Cortical myelin profile variations in healthy aging brain: A T1w/T2w ratio study

Abstract

Demyelination is observed in both healthy aging and age-related neurodegenerative disorders. While the significance of myelin within the cortex is well acknowledged, studies focused on intracortical demyelination and depth-specific structural alterations in normal aging are lacking. Using the recently available Human Connectome Project Aging dataset, we investigated intracortical myelin in a normal aging population using the T1w/T2w ratio. To capture the fine changes across cortical depths, we employed a surface-based approach by constructing cortical profiles traveling perpendicularly through the cortical ribbon and sampling T1w/T2w values. The curvatures of T1w/T2w cortical profiles may be influenced by differences in local myeloarchitecture and other tissue properties, which are known to vary across cortical regions. To quantify the shape of these profiles, we parametrized the level of curvature using a nonlinearity index (NLI) that measures the deviation of the profile from a straight line. We showed that NLI exhibited a steep decline in aging that was independent of local cortical thinning. Further examination of the profiles revealed that lower T1w/T2w near the gray-white matter boundary and superficial cortical depths were major contributors to the apparent NLI variations with age. These findings suggest that demyelination and changes in other T1w/T2w related tissue properties in normal aging may be depth-specific and highlight the potential of NLI as a unique marker of microstructural alterations within the cerebral cortex.

Keywords: Aging; Cerebral cortex; Magnetic resonance imaging; Myelin sheath.

Fig. 1.

(a) Human Connectome Project in Aging (HCP-A) dataset age distribution separated by sex. The ages 55 to 85, which were used for examining typical aging in the current study, are highlighted; (b) Example T1w/T2w ratio image of one participant in axial view. The pial and white surface of the left hemisphere are marked red. The expanded 11 surfaces are drawn in yellow; (c) Cortical T1w/T2w profiles of selected regions of interest (ROIs) in the left hemisphere of one example participant. Regions are selected to show cortical profiles of varying nonlinearity index (NLI) levels. Mean T1w/T2w values at different cortical depth of each ROI are plotted as gray dots with the linear fitting line drawn in orange.

Fig. 2.

(a) T1w/T2w trajectories in example regions (significant quadratic age effect in left caudal middle frontal and significant linear age effect only in left precentral region) across age groups (for full results see Supplementary Table S2, Fig. S4). T1w/T2w ratio values are extracted from 70% cortical thickness depth from the pial surface for comparison with previous results (Grydeland et al., 2013). Linear and quadratic fitting lines and corresponding 95% confidence intervals are shown; (b) Scatter plot of regional nonlinearity index (NLI) values against the 70% depth T1w/T2w ratio across age groups, color coded by cortical area. Error bars show $\frac{1}{2}$ of each metrics’ standard deviation (SD) across the whole sample. The entire length of the error bar represents one SD range.

Fig. 3.

Average regional T1w/T2w ratio at 70% cortical depth (a) and nonlinearity index (NLI; b) across cortical regions of interest in the aging (ages 55-85) group.

Fig. 4.

Nonlinearity index (NLI; blue color scheme) and cortical thickness (CT; yellow color scheme) associations with age in the aging group, controlling for participants’ sex and body mass index. (a) Bar plots show the Pearson’s correlation coefficient r for the relationship with age in regional NLI and CT. The shade of the bar color reflects statistical significance after multiple comparison correction; (b) the slopes of linear fitting lines of standardized NLI and CT changes with age across cortical regions. Only those with significant relationships are shown.

Fig. 5.

(a) Scatter plots describing the relationship between the nonlinearity index (NLI), cortical thickness (CT) and age in an example region (left caudal anterior cingulate). Far right shows the partial plot of NLI against age controlling for participants’ sex, body mass index (BMI), and regional CT. Pearson’s correlation coefficient r and corrected p-values (p* ) are shown. Shaded areas indicate 95% confidence intervals; (b) The slopes of linear fitting lines of the NLI as a function of age, controlling for participants’ sex, body mass index (BMI), and regional CT. Color reflects slope values for significant partial correlations (e.g., darker blue indicates faster NLI decline with age controlling for covariates).

Fig. 6.

Differences in T1w/T2w ratio at specific depth behind profile nonlinearity index (NLI) variations. (a) Average T1w/T2w profiles of those aged 55-60 (black) and 80-85 (grey) shown for representative regions of interest (Fig. 1c) to highlight differences in profiles. Error bars indicate one standard deviation range; (b) Individual T1w/T2w profiles colored by participants’ age. To better visualize T1w/T2w profile variations with age, individual profiles are superimposed (with 30% transparency) and centered to mean T1w/T2w values at 50% cortical depth; (c) Percentage of age-related NLI variation that is explained by the mediation effect of average T1w/T2w values from specific surfaces (superficial/deep 20% depths, and at 50% depth). Variations due to participants’ sex, body mass index (BMI), and regional cortical thickness (CT) are controlled. Partial plots of depth-specific T1w/T2w values against age in example regions, indicated by black arrows in the brain surface graphs, are shown on the right. Pearson’s correlation coefficient r and corrected p-values (p* ) are included. Shaded areas in scatter plots indicate 95% confidence intervals.