0717 Infraslow Oscillations During NREM Sleep in CNS Disorders of Hypersomnolence

Abstract Introduction Infraslow oscillations (ISO, < 0.1 Hz) during NREM sleep are strongly modulated by noradrenergic locus coeruleus (LC) activity, are synchronized with NREM–REM transitions and spontaneous awakenings, and are most evident in the modulation of sigma power (10–15 Hz) in the scalp EEG. Based on animal studies, these oscillations are proposed to act as “gatekeepers” of the NREM–REM sleep cycle: high LC activity promotes cortical microarousals, whereas low LC activity permits NREM-to-REM transitions. However, the role of ISO in human sleep disorders remains poorly understood. Here we investigate ISO alterations across CNS disorders of hypersomnolence. Methods This multicenter study included 1,217 participants: 85 idiopathic hypersomnia (IH; 60 females), 177 narcolepsy type 1 (NT1; 86 females), 27 narcolepsy type 2 (NT2; 11 females), 551 obstructive sleep apnea (OSA; 245 females), and 377 healthy controls (229 females). We quantified group differences, sex effects, and associations with mean sleep latency (MSL) and Epworth Sleepiness Scale (ESS), adjusting for age, sex, and study, with FDR correction. We further computed standard sleep macro- and EEG micro-architecture metrics for comparative analyses. Results NT1 showed widespread ISO abnormalities (121 significant features at FDR 0.05), including increased N2 infraslow spectral peak amplitude in fast-sigma ISO modulation and disruptions in intra-band ISO alignment. In contrast, IH and NT2 showed no significant ISO alterations relative to controls, and OSA showed only two. Altered ISO features were unrelated to ESS, but several—including ISO peak amplitudes in higher bands—were associated with MSL, suggesting links to physiological sleep propensity. Sex effects were also substantial (81/196 features), mainly in ISO peak amplitude in higher bands and intra-band alignment, with NT1 showing additional disease-by-sex interactions. Conclusion ISO alterations represent a distinct electrophysiological pattern characteristic of NT1 but not IH, NT2, or OSA, consistent with orexin-deficiency–related instability of arousal regulation. ISO appear independent of subjective clinical sleepiness measures (ESS) and may serve as complementary markers of NT1-specific sleep–wake dynamics. Strong sex differences underscore the importance of including sex as a biological variable. Support (if any) 5R61NS130215-02 (Maski)