Stimulating Brain Waves During Deep Sleep

1. Background and Rationale

Insomnia is estimated to be the most prevalent sleep disorder, with nearly 10% of the general population meeting diagnostic criteria. Extensive work is still being deployed to better delineate the multiple subtypes of insomnia, and major gains are to be made using multi-domain physiological monitoring to deepen our understanding of this heterogeneous disease. Some individuals with insomnia show low levels of slow wave sleep (SWS). Novel devices which can be used in the field over multiple days now enable longer term monitoring of EEG features such as sleep slow waves to assess not only inter-individual variability, but also intra-individual variability, a phenomenon of high importance to assess the stability of slow wave abnormalities in insomnia subtypes. Recent findings show that carefully timed auditory stimulation can increase sleep slow waves. Whether such auditory stimulation can potentiate slow waves in people with insomnia symptoms remains to be tested.

Furthermore, sleep architecture and quantitative EEG measures undergo significant alterations in many people with insomnia. Insomnia is notably linked to prolonged sleep onset latency, short total sleep time, numerous nocturnal awakenings, poor sleep efficiency and low amounts of SWS. For instance, it is estimated that people with chronic insomnia spend 20 minutes less in SWS per night compared to good sleepers. Individuals with insomnia have also been reported to have less slow wave activity (SWA; lower spectral power in the delta frequency range), with a shift towards elevated high frequency EEG activity, a potential physiological marker of increased cortical arousal. SWS and SWA are thought to be reflective of sleep depth and to play a central role in sleep maintenance and restorative sleep functions. SWS/SWA alteration may thus represent one of the factors contributing to the lower awakening threshold of people with insomnia and to some of their daytime symptoms, including cognitive difficulties and significant daytime fatigue.

Of note, it has been proposed that SWS abnormalities in insomnia may result in part from dysfunctions in thermoregulatory processes, especially around sleep onset. Autonomic alterations are also visible through elevated heart rate and abnormally low heart rate variability in people with insomnia. Yet very little is known about how daily changes in body temperature and heart rate are related to SWS/SWA dynamics in people with insomnia. There is thus a need for simultaneous ambulatory monitoring across potentially interacting physiological systems.

Enhancement of Slow Oscillations Recent studies demonstrated that slow oscillations (SO), a SWA component in lower frequencies (<1Hz), can also be increased with auditory stimulation. For instance, 50ms pink noise pulses administered during SWS, specifically during the ascending phase of the SO detected in the frontal cortex, increased SO activity. The ascending phase of the SO reflects the depolarization of the cell membrane and increased excitability of the neural network. Further studies confirmed these findings, notably reporting that this may translate across the SWA spectrum. EEG headbands are ambulatory devices for EEG recording capable of stimulation that is phase-locked to SOs. A recent double-blind randomized sham-controlled study using a beta version of these devices in health adults reported a 0.70 specificity and 0.90 sensitivity to automatically detect N3 sleep (as compared to expert human scoring) and rather effective real-time closed-loop detection and stimulation in the SO ascending phase. This yielded an 11-43% increase in spectral power within the delta frequency band during the 4 seconds following stimulations. Importantly, this effect persisted over a sustained period of 10 consecutive nights of stimulation, suggesting no major sign of desensitization over this period. Whether such auditory stimulation can also potentiate slow waves in people with insomnia symptoms remains to be tested.