0117 Multi-Organ Infraslow Coupling Among Cyclic Alternating Pattern, Cardiopulmonary Coupling, and Breathing Instability

Abstract Introduction Cyclic alternating pattern (CAP) occurs during NREM sleep and is a marker of sleep instability. The CAP A phases occur at intervals of mostly 30-50 seconds (2-60 seconds by definition) in the infraslow frequency range (< 0.05Hz). Low-frequency coupling (LFC) in cardiopulmonary coupling (CPC) and breathing instability are more commonly observed during CAP phase A, reflecting autonomic instability. However, it is unknown whether there is a coupled network of the brain, heart, and respiratory system. Here, we hypothesized that CAP, CPC, and breathing instability are coupled and therefore form a multi-organ infraslow oscillation, which we term “MISO”, and that the strength of this coupling differs across A1, A2, A3, and B phases of CAP, and across diseases. Methods We analyzed overnight polysomnograms (PSGs) from 108 participants in the PhysioNet CAP Database, including 16 healthy adults and 7 diseases. CAP phases were manually annotated. For 107 participants with ECG, CPC was calculated as coherence between RR-intervals and ECG-derived respiration, and then converted to the log-ratio between LFC (0.01-0.1Hz) and HFC (0.1-0.4Hz) as log(L2H). For 34 participants with respiration belts, breathing instability (BSI) was computed from chest and abdomen belts. The coupling was estimated as Cohen’s d between a CAP phase vs. non-CAP for CPC or BSI. Comparisons among CAP phases were assessed using Kruskal-Wallis test (omnibus) followed by Dunn’s test. The omnibus test was Bonferroni-corrected. Same-CAP-phase across-disease differences were assessed using ANCOVA, controlling for age and sex. Results The participants were aged 14-82 years, with 39% female. In healthy participants, CAP-CPC coupling was stronger for A3 (Cohen’s d=0.51 for log(L2H) compared to non-CAP) and A2 (0.24), than A1 (-0.07) and B (0.05). CAP-BSI coupling was stronger for A3 (1.0) than A2 (0.19), A1 (-0.06), and B (0.04). However, there were no significant across-disease differences in CAP-CPC or CAP-BSI coupling within the same CAP phase. A3 showed stronger coupling to CPC and BSI across diseases. Conclusion CAP (especially A3), CPC, and breathing instability exhibit temporal coupling across healthy and pathological sleep, supporting a multi-organ infraslow oscillation (MISO) underlying NREM sleep stability. The clinical significance should be investigated in neurological and cardiopulmonary disorders. Support (if any) AASM Foundation 370-SR-25.