Human brain organoids have been implanted into mice that are missing half their brain. Tiny versions of the human cerebral cortex – a region involved in memory, movement and thinking – were put into mice that lacked this major brain region. Not only did the organoids integrate into the mice’s brains, but they also restored most of their cognition.

“The mouse is [relatively] sick without a cortex, then you transplant these organoids in, and it behaves more like the normal mouse,” says at the University of Cambridge, who wasn’t involved in the research.

at Stanford University in California and his colleagues genetically engineered mice to lack more than 90 per cent of their cortex, or about half their brain. These mice experience only some memory and movement deficits, since their brain adapts to compensate for their missing cortex, says Pașca.

In about half of these mice, the team surgically implanted four human brain organoids, generated by bathing human stem cells in chemicals for about 40 days. These filled the cavity in each mouse’s skull, producing what the researchers called XCX mice. The remaining mice, apallial mice, didn’t receive the transplants.

A few months later, the apallial mice performed worse in a memory test, where they had to navigate a maze, than a third group of normal mice with intact brains. But this deficit was almost completely reversed in the XCX mice. The XCX mice also had a gait between that of the apallial and normal mice.

Scans revealed that the organoids had grown to form cortex-like grafts. “Half the volume of the brain is [initially] gone, and now largely 90 per cent of that missing volume is covered by human cells,” said Pașca.

This builds on prior studies that have implanted human brain organoids into rat or mouse brains, but without such a large part of the rodent brain being missing initially, says Pașca. These studies showed only that such organoids can alter cognition, rather than improving it, he says. For instance, in one study, light stimulated human brain organoids in rats to make them anticipate water.

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The grafts in the latest study were also the first to contain a kind of nerve cell, called von Economo neurons, that influences social skills, as well as neurons that extended from the cortex to the spinal cord. The latter could explain why these grafts reduced impairments in motor skills, says Balmuș.

The team’s organoids were larger and more akin to the human cerebral cortex than those used in previous experiments, says Pașca. But according to at the Institute of Molecular Biotechnology in Vienna, Austria, they still lack the proper arrangement and structure of the cortex. “It’s a bit of a mishmash of neurons” and other cells, he says. “Most of the cell types are there, but they’re not separated into regions like in a normal cortex.”

In another experiment, the team showed that human organoid transplants made mice respond to hypoxia, or low oxygen levels, in a way similar to people. Mice have evolved to be highly resilient to low oxygen levels, due to living underground, so it is hard to replicate this in a normal mouse, says Balmuș. This suggests that these experimental animals could provide a better way to study cerebral palsy, a condition that causes movement problems and can be caused by hypoxia around birth, says Balmuș.

But such experiments come with ethical concerns, says Knoblich. These mice “deserve the same kind of protection that we ascribe to any animal experiment, meaning that we need to make absolutely sure that there’s no sensation of pain, that there is no unnecessary suffering, and that the risk of the experiment is matched to the medical gain,” he says. The latest study achieved this, he says.

A common concern is whether mice with human brain organoids will gain a human-like level of consciousness. “The data so far doesn’t say that putting [a human organoid] in makes the mouse smarter or more conscious than a normal mouse,” says Knoblich. “It’s similar to taking a wheel from a car and putting it on a tree and saying that’s a car.”

A brain implant has enabled people with paralysis to speak while gesturing, such as nodding or waving. These sorts of exchanges, done via an avatar, could help them communicate with more nuance.

“In our everyday life, gestures play an important role in communication,” says at the University of California, San Francisco. “Saying ‘maybe’ and nodding your head has a very different connotation than if you shake your head.”

Experimental brain implants have boosted the ability to either speak or move among people with paralysis, but simultaneously haven’t been very successful. To achieve this, implants need to cover a large part of the sensorimotor cortex, a brain region involved in speech and movement, says Brosler.

Now, Brosler and her colleagues have tested an iPhone-sized implant in this part of the brain in two people with paralysis. The first participant, who the researchers call Bravo-1r, became paralysed after a stroke, while the second, Bravo-6, had amyotrophic lateral sclerosis, the most common form of motor neuron disease.

Both participants had lost almost all movement in their limbs. They also couldn’t speak and could only make unintelligible sounds.

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First, the team recorded the participants’ brain activity while they repeatedly attempted to say 10 phrases – such as “hello”, “nice to meet you” and “how’s it going?” – or perform 10 gestures, like waving, clapping and shaking their head. In some cases, the participants attempted to do these separately, while in others they tried both simultaneously.

The team then used each of the participants’ brain recordings to train customised machine learning models to predict their intended phrases and gestures.

To put the models to the test, the participants attempted to repeat various pairs of phrases and gestures that were displayed on a screen. The models interpreted their brain activity and used that to control the movement of an avatar resembling the participants, while the speech predictions flashed up on the screen. 

The team chose to use avatars, rather than attempting for the individuals themselves to speak and gesture, because this offered a relatively simple way to prove that both actions could be simultaneously decoded from brain activity, says Brosler.

Paralysed man can feel objects through another person’s hand

Keith Thomas, a man in his 40s with no sensation or movement in his hands, is able to feel and move objects by controlling another person’s hand via a brain implant. The technique might one day even allow us to experience another person’s body over long distances.

Bravo-1r’s intended gestures and speech were predicted with 88 and 84 per cent accuracy, respectively, while Bravo-6’s were predicted with 66 and 70 per cent accuracy. “If those models were operating on complete chance, the accuracy would be like 9 per cent,” says Brosler. “It was really exciting.”

“It’s a very nice piece of work, with robust results,” says at the University of Lausanne in Switzerland. But it’s based on a very limited set of phrases and gestures, and these still need improving, he says. “For daily use without frustration, there needs to be higher accuracy.”

Brosler says the team is working to address this by further training the models and tweaking the algorithms. She also says that future models could move a person’s own body – if their joints and muscles are in a good enough condition – and produce a synthetic voice, rather than having to do this via an avatar.

Sleeping while listening to bursts of pink noise – background sounds akin to gentle radio static – 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’s disease. The pink noise seems to bolster the slow brainwaves that enhance the pumping of blood vessels, which drives the brain’s 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 non-REM sleep, known as N3 (deep sleep) and N2 (the lighter stage before it). This effect occurs when the bursts coincide with the peaks of slow brainwaves.

“They really don’t sound like much, they’re just little staticky beeps,” says at Boston University in Massachusetts.

Prior research has also shown that boosting slow brainwaves – using drugs, for instance – can enhance the flow of the brain’s 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’s because measuring the brain’s 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’t be detected fast enough to align bursts of pink noise with their peaks.

“You have to do a lot of extensive processing of the EEG signals to detect slow brainwaves, so it’s hard to do that fast enough in real-time,” 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’s slow waves will peak. “[The AI] says, ‘In about 70 milliseconds, a slow wave peak is coming,’ so now we should schedule our sound stimulation to arrive in accordance with that,” says Levitt.

“This, methodologically, really moves the field forward,” 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. “It’s a difficult place to fall asleep,” says Lewis.

At the peak of half of each participant’s 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. “We know that the flow in is usually balanced with the flow that comes out,” says Lewis.

The increased CSF flow seemed to be driven by enhanced pumping of the brain’s blood vessels, which is known to push fluid through the brain’s 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’s 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 – a condition that often precedes dementia – and the early stages of Alzheimer’s disease.

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Physical activity causes a type of brain cell called astrocytes to contract, which then leads to the formation of new neurons, according to a study in mice

There is reason to think this could work. Exposing people to sounds and flickering lights – while they are awake – has previously shown promise at slowing cognitive decline in people with Alzheimer’s, 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.

Hubs of immune cells in the skull may help to defend our brain from ill health. A study into the brains of mice and human genetic data suggests that immune cells cluster in a particular area at the back of our skull. The discovery implies that targeting these hubs with drugs could bring new treatments for conditions where immune cells go rogue, such as brain cancer.

“It’s an important step forward in understanding the brain’s immune response,” says at the University of Oulu in Finland, who wasn’t involved in the study. As well as being applicable for cancer, “it’s relevant for understanding things like infections, inflammatory brain diseases, multiple sclerosis [and] neurodegenerative diseases”, he says.

Immune cells called T-cells and B-cells are activated to act in the brain if they are presented with signs of threats, like fragments of tumours, in the lymphatic system. Now, at Washington University in St. Louis, Missouri, and his colleagues have uncovered another way these T- and B-cells are activated.

By imaging and analysing the skulls of mice, the team found that B- and T-cells cluster together with immune cells called antigen-presenting cells in immune hubs at the back of the skull. “These haven’t been described before,” says Kiviniemi. These hubs resemble lymph nodes, where antigen-presenting cells expose threats like tumour fragments to T- and B-cells.

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The team thinks these immune hubs are also in people. This is based on gene activity data collected from human skulls in prior studies, which suggest that T-cells were activated and helped activate B-cells in this part of the body. “It indicates the same is present in humans”, says Kiviniemi, although further studies analysing the skulls of cadavers are needed to confirm this.

To explore whether these hubs launch protective immune responses, the researchers injected cancer cells into the brains of mice. They then injected half the mice beneath the scalp with an experimental drug that disrupts the activation of B- and T-cells in the skull. This works by blocking a protein called CD40L on antigen-presenting cells, which helps them activate these immune cells. The remaining mice received saline injections.  

‘Remarkable’ discovery upends our understanding of how brains store memories

Memories in mice persisted even after they lost the connections that we thought were needed for recall, expanding our knowledge of memory in the mammalian brain

The mice that received the drug went on to live for about 25 days, on average, after the tumour injection, whereas those in the placebo group lived about 30 days. This suggests the immune hubs help to generate an anti-cancer immune response, says Kiviniemi.

In another experiment, a group of mice was given the same tumour injection, but this time, half received three drugs that enhanced the activation of B- and T-cells in their skull. These mice survived for about 10 days longer than others that got placebo injections.

If the same immune hubs are confirmed to exist in people, targeting them could bring new therapies for many brain-related conditions, says Kiviniemi. “We could figure out how to awaken and strengthen these [hubs],” he says.

Tiny versions of the cerebral cortex, a brain region involved in thinking and memory, have been grown for five years, making them the longest-lived brain organoids that have been studied in detail. Their genetic activity also mimicked that typically seen in the brain of a 4-year-old child, suggesting that the organoids could sense time passing.

“This demonstrates for the first time that not only can human brain organoids be grown for about five years, but they also show an ageing profile that corresponds with that of the developing brain of a similar age,” says at the University of Cambridge, who wasn’t involved in the study.

Brain organoids are clumps of brain cells grown in a lab dish. They are created by bathing stem cells in chemicals that coax them to form clumps resembling fetal brains. Studying them has already provided insights on autism and conditions like dementia. But the expense and manual labour involved means they are usually only grown for a few months, says Lakatos.

In 2021, researchers reported growing , with these structures mimicking the cerebral cortex from its development during pregnancy to nearly one year after birth.

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Now, at Harvard University and her colleagues have analysed the genetic activity of five-year-old cortical organoids grown from human stem cells. The team has grown the same kind of organoids for seven years, but there are too few of these older organoids to reliably analyse them, she says.

The researchers analysed the genetic activity and epigenetic marks – chemical tags added to DNA that regulate gene activity and shift with age – in cells within the five-year-old organoids. When comparing these measurements against those recorded from the brains of fetuses in previous research, they found that, at three to six months, the organoids resembled the fetal brain at around three to six months post-conception.

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Research that involves creating “mini-organs” from human cells, including those from fetuses, may leave people uncomfortable – so the best approach is to explain the reasoning behind the work and its potential benefits

With time, the organoids resembled the later stages of brain development, with the activity of five-year-old organoids mimicking that seen in the cerebral cortex of a typical 4-year-old child. “They were recording the passage of time in their epigenetic signatures [and gene activity],” says Arlotta.

Such long-lived organoids could offer a way to study how autism and conditions such as epilepsy emerge during the later stages of brain development, says Lakatos. Arlotta says she and her colleagues are using their organoids for this purpose, as well as to screen for drugs that may be able to alter the progression of conditions like epilepsy.

Other groups of researchers won’t be readily able to do this, due to the challenges of growing organoids, says Lakatos. Finding ways to speed up organoid ageing will be important for research, he says.