury, aged 5.6 to 29.2 years (mean age ± standard deviation: 15.2 ± 6.1, 98 females, 104 males, 187 right-handed, 13 left-handed, 2 no preference). Subjects were approximately equally distributed across the age range, with a minimum of 3 males and 3 females for each year from 6 to 22 years. Health was verified by asking participants a series of questions to ensure there was no
FA increases with age
For almost all structures, an exponential curve best represented the cross-sectional age-related increases of FA; only the uncinate fasciculus showed a linear increase of FA. The increases occurred rapidly initially, then slowed and reached a plateau; for most structures, the plateau was reached during the late teens or twenties. FA increased significantly in 17 of 20 structures measured; however, no significant age-related changes were observed in the fornix, corona radiata or centrum
Discussion
Although DTI has demonstrated that much of brain development occurs during the first few years of life (Hermoye et al., 2006, Dubois et al., 2008, Provenzale et al., 2007), our results illustrate that this process continues well beyond infancy. Tractography and ROI analyses have provided direct evidence that maturation of brain white matter and deep gray matter is widespread throughout the brain and continues throughout adolescence and, in some structures, into the twenties.
The putative rate of
Acknowledgments
The authors thank the Networks of Centres of Excellence – Canadian Language and Literacy Research Network (CLLRNet) for operating grants, and the Alberta Heritage Foundation for Medical Research (AHFMR) (CB) and the Natural Sciences and Engineering Research Council (NSERC) (CL) for salary support. MRI infrastructure was provided by the Canada Foundation for Innovation, Alberta Science and Research Authority, AHFMR, and the University Hospital Foundation.
References (47)
- et al.
White matter development during late adolescence in healthy males: a cross-sectional diffusion tensor imaging study
Neuroimage
(2007) - et al.
MR diffusion tensor spectroscopy and imaging
Biophys. J.
(1994) - et al.
Comparing microstructural and macrostructural development of the cerebral cortex in premature newborns: diffusion tensor imaging versus cortical gyration
Neuroimage
(2005) - et al.
Assessment of the early organization and maturation of infants' cerebral white matter fiber bundles: a feasibility study using quantitative diffusion tensor imaging and tractography
Neuroimage
(2006) - et al.
Changes in white matter microstructure during adolescence
Neuroimage
(2008) - et al.
A voxel-based morphometric study of ageing in 465 normal adult human brains
Neuroimage
(2001) - et al.
Pediatric diffusion tensor imaging: normal database and observation of the white matter maturation in early childhood
Neuroimage
(2006) Processing time decreases globally at an exponential rate during childhood and adolescence
J. Exp. Child Psychol.
(1993)- et al.
Sexual dimorphism of brain developmental trajectories during childhood and adolescence
Neuroimage
(2007) - et al.
Mapping anatomical correlations across cerebral cortex (MACACC) using cortical thickness from MRI
Neuroimage
(2006)
Diffusion tensor imaging of the corpus callosum: a cross-sectional study across the lifespan
Int. J. Dev. Neurosci.
Diffusion tensor imaging of neurodevelopment in children and young adults
Neuroimage
Demyelination increases radial diffusivity in corpus callosum of mouse brain
Neuroimage
Mapping brain maturation
Trends Neurosci.
White matter development during childhood and adolescence: a cross-sectional diffusion tensor imaging study
Cereb. Cortex
In vivo fiber tractography using DT-MRI data
Magn. Reson. Med.
The basis of anisotropic water diffusion in the nervous system—a technical review
NMR Biomed.
Normal white matter development from infancy to adulthood: comparing diffusion tensor and high b value diffusion weighted MR images
J. Magn. Reson. Imaging
Myelination of cortical-hippocampal relays during late adolescence
Schizophr. Bull
White matter asymmetry in the human brain: a diffusion tensor MRI study
Cereb. Cortex
Occipito-temporal connections in the human brain
Brain
Tracking neuronal fiber pathways in the living human brain
Proc. Natl. Acad. Sci. U. S. A.
Asynchrony of the early maturation of white matter bundles in healthy infants: Quantitative landmarks revealed noninvasively by diffusion tensor imaging
Hum. Brain Mapp.
Cited by (1096)
Excitatory and inhibitory neurochemical markers of anxiety in young females
2024, Developmental Cognitive NeuroscienceWhite matter and literacy: A dynamic system in flux
2024, Developmental Cognitive NeuroscienceAdolescent neurocognitive development and decision-making abilities regarding gender-affirming care
2024, Developmental Cognitive NeuroscienceImproving Pediatric Normal Tissue Radiation Dose-Response Modeling in Children With Cancer: A PENTEC Initiative
2024, International Journal of Radiation Oncology Biology PhysicsAn intracellular isotropic diffusion signal is positively associated with pubertal development in white matter
2023, Developmental Cognitive NeuroscienceLateralization of the cerebral network of inhibition in children before and after cognitive training
2023, Developmental Cognitive Neuroscience
- 1
These authors contributed equally to this work.