Sleep and Performance

Sleep is a fundamental element of brain health and function, supporting the processes of learning and memory consolidation, maintenance and repair, and waste clearance. Acute sleep deprivation, a frequent operational necessity among warfighters, significantly impairs attention, vigilance, processing speed, executive function, motor coordination and memory. Chronic sleep restriction, a condition common among service members during combat deployments and operations, erodes cognitive and physical performance and is a major limitation on sustained operational readiness. The newly-discovered glymphatic system supports the rapid exchange of fluid through brain tissue during sleep, facilitating the clearance of wastes that accumulate through the course of waking activity. Increased glymphatic clearance occurs in the deepest (slow wave, N3) stage of sleep and is facilitated by the dynamic enlargement of the brain's extracellular space during slow wave activity. Sleep-active glymphatic function is postulated to underlie the restorative function of sleep on cognition, and its impairment is proposed to drive the cognitive impacts of sleep disruption. This suggests that improving glymphatic function, whether pharmacologically or by means of a device, could ameliorate the cognitive effects of acute sleep deprivation and chronic sleep restriction. The proposed technology, Augmented Neural Oscillation Driver or 'AugNOD', is an easily-applied, wireless, combined electroencephalography (EEG)/transcranial electrical stimulation (TES) headband that can be applied before sleep to monitor and improve slow wave sleep and glymphatic clearance. The AugNOD system utilizes two complimentary protocols to support glymphatic function: 1) the integrated TES Slow Oscillation (TES SO) promotes slow wave sleep, engaging sleep-active glymphatic clearance; 2) the Direct Current Glymphatic Clearance (DCGC) protocol directly improves glymphatic function through enhancement of brain extracellular diffusion. BEL has obtained an FDA presubmission query for the Neurosom EEG Assessment Technology (NEAT) for automated sleep staging using machine learning (Convolutional Neural Nets) with validation from AASM-Certified commercial scoring. This should complete soon, and the Investigators expect FDA clearance for NEAT by early 2022. In addition, BEL has obtained an FDA review for TES synchronization of SOs with the Intended Use of improving deep sleep (N3) in healthy adults. Although the presence of sleep-active glymphatic exchange has only recently been confirmed in human subjects, no pharmacological or device-based approach has yet demonstrated that glymphatic function can be modulated in the human brain. In Objective 1, the investigators will test whether enhancing slow wave sleep using the AugNOD TES SO protocol improves overnight glymphatic function measured by MRI. By comparing effects between subject undergoing total sleep deprivation, restricted natural sleep, and restricted natural sleep with TES slow wave synchronization, this study will determine whether extending slow wave sleep with TES leads to improvement of glymphatic clearance and regional molecular diffusion by multimodal MRI, The Investigators will also perform Magnetic Resonance Elastography (MRE) on the healthy human brain in multiple directions to calculate directional stiffness of the brain tissue. An MRE actuator vibrational device (pillow) will be used to apply vibration to the subject's head in one direction and then another, and then to use this information to calculate the stiffness of brain tissue. The investigators will combine the information from the MRE scan and the information from the other MRI scans performed to simulate brain motion and calculate accurate mechanical properties of the brain. Although glymphatic function has been proposed to underlie the restorative effects of sleep on cognitive function, and its impairment has been thought to contribute to cognitive deficits resulting from sleep deprivation, this connection has never been directly tested experimentally in animal models or in human subjects. In Objective 2, the research will test whether AugNOD TES SO improves sleep restriction-associated cognitive impairment. Sleep restriction will be coupled with a demanding vigilance task to simulate the challenges of performance under operational conditions. Since slow wave sleep likely exerts a restorative effect on cognitive function independent of glymphatic clearance, the TES SO protocol may also improve subsequent cognitive performance through enhancement of sleep efficiency.