Sex differences in white matter development during adolescence: A DTI study

Department of Biomedical Engineering, University of Cincinnati, Cincinnati, OH, United States. Electronic address: .
Brain research (Impact Factor: 2.84). 08/2012; 1478:1-15. DOI: 10.1016/j.brainres.2012.08.038
Source: PubMed


Adolescence is a complex transitional period in human development, composing physical maturation, cognitive and social behavioral changes. The objective of this study is to investigate sex differences in white matter development and the associations between intelligence and white matter microstructure in the adolescent brain using diffusion tensor imaging (DTI) and tract-based spatial statistics (TBSS). In a cohort of 16 typically-developing adolescents aged 13 to 17 years, longitudinal DTI data were recorded from each subject at two time points that were one year apart. We used TBSS to analyze the diffusion indices including fractional anisotropy (FA), mean diffusivity (MD), axial diffusivity (AD), and radial diffusivity (RD). Our results suggest that boys (13-18 years) continued to demonstrate white matter maturation, whereas girls appeared to reach mature levels earlier. In addition, we identified significant positive correlations between FA and full-scale intelligence quotient (IQ) in the right inferior fronto-occipital fasciculus when both sexes were looked at together. Only girls showed significant positive correlations between FA and verbal IQ in the left cortico-spinal tract and superior longitudinal fasciculus. The preliminary evidence presented in this study supports that boys and girls have different developmental trajectories in white matter microstructure.

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    • "During brain development, synaptic pruning and ongoing axonal myelination depend on both intrinsic genetic and extrinsic environmental factors (Emery 2010; Yeatman, Dougherty, Ben-Shachar, et al. 2012; Wandell and Yeatman 2013). These white matter maturation processes are quantified by changes of FA values and have been shown to be integral to the development of cognition (Paus et al. 1999; Schmithorst et al. 2005 Schmithorst et al. , 2011 Wang et al. 2012; Yeatman, Dougherty, Ben-Shachar, et al. 2012; Saygin et al. 2013; Myers et al. 2014). For the first time, this study provides insights on how FA-development rate differs between FHD− and FHD+ children along a tract instead of a merely global mean FA of the tract, and how it relates to the development of reading abilities. "
    [Show abstract] [Hide abstract] ABSTRACT: Developmental dyslexia is a neurodevelopmental disorder with a strong genetic basis. Previous studies observed white matter alterations in the left posterior brain regions in adults and school-age children with dyslexia. However, no study yet has examined the development of tract-specific white matter pathways from the pre-reading to the fluent reading stage in children at familial risk for dyslexia (FHD+) versus controls (FHD−). This study examined whitematter integrity at pre-reading, beginning, and fluent reading stages cross-sectionally (n = 78) and longitudinally (n = 45) using an automated fiber-tract quantification method. Our findings depict white matter alterations and atypical lateralization of the arcuate fasciculus at the pre-reading stage in FHD+ versus FHD− children. Moreover, we demonstrate faster white matter development in subsequent good versus poor readers and a positive association between whitemattermaturation and reading development using a longitudinal design. Additionally, the combination of white matter maturation, familial risk, and psychometric measures best predicted later reading abilities. Furthermore, within FHD+ children, subsequent good readers exhibited faster white matter development in the right superior longitudinal fasciculus compared with subsequent poor readers, suggesting a compensatory mechanism. Overall, our findings highlight the importance of white matter pathway maturation in the development of typical and atypical reading skills.
    Full-text · Article · Apr 2016 · Cerebral Cortex
    • "The girls also had higher LT in the stria terminalis and higher L1 in the inferior cerebellar peduncle and pontine crossing fibers than the male group. The earlier maturity of girls compared with boys was evident in longitudinal study of mid-adolescents that showed the regressed FA mean values to be highest at younger ages in girls than boys (Wang et al., 2012). A 4-year longitudinal study of healthy youth, 12–14 years old at initial DTI, found that in general girls showed earlier FA increases in motor-related tracts than boys, whereas boys showed greater changes in projection and association tracts, although these sex differences were not statistically related to pubertal status (Bava et al., 2011). "
    [Show abstract] [Hide abstract] ABSTRACT: Neurodevelopment continues through adolescence, with notable maturation of white matter tracts comprising regional fiber systems progressing at different rates. To identify factors that could contribute to regional differences in white matter microstructure development, large samples of youth spanning adolescence to young adulthood are essential to parse these factors. Recruitment of adequate samples generally relies on multi-site consortia but comes with the challenge of merging data acquired on different platforms. In the current study, diffusion tensor imaging (DTI) data were acquired on GE and Siemens systems through the National Consortium on Alcohol and NeuroDevelopment in Adolescence (NCANDA), a multi-site study designed to track the trajectories of regional brain development during a time of high risk for initiating alcohol consumption. This cross-sectional analysis reports baseline Tract-Based Spatial Statistic (TBSS) of regional fractional anisotropy (FA), mean diffusivity (MD), axial diffusivity (L1), and radial diffusivity (LT) from the five consortium sites on 671 adolescents who met no/low alcohol or drug consumption criteria and 132 adolescents with a history of exceeding consumption criteria. Harmonization of DTI metrics across manufacturers entailed the use of human-phantom data, acquired multiple times on each of three non-NCANDA participants at each site's MR system, to determine a manufacturer-specific correction factor. Application of the correction factor derived from human phantom data measured on MR systems from different manufacturers reduced the standard deviation of the DTI metrics for FA by almost a half, enabling harmonization of data that would have otherwise carried systematic error. Permutation testing supported the hypothesis of higher FA and lower diffusivity measures in older adolescents and indicated that, overall, the FA, MD, and L1 of the boys were higher than that of the girls, suggesting continued microstructural development notable in the boys. The contribution of demographic and clinical differences to DTI metrics was assessed with General Additive Models (GAM) testing for age, sex, and ethnicity differences in regional skeleton mean values. The results supported the primary study hypothesis that FA skeleton mean values in the no/low-drinking group were highest at different ages. When differences in intracranial volume were covaried, FA skeleton mean reached a maximum at younger ages in girls than boys and varied in magnitude with ethnicity. Our results, however, did not support the hypothesis that youth who exceeded exposure criteria would have lower FA or higher diffusivity measures than the no/low-drinking group; detecting the effects of excessive alcohol consumption during adolescence on DTI metrics may require longitudinal study.
    No preview · Article · Feb 2016 · NeuroImage
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    • "We also observed ageassociated FA increases and MD reductions in the corpus callosum and cerebellum, suggesting that structural refinement might also continue into adulthood. In the human adolescent brain, DTI revealed FA increases and MD decreases in white matter structures, which is consistent with increased myelination (Wang et al. 2012). Indeed, FA increases and MD decreases from early adolescence to early adulthood were observed in the corpus callosum and cerebellum of the rhesus monkey (Shi et al. 2013). "
    [Show abstract] [Hide abstract] ABSTRACT: Adolescence is characterized by considerable brain maturation that coincides with the development of adult behavior. Binge drinking is common during adolescence and can have deleterious effects on brain maturation because of the heightened neuroplasticity of the adolescent brain. Using an animal model of adolescent intermittent ethanol [AIE; 5.0 g/kg, intragastric, 20 percent EtOH w/v; 2 days on/2 days off from postnatal day (P)25 to P55], we assessed the adult brain structural volumes and integrity on P80 and P220 using diffusion tensor imaging (DTI). While we did not observe a long-term effect of AIE on structural volumes, AIE did reduce axial diffusivity (AD) in the cerebellum, hippocampus and neocortex. Radial diffusivity (RD) was reduced in the hippocampus and neocortex of AIE-treated animals. Prior AIE treatment did not affect fractional anisotropy (FA), but did lead to long-term reductions of mean diffusivity (MD) in both the cerebellum and corpus callosum. AIE resulted in increased anxiety-like behavior and diminished object recognition memory, the latter of which was positively correlated with DTI measures. Across aging, whole brain volumes increased, as did volumes of the corpus callosum and neocortex. This was accompanied by age-associated AD reductions in the cerebellum and neocortex as well as RD and MD reductions in the cerebellum. Further, we found that FA increased in both the cerebellum and corpus callosum as rats aged from P80 to P220. Thus, both age and AIE treatment caused long-term changes to brain structural integrity that could contribute to cognitive dysfunction. © 2015 Society for the Study of Addiction.
    Full-text · Article · Feb 2015 · Addiction Biology
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