Regional growth trajectories of cortical myelination in adolescents and young adults: longitudinal validation and functional correlates.

The Multiple Mediation Model examined which of two regional myelin scores had a significantly stronger indirect effect (i.e., accounted for greater variance) on the correlation cM between age and the Grooved Pegboard Test scores (total time in seconds). Path cM represents the direct effect and the paths a1b1, and a2b2 reflect the indirect effects. The model was applied separately with respect to the dominant and non-dominant hand.

Cortical myelin development hypothesis for NCANDA adolescents and HCP young adults. The developmental trajectories of the raw (left) and the normalized (right) myelin content are displayed for primary motor cortex (red), mean over the entire cortex (yellow) and midcingulate cortex (blue). The predicted variances are shown as shaded error bounds with corresponding colors. Between the raw and normalized myelin content, the deviation from the mean of the entire cortex is preserved in primary motor and midcingulate cortices. The age-dependent inter- subject variance is now much smaller for the normalized myelin content.

Cross-sectional myelin development patterns for adolescents (NCANDA) and young adults (HCP). (A) For both cohorts, age-related differences are computed from the normalized myelin content (i.e., the change in myelin content relative to the mean over the entire cortex) by applying a general linear model that views age as a predictor and sex, ethnicity, svol, and site (omitted in HCP) as confounding factors. Each value is displayed on the averaged (inflated) brain surface of the corresponding cohort with the boundaries of the HCP multimodal parcellation atlas (MMP 1.0) overlaid. The vertex-wise (B) and regional (C) P values of those slopes are FWER corrected via permutation testing (iterations: 5000). They are grayed out if non-significant (i.e., P ≥ 0.01), have a negative sign (i.e., βage < 0) if the gain in myelin density with respect to age was smaller and positive (i.e., βage > 0) if the gain was larger than the entire cortex.

Combined cross-sectional myelin development plots of adolescents (NCANDA) and young adults (HCP). Plots of the normalized myelin content for areas 4, 23c, and p24' are shown for left [L] and right [R] hemispheres. In each plot, blue circles represent male and red represent female adolescents; green diamonds represent male and yellow represent female young adults; and the fits of the general liner model +/− SD (standard deviation) are displayed in gray lines. The horizontal axes represent age in years and the vertical axes represent the myelin content (left for adolescents, and right for young adults). Left vertical axis is normalized myelin content for adolescents, and the right is for young adults. To improve visualization, the offset of the vertical axis for young adults is adjusted to match with adolescents while the scale is the same. Furthermore, the age of the HCP samples was perturbed by a random number generator (range: [−0.5 0.5]). Note, the regression is separately performed for each data set so that neither adjusting the offset nor perturbing the age would result in significantly different findings.

The normalized myelin content is displayed on the averaged (inflated) brain surface for different adolescent age groups. Blue/black colors represent lightly myelinated regions and yellow/red colors show heavily myelinated regions. The images confirm our previous finding, i.e., they show greater gains in normalized myelin content in area 4 and smaller gains in area 23c and p24.

Correlation tests for the normalized myelin content and Grooved Pegboard Test scores (total time in seconds) for NCANDA adolescents. Shorter performance time represents better performance. Plots between the normalized myelin content and grooved pegboard time performed by dominant (top row) and non-dominant (bottom row) hands are shown for areas 4, 23c, and p24'. Both myelin content and pegboard scores are the residuals with respect to age. Blue circles represent male and red represent female adolescents; the fits of the general linear regression are in gray.

Longitudinal normalized myelin content for adolescents (NCANDA) based on the longitudinal approach. Longitudinal plots of areas 4, 23c, and p24' are shown for left [L] and right [R] hemispheres. In each plot, blue circles stand for male and red for female adolescents. Visits are connected for each subject and the fits of the linear mixed effects model with +/− 1 and 2 SD are drawn in gray lines. The horizontal axes represent age (in years) and vertical axes the normalized myelin content.