A randomized controlled trial of alpha phase-locked auditory stimulation to treat symptoms of sleep onset insomnia.

Sleep onset insomnia is a pervasive problem that contributes significantly to the poor health outcomes associated with insufficient sleep. Auditory stimuli phase-locked to slow-wave sleep oscillations have been shown to augment deep sleep, but it is unknown whether a similar approach can be used to accelerate sleep onset. The present randomized controlled crossover trial enrolled adults with objectively verified sleep onset latencies (SOLs) greater than 30 min to test the effect of auditory stimuli delivered at specific phases of participants' alpha oscillations prior to sleep onset. During the intervention week, participants wore an electroencephalogram (EEG)-enabled headband that delivered acoustic pulses timed to arrive anti-phase with alpha for 30 min (Stimulation). During the Sham week, the headband silently recorded EEG. The primary outcome was SOL determined by blinded scoring of EEG records. For the 21 subjects included in the analyses, stimulation had a significant effect on SOL according to a linear mixed effects model (p = 0.0019), and weekly average SOL decreased by 10.5 ± 15.9 min (29.3 ± 44.4%). These data suggest that phase-locked acoustic stimulation can be a viable alternative to pharmaceuticals to accelerate sleep onset in individuals with prolonged sleep onset latencies. Trial Registration: This trial was first registered on clinicaltrials.gov on 24/02/2023 under the name Sounds Locked to ElectroEncephalogram Phase For the Acceleration of Sleep Onset Time (SLEEPFAST), and assigned registry number NCT05743114.

A wearable EEG system for closed-loop neuromodulation of sleep-related oscillations.

Objective.Healthy sleep plays a critical role in general well-being. Enhancement of slow-wave sleep by targeting acoustic stimuli to particular phases of delta (0.5-2 Hz) waves has shown promise as a non-invasive approach to improve sleep quality. Closed-loop stimulation during other sleep phases targeting oscillations at higher frequencies such as theta (4-7 Hz) or alpha (8-12 Hz) could be another approach to realize additional health benefits. However, systems to track and deliver stimulation relative to the instantaneous phase of electroencephalogram (EEG) signals at these higher frequencies have yet to be demonstrated outside of controlled laboratory settings.Approach.Here we examine the feasibility of using an endpoint-corrected version of the Hilbert transform (ecHT) algorithm implemented on a headband wearable device to measure alpha phase and deliver phase-locked auditory stimulation during the transition from wakefulness to sleep, during which alpha power is greatest. First, the ecHT algorithm is implementedin silicoto evaluate the performance characteristics of this algorithm across a range of sleep-related oscillatory frequencies. Secondly, a pilot sleep study tests feasibility to use the wearable device by users in the home setting for measurement of EEG activity during sleep and delivery of real-time phase-locked stimulation.Main results.The ecHT is capable of computing the instantaneous phase of oscillating signals with high precision, allowing auditory stimulation to be delivered at the intended phases of neural oscillations with low phase error. The wearable system was capable of measuring sleep-related neural activity with sufficient fidelity for sleep stage scoring during the at-home study, and phase-tracking performance matched simulated results. Users were able to successfully operate the system independently using the companion smartphone app to collect data and administer stimulation, and presentation of auditory stimuli during sleep initiation did not negatively impact sleep onset.Significance.This study demonstrates the feasibility of closed-loop real-time tracking and neuromodulation of a range of sleep-related oscillations using a wearable EEG device. Preliminary results suggest that this approach could be used to deliver non-invasive neuromodulation across all phases of sleep.