Sleep appears in the brain as slow waves surging across the surface at a rate of around one every tenth of a second – or so we thought.
A new study in mice suggests there are patterns of brain activity related to sleep that we've overlooked – and that reflect the state of individual brain cells rather than the collective activity of millions or billions of neurons.
What's more, in measuring these hyperlocal, sub-millimeter brain signals using single-wire electrodes, researchers have found that parts of the mammalian brain might be dozing off for brief naps while other regions remain wide awake.
"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," says David Haussler, a bioinformatician at the University of California (UC) Santa Cruz.
For a century or so, brain-wide patterns of electrical activity have been used to define, in a quantitative sense, the difference between being asleep and awake. These brain waves are most often detected using an electroencephalogram (EEG), via electrodes placed on the scalp.
"With powerful tools and new computational methods, there's so much to be gained by challenging our most basic assumptions," says Keith Hengen, a neuroscientist at Washington University in St. Louis and senior author of the study.
"The more we understand fundamentally about what sleep and wake are, the more we can address pertinent clinical and disease related problems."
Hengen and his team questioned how we've measured sleep and distinguished it from wakefulness – when clearly there is some crossover in the brains of animals that stay alert while sleeping, a skill known as unihemispheric slow-wave sleep.
In the 1960s, researchers first suspected and then detected how dolphins and other cetaceans can rest half of their brain while remaining active, sometimes keeping one eye open to monitor for predators and maintain contact with others in their pod.
Seals and birds also display variations of this part-sleep, part-awake rest – a clever trade-off between sleep and survival.
Humans, too, can temporarily display asymmetrical sleep patterns that are reminiscent of, but not the same as, those seen in animals.
In 2016, researchers at Brown University in the US found that the first night people slept in an unfamiliar place, the left side brain was more alert to deviant sounds than the right. Once we become accustomed to a sleep environment, this difference subsides.
"The human brain, it turns out, is endowed with a less dramatic form of the unihemispheric sleep found in birds and some mammals," neuroscientist Christof Koch wrote in Scientific American when those results were published.
If the mouse brain is anything to go by, the blurring of wake and sleep states in humans might be a neurological feature we share with other animals after all.
Haussler and the team collected weeks of data from nine mice that had thin-wire electrodes implanted into 10 different regions of their brains, and fed this data into an artificial neural network that learned to distinguish between sleep and wake states.
Recordings were sampled from 100 micrometers (one-tenth of a millimeter) of brain tissue, and the algorithm could reliably identify sleep-wake cycles based on short 'flickers' in brain cell activity lasting just 10 to 100 milliseconds.
These 'hyperlocal' signals suggested that part of the animals' brains dozed off to sleep while other regions stayed active and awake. Coincidentally, the researchers noticed this happened right when the mouse might stop moving for a split second, almost like it had 'zoned out'.
"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," explains Aiden Schneider, a computational biologist at Washington University in St. Louis, who co-led the study with David Parks, a computer science graduate student at UC Santa Cruz.
"In some cases, these flickers might be constrained to the area of just an individual brain region, maybe even smaller than that."
The team thinks their new method of measuring sleep-wake states could reveal new secrets about how we slumber, if these 'flickers' can be observed by other research groups.
"They [the flickers] break the rules that you would expect based on a hundred years of literature," says Hengen.
The study has been published in Nature Neuroscience.