Abstract
Sleep spindles, bursts of electroencephalogram (EEG) activity in the sigma-frequency (11-16 Hz) range, may be biomarkers of cortical development. Studies capturing the transition to adolescence are needed to delineate age-, sex- and pubertal-related changes in sleep spindles at the population-level. We analyzed the sleep EEG of 572 subjects 6-21y (48% female) and 332 subjects 5-12y (46% female) followed-up at 12-22y. From 6y to 21y, spindle density (p-quadratic=0.019) and fast (12-16 Hz) spindle percent (p-quadratic=0.016) showed inverted U-shaped trajectories, with plateaus after 15y and 19y, respectively. Spindle frequency increased (p-linear<0.001), while spindle power decreased (p-linear<0.001) from 6y to 21y. The trajectories of spindle density, frequency and fast spindle percent diverged between females and males, in whom density plateaued by 14y, fast spindle percent by 16y, and frequency by 18y, while fast spindle percent and spindle frequency continued to increase until 21y in females. Males experienced a longitudinal increase in spindle density 31% greater than females by 12-14y (p=0.006). Females experienced an increase in spindle frequency and fast spindle percent 2% and 41% greater, respectively, than males by 18-22y (both p=0.004), while males experienced a 14% greater decline in spindle power by 18-22y (p=0.018). Less mature adolescents (86% male) experienced a longitudinal increase in spindle density 36% greater than mature adolescents by 12-14y (p=0.002). Overall, males experience greater maturational changes in spindle density in the transition to adolescence, driven by later pubertal development, and sex differences become prominent in early adulthood when females have greater spindle power, frequency and fast spindle percent.
Significance Statement
Age-related changes in sleep spindles reflect maturation of the thalamocortical network. We provide evidence that spindle metrics follow distinct developmental trajectories from each other and previously described sleep oscillations shown to index brain maturation in the transition to adolescence. Importantly, we report novel data regarding the association between spindle activity and pubertal development. Specifically, we found that less mature adolescents (86% male) experienced a greater increase in spindle density in the transition to ages 12-14y, while more mature adolescents (75% female) experienced a greater decline in sigma/spindle power by the same age. These data suggest that females, who enter pubertal development earlier than males, may also begin brain maturational processes in the thalamocortical network at an earlier stage than males.
Footnotes
A.R., F.H., S.L.C., A.N.V., D.L., E.O.B. and J.F.M. declare they have no competing or potential conflicts of interest. J.F. discloses ownership of Biosoft Studio (Hershey, PA), which developed and maintains sleepFFT software. M.Y. discloses having developed, and having a patent on, the spindle analysis technology, which has been licensed to Cerebra Health (Winnipeg, Manitoba, Canada), and he is a shareholder and receives royalties and consultation fees from Cerebra Health.
Research reported in this publication was supported by the National Institute of Mental Health (NIMH), National Heart, Lung, and Blood Institute (NHLBI) and the National Center for Advancing Translational Sciences (NCATS) of the National Institutes of Health (NIH) under Awards Number R01MH118308, R01HL136587, R01HL97165, R01HL63772 and UL1TR000127. The content is solely the responsibility of the authors and does not necessarily represent the official views of the NIH.
This is an open-access article distributed under the terms of the Creative Commons Attribution 4.0 International license, which permits unrestricted use, distribution and reproduction in any medium provided that the original work is properly attributed.
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