Developmental stages and sex differences of white matter and behavioral development through adolescence: A longitudinal diffusion tensor imaging (DTI) study

Abstract

White matter (WM) continues to mature through adolescence in parallel with gains in cognitive ability. To date, developmental changes in human WM microstructure have been inferred using analyses of cross-sectional or two time-point follow-up studies, limiting our understanding of individual developmental trajectories. The aims of the present longitudinal study were to characterize the timing of WM growth and investigate how sex and behavior are associated with different developmental trajectories. We utilized diffusion tensor imaging (DTI) in 128 individuals ages 8-28, who received annual scans for up to 5 years and completed motor and cognitive tasks. Flexible nonlinear growth curves indicated a hierarchical pattern of WM development. By late childhood, posterior cortical-subcortical connections were similar to adults. During adolescence, WM microstructure reached adult levels, including frontocortical, frontosubcortical and cerebellar connections. Later to mature in adulthood were major corticolimbic association tracts and connections at terminal gray matter sites in cortical and basal ganglia regions. These patterns may reflect adolescent maturation of frontal connectivity supporting cognitive abilities, particularly the protracted refinement of corticolimbic connectivity underlying cognition-emotion interactions. Sex and behavior also played a large role. Males showed continuous WM growth from childhood through early adulthood, whereas females mainly showed growth during mid-adolescence. Further, earlier WM growth in adolescence was associated with faster and more efficient responding and better inhibitory control whereas later growth in adulthood was associated with poorer performance, suggesting that the timing of WM growth is important for cognitive development.

Differential patterns of age‐related cortical and subcortical functional connectivity in 6‐to‐10 year old children: A connectome‐wide association study

“…Several previous studies have found gender differences in structural connectivity (Hänggi et al., 2010; Schmithorst, 2009; Simmonds, Hallquist, Asato, & Luna, 2014), however, a recent DTI study in the current cohort did not show gender differences (Muetzel et al., 2015). Gender differences have also previously been observed in neuroanatomical studies.…”

Individual differences in frontolimbic circuitry and anxiety emerge with adolescent changes in endocannabinoid signaling across species

“…Posthoc Student's t tests between genotypes within each age group showed enhanced projections from IL to BLA in adolescent [t(12) = 13.81; P < 0.0001] and adult [t(12) = 12.49; P < 0.0001] FAAH A/A mice relative to FAAH C/C mice but no differences in fiber density in preadolescent mice [t(12) = 0.56; P = 0.583] as a function of FAAH C385A genotype. Prior studies have shown that anxiety disorders peak during adolescence (1, 2) when there are dynamic changes in AEA levels (10, 11) that impact anxiety-related frontolimbic circuitry (28)(29)(30)(31). Moreover, we have shown that the FAAH A385 allele is associated with increased frontolimbic connectivity and lower anxiety in both mice and humans in adulthood (14).…”

Sex-specific association between infant diet and white matter integrity in 8-y-old children

“…Sex differences in white matter integrity as a function of infant diet have not been reported in young children who were term-born. However, sex differences in developmental trajectories of white matter in healthy adolescents, as well as sex differences of white matter in healthy adults, have been previously reported by DTI studies (28,33). Furthermore, a number of studies have shown that effects of infant diet on later growth and development are more prominent in male children.…”

“…Furthermore, sex differences were found in white matter growth profiles (28), but sex-specific evaluation of diet effects on healthy children (term-born) at school age has not been studied. In this study, we used DTI TBSS to evaluate brain white matter integrity in healthy 8-y-old children who were predominately BF or FF as infants.…”