For the first time, scientists have discovered that a small region of our brain shuts down to take microsecond-long naps while we're awake. What's more, these same areas 'flicker' awake while we're asleep. These new findings could offer pivotal insights into neurodevelopmental and neurodegenerative diseases, which are linked to sleep dysregulation.
Scientists from Washington University in St. Louis (WashU) and the University of California Santa Cruz (UCSC) made these findings by accident, noticing how brain waves in one tiny area of the brain shut down suddenly for just milliseconds when we're awake. And in this same region, those brain waves jolt suddenly, for the same amount of time, when we're asleep.
“With powerful tools and new computational methods, there’s so much to be gained by challenging our most basic assumptions and revisiting the question of ‘what is a state?’” said Keith Hengen, Assistant Professor of Biology at WashU. “Sleep or wake is the single greatest determinant of your behavior, and then everything else falls out from there. So if we don't understand what sleep and wake actually are, it seems like we’ve missed the boat.”
Until now, sleeping and awake states have been defined by overall brain wave patterns – alpha, beta and theta waves when we're awake, delta when we're not – so these 'flicker' anomalies challenge what we've so far understood about these distinct states.
“It was surprising to us as scientists to find that different parts of our brains actually take little naps when the rest of the brain is awake, although many people may have already suspected this in their spouse,” joked David Haussler, Professor of Biomolecular Engineering at UCSC.
In a four-year study that gathered a massive amount of electrophysiology data, the scientists recorded the brain-wave voltage in 10 different regions of the brain in mice. Over several months, they tracked activity from small groups of neurons down to the microsecond. Petabytes of data was then analyzed by an artificial neural network, to pick up patterns and isolate microsecond anomalies that human studies have missed.
“We're seeing information at a level of detail that’s unprecedented,” Haussler said. “The previous feeling was that nothing would be found there, that all the relevant information was in the slower frequency waves. This paper says, if you ignore the conventional measurements, and you just look at the details of the high frequency measurement over just a thousandth of a second, there is enough there to tell if the tissue is asleep or not. This tells us that there is something going on a very fast scale – that's a new hint to what might be going on in sleep.”
Through machine learning, the scientists homed in on millisecond stretches of brain activity data and found that rapid activity between a couple of neurons in one region appeared to go against the grain but be fundamental to sleep, which is typically represented by slow-moving delta waves. And they observed the opposite rate of activity during periods classically defined as being awake – which the team termed 'flickers.'
“We'd taken out all the information that neuroscience has used to understand, define, and analyze sleep for the last century, and we asked, ‘Can the model still learn under these conditions?’” said David Parks, a researcher at UCSC. “This allowed us to look into signals we haven’t understood before.”
Essentially, what the data was showing was that, even while we're awake, in that small area of the brain, a few neurons are switching into sleep mode, while the rest of the organ continues to operate as normal.
“We could look at the individual time points when these neurons fired, and it was pretty clear that [the neurons] were transitioning to a different state,” said Aidan Schneider, a researcher at WashU. “In some cases, these flickers might be constrained to the area of just an individual brain region, maybe even smaller than that.”
The researchers then attempted to see what, if any, physical response could be observed during these split-second micro-naps. They were surprised to see that mice briefly looked to have 'zoned out', and during sleep, the animals twitched at these same 'flicker' moments.
“We are seeing wake to REM flickers, REM to non-REM flickers – we see all these possible combinations, and they break the rules that you would expect based on a hundred years of literature,” Hengen said. “I think they reveal the separation between the macro-state – sleep and wake at the level of the whole animal, and the fundamental unit of state in the brain – the fast and local patterns.”
The findings may offer new insights into conditions that are associated with dysregulated sleep, providing a new target for treatment of neurodevelopmental and neurodegenerative diseases.
“This gives us potentially a very, very sharp scalpel with which to cut into these questions of diseases and disorders,” Hengen said. “The more we understand fundamentally about what sleep and wake are, the more we can address pertinent clinical and disease related problems.”
The study was published in the journal Nature Neuroscience.
Source: University of Santa Cruz