Application of down-phase targeted auditory stimulation during sleep in a home setting: A feasibility study across...

Sleep deprivation, also known as "wake therapy", has long been recognized as a powerful antidepressant. Phase-targeted auditory stimulation (PTAS) has been suggested as an auspicious non-invasive nocturnal substitute for sleep deprivation. Down-PTAS with stimuli presentation during the down-phase of slow waves, in particular, may have therapeutic potential to improve mood by selectively reducing slow-wave activity (SWA). With down-PTAS being more nuanced than sleep deprivation, its effects presumably develop over multiple nights, thus necessitating transfer from sleep laboratory to home settings. Therefore, in this study, we investigated the technical feasibility, tolerability, and potential risks associated with a wearable device employed for down-PTAS in an unsupervised home setting.

We recorded frontal EEG using the MHSL Sleepband Version 3 (MHSL-SB) in five healthy participants (23.8 ± 0.8 years, three women) over seven consecutive nights with (STIM) and without (SHAM) tone application at their homes. Tones were delivered shortly before the negative peak of slow waves during N2/N3 sleep, using alternating 10-s ON-OFF windows. Sleep staging followed American Academy of Sleep Medicine (AASM) guidelines. Of the 67 available sleep recordings, we excluded three due to parameter adjustments and another six for technical issues, leaving 58 sleep recordings (29 SHAM, 29 STIM) for further analyses. Low SWA (0.5-2 Hz, lSWA) was computed across the entire night, ON-OFF windows, and sleep cycles. Time-frequency analyses were performed time-locked to stimulus onset. We computed linear mixed effect models with condition (STIM vs. SHAM) as a fixed effect and random participant intercepts.

Data quality was sufficient for analyses in 87 % of the available sleep recordings, with an average of over 1500 correctly delivered stimuli per recording. Down-PTAS did not affect sleep architecture, but it reduced lSWA primarily during the first sleep cycle when sleep pressure and lSWA were highest, and particularly in OFF windows. Additionally, stimulation elicited a K-complex-like auditory evoked response, aligning with previous laboratory findings.

Our results demonstrate the successful implementation of down-PTAS in a home setting, confirming its feasibility for long-term, unsupervised use. The K-complex-like auditory evoked response may mask potential reductions in lSWA during ON windows, posing a scientific analytical challenge. Taken together, future clinical research should now assess the effects of down-PTAS in depressed patients, in whom reducing lSWA may partly mimic sleep deprivation.