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

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. 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. 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). 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.