Association of novel EEG biomarkers of sleep depth and cortical arousability with cardiac autonomic modulation in adolescents

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 = 16 years). 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-hour Holter ECG monitoring. Longitudinal and cross-sectional, multivariable-adjusted, regression models examined the association between ORP and ORP-9 with adolescent 24-hour 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 < .05). A greater increase in ORP since childhood was associated with lower nighttime Log-LF and SDNN (p < .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 < .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.