Proceedings #11: Replay of Endogenous Sleep Rhythms to Produce Sleepiness

Abstract

Varying modes of non-invasive electrical stimulation techniques have been investigated to induce endogenous sleep-like states (historically called Electrosleep). These include transcranial pulsed current stimulation (tPCS) such as Cranial Electrical Stimulation, transcranial direct current stimulation (tDCS), and transcranial alternating current stimulation (tACS) such as 10 Hz sinusoidal stimulation. Prior efforts used synthetic (simple) waveforms selected to modulate excitability (e.g. tDCS) or reproduce a single predominant frequency of endogenous neuronal rhythms of sleep induction (e.g. 10 Hz). To examine the effects of electrical stimulation with a complete spectrum sleep-related endogenous neural activity, we designed and applied an endogenous sleep-derived stimulation waveform to subjects while assessing a range subjective performance and objective physiological data. We hypothesized that a stimulation with complex high-bandwidth waveform reflecting endogenous sleep-associated neuronal activity patterns (transcranial Endogenous Sleep-Derived; tESD) would be more effective, than synthetic frequency-specific waveforms such at tACS, in supporting the transition to sleepiness. The basis for the transcranial Endogenous Sleep-Derived (tESD) waveform was acquired during a resting, sleepy-state EEG session. Data were examined for markers of sleepiness and corresponding segments were extracted, compressed, and scaled to produce a current signal. Stimulation was applied through a custom, high-bandwidth current-control stimulator. Subjects were supine in a light and sound attenuated environment. Using HD bipolar montage (AF7, AF8) with a maximal current amplitude of 0.5 mA over 10 minutes. tESD was also simulated in a computational model. Physiology (EEG, ECG, respiration, EOG, EMG) and behavior (questionnaires, reaction time) was assessed before, during (only for physiology), and after stimulation. Each subject underwent tESD, 10 Hz tACS, and a no-stimulation (non-interventional) sessions in a counterbalanced manner with at least 24 hours between each session. tESD polarized the frontal lobe. Changes in the no-stimulation condition confirms the testing environment was conducive to a wakefulness–sleep transition. Preliminary data indicate an enhanced shift in physiological measures in directions consistent with a relaxed and sleepy state with tESD compared to tACS and no-stimulation conditions. Behavioral data indicate a delay in reactions times post stimulation and subjective sleepiness reports indicate higher sleepiness post stimulation. tESD was well tolerated and blinding was effective. tESD aims to “replay” the endogenous neuronal signature of sleep. Neurophysiological (EEG), physiological (heart rate, respiration) and behavioral (simple reaction time, PVT) indicate that tESD, directed to frontal brain regions, that are associated with top-down thalamo-cortical sleep control mechanisms, accelerated wakefulness–sleep transition in subjects in a baseline relaxed state.