The study describes how the body clears toxins out of the brain while we sleep, and may open new paths for treating and preventing Alzheimer’s and other neurodegenerative disease. Lewis was curious as to how toxins were cleared and why the process only happened during sleep; cerebrospinal fluid was suspected to be involved, but it was not clear if this was unique to sleep.
While sleeping the brain travels through several phases from light sleep to deep sleep, to rapid eye movement. This study was designed to measure several different variables at the same time, and examines non-REM sleep, the deep phase which generally happens earlier on and has been previously associated with memory retention.
Participants went to sleep inside an MRI machine, to get realistic sleep cycles testing was done at midnight, subjects stayed up late the night before so they would be primed to drift off when the testing began. Participants were outfitted with EEG caps to examine electrical currents flowing through the brain to show which state of sleep each participant was in; and the MRI measured blood oxygen levels in the brain and showed how much cerebrospinal fluid was flowing in and out of the brain.
“We had a sense each of these metrics was important, but how they change during sleep and how they relate to each other during sleep was uncharted territory for us,” says Lewis.
During non-REM sleep large slow waves of cerebrospinal fluid were discovered to be washing over the brain, EEG readings helped to show why. During this period neurons start to synchronize to turn on and off at the same time. “First you would see this electrical wave where all the neurons would go quiet,” says Lewis. The neurons had momentarily stop firing and didn’t need as much oxygen, meaning less blood would flow to the brain; cerebrospinal fluid was observed to then rush in filling the spaces left behind.
“It’s a fantastic paper,” says Maiken Nedergaard, a neuroscientist at the University of Rochester. “I don’t think anybody in their wildest fantasy has really shown that the brain’s electrical activity is moving fluid. So that’s really exciting.” “It’s telling you sleep is not just to relax,” says Nedergaard. “Sleep is actually a very distinct function.”
While we are awake neurons don’t turn all the way off, meaning blood levels won’t drop enough to allow the substantial waves of cerebrospinal fluid to move in to circulate around the brain and clear out all the metabolic byproducts that have accumulated such as beta amyloid and tau molecules.
Finding a way to clear out all of the garbage that accumulates in the brain is important, and it may be more powerful than focusing on just a single piece of the problem such as the many failed attempts at developing medications. “This opens a new avenue. Aging is not just about one molecule,” says Nedergaard. “Everything fails.”
Such discoveries bring about their own questions, including what happens during other stages of sleep and what happens in groups of people other than healthy young adults. Methods used in this study were entirely noninvasive as they could be including not injecting any dye. This may make it easier to study older populations who may be developing neurodegenerative diseases. This also means that there are likely more late nights to come at the lab for Lewis.
