Reduced Cross-Frequency Coupling and Daytime Sleepiness in Obstructive Sleep Apnea Patients

SIMPLE SUMMARY: Obstructive sleep apnea (OSA) is one of the most common breathing-related sleep disorders. The processes that take place in specific areas of the brain during distinct sleep stages and specific respiratory events are suspected to be impaired in OSA patients. These brain processes may be described in complex (mathematical) terms. Using one of these descriptions (phase–amplitude cross-frequency coupling), we demonstrated in electroencephalographic (EEG) recordings of OSA patients that the process sequences in certain areas of the brain are altered in distinct sleep stages of OSA patients compared to patients who do not suffer from clinically relevant OSA. In addition, we were able to find a physiological marker that assesses the severity of daytime sleepiness, one of the main symptoms of OSA. This study supports the hypothesis that OSA is a neuronal/neuromuscular disorder. Thus, it contributes to a better understanding of the so-far-unexplained cause for the development of OSA and opens new possibilities for the exploration of alternative therapeutic approaches. ABSTRACT: Obstructive sleep apnea (OSA) is associated with sleep-stage- and respiratory-event-specific sensorimotor cortico-muscular disconnection. The modulation of phase–amplitude cross-frequency coupling (PACFC) may influence information processing throughout the brain. We investigated whether sleep-stage-specific PACFC is impaired at the sensorimotor areas in OSA patients. C3 and C4 electrode EEG polysomnography recordings of 170 participants were evaluated. Different frequency band combinations were used to compute CFC modulation index (MI) to assess if MI differs between OSA and non-significant OSA patients in distinct sleep stages. We tested if the CFC-MI could predict daytime sleepiness in OSA. Theta–gamma CFC-MI at cortical sensorimotor areas was significantly reduced during all sleep stages; the delta–alpha CFC-MI was significantly reduced during REM and N1 while increasing during N2 in patients with respiratory disturbance index (RDI) > 15/h compared to those with RDI ≤ 15/h. A sleep stage classification using MI values was achieved in both patient groups. Theta–gamma MI during N2 and N3 could predict RDI and Epworth Sleepiness Scale, while delta–alpha MI during REM predicted RDI. This increase in disconnection at the cortical sensorimotor areas with increasing respiratory distress during sleep supports a cortical motor dysfunction in OSA patients. The MI provides an objective marker to quantify subjective sleepiness and respiratory distress in OSA.