Supplementary Fig. 3: Longitudinal and cross-sectional increase, sexual dimorphism and nonlinearities of the myelin marker during transitioning into adulthood. | Nature Neuroscience

Supplementary Fig. 3: Longitudinal and cross-sectional increase, sexual dimorphism and nonlinearities of the myelin marker during transitioning into adulthood.

From: Compulsivity and impulsivity traits linked to attenuated developmental frontostriatal myelination trajectories

Supplementary Fig. 3

(a) We show longitudinal increase of myelin-sensitive MT over study visits/time, from baseline to follow-up (mean (std) 1.3 (0.32) years). We observed more emphasized change of MT especially in cingulate cortex (max z-value voxel [z = 6.03, p = .004, voxelwise FDR, p < .001, clusterwise FWE] in posterior cingulate [MNI: 13 −48 30], n = 497/288 scans/subjects apply for panels a-d, 51.7% female) and lateral fronto-parieto-temporal gray matter regions. All statistical maps in panels a-d were obtained from one-sided Wald-tests using longitudinal sandwich estimator for Voxel-Based-Quantification analysis (VBQ). Here, surface projections for Z-maps (p < .05, voxelwise FDR) are shown, testing for positive main effect of study visit/time. (b) We show MT increases with higher age_mean of participants (14–25 years) in widespread cortical areas (max z-value [z = 7.33, p = .005, voxelwise FDR, p = .001 clusterwise FWE] in posterior superior temporal gyrus [63 −36 11]). Here age_mean refers to mean of each individual’s age over all visits of the longitudinal study. The effect of age_mean is independent from the effect of changes over time/visits and estimated separately, while the former is purely cross-sectional and the latter is purely longitudinal. We find that cross-sectional effects of age_mean are linked to local MT differences in fronto-parieto-temporal cortical gray matter. Notably, the observed differences of longitudinal and cross-sectional effects have been previously discussed in context of Simpson’s paradox (Kievit et al., 2013, Front Psychol). In addition to statistical processes (design, cohort differences, selective attrition, sampling bias, ground truth between/within-subject variability ratio) any image processing pipelines might affect between- and within-subjects differentially and result in regional sensitivity differences (Bernal-Rusiel et al., 2013, NeuroImage). Here, surface projections for z-maps (p < .05, FDR) are shown, one-sided Wald-test for positive effects of age_mean on MT. (c) Females have a significantly higher myelin-sensitive MT in bilateral insula (max z-value [z = 6.32, p = .012 voxelwise FDR, p = .001 clusterwise FWE] in left posterior insula [−43 −10 8]), amygdala, superior frontal gyrus, anterior and midcingulate cortex, middle frontal gyrus and lateral temporal cortex. We test for females over males in the same longitudinal model as shown in Figs. 1, 2. In contrast to cortical regions only very minor significant sex-related differences observed in cortical and striatal adjacent white matter regions (not shown). All presented z-maps are peak/voxel level corrected, p < .05 (FDR). Right panel shows a plot of myelin-sensitive MT in females/males with adjusted data (gray/black) and age-related models (red/orange, effect of interest: intercept, time/visit, age_mean, sex, sex by age_mean, that is assuming major trend is linear) in insular peak (for fixed other covariates, interactions etc.). X-axis: age refers to the chronological age of each individual at each visit (cf. supplemental experimental procedures). (d) Testing nonlinearities in terms of a deceleration of MT changes (that is an age-dependent reduction of individual slopes) during the developmental transition into adulthood. In particular, we observe minor tendencies to deceleration of within-subject MT growth with higher ages, in posterior cingulate (max z-value [z = 3.45, p = .0003 unc.] in right PCC [13 −48 30]) and orbitofrontal superficial white matter (z-value [z = 3.62, p = .0002 unc.] in right OFC [33 30 −13]) testing for a negative time/visit by age_mean interaction (for fixed covariates, time/visits, age_mean, sex etc.). Shown z-maps are peak/voxel level uncorrected, p < .005. Right panel shows a plot of peak cluster in orbitofrontal white matter MT with females/males data (gray/black) and full model predictions (red/orange, all predictors). X-axis: age refers to the chronological age of each individual at each visit. Left panel shows zoom on estimated longitudinal model predictions (red/orange for females/males) suggesting the age-related linear decreases of rate of within-subject change.

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