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.  

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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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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.

Our memories may persist even when half of the brain connections that store them are wiped out, according to a study in dormant mice. The “remarkable” discovery tells us more about how memory works and could one day reveal ways to improve it.

“Memories may be harder to break than we thought,” says at Boston University, who wasn’t involved in the study. “This absolutely, substantially advances our understanding of how memory works.”

When we experience a stimulus, neurons in our sensory organs, like our eyes, transmit electrical signals to our brain. Neurons then process this information by firing electrical signals to each other via junctions called synapses.

These neurons, called engram neurons, encode information into a memory by forming new synapses and strengthening existing ones. Recalling a memory .

Many scientists think a memory persists as long as the specific pattern of synapses on the engram neurons encoding that memory is maintained. This is partly based on experiments that have used drugs or genetic tools to , says at the Okinawa Institute of Science and Technology in Japan.

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But recent studies suggest a memory persists in location or number. This has called into question “what’s necessary and sufficient to have a memory preserved”, says at Yale University.

To address this, Tanaka and his colleagues took inspiration from hibernating animals. “Under hibernation, brain activity seems to drop significantly,” he says. “But studies in natural hibernators show that somehow those animals, after arousal in the spring, seem to remember their friends and the location of food they hid before hibernation.”

By examining how memory is retained during hibernation, a situation in which the brain changes dramatically, the researchers hoped to unpick basic principles by which the mammalian brain stores memories long term. “The [researchers] very cleverly and creatively get at the question of memory by using hibernation as a way to poke and prod at the brain,” says Ramirez.

They applied weak electric shocks to the feet of mice – which don’t naturally hibernate – while they were in a chamber that smelled of alcohol, creating a fearful memory associated with that scent. The next day, the mice froze in fear upon being placed in the same chamber, without receiving shocks.

The researchers induced an artificial state of hibernation in about half the mice for two days. This was done by injecting them with drugs that slow metabolism and placing them in a dark chamber.

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Five days later, mice that had artificially hibernated still froze when placed in the alcohol-smelling chamber. This was despite brain scans revealing that more than half of the synapses within the engram neurons in their hippocampus – a brain region crucial for memory – disappeared during hibernation. “Despite massive brain remodelling during hibernation, the memories were retained,” says Tanaka.

Dragoi says the findings are relevant to people, since prior research has shown that our brains store information very similarly to mice. “It tells us something about how our mammalian brains may work,” says Ramirez.

The team also found that the hibernating rodents’ brains retained synapses that clustered closely together on the surface of engram neurons, while those outside these clusters disappeared. This suggests that clustered synapses specifically are crucial for retaining memory in the brain, says Tanaka.

Non-clustered synapses that were wiped out by hibernation reappeared within a day post-hibernation, indicating that, while clustered engram synapses are necessary to retain the information within memories, the non-clustered synapses may be important for accessing memories, he says.

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“This study is a remarkable step forward because it addresses a long-standing puzzle in memory research: how the brain retains long-term memories,” says at Vrije University Amsterdam in the Netherlands.

The team is exploring the molecular pathways through which clustered engram synapses store information and plans to dig into how non-clustered ones reappear, says Tanaka.

Targeting such pathways with drugs could even reveal ways to prevent or slow memory impairment, says Ramirez. “It gives hope that even in instances where information seems to be lost in the brain, whether it’s amnesia or Alzheimer’s disease, memory may nonetheless persist.”

A man who became paralysed after a diving accident six years ago regained the ability to move and feel pressure in his hands thanks to brain stimulation. Now, researchers have revealed he maintained this ability for months after the stimulation was turned off. This suggests the intervention has caused a rerouting of his neuronal connections through neuroplasticity.

“We turned everything off completely, for many months, and yet he’s maintained these gains,” says at the Feinstein Institutes for Medical Research in New York. “That’s unheard of.”

Keith Thomas, 48, was paralysed from the chest down in July 2020. He had no sensation or control over his limbs and had significant muscle wasting, says Bouton.

In 2023, Bouton and his colleagues performed a double neural bypass surgery on Thomas, placing five electrodes into his brain in regions associated with arm movements and feeling. They then connected computer cables to these electrodes, so artificial intelligence could interpret his movement intentions. That information was then wired into electronic splints that stimulated his arms, hands and fingers to carry out his intended movements, enabling him to pick up coffee cups and scratch his face.

To recreate the sense of feeling, the team embedded force sensors into 3D-printed wearable devices for Thomas’s hands and fingers, which sent feedback via electrical stimulation into the brain’s sensory areas.

After conducting a series of experiments – which even involved Thomas feeling objects through another person’s hand – Bouton says the team planned to stop the stimulation for about a month, to test for any lingering effects. “Then we had a fire in the building, and it actually forced us to stop stimulation for even longer than we’d planned, for about three months.”

The unexpected interruption led to surprising findings: Thomas continued to maintain strength, feeling and function in his hands. “He’s now also controlling individual fingers with even more accuracy, so that’s big,” says Bouton.

In a video interview with 91av, Thomas raised his elbows nearly to shoulder level and described feeling “tingling” in his wrist in response to pressure, even when he’s “unplugged from the computer”. “When I first felt it, it was amazing,” he says. “I’m used to it now.”

 at the University of California, Davis, says the work suggests that this approach promotes lasting recovery of the nervous system. “The goal is to help the nervous system partially heal so the person can move their own body better,” he says.

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“If these improvements persist even when the system is turned off, then the device is doing more than temporarily restoring function,” says at the University of California, Los Angeles. “It may be helping the nervous system reorganise itself through neuroplasticity.”

This describes the brain’s ability to rewire itself by forming new neural connections, such as or even . “After an injury such as spinal cord injury, those same mechanisms may help restore function by strengthening spared pathways or recruiting alternative circuits, allowing neural signals to travel through networks that were previously too weak to support meaningful movement,” says Lu.

The researchers have observed stronger neural responses in Thomas’s sensory cortex since the intervention.

But this is just a single case report, so it’s unclear how well this approach would work on other people with paralysis from different types of injuries. at the University of Chicago says he has spent years working on stimulation and continues to find that some respond better than others, and some not at all. “And we have no idea why,” he says. “So, the question is: can you replicate it? This is a really ambitious study, but we need to see them replicating their results in more participants before we believe the hype.”

As to Thomas’s future, “at this point now we know nothing’s impossible, or anything’s possible”, says Boulton. “I think it’s possible he will continue to to improve,” he adds.

A cognitive “speed training” game that cuts dementia risk by 25 per cent alters levels of beta-amyloid, a protein that clogs up the brain in Alzheimer’s disease, in men, but not in women.

It is the first time brain training has been shown to influence the levels of a neurodegenerative marker, strengthening the evidence suggesting that mental exercises can boost brain health.

“One of the main markers that’s indicative of future dementia risk got better for men who completed cognitive speed training,” says  at Clemson University in South Carolina, who presented the research at the Alzheimer’s Association International Conference in London on 12 July.

The computer-based speed training involves recalling where objects have flashed up, with the task becoming harder as performance improves. A prior 20-year study by some of Chai’s colleagues showed that people aged 65 and older, who did the training were 25 per cent less likely to be diagnosed with Alzheimer’s disease or a related form of dementia compared with a control group.

In the latest study, Chai and her team recruited a separate group of 53 people from the US aged 65 and older, 13 of whom were male. About a third of the participants were asked to complete between 2 and 4 hours of speed training each week for 4.5 months.

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The remaining participants were either told to spend the same amount of time playing games such as Solitaire, word search and a game similar to Connect 4, or to complete another kind of brain training in which they had to strategically track objects and switch between tasks.

To explore how speed training may reduce dementia risk, the team collected blood samples from all of the participants at the start and end of the training period.

This revealed that, among men, speed training increased the ratio of two forms of beta-amyloid found in the blood, which suggests the training boosted the brain’s ability to clear beta-amyloid 42. This protein forms clumps called plaques in the brain during Alzheimer’s disease, disrupting brain function. The other two kinds of training had no effect.

“It’s a really cool finding,” says  at McGill University in Montreal. “It is definitely strengthening what they’ve [previously] shown with the reduction in dementia.”

Some Alzheimer’s treatments, such as lecanemab, have been designed to help clear amyloid from the brain, but they only marginally slow cognitive decline during Alzheimer’s disease. The limited benefit seen in trials is probably down to these treatments being taken at a relatively late stage of the condition, when substantial brain damage has already occurred, says at University College London.

Engaging in cognitive training to reduce beta-amyloid build-up before dementia develops may have a bigger effect on dementia because it would be done before much brain damage has occurred, says Castegnaro.

However, cognitive training had no effect on amyloid levels in female participants in the study. This suggests that speed training reduces dementia risk in different ways in women and men, says Chai.

The team hopes to explore how speed training may benefit women in future studies, says Chai. But first, the findings need to be verified in geographically and ethnically diverse groups, says Novozhilova.