As he gets ready for sleep each night, Don Tucker slips on an electrode cap and checks a little computer on his bedside table. Many workers at the private lab, run by the professor emeritus at the University of Oregon, follow the same routine.
The goal is not just a more restful slumber. Groundbreaking discoveries made in the past decade have revealed that the brain has a power-washing system that switches into high gear during deep sleep, flushing away harmful waste. This nightly cleanup is part of the restorative power of sleep and revives concentration, memory and motor skills.
As we age, however, this cleansing system gets sloppier, and it can begin to leave behind some of the metabolic detritus of the day, including the amyloid beta proteins found in the plaque that characterize Alzheimer’s disease and other devastating neurological disorders.
The stunning revelation in 2012 of this previously unknown brain infrastructure — dubbed the glymphatic system — has ushered in a new age of research and invention not only about sleep but also aging, dementia and brain injury. Nearly 300 research papers were published last year on the glymphatic system.
One of those research paths leads to Tucker’s lab and the invention on his bed stand, called AugNOD for Augmented Neural Oscillation Driver. In prototype, it looks like a particularly severe orthodontic apparatus with a toll-road transponder strapped to the top. Refined, slighter versions are in the works.
By stretching the length of deep sleep, Tucker’s device aims to boost that overnight wash cycle. Someday soon, he hopes, something like it will be widely used by people to clear their heads — literally. “It’s a way of keeping the brain young,” Tucker, 75, said.
The U.S. Army has taken interest. In October, the Department of Defense awarded Tucker, the University of North Carolina and several partner universities $4.25 million to explore a possible military application of the device to restore mental sharpness to sleep-deprived soldiers on the battlefield.
Jeffrey Iliff, a member of the research team from the University of Washington School of Medicine, said that, within five years, consumer devices may allow anyone to track their brain-cleansing deep sleep.
“And I think within the next seven years we are going to start to see approaches — like maybe this device, maybe some pharmacological approaches — that can begin to modulate it, that can maybe turn it up if you want to try to turn it up,” Iliff said. “I think things are starting to move very quickly in this field as work starts to move out into human populations.”
Iliff holds a significant place in the history of sleep science. He was lead author of several papers that in 2012 began describing the brain-scrubbing glymphatic system, based on work done at the University of Rochester with principal investigator Maiken Nedergaard.
Iliff said that when he joined her lab as a postdoctoral fellow, Nedergaard set him on a course to answer lingering questions about how fluid moves through the brain. What they discovered, hiding in plain sight, was a separate plumbing system wrapped around blood vessels in the head, pushing fluid into the brain.
In part by peering through tiny holes in mouse skulls, scientists hypothesize that human brain cells shrink during deep sleep, creating space for this fluid to surge between them and give each cell a bath.
This washes away harmful waste proteins produced by the brain, a tireless metabolic engine that keeps chugging round-the-clock.
The volume of fluid coursing around the cells could be measured in thimbles, Iliff said. Yet scientists are discovering it is key to human well-being.
“We think that this is relevant not just to Alzheimer’s disease, but we actually think this is probably relevant to all sorts of neuroimmunological conditions like multiple sclerosis, and neurovascular disorders like traumatic brain injury and stroke,” Iliff said. “There is evidence that it is involved in headaches. There is evidence it may be involved in mood disorders and other neuropsychiatric conditions like depression or bipolar disorder.”
“It seems that it is actually much more foundational and fundamental than we thought it was,” Iliff said.
Sleep — particularly the electrical score the brain plays through each night — is at the heart of the process.
Each kind of sleep — from the lighter stages, through deep sleep, to rapid eye movement or REM — is marked by a distinct pattern of brain waves, which scientists have been eavesdropping on for almost a century with electroencephalography (EEG).
The deepest sleep, just before REM, produces slow brain waves that help organize and store away memories of the day and kick the glymphatic washing cycle into high gear.
EEG tests show that as people age, they spend less time in deep sleep and more in lighter sleep.
“Many people, after age 30, their deep sleep goes to hell,” Tucker said. “We think that can explain much of the memory decline in older people, and it starts at age 30 — it’s not like you have to get old and decrepit.”
Tucker has been working on these problems for decades, founding a company in 1992 that pioneered a high definition EEG worn like a wired-up hairnet. That company, Electrical Geodesics, was bought for nearly $37 million by Philips in 2017.
His new company, Brain Electrophysiology Lab, in Eugene, Ore. seeks not just to monitor the brain’s electrical activity but also to influence it. The work emulates findings from labs around the world that have begun to coax the brain from one stage of sleep to another with minuscule doses of current.
These artificial impulses mimic the ones produced in the head during deep sleep, and the brain follows their lead and also begins producing these slower brain waves, plunging itself into the deepest realms of sleep.
“If you change the electrical current going through the head, the neurons naturally synchronize with that,” Tucker said.
Tucker and others published last May a small, peer-reviewed study where by administering tiny pulses of electricity for five minutes at a time to snoozing test subjects, they increased time in deep sleep by an average of 13 percent. He said that is enough to begin making the brain more effective at organizing memory and clearing waste.
Applying small amounts of electricity to the brain, called transcranial electrical stimulation, is not new. A sweeping 2017 review determined that it appears to be safe, noting no serious side effects in over 18,000 sessions included in the survey. It has been touted for providing a host of possible neurological benefits, many of which remain unproven.
“Given the amount of research and the amount of promise and the amount of media attention dedicated to transcranial electrical stimulation, that hasn’t really translated into home devices that are FDA-approved for various indications,” cautioned Anna Wexler, a bioethicist at the University of Pennsylvania and one of the authors of the safety study.
Determining whether Tucker’s device can effectively dial up the brain’s cleaning system is complicated by how difficult it is to watch the glymphatic system in action.
Swati Rane Levendovszky, a member of the research team and a radiology professor at the University of Washington School of Medicine, has been developing MRI techniques to observe and measure the speed and flow of the fluid that washes the brain. If successful, the techniques could show whether Tucker’s device increases that flow.
It might also someday help doctors assess patients for Alzheimer’s disease, Parkinson’s disease, and dementia, she said. “All of these are associated with an inability to clear one type of toxic protein in the brain, and glymphatics is related to that,” Levendovszky said.
Beyond diagnostics, the project will assess the potential to help with those conditions, said Dawn Kernagis, a neuroscientist at the University of North Carolina School of Medicine and co-lead of the project.
“If this device does have an impact, we could be looking at some really positive effects in those populations where they have seen increased risk of neurodegenerative disease,” Kernagis said.
The possibility of broader applications appealed to the Army, along with the potential to improve readiness of sleep-deprived soldiers and help heal injured ones, said Christopher Steele, a director at the U.S. Army Medical Research and Development Command.
For the DOD, “the glymphatic system presents an opportunity to understand how chronic stressors might build over time, but also may provide insight into more rapid recovery from some types of brain injuries,” Steele said.
The Army is funding a parallel project that also is trying to develop a brain-clearing device, led by Rice University, Baylor College of Medicine and Houston Methodist Hospital.
As the military research project proceeds, a separate company founded by Tucker is working to begin a Food and Drug Administration trial of a consumer version of his cap to increase deep sleep. (Others on the research team have no financial interest in Tucker’s device or his companies, they said.)
“I want to be a consumer of this sleep therapy device,” Tucker said. “I want to be sure for the next decade I can maintain the best function I can for an increasingly old guy.”