cerebrospinal
© LAURA LEWIS
ABOVE: During sleep, waves of fluid surge into the brain and can be visualized with functional MRI. At an earlier timepoint (left), a wave of blood (red) is followed (right) by a pulse of cerebrospinal fluid (blue) into the fourth ventricle.
While humans sleep, huge waves of the cerebrospinal fluid that envelops the brain rhythmically flow in and out of the organ, according to a new study published today (October 31) in Science. The authors show that these CSF dynamics are connected to slow waves of neuronal activity, which are characteristic of deep sleep, and corresponding oscillations in the brain's blood volume. Coupled with recent indications that CSF clears waste products from the brain, the findings shed light on the benefits of sleep for the central nervous system.

The work "is exciting because it's linking neural activity to blood flow and cleaning the brain. Most neuroscientists would not say those are linked," Maiken Nedergaard, a neuroscientist at the University of Rochester Medical Center, tells The Scientist. She did not participate in the study, but work from her group has indicated that CSF helps take out the brain's garbage.

It was this idea of CSF as a brain wash — combined with recent evidence showing that sleep is important for clearing toxic metabolic waste products from the brain — that led Boston University's Laura Lewis and colleagues to investigate what CSF does during sleep. For the current study, they designed a new approach combining simultaneous electroencephalograms (EEGs) to measure the brain's electrical activity and blood oxygen level dependent functional magnetic resonance imaging (BOLD fMRI) to collect blood oxygen levels and the flow of CSF in the brain.

The team recorded neuronal activity, blood levels, and CSF flow in two men and 11 women while they wore caps with EEG electrodes and slept in an fMRI scanner for up to two and a half hours. The researchers knew from previous studies that when people are awake there's some pulsing of CSF associated with breathing, heart rate, and other motions of the body — a finding they also confirmed in this study. But in their sleeping subjects, they saw large waves of CSF flow into the fourth ventricle of the brain about every 20 seconds. Plus, the CSF dynamics were coupled to the brain's electrical activity. Specifically, an electrical slow wave and corresponding increase in blood flow was followed a few seconds later by a decrease in blood oxygenation and volume and then a surge of CSF.

"This team has found this wonderful way of measuring these interrelated signals that are implicated heavily in just about every brain disease we know," says Christopher Moore, a neuroscientist at Brown University who did not participate in the study. It's possible the relationship between circulatory dynamics, neuronal activity, and CSF flow comes into play in neurological disorders such as stroke and Alzheimer's where the vasculature is known to play a role, he explains. "The clinical potential of this as both a research tool [and] maybe diagnostically is tremendous."

"We know that electrical slow wave activity declines in aging and declines even more so in neurodegenerative disease," says Lewis, adding that all of the subjects in the current study are young adults."We're working now on trying to understand how these CSF waves are affected across the lifespan and in patient populations."

Right now, the paper draws a correlation between neural activity, blood flow, and CSF rhythms, Moore adds, so another extension of the work will be to use animal models to manipulate each oscillation and see what happens downstream. An additional question, he says, is "how do all these vascular and CSF dynamics impact neurons? They could be for taking out the garbage, but maybe they're . . . doing something far more interesting."
N.E. Fultz et al., "Coupled electrophysiological, hemodynamic, and cerebrospinal fluid oscillations in human sleep," Science, doi:10.1126/science.aax5440, 2019.

Abby Olena is a freelance journalist based in North Carolina. Find her on Twitter @abbyolena.