Researchers know that sleep is important — not just in terms of allowing the brain to reactualize, but also for “making space” for “cleaning” processes to take place.
However, many of the mechanisms through which this clearing out of brain waste takes place during sleep remain unclear.
Now, researchers at Boston University in Massachusetts have found that during sleep, the fluid present in the brain and spinal chord — called the cerebrospinal fluid — washes in and out, like waves, helping the brain get rid of accumulated metabolic “trash.”
“We’ve known for a while that there are these electrical waves of activity in the neurons. But before now, we didn’t realize that there are actually waves in the cerebrospinal fluid, too,” study co-author Laura Lewis explains.
“Sleep is critical to the function of the brain’s waste removal system and this study shows that the deeper the sleep the better,” says Maiken Nedergaard, codirector of the Center for Translational Neuromedicine at the University of Rochester Medical Center (URMC) and lead author of the study.
“These findings also add to the increasingly clear evidence that quality of sleep or sleep deprivation can predict the onset of Alzheimer’s and dementia.”
The study, which appears in the journal, indicates that the slow and steady brain and cardiopulmonary activity associated with deep non-REM sleep are optimal for the function of the glymphatic system, the brain’s unique process of removing waste. The findings may also explain why some forms of anesthesia can lead to cognitive impairment in older adults.
The researchers used electroencephalography (EEG) to monitor the brain waves of 13 sleeping healthy adults, while also using a cutting-edge, “accelerated” fMRI technique to capture faster changes than standard fMRI can manage. That allowed for the measurement of both blood-oxygenation changes (which indicate blood flowing to electrically active, oxygen-hungry regions) and CSF flows. The latter was only possible due to a flaw in this method that means any newly arriving fluid (not just oxygenated blood) lights up in the image. “We realized we could take advantage of this to measure CSF flow at the same time as blood oxygenation,” Lewis says. “That was critical, because it turns out these things are coupled to each other in a way we never would have seen if we didn’t measure blood, CSF and electrical activity simultaneously.”
What the team found was that the slow waves seen in non-REM sleep occur in lockstep with changes in both blood flow and CSF. Just because things occur together doesn’t necessarily mean one causes the other, but the team also built a computer model incorporating what we know about the physics linking these processes, which predicted that slow waves would have just these kinds of effects on blood and CSF. What seems to be happening is that as brain activity alters blood flow, this reduces the volume of blood in the brain, and because the brain is a closed vessel, CSF flows in to fill the space. “It’s very convincing,” says neurologist Maiken Nedergaard of the University of Rochester, who was not involved with the research. “It also really makes sense: electrical activity drives blood flow changes, that then drive CSF changes.”
The team measured this CSF inflow going into the fourth ventricle, one of four fluid-filled cavities involved in producing CSF (by filtering blood plasma) and circulating it around the brain. As CSF usually flows out of the fourth ventricle, this suggests a “pulsatile” flow, like a wave. This pushes CSF around the ventricles and into spaces between membranes surrounding the brain and spinal cord, called the meninges, where it mixes with “interstitial fluid” within the brain to carry away toxic waste products.
As slow waves are important for memory consolidation, this links two disparate functions of sleep. “What’s exciting about this is it’s combining features of brain function that people don’t normally think of as connected,” Nedergaard says. It isn’t obvious things had to be this way, Lewis says, but it may represent an example of nature being efficient. “It’s a matter of nature not dividing tasks between higher level and lower level, like how you run a company, where you have a boss making decisions and cleaning people coming in,” Nedergaard says. “In biology, it’s everybody contributing, as it makes more sense.”
Researchers who study Alzheimer’s say Nedergaard’s research could help explain a number of recent findings related to sleep. One of these involves how sleep affects levels of beta amyloid, says Randall Bateman, a professor of neurology Washington University in St. Louis who wasn’t involved in the study.
“Beta amyloid concentrations continue to increase while a person is awake,” Bateman says. “And then after people go to sleep that concentration of beta amyloid decreases. This report provides a beautiful mechanism by which this may be happening.”
The report also offers a tantalizing hint of a new approach to Alzheimer’s prevention, Bateman says. “It does raise the possibility that one might be able to actually control sleep in a way to improve the clearance of beta amyloid and help prevent amyloidosis that we think can lead to Alzheimer’s disease.”