Sleeping while listening to bursts of pink noise 鈥� background sounds akin to gentle radio static 鈥� seems to boost the flow of fluid through the brain, and so might enhance the clearance of waste products that are linked to conditions like Alzheimer鈥檚 disease. The pink noise seems to bolster the slow brainwaves that enhance the pumping of blood vessels, which drives the brain鈥檚 waste-disposal system.

We already knew that listening to bursts of pink noise during sleep , a kind of electrical activity that occurs during certain phases of聽non-REM聽sleep, known as聽N3 (deep sleep) and N2 (the lighter stage before it). This effect occurs when the bursts coincide with the peaks of slow brainwaves.

鈥淭hey really don鈥檛 sound like much, they鈥檙e just little staticky beeps,鈥� says at Boston University in Massachusetts.

Prior research has also shown that boosting slow brainwaves 鈥� using drugs, for instance 鈥� can enhance the flow of the brain鈥檚 cerebrospinal fluid (CSF), which bathes the brain and carries away waste products.

But it was unknown whether listening to pink noise has the same effect. That鈥檚 because measuring the brain鈥檚 CSF flow involves imaging it with MRI scans, but MRI interferes with EEG, the technique used to measure waves of electrical activity in the brain. One consequence of this interference is that slow waves recorded via EEG during MRI scans can鈥檛 be detected fast enough to align bursts of pink noise with their peaks.

鈥淵ou have to do a lot of extensive processing of the EEG signals to detect slow brainwaves, so it鈥檚 hard to do that fast enough in real-time,鈥� says at the Massachusetts Institute of Technology.

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To overcome this problem, Levitt, Lewis and their colleagues used EEG data collected during MRI scans from prior studies to train an AI model to rapidly predict when the brain鈥檚 slow waves will peak. 鈥淸The AI] says, 鈥業n about 70 milliseconds, a slow wave peak is coming,鈥� so now we should schedule our sound stimulation to arrive in accordance with that,鈥� says Levitt.

鈥淭his, methodologically, really moves the field forward,鈥� says at the University of New Mexico.

The researchers then recruited 27 healthy adults, aged 29 on average, to wear EEG electrodes on their scalp while taking an afternoon nap in an MRI scanner. Of these, 14 managed to fall asleep and enter N2 sleep. 鈥淚t鈥檚 a difficult place to fall asleep,鈥� says Lewis.

At the peak of half of each participant鈥檚 slow brainwaves, the researchers used the AI model to play 50-millisecond bursts of pink noise. During the remaining slow brainwaves, they played no noise as a control.

By analysing the MRI and EEG recordings, they found that bursts of pink noise strengthened the slow waves they coincided with and briefly boosted the flow of CSF into the brain, compared with no sonic stimulation. This suggests the pink noise also enhanced the flow of CSF through, and out of, the brain. 鈥淲e know that the flow in is usually balanced with the flow that comes out,鈥� says Lewis.

The increased CSF flow seemed to be driven by enhanced pumping of the brain鈥檚 blood vessels, which is known to push fluid through the brain鈥檚 waste-disposal system, called the glymphatic system.

Off the back of these results, the team is exploring whether the approach also works in older adults and whether it can boost the clearance of proteins, such as beta-amyloid, that are linked to conditions like Alzheimer鈥檚 disease. If the results are positive, the researchers hope to test whether the technique can slow cognitive decline in people during normal ageing, mild cognitive impairment 鈥� a condition that often precedes dementia 鈥� and the early stages of Alzheimer鈥檚 disease.

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There is reason to think this could work. Exposing people to sounds and flickering lights 鈥� while they are awake 鈥� has previously shown promise at slowing cognitive decline in people with Alzheimer鈥檚, potentially by boosting the glymphatic system.

But one benefit of the new approach is that it could eventually be delivered via a portable device while people are sleeping, which could be less disruptive, says Ryman.

Researchers have identified specific groups of neurons in the brains of mice that are activated after the rodents have been awake for a long time, driving them to get some sleep.听If a similar system exists in humans, it could be targeted to help improve treatments for some sleep disorders.

Inside the brain, several neural circuits聽, including neurons in the hypothalamus that聽.听

One or more of these circuits might be involved in why it is that, the longer we are awake, the more irresistible the urge to close our eyes becomes. But what actually drives this impulse has long been a mystery.

To find out,聽聽at the University of Basel in Switzerland and his colleagues have compared brain activation patterns in mice during normal sleep-wake cycles, sleep deprivation and recovery sleep. They did this by tracing how much protein is produced in cells by a gene called听贵辞蝉, which is turned on when neurons are in the process of activating.

鈥淲e saw that very specific parts of the brain were correlated with wakefulness,鈥� says Joo. This allowed the researchers to identify areas in which activity correlated with time spent awake.听

Within one of these regions, the median raphe nucleus, they found two distinct neuronal populations that were increasingly activated the longer the animals stayed awake and that got quieter again after sleep started. These populations are the GABAergic and serotonergic neurons, so named because the chemical messenger molecules they respond to are gamma-aminobutyric acid (GABA) and serotonin, respectively.

鈥淭his is an outstanding study. The whole-brain Fos mapping is a real tour de force,鈥� says聽聽at the University of Wisconsin鈥揗adison.

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To see whether these neuronal populations became more active simply because the mice had been awake for a long time or whether they do something more, Joo and his colleagues then used viruses to deliver a genetic package to the neurons to either activate or inhibit their action.

When both sets of neurons were artificially activated, the mice slept for twice or three times as long as control mice and spent more time in non-REM slow-wave sleep 鈥� in a way that resembles the deeper recovery sleep humans have after we have been up for a long time.听

鈥淣ot only does it increase the amount of time the animal spends sleeping, but it also increases the quality of the sleep,鈥� says Joo.

When the neurons were inhibited, the mice slept about 70 per cent less than control mice 鈥� spending around 6.5 extra hours awake a day 鈥� without showing more of the anxiety-like behaviours that usually come with sleep deprivation for mice. However, the lack of sleep was lethal in about 17 per cent of the mice.听

The strong effect of activating and inhibiting the neurons means they don鈥檛 just signal that an animal has been awake, says team member聽, also at the University of Basel. 鈥淭hey are crucial to promote sleep, and may be key components of the neural circuitry that generates sleep drive.鈥澛�

The study 鈥渁dds to a growing body of work showing that there are distinct sleep circuits that are activated by wakefulness, yet promote sleep鈥�, says聽聽at Johns Hopkins University in Maryland, whose research has shown that neurons in a brain region called the thalamic nucleus reuniens聽track the gap between how much sleep we need and how much we actually get.

It isn鈥檛 known if the same sleep-driving neuron populations exist in humans, but if they do, the findings could open doors to new therapies for some sleep-related conditions 鈥� once we know how the cells are communicating with other brain regions, say the researchers.听

Projections from these neurons in the median raphe nucleus , and these areas are known to work together to control the sleep-wake cycle.

鈥淭he effect of this major neuronal path on sleep is very strong, but, as we have learned since we started manipulating neuronal circuits, each path provides nuances. The brain has many ways to wake up and fall asleep,鈥� says聽 at Stanford University in California.

For example, there are hints from experiments in fruit flies that聽mitochondria, which power cells, in the brain may play a crucial role in the onset of sleep.听

It may one day be possible to reap some of the benefits of sleep without ever closing our eyes. Stimulating specific brain activity in awake mice led to some of the same effects as deep sleep, including a boost in memory.

鈥淚t should be possible, at least in theory and to some extent, to replicate these results in our species,鈥� says at the University of Oxford, who wasn鈥檛 involved in the research. 鈥淚t would be fascinating to explore whether artificially inducing [this activity] during waking [hours] in humans can result in a subjective feeling of being more refreshed and rested afterwards.鈥�

Sleep is thought to be an essential way for the brain to carry out most of its maintenance work. This includes synaptic homeostasis, the process whereby the brain declutters the thousands of new neural connections made during the day 鈥� storing important ones and weakening or cutting away ones that aren鈥檛 as necessary.

During non-rapid eye movement (NREM) sleep 鈥� the deep sleep state that makes up around 80 per cent of sleep in adults 鈥� the brain鈥檚 cortex repeatedly fires signals at the exact same time and then shuts those neurons off, in a pattern called slow-wave sleep activity. 鈥淭his has been linked to synaptic homeostasis, and may be a key mechanism underlying sleep鈥檚 restorative functions,鈥� says at the University of Wisconsin-Madison.

Cirelli and her colleagues wondered if a small part of the cortex could be nudged into entering this deep sleep state while an individual is still awake. Some animals do this naturally, such as dolphins, ducks and fur seals, in which one half of the brain enters NREM sleep while the other remains alert and vigilant for predators.

To see if a similar state could be induced, the researchers genetically engineered mice so their neuronal activity could be switched off using light. They implanted a probe into one half of their brain and kept the mice awake for five hours by giving them new things to explore. Near the end of this time period, the light probe was repeatedly turned on and off for 30 minutes, mimicking NREM sleep.

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Afterwards, when the mice were allowed to sleep, brain recordings showed that the stimulated side of the brain didn鈥檛 show the usual signs of exhaustion caused by sleep deprivation. 鈥淏ecause that small part of the brain did its decluttering while awake, it no longer needed extra deep sleep afterwards,鈥� says Cirelli.

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Next, the researchers wondered whether forcing sleep during wakefulness boosts memory. So they placed the genetically modified mice in a square box with carpet that had the same texture on both sides of the container. After 15 minutes of exploring the space, the mice were assigned to either a sleep group, a group that was sleep-deprived for 1 hour, or a group that was sleep-deprived for 1 hour but received the artificial deep-sleep stimulation.

The next day, the mice went back into the box, but one side of the container had a new texture. Mice are naturally drawn to novelty, so the researchers measured how much they remembered the old environment by the amount of time they spent on the new side. They found that the sleep-deprived mice that received no stimulation seemed to struggle to tell the new and old side apart, while both the sleep group and the sleep-deprived mice that received the stimulation spent more time on the new side.

The team plans to study whether similar effects could come about in people if this brain activity were induced non-invasively via transcranial electrical stimulation. However, Vyazovskiy stresses that sleep can probably never be replaced. 鈥淪leep is of two kinds 鈥� NREM and REM [rapid eye movement] 鈥� and we still do not know what it is about the alternation of these two states that makes sleep complete,鈥� he says.