0267 Development and validation of low-level Transcranial Electrical Stimulation to enhance slow oscillations during human NREM sleep

Abstract Introduction Sleep disruption, and in particular decreased NREM stage N3 sleep, has been implicated in cognition and pathogenesis of Alzheimer's Disease (AD). Several recent findings suggest that enhancing N3 sleep may mitigate impairments due to chronic sleep disruption. However, approaches such as transcranial electrical stimulation (TES) have been limited by discomfort, awakenings, and lack of blinding. In response to the need to develop low-level TES, our team first identified the source of slow oscillations (SOs) of N3 sleep using high-density EEG array modeling (Sourcerer®), which localized within anterior limbic brain structures. Next, we showed that low-level TES targeted to this region induced and enhanced SOs during N3 sleep in the laboratory. More recently, we developed a portable TES device with the minimum deployable set of stimulation electrodes targeting the anterior limbic SO-generating regions: Wireless Interface Sensor Pod (WISP). Methods Thirteen healthy adults (m = 42 years) participated in three all-night sleep EEG recordings where they received low level (0.5 mA) TES designed to target anterior limbic SO-generating regions and a sham stimulation (placebo). TES was initiated after 4 minutes of naturally occurring NREM N2 sleep and included five TES blocks of five minutes each separated by one minute rest periods. Subjects were blinded to stimulation and sham conditions, and outcomes included feasibility, acceptability, and total time in each sleep stage. A convolutional neural network (CNN) was developed, trained, and tested on manually scored EEG sleep staging for automated sleep scoring. Results Subjects rated that the WISP device was highly feasible and acceptable. Subjects were adequately blinded to sham versus stimulation. When compared to the sham session, limbic-targeted TES significantly increased the duration of N3 sleep and spectral power in the 0.5-1 Hz frequency band. Finally, our CNN was able to detect sleep stages with good accuracy (84%, kappa 0.77). Conclusion These results suggest that low-level portable TES using a minimum deployable set of electrodes, when specifically targeting anterior limbic sites, is feasible, acceptable, maintains blinding, and increases deep (N3) sleep. The WISP device is a promising method to both assess and manipulate sleep in the home setting. Support (if any) DoD MOMRP MTEC-21-06-MPAI-129