Intracerebral dynamics of sleep arousals: a combined scalp-intracranial EEG study

As an intrinsic component of sleep architecture, sleep arousals represent an intermediate state between sleep and wakefulness and play an important role in sleep-wake regulation. They have been defined in an all-or-none manner, whereas they actually present a wide range of scalp-electroencephalography (EEG) activity patterns. It is poorly understood how these arousals differ in their mechanisms. Stereo-EEG (SEEG) provides the unique opportunity to record intracranial activities in superficial and deep structures in humans. Using combined polysomnography and SEEG, we quantitatively categorized arousals in non-rapid eye movement sleep into slow wave (SW) and Non-SW arousals based on whether they co-occurred with a scalp-EEG SW event. We then investigated their intracranial correlates in up to 26 brain regions from 26 patients (12 females). Across both arousal types, intracranial theta, alpha, sigma, and beta activities increased in up to 25 regions ( p <0.05, d =0.06-0.63), while gamma and high frequency (HF) activities decreased in up to 18 regions across five brain lobes ( p <0.05, d =0.06-0.44). Intracranial delta power widely increased across five lobes during SW arousals ( p <0.05 in 22 regions, d =0.10-0.39), while it widely decreased during Non-SW arousals ( p <0.05 in 19 regions, d =0.10-0.30). Despite these main patterns, unique activity was observed locally in some regions such as the hippocampus and middle cingulate cortex, indicating spatial heterogeneity of arousal responses. Our results suggest that Non-SW arousals correspond to a higher level of brain activation than SW arousals. The decrease in HF activities could potentially explain the absence of awareness and recollection during arousals. Significance Statement Intrinsic to sleep architecture, sleep arousals play an important role in sleep-wake regulation. They are defined in an all-or-none manner, whereas they actually present various scalp electroencephalography (EEG) patterns. Using simultaneous scalp and intracranial EEG in humans, we analyzed the intracranial activity during two types of arousals marked on scalp EEG, quantitatively categorized by whether they co-occurred with a scalp-EEG slow wave (SW). Non-SW arousals present prevalent low-voltage fast activity, while SW arousals exhibit high-voltage slow waves alongside fast activities. This work represents the first intracranial study of different types of NREM sleep arousals and provides a comprehensive description of local brain activities during both arousal types, serving as a foundation for future studies investigating regional behaviors during sleep-wake transition.