The mediating role of cortical thickness and gray matter volume on sleep slow-wave activity during adolescence

Abstract

During the course of adolescence, reductions occur in cortical thickness and gray matter (GM) volume, along with a 65% reduction in slow-wave (delta) activity during sleep (SWA) but empirical data linking these structural brain and functional sleep differences, is lacking. Here, we investigated specifically whether age-related differences in cortical thickness and GM volume and cortical thickness accounted for the typical age-related difference in slow-wave (delta) activity (SWA) during sleep. 132 healthy participants (age 12-21 years) from the National Consortium on Alcohol and NeuroDevelopment in Adolescence study were included in this cross-sectional analysis of baseline polysomnographic, electroencephalographic, and magnetic resonance imaging data. By applying mediation models, we identified a large, direct effect of age on SWA in adolescents, which explained 45% of the variance in ultra-SWA (0.3-1 Hz) and 52% of the variance in delta-SWA (1 to <4 Hz), where SWA was lower in older adolescents, as has been reported previously. In addition, we provide evidence that the structure of several, predominantly frontal, and parietal brain regions, partially mediated this direct age effect, models including measures of brain structure explained an additional 3-9% of the variance in ultra-SWA and 4-5% of the variance in delta-SWA, with no differences between sexes. Replacing age with pubertal status in models produced similar results. As reductions in GM volume and cortical thickness likely indicate synaptic pruning and myelination, these results suggest that diminished SWA in older, more mature adolescents may largely be driven by such processes within a number of frontal and parietal brain regions.

Keywords: Adolescence; Cortical development; Sleep; Slow-wave activity.

Figure 1

A graphical representation of how brain structure may mediate the relationship between age and SWA. We posit that the total effect of age on SWA (path c) is partly driven by the indirect effect of age on cortical thickness and gray matter (GM) volume. These indirect effects of age are calculated by a₁*b₁ (cortical thickness) and a₂*b₂ (GM volume). Finally, path c’ depicts the remaining direct effect of age on SWA, that is not mediated by brain structure.

Figure 2

Brainstorm (Tadel, Baillet, Mosher, Pantazis, & Leahy, 2011) was used to create the embedded figure, which depicts each of these cortical regions (from the Desikan-Killiany cortical atlas (Desikan et al., 2006)) on an inflated, average, brain template. SFG= Superior frontal gyrus, PCL= paracentral lobule, IPC= inferior parietal cortex, PC= precuneus, LOC= lateral orbital cortex and FG= fusiform gyrus.

Figure 3

Depiction of the relationship between age and cortical thickness (CT) for the brain regions where structure was found to significantly mediate the age-SWA relationship. Cortical thickness values presented in the figures are residuals, after regressing the effects of site and svol. Blue and red circles represent the cortical thickness of left and right hemispheres, respectively, for each region. SFG= Superior frontal gyrus, PCL= paracentral lobule, IPC= inferior parietal cortex, PC= precuneus, LOC= lateral orbital cortex and FG= fusiform gyrus.

Figure 4

Depiction of the relationship between age and GM volume (GMV) for the brain regions where structure was found to significantly mediate the age-SWA relationship. GM volume values presented in the figures are residuals, after regressing the effects of site and svol. Blue and red circles represent the GM volume of left and right hemispheres, respectively, for each region. SFG= Superior frontal gyrus, PCL= paracentral lobule, IPC= inferior parietal cortex, PC= precuneus, LOC= lateral orbital cortex and FG= fusiform gyrus.

Figure 5

Figures depicting the significant relationships between log transformed SWA averaged across electrodes C3 and C4 (residuals after regressing site) and a) IPC cortical thickness (residuals after regressing site and svol) and b) PC gray matter (GM) volume (residuals after regressing site and svol). These figures depict the typical associations between cortical thickness/GM and SWA for the regions where a significant mediating effect was identified.

Figure 6

The significant association between age and log transformed SWA for: a) ultra-SWA (0.3 to 1Hz) and b) delta-SWA (1Hz to <4Hz). Values are residuals after controlling for site.