Association of Novel EEG Biomarkers of Sleep Depth and Cortical Arousability with Cardiac Autonomic Modulation in Adolescents.

Abstract

Study objectives: To examine the developmental association of the odds ratio product (ORP), an electroencephalographic measure of sleep depth, during non-rapid eye movement (NREM) sleep with 24-hour heart rate variability (HRV), an electrocardiographic measure of cardiac autonomic modulation (CAM), in the transition to adolescence.

Methods: Leveraging data from the Penn State Child Cohort, we performed longitudinal analyses on 313 children (median [Md] age 9 years) followed-up after Md=7.4y and cross-sectional analyses on 344 adolescents (Md=16y). We extracted ORP during NREM sleep and in the 9 seconds following cortical arousals (ORP-9) from 9-hour, in-lab polysomnography, and frequency- and time-domain HRV indices from 24-h Holter ECG monitoring. Longitudinal and cross-sectional, multivariable-adjusted, regression models examined the association between ORP and ORP-9 with adolescent 24-h HRV indices.

Results: Longitudinally, a greater increase in ORP-9 since childhood was associated with lower daytime Log-LF, SDNN, RMSSD and higher HR in adolescence (p<0.05). A greater increase in ORP since childhood was associated with lower nighttime Log-LF and SDNN (p<0.05). Cross-sectionally, higher ORP and ORP-9 were associated with lower daytime and nighttime Log-LF, SDNN or RMSSD and higher HR within adolescence (p<0.05).

Conclusions: A greater increase in cortical arousability since childhood is a strong developmental predictor of daytime cardiac autonomic imbalance in adolescence. Shallower sleep depth additionally arises as a proximal determinant of both daytime and nighttime cardiac autonomic imbalance within adolescence. These data suggest a coupling between fine-grained spectral measures of the sleeping brain and those of CAM, which may inform sleep-related cardiovascular risk early in life.