Elsevier

Brain Research

Volume 1327, 23 April 2010, Pages 38-46
Brain Research

Research Report
Longitudinal characterization of white matter maturation during adolescence

https://doi.org/10.1016/j.brainres.2010.02.066Get rights and content

Abstract

Background. Late adolescence is comprised of considerable developmental transitions, though brain maturational changes during this period are subtle and difficult to quantitatively evaluate from standard brain imaging acquisitions. To date, primarily cross-sectional studies have characterized typical developmental changes during adolescence, but these processes need further description within a longitudinal framework. Method. To assess the developmental trajectory of typical white matter development, we examined 22 healthy adolescents with serial diffusion tensor images (DTI) collected at a mean age of 17.8 years and 16-months later. Diffusion parameters fractional anisotropy, and mean, radial, and axial diffusivity were subjected to whole-brain voxelwise time point comparisons using tract-based spatial statistics. Results. At follow-up, adolescents showed a significant change (≥ 153 contiguous voxels each at p < 0.01) in diffusion properties, including in bilateral superior longitudinal fasciculi, superior corona radiata, anterior thalamic radiations, and posterior limb of the internal capsule. Overall, correlations with cognitive performances suggested behavioral improvement corresponding with white matter changes. Conclusion. These longitudinal DTI findings support continued microstructural change in white matter during late adolescence, and suggest ongoing refinement of projection and association fibers into early adulthood.

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.

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