This study applied slowly oscillating (0.5 hz) transcranial electrical stimulation (TES; frontopolar and lateral frontal electrodes versus mastoid and occipital electrode returns) to synchronize the endogenous slow oscillations (SOs) of deep sleep (N3 or stage 3 Non-REM). A double-blind placebo control provided no stimulation. The primary endpoint was duration of N3 sleep during the night. Thirteen normal adults completed the study (before the study was terminated because of COVID-19), and usable data were obtained from ten. The synchronizing stimulation resulted in significantly longer N3 sleep compared to placebo.

Previous studies have demonstrated successful synchronization of SOs with slow TES pulses. However, the stimulation in those studies used electrodes in dorsolateral frontal areas (F3, F4 versus contralateral mastoids), consistent with the assumption that human SOs emanate from frontal neocortex. In the present study, we hypothesized that transcranial electrical stimulation (TES) could be applied to frontopolar and inferior frontal head sites in order to synchronize the limbic sources of SOs specifically and thereby enhance the duration of N3 sleep. Furthermore, based on our computational modeling with this more optimal targeting of the limbic sites, we hypothesized that we could use lower TES current levels (0.5 mA versus 1 or 2 mA in previous studies) that would be unlikely to disrupt sleep and that may still be successful in synchronizing SOs to enhance the adaptive neurophysiology of deep sleep.

Inclusion Criteria:

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Exclusion Criteria:

• history of seizures
• epilepsy
• brain trauma or injury
• insomnia
• sleep apnea
• medications that may affect the EEG.

Participants were blind to which night was stimulation. Experimenters were blinded until the participant was asleep, when they opened an email that specified delivery of stimulation or sham.