PT - JOURNAL ARTICLE AU - Ricci, Anna AU - He, Fan AU - Calhoun, Susan L. AU - Fang, Jidong AU - Vgontzas, Alexandros N. AU - Liao, Duanping AU - Bixler, Edward O. AU - Younes, Magdy AU - Fernandez-Mendoza, Julio TI - Sex and Pubertal Differences in the Maturational Trajectories of Sleep Spindles in the Transition from Childhood to Adolescence: A Population-based Study AID - 10.1523/ENEURO.0257-21.2021 DP - 2021 Jun 21 TA - eneuro PG - ENEURO.0257-21.2021 4099 - http://www.eneuro.org/content/early/2021/06/21/ENEURO.0257-21.2021.short 4100 - http://www.eneuro.org/content/early/2021/06/21/ENEURO.0257-21.2021.full AB - 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 StatementAge-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.