Bilateral Theta Transcranial Alternating Current Stimulation (tACS) Modulates EEG Activity: When tACS Works Awake It Also Works Asleep

Aurora D’Atri,1,2 Serena Scarpelli,1 Maurizio Gorgoni,1 Valentina Alfonsi,1 Ludovica Annarumma,1 Anna Maria Giannini,1 Michele Ferrara,3 Fabio Ferlazzo,1 Paolo Maria Rossini,4,5 Luigi De Gennaro1,2 1Department of Psychology, University of Rome “Sapienza”, Rome, Italy; 2Area of Neuroscience, IRCCS San Raffaele Pisana, Rome, Italy; 3Department of Biotechnological and Applied Clinical Sciences, University of L’Aquila, L’Aquila, Italy; 4Institute of Neurology, Catholic University of the Sacred Heart, Rome, Italy; 5Department Geriatrics, Neuroscience & Orthopaedics, Policlinic A. Gemelli Foundation-IRCCS, Rome, ItalyCorrespondence: Luigi De GennaroDepartment of Psychology, University of Rome “Sapienza”, Via Dei Marsi, 78, Rome 00185, Italy, Tel +39 06-49917647Fax +39 06-49917711Email luigi.degennaro@uniroma1.itPurpose: Recent studies demonstrate that 5-Hz bilateral transcranial alternating current stimulation (θ-tACS) on fronto-temporal areas affects resting EEG enhancing cortical synchronization, but it does not affect subjective sleepiness. This dissociation raises questions on the resemblance of this effect to the physiological falling asleep process. The current study aimed to evaluate the ability of fronto-temporal θ-tACS to promote sleep.Subjects and methods: Twenty subjects (10 F/10 M; mean age: 24.60 ± 2.9 y) participated in a single-blind study consisting of two within-subject sessions (active/sham), one week apart in counterbalanced order. Stimulation effects on EEG were assessed during wake and post-stimulation nap. The final sample included participants who fell asleep in both sessions (n=17).Results: Group analyses on the whole sample reported no θ-tACS effects on subjective sleepiness and sleep measures, while a different scenario came to light by analysing data of responders to the stimulation (ie, subjects actually showing the expected increase of theta activity in the wake EEG after the θ-tACS, n=7). Responders reported a significant increase in subjective sleepiness during wakefulness after the active stimulation as compared to the sham. Moreover, the sleep after the θ-tACS compared to sham in this sub-group showed: (1) greater slow-wave activity (SWA); (2) SWA time-course revealing increases much larger as closer to the sleep onset; (3) stimulation-induced changes in SWA during sleep topographically associated to those in theta activity during wake.Conclusion: Subjects who show the expected changes during wake after the stimulation also had a consistent pattern of changes during sleep. The enhancement of cortical synchronization by θ-tACS during wakefulness actually corresponds to increased sleep pressure, but it occurs only in some individuals. Thus, θ-tACS can enhance sleep, although individual factors to be further investigated affect the actual responsiveness to this treatment.Keywords: transcranial alternating current stimulation, sleep, EEG, slow-wave activity, sleep onset