Local REM sleep-N1-wake sleep stage mixing in narcolepsy type 1
medRxiv February 17, 2026 Constantin Weberpals, A. Specht, Natasja Bonde Andersen et al.
Type 1 narcolepsy (NT1) involves the loss of hypocretin/orexin transmission, causing daytime sleepiness and abnormal mixing of REM sleep with wakefulness, leading to cataplexy, sleep paralysis, and dream-like hallucinations. Using deep learning of nocturnal sleep polysomnography signals (EEG, EMG, EOG), the study found that NT1 patients show abnormally short wake-to-REM transitions and mixing of wake, N1, and REM sleep stages. This mixing fluctuated across cortical locations, strongest in frontal and central regions, particularly the left hemisphere. The strongest discriminator was N1-REM mixing across central electrodes, with 4.3-fold higher dissociation in NT1 patients (Cohen’s d = 0.61). Local dissociations correlated with CSF orexin/hypocretin levels and MSLT severity. Hypnagogic hallucinations correlated with occipital dissociations, aligning with visual content. Orexin deficiency likely destabilizes REM sleep organization across cortical areas.