Research ReportLongitudinal characterization of white matter maturation during adolescence
Introduction
Late adolescence is comprised of extensive social, biological, and cognitive changes. Despite significant developmental transitions, brain maturation during this period is comparatively subtle. Conventional MRI has typically shown a global increase in white matter volume during adolescence (Giedd et al., 1999, Giedd, 2008), with a prominence of fronto-parietal development (Benes, 1989, Huttenlocher, 1990, Yakolev and Lecours, 1967; but see also Nagel et al., 2006). Concomitant decline in cortical volume and thickness occurs during this time, likely reflecting the selective pruning of superfluous neuronal connections (Tamnes et al., 2009), while axonal myelination of neurons continues through early adulthood (Giedd, 2004, Lenroot and Giedd, 2006, Sowell et al., 2002). These combined processes refine the adolescent brain and contribute to more efficient functioning and complex behaviors (Giedd, 2008).
These findings have been expanded with the use of diffusion tensor imaging (DTI), which allows in vivo access to the microstructure of brain pathways through gradients that measure the rate and direction of water molecule dispersion. Two common scalar measures used to infer tissue structure are fractional anisotropy (FA), or directionally-restricted diffusion, and mean diffusivity (MD), or the overall magnitude of diffusion. FA values range from 0 for isotropic (unrestricted) diffusion to 1 for anisotropic (restricted) diffusion. Water diffuses equally in all directions in mediums without structural barriers, as in cerebrospinal fluid (Cascio et al., 2007). This is in contrast to the myelinated fibers of white matter, where diffusion is restricted and greater parallel than perpendicular to fiber tracts. Thus, high FA values indicate greater anisotropy and highly organized and myelinated bundles, but are also influenced by axon size and density, pathway geometry, and fiber intersections (Beaulieu, 2002, Mamata et al., 2002, Shimony et al., 1999).
Cross-sectional studies have documented linear increases in FA and decreases in MD across typical adolescent development continuing through the second decade of life (Barnea-Goraly et al., 2005, Bonekamp et al., 2007, Giorgio et al., 2008, Mukherjee et al., 2001, Schmithorst et al., 2002). Recent evidence suggests an exponential trend in FA increase, with the most rapid change occurring from about 5 to 8 years of age and plateauing by the late teens to early twenties (Lebel et al., 2008). The growth in FA is associated with a decrease in diffusion perpendicular to fiber pathways, which suggests heightened bundle density or myelination. While decreases in radial diffusivity (RD) and to a lesser extent, axial diffusivity (AD) are reported during early development (Mukherjee et al., 2002, Qiu et al., 2008, Snook et al., 2005, Suzuki et al., 2003), there is an indication that AD increases may occur during adolescence (Ashtari et al., 2007). Some regions in the periphery of tracts show an increase in FA but do not exhibit corresponding increases in white matter density. This pattern may reflect ongoing strengthening of connections and increased organization and coherence (Barnea-Goraly et al., 2005).
A few cross-sectional studies and one longitudinal study have shown FA increases in young adolescents in bilateral superior longitudinal fasciculus, superior corona radiata, thalamic radiations, posterior internal capsule, corticospinal tract, arcuate fasciculus, superior and mid-temporal white matter, inferior parietal white matter, and the corpus callosum (Ashtari et al., 2007, Bonekamp et al., 2007, Giorgio et al., 2008, Giorgio et al., 2010, Tamnes et al., 2009). Cross-sectional evidence from diffusion kurtosis imaging has identified ongoing increases in FA and mean kurtosis in prefrontal areas in adolescents indicating growth in microstructural complexity (Falangola et al., 2008).
The ability to engage in complex cognitive processing in adolescence is associated with coordinated neurobiological mechanisms that include synaptic proliferation and pruning as well as axonal ensheathment (Huttenlocher, 1979). Although it is widely accepted that myelination correlates with efficient cognitive performance (Luna and Sweeney, 2001, Paus et al., 1999, Paus et al., 2001), the correspondence between white matter maturation and cognitive improvement has only recently been characterized with specificity. DTI has provided the basis for much of this work, demonstrating, for instance, that intellectual functioning in youth is associated with the development of white matter circuitry in bilateral frontal, occipito-parietal, and occipito-temporo-parietal regions (Schmithorst et al., 2005). In addition, the reading skills of children and adolescents improve with white matter changes in the internal capsule, corona radiata, and temporo-parietal regions (Beaulieu et al., 2005, Nagy et al., 2004, Niogi and McCandliss, 2006, Qiu et al., 2008), and greater left lateralization of the arcuate fasciculus fibers is associated with improved phonological processing and receptive vocabulary (Lebel and Beaulieu, 2009). Visuospatial working memory capacity is linked to a fronto-intraparietal network (Olesen et al., 2003), while better visuospatial construction and psychomotor performance are associated with high corpus callosum FA (Fryer et al., 2008). Faster response inhibition in children is associated with higher FA and lower perpendicular diffusivity in the right inferior frontal gyrus and presupplementary motor cortex (Madsen et al., 2009).
To date, studies of microstructural white matter changes have been primarily cross-sectional and therefore results offer limited conclusions. The current study employs a longitudinal framework to characterize maturational changes in white matter during a critical adolescent juncture, representing the transition into early adulthood (ages 16–21). Using DTI, youth were examined at two time-points across a 16-month period. Based on previous findings, we expected age-related changes in white matter within frontal and fronto–parietal tracts, thalamic pathways, the internal capsule, corticospinal tracts, and corpus callosum. Specifically, we hypothesized an increase in FA and a decrease in MD over time in these areas. To further explore anisotropic alterations, we examined RD and AD changes over time (Le Bihan et al., 2001). A secondary aim was to determine whether degree of white matter maturation during late adolescence would be linked to performance on measures of working memory, executive functioning, and learning and recall measured at the end of the white matter assessment interval.
Section snippets
Results
Paired samples t-tests, corrected with intensity and cluster-based thresholding (≥ 153 contiguous voxels with each showing the effect at p < 0.01), revealed 4 clusters in which adolescents showed significantly higher FA at Time 2 than at Time 1. FA increased over time in the right hemisphere in: the superior longitudinal fasciculus (SLF), superior corona radiata (SCR), anterior thalamic radiations, and posterior limb of the internal capsule (PLIC) (p < 0.005, see Fig. 1); no FA decreases were
Discussion
The current study provides a longitudinal characterization of microstructural white matter maturation during late adolescence. We found significant changes in anisotropy and diffusivity that reflect widespread alterations in fiber pathways during this developmental period. Our findings are consistent with previous cross-sectional studies that show increased anisotropy in the SLF, corona radiata, thalamic fibers, internal capsule, and IFOF with age (Barnea-Goraly et al., 2005, Giorgio et al.,
Participants
Twenty-two typically developing adolescents (15 males and 7 females; Time 1 mean age 17.8 ± 1.4 years, range 16.2–20.6) were recruited from local high schools as part of an adolescent brain imaging project (Tapert et al., 2007). Participants and their parents or legal guardians were screened with separate, private interviews to ascertain eligibility. Exclusionary criteria were: parental history of bipolar I or psychotic disorder; complicated or premature birth (< 33 weeks gestation); evidence of
Acknowledgments
This research was supported through grants from the National Institutes of Health (grant R01 DA021182 to S.F. Tapert and F32 DA024476 to S. Bava). We extend our appreciation to the participants and their families, as well as to Christine Burke, Diane Goldenberg, Amanda Gorlick, Tim McQueeny, Ann Park, Anthony Scarlett, Jennifer Winward, and Drs. Lawrence Frank and MJ Meloy whose support was vital to the completion of this research.
References (88)
- et al.
A model-based method for retrospective correction of geometric distortions in diffusion-weighted EPI
Neuroimage
(2002) - et al.
White matter development during late adolescence in healthy males: a cross-sectional diffusion tensor imaging study
Neuroimage
(2007) - et al.
Altered white matter microstructure in adolescent substance users
Psychiatry Res.
(2009) - et al.
Imaging brain connectivity in children with diverse reading ability
Neuroimage
(2005) - et al.
Diffusion tensor imaging in children and adolescents: reproducibility, hemispheric, and age-related differences
Neuroimage
(2007) - et al.
Diffusion tensor imaging: application to the study of the developing brain
J. Am. Acad. Child Adolesc. Psychiatry
(2007) Software for analysis and visualization of functional magnetic resonance neuroimages
Comput. Biomed Res.
(1996)- et al.
Microstructural integrity of the corpus callosum linked with neuropsychological performance in adolescents
Brain Cogn.
(2008) - et al.
Sex and performance level effects on brain activation during a verbal fluency task: a functional magnetic resonance imaging study
Cortex
(2009) The teen brain: insights from neuroimaging
J. Adolesc. Health
(2008)
Changes in white matter microstructure during adolescence
Neuroimage
Longitudinal changes in grey and white matter during adolescence
Neuroimage
Morphometric study of human cerebral cortex development
Neuropsychologia
White matter integrity in adolescents with histories of marijuana use and binge drinking
Neurotoxicol. Teratol.
Microstructural maturation of the human brain from childhood to adulthood
Neuroimage
Brain development in children and adolescents: insights from anatomical magnetic resonance imaging
Neurosci. Biobehav. Rev.
Sexual dimorphism of brain developmental trajectories during childhood and adolescence
Neuroimage
Stereotaxic white matter atlas based on diffusion tensor imaging in an ICBM template
Neuroimage
The development of corpus callosum microstructure and associations with bimanual task performance in healthy adolescents
Neuroimage
Left lateralized white matter microstructure accounts for individual differences in reading ability and disability
Neuropsychologia
Combined analysis of DTI and fMRI data reveals a joint maturation of white and grey matter in a fronto-parietal network
Brain Res. Cogn. Brain Res.
Maturation of white matter in the human brain: a review of magnetic resonance studies
Brain Res. Bull.
Sex differences in the growth of white matter during adolescence
Neuroimage
Diffusion tensor imaging of normal white matter maturation from late childhood to young adulthood: voxel-wise evaluation of mean diffusivity, fractional anisotropy, radial and axial diffusivities, and correlation with reading development
Neuroimage
Advances in functional and structural MR image analysis and implementation as FSL
Neuroimage
Tract-based spatial statistics: voxelwise analysis of multi-subject diffusion data
Neuroimage
Diffusion tensor imaging of neurodevelopment in children and young adults
Neuroimage
Problem solving, working memory, and motor correlates of association and commissural fiber bundles in normal aging: a quantitative fiber tracking study
Neuroimage
Manual for the ASEBA School-age Forms & Profiles
White matter development during childhood and adolescence: a cross-sectional diffusion tensor imaging study
Cereb. Cortex
The basis of anisotropic water diffusion in the nervous system — a technical review
NMR Biomed.
Beck Depression Inventory (BDI)
Myelination of cortical–hippocampal relays during late adolescence
Schizophr. Bull.
Psychometric evaluation of the Customary Drinking and Drug Use Record (CDDR): a measure of adolescent alcohol and drug involvement
J. Stud. Alcohol
Statistical Power Analysis for the Behavioral Sciences
Efficient, robust, nonlinear, and guaranteed positive definite diffusion tensor estimation
Sex differences in brain maturation during childhood and adolescence
Cereb. Cortex
Manual for the California Verbal Learning Test
Delis–Kaplan Executive Function System (D-KEFS)
Meta-analysis of experiments with matched groups or repeated measures designs
Psychol. Methods
Quantitative diffusion tensor tractography of association and projection fibers in normally developing children and adolescents
Cereb. Cortex
Age-related non-Gaussian diffusion patterns in the prefrontal brain
J. Magn. Reson. Imaging
Structural magnetic resonance imaging of the adolescent brain
Ann. N. Y. Acad. Sci.
Brain development during childhood and adolescence: a longitudinal MRI study
Nat. Neurosci.
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