Clarifying the math behind Anthropic’s representation workspace

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The Alzheimer’s brain faces a double whammy. Toxic protein clumps build up inside and outside neurons to torpedo normal function and destroy delicate structures. Eventually, the cells die. The adult brain has an extremely limited ability to grow new neurons. Once gone, they’re rarely replaced. Over time, the brain withers, taking learning, memory, and cognition with it.

But there might be a sneaky workaround. The brain is packed with star-shaped cells called astrocytes that keep neurons healthy. They’re also shape-shifters. Under certain conditions, astrocytes can shed their identity and transform directly into mature neurons. In other words, they could be an abundant, untapped source of replacement neurons.

A team at the University of South Carolina has now taken advantage of this quirk. They engineered a tiny molecular cage and filled it with antibodies. Once inside astrocytes, the antibodies released a protein “brake” that normally keeps the cells’ identity stable. Free from this constraint, astrocytes in lab dishes and human brain organoids adopted the molecular signatures of neurons and eventually sparked with electrical activity.

In mice modeling Alzheimer’s disease, the treatment increased the number of neurons in the hippocampus, a brain region crucial for learning and memory and one of the first to falter in the disease. Treated mice resumed normal behavior and performed similarly to healthy mice on tests of learning and memory in a maze.

The approach fundamentally differs from existing methods and could “unlock previously inaccessible regenerative mechanisms,” wrote the team. If it proves safe and effective in clinical trials—and that’s a big if—the approach could one day tackle diseases beyond Alzheimer’s, such as Parkinson’s or amyotrophic lateral sclerosis (ALS).

Born Identity

The quest to treat Alzheimer’s has often been called the “graveyard of dreams.” The most common form of dementia, the disease affects roughly 24 million people worldwide and slowly eats away at thinking, memory, learning, and emotional regulation. Experts still debate Alzheimer’s root cause, but they largely agree that clumps of misshapen proteins called amyloid beta and tau exacerbate the disease.

Current FDA-approved treatments have had limited success. Antibodies that clear clumps offer only modest benefits to cognition and carry the risk of serious side effects. Other drugs, such as memantine, alter brain chemicals to protect damaged cells, rev up faltering brain circuits, and ease symptoms. But they don’t halt degeneration. As the disease progresses, benefits fade.

The central problem is frustratingly clear. Neurons die faster in Alzheimer’s than the brain can replace them. That’s why a landmark study nearly two decades ago made waves. Scientists once thought mature astrocytes were set in their fate. But the study showed the cells could be reprogrammed into neurons that generated electrical activity and formed connections with neighboring neurons in lab dishes to form working circuits.

Scientists later found a protein called PTBP1 that prevented this conversion. In 2020, a team injected an RNA-targeting form of CRISPR into the brains of mice modeling Parkinson’s disease. This reduced PTBP1 levels, which in turn, triggered the production of new neurons. The treatment restored the mice’s balance and motor skills, although some experts were skeptical.

While promising, CRISPR-based approaches can have unintended effects, and brain surgery is a tall order for any treatment. So, the team developed another way to release the PTBP1 brake.

Erase, Rewind

They turned to a duo of technologies that transport antibodies inside nanoparticle cages to degrade specific proteins inside cells. In this case, they used antibodies targeting PTBP1 and packaged the concoction in a biocompatible gel injected into the bloodstream.

Because of their large size, antibodies can’t usually cross the blood-brain barrier, a tightly sealed wall that keeps many molecules out of the brain. But the nanoparticle system helped ferry the antibodies across the blockade, nixing the need for brain surgery.

The team first tested the drug, called TN-PTBP1, on astrocytes grown in lab dishes. Within days, the cells lost their star shapes and began growing long, willowy branches characteristic of neurons. Their molecular profile also shifted, and the cells eventually burst with electrical signals.

The team recorded similar results in brain organoids, or “mini brains,” grown from human stem cells. Given a small electrical zap, the converted neurons responded in synchrony with neighboring neurons, suggesting they had integrated into existing neural circuits.

“The new neurons can become mature and survive,” said study author Peisheng Xu in a press release.

Next, they tested the drug in a mouse model of Alzheimer’s disease. By eight months, the mice showed clear signs of the disease. Their brains were highly inflamed and littered with toxic protein clumps. Neurons in the hippocampus had also substantially died off, similar to the loss seen in moderate to severe Alzheimer’s in humans.

The mice struggled with everyday behaviors, such as foraging for material to build nests. And they consistently performed poorly on a classic memory test where they had to find a location using visual cues (a bit like remembering where you parked your car).

Half the mice received TN-PTBP1 for two weeks; the others received saline. As expected, the drug reliably slashed PTBP1 levels in the brain. Over the course of the trial, treated mice increasingly improved on tests of cognition and memory, eventually performing at levels similar to healthy peers. Mice treated with saline showed no improvement.

“After just two injections, these mice became smarter,” said Xu. “Even after one injection, we already saw these mice’s behavior differ from that of the nontreated ones.”

The team found broader benefits too. The drug reduced inflammation and, surprisingly, the number of toxic protein clumps, suggesting it may have helped restore some of the brain’s ability to rid itself of waste. Neuron density also increased throughout the brain, and the treatment boosted production of proteins involved in maintaining the blood-brain barrier, which is often damaged in Alzheimer’s.

One unexpected, and welcome, effect was neurogenesis, the birth of new neurons in the hippocampus and another brain region. Neurogenesis declines with age, and whether it exists at all in adult humans is hotly debated. How TN-PTBP1 triggered it in mice remains a mystery. It’s also unknown how much the new neurons contributed to the animals’ recovery versus the direct conversion of astrocytes into neurons.

Still, it’s clear the drug boosted neuron numbers and “successfully reversed Alzheimer’s disease progression” in the mice, wrote the team.

The approach has a long road ahead. Many promising treatments in mice have failed in clinical trials. In the next few years, the team hopes to test the approach in monkeys, dial in the dose, and assess long-term safety. Astrocytes perform many tasks that keep the brain humming, and forcing them to abandon their identity could have unexpected consequences. There’s also the possibility newly converted neurons could scramble existing brain circuits rather than integrating safely, causing more harm than good.

But with rigorous testing, the drug could offer new hope.

The post This Drug Makes New Neurons in the Brain. Scientists Say It Reversed Alzheimer’s Symptoms in Mice. appeared first on SingularityHub.

Five years is an eternity for brain organoids. Also called mini brains, these blobs of tissue have taken neuroscience by storm for their ability to capture the intricacies of developing brains.

Organoids begin life as a collection of stem cells. Within weeks, they spontaneously produce a range of brain cells. Neurons form circuits that spark with electrical activity. Gene expression resembles that of early fetal brains. Some organoids learn to control small, isolated muscles. Others link to spinal cord organoids and process pain signals.

Over time, they grow more sophisticated in both structure and function—eerily similar to near-term fetuses—prompting bioethicists to ask if they could one day become conscious.

But time isn’t on their side. Most mini brains survive only a few months before their sensitive neurons start to wither. Circuits break down, structures collapse, and eventually the organoids die. As a result, they can model only the early stages of human brain development, leaving what happens during the later months of pregnancy and after birth largely mysterious.

These periods are especially relevant to schizophrenia, epilepsy, severe autism, and a host of other disorders. Scientists have studied late-stage development using donated tissue, but samples are scarce and raise ethical concerns.

A team led by Harvard’s Paola Arlotta is now pushing the boundaries with organoids. Last week, they described a method that kept mini brains alive for over five years—the longest yet—and tracked their development throughout. Despite growing outside the body, the organoids matured on a timetable similar to normal brains. Genetic activity in the oldest ones resembled that of a typical 4-year-old.

The findings were originally reported in a preprint and have now been peer-reviewed and published in Nature.

The developmental lockstep surprised the team. Cells from older organoids, when mixed with younger ones, continued maturing on schedule, suggesting they carried an internal developmental clock that keeps track of their progress.

“The brain doesn’t develop in a vacuum. It’s an organ of incredible complexity that interacts with so many other systems,” study author Irene Faravelli said in a press release. “It was not a given at all that our simplified model would match natural development in this many ways.”

Brain, Interrupted

Because mini brains generate nearly the full range of human brain cells, they’re promising models for the study of early brain development. But early versions survived only a few weeks. Without blood supply, cells at their centers starved and died.

Through trial and error, researchers learned to coax them into increasingly sophisticated structures that included layers resembling the cortex and had integrated blood vessels. This vastly extended their lifespan.

In 2021, a study kept mini brains alive for up to two years, capturing cortical development from pregnancy to roughly a year after birth. Four years later, Arlotta’s team announced a way to extend organoid lives to a staggering seven years. Roughly the size of a pea, each nugget was packed with some two million healthy neurons and other brain cells.

Following these organoids for years offers an unprecedented window into how the brain grows and wires itself—and how genetic changes early on might contribute to diseases later in life.

Our brains take roughly two decades to mature. Throughout this period, neurons constantly rewire their connections. Scientists have long known that conditions such as schizophrenia and some forms of epilepsy first emerge during adolescence. Because mini brains can be grown from a person’s skin cells and retain genetic mutations associated with neurodevelopmental disorders, they offer a way to probe how, and when, neural wiring goes awry.

But timing matters. The question is, how faithfully does a growing blob in a dish follow the developmental journey of a human brain?

Time Stamp

To answer that question, the team grew 34 organoids and tracked them at regular intervals. They collected data every three to six months for the first 18 months, then annually until the organoids were over five years old.

Crucial to the brain blobs’ longevity was switching the growth medium—a nutrient- and protein-rich slurry—halfway through development. The new recipe kept neurons alive longer, giving them time to support increasingly complex activity.

The team then tracked changes in gene activity and epigenetic markers (chemical tags that control which genes are turned on or off). They then compared the findings with data from younger organoids—ranging from 15 days to six months old—and donated human tissue.

The developmental timeline was surprisingly similar to that of a human brain. Young organoids showed gene activity resembling the first trimester; by three to six months, they looked more like second-trimester brains. After a year, their gene activity profiles resembled those of newborns. By the end of the experiment, they most closely matched a typical 4-year-old.

The team also tested them with epigenetic methods used to gauge biological age as opposed to calendar years. The organoids gained and shed epigenetic markers in patterns that broadly tracked those seen in natural brain development.

The organoids seemed to retain a “sense” of time. The team mixed cells from year-old organoids with those from 15-day-old organoids. Both followed their usual trajectory: The younger cells developed into early-stage neurons. But the older ones skipped those stages and rapidly produced more mature neurons often requiring months to grow.

“I like to think of this as a sort of ‘warping of developmental time’ indicating that the organoid cells record and recall the time they have already spent in culture,” said Arlotta.

In other words, the cells seem to carry an internal developmental clock, which could be especially useful for studying disorders with symptoms emerging long after the early stages of development.

To be clear, though, a mini brain resembling a 4-year-old’s brain at the molecular level doesn’t mean it has the same wiring or computational capabilities. Gene activity only captures part of a brain’s development; real brains are shaped by experiences and interactions with the rest of the body. Without input, mini brains can only offer a molecular blueprint of brain development, not its entire rich tapestry.

Still, long-living organoids are a breakthrough. Researchers could freeze cells from organoids at different developmental stages and later thaw them for experiments. This could speed up discoveries because scientists wouldn’t have to grow new organoids from scratch for each new study. Think of it as a save point in video games.

The team plans to grow long-lived organoids from people with schizophrenia or epilepsy and use them to study disease progression and screen drugs. Keeping ethics in mind, they’re also considering exposing mini brains to sensory stimuli such as sight, sound, or touch.

“There is still much to learn about how the embryo naturally builds a progressively more complex and mature brain,” Arlotta said. “Applying these lessons to organoids will allow us to model unexplored events of human brain maturation that occur after birth.”

The post Mini Brains Grown for Five Years Matured Like Human Brains appeared first on SingularityHub.

Our cherished memories may be more resilient than previously thought.

Long-term memories are stored in synapses, the connections between neurons. These structures sit on tiny protrusions called dendritic spines, which dot neurons’ branching arms.

When we learn, these spines grow. Larger spines tend to form stronger synapses and are more likely to persist during learning. In Alzheimer’s and other diseases that eat away at these connections, memories can fade.

At least, that’s the traditional picture. A new study suggests the story is more complicated.

Mice in artificial hibernation rapidly lost roughly half of their synapses, both large and small. Yet once awakened, they resurfaced memories of previously learned tasks. Spines that had withered during the induced deep sleep regrew in their original spots, once again forming functional synapses. This suggests their brains had rebuilt parts of broken circuits.

A small number of stubborn synapses that survived hibernation may explain how this happened. These synapses formed clusters that preserved memories as patterns of neural activity called engrams. The more surviving clusters the mice had, the better they performed on a previously learned task after awakening.

“It was astonishing. Logically, if all our engram synapses were essential in memory retention as traditionally thought, memory should have massively deteriorated,” said study author Yu-Ju Lin at Japan’s Okinawa Institute of Science and Technology Graduate University in a press release.

The findings suggest that memories may not depend on preserving every individual synapse. Instead, they may be distributed across a higher-level architecture of connections, with some synapses acting as anchors that can reconstruct the rest.

Artificial hibernation is an extreme case, and it’s far too early to know how the findings translate to diseases like Alzheimer’s. Still, they suggest that even under extreme circumstances, the brain can bring back memories once thought lost.

Forest for the Trees

Neurons are often called the brain’s computational units. But each one is actually a sophisticated mini computer in its own right.

A neuron’s branching arms receive signals from neighbors, while a long, winding extension carries outgoing messages to other neurons. Spines dot the receiving branches. These structures can strengthen, weaken, appear, and disappear depending on the input. This allows synapses to simultaneously gather data, learn, and store memories. When neurons repeatedly activate each other, the connections between them grow stronger, mostly because of larger spines. This is the idea behind the popular neuroscience saying: “Neurons that fire together, wire together.”

For episodic memories—the when, where, what, and who of our lives—these changes begin in the hippocampus, a region central to forming and retrieving memories, and one of the first areas damaged by Alzheimer’s disease.

During the day, the hippocampus forms engrams associated with individual memories. During sleep, some of these are erased, while others are gradually incorporated elsewhere in the brain for long-term storage. The hippocampus also helps recall memories by adding context, such as where something happened or how you felt at the time.

All of this should, in theory, require relatively stable brain circuits. “Long-lasting changes in synaptic connections are widely thought to provide the structural basis of memory,” wrote the team.

But recent studies have challenged that view. The brain is anything but static. Synapses are constantly being remodeled. Even which neurons are recruited into a particular engram can change over time. Some synapses may effectively hand off information to others, freeing themselves to encode something new.

If physical traces of memories are always shifting, why don’t our memories disappear with them? That’s the question the new study explored.

Going Under

To probe the paradox, the team turned to an unorthodox method: Artificial hibernation. Like natural hibernation in bears and other animals, artificial hibernation dramatically lowers body temperature and metabolism and causes animals to enter a sleep-like state. As the brain decreases its activity to conserve energy, synapses begin to wither.

Yet hibernating animals do retain memories. Chipmunks, for example, remember where they’ve stored food, returning to their stashes when periodically awakening for “midnight” snacks. This suggests hibernation could be a useful way to study how memories survive major changes in the brain.

“Our brains are incredibly complex. If hibernation can reduce and simplify brain activity and structure, it could make studying these convoluted systems a bit easier,” said study author Kazumasa Tanaka. “That’s why I wanted to use artificial hibernation techniques to study memories.”

The team first trained mice on two standard memory tasks. In one, the critters received a mild electrical zap to their paws inside a chamber with distinctive smells and decorations, teaching them to associate that setting with danger. In the other, they learned to navigate a maze towards a sugary reward.

The researchers then activated a neural circuit that drove the mice into artificial hibernation for two days. Using fluorescent proteins, they tracked changes in the animals’ synapses throughout the process.

Spine remodeling began within minutes. Some rapidly shrank and disappeared, taking their synapses with them. Within a day, over half of the synapses were gone. Even the larger spines thought to be especially important for long-term memories were pruned.

Yet memories survived. When the mice awoke and revisited the shock chamber, they froze in fear. In the maze, they still knew how to find the reward. Previously pruned spines also returned, with roughly 80 percent growing back at their original locations along the neuron’s branches.

To test whether this recovery is unique to hibernation, the team compared the animals with a second group that underwent anesthesia and were dosed with a drug that blocks synaptic changes—a combination known to cause amnesia. These mice also lost a large number of synapses but never recovered their memories.

A core cluster of unusually resilient synapses may explain the difference. These synaptic clusters formed a unique architecture in which one neuron linked to multiple neighbors like Grand Central Station. The clusters were often located in areas where spines were tightly grouped—making them more likely to receive inputs from multiple sources at once. Somehow, they kept memories intact even as surrounding synapses disappear.

“This suggests that for long-term memory, only particular clusters of synapses matter—the rest may be dispensable,” said Tanaka.

Exactly how these clusters preserve memories remains unclear. How does the brain create and maintain them? Do they anchor multiple memories? And could the same mechanism help explain why some memories remain as synapses are lost in disease?

The team is now using genetic and molecular tools to decipher what makes the clusters so resilient. Tinkering with their formation could better reveal their role preserving memories and, in theory, inspire ideas for tackling synapse loss in the early stages of diseases.

Beyond neuroscience, demystifying how memories linger could inspire neuromorphic chips—hardware that loosely mimics the brain—or even new AI models. For now, the findings offer a twist on an old idea: A memory may not need every single synapse that helped create it. It may just need the right ones to rebuild the rest.

The post We May Be Wrong About How the Brain Stores Memory appeared first on SingularityHub.

Stress does more than take a toll on mental health. After a particularly taxing week or month, it’s easier to catch a cold and harder to recover. Health issues build up as stress lingers, raising the risk of heart disease, diabetes, cancer, and a weakened immune system.

Chronic stress is often treated as an unavoidable part of modern life. While therapy can help people cope, researchers are increasingly asking a deeper question: How do stress signals in the brain ripple through the rest of the body, and can that damage be stopped?

A new study offers one of clearest answers yet. In mice modeling chronic stress, activity dropped in two brain regions governing emotional resilience. By way of a large nerve to the digestive track, the change wiped out a beneficial bacterial strain key to a healthy microbiome.

Without those microbes, the gut produced less of a crucial molecule that helps cells clear damaged proteins and other molecular  junk. These effects impacted the bone marrow, where stem cells generate oxygen-carrying blood cells and components of the immune system. Over time, these stem cells dwindled, leaving signs of premature immune aging in stressed mice.

“One surprising finding of our study was that suppression of only two specific brain regions was sufficient to produce many of the hematopoietic [blood stem cell] defects caused by psychological stress,” study author Linjia Jiang at Sun Yat-sen University said in a press release.

By tracing a direct pathway from brain to gut microbiome and bone marrow, the results could inspire new ways to blunt the biological toll of stress, from targeted probiotics to non-invasive brain stimulation.

Three-Piece Puzzle

De-stressing has become synonymous with self-care. Whether it’s work, family obligations, or a stream of notifications stressing you out, escaping into a good book or a walk in the woods feels like a deep mental exhale.

Stress has its perks. A product of the “fight-or-flight” response, it activates the sympathetic nervous system, a kind of highway connecting brain and body. In extreme cold, the system redirects blood from the skin to vital organs and temporarily slows digestion to prioritize muscles during a marathon. Brief bursts of stress aren’t detrimental. They’re an evolutionary survival hack.

But chronic stress is another story. Decades of research have found that prolonged or repeated mental strain disrupts brain activity and increases the vulnerability to a range of diseases. This is largely related to stress hormones released by the brain. But direct electrical signals traveling to the gut—which is often nicknamed the “second brain”—may also play a major role.

The garden of microbes in our gut roughly matches the number of cells in the body. These bacteria regulate digestion, metabolism, and immunity. They also communicate with the brain. When the ecosystem falls out of balance, it contributes to conditions ranging from diabetes to brain disease.

These beneficial effects can be traced to chemicals gut microbes manufacture. Lactobacillus reuteri, for example, boosts production of spermidine, a molecule that helps cells and tissues clear toxic debris. The process, called autophagy, is essential for the maintenance of healthy tissues but declines with age.

Stress also makes blood stem cells less resilient. Studies have linked prolonged stress to shortened telomeres, the protective caps at the ends of chromosomes, and an accumulation of senescent “zombie” cells. Both are hallmarks of accelerated biological aging.

The brain, gut microbiome, and bone marrow all respond to chronic stress. The new study aimed to find out if they’re connected.

Chain Reaction

To trace how chronic stress ages the body, the team tested four mouse models. Some experienced mild nerve injury. Others faced subtle disruptions to their daily routines, such as lights switching on earlier than expected or their home cages gently rocking at unpredictable times.

The changes put the mice on edge based on established behavioral tests. Mapping brain activity, the team zeroed in on two regions that consistently quieted. One, the medial prefrontal cortex, orchestrates executive control, or the ability to keep ideas in mind while reaching towards a goal. The other, the periaqueductal grey, coordinates attention to potential threats.

As activity decreased in both regions, blood stem cells struggled to divide and replenish immune cells. Inflammation and other toxic pathways flared up, and the cells developed molecular signatures similar to those seen in much older animals. Silencing either brain region with genetic tools reproduced many of the same symptoms, suggesting neural changes are a cause, not just a correlation.

But how was the brain communicating with the bone marrow? The answer lay in the gut microbiome.

Comparing the levels of chemicals surrounding the bone marrow in stressed and unstressed mice, the team zeroed in on spermidine. The molecule is made by gut bacteria and boosts autophagy, a process that’s linked to healthy aging.

Spermidine levels plummeted in stressed mice due to the loss of Lactobacillus reuteri, a beneficial strain of bacteria in the gut ecosystem that supports spermidine production. Stress-related nerve signals from the brain depleted these microbes, which caused spermidine levels to collapse and leaves blood stem cells unable to maintain themselves.

In another test, transplanting gut microbes from a stressed mouse into a happy-go-lucky mouse triggered early blood stem cell aging in the recipient—even though it didn’t experience stress itself. The results strengthen the case that the gut microbiome is a major link between the brain and bone marrow.

Rather than stress hormones, the pathway seems largely driven by electrical signals traveling from stress-sensitive brain regions to the gut. This means targeted brain stimulation could interrupt the cascade. Supplementing Lactobacillus reuteri as a probiotic or directly providing spermidine in a pill may also restore the missing molecule and slow blood stem cell aging.

This is just speculation though. Stress is deeply personal, and mice can’t capture the entire human experience. The team is now investigating whether the same brain circuits operate in people and if targeting this brain-gut-bone marrow axis can benefit the immune system.

“Our findings raise the possibility that managing psychological stress may not only improve mental well-being but also help preserve immune function and promote healthy aging,” said Jiang.

The post Scientists Find a Surprising New Way Stress Cascades From Brain to Body appeared first on SingularityHub.

My octogenarian father-in-law is trilingual and a lifelong fan of the World Cup. As he cheers on his favorite teams in English, Spanish, or French—sometimes switching between them mid-sentence—I’m always amazed at how easy it seems.

Scientists have long been fascinated by the brain’s ability to learn and retain multiple languages. Even after years of disuse, a brief exposure can quickly revive a language without having to consciously relearn its grammar or vocabulary. Bilingualism may offer other cognitive perks. Small studies suggest it delays brain aging, lowers dementia risk, and provides a slight edge in executive function (the ability to stay focused on a goal).

But most  of the evidence is from brain imaging studies that offer only a bird’s-eye view of neural activity and miss the finer details.

Now, scientists from the Baylor College of Medicine and collaborators have recorded activity from single neurons in four bilingual volunteers with epilepsy as they listened, read, and spoke in English and Spanish. The participants already had electrodes implanted in the hippocampus—a brain region critical for learning and memory—to track the source of their seizures.

“This is the very first study to look at how bilingual brains work at the level of individual neurons, and to do so in real time,” said study author Xinyuan Yan in a press release.

The results suggest the bilingual brain operates on two levels. Individual neurons often showed a strong preference for one language when participants heard or spoke words with the same meaning. But networks of neurons were largely language independent. They spontaneously organized into a concept map, placing words with related meanings—such as “dog” and “wolf”—closer together than unrelated words like “fork.”

Surprisingly, both languages relied on the same underlying map. Using the English concept map alone, the team could accurately predict clusters of related Spanish words.

“It’s like looking into a room from a different window. Everything inside is the same, but the perspective is different,” said study author Sameer Sheth.

Bridging Worlds

Language is central to human connection. Although some words don’t directly translate, people can express the same ideas across multiple languages without losing their core meaning.

Children raised in multilingual households are especially adept at switching between languages, often blending words and phrases together. Even when languages differ dramatically in grammar, syntax, and pronunciation, the brain somehow keeps their structures distinct while fluidly merging their meanings.

Long before we learn to speak, neural networks transform thoughts into electrical patterns that form words and sentences. Because languages are built differently—for example, where a verb falls in a sentence—it seems reasonable that each language would have a unique neural fingerprint.

But that might not be the case. A recent AI-powered analysis of functional MRI (fMRI) scans from monolingual speakers of 21 languages suggested that languages share a similar neural scaffold that represents meaning and concepts. Even fictional languages, including Klingon from Star Trek and Na’vi from Avatar, appear to tap into the same underlying system.

A growing body of evidence from bilingual speakers echoes these findings. One fMRI study found native Chinese speakers learned English more efficiently when they recruited brain networks used for Chinese. Another study identified shared speech-related brain activity sufficient for decoding words across languages.

Despite hinting at a universal language map, these standard imaging technologies struggle to capture detailed patterns as people switch languages in real time. To see how bilingual brains actually pull off the feat, we need to listen in on single cells.

Mapping It Out

The team studied four volunteers fluent in English and Spanish. All had learned the languages before age five and continued to use them regularly. Each also had electrodes implanted in the hippocampus to monitor seizures as part of epilepsy treatment, allowing researchers to track individual neuron activity as they listened and spoke.

Though often overlooked in language research, the hippocampus is increasingly recognized as a hub for word meaning, and it may also link concepts together. Here, the team monitored more than 100 neurons in each participant as they completed three language tasks.

First, the participants listened to roughly an hour of YouTube videos and the audiobook Eat Pray Love (Come Reza Ama). Next, they read aloud nearly 100 phrases displayed on a screen, such as “let’s have fun” and its Spanish equivalent “vamos a divertirnos.” Finally, they spent up to 90 minutes chatting with native speakers of each language, discussing everything from family to their epilepsy journey.

By the end, the team had compiled thousands of spoken words, hundreds of matched phrases, and hours of natural conversation.

A Language Landscape

Only a handful of neurons appeared truly bilingual, responding similarly to equivalent words such as “friends” and “amigos.” To better interpret the neural activity, the team turned to mBERT, Google’s multilingual language model that understands more than 100 languages. Like other LLMs, the model represents words according to their relationships and context rather than simple dictionary definitions.

The comparison revealed a similar pattern in brains and machines. Individual neurons rarely encoded the same word across languages. Instead, meaning emerged at the population level.

Both neural activity and mBERT tracked broader context, organizing words into an abstract conceptual landscape called semantic geometry. In this map, related concepts cluster together—“cat” sits closer to “dog” than to “galaxy,” for example—even if the precise features defining those relationships are unclear.

Yet the map remained largely unchanged across languages, suggesting it captured a fundamental mechanism for language processing in the brain. Using the English map alone, the team could predict which Spanish words would cluster around “perro” (or “dog”).

“This is how the brain encodes the meaning of words across languages,” said Yan. “It doesn’t rely on individual neurons translating individual words, but groups of neurons adjusting their activities to create the similar pattern for equivalent words in both languages.”

The study focused on semantics, or meaning, as opposed to syntax, the rules governing sentence structure. A recent study also using single-cell recordings from people with epilepsy suggests that other groups of neurons, particularly those in the frontal parts of the brain, may specialize in grammar while ignoring semantics. Whether they also share a “map” across languages remains to be seen.

The next step is to watch these maps emerge. The team hopes to track people as they learn a new language, revealing how new words and concepts are woven into semantic landscapes in real time. The results could deepen our understanding of one of the most fundamental communication skills and even inspire more capable and efficient language models in AI.

“Our study shows that the brain is wired to learn multiple languages,” said study author Benjamin Hayden.

The post How the Bilingual Brain Switches Languages With Ease appeared first on SingularityHub.

For five years, Alzheimer’s slowly stripped away a Japanese-American woman’s ability to speak more than one syllable at a time. The woman, now in her 80s, was diagnosed roughly a decade ago, and her condition steadily worsened. She struggled to walk and recognize family members.

Then, under medical supervision, she took a large dose of mushrooms containing the psychedelic psilocybin. Within three days, her symptoms had improved. She began spontaneously recounting memories and initiating conversations in full sentences. Her alertness returned, and she could move around independently.

A week later, she was recognizing family members, asking where they were, and pointing out cars that seem out of place.

Psilocybin has been maligned for decades. But renewed interest in its unique effects on the brain has pushed it into mainstream research. Early studies suggest it may help treat depression, anxiety, addiction, post-traumatic stress disorder, and other psychiatric conditions. A clinical trial is underway to gauge whether it can protect the aging brain.

The case study, conducted in Brazil, adds to that momentum. The team emphasizes that it describes a single patient and is purely observational. Because of the severity of her disease, they could not perform brain scans, measure biomarkers, or conduct standard cognitive tests. Exactly why her symptoms improved remains unknown.

Even so, they propose that psilocybin may have temporarily unlocked brain function in late-stage Alzheimer’s, potentially allowing dormant neural networks to rewire.

Brain Under Fire

Alzheimer’s is often synonymous with memory loss. Sadly, symptoms range far beyond forgetting names or misplacing glasses.

As the disease progresses, people gradually struggle to find the right words or follow conversations. Their ability to tackle everyday tasks—cooking, managing finances, planning ahead—erodes. Depression, irritability, and anxiety often emerge. Over time, their personalities flatten, leaving them less outgoing, engaged, or empathetic.

These stories are far too common. According to the World Health Organization, roughly 57 million people worldwide were living with dementia in 2021. Alzheimer’s may account for up to 70 percent of cases. As populations age, that number is expected to climb.

Alzheimer’s has no single cause. Genetics likely play a role. Some gene variants are linked to early-onset forms of the disease, an area scientists are now tackling with gene therapy.

Another hallmark of the disease is a buildup of abnormal protein clumps, or plaques, in and around neurons, which disrupts normal function and wrecks their ability to form neural networks supporting memory and cognition. Years of efforts to remove plaques have largely failed, though the FDA recently approved two antibodies that reduce them and modestly slow cognitive decline.

Then there’s inflammation. In Alzheimer’s, the brain’s immune system can become overactive. Rather than responding only to damage, inflammation drives disease progression, spreading toxic protein clumps through the brain and further damaging its ability to form new connections.

Here’s where psilocybin, the active ingredient in magic mushrooms, may help. Psilocybin alters serotonin signaling, a brain chemical involved in mood, perception, and cognition. But its effects likely extend far beyond that.

Studies in mice suggest the chemical boosts the brain’s ability to rewire, a process known as neuroplasticity. Human brain imaging studies have found that the psychedelic temporarily reorganizes communication between large brain networks, changing how distant regions interact. In some participants, supervised treatment has been linked to greater cognitive flexibility, deeper self-reflection, and improved well-being.

Other studies hint at a protective role. Psilocybin triggers the release of “nurturing” proteins. This process helps neurons survive stress and extend their branching connections. It’s these delicate structures that build up neural networks, and they wither away during depression, aging, and dementia. Inside the hippocampus, a region crucial for learning and memory, the drug stimulates the birth of new neurons, at least in mice.

Given its positive effects on brain plasticity, psilocybin is now being tested in multiple psychiatric disorders characterized by unusually rigid patterns of brain activity. Older adults remain largely absent from these studies, even though they could benefit the most.

Tale of One

Before treatment, the woman struggled with everyday life. For five years, she could communicate using only single-syllable words. Her mobility was severely limited, and she struggled with incontinence.

With the consent of her caretaker, she received five grams of the Enigma strain of Psilocybe cubensis. Because psilocybin levels vary widely between mushrooms, the exact dose is unknown. But compared to other clinical trials, it was relatively high.

The team chose the dose “based on prior experiential observations regarding depth and duration of psychedelic-induced neurobehavioral effects,” wrote the team.

Initially, the woman fell into a deep sleep-like state accompanied by elevated body temperature and heavy sweating. Roughly 19 hours later, she suddenly awoke and began speaking to caregivers in complete sentences, recounting memories from her life. The conversation lasted around four hours.

Over the following days, she became increasingly alert and engaged. She recognized family members, regained mobility, and could pick out matching clothes to dress herself. A week later, she was noticing small details in her environment, including a rental car parked outside the house. When a family member was absent, she asked, “Where did Celso go?” She also seemed to rediscover her love of social interactions, making eye contact, smiling back, and actively starting conversations.

A month after the initial session, she returned for a second supervised dose of three grams. After the second dose, she became even more verbally expressive, displayed a sense of humor, and described memories of surfing with her son on a peaceful island. Throughout the trial, the drug alleviated incontinence and improved her quality of life.

The results come with major caveats. The improvements were observational and largely reported by caregivers, leaving room for bias. The team didn’t administer standardized tests for cognition, dementia, depression, and anxiety. Nor did they perform brain scans or monitor sleep, making it impossible to determine what brain changes were behind her apparent “awakening.”

“Causality cannot be established, and spontaneous fluctuations inherent to neurodegenerative disease cannot be completely excluded,” they wrote.

But the study touches on a provocative idea in Alzheimer’s: Cognitive reserve. The theory proposes some people can tolerate greater levels of harm to the brain and continue functioning despite significant damage. Psilocybin may have temporarily tapped into these reserves, allowing dormant neural circuits to engage and rewire to compensate for impaired ones. The hypothesis is highly speculative and needs to be rigorously tested.

Meanwhile, a clinical trial is investigating whether psilocybin can reduce depression and improve quality of life in people with mild cognitive impairment or early Alzheimer’s disease, moving the needle beyond a single case study.

For one family, however, the benefits are already substantial. At a follow-up visit, the woman spontaneously said to everyone in the room, “It is pleasant to come here.”

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A handful of healthy senior citizens are about to trip on psilocybin—to see if the psychedelic protects aging brains.

Psilocybin, the active ingredient in magic mushrooms, is best known for its ties to 1960s counterculture. But now it may also herald a new genre of mental health treatment. From severe depression to post-traumatic stress disorder, studies have highlighted psychedelic drugs’ ability to reshape brain networks and relieve debilitating symptoms.

Most of these studies have focused on younger people with mental health conditions that don’t respond to standard treatment. The field’s success is prompting scientists to ask if psychedelics could also help healthy brains age better.

A team from the UC Berkeley Center for the Science of Psychedelics is about to find out. In a first-of-its-kind study focused on adults between the ages of 60 and 85, they’ll investigate how psilocybin affects perception, emotion, and memory using a battery of psychological tests.

Multiple scans before and after dosing will track changes in the brain. And detailed surveys will gauge broader shifts in well-being: Do participants feel more “in tune” with their emotions, feel less isolated, or experience a renewed sense of wonder about the world?

“What really excites me is that we’re focused on healthy older adults,”  said Tyler Toueg, who co-led the study’s design, in a press release. “Most clinical trials with older adults are focused on people who already have a diagnosis. We’re asking whether we can actually promote positive outcomes in older adults who are healthy.”

Called PLASTICITY, the trial could also open a rare window into how a psychedelic experience reshapes healthy brain networks. And because the drug alters our sense of self, psilocybin could help researchers probe the ways in which the brain constructs reality.

“I’m very interested in psilocybin as a potential mental health treatment, but I’m also interested in it as a way to shed light on these central mysteries in neuroscience and psychology,” said study designer Michael Silver.

Chasing the White Rabbit

Psychedelic research was highly restricted for decades. But advocates, including the non-profit Multidisciplinary Association for Psychedelic Studies, have steadily pushed to reopen the field, arguing that these drugs might keep mental health symptoms at bay.

Early results helped usher psychedelics into the mainstream. In 2023, a randomized, placebo-controlled trial found that a single dose of psilocybin, paired with therapy, eased depression. Oregon later approved supervised psilocybin therapy—though the drug remains federally illegal in the US—and Australia became the first country to greenlight it for depression and post-traumatic stress disorder. More recently, two late-stage studies reported strong effects in severe depression, potentially paving the way for FDA approval.

Scientists still don’t fully understand how psilocybin works in the brain. But there are hints. The drug appears to rapidly reorganize the connections between brain cells, particularly in the hippocampus, a region of the brain central to learning, memory, and navigation.

Neurons constantly change their connections in a process called plasticity that encodes experiences into neural networks, allowing the brain to process information, learn, and lock in memories. In youth, these connections are flexible and expansive. But with age and in conditions like depression, the brain’s flexibility wanes.

The birth of new neurons, or neurogenesis, also contributes to plasticity. Neurogenesis only occurs in two brain regions, one of which is the hippocampus. Although whether it actually takes place in humans is controversial, it is strongly linked to learning, memory, and emotion, and it declines in both psychiatric disorders and aging.

Psilocybin may reset brain plasticity to a more youthful state.

In rats modeling depression, for example, a study showed the drug shifted dark moods into behavior that was more exploratory and engaging. Where traditional antidepressants, like Prozac, tend to blunt symptoms, psilocybin seems to overwrite entrenched negative patterns. This suggests deeper circuit-level changes.

In another study, the drug reopened a critical window for learning in mice. During adolescence, the brain is highly plastic, but it begins to stiffen in adulthood. Psilocybin temporarily restored malleability and changed the mice’s social behavior. In some brain regions, the drug increased sensitivity to oxytocin, the so-called “love hormone.” The authors suggested the drug induced a state called metaplasticity, in which neurons are more likely to respond to oxytocin and other regulators to rewire, form new connections, and grow their branches.

Psilocybin’s effects may extend beyond the brain. Depression, chronic stress, and the immune system are tightly linked. In a third study, researchers identified a brain-spleen connection that drives fear and anxiety. Psilocybin suppressed inflammatory immune cells associated with brain inflammation and dampened anxiety-like behavior in stressed mice, even under threat.

Both effects—dialing up plasticity and lowering inflammation—make psilocybin an intriguing way to potentially counter changes in the aging brain.

“We know that with age, we lose synaptic connections, especially in certain brain regions like the hippocampus and prefrontal cortex,” said Toueg. “There’s a lot of overlap between the mental states that psychedelics influence and those associated with successful aging.”

Tomorrow Never Knows

The PLASTICITY trial is designed to test whether psilocybin can produce lasting changes in neuroplasticity in healthy adults aged 60 to 85. Participants will first undergo assessments of cognition, visual perception, and brain structure using advanced MRI techniques.

Diffusion MRI scans will focus on the hippocampus to capture microscopic changes in its structure. Functional MRI will focus on brain activity as participants perform learning and memory tasks, offering a dynamic view of how activity shifts after dosing.

The study will also see if psilocybin increases vagus nerve activity, which has been linked to better stress recovery. Participants will complete detailed surveys about the experience ranging from emotional responses, like wonder, to potential shifts in outlook and social cognition.

“Things like depression, anxiety, stress and rumination are all associated with worse aging outcomes,” said Toueg. “Things like having purpose in life, emotional regulation, and awe are all associated with more successful aging.”

The trial began enrolling participants in November last year. Two volunteers have already completed the tests, and the team aims to dose 20 people by the end of 2026.

Although psilocybin trials are now widespread, older adults remain underrepresented. One estimate suggests just 1.4 percent of participants are 65 or older, despite potentially being among those most likely to benefit from interventions that enhance plasticity.

“This study allows us to directly test whether the promising findings from animal models translate to older humans and to generate data that will inform future research on aging, cognition, and mental health,” said Silver.

Toueg agrees. “I think that no matter what we find, this study will have implications for how we think about intervening in the aging brain,” he said.

The post Can Psychedelics Reboot Aging Brains? We’re About to Find Out appeared first on SingularityHub.

Huntington’s disease is tragically predictable. An inherited genetic mutation causes neurons to make distorted, sticky proteins. These proteins clump together and gradually overwhelm brain cells. The brain loses its ability to learn, remember, and make decisions.

This story is dogma in neuroscience. But decades of research and drugs targeting the clumps have had little success. Scientists are now wondering: Is there more to the story? In a twist, a team from the Hebrew University of Jerusalem and collaborators found that protein clumps may be a neuron’s first line of defense against damage.

The misfolded or malfunctioning proteins are quarantined inside bubbly hubs called “inclusion bodies.” Often considered detrimental to cell health, disrupting their formation unexpectedly led to cells becoming more sensitive to stressors often seen in neurodegenerative diseases.

Physical separation played just one part. Inclusion bodies also changed the activity of genes involved in neuroinflammation—even in the absence of immune cells. Scouting the genetic landscape of cells derived from patients with severe Huntington’s disease, the team homed in on a “master regulator” gene, ATF3, that orchestrates immune responses. Removing the gene lessened inclusion bodies’ protective effects against damage in cultured cells.

To be clear, the findings are only for a cell model of Huntington’s disease in a petri dish. And inclusion bodies could be a double-edged sword: protective in the beginning and detrimental later on. Still, acknowledging them as a more complicated villain could better inform strategies for disorders that take over our minds like Huntington’s.

“Our results reveal…that these structures are not merely byproducts of disease, but a central factor in the cell’s ability to mount a protective response against stress,” said study author Eran Meshorer in a press release.

The Problem With PolyQ

It’s long been believed that protein clumps in the brain gradually erode cognition. Whether they’re the main driver of neurodegenerative disorders is still debated, but their presence accelerates brain cell injury, causing neurons to wither away.

Alzheimer’s disease, for example, is associated with two sets of protein clumps. One lives inside neurons (tau) and another gunks up the space between cells (amyloid). Decades of research aimed at removing amyloid clumps have met with minimal success, earning these doomed efforts the notorious nickname “graveyard of dreams.” Despite their struggles, the FDA recently approved two major drugs that remove amyloid clumps and modestly slow cognitive decline, though the approval has been controversial due to doubts about safety.

Other untreatable neurodegenerative disorders also fall into this category. Clumps formed in Parkinson’s disease erode the brain’s ability to control movement, emotion, and even the perception of time. Lou Gehrig’s disease, or ALS, produces inclusion bodies inside motor neurons, leading to muscle weakness and trouble swallowing. The disease eventually robs people of speech and motion.

These diseases often have multiple genetic and environmental triggers. Huntington’s, in contrast, is entirely genetic. The condition stems from the genome over-copying parts of the huntingtin gene (HTT), which normally makes a key protein also called huntingtin.

Normally, cells use the protein’s large, stackable structure to build highways that transport all sorts of biological cargo, from molecules to organelles. The protein also plays an essential role during early brain development and neural wiring in adulthood.

But a mutant form of the HTT gene can wreak havoc. A common mutation, called polyQ expansion, produces unwieldy, misfolded proteins. Nearly 30 years ago, researchers found that these errant proteins aggregate inside parts of the cell. The clumps, or inclusion bodies, were widely thought to be detrimental. Some act like sticky tape that captures healthy proteins, such as those involved in gene expression, and torpedoes cellular health.

But telltale signs in cultured rat brain cells suggest a more nuanced story: Inclusion bodies could also be protective, sequestering mutant proteins as an early form of protection.

A Tale of Two

The common factor in diseases featuring polyQ mutation is repetition. Mutated genes have long, duplicated sequences of the DNA letters cytosine, adenosine, and guanine (CAG). More CAG repeats in the genome translates into earlier disease onset.

We all have this DNA triplet in our HTT gene. But more than 39 repeats results in longer, toxic huntingtin proteins. Severe cases of Huntington’s can feature over 100 CAG repeats, transforming the usually free-floating protein workers into sticky, dysfunctional layabouts.

In the new study, the researchers first established a baseline. They used the gene editing tool CRISPR-Cas9 to reduce CAG repeats in cells derived from Huntington’s patients—which carried over 180 copies—to near normal levels.

They then tagged the cells with a fluorescent marker that causes huntingtin proteins to glow bright green under the microscope. This let the team track protein aggregation in real time. Though they shared the same genetics, some cells formed inclusion bodies; others didn’t.

The team next challenged them with a chemical known to cause cellular stress. Those that formed clumps survived far more regularly than those that didn’t. It was a “striking difference,” the authors wrote. “Once a mutant PolyQ protein is expressed, the formation of IBs [inclusion bodies] protect[s] the cells rather than inflict[s] harm, at least short-term.”

Inflammation seems to be key. Although grown side-by-side, a genetic screen revealed cells with inclusion bodies were especially abundant in a gene called ATF3, which is known to regulate inflammation. Getting rid of the gene wiped out the neurons’ ability to form inclusion bodies, making them more vulnerable.

“Our results reveal a previously unknown role for ATF3 in orchestrating the formation of inclusion bodies in human neurons,” said Meshorer.

These are very early results. An immune molecule bridges ATF3 and inflammation and is associated with Huntington’s disease. Its levels are higher in patients with the condition. Increasing ATF3 activity could amp up the number of protective inclusion bodies and give neurons a fighting chance.

The findings suggest inclusion bodies gather free-floating mutant proteins into clumps to protect neurons and reduce brain damage—at least at the beginning of the disease. However, lab experiments rarely translate to treatments. How fast inclusion bodies form and when they begin to stress cells remains to be seen. Meanwhile, a gene therapy for Huntington’s is underway, and promising results in a small trial suggest an alternative path for treatment.

Still, the study challenges the idea that protein clumps are always detrimental. If replicated in other neurodegenerative diseases such as Alzheimer’s or ALS and if we can learn how long protection lasts, the results could pave the way for better-timed treatment that works with the body’s protection, not against it.

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