Sleep and Performance

University of Washington16 enrolled

Overview

This research is being done to apply new, contrast-free MRI (Magnetic Resonance Imaging) methods to understand the brain's waste clearance system (the "glymphatic" system) in younger adults. The Investigators hope the study will show how the different brain regions are involved in maintaining memories and how poor sleep affects these regions and our ability to remember. The Investigators will test whether the Wireless Interface Sensor Pod (WISP) improves brain function after poor sleep. The WISP is a headband that combines tracking brain waves and transcranial electrical stimulation (TES) to monitor and improve slow wave sleep and glymphatic clearance. IParticipants will be asked to: * Complete 4 in-person study visits (1 per week) over 4 weeks at the Diagnostic Imaging Sciences Center (DISC), located at the University of Washington Medical Center at Montlake, Seattle. Each visit will last 2 hours and includes a 1 hour MRI and 1 hour of cognitive testing. * Complete a daily journal about sleep, daily habits, etc. * The night before each of the four study visits, participants will sleep while wearing the WISP headband. * For two of these nights, participants will sleep only 3 hours prior to normal time of awakening. The WISP will deliver a small electrical current for one night and not for the other night, but participants will not know which. * For the other two nights, participants will follow a normal sleep schedule. The WISP will deliver a small electrical current for one night and not for the other night, but participants will not know which.

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.

Eligibility

Sex: ALLMin age: 18 YearsMax age: 30 YearsHealthy volunteers:

Medical Language ↔ Plain English

Inclusion Criteria: 1. Physically and psychologically healthy 2. Good habitual sleep between 6 and 10 hours in duration, as assessed by questionnaire and pre-study week sleep/wake diary 3. Regular bedtimes, habitually getting up between 05:00 and 09:00, as assessed by questionnaire and pre-study week sleep/wake diary Exclusion Criteria: * Subjects who have any type of non-MRI compatible bioimplant activated by mechanical, electronic, or magnetic means (e.g., cochlear implants, pacemakers, neurostimulators, biostimulators, electronic infusion pumps, etc.), because such devices may be displaced or malfunction. * Subjects who have any type of ferromagnetic bioimplant that could potentially be displaced. * Subjects who have cerebral aneurysm * Subjects who may have shrapnel imbedded in their bodies (such as from war wounds), metal workers and machinists (potential for metallic fragments in or near the eyes). * Minors (younger than 18 years) * Pregnant women ( Participants of childbearing potential will receive a urine pregnancy test. If the test is positive, the participant will be excluded) * Breastfeeding * Subjects who cannot adhere to the experimental protocols for any reason, or have an inability to communicate with the researcher. * no clinical disorders and/or illnesses, no psychiatric illnesses), as assessed by history and questionnaires * no alcohol during study and no normal excessive alcohol consumption assessed by questionnaire * No history of drug or alcohol abuse in the past year and no history of methamphetamine abuse, as assessed by questionnaires. * Not a dependent smoker or vaper, and not morning dependent on tobacco, nicotine, or cannabis, as assessed by questionnaire. * No history of moderate to severe brain injury, as assessed by questionnaire * No anti-psychotic medication for ADHD/ADD, as assessed by questionnaire * No previous adverse reaction to sleep deprivation, as assessed by questionnaire * Not vision-impaired unless corrected back to normal. * Not hearing impaired unless corrected to normal, as assessed by questionnaire * Not pregnant, as assessed by history and questionnaire * No sleep or circadian disorder, as assessed by questionnaires * No use of melatonin within 1 week of study enrollment * No travel across more than one time zone within one month of entering the study and no crossing times zones during study participation, as assessed by questionnaire. * No shift work within three months of entering the study and no shift work during duration study participation, as assessed by questionnaire. * epilepsy

Outcomes

Primary Outcomes

Multimodal MRI

We will test whether enhancing slow-wave sleep using the AugNOD TES SO improves overnight glymphatic function, as measured by non-invasive multimodal MRI-based markers of glymphatic activity: (i) diffusion-based intravoxel incoherent motion (IVIM)-MRI assessing long-distance water transport (diffusion signal); (ii) fast functional MRI (f-MRI) measuring low-frequency vasomotor oscillations; (iii) T1/FLAIR-based assessment of MRI-visible perivascular spaces (MV-PVS), which serve as structural indicators of perivascular impairment; (iv) multi-echo arterial spin-labeling (ME-ASL)-MRI assessing glial-vascular water transport ; and (v) Magnetic Resonance Elastography (MRE) measuring brain tissue stiffness.