0661 Slow Wave Alterations During Nocturnal Sleep in Hypersomnolence Disorder

Abstract Introduction Hypersomnolence disorder (HD) is characterized by excessive daytime sleepiness of undetermined etiology. HD is poorly understood with no established biomarkers. Slow waves during non-rapid eye movement (NREM) sleep are associated with the restorative aspects of sleep. Since nonrestorative sleep is a core feature of HD, it is hypothesized that alterations in sleep slow waves may be an HD feature. Thus, this investigation was designed to evaluate slow wave activity (SWA) and characteristics (SWC) in HD, relative to healthy sleeper controls (HSC). Methods 60 unmedicated clinical patients meeting criteria for HD were compared against 29 HSC. All participants underwent polysomnography (PSG) and multiple sleep latency testing (MSLT) at Wisconsin Sleep, with other subjective and objective measures also collected. All-night, six-channel electroencephalography (EEG) data from ad libitum, nocturnal PSG were processed using a validated automatic protocol followed by manual inspection. For each channel of artifact-free EEG from NREM staged epochs, normalized SWA (1-4.5hz) and SWC (incidence, pre-slope, post-slope, and peak amplitude) were calculated in accordance with previously utilized methodology. Post-hoc analyses evaluated slow wave characteristic differences between low- and high-amplitude (≥40μV) slow waves. Linear regression compared groups across normalized SWA and SWC, with adjusted models accounting for relevant, available covariates. Results HD participants were young- to middle-aged (mean age = 28.6 ± 8.6) and predominantly female (percentage female = 78.3%), and HSC were comparable. HD participants displayed significantly reduced SWA across all channels, with effects most pronounced frontally and centrally, and greater in the left relative to right hemispheres. HD participants displayed significant alterations across all SWC, with generally consistent patterns of reductions in incidence, amplitude, and slope across frontal and central EEG derivations. SWC alterations varied significantly by both brain region and low- versus high-amplitude waves. Conclusion This study demonstrates and expands on a growing evidence base that alterations in slow waves may be a core feature of HD. Targeted studies that manipulate NREM slow waves in disorders of unexplained hypersomnolence, including modification of incidence and morphology varied by brain region and hemisphere, are required to clarify whether alterations in slow waves are causal to symptoms of hypersomnolence. Support (if any) AASM Foundation (138-SR-16) and NINR (R21NR018288)