Variations in Loop Gain and Arousal Threshold During NREM Sleep Are Affected by Time of Day over a 24-hour Period in Participants with Obstructive Sleep Apnea

We investigated whether time of day affects loop gain (LG) and the arousal threshold (AT) during non-rapid eye movement (NREM) sleep. Eleven men with obstructive sleep apnea (apnea-hypopnea index > 5 events/h) completed a constant-routine protocol that comprised 3-h sleep sessions in the evening [10 PM (1) to 1 AM], morning (6 AM to 9 AM), afternoon (2 PM to 5 PM), and subsequent evening [10 PM (2) to 1 AM]. During each sleep session LG and the AT were measured during NREM sleep with a model-based approach. Our results showed the presence of a rhythmicity in both LG ( < 0.0001) and the AT ( < 0.001) over a 24-h period. In addition, LG and the AT were greater in the morning compared with both evening sessions [6 AM vs. 10 PM (1) vs. 10 PM (2): LG (1 cycle/min): 0.71 ± 0.23 vs. 0.60 ± 0.22 ( = 0.01) vs. 0.56 ± 0.10 ( < 0.001), AT (fraction of eupneic breathing): 1.45 ± 0.47 vs. 1.28 ± 0.36 ( = 0.02) vs. 1.20 ± 0.18 ( = 0.001)]. No difference in LG and the AT existed between the evening sessions (LG: = 0.27; AT: = 0.24). LG was correlated to measures of the hypocapnic ventilatory response (i.e., a measure of chemoreflex sensitivity) ( = 0.72 and = 0.045) and the critical closing pressure (i.e., a measure of airway collapsibility) ( = 0.77 and = 0.02) that we previously published. We conclude that time of day, independent of hallmarks of sleep apnea, affects LG and the AT during NREM sleep. These modifications may contribute to increases in breathing instability in the morning compared with other periods throughout the day/night cycle in individuals with obstructive sleep apnea. In addition, efficaciousness of treatments for obstructive sleep apnea that target LG and the AT may be modified by a rhythmicity in these variables. Loop gain and the arousal threshold during non-rapid eye movement (NREM) sleep are greater in the morning compared with the afternoon and evening. Loop gain measures are correlated to chemoreflex sensitivity and the critical closing pressure measured during NREM sleep in the evening, morning, and afternoon. Breathing (in)stability and efficaciousness of treatments for obstructive sleep apnea may be modulated by a circadian rhythmicity in loop gain and the arousal threshold.