In a new study, scientists reared lab mice that were missing sections of their brains and then replaced the missing tissue with human cells.

The experiment represents a step forward in the study of human brain organoids ‪—‬ tiny models of the human brain grown from stem cells. In the long run, scientists aim to use organoids to better understand how the brain develops and how its structure and function change in the context of disease.

"It is definitely an advance in the field," said Dr. H. Isaac Chen, an associate professor of neurosurgery at the University of Pennsylvania Perelman School of Medicine. Chen was not involved in the current study but has conducted experiments transplanting human brain organoids into rodents' heads.

Organoids offer a window into early brain development that's impossible to observe closely in humans, namely because it unfolds inside developing fetuses. Although organoids are not perfect re-creations of full-size human brains, scientists think organoids are useful models for studying the developing brain in both health and disease.

The model in the new study "certainly creates some pretty interesting options in terms of modeling human neurodevelopment and various types of neurodevelopmental disorders," Chen said. "If you're looking for a model that really allows you to look at larger areas of human neural tissue from a cellular, molecular perspective, I think there's a lot that this model has to offer."

Making space for human cells

Often, brain organoids are grown outside living organisms, either in lab dishes or devices that keep these "minibrains" suspended in a solution. Multiple organoids representing different parts of the brain, or even different people's brains, can also be brought together to form more-complex structures.

Why, then, are some scientists growing human organoids inside mice? One reason is that there's a secret sauce inside living organisms that helps organoids mature better in animals than they do in lab dishes. In the body (in vivo), there are mysterious signals that help direct neurons' development and organization, and these signals are missing in lab dishes (in vitro).

"There are some cues that are present in vivo that are really important, and we simply don't know what to add in, in vitro," said study co-author Dr. Sergiu Pașca, a professor of psychiatry and behavioral sciences at Stanford University. The team demonstrated this phenomenon by transplanting organoids into lab rats in a study published in 2022; the transplanted organoids grew larger, formed better connections and were more active than organoids grown in dishes.

But transplanting human brain cells into rodents comes with different challenges. One is that human brains mature at a slower rate than rodent brains do. "Even when they're put in an animal, in a mouse or in a rat, they will still develop about 20 times slower than the mouse or the rat," Pașca told Live Science.

The host's brain cells quickly grow and form new connections, while the human cells lag behind and get outcompeted, Pașca explained. This limits the amount of space that the human cells can take up. As neurons mature, they become myelinated, meaning they gain fatty insulation that helps them communicate more efficiently. The rodent neurons become myelinated more quickly than the human cells do, and that fat creates a physical barrier that the human cells struggle to penetrate, Pașca said.

In their study, described Wednesday (Sept. 16) in the journal Nature, Pașca and colleagues aimed to give the human neurons a leg up. They couldn't solve the issue of human cells maturing slowly, but they could lend the cells extra space to grow in.

Through years of work, they developed a genetically modified mouse that develops only 2% of its cerebral cortex. The majority of its hippocampus — a major memory center in the brain — is also missing. Within a few days of the mouse's birth, the team transplants human neural tissue into that vacant space, and about 90% of the time, that human tissue integrates successfully and starts to grow, Pașca said.

"We just took cortical organoids, about four of them, and transferred them with a syringe into that vacant space," he said. "That's it. They go in there, they graft, and within a few weeks, they start to grow. And then within a few months, they've taken most of that volume."

In the weeks following the transplantation procedure, the human brain cells in the mice's heads grew, formed connections and extended projections into the underlying mouse tissue. The human tissue didn't organize itself into distinct layers as it normally would inside a human's head, but it included many cell types that are typically seen in the human cerebral cortex.

Future of the field

The researchers compared the mice imbued with brain organoids with mice that were missing the same amount of brain tissue but didn't get organoids. They also compared both groups to unmodified lab mice.

Perhaps surprisingly, the mice missing large chunks of their brains still functioned fairly well. "You look at them, and you can't really honestly tell," Pașca said. Upon closer inspection, though, the mice had subtle deficits in their fine-motor skills, working memory and socialization, he noted.

"From our perspective as humans, so much of what we do day to day depends on the cortex," Chen noted. But in a mouse, the cortex makes up a minority of the overall brain, and various studies have suggested that the animals can get by without it, he said. "I don't think the transplantation process itself is significantly hurting the animal," he added.

In the future, the ability to compare these three sets of mice — with organoids, without organoids, and unmodified — could help scientists tease apart how the human tissue is contributing to a given experimental result. Pașca envisions that the approach will be useful for studying the effects of insults to the brain, such as hypoxia (low oxygen) and exposure to toxins or drugs in the womb. Additionally, the genetics of the human organoids could be tweaked to see how those changes affect the brain's development, structure and function. That could be useful for studying cerebral palsy or autism, he suggested.

Chen expects that this new approach will be useful for studying aspects of early brain development at the molecular and cellular levels. The new model incorporates a larger volume of human tissue than models have done in the past, and that's an additional advantage. The human tissue doesn't organize itself into layers or lobes as you'd see in a real human brain, he noted, but he thinks there's still a lot that can be learned from it.

From an ethical standpoint, Pașca consulted with experts at Stanford and an external ethics committee regarding the welfare of the animals used in the study. Studies that involve putting human brain tissue into animals also raise questions about whether that added tissue could grant the animals new cognitive abilities — make them more human-like, in essence. The ethics committee fielded these concerns as well.

"We have not seen emergence of any new properties," Pașca noted. "It's not surprising because we're still at a very early stage of development." They grew the organoids for only six months, so the human organoids were roughly as developed as a 6-month-old fetus's brain tissue.

If the organoids matured to be more human-like — developing layers and lobes — that might present more of a concern. But both Pașca and Chen said that type of development might be hard to recreate in a mouse anyway.

Chen argued that the sheer size of the human brain contributes to its complexity, and it also contains specialized regions that work together to execute different tasks. A mouse's head cannot support the scale of a human brain, and at this point, organoids don't develop the same organization and specialization that we see in people, he said.

"It would be much more problematic if this was to happen in a species that has a larger brain and is closer to humans evolutionarily," Pașca argued. Pigs and nonhuman primates, such as monkeys, would be examples. Especially in regard to transplanting human organoids into monkeys, "that would be an experiment that I don't see is justified at this point," Pașca said.

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The brain undergoes dramatic changes during puberty and pregnancy, but during menopause, the organ's structure remains remarkably stable, a new study suggests.

The research, published Sept. 8 in the journal Nature Communications, examined the brain's gray matter, which mostly includes the wrinkled outer surface of the organ, called the cerebral cortex. Past studies have found that the volume of gray matter shrinks markedly during puberty and pregnancy, likely reflecting a fine-tuning of neural circuits during those periods.

There's also a gradual decline in gray matter during adulthood that's seen as a normal part of aging, said study co-author Sophie van't Hof, a doctoral student in psychiatry at Amsterdam University Medical Center. However, during the transition leading up to menopause, that gradual loss of gray matter levels off temporarily, the study found.

"This study provides the first direct longitudinal comparison of brain structural changes across all three major female hormonal transitions," said Magdalena Martínez-García, scientific director of maternal health for the Ann S. Bowers Women's Brain Health Initiative, a brain imaging consortium headquartered at the University of California, Santa Barbara.

"I really appreciate the effort that went into finding and curating such an impressive longitudinal dataset of the female brain," Martínez-García, who was not involved in the study, told Live Science in an email.

Declines in puberty and pregnancy

For their analysis, the researchers gathered data from the UK Biobank, a biomedical database that contains information from 500,000 U.K.-based adults. That data includes MRI scans of people's brains, which the team used to study brain changes in menopause.

To look at puberty and pregnancy, the researchers pulled from several brain-scan datasets that had been compiled by Leiden University in the Netherlands.

In all, the study included data from 1,095 brains across the three life stages. They analyzed each participant's brain at two different time points, examining how each person's brain changed over time and how it compared to others' brains.

The youngest cohort included participants who hadn't started menstruating yet, as well as those who'd recently started and those who'd already had periods for an average of 19 months. The pregnancy cohort included 40 who'd had their first pregnancy during the study and 30 who'd had second pregnancies, as well as 40 women who'd never been pregnant, as a point of comparison.

As in previous studies, the researchers observed that both the girls entering puberty and the pregnant women lost gray matter. But scientists don't necessarily see these declines in gray matter at puberty and pregnancy as negative.

It’s a hypothesis, but "we actually see it as something positive," van't Hof said. "We see it as neural fine-tuning."

During puberty, that gray-matter loss is thought to be a normal part of the brain's development into adulthood. Its function in pregnancy is not well understood, van't Hof noted, but the evidence to date doesn't suggest that it contributes to "mommy brain" — the brain fog and forgetfulness some women can experience postpartum.

"I'm not saying that there's no neurobiological basis for this mommy brain, but up until now, we haven't found it," van't Hof said. "But what's really important is that gray matter decline is not equal to cognitive complaints."

Stability in menopause

The analysis included 120 women who entered menopause during the study. At the first time point, these women had not gone a full year without a period, but by the second time point about 3.5 years later, they had. Menopause is defined as the point at which a full year has elapsed since a person's final period.

The researchers compared these women to two other groups: about 50 women (average age 51) who had not had their last period yet and over 670 women (average age 55.5) who had already had their last period.

During late perimenopause — the final stages of the transition to menopause — the brain's gradual decline in gray matter paused, van't Hof said. Then, in postmenopausal women, that gradual decline of gray matter resumed. The exact timing of that pause differed for each woman, but it occurred consistently across the group, van't Hof noted.

The most striking finding was the lessening of the "ongoing age-related decline in brain volume during the transition into and out of menopause, compared with the more stable premenopausal and postmenopausal groups," Martínez-García said. This is an "interesting finding that adds to our understanding of how dynamic the female brain can be across the lifespan."

Factors such as whether participants had taken hormone replacement therapy for menopause and the number of children they had given birth to did not have a measurable impact on the results, the study authors noted.

In general, complaints of brain fog are widespread just before, during and after menopause, van't Hof said. This could be attributed to declining hormone levels and sleep disruptions.

"We have no clue if there's a neurological basis [for that brain fog], because, again, this is the first study to look at it," she said, adding that more studies are still needed to learn more.

"As with any study, there are some limitations to consider, but overall, I think the methods and conclusions are well supported by the data available," Martínez-García said. Both Martiniz-Garcia and van’t Hof said that they hope other researchers build on these findings to deepen scientists’ understanding of female neurobiology at every stage of life.

This article is for informational purposes only and is not meant to offer medical advice.

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A fruit fly's brain is roughly the size of a poppy seed — and yet that tiny package contains over 100,000 neurons. A new map charts every single neuron in the male fruit fly brain, as well as the insect's equivalent of a spinal cord, totaling more than 166,000 neurons.

This new map joins a map of a female fruit fly brain that was unveiled in 2024 and covers about 140,000 neurons. These two wiring diagrams, also called "connectomes," can now be compared to see if there are differences between the sexes' brains that help to explain behavioral differences reflected during mating or in aggressive actions, including sex-specific fighting moves.

"It is the first time we can compare both sexes of an animal with complex social behavior," study co-author Gerry Rubin, head of biology and a senior group leader of the Howard Hughes Medical Institute's Janelia Research Campus, said in a statement. "Male and female flies have a lot of differences in their behavior, and neuroscientists want to understand how the brain controls those behaviors. This now allows us to easily home in on the neurons that are causing those differences."

Initially released as a preprint, the new fly brain map was published in the journal Cell and Current Biology Thursday (Sept. 3). The study describing the map was published alongside three other papers, each of which uses the new data to explore a specific aspect of fruit fly neurobiology.

"The fly nervous system performs remarkably sophisticated computations with relatively few neurons and little energy, and its architecture could suggest principles for designing more efficient artificial systems," said Carlos Ribeiro, a principal investigator at the Champalimaud Foundation in Lisbon, Portugal, whose team contributed to the brain map and led one of the related studies.

"This work also provides a technical roadmap for more ambitious connectomics projects in the future, such as those for mice and humans," Ribeiro said in a separate statement from the Champalimaud Foundation.

In the near term, the scientists aim to map the brains of larval zebrafish (Danio rerio) and adult danionin fish (Danionella). In the long run, the goal of this research is to understand how vertebrates' brains enable complex behaviors, and then use that knowledge to help unravel the basis of neurological and psychiatric disorders in humans.

The study led by Ribeiro and other Champalimaud Foundation scientists aimed to map the circuits in the fly brain dedicated to the insect's sense of taste. Fruit flies have taste receptors in many body parts, including their legs, wings, mouthparts and inside of the throat. The researchers identified these taste receptors and traced their connections back to the fly brain. From there, they examined how those circuits interacted with those that govern behaviors such as swallowing or walking. When it comes to eating behaviors, this circuitry helps the fly determine whether a given morsel is safe or harmful and ultimately choose whether to eat it, the researchers concluded.

This diagram of taste processing is a "hypothesis-generation tool," study co-author Inês de Haan Vicente, a research technician in Ribeiro's lab, said in the Champalimaud statement. "Suppose you are interested in how taste controls locomotion. Now you can go to the map and ask: which sensory neurons are connected to the neurons controlling locomotion? Which intermediate neurons should I manipulate? It gives you a place to start."

The other two papers published alongside the map respectively explore the circuits behind vision processing in the fly brain and sex-specific differences in male and female fly brains. The first showed that visual processing extends deep into the brain, involving more than half of the 11,000 or so types of neurons identified in the map. The latter study found a network of cells that's specific to the male brain and appears to coordinate male-specific behaviors, such as specific aspects of fly courtship and physical aggression. (For example, female flies tend to headbutt while males lunge at their targets.)

While there were some networks specific to each sex, the circuits for sensation and movement are largely shared between males and females, the research found. At times, specific switches within those circuits reroute signals to different destinations in the male and female brain; the consequences of that rerouting will be a focus of future investigations.

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Football is a high-impact sport. A player may take hundreds of hits over the course of their career, including some that cause concussions. Other impacts may seem minor at the time, but there are concerns that repeated head blows can negatively impact long-term brain health.

Those worries gained new attention after a recent study estimated that at least 25% of recently deceased NFL players had chronic traumatic encephalopathy (CTE). CTE is a degenerative brain disease linked to repeated head impacts. Although the study doesn't necessarily mean that 25% of current NFL players have CTE, it does add to the growing evidence that repeated hits may carry serious consequences.

The NFL has taken steps to reduce those risks, including strengthening concussion protocols and investing in safer equipment, like Guardian Caps. But are those measures enough? With new research continuing to shed light on CTE, we want to know what you think. Weigh in via our poll below, and let us know your thoughts in the comments.

Of the former National Football League (NFL) players who died in recent years, at least 25% had brain changes related to chronic traumatic encephalopathy (CTE), a new study suggests.

The study, published Aug. 25 in the journal The BMJ, examined donated brain tissue from 338 former NFL players who died between 2008 and 2021. A total of 1,712 former players died in that time frame, so the analysis included only about 20% of the players' brains that could theoretically have been examined. Then, the researchers used that subset of brains to estimate the likely prevalence of CTE in the overall group.

Among the donated brains, over 93% showed physical signs of CTE, meaning an accumulation of abnormal proteins in specific places within the tissue. About 30% had stage IV CTE, the most severe form that comes with the most extensive brain changes.

These physical signs of CTE aren't always associated with overt symptoms, such as cognitive decline, mood and behavioral changes, or dementia. Only about 60% of the individuals with CTE-related brain changes were also diagnosed with dementia in this study. That said, those with stage IV CTE were more likely to have dementia, with 90% having a diagnosis.

Across the full study time frame, the researchers estimated that between 18.5% and 98.7% of the deceased players likely had CTE. Zooming in on the period with the highest number of brain donations — 2016 to 2021 — they estimated the rate to be between 24.5% and 97.7%. That latter time frame was likely the more representative sample, the researchers determined.

What can this study tell us about the CTE risk that current football players face, from youth sports to the professional level? To put the research into context, Live Science spoke with Thayne Munce, an associate professor and director of the Jayhawk Athletic Performance Laboratory at the University of Kansas, who was not involved in the BMJ study. Munce researches brain health and concussion in contact sports, primarily among young athletes. He cautioned that the BMJ study's findings shouldn't be extrapolated to all levels and ages of play, or even to today's NFL players.

Nicoletta Lanese: This study estimated the rate of CTE among this era of NFL players. Was the prevalence surprising to you, or in line with your expectations?

Thayne Munce: It's not surprising to me. This group and their colleagues have published previous work from donors — so these are former players who have donated their brains for research. They have reported even higher rates than 25% among just their donor sample [in this study]. This really high rate — over 90% of CTE cases in the donor group — is in line with what previous research has shown for these brain banks. So that's not terribly surprising.

What's different in this study is they compared the donors over a certain period of time versus all of the deaths among NFL players during that period of time and estimated the range based on how representative that donor sample was to the overall group of NFL players.

For example, if players just randomly selected to donate their brain to the brain bank and then they found that 98% of all of their samples had CTE — if that's representative of all the players from that era, then that's where you get the higher estimate. But if the majority of players that actually had CTE were the only ones who donated their brains because maybe they were showing outward signs or symptoms of dementia or cognitive decline or behavioral changes while they were living, then it becomes a very highly biased sample.

So that's where you get this big range. [The true prevalence] really depends on how representative that donor sample was to the peer group of players from that era.

NL: Does that broad range of estimates make it difficult to pin down the risk for current players?

TM: I think even more problematic than that big range is to understand that this is a historical study.

So these were players who died between 2008 and 2021, and the average age, I believe, was a little over 70 years of age. So if you extrapolate backwards, they probably played in the NFL starting around age 21 or 22 or 23 — that puts their playing days back in the '60s and '70s. So these were players who played in the NFL predominantly in the '60s and '70s, and would have played college and high school football in the '60s and '50s.

This is a different era of football. So we should not be making any estimations about what current CTE rates are based on this study, because a lot has changed in 50 years. It [the CTE rate] could be the same. It could be greater. It could be less. We really don't know.

I suspect, based on improvements in protective equipment and rules and advances in sports medicine, that the risk is likely lower. I don't have evidence that that's the case, but nobody does. We don't really know how the rates today compare to in the past, since CTE can't be diagnosed in the living. We can't take a sample of current players and look to see how many of them have CTE.

But that is the challenge of this study. It's interesting [in that] it gives us a range of what CTE may be in that group of former players. But it doesn't give us a lot of information about what rates are in current players in the NFL. And even more so, whatever the CTE rate is in professional NFL players does not translate to former collegiate, high school or youth football players, because CTE is an exposure-related disease. For players who have less exposure to these repetitive head impacts, it should follow that they have a considerably lower risk of CTE.

We don't want to confuse a range of CTE prevalence from players who played 50 years ago with contemporary NFL players and definitely don't want to conflate that with what CTE rates may be for current high school and youth players, who have far less levels of exposure.

NL: You mentioned that football has become safer over time. Could you spell out how the game has changed?

TM: We can look at different categories: With the rules back in that era, spearing — hitting with the crown of the head — was allowed, and oftentimes encouraged, as a style of play. That's now penalized and not taught, or shouldn't be taught.

There are changes in equipment, for sure. Modern football helmets — the material, the padding, the way in which these manufacturers are using head impact data to construct position-specific helmets and materials that are designed now to not just prevent catastrophic injuries, like skull fracture, but also to minimize the force from having repetitive head impacts — that's come a long way.

There's the Guardian Caps; you may have seen the NFL has adapted those. So they wear these soft-shell hats on their helmets during the preseason and during practices. That's now required for many of the position groups.

Virginia Tech has a helmet rating system where they test football helmets, and every year, the helmets score better on these tests. They now have star ratings for youth helmets, so manufacturers of youth football helmets are now being held to account, as well.

Maybe the most important thing is just the education around and recognition of concussion and brain injury in the sport. Now, when an athlete has a concussion, they are more likely to be recognized for having a concussion and be pulled from play and have an opportunity to recover before they return to the game. You hear anecdotal stories of former NFL players from that era, like the '60s and '70s, that suffered multiple concussions, oftentimes in the same game, and were not removed from play and continued to practice under those conditions. That medical recognition and treatment management of concussion and brain injury has moved ahead.

You look at the way in which practice was conducted, from full contact, two-a-day practices, which were common even in high school 15, 20 years ago. Now it's really not allowed at any level of play. So the amount of hitting that they do, the amount of contact that players are exposed to in practice and in the preseason is far less.

NL: When players weren't able to recover from concussions, did that likely increase their brain-injury risk?

TM: Theoretically, yes. There's evidence that if the brain is injured and then it's exposed to a second insult or injury before it's properly recovered, that makes the condition even worse.

There's actually a term called "second-impact syndrome," and it's very rare, so I don't want to scare people. But there have been instances where players — it's often, unfortunately, young players, high school players — who have had a concussion which, in retrospect, went undiagnosed and then there was a second concussive blow that led to brain swelling and death. That's the extreme, but there are cases of that [repetitive damage] happening even on a lower scale.

Even if you don't get another concussion, just those nonconcussive repetitive head impacts on top of an injured brain would not be good. It certainly is only going to delay recovery, likely is going to compound your inflammation and all of the downstream consequences of that initial injury.

I suspect that that was fairly common in years past, mainly because concussions generally weren't diagnosed. No one was looking for them, and players certainly weren't encouraged to report if they had the symptoms. So it's very likely that many of these players, including the players that were in the [brain donor] sample, had concussions and played through them and continued to receive additional trauma on top of a brain injury.

Now whether that leads to CTE, we can't really say. But I think it's reasonable to suspect that it probably would increase that risk.

NL: Could you explain whether the physical signs of CTE in the brain tend to come with symptoms, like cognitive decline? Or is the link more nuanced?

TM: So CTE is a neurodegenerative disease that can only be diagnosed by neuropathologists — people that look at slices of the brain and look for particular proteins that are present in certain regions of the brain. [This examination is done after death.] It's a pathological marker. It means that there are changes in the structure of the brain.

The clinical side of that is changes in mood, cognition, behavior, things like dementia or cognitive decline.

Even in the study, they showed that they [the CTE brain changes and symptoms] weren't necessarily linked. Now I believe they showed that for those who had more severe CTE — like the stage IV — that there was a pretty high rate of those individuals who also had subsequently diagnosed dementia. They had these clinicians that looked at the records and diagnosed them. That's a little bit of a limitation of the study: that a lot of the dementia cases were diagnosed after the person had passed away, based on medical records.

To your more immediate point, the presence of CTE: So the presence of these markers in your brain does not necessarily translate into a clinical disease or a clinical diagnosis. There can be signs or symptoms that somebody may have — let's say memory loss or changes in behavior — that may lead someone, like a former football player, to suspect that, "Oh, maybe I have CTE because I played football and I've heard that that's linked with dementia."

That may be true, but it may also be that it's due to old age, or it could be due to genetics or some other condition.

Many of these neurological diseases and conditions can be managed clinically, and there's treatment. There's therapy; there's pharmacological treatments. There's a whole toolbox available for people to seek help. That's, I think, an important message for former athletes or individuals who may be concerned about developing CTE, is to recognize that there is a disconnect between clinical disease and the pathological disease. Just because you have some outward signs or symptoms that doesn't mean that you have CTE.

NL: Since there was a higher likelihood of dementia in the stage IV cases, it seems like there's a stronger link between the pathological and clinical diagnoses at advanced stages. Is that a fair read?

TM: Again, from this study and other studies, just the presence of CTE does not necessarily mean that somebody's mood, behavior, cognition is altered. It seems to be more likely — it seems to be a tighter relationship at the more severe stages, which would kind of speak to what you're talking about. A certain threshold of disease progression seems to be more likely to manifest itself in clinical disease [with overt symptoms].

NL: What should current NFL players take from this study?

TM: I would go back to what we discussed earlier: just understanding the time frame in which the study was performed and when those players were in the NFL. I think we need to be cautious about projecting those rates; it's a pretty wide range of estimates, and it has to do with how representative the sample is. We need to use caution if we are trying to interpret those rates for the current players.

If anything, I think it probably validates all of these efforts that we discussed to try to improve brain health and minimize risk of exposure.

Even if the prevalence is on the low end ‪—‬ that 25% of players who played in the '60s and '70s developed CTE ‪—‬ that's pretty alarming. That in and of itself should get the NFL's attention. Players shouldn't have a 1-in-4 chance or greater of developing this disease.

So let's take steps to reduce that risk — and I think it validates all of the changes that have taken place over the last 50 years. I mean, a lot of them have taken place over the last 10 to 15 years. That's probably the biggest message: to say we were right to do these things and we need to continue to see if there are further opportunities to make the game safer.

Hopefully we've made a lot of progress and current-day rates are much lower than they were in the past. We don't know that, but let's not be idle. Let's continue to push forward to reduce as much risk as possible in a game where you can't completely eliminate the risk. That's something that I think everyone acknowledges; every player has to acknowledge that there is some risk.

NL: Looking forward, what further improvements could be made?

TM: There's a couple of areas that are really in the infancy stages right now. If you think about brain health as a continuum where you would have a disease like CTE on one end and then optimal health on the other end — let's say repetitive head impacts take away from your brain health and tip the scale in favor of developing disease, what are things we can do to tip the scale back in favor of improving brain health?

We know that sleep is really powerful and could learn more about that in and of itself. And what about nutrition? What about pharmacological interventions? Wouldn't it be great if we could develop a medicine, a drug at some point that could be taken preventatively to reduce athletes' inflammation? Really looking into ways in which we can optimally improve brain health as a countermeasure to the damage or the trauma that is occurring.

It's not just football where these treatments could be helpful; it's also with soccer, hockey, other sports and occupations where there is exposure to [head] trauma. I think that's a promising area.

And then, certainly, diagnostic techniques. We talked about CTE only being able to be diagnosed at death. It would certainly be a game changer if we could diagnose it convincingly in the living so it could be recognized early. People are going to have different risks, and some of that is probably genetically determined; some people are going to have the same level of exposure and develop CTE while some aren't. If we could identify individuals who are at higher risk or in the earliest stages of the development of the disease, you can then change lifestyle, behavior, exposure — that would be huge as well.

NL: To shift gears slightly, could you describe your own research in youth sports?

TM: Most of my work over the last 15 years has been focused on youth football players. That's been an interest in measuring repetitive head impacts and neurologic function in youth football players and some work in high-school-age players, as well. So a lot of that is focused around subconcussive injury [head trauma that does not trigger overt symptoms of concussion, like nausea, light sensitivity or thinking issues]. We're looking at the effects of these nonconcussive head impacts on brain health.

That ties into the CTE question in the sense that CTE is thought to be due to cumulative exposure to brain trauma — repetitive head impacts — and certainly most of the work, like in this study, has been done in NFL players. The question for a lot of the general population is, "What about youth players, high school players, that make up 90% of all football players?" So from a public health perspective, it's those younger players that I think we really need to be studying and concerned about.

That's not to say this study isn't really important. It certainly is, but my focus has been on that younger population. And then I do have some experience working more in a hospital background [on] clinical concussion management and [developing] objective pictures of concussion.

NL: With recent research, do we better understand how those nonconcussive impacts affect brain health?

TM: Going back maybe 15 to 20 years, people started to recognize that there were some cumulative effects of concussion. Those were some of the earlier studies showing that former NFL players who had multiple diagnosed concussions had worse outcomes later in life — that kind of put the spotlight on concussion. Concussion went to the forefront, in terms of how we thought about brain injury in football.

And then, over time, this recognition of what has been termed subconcussive or nonconcussive brain injury has emerged, as there's been some imaging studies in collegiate athletes, and even high school athletes, that have found that players who don't get concussed sometimes have changes in their brain, even over the course of the season.

That dovetails with some of the CTE research which has shown that history of concussions isn't necessarily predictive of who developed CTE. It's more of a cumulative effect of repetitive brain trauma. So the CTE researchers have essentially concluded that it's history of repetitive brain trauma, rather than history of concussion, per se, that's a leading risk factor for CTE.

With CTE, it's always looking backwards, because it's something that's diagnosed at death. For researchers like myself who study concussion, or study active football players, that has also then been a reaction of saying, "Well, if it is repetitive trauma, if it's repetitive head impacts, that is a risk factor for neurodegenerative disease such as CTE, then that makes it even more important to study it in active players." What does that head impact exposure look like at different ages, and how can we reduce that exposure? How can we reduce the number and severity of head impacts that players are experiencing?

So there's both the CTE angle, which is, again, retrospective — I'm looking at former players. And the contemporary issues of players who are currently playing and what's the risk for concussion, but also what's their exposure to repetitive head impacts? So it's really tied together.

That's why there's so much concern about repetitive head impacts and why there have been rule changes at the collegiate and high school level about the amount of contact and limiting those types of activities, with the idea of reducing that overall head-impact burden.

NL: When you talk about repetitive head impacts broadly, I assume that covers both concussive and nonconcussive impacts?

TM: Yep — so every hit would be considered a head impact, and then certain impacts are strong enough, or hit you in the right spot, to cause a concussion. The vast majority of impacts are nonconcussive.

NL: How do you speak to these athletes' families about the risks of concussion and CTE?

TM: When I do talk to players and coaches and parents, I often like to remind them that, generally, the benefits of playing sports, including tackle football, outweigh the risk. Oftentimes we get so concerned about the risk, which is real, that we forget about the benefits and about the alternatives of not playing. Almost always, the benefits — from the physical, the psychological and social components, the mental health components — are going to outweigh the risks. That's one thing to keep in mind.

Second, the risk of injury — in this case, CTE — is likely going to be far less in those younger players than older players, NFL players because their exposure, the number of impacts, the severity of impacts is far less. With my research, I've measured those head impacts and compared them to high school players and collegiate players, and extrapolated to NFL players because that data isn't available. And you see this big stepwise increase in exposure from the youth, the high school, the collegiate, to the NFL players.

[With parents], I'm reassuring them that the risk is far less for the younger players than what they hear about in this type of study. We're talking about an apples-to-oranges comparison.

I also like to remind them that, in my opinion, the game of football has never been safer. I've got a bit of a personal perspective on this as well, because I played football myself through college.

NL: Who did you play for?

TM: I played for a Division II school in South Dakota called — it's Augustana University now; it was Augustana College when I played there.

So I played 12 years of tackle football, and I can compare what tackle football was like when I was in fifth grade versus now — with the training that coaches have and the type of equipment they have and the way the practices are structured. It's completely night and day.

Even at the collegiate level, the way in which collegiate practices are conducted and the safety measures that are in place for current collegiate players is nothing like what we had when I was playing. So I like to reassure players that this is probably the safest time to be playing the sport of football.

At the same time, I acknowledge that this is an individual decision that parents need to make with their kids and evaluate that risk. One of my goals as a researcher is that I want to provide more empirical evidence so that they can make an informed decision, so that a parent would be able to say, "My son's risk of getting a concussion while playing youth football is 1 in whatever" — you know, 1 in 10, 1 in 5, or 1 in 100, whatever that case may be. And his risk of getting CTE by playing four years of youth football or four years of high school football would be this. Then you make an informed decision. Is that risk worth the benefit of participation?

Unfortunately, we don't know what that risk is [currently]. We can't tell parents, "Here's objectively what your risk of injury is going to be." It makes it tough for parents. So I like to reassure them that a lot of the concerns that are expressed for NFL players are greater than they should have as parents of youth players.

This interview has been condensed and edited lightly for clarity. It is for informational purposes only and is not meant to offer medical advice.

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In 2013, MIT neuroscientists Steve Ramirez and Xu Liu published a paper detailing how they had created false memories in mice. They'd used optogenetics — where cells' activity is manipulated using light — to plant a fearful memory in the brain and then reactivate this memory with these pulses of light. The breakthrough helped to propel research in the field by showing that memories can be artificially constructed.

The initial experiments involved using a protein to tag brain cells in the hippocampus (a key memory center in the brain) that were active during the formation of a fearful memory. They then reactivated these "fear memory-bearing cells" while the mice were perfectly safe. The first four mice showed no response, but the fifth froze in fear. After analyzing the fifth mouse's brain, it turned out they had placed the protein in a slightly different location of the hippocampus to the others by accident — and inadvertently found the exact spot where the memory was stored — and that it could be manipulated and controlled.

In his book "How to Change a Memory: One Neuroscientist's Quest to Alter the Past" (Princeton University Press, 2025), Ramirez, now an associate professor at Boston University's Center for Memory and Brain,explores fundamental questions about memory: What is it, and can we manipulate it? He uses his personal experiences ‪—‬ including with loss, PTSD and addiction — to probe these ideas, asking whether this line of research could open new paths to treatments. He conceptualizes a world where memories could be manipulated to help ease a person's PTSD, or guard against dementia.

Live Science spoke with Ramirez about the book, the future of memory research, the ethics and implications for treating disease, and our brains' extraordinary power to recall our past. "How to Change a Memory" has been short-listed for the 2026 Royal Society Trivedi Science Book Prize.

"How to Change a Memory" excerpt: 'As if a shudder ran from its brain to its body': The neuroscientists that learned to control memories in rodents

Hannah Osborne: In the book, you reflect on your and Xu's major 2013 paper, noting that it was initially the result of a botched surgery in a single mouse. What if that little mistake hadn't happened?

Steve Ramirez: If we hadn't accidentally botched the surgery, I'd like to think we still would have gotten there, because what would have happened was that we would have done all the surgeries correctly, we would have hit the wrong spot, and everything would have been a negative result. And then, we would have said, "Maybe this is the wrong area to try to activate a memory." Now, where we would go next, I don't know.

I'd like to think that we would stay within the hippocampus and we would say, "Why not this other part or this other part?" Or maybe we would have moved to another brain area. But I think it would have delayed the inevitable by maybe six months or less.

Having hit the area, I think we realized that these mistakes — I shouldn't say mistakes; these unintended outcomes of an experiment — are certainly something that I think are pretty common. We just don't look for them often. A lot of times, we'll see a negative result and say, "OK, there's a million reasons why this experiment may not have worked as predicted," because it's very hard to touch base with reality and test the hypothesis. But I think it taught us to look a little bit more deeply when we see results that are either confusing or head-scratching.

The more I talk to people in science, I think everyone has this version of this one hiccup in an experiment [that] led us down a completely different rabbit hole that ended up being the basis of a paper or a series of papers ‪—‬ or, in mine and Xu's case, a career and then some.

I wouldn't say that they're universally common in every experiment, but I think that biology is so squishy, we're going to get things that kind of zig when we think that they're going to zag.

HO: Throughout the book, you talk about engrams. What are they, and why are they so important to memory research?

SR: An engram is a theoretical construct. It's a theoretical topic that certainly elicits every possible opinion out of memory researchers because it's kind of the holy grail of "what is memory." We think of an engram as whatever the physical basis of memory is.

It's almost like, what are the cellular building blocks of a memory in the brain? Whatever those building blocks are, that's what we consider an engram. And the reason I say that it's theoretical is because we don't really have a clean-cut "This is where an engram begins and ends in the brain."

We're not at the point where we have a Google Maps for an engram and we can zoom in to "This is the emotional part, and this is the smell associated with the memory." We have more of a zoomed-out satellite view of what an engram looks like. But we'll get there, and it's important, because if we have a full understanding of the physical manifestation of memory in the brain, then we have a way better chance of predicting what's going to happen when those building blocks break down and give rise to certain kinds of amnesia or cognitive impairments or memory loss.

By analogy, we have a pretty good understanding of how the heart works down to the physics of how a pump works, for example. Now that, thankfully, has enabled us over the past 200-plus years of cardiology, to have heart valves that we could 3D print or grow in pigs or things like that. With the brain, there's no law of physics saying that we can't get there to turn the brain into how we view the heart, where we can 3D print pieces to replace what was broken, or we understand a bit of clogging in this artery will lead to all of these different impairments.

We're only beginning to understand what those [metaphorical] clogged arteries look like in the brain, especially when it comes to memory. So if we have an understanding of the detailed physical picture of what an engram is, then we'll have a better shot of being able to predict what happens to ideally even prevent its breakdown, for example.

The goal is to understand the physical basis of memory and to use that understanding to try to enable well-being to an individual.

HO: In your experiments, you've used optogenetics to manipulate memories in mice, but that technique isn't widely used in human medicine yet. If you wanted to apply it in humans as a therapy, are there hurdles we'd need to get over? How are we going to be thinking about changing memories in 10 years?

SR: I'm so glad you asked, because I think it can go in two directions. Optogenetics is not really used in humans at all, except for maybe like eye retinal therapy, because you can flash light into the eyes and it's noninvasive and pretty straightforward. [Editor's note: Optogenetic retinal therapies are currently in clinical trials.]

There are groups working on some pretty remarkable technologies on being able to deliver [genetic] payloads into the brain, such as an optogenetic tool, but in a way that doesn't even require putting a virus in the brain [as is often done in gene therapies] or the optic fiber. There's groups working on giving even injections peripherally — like in the arm or in the rodent tail — and have that make its way into the brain, so it's way less invasive.

I'd like to think that technologically, we [researchers in the field] are working on trying to get optogenetic tools as noninvasively in humans as possible. But maybe the question becomes, do we want to do optogenetics in humans? And I just think that we may not have to, because there's so many other ways of doing what optogenetics does in rodents in humans, but especially with regards to memory.

In rodents, we have to go in and find those cells that hold on to a particular memory, that part of an engram, and activate those cells to get the animals to recall the memory. In humans, I can just ask you, "How was your night last night? How was your dinner? Did you have anything particularly savory or sweet?" Then, just through noninvasive verbal communication, a world of memory can come back in your mind.

I'd like to think of what we're doing in rodents as setting a blueprint for the kind of work that we could do in humans and that we can be clever about how to access things like memories in humans, where invasiveness like deep brain stimulation or transcranial magnetic stimulation is probably a last line of defense, whereas maybe the first lines of defense would be more cognitive behavioral [therapy, or CBT] because it requires no invasiveness into the brain at all.

HO: You look at the ethics around memory research a lot in the book. Where do you think the line is for whether we can apply memory manipulation, versus whether we should?

SR: I think there's two things happening simultaneously here. I don't think we should ever, for example, remove personal agency from the decision-making process here unless our personal agency has been removed by a particular disorder or something that can be medically considered [as having] robbed us of our ability to do the things that we want to do.

For instance, a patient living with depression, we may not just be able to tell them, "Think positive memories." Well, no, that's the very thing that we can't do, right? It's like asking someone with a broken leg to walk it off. So I think of it this way, where this kind of work can go with humans: we have to have some morally or ethically bounded goal of why we're doing what we're doing.

The goal of our research is truly to understand memory and to use that understanding to restore health and well-being to an individual. Now that's pretty arbitrary. That's human-made. We've made that up. We're the ones that made up this ethical boundary that this has to be used as a force for good — but by having that either ethically, or morally, or even medically bound goal, it can prevent us from derailing because we have a goal in sight that considers the overall well-being of people.

This is kind of like a sinister example, because people have compared this to the Manhattan Project. The goal was to build the bomb — it was to build or use nuclear fission; create it so that we can create a bomb. Now that's not necessarily an ethically bounded goal. The goal there is "win a war," and it's kind of the opposite of how I think about our research. The goal of our research is to prevent misuse by anticipating it first.

So what are the seat belts and what are the guardrails here? If we start by considering memory manipulation as part of our tool kit to help tackle disorders of the brain, then we have to use that inherently into some sense of good or medical good.

If we keep memory manipulation in the province of medicine, and in the clinic, then we can at least start in a way that takes the person into consideration first and foremost. We can study it to see, what are the side effects? Just like with any other drug, long-term use, is there desensitization? Are there clinics popping up everywhere that's doing this underground? We can anticipate all of this, right? Begin with it in the clinic, because we can have a kind of social infrastructure that can prevent its misuse and really hit the accelerator on using it for good.

The second part — and where I take my academic hat off and just become part of the public like everyone else — is, it's on us, society as a whole, to at least engage with some semblance of science literacy in a way that I think science can really be conveyed and used for good, whether it's storytelling or as a tool. Right now, it's so easy to fall under the traps of misinformation.

When we think of memory manipulation, everyone thinks Hollywood: "Eternal Sunshine [of the Spotless Mind]," "Total Recall." That's good for getting the conversation started and saying, what did "Total Recall" get right and wrong? What did "Eternal Sunshine" get right and wrong? But let's look at Hollywood, and let's use it as a case study of, where did memory manipulation go wrong here? Let's avoid that, or let's try to come up with some infrastructure that can avoid it. Where did memory manipulation go right? Let's try to do more of that and build some infrastructure around that.

HO: In the book, you note neuroscience is a relatively young discipline compared to things like astronomy. What do you think is the weirdest and most mind-blowing thing about memory that we still don't understand?

SR: The first thing that comes to mind is — I don't know how many memories we have, but let's just say we have a million memories or 10 million memories — that it's amazing to me that if I had 10 million memories, they all exist in my brain right now. They're all there. I can randomly think of the last time I ate steak, and my steak memories come up. Or I can randomly think of the last time I played a song on the piano, or me and Maple [his dog] going out for a walk, and then all of those memories come back.

So, 9,999,999 memories are quiet right now in my brain, except for one, which is me going out for a walk with Maple yesterday. But presumably, the other memories are still shaping me and sculpting my brain and influencing very much my biology, my sense of self, my personality, my identity, because they are me. They're just not bubbling into consciousness at the moment.

I think it's amazing that I can recall one memory and on the basis of what that memory is, I can either be moved to euphoria because I'm thinking of some of the happiest days of my life or be moved to tears because I'm thinking of more somber days of my life. And both of those can happen within like five seconds or less, depending on which memory I chose. I can experience the peaks of happiness or the valleys of sadness within five seconds or less. It's crazy that we can do that without really breaking a sweat.

What is everything else [the other memories] doing simultaneously? They might be helping to sculpt things like our imagination or our dreaming or our sense of self, which is an aggregate of all the sum of all of our experiences. I think that the fact that memories can move us through the entire landscape of emotion within seconds and that we have so many more memories that just fly under the radar of consciousness that are probably doing that and more is pretty remarkable. It's kind of scary, but it's kind of remarkable to think about it that way.

HO: On a related note, why do we wake at 3 a.m. and think of something stupid we did 20 years ago?

SR: As someone that wakes up like every other night at 3 a.m., I totally resonate here. There's a couple of theories. The first is less of a theory and more of a point. In terms of like the previous question about how remarkable memory can be, it's amazing that we have dormant memories that are decades old that, up until right now, we have every reason to believe we'd forgotten them. They don't exist anymore ‪—‬ out of sight, out of mind ‪—‬ and they're off into the ether now. But the fact that we can wake up at 3 a.m. and randomly remember something from 20 years ago is beautiful evidence that memories might go into dormancy for decades, but they may not actually be gone or erased or forgotten.

It's kind of wild, because I think that we have more possible connections in our brain than we do seconds of life. I don't think we would ever run out of space in our brain. I don't think that would ever happen.

But in terms of like waking up and the kinds of memory or waking up and recalling memories from the distant past, one theory is that whatever was happening when we formed that memory, there were particular sights and sounds and smells happening around us, and presumably we also felt a particular way during the formation of that memory, like our inner state was something when we were making that memory. Probably through random chance, when we wake up …our inner state happens to match the state that we were in when we made that memory, plus maybe a couple of more cues ‪—‬ a random song in the background that was playing that reminds us of it, or a particular odor, or maybe even something subtle like we saw a commercial an hour ago that just primed that.

I think it's evidence that some memories may truly live on in the brain for the entire life of a person, even though we don't recall them for decades, meaning we have access to an insane amount of memories in the brain that we don't always actually intentionally access.

We don't have an answer for it yet, but it gives me hope that some memories that are thought to be gone are not and actually way more restorable.

Hannah Osborne: It's a very personal and moving book, which you dedicated to Xu Liu, who passed away in 2015. What made you want to write it, and was it a difficult process?

Steve Ramirez: There's two things that made me want to write this book. The long-term reason was because I've always wanted to write a book since I was a kid. I do think that there's this inner 5-year-old core of me that thinks that if you're on a bookshelf, you matter somehow, like you did something that was important that all of humanity can read and presumably benefit from or learn from in some way, and I always found that cool as a kid.

More personally, in 2015, a book agent had reached out, asking if I was interested in writing a book. And I said, "Absolutely — but I have no idea about what." It wasn't until Xu passed away that all of the puzzle pieces clicked, [and] I was like, "I know what I want to write about" because I now have a real passion project. I knew that I always wanted to intertwine a bit of myself in this project because that's the way that I teach. In the classroom, I often bring my lived experiences.

More than anything, it was a way of honoring my friend, and that really felt like the purpose of the book — to honor my friend and, along the way, teach neuroscience, because that was kind of the basis of our friendship to begin with. I realized it's not so much that I want to as much as I have to write this book. That turned into very much benefiting from it in all of the weird ways that writing a book can change a person.

HO: Could you tell me about how you and Xu met and when your friendship clicked?

SR: Our friendship really did click on the first day that we met. We met in the lab, so we knew that science was going to be the common denominator of conversation, but it just so happened that there was a social that day for our building, which just meant free food and drinks for everybody. When we started chatting, we said, "Let's go; let's not miss the free drinks and food. Let's go to the social, and we'll continue our conversation there."

Then we spent the next couple of hours talking about all of these ideas of trying to artificially reactivate memories and why we thought they were important. It was such an easy conversation to have because I felt like I could let my academic guard down around him because, at least in the first year of grad school for me, it felt very stuffy and everyone at MIT was like an insane hotshot in some way and very intimidating. But Xu was just someone that I could level with; I could ask my quote unquote dumb questions, and I could just have a regular conversation about science.

When we were in the elevator ride back up to the lab, he mentioned just in passing that since it looks like we might be working together, we should just be co-first authors on everything that we do. It was just so perfectly emblematic of how our friendship would evolve, where all of our talks, all of our presentations, even awards, we were very like down the middle because there was no one without the other when it came to how we did our projects together. The combination of the scientific and the interpersonal made it easy. We were quite different people but very complementary, and I think that's what made it work.

This interview has been condensed and edited lightly for clarity.

Scientists may have found a way to regenerate the neurons that are lost due to conditions like Alzheimer's disease, a new laboratory study hints.

The research, published Aug. 26 in the journal Cell Biomaterials, suggests that reducing levels of a key protein in another type of cell in the brain, called astrocytes, may convert those cells into neurons. The adult brain has a limited capacity to produce new neurons, at baseline, and an even more limited ability to replace neurons lost to disease.

If successfully developed into a treatment for humans, this new approach could replenish lost neurons and thus restore brain function, the study authors say.

Astrocytes are abundant, star-shaped cells in the brain that protect and support the functions of neurons. A crucial protein for astrocyte development is called PTBP1, and previously, scientists suggested that eliminating this protein in astrocytes may convert them into neurons. In that study, researchers reported converting astrocytes in the mouse brain into neurons by eliminating the gene that coded for PTBP1.

However, later experiments contradicted these results, suggesting that newly formed neurons could not be traced back to the astrocytes. So Peisheng Xu, a co-author of the new study and a pharmaceutical scientist at the University of South Carolina, set out to investigate that contradiction.

"We felt it's strange [that] two groups of people got different conclusions," he told Live Science.

He used a technique called Nano-Eraser, developed earlier in his lab, to delete PTBP1 from astrocytes without editing any of their genes. The team accomplished this by packaging an antibody that targets PTBP1 into a polymer gel. That gel helped sneak the antibody across the blood-brain barrier, a gatekeeper that prevents certain substances in the bloodstream from entering the brain.

Once it reaches astrocytes in the brain, the antibody binds to PTBP1 and drives the cell's internal machinery to destroy the protein.

"I think it's quite interesting, intriguing and an innovative approach," said Dr. Christiane Wrann, a neuroscientist at Harvard Medical School, who was not involved in the study. "They show that [the gel] can cross the blood-brain barrier," which is important for developing therapies for the brain, she told Live Science.

The team first tested the gel in human astrocytes grown in lab dishes. Over the course of days, astrocytes exposed to the gel lost their characteristic star shape and started to form axons — the wires from which neurons send messages. Proteins typically found in neurons also became more abundant in the astrocytes.

The cells later showed electrical activity that further confirmed that they were functioning similarly to neurons and could fire synchronously. The gel also showed similar results in miniature models of the brain, called organoids, which had been grown from human stem cells.

The researchers then tested the gel in mouse models of Alzheimer's disease. These lab mice had lost neurons and had developed some characteristic features of Alzheimer's disease, such as inflammation, loss of cognitive function, and sticky clumps of a protein in the brain.

The team gave these mice two intravenous doses of the gel, eight days apart. Over the next four weeks, behavioral tests suggested that the treated mice's memories improved and they were able to build better nests than untreated mice; that's an indication of improved behavioral function. Later, the researchers examined the brains of the treated mice, finding that the density of their neurons had increased while their levels of inflammatory molecules decreased.

However, while the lab-dish experiments indicated that astrocytes converted into neurons, that finding has not been confirmed in live mice, Xu said.

"We observed that neuron density increased in treated mice compared to untreated ones," he said, "but we cannot yet eliminate the possibility that some other neural stem cells might have also converted into neurons."

Wrann agrees that additional experiments would have been required to see whether a particular astrocyte in the mouse brain changed into a neuron. While the results are "intriguing," a lot more research is needed to see the long-term effects of such a treatment on different types of brain cells, she said.

Xu and his team now plan to probe further into astrocyte conversion in live mice. Before they can move to clinical trials with people, he said, the safety and effectiveness of the treatment would need to be tested in nonhuman primates.

Notably, astrocytes themselves serve important functions in the brain. So there's a question about what having "chronically reduced PTBP1 could do to the brain," Wrann noted. She agreed that careful studies would be needed for this to translate to humans.

"That's something that needs to be tested step by step," she said.

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The brain develops in stages, and it's important that certain cells form before others so that precise neural connections can emerge later. But miniature models of the brain, called organoids, may not share this same sense of time, a new study finds.

These brain organoids are clusters of lab-grown neurons that mimic structural and functional aspects of full-size brains. Some scientists use these "minibrains" to study brain disorders that can arise during fetal development.

If the precisely timed processes involved in brain development go wrong, it can lead to conditions like macrocephaly and microcephaly in which the brain grows abnormally large or small, said study co-author Simon Hippenmeyer, a neuroscientist at the Institute of Science and Technology Austria.

Because it's not possible to directly study these conditions in human fetuses, scientists like Hippenmeyer turn to brain organoids. But the new study, published Aug. 12 in the journal Nature, suggests that organoids may be missing some crucial ingredients that would help them resemble real brains.

A matter of time

In earlier experiments in mice, Hippenmeyer's team tracked the stem cells that make neurons, called radial glial progenitors (RGPs), during early embryonic development. They did this by giving pregnant mice a drug that activated fluorescent labels on individual stem cells. Then, they traced the resulting lineages of those stem cells after birth to see how many cells they produced and how that number changed as development progressed.

In the new study, they used that data as a reference to compare with brain organoids grown from mouse embryonic stem cells. They aimed to see if the developmental sequence in the organoids resembled that in the real brains.

The organoids produced the same major types of cells as the real brain did, the team found. However, the sequence of development was not preserved.

During normal brain development, RGPs in the cerebral cortex — the brain's outermost tissues — divide to increase their numbers and then differentiate, forming neurons and glial cells, which help to support, nourish and insulate neurons. In the organoids, however, some RGPs formed neurons too early, while others were still proliferating.

Normally, RGPs from later stages of development produce fewer descendants than the stem cells do in early development. But in the organoids, they produced more descendants regardless of the developmental time frame.

After seeing these patterns, the team investigated the variety of neurons that a single RGP could produce in an organoid. The cortex is made up of six layers of tissue, and normally, an individual RGP can produce both deeper-layer neurons (earlier in development) and upper-layer neurons (in the later stages). But in the organoids, about one-third of the RGPs became restricted to just one of these fates and then couldn't make the other type of neuron.

In a real brain, Hippenmeyer noted, there are blood vessels, extracellular structures and metabolic signals that affect the organ's development but are absent in the organoid. The researchers think these external signals may help coordinate the timing of neuronal development and the later formation of neural circuits.

"This suggests that there is something about the local environment of the cells [in the brain] that gives rise to the neurons," said Denis Jabaudon, a neurobiologist at the University of Geneva who was not involved in the study. However, scientists don't have a precise understanding of what those signals are yet, Jabaudon said.

For neurons to find each other, they have to be in the right place at the right time, Jabaudon added. "So, if you shift the timing of development, you're going to be shifting the opportunities for connections and the opportunities for specific circuits" to form, he told Live Science.

Identifying what's missing from these organoids will involve identifying and investigating those external signals neurons receive in the live brain. Then, scientists can identify differences between real brains and organoids that inform us about how the process naturally happens, Hippenmeyer said.

Once these missing ingredients are identified, this could "open the door" to systematically add back those signals in organoids in a way that would mimic the real brain closely, he told Live Science. Hippenmeyer added that the team also plans to grow brain organoids with human cells and investigate the same questions.

"We are very keen on finding out how those radial glial stem cells would behave in a human system," he told Live Science.

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Long-term memories may not "stick" in the brain for the reasons we thought, a study of mice in artificial hibernation reveals.

Instead of relying on many individual, strong links between neurons — which would typically be pared down during hibernation — long-lasting memories seem to require higher-level patterns in connectivity, the study found.

"This topological architecture of the broader network seems to be more important" than individual, sturdy connections, said study co-author Kazumasa Tanaka, head of the Memory Research Unit at the Okinawa Institute of Science and Technology.

The findings, published Thursday (Aug. 13) in the journal Science, may complicate the picture of how memory retention works.

Tanaka and colleagues used hibernation to study memory because past studies of hibernating animals have found that their brains shrink and pare down cell-to-cell connections during these extended periods of low metabolic activity. At the same time, the brain's activity slows to a crawl, and the loss of connections is thought to be related to this energy-saving mechanism.

Despite this brain shrinkage, hibernating animals, such as alpine marmots (Marmota marmota) and European ground squirrels (Spermophilus citellus), still retain memories they formed before they went into hibernation. "Some studies report their memories are intact, even after, so they can remember conspecifics [members of the same species], like their friends, or they can remember the locations of their food," Tanaka told Live Science.

The new study aimed to tackle the question of what allows those memories to stick around even after many connections between brain cells disappear.

A "switch" in the brain to turn on hibernation

A central dogma of neuroscience holds that memories are made when connections between neurons grow stronger.

Through a process called long-term potentiation (LTP), neurons that send frequent chemical messages to their neighbors start to release more of those signals. In turn, their neighbors grow more sensitive to the signals by increasing their number of receptors and the size of their dendritic spines — the physical structures that receive inputs from other neurons. Ultimately, LTP forges a strong bond at the point where two neurons meet, called the synapse.

An old adage in neuroscience sums up the idea: "Neurons that fire together, wire together."

"I don't think our study argues against this LTP hypothesis," Tanaka said, noting that many studies support the idea that LTP is critical for the brain to forge new memories. However, when it comes to holding on to memories over time, LTP may not be the most essential ingredient.

Recent studies have found that the structures of memories in the brain are actually very dynamic. Rather than relying on a strict and consistent set of connections between specific neurons, these physical traces of memories "drift" over time, within days, Tanaka noted. As a memory drifts, the original LTP-strengthened connections that made that memory can be lost — and yet, the memory persists.

The question is how.

The new study zoomed in on the hippocampus, a major memory processing hub in the brain. It focused on episodic memories, meaning those concerned with specific events and personal experiences. These memories are born in the hippocampus, remain there for a time, and then get transferred to other parts of the brain for super-long-term storage. That transfer can take weeks, months or more, and some neuroscientists think contextual details of the memories — such as the environment where they were formed — remain forever embedded in the hippocampus.

In this case, the researchers were interested in that initial period of memory storage in the hippocampus, so they ran lab mice through several experiments to imbue them with new memories. In one experiment, they'd been taught to associate a specific setting with a mild shock to their paws; in another, they'd learned the locations of sugar pellets placed within a maze.

Then, they pushed those mice into artificial hibernation for two days, by switching on a special set of neurons in the brain that had been identified in past work. In mere minutes, the mice's brains started to change.

"We knew that some degree of the remodeling happens, but the degree was much bigger than what we expected," Tanaka said. Within 30 minutes, the brain was already paring down synapses, and within 24 hours, they "found more than half of the synapses were already gone," he said.

Completely intact memories

Despite this drastic change in the hippocampus, the mice remembered what they'd learned prior to hibernation. After hibernation, the mice froze in place when they were placed in the setting where they were shocked, ‪and in the maze, they navigated to the food as easily as they did before hibernation ‪—‬ indications that they remembered both events.

"To compare the animals with or without hibernation, their behaviors are not different whatsoever," Tanaka said.

To get to the bottom of how that could be possible, the team compared the hibernating mice to another set of lab mice, which were instead put under long-term anesthesia and treated with a molecule that blocks neurons from strengthening their synapses. The latter group of mice also saw dramatic synapse loss, but unlike the hibernating mice, their memories didn't linger after the treatment. What made the difference?

Peering closer into both sets of brains, the scientists spotted a distinction: In the hibernating mice, certain clusters of synapses appeared to be resilient and survived the culling.

These spared connections tended to be hubs where a single neuron sending outgoing messages linked up with several neighboring cells, broadcasting its messages. They also appeared in places where many dendritic spines — the points where neurons receive messages — were bunched close together and received messages from multiple neurons at once.

"That unique structure is preserved during hibernation, Tanaka said. "Under anesthesia, we found they're completely disrupted."

The size of the dendritic spines didn't seem to matter, he added. It was this clustering pattern that seemed to be key for memories' survival.

Looking forward, there's much more to learn about these clusters and their relationship to memory retention. The scientists are now working to characterize the clusters at a molecular level. Eventually, they hope to manipulate the clusters' structure and formation to see what that does to memory. They are also running experiments to figure out how the brain preferentially spares these clusters while pruning away so many other connections in the hippocampus, Tanaka said.

Beyond neuroscience, the research could help engineers design better ways to store data in computer systems, he noted. But when it comes to the memory of living creatures, the study furthers scientists' understanding of how the physical traces of memory in the brain can change so much without sacrificing the memories themselves.

"With this study," Tanaka said, "we just opened up another door to tackle this problem."

Inflammation may be behind a mysterious phenomenon known as dissociation, a mental state that includes "out-of-body" experiences and the feeling that the world is "unreal," emerging research suggests.

Scientists have long known that this altered state of consciousness is often triggered by trauma. But new research hints at how: Trauma triggers a stress response, which dials up chronic inflammation. The findings are part of a broader shift in psychiatric research as experts increasingly examine how the immune system may play a role in mental health conditions.

The research, which has been accepted for publication and is currently under peer review, is still preliminary, and it is based on correlations between blood markers and symptoms, which cannot prove inflammation causes dissociation. But if follow-up work shows inflammation fuels dissociation, that raises the possibility that anti-inflammatory drugs could treat disorders in which people spend much of their time feeling detached from themselves or reality, experts told Live Science. Interventions that broadly target reducing inflammation could also be beneficial, the study suggests.

Research in this area could provide a "whole new avenue for potential treatment options," study lead author Evelyn Dilkes, a psychology researcher at the University of Essex in England, told Live Science.

A common experience, a rare disorder

Dissociation encompasses both out-of-body experiences, known as depersonalization, and the feeling that everything around you is unreal, called derealization, said Dr. Ruth Lanius, a psychiatry professor and Harris-Woodman chair of mind-body medicine at Western University in Ontario. Both of these experiences are related to a person's sense of self and embodiment.

As a short-term phenomenon, it is common; between a quarter and three-quarters of the population may experience dissociation at some point in their lives. It can also be a symptom of many conditions, such as schizophrenia, depression, anxiety, panic disorders and epilepsy.

In around 1% of the population, people may experience prolonged dissociation, in what's known as depersonalization-derealization disorder (DPDR). People with this condition may frequently feel detached from their body or from reality for hours, weeks, months or years at a stretch.

Research suggests DPDR is often associated with past trauma, such as a life-threatening event or childhood abuse. During a traumatic event, dissociation may be helpful because it may offer "a psychological escape when a physical escape is not possible," Lanius told Live Science. It may also help a person stay calm and focused on the threat at hand.

The problem arises when dissociation continues after the threat has passed.

"[Dissociation] helps you to survive, but in the aftermath of trauma, it leaves you detached from all of your emotions, positive and negative, and so often individuals lose the capacity to feel fully alive," Lanius said.

So why does dissociation linger long past the immediate trauma for some people?

From stress to inflammation and then dissociation

Past research showed that inflammation, which can be the immune system's response to infection or injury, seems to be dysregulated in individuals with dissociative conditions. So Dilkes wondered whether the link between trauma and prolonged dissociation runs through the body's response to stress as a kind of "biological embedding," in which life experiences alter a person's physiology. That hypothesis proposes that trauma initially triggers a stress response. When that stress response doesn't subside, the body's stress system stays activated, continually releasing the hormone cortisol from the adrenal glands.

Cortisol is typically anti-inflammatory in short exposures, but when it remains elevated over long periods, it can contribute to chronic inflammation. This can show up in blood levels of interleukin-6 and C-reactive protein.

So Dilkes' lab looked for those inflammatory markers in the blood of children in the U.K. who were followed, starting in the 1990s, as part of the Avon Longitudinal Study of Parents and Children. The study collected samples at age 9 and 12 and again at age 17 and 24. The study asked participants when they were adults whether they “ever felt that they were not a real person, not part of the living world,” or if they “ever felt that the world was unreal, that things around them were like a stage set.”

Early results suggest that high interleukin-6 levels at age 9 seem to be correlated with people experiencing depersonalization in adulthood, while elevated C-reactive protein levels in earlier childhood, but lower ones in adulthood, are linked with experiencing derealization as an adult.

In the latter case, the study authors suggest that chronic stressors could dampen the immune response, leading C-reactive protein levels to drop over time even as symptoms linger.

The researchers also speculated that interleukin-6 and C-reactive protein may differentially act on the different brain regions affected in depersonalization and derealization, respectively. These findings may reflect differences in how stress and immune activity shift across the lifespan following trauma. "It's suggestive of a very intricate system," Dilkes said.

Affected brain regions and networks

Dilkes' research can't answer which brain regions and networks are likely affected, but past research suggests dissociation involves emotional blunting in the brain. In this response, the prefrontal cortex, which is involved in planning and decision-making, acts as a brake on the limbic system, which helps people experience emotions, Lanius said.

According to this theory, dissociation occurs because circuits in the amygdala, the fear-processing part of the brain, hyperactivate the prefrontal cortex. The overactive prefrontal cortex then disrupts normal signaling to the limbic system. The overall result is a dampening of emotions, which may enable people to stay focused and rational during a scary event.

This brain activation pattern, which is characteristic of DPDR, is the opposite of that classically found in post-traumatic stress disorder (PTSD), in which the amygdala is hyperactive, while parts of the prefrontal cortex are underactive. (There is, however, a subtype of PTSD associated with dissociation.)

Some early research hints that the default mode network and the temporoparietal junction, which are thought to be involved in maintaining a sense of self, may be affected in dissociation.

In the new study, the researchers speculate that interleukin-6 exposure in youth may influence the development of the default mode network, which could result in depersonalization symptoms later in life.

Many unanswered questions

While Dilkes' findings are intriguing, outside experts cautioned against overinterpreting early results.

Extrapolating results from studies that investigate dissociative disorders is difficult because patient groups with different diagnoses differ a lot from each other, said Judith K. Daniels, a professor of clinical psychology at the University of Groningen in the Netherlands. What's more, many symptoms can overlap between different dissociative disorders. Dissociation fueled by childhood abuse may differ biologically from dissociation found in a panic disorder, but current research isn't able to distinguish these groups.

What's more, biomarkers of inflammation like C-reactive protein and interleukin-6 are often elevated in other inflammatory and autoimmune conditions ‪—‬ such as rheumatoid arthritis, lupus and multiple sclerosis, while, most people who experience trauma do not develop a dissociative disorder, which suggests that additional genetic or environmental factors are likely involved, Lanius said.

The nonspecific nature of these blood markers would also make it challenging to use them to diagnose DPDR, though in the future they could potentially be used alongside traditional DPDR screening tools, experts told Live Science.

One big limitation is that scientists do not yet fully understand how the brain constructs conscious reality in the first place.

"In my opinion, if we don't understand altered states of consciousness and dissociation, we can't understand psychopathology fully," Lanius said.

For now, more research is needed to determine whether therapies targeting inflammation would benefit people with dissociative disorders. Conditions like DPDR are thought to be rare, but symptoms are often overlooked, which can make it hard to both determine how common it is and to find study participants. But Dilkes thinks dissociation is underdiagnosed.

"So many people experience this, but no one has the words or knowledge of what it is," Dilkes said.

Editor's Note: This article was produced as part of the Dalla Lana Fellowship in Journalism and Health Impact program at the University of Toronto.

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The patient: An 8-year-old girl in the U.S.

The symptoms: The girl arrived at an emergency department after waking up with sudden, severe pain in her upper back. Within hours of the pain emerging, she developed rapidly worsening weakness in all four limbs, making it impossible for her to stand or walk.

She also reported painful tingling and loss of sensation in her hands, and doctors discovered that she had diminished reflexes and sensory changes beginning at her upper chest and moving down her body. In multiple instances at the hospital, she lost control of her bladder and bowels.

The combination of acute paralysis, severe back pain and incontinence suggested damage to the spinal cord, but the cause wasn't immediately clear, her doctors wrote in a report of the case.

What happened next: The medical team launched an extensive search for the underlying cause. An MRI of her neck and torso showed evidence of extensive inflammation or injury that stretched from her lower neck to the middle of her back. The scan also showed a small tear in one of the disks in her lower neck, with a small amount of disk material pushing outward.

However, the girl and her parents did not report any recent falls or injuries, and the MRI alone couldn't determine what had caused this apparent damage.

The girl's medical team then performed blood tests, a spinal fluid analysis and more imaging to look for signs of infections, autoimmune diseases or other inflammatory conditions that can trigger acute paralysis in children. These tests all came back negative.

While clinicians continued investigating, the girl was treated with intravenous steroids and underwent a procedure called plasmapheresis, during which blood is drawn from the patient into a machine which separates blood plasma (the liquid portion of blood) from blood cells and then returns the blood cells to the patient mixed with fresh plasma from donors. This process helps to filter out harmful antibodies and abnormal proteins that can be present in people with autoimmune or blood disorders.

Over the following days, the girl gradually regained her ability to feel, walk and control her bladder. However, repeat MRI scans showed worsening inflammation, which didn't seem to match the girl's improving condition.

The diagnosis: Throughout her hospital stay, the medical team suspected a diagnosis of transverse myelitis, which is a rare neurological disorder that involves swelling in the spinal cord. However, as infectious and autoimmune causes became increasingly unlikely, the physicians changed their minds.

They instead concluded that the girl had experienced a spinal cord infarction, or essentially a stroke affecting the spinal cord. This blood-flow blockage was most likely caused by an exceptionally rare condition called fibrocartilaginous embolism (FCE).

In FCE, a small piece of jelly-like material from the soft center of an intervertebral disk breaks off, enters the bloodstream and blocks one of the arteries supplying the spinal cord. The resulting loss of blood flow can cause sudden paralysis, sensory loss and bowel and bladder dysfunction.

It's unknown exactly how many people experience FCE, as it's difficult to diagnose and frequently underreported. One literature review found only 30 suspected cases and 41 confirmed cases of FCE that had been documented in the U.S.

The case study notes that FCE is most common in children and young adults ages 10 to 20, and that rate also jumps up later in adulthood, around ages 40 to 60. It is slightly more common among female patients than male. While slightly younger than the most commonly affected demographic, the 8-year-old patient in this case otherwise fit this description.

FCE is difficult to diagnose because there is no definitive laboratory or imaging test for it. Instead, physicians must rule out more common causes of spinal cord injury while looking for imaging findings and clinical signs and symptoms that might fit the diagnosis of FCE.

The treatment: There isn't a specific treatment for FCE; instead, care focuses on managing the symptoms caused by the spinal stroke.

The patient was treated with corticosteroids to reduce inflammation, medications to manage pain and plasmapheresis. After a few weeks, and with extensive rehabilitation therapy, the girl regained nearly all of her strength and functional abilities. Her only lingering symptom was weakness in her hands.

What makes the case unique: The case study notes that FCE is often linked to minor trauma to the spine, such as that caused by heavy lifting or other activities that briefly increase pressure inside the spinal disks. In this case, however, the medical team was unable to identify a clear triggering event, and the girl was otherwise healthy and had no reported history of physical trauma. The girl simply woke up with symptoms, which made the diagnosis even more unexpected.

The case also highlights that, although FCE is rare and often carries a poor prognosis — as many patients experience long-term disability and some may even die from complications — meaningful recovery is also possible. The case report authors concluded that, with early recognition and supportive treatment, patients with FCE may achieve improved outcomes and a return to their normal activities.

For more intriguing medical cases, check out our Diagnostic Dilemma archives.

This article is for informational purposes only and is not meant to offer medical advice.

Kakadiya, J., Lakhani, D. A., Gaddamanugu, S., Goncalves, F. G., & Mullen, A. J. (2026). Presumed fibrocartilaginous embolism causing spinal cord infarct in 8-year-old female: A case report. Radiology Case Reports. https://doi.org/10.1016/j.radcr.2026.03.047

Can you guess the diagnosis in these strange medical cases? Find out with our diagnostic dilemma quiz!

One of the central assumptions of modern neuroscience research is that the brain's shape and structure affect behavior. Scientists have linked a thicker cortex (the brain's outer layer) to higher intelligence, certain brain wave patterns to better volleyball ability, and higher connectivity between parts of the brain to chess-playing skills. There's a vast number of these so-called brain-wide association studies (BWAS).

But when experts repeat these studies, they can't replicate the results.

This "replication crisis" suggests that a substantial amount of brain-behavior imaging research rests on a shaky foundation. There are myriad problems affecting this area of research, said Randy Ellis, a senior scientist at Oracle who wrote about these issues while working as a biomedical informatician at the Icahn School of Medicine at Mount Sinai in New York.

Some of these issues aren't unique to neuroscience. They begin with what Ellis called the "original sin" of science: Academics are put under huge pressure to publish positive research findings.

But some of these factors do apply specifically to this field.

The problems are big enough that they are "halting the growth and development of science and the curing of diseases," Ellis told Live Science.

Tiny differences, small samples

Several brain studies that could not be reproduced in follow-up work show how problems can creep in. Each of the original papers has over 500 citations, with the number of citations reflecting how much these studies may influence thinking in the field.

For example, a landmark study in 2007 found that the brains of kids with attention-deficit/hyperactivity disorder took longer to mature. But a study published earlier this year found that this link vanished once the different rates of aging between boys and girls were taken into account. "That's what made the whole house of cards topple," Matthew Albaugh, co-author of the replication paper and a clinical neuroscientist at the University of Vermont, previously told Live Science.

In 2011, researchers at University College London published a study that found that the density of gray matter, the part of the brain where brain cell bodies are found, in several brain areas was linked to participants' number of Facebook friends. (In 2011, this was a vital social metric.)

A 2015 paper failed to replicate this finding, but the authors of the original paper argued that was because the follow-up study didn't follow the same protocol.

"It's hard to do exactly what was done in the original studies," said Sarah Genon, a neuroscientist at the Research Center Jülich in Germany who was not involved in either the Facebook study or its replication.

So, in 2019, Genon and her colleagues tried a different type of replication analysis.

They used a vast database and conducted more than 10,000 analyses of MRI scans from hundreds of volunteers. The median neuroimaging study sample size was around 25, so they divided this larger dataset into smaller ones and then looked for significant associations within each.

If one of these micro-studies reported a significant association between a behavior and a brain structure, the team tried to reach the same findings using a different subset of the data. Very few of the repeat studies replicated the results of the first. "It was clear evidence that the replicability of those brain-behavior associations is relatively weak," Genon said.

One of the key problems is that in healthy volunteers, variation among individual brains is relatively small, which means you need a large number of participants to detect average differences that tie to behavior, Genon said. That's similar to genome-wide association studies, which pick up the very tiny effects of individual genes, and they must sample tens or hundreds of thousands of people to find robust effects. To detect meaningful differences in brain-wide imaging studies, only sample sizes in the thousands would do the trick, a 2022 paper suggested. Because brain scans are expensive and time-consuming to capture, most studies have relied on much smaller samples.

Additionally, the behavioral tests used to establish psychological variables can be inconsistent, Genon said. What's more, some of these studies may be operating on the outdated assumption that small brain regions control complex characteristics like intelligence, she added. In reality, however, "those types of abilities are usually relatively distributed across the brain," she said. When researchers analyze multiple small brain areas with that assumption in mind using separate statistical tests, it can raise the risk of producing mirage associations.

Some of these studies may be flawed at the outset. A 2017 brain imaging study by researchers at Weill Cornell Medical College explored whether MRI data could be used to stratify patients with depression. The researchers found that brain activity clustered into four "biotypes" of depression, each of which featured distinct, unusual activity patterns in key brain networks.

But a follow-up study found that the differences among the clusters weren't statistically significant, meaning they could have occurred by chance. Richard Dinga, a neuroscientist at the Friedrich Schiller University Jena in Germany who worked on the follow-up study, said the main problems lay in its design.

Its statistical approach, he said, essentially guaranteed that significant links would be detected. That's because of a problem called overfitting, in which a model is so well tuned to one set of data that it struggles to find real patterns in other datasets. This design correlated 17 clinical features of depression with 30,000 brain imaging features, but Dinga said the authors could have used "30,000 coin flips" and still produced the same strong correlation.

Conor Liston, a psychiatrist at Weill Cornell Medicine and co-author of the original paper, acknowledged the model's susceptibility to overfitting. "That was not at all our intention, but that was the result," Liston told Live Science

Still, he argued that the biotype finding they identified was real, pointing to later studies his team had published to back up their original finding. When asked why his team hadn't updated the original paper to acknowledge that their analysis method had serious flaws, Liston said their subsequent publications were sufficient to correct the record. "I think the message is out there, and I think the solutions to those overfitting issues are very clear," he said.

Solving the problem

The results of many studies that share the same issues as these papers will never be replicated and yet will be left to stand. For one thing, there's no money in replication efforts. "Grant agencies wouldn't be really excited" to fund a study whose goal was to confirm past work, Genon said. And even when these studies get done, they aren't as likely to get published when they undermine prior findings.

For Dinga, the way forward is to collect more data. "That's what solved the same irreproducibility problem in genetics," he said, referring to genome-wide association studies that have produced important findings over the past two decades by using sample sizes that have reached the millions. But it's also important to improve study design, he added, since bigger datasets won't fix studies with incorrect analysis approaches. "The methods just don't have a chance to produce something useful," he said.

Some researchers are leveraging large brain imaging datasets. Martin Hebart, a group leader at the Max Planck Institute for Human Cognitive and Brain Sciences in Germany, and Luca Kämmer, a doctoral student in Hebart's lab, are developing re:vision, a project that is collecting imaging data ‪—‬ the largest initiative yet to capture how the brain responds to visual stimuli. They plan to make this information available to other researchers, who will then explore whether hypotheses tested in other papers can be replicated in re:vision's dataset.

Hebart and Kämmer said they have already received over a dozen applications for their project. Reception has been particularly positive among younger researchers in the field. But convincing senior scientists to retest their data might take more work because they have more to lose if their long-standing finding is ultimately not replicated, Kämmer said.

"Everybody always says that replication is great," he told Live Science. "But then when I suggest that their specific studies could be replicated, often they are a bit more skeptical."

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Science word of the day: Neuroplasticity

Pronunciation: Nur-roh-pla-STISS'-ih-tee

What it means: Neuroplasticity is the ability of the nervous system to adapt to the environment or to injuries by forming new connections and modifying and strengthening existing connections. Neuroplasticity can happen after an injury, such as a stroke or trauma to the brain, but it also occurs during ordinary learning. Just by reading this definition, you may be making new, sustainable brain connections.

How to use it in a sentence: Scientists used to think neuroplasticity was an ability only the the young had, but researchers are increasingly learning that aging brains can adapt throughout the lifespan, much to everyone's relief.

Can you crack our science word of the day puzzle, Chain Word?

The brain's memory center may come "prewired," rather than being built from scratch after birth, a new study in mice finds.

The research, published in April in the journal Nature Communications, offers a new perspective on a long-standing question in neuroscience: Does the brain begin as a blank slate and build memories by adding connections through experience, or does it come with built-in wiring? The new research focused on the hippocampus, a seahorse-shaped structure deep in the brain that's essential for forming memories.

Rather than supporting either theory directly, the research points to the latter idea but adds a significant twist.

The researchers focused on a region of the hippocampus called cornu ammonis 3 (CA3), which plays a central role in storing and recalling memories. A trait known as plasticity enables neurons within CA3 to continuously strengthen and weaken their connections and thus strengthen or weaken different memories.

The team examined mouse brain tissue collected shortly after birth, during adolescence or during adulthood. They found that early in life, hippocampal networks are densely wired, with many neurons hyperconnected in a seemingly random pattern. As the brain matures, these haphazard networks become sparser yet more structured as connections are pruned. This pruning begins soon after birth, with significant declines in connectivity by adolescence.

The finding discounts the idea that the hippocampus starts out as a blank slate, or "tabula rasa."

"We find, in a nutshell, that the system is not a tabula rasa, as we thought originally, where you can just write information and then at some point, this information fills the system," said study co-author Peter Jonas, a neuroscientist at the Institute of Science and Technology Austria. "Rather, it starts out as a tabula plena [full slate] and then becomes more sparser and specifically connected."​​

This pattern may help to explain why we remember so little from infancy.

Memories are thought to be stored within networks of neurons that fire together, representing specific experiences. In a young brain, however, these connections between neurons, called synapses, behave differently, the study suggests. In young brain tissue, a single input could cause a neuron to fire, the team found, while in mature networks, neurons typically require multiple inputs to fire.

Jonas said the team was surprised by not only the early pruning of connections but also how strong those early connections were. "You might think that early in development, you have poor synapses and weak synapses, but we found the opposite," he told Live Science.

This excitability comes at a cost, however: When neurons are activated too easily, different experiences can trigger overlapping patterns of activity. If that overlap is too great, the brain may struggle to distinguish one memory from another. Instead of forming distinct networks, it may generate broader, less-specific memories. In other words, the system is very active but not very precise.

This imprecision may affect behavior, too. For example, rodent studies show that young animals learn to fear an area of a cage where they received a mild shock, freezing when they return to it. But unlike adults, who freeze at that exact location, young animals also have this response in similar environments — so the memory is there, but it's not precise.

As the brain matures, neurons become more selective and require multiple inputs to fire. The result is more distinct, separate networks that translate to specific and stable memories. So in regard to the inability to recall early childhood, it may be that our earliest memories are too poorly defined to be retained in the long term.

The findings are consistent with a growing body of research on how memory develops, said Hauður Freyja Ólafsdóttir, an assistant professor at the Donders Institute for Brain, Cognition and Behaviour at Radboud University in the Netherlands.

"It's exciting on multiple fronts," Ólafsdóttir, who was not involved in the study, told Live Science. "There is plenty of developmental psychology work that suggests that memory becomes more specific with age. And so it's kind of interesting that now, at the circuit level, we're also seeing that the connectivity patterns are becoming sparser."

So what drives brain wiring before birth? That dense, early connectivity may result from a genetically programmed developmental process. Then, after birth, experience refines the wiring, Jonas suggested.

The findings do not rule out the possibility that experiences before birth leave lasting traces in the brain. But Ólafsdóttir thinks those early forms of learning rely on different neural systems than mature hippocampal circuits.

"I'm not disputing that they're there and that they have influence," she said, referencing prenatal experiences. "They leave a trace, let's say, in our brain and probably in our psychology even." But those traces may not resemble the detailed memories formed later in life.

When asked whether the connections that form before birth represent true memories or are just a byproduct of prenatal development, Jonas said, "The latter is more likely."

The "full slate" may give the brain a crucial head start by enabling neurons to quickly link different types of information, such as sights, sounds and smells. If the brain began as a blank slate, neurons might be too sparsely connected to find each other, making early communication difficult, the study authors think.

By starting with an overconnected network, the hippocampus may ensure that the necessary wiring is already in place, Jonas theorized.

This article was first published May 6, 2026.

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Using drugs to induce a hypothermia-like state may slow stroke-related brain damage, according to a new study involving lab animals and human patients.

The study used two existing drugs: the antipsychotic chlorpromazine and the sedative promethazine, called "C+P" when they're used together. This drug combo induced hypothermia and protected brain tissue in mouse and monkey models of stroke.

Additionally, an infusion of C+P was safe in an early trial including 32 human stroke patients, causing no notable side effects. However, no significant improvements in stroke outcomes were reported in a paper describing the results, which was published June 17 in the journal Science Translational Medicine.

More research is needed to determine what benefits C+P treatment may offer stroke patients. But the research sheds new light on the metabolic dynamics believed to be responsible for hypothermia's therapeutic effects, said Dr. Eric Landsness, an assistant professor of neurology at the Washington University School of Medicine in St. Louis who was not involved in the work.

"What's exciting about this study is that it's clear that it's not just the hypothermia, but it's the hypometabolism," said Landsness, who reviewed the paper before it was published.

Brain freeze?

The researchers tested C+P as a therapy for acute ischemic stroke, in which blood flow to the brain is blocked. Ischemic strokes are the most common form of stroke, accounting for over 85% of cases; "acute ischemic stroke" specifically refers to the medical emergency brought about by a sudden loss of blood flow to the brain and corresponding loss of neurologic function.

When blood flow is restored through a therapy called reperfusion treatment, "you can get significant injury from a lot of processes that were set in motion during the ischemia," said Dr. Patrick Lyden, a professor of physiology and neuroscience, neurology, and neurosurgery at the University of Southern California Keck School of Medicine who was not involved in the study.

To protect brain tissue from this double whammy of ischemia and reperfusion injury, some researchers have tried to harness hypothermia, which is "one of the most powerful ways of protecting the brain that we've ever studied in lab animals," Lyden told Live Science. "It's the standard by which all other brain protectants are measured."

In hypothermia, body temperature drops below 95 degrees Fahrenheit (35 degrees Celsius). Under normal circumstances, this can be very dangerous because the cold can slow down the heart and nervous system to the point that the body's cardiac and respiratory systems fail.

But one of the biggest theories for why hypothermia works in a therapeutic context is that it slows down our metabolism, similar to what's seen in animals during hibernation, Lyden said. "Because the metabolism is slowed, the death process in the brain is also slowed down."

Therapeutic hypothermia can protect the human brain following cardiac arrest, and it is also sometimes used to treat newborns with hypoxic ischemic encephalopathy, an injury that blocks blood and oxygen to the brain around the time of birth. However, studies of hypothermia in adult stroke patients have been less successful, Lyden said.

The C+P approach may be a more effective way to slow metabolism in stroke patients, the researchers hypothesized. In previous experiments, C+P reduced neuroinflammation in rodent models of stroke, possibly through changes in metabolic activity independent of hypothermia.

In the new study, the treatment was compared with two other methods of reducing core temperature in mice: a different drug, called adenosine 5'-monophosphate, and surface cooling using cold water and ice packs. While all three approaches induced hypothermia in the mice, only C+P treatment reduced their overall oxygen consumption and energy expenditure, two important indicators of slowed metabolism.

The paper highlights metabolism as more than a mere secondary effect of hypothermia, Landsness said; it's a process worth studying in its own right.

In mice, C+P treatment reduced the burning of sugar by the brain and brown fat, which burns fuel to generate heat. The treatment was also associated with less brain tissue damage and lactate accumulation, which can drive cell death, after stroke. These effects were also observed in rhesus monkeys treated with C+P.

According to the small safety trial with humans, the metabolic effects of C+P appear to extend to people.

The researchers measured lower levels of metabolism-associated proteins in the blood of patients who received the highest dose of the treatment tested. These were also the only patients to experience a significant decrease in body temperature at four hours after treatment, although their temperatures never dipped into true hypothermia. (Temperatures did fall that dramatically in the mice and monkeys.)

In people, C+P infusion did not reduce the degree of brain damage seen 72 hours after treatment, nor did it affect the participants' ability to perform daily activities without assistance after 90 days. Alongside the C+P treatment, the patients had also received standard reperfusion therapies.

The study authors, based at Capital Medical University in Beijing, did not respond to Live Science's request for comment. In their paper, they wrote that future trials could potentially establish the protective value of the C+P treatment in stroke.

In the current study, C+P did not trigger notable side effects in humans, but Lyden worried that the medications may still pose a risk of worrying effects. The two drugs could potentially interact in ways that cause symptoms like muscle spasms, seizures or changes in heart rhythm, for example. For that reason, it may be best to find different drugs that still slow metabolism but don't come with those risks, Lyden suggested.

To find an alternative to the C+P regimen, researchers will need a better sense of how the drugs exert their effects. The new paper "happened to fall upon a drug [combo] that happens to induce hypothermia and hypometabolism, but we don't necessarily know why," Landsness said. His lab is studying the neural circuits involved in hypothermia and hypometabolism, which could reveal new therapeutic targets.

This article is for informational purposes only and is not meant to offer medical advice.

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High estrogen in the brain's memory center may worsen one's resilience against traumatic events, swaying the tendency to develop memory problems or post-traumatic stress in the aftermath, a recent study in mice suggests.

The research, published in April in the journal Neuron, explored the effects of estrogen in the mouse brain. It zoomed in on the hippocampus, a key part of the brain involved in learning and memory. Both male and female mammals produce significant amounts of estrogen in the hippocampus, despite it often being framed as a "female" hormone.

"We're so biased to think of female high estrogen, male low estrogen," said study co-author Elizabeth Heller, an associate professor of pharmacology at the University of Pennsylvania Perelman School of Medicine. But "in this local brain region, where you have local production of estrogen, actually sometimes the males are higher than the females depending on the female's cycling," Heller told Live Science. Estrogen levels in the female hippocampus rise and fall in line with the body-wide hormone cycle, while its levels in the male hippocampus remain fairly steady.

The study suggests that these local estrogen concentrations may influence one's vulnerability to memory problems following major acute stress. Although the research was conducted in mice, the authors think it likely has relevance to humans.

"I think this is highly translatable," study senior author Dr. Tallie Z. Baram, a professor, developmental neuroscientist and child neurologist at the University of California, Irvine, told Live Science.

Estrogen isn't always a memory booster

Traumatic experiences can cause memory disturbances, including difficulty remembering specific personal experiences and having fearful reactions to formerly safe, familiar situations. When these issues persist and are accompanied by intrusive memories of the traumatic event, they are classified as post-traumatic stress disorder (PTSD).

About 10% to 12% of women experience PTSD in their lifetime, compared with 5% to 6% of men. Some of that difference may stem from variance in men's and women's lived experiences; for instance, women have higher rates of sexual assault at young ages than men do. Biological differences between women and men are another potential factor, but their contribution to the phenomenon is poorly understood.

The new study highlights hippocampal estrogen as one difference that might matter. "The research has uncovered important new avenues for research on PTSD," Victoria Luine, a professor emerita of psychology at Hunter College in New York City who wasn't involved in the work, told Live Science in an email.

In the study, researchers simulated acute traumatic events by exposing lab mice to multiple stressors at the same time, including bright lights, loud music and the odors of other stressed-out mice. They ran the mice through various memory tests before and after the stressful experience and compared these rodents with a group that did not experience such stressors.

Compared with unstressed mice, the stressed-out male mice performed worse on the various memory tests, and those deficits persisted for weeks. "Even a month later, they had a memory deficit — so it's a really perseverative effect," Heller said.

A similar pattern was seen in female mice that were stressed out during proestrus, the phase of their hormone cycle when estrogen peaks and the body prepares for ovulation. Both sets of mice learned to associate certain cues with the stressful experience and avoid them, with females being more sensitive to those cues than males were.

But interestingly, female mice that were stressed during estrus, when estrogen plummets and ovulation occurs, showed resilience. Their behavior and memory remained comparable to those of unstressed mice. "The female mice that had low levels of estrogen laughed it off — they were completely protected," Baram said.

Studies suggest hippocampal estrogen levels are similar in male and proestrus female mice, while estrus females have lower levels. The researchers confirmed this using a technique called mass spectrometry, finding that estrus mice had half the amount of hippocampal estrogen that the males and proestrus females did.

In this context, that lack of estrogen in the hippocampus appeared to guard against the negative effects of stress. This finding was surprising, Baram noted, because estrogen is generally thought to promote memory function in both sexes and declines in estrogen, as seen during menopause, are tied to memory problems. That said, menopause takes place over a much longer timeline than the female mouse hormone cycle, which takes only four or five days.

A connection to DNA

Why do estrogen levels matter for memory? "Estrogen receptors directly control gene expression," Heller said. By binding to its receptors, estrogen turns the activity of certain genes up or down.

Heller's lab studies mechanisms that control gene activity in the context of psychiatric disorders. One of those mechanisms is chromatin remodeling, meaning changes in how DNA is packaged in a cell that can shift which genes can be activated at a given time. A portion of the chromatin can be "open," exposing genes to machinery that turns them on, or "closed," which typically shuts genes down.

It turns out that the high hippocampal estrogen in male mice and proestrus female mice opens up their chromatin in a way that might leave them vulnerable to memory issues ushered by severe stress. Female mice in estrus, by contrast, have a totally distinct chromatin profile that appears to be protective.

"We can see that the function of many of those [open] genes relates to synapse biology," Heller said. Synapses are the points at which different neurons meet and exchange electrical signals, and they're central to the physical structure of memories in the brain.

It may be that, in most circumstances, it's useful to have high levels of hippocampal estrogen because they "open" the chromatin, enabling the hippocampus to forge new memories quickly in response to new experiences, Baram noted. But when these experiences consist of severe acute stress, "that same plasticity, that same ability of the brain to learn, turns problematic," she said. If the results carry over to humans, women may be particularly vulnerable to these memory impacts in certain phases of their menstrual cycles or points in their lifespans when estrogen is high.

In males and females, different flavors of estrogen receptor were responsible for the stress-induced memory issues. The reasons for this difference will be a matter of future study, Baram said. Additionally, future research could attempt to pinpoint exactly where the different estrogen receptors are located throughout the hippocampus, Heller said.

The study provides a "strong demonstration that estrogens drive sex-dependent, stress-induced changes in chromatin networks which can dramatically alter neural functions like memory," Luine said. What's more, "these results present cogent evidence that sex is a powerful biological variable."

Historically, female lab animals were excluded from studies because it was thought that their hormone cycles were too complex and would muck up the findings. The field of neuroscience exemplified this trend. In recent years, the U.S. National Institutes of Health (NIH) has required that scientists take sex differences into account when designing NIH-funded human and animal studies, but progress has been slow on both fronts — and current federal leadership has signaled a lack of support for the initiative.

It's important to include both sexes in research to truly understand how the brain functions and responds to external factors, like stress, Luine said. "An important aim of this and other studies is to protect humans against PTSD," she added, and this study strongly suggests preventive treatments for PTSD might need to be tailored by sex.

Beyond PTSD, Baram thinks the research could have implications for women's risk of aging-related memory problems and dementia.

The decline of estrogen in menopause is thought to raise this risk, but prior to menopause comes perimenopause — a period with massive spikes in estrogen. The study's findings hint that if stress shows up during perimenopause, the combination of stress and high estrogen levels may contribute to memory problems. Thus, perimenopause may represent another time when women are particularly vulnerable to memory disturbances, Baram suggested.

"We need to start thinking a little bit differently," she said. "What is it about women at that stage in life that makes them more vulnerable to memory loss with aging?"

This article is for informational purposes only and is not meant to offer medical advice.

This article was first published May 4, 2026.

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To our human eyes, a mouse's furred face doesn't betray much emotion. But if you watch the body language of a mouse who's reunited with one of her sisters after five days in a cage alone, you might suspect you know what she’s feeling.

The formerly isolated mouse chatters in squeaks too high for a human to hear. She follows her sister, crawling beneath the other mouse's body as if trying to get a hug. She looks like she's feeling what you or I feel when meeting a long-lost friend or a family member — maybe with more sniffing.

She looks like she's been lonely.

Loneliness isn't just for humans, and neither are its harms. Over the past decade or so, some researchers have come to believe that an animal's craving for the company of others isn't just a preference, but a basic, deeply held need. When we don't socialize enough, we feel the lack like hunger or thirst, they say. When we've had our fill of togetherness, we feel satisfied or quenched.

The amount of socializing a creature needs may be particular to that species, and even to that individual. Scientists have found within-species social differences in birds, monkeys, fish and even cockroaches.

Among humans, "you can feel lonely at a party, or you can feel fine alone in your office," says Kay Tye, a neuroscientist at the Salk Institute for Biological Studies in California. Whatever the ideal degree of togetherness, Tye and others think that an animal’s need to balance time alone and time with others represents a kind of homeostasis: an equilibrium that's critical for survival. Today, they are on a hunt to find where, in the brain, this equilibrium is controlled — and hoping their work will hold dividends for lonely humans.

A range of socializing

Beavers live with their immediate families. Starlings flock in huge murmurations. Adult male orangutans roam solo until it’s time to find a mate. What determines an animal's ideal amount of socializing?

Tim Clutton-Brock, an evolutionary biologist retired from the University of Cambridge, says several factors can push species to become more or less social as they evolve. One is the need to keep warm. Another is foraging: Does searching for food in a group make it easier for that animal to eat, or harder? What about predation — is there safety in numbers, or is it better to be alone and inconspicuous? Do females need help from others to raise their young?

"Dealing with the neighbors" is also important, Clutton-Brock says. For example, the meerkats he studies in the Kalahari Desert live in territorial groups, and constant conflict means it’s better to live in packs. A wild meerkat who's separated from the group is visibly distressed and looks around constantly. "They very clearly get extremely worried," he says.

Within each species, Clutton-Brock says evolution has probably allowed for a range of personality types around a certain species average. "There are costs to too much anxiety" about being alone, he says, "and costs to too little anxiety." A species may do best with a mix of social styles.

Whatever an animal's right amount of social activity, research suggests there can be dire consequences to mental and physical health when it's not met. People who are socially isolated, or feel lonely, die sooner. Poor social connections are linked to heart disease and stroke. Certain female rats, when housed alone, are more likely to develop cancer.

Tye started investigating loneliness well before the pandemic brought the subject to the forefront. In 2016, she showed that certain neurons in the brainstem — the deepest, oldest part of the brain — are active in male mice who are isolated for a day and then meet another mouse. When scientists inhibited those neurons, the formerly isolated mice were more standoffish; when scientists activated the neurons, the mice were more eager to seek out company.

The researchers realized they might be getting a glimpse, Tye says, of "the cellular substrate of loneliness."

In 2019, Tye and coauthor Gillian Matthews proposed that those brainstem neurons are part of a system of social homeostasis. Like a thermostat, they theorized, a mouse's brain senses how much company the animal has been getting, and measures that against an ideal. This ideal can also be called a set point. In the human body, for instance, the set point for temperature is around 37 degrees Celsius (98.6 degrees Fahrenheit); when we deviate from that we'll shiver or sweat. Likewise, the researchers suggested, the mouse's brain drives its behaviors to maintain the right balance of social activity.

The scientists hypothesized that other animals, including humans, share this system. Though it's not easy to test such a thing in people, Tye did team up with a research group at the Massachusetts Institute of Technology for an experiment in which people sat alone in a room for 10 hours.

Afterward, subjects reported craving social interaction. When they viewed pictures of people laughing together, their brains lit up in the same region as the brains of fasting subjects who viewed pictures of food: an area, also within the brainstem, packed with dopamine neurons that are involved in cravings.

For more evidence that this craving is part of a true homeostatic system, Catherine Dulac, a neuroscientist at Harvard University and the Howard Hughes Medical Institute, looked in another part of the brain: the hypothalamus, a deep region just above the brainstem that houses control centers for hunger, thirst and our need for sleep. It calibrates each of these basic needs using a kind of neural thermostat — or, as Dulac likes to call it, a "bean counter."

In the case of hunger, for example, scientists have found one set of neurons within the hypothalamus that drives appetite and tells an animal to eat. A separate set of neurons drives fullness — what biologists call satiety — and tells the animal to stop eating. Dulac guessed that she'd find a similar system in the hypothalamus for loneliness, comprising two sets of neurons: "one that encodes the need" for company, she says, "and one that encodes the satiety."

In a study published in 2025, she and her colleagues isolated adult female mice for five days. On days one, three and five, each isolated mouse got to have a 10-minute visit with her sister. Peering inside the heads of the mice undergoing these separations and reunions, the researchers saw just what they were looking for: One cluster of neurons in the hypothalamus started firing when animals were isolated, and turned off when they were reunited. A second cluster of neurons did the opposite.

What's more, when scientists used a technical trick called optogenetics to artificially activate the separation neurons every time the animals entered a certain chamber, the mice avoided spending time there. That suggested that these brain cells, when activated, give the mice a bad feeling. "It's unpleasant to be alone, in the same way it has been shown that it's unpleasant to be hungry," says Dulac, who coauthored an overview of social interaction as a fundamental need in the 2026 Annual Review of Neuroscience.

But activating the opposite cells — the reunion neurons — led the mice to spend more time in the chamber. These cells are connected to the brain's dopamine system, which doles out pleasure and rewards.

Aside from making us feel good or bad, Dulac says, the hallmark of a homeostatic system is a "rebound" effect — the greater the deprivation, the more an animal needs to make up for it. When we're parched, we drink more. And the researchers saw the same thing in their mice: The longer a mouse had been isolated, the more time she spent following, sniffing and squeaking to the other one.

Dulac says that her findings in the hypothalamus and Tye's in the brainstem probably represent different components of the same system. Other studies have found neurons in still more parts of the brain that may be involved.

Like our appetite for food, the mechanism for social homeostasis may be distributed through many parts of the brain, Tye says. After all, our brain needs to detect the amount of socializing we're getting, compare it to an ideal, and then drive our behavior so we get more or less company.

The scientists also believe that the circuitry that senses and manages loneliness is likely to be similar in the human and rodent brains. Unlike our more recently evolved cortex, our deep brain regions look much the same as what's inside a mouse's head. A lonely human may be feeling the effects of wiring laid down long ago in our evolution.

The importance of touch

After studying female mice, Dulac has now turned to studying male mice, who have competing social motivators because they're territorial toward other males.

Tye, for her part, has begun to look at females after studying males. So far, she's observed that they get more and more social over time — unlike the males, which become antisocial after two weeks in isolation and don't seem happy when reunited with other mice. "It's like avoidant, territorial, get-off-my-lawn vibes instead of wonderful-to-see-you-again vibes," Tye says. The scientists don't yet understand this fundamental sex difference.

Intriguingly, researchers have also observed an antisocial effect in human prisoners subjected to long-term solitary confinement. In addition to other psychological harms, prisoners may stop craving social contact, and start to fear it.

Besides attempting to understand the differences between chronic and short-term isolation, researchers are also trying to learn how creatures use their senses to gauge how much company they have.

In Dulac's experiments, vision didn't seem to be necessary: Blind mice reacted to separation similarly to sighted mice. Nor did scent or sounds hold the answer: When mice were physically separated by a perforated divider within the same cage — so they could still hear and smell their companions — they reacted as if they’d been fully isolated.

The only sense that seemed to matter was touch: The brush of another mouse's body told mice they had a friend nearby.

When the researchers lined a tube with soft cloth for mice to walk through, they saw that isolated animals preferred the soft tunnel to a hard one. Like a weighted blanket for humans, perhaps, the touch of the furry walls made the lonely mice feel a little better.

Ishmail Abdus-Saboor, a neurobiologist at Columbia University's Zuckerman Institute who studies touch and was a coauthor on Dulac's study, says the result didn't surprise him. "It is consistent with touch being perhaps one of the most essential sensations for well-being," he says.

Our sense of touch is not just one thing. Bodies have different pathways for processing different sensations, such as pain or itch — or social touches. We humans have specific neurons in the hairy parts of our skin, for example, that are activated by slow stroking. (Mice have related neurons.) And deep pressure, akin to a hug or a massage, activates a similar brain region to stroking touch.

Abdus-Saboor is now working with naked mole rats in his lab. These quirky, colony-living rodents are both the world's most social mammals, and conspicuously cuddly. He hopes studying them will provide more answers about the connection between touch and sociality. He even thinks they might be better models than mice for social touch in humans, because their nearly hairless skin is more similar to ours than a mouse's.

These social touch neurons may carry signals from an animal's skin to its brain that tell its bean counter it's not alone, making the animal feel better. "If we can hijack this pathway, can this be used as a therapeutic to promote health and well-being? I think so," says Abdus-Saboor, who wrote an overview of social touch research in the 2026 Annual Review of Neuroscience.

Even before scientists use this research to develop new treatments, Dulac says it highlights the danger of solitary confinement in prisons. "When individuals are left alone, their brain is just sending this danger signal: 'You should not stay alone,'" she says.

Tye imagines that if scientists better understood the brain's social bean counter, they could one day find a way to lessen the health effects of isolation. For now, she and coauthors suggest that spending time in a variety of social settings is the best way to buffer yourself against discomfort.

Before Covid, Tye recalls, she was always with other people. Then, "during the pandemic, I was alone a lot. And it was really stressful for me," she says. She thinks that giving ourselves regular alone time, as well as time in small and large groups, can make us more tolerant of changes.

Because we're not rodents, we might be able to get our social needs met — at least partially — in ways that they can't. We can connect with a loved one through a call or text. Still, Tye says, touch seems to be especially vital.

Abdus-Saboor, who is married with two children, says he's "very intentional" about touching his family: a supportive tap, a back rub. His kids are old enough to walk to school on their own, but he makes sure to check in before they go.

"It's like, 'Let me get that hug before you leave,'" he says.

This article originally appeared in Knowable Magazine, a nonprofit publication dedicated to making scientific knowledge accessible to all. Sign up for Knowable Magazine's newsletter.

Heading a soccer ball just once is enough to temporarily release proteins into the blood that are associated with damage to brain cells, a new study suggests.

For two of the six proteins tracked, their levels rose higher the more frequently and the harder soccer players headed balls. The study authors say that while this could be evidence of acute brain injuries, further studies are needed to determine whether the cumulative effects of heading could increase a player's risk of developing a neurodegenerative disease like Alzheimer's.

In the research, published May 18 in the journal JAMA Neurology, researchers at Amsterdam University Medical Center found that amateur soccer players who headed balls had higher concentrations of the protein S100B in their blood right after a match compared with players who didn't perform headers. S100B, which is produced primarily by star-shaped cells called astrocytes, is widely used to assess for traumatic brain injury (TBI) and usually increases within one hour following a TBI.

Players who performed more than two headers, as well as those who struck multiple high-impact headers, also immediately experienced increases in a protein called p-tau217. This protein is one of the main blood-based signatures, or biomarkers, for Alzheimer's disease.

Tau is a protein that normally helps stabilize the internal scaffolding of neurons, but mechanical stress on the brain's transmission cables detaches it as enzymes then modify the protein, turning it into one of several forms of p-tau, including p-tau217.

Levels of p-tau217 and S100B returned to their original levels within 24 to 48 hours after each match, but the study authors said this does not exclude lasting harm.

"The evidence we have so far suggests that brain damage is occurring from heading soccer balls, both short and long-term," said Samantha Bureau, assistant executive director of the Concussion Legacy Foundation Canada (CLFC), who wasn't involved in the new study. "Long-term consequences are more difficult to track due to the latency between exposure and symptom onset, but several studies have raised concerns about the risks associated with heading in soccer," she told Live Science in an email.

This latest study in the Netherlands incorporated blood samples from 302 higher-level amateur male soccer players taken over the course of 11 matches ‪—‬ before, immediately after, and between 24 and 48 hours after each match. While 86 participants opted not to participate in the third blood draw, study co-author Marsh Königs, an assistant professor of developmental neuroscience at Emma Children's Hospital at Amsterdam UMC, told Live Science that this is unlikely to have affected the results. The study also relied on cameras to record how often each player headed the ball and to estimate the intensity of each header.

Königs said they don't know exactly how headers caused the two biomarkers to rise. However, there are a few potential explanations. The head's acceleration and deceleration within a short time frame could cause a "concussion-like" effect on a much smaller scale, Königs said. Another study, published in April, showed that when someone's head makes contact with a ball, a pressure wave travels through their head.

Regardless of the precise mechanism, scientists hypothesize that the effects of heading accumulate over time, contributing to neurodegenerative disease. A 2025 study found that years of repeated head trauma in soccer and football players kills neurons and leads to brain inflammation.

"It's not the rise in biomarkers itself but rather what it reflects, which is concerning," Königs said. What's more, Königs thinks repeating the team's study among the world's best soccer players would lead to more pronounced results.

Peter Theobald, a medical engineer leading research on brain biomechanics at Cardiff University who was not involved in the study, told Live Science in an email that soccer governing bodies, such as England's Football Association, are reducing the permitted practice loads for headers, despite a lack of meaningful evidence that prescribes a "safe"' level of heading. It is challenging to say whether the biomarker concentrations measured in the Dutch study were enough to cause concern, he added.

According to Königs, the elevations they observed do not exceed thresholds used in clinical settings to diagnose injuries. However, "these cutoffs are mostly designed to detect much more serious injuries, such as severe brain injuries or dementia," he noted. Königs is concerned that issues could arise if this action is repeated hundreds or thousands of times.

"This is a relatively strong study, as it also features athletes from non-contact sports and so does provide confidence that heading is the cause of change," Theobald said. "Tracking the same players throughout a season would have been interesting for example, as this would have enabled reporting of the cumulative effect of heading."

This article is for informational purposes only and is not meant to offer medical advice.

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The wind picks up dust from the unpaved road one afternoon in December as Jack van Honk turns into a ramshackle neighborhood in Lambert's Bay, on the west coast of South Africa. A stocky woman in a red patterned sundress steps out of a small home painted palest sea green, her ochre-dirt yard crowded with potted plants, many medicinal. She smiles broadly, deep wrinkles creasing a face that is cherubic and yet careworn beyond her 47 years. "Doctor! I missed you," she beams, her husky voice barely more than a hoarse whisper.

Maria carries a rare genetic mutation that is almost unknown outside of southern Africa. Its effects have been to calcify a part of the brain called the basolateral amygdala, and to thicken and scar the vocal cords. A friend of Maria with the same condition lives several hours inland, and sometimes they meet when van Honk brings them to Cape Town for brain scans and other tests. "It helps to know I'm not alone," Maria says.

By every measure of daily life — holding down a job, keeping a household running, raising two teenage sons — Maria is competent and engaged. "You talk to her, and you don't see anything wrong," says van Honk, a social neuroscientist at the University of Cape Town. She and others he knows with her condition, Urbach-Wiethe disease, "are kind, sweet people by nature." In an interview in her kitchen, Maria struggles to recollect even a fleeting moment of unhappiness — before mentioning that she kicked out her partner some years ago because of his drinking.

Yet on tests and questionnaires designed to shed light on moral choices, Maria and others with Urbach-Wiethe fail in perplexing ways that challenge one of neuroscience's most durable assumptions.

Fear factors

The amygdala, a brain region the size and shape of an almond, has long been described — almost mythologized — as the brain's fear center. That view emerged from early rodent experiments showing its role in defensive reactions. "There were a lot of discoveries linking the amygdala to fear conditioning," says Steve Chang, a neuroscientist at Yale University who studies social cognition and decision-making in monkeys. In such studies, mice and rats learn to associate a neutral cue — such as a tone — with a mild foot shock. Soon the sound alone makes them freeze in anticipation, a learned fear response that disappears after the amygdala is damaged.

But in recent years, studies in animals and humans have painted a more complex picture. Rather than a simple switch for fear, the amygdala is now understood as a Grand Central Station in the brain: a network of specialized nuclei that help detect what we care about so that we can make decisions, says Elizabeth Phelps, a psychologist at Harvard University who studies how emotions affect cognition. The rare cases of Urbach-Wiethe disease in South Africa offer a unique window into that circuitry. Because the condition appears to damage the basolateral amygdala while sparing other regions of the structure, it has helped to clarify how different amygdala neural circuits interact with each other and with other brain regions — not only in fear-learning, but in social judgment and decision-making.

Van Honk "is doing a really good job at linking his research to animal work to come up with a bigger theory," says Phelps, who is not affiliated with the project. The emerging picture is intriguing, she says, though not yet entirely convincing to her: Van Honk and his colleagues now posit that the basolateral amygdala functions primarily as a kind of social compass, helping to weigh the needs and intentions of others and decide who matters to us.

Earlier research had painted a simpler picture. Scientists in the 1990s unveiled the sensational case of a young woman with Urbach-Wiethe disease whose amygdala had almost entirely calcified, and she fit the prevailing fear-amygdala model. Unstintingly cheerful like Maria, S.M. (identified only by her initials) could not recognize fear in the facial expressions of others, neuroscientist Antonio Damasio and colleagues reported in Nature in 1994.

As the scientists got to know S.M., she confided repeatedly how she hated snakes and spiders and would try to avoid them. But when they took her one day to an exotic pet store, she gleefully held and stroked a snake for three minutes — remarking, "This is so cool!" — and had to be deterred from touching larger, more dangerous snakes. She was unflappable in a haunted house and unfazed by horror films. Damasio's team concluded that S.M. exhibited "a profound and pervasive impairment in the induction and experience of fear."

Like many in his field, van Honk, a young researcher at the time at Utrecht University in the Netherlands, was gripped by S.M.'s story. "She has to be the world's most famous living neurological patient," he says. Then in 2003, on van Honk's first visit to South Africa, clinical psychologist Helena Thornton of the University of Cape Town bent his ear about her efforts to track down people with Urbach-Wiethe in South Africa. She realized that the country offered something neuroscientists almost never encounter: not just one famous patient, but an entire cluster of people living with a rare neurological disorder.

Also known as lipoid proteinosis, Urbach-Wiethe disease was first described scientifically in 1929 by the Austrian medical researchers Erich Urbach and Camillo Wiethe. Medical sleuthing later traced back the disorder's presence in South Africa to a brother and sister, Jacob and Else Cloete, who had immigrated from Cologne, Germany, in the mid-1600s. The pair had married into a colony of Dutch settlers. Around the turn of the 19th century, a Cloete descendant transferred a gene for the trait into the mixed-race population of Namaqualand, the arid highlands in the Northern Cape, near the border with Namibia.

Urbach-Wiethe is recessive, which means that people must inherit copies of the defective gene from both parents to develop the condition. It has been associated with at least three dozen different mutations, all of them in a gene that carries instructions for a protein called ECM1, which is integral to the skin's connective tissue. Those with the mutation tend to have papery, inflamed skin and vocal cord lesions. They can have different patterns of calcification in brain regions, primarily in the amygdala, and in severe cases can suffer epilepsy, paranoia or other psychiatric symptoms.

Thornton and her colleagues found 34 Urbach-Wiethe individuals, most of them scattered across the rocky deserts of Namaqualand. Numbers had dwindled since the days of the Dutch colony — "a small community that suffered from inbreeding," van Honk says. Without close-kin marriages to sustain it, the condition was dying out. But with just 100-odd known cases globally, Namaqualand still had the most in the world.

The implications were extraordinary: a rare chance to study how selective damage to the amygdala shapes behavior. In 2005, the University of Cape Town organized another research trip to Namaqualand. Van Honk climbed aboard, and later recruited Utrecht social neuroscientist David Terburg, then a student. "We went into this research with the basic idea that the amygdala is the fear center, and we'd find fearless people, like S.M.," Terburg says. "But we got totally opposite results." Although individuals with Urbach-Wiethe disease in the Northern Cape appeared calm and good-natured, behavioral testing showed heightened fear responses and high rates of anxiety.

How could that be, the scientists wondered, if the brain region thought to govern fear had been compromised? At first, the revelations appeared to undercut the iconic case of S.M. and were coolly received by peers. "We spent five years to get those initial findings published," Terburg says. One clue to the apparent contradiction was that individuals in Namaqualand had a unique Cloete mutation not seen on other continents. Another clue came in 2007, after a powerful 3 Tesla MRI machine came to Stellenbosch University near Cape Town. "We were the first to use it," says van Honk. That's when the team discovered that the damage was concentrated in the basolateral amygdala. "Nothing like that had been seen before," van Honk says — in people, that is. Researchers had induced selective lesions to this and other parts of the amygdala in rats.

Rats are social creatures, and studies on these lesioned animals revealed that the basolateral amygdala helps them weigh outcomes and consequences; the central-medial amygdala, meanwhile, is more closely tied to fast, defensive reactions, such as freezing or fleeing from danger. It dawned on van Honk that the South Africans with Urbach-Wiethe disease were a kind of Rosetta Stone for seeing if what held for rats held for humans. Perhaps, he thought, different amygdala circuits might push human behavior in opposite directions, too.

Personal stakes

The brain had long fascinated van Honk, in part because of his own history. As a young adult, after his older brother died in a motorcycle accident, he struggled with mental health crises. The experience shaped how he related to the Urbach-Wiethe patients he later met — people whose raspy voices and visible skin changes often set them apart in their communities — and deepened his determination to unravel a living neurological mystery.

In 2008, after studying Urbach-Wiethe from afar, van Honk landed a visiting professorship in the University of Cape Town's department of psychiatry and mental health and moved from the Netherlands with his wife and their young children. He winnowed down the study population of people with Urbach-Wiethe, excluding individuals with afflictions such as alcoholism so that the team could be sure the effects they observed were truly due to the mutation. That reduced their pool of subjects to a handful of women, including Maria.

Then, to dive deeper into their behavior and cognition, van Honk and his colleagues turned to tools borrowed from economics and moral philosophy: simple games and thought experiments designed to reveal how people weigh risk, reward and responsibility. Classical economic theory assumes that humans shrewdly tally costs and benefits. Decades of behavioral research suggest otherwise: Decisions are often guided by gut feelings, impulses and social instincts that defy narrow self-interest.

In one widely used experiment known as the trust game, participants are given a sum of money and asked how much to invest with a stranger — with no guarantee of a return on that investment. Most people hedge their bets. The women with Urbach-Wiethe did not. Again and again, they invested generously with unfamiliar partners. With regard to their finances, their choices were reckless. To van Honk and his colleagues, the behavior suggested a diminished ability to flexibly weigh uncertainty, self-interest and the intentions of others — the kind of calibration they believe an intact basolateral amygdala normally helps provide.

A different pattern emerged in moral dilemmas. A classic thought experiment is the "trolley problem," in which a runaway trolley could kill five people, but intervening would mean you actively killed just one. When asked what they would do in variations on this theme, the women with Urbach-Wiethe disease consistently refused to endorse sacrificing a life, even as the numbers of people to be killed — were they not to intervene — grew extreme. "It's very nice to resist sacrificing a person, but if so many people were to die, it's a bit weird," van Honk says. "Something in the computation isn't working." The women understood the consequences but could not bring themselves to intervene. Some of them explained to the researchers that causing harm, even for the greater good, "hurts too much."

Intrigued, psychologist Tobias Kalenscher of the University of Dusseldorf in Germany took a sabbatical in 2023 to work with van Honk in South Africa. Kalenscher's team had earlier found striking behavioral changes in rats with lesions in their basolateral amygdala. Normally, when a rat is presented with two options — getting a treat just for itself, or the exact same treat for itself and for another rat — it often prefers the mutual reward. The rats with brain lesions couldn't care less about other rats, suggesting that the basolateral amygdala helps to assess the social value of a choice.

Social behavior in rats is only a rough proxy for humans. "Generosity is a genuinely human topic that you need to study in humans," Kalenscher says. He and van Honk asked the Urbach-Wiethe women in the Northern Cape to think of real people in their lives — those closest to them and those increasingly distant, all the way out to an anonymous stranger. For each person, the women were to decide how much money they were willing to share. A control group of women without the disease were asked the same questions. Generosity declined with distance in everyone, but among the Urbach-Wiethe women it dropped off far more steeply, the team reported in 2025 in PNAS.

The duo suspected that the women's behavior reflected a difficulty in balancing self-interest with concern for others, rather than a fixed tendency toward generosity or selfishness. So, starting in November 2025, they conducted a variation of the experiment that removed the need to divide resources. They asked Maria and others to squeeze a handheld device called a dynamometer. Pressing harder would generate more money for people at various social distances. In such tests, people without amygdala lesions are consistent: "They press much harder for people they love or feel close to than for strangers," Kalenscher says. The women with Urbach-Wiethe, by contrast, pressed just as hard for strangers as for loved ones — suggesting that they were not adjusting their behavior to social distance.

Across responses to threat, moral judgment and social decision-making, a striking pattern emerges. The women with Urbach-Wiethe are hampered in their ability to adjust their decisions as circumstances change. This suggests that the basolateral amygdala enables us to imagine others' outcomes and weigh them against our own when making decisions. "This is what we do, and I think what the Urbach-Wiethe patients cannot do," Kalenscher says.

In other words, while earlier theories framed the amygdala mainly as a detector of danger — a switch that turns fear on or off — the new evidence points to the brain region's broader role in calibration of behavior. Van Honk and his colleagues propose that the basolateral amygdala integrates emotional signals with possible consequences, allowing us to trade off our own gain against potential harm or benefit to others. The women with Urbach-Wiethe disease show what happens when that calibration system is disrupted: They are less able to reconcile competing considerations when making decisions. "It appears that they can't trade off their own benefit versus the benefit of others," Kalenscher says.

One possible explanation for that breakdown lies in how the basolateral amygdala interacts with the ventromedial prefrontal cortex, a region involved in evaluating reward and guiding decisions. In a healthy brain, the two appear to work together, integrating self-interest with concern for others into a single signal that guides behavior. When the basolateral amygdala is damaged, that communication may break down, leaving decisions to be driven by simpler, intact circuits. The idea remains speculative, Kalenscher says, but it fits with what is known about how these regions interact.

Translating the women's behavior in experiments into everyday life is a challenge. But Kalenscher says he sees clues in Maria. On the visit with her in January, she was caring for two orphaned children, apparently unrelated to her. From his brief window on Maria's day-to-day life, Kalenscher believes her computational deficit may translate into a kind of extreme altruism: a willingness to help others without the usual filtering of context. It makes her someone people can rely on, he says, but also someone who could potentially be taken advantage of. Echoing Maria's heroism is an observation about S.M. reported in 2018: S.M. told researchers how she'd once given her only coat and scarf to a homeless man she'd met under a freeway ramp in the dead of winter.

An enduring riddle

Every visit to the Northern Cape, it seems, brings to light another hidden oddity of Urbach-Wiethe disease. Sitting at Maria's kitchen table in Lambert's Bay, van Honk chats with his research subject as if she is an old friend — and, indeed, they've known each other for more than 15 years. As the visit winds down, he asks her about her sense of smell. "Yes, it's very good," she says, without hesitation. She talks easily about cooking, about knowing when food has gone off. Nothing in her answer suggests impairment.

Later, van Honk shows me unpublished results of a smell test he and colleagues recently ran with Maria and the others with Urbach-Wiethe disease. While their basic odor sensitivity is intact —they can detect smells just fine — the women struggle to identify what those smells are, a pattern that points to what the researchers call olfactory amnesia. "They understand the smell of fish, and coffee. But other smells they can't really differentiate," van Honk says. More striking, the women are unaware of the deficit, a phenomenon known as olfactory anosognosia.

In rodents, the basolateral amygdala plays a key role not in detecting odors but in learning what they mean — linking a smell to memory or consequence. When that region is damaged, animals can still sense odors, but they fail to learn that a particular scent predicts danger or reward. The Urbach-Wiethe data suggest something similar, the scientists say. Smell, one of the most ancient sensory systems, appears to rely on the same circuitry that helps humans learn from experience and revise their internal models of the world.

Despite the obstacles they face because of a steady, irrevocable loss of their basolateral amygdala, the women with Urbach-Wiethe in the Northern Cape cope and adapt, with resilience that impresses van Honk. And as they live out their lives, they gift science with a glimpse of how small changes in the brain can reshape how we fear, whom we trust and how far our concern for others extends.

This article originally appeared in Knowable Magazine, a nonprofit publication dedicated to making scientific knowledge accessible to all. Sign up for Knowable Magazine’' newsletter.

Two decades ago, a landmark study showed that the brains of kids with attention-deficit/hyperactivity disorder (ADHD) take longer to mature. But new research suggests that this result, which was based on brain scans from a few hundred children, was a mirage.

What was thought to be a hallmark of the ADHD brain, the study found, instead reflects average sex differences in how the brains of boys and girls develop over childhood. The earlier dataset, which used a smaller sample size, may have become skewed to more closely reflect the average boy's brain development, the new research suggested.

In 2007, a research project forged a new path in the study of ADHD. A team based at the National Institute of Mental Health showed that children with ADHD, who outwardly struggled with attention and impulsivity, had differences in their brains underlying these behavioral symptoms, compared with children without ADHD.

The team used MRI to look inside the brains of 223 children with ADHD and a similarly sized control group of children without the condition. The study found that the brains of children with ADHD developed differently than the brains of kids without ADHD. Throughout childhood, the thickness of the cortex — the outer layer of the brain — increases and then decreases. The team showed that this process was significantly delayed in kids with ADHD.

At the time, this finding made perfect sense, because it matched well with ADHD behaviors, said Matthew Albaugh, a clinical neuroscientist at the University of Vermont. "You see kids that maybe are acting a little younger than their chronological age," he told Live Science.

The 2008 paper was "foundational" in the field, Albaugh said. The study even showed that kids with ADHD had earlier maturation in the areas of the brain responsible for movement, which was thought to explain their hyperactivity. The work told a commonsense story, researchers thought at the time.

Sex differences undermine brain data

But science is rarely that neat. In their new study, published May 18 in the journal PNAS, Albaugh and his colleagues cast doubt on those earlier findings.

The new work exploited a powerful data source to show that the previously reported delayed maturation is likely a mirage in the data, caused by differences in how boys' and girls' brains develop. When these different patterns are taken into account, there's no difference between ADHD and non-ADHD brain maturation, the study authors wrote.

The team set out to replicate the 2008 paper, using data from the Adolescent Brain Cognitive Development (ABCD) study, a National Institutes of Health-funded project that is tracking over 11,000 9- and 10-year-olds for roughly a decade, said study first author Shannon O'Connor, a research project assistant at the University of Vermont. The study measures various behavioral traits and brain metrics and is the largest imaging study of its kind to follow people over time in the United States, O'Connor told Live Science.

The ABCD study asked parents to report any problems with their child's attention. When the researchers initially examined the relationship between attention problems and cortical thickness, they found the same associations as the original study uncovered nearly 20 years earlier.

But the team wanted to use the rich dataset provided by the ABCD to test what would happen if they accounted for other factors in the children's lives. O'Connor had noticed that, in other studies of the ABCD data, boys tended to show a lower rate of cortical thinning than girls. When the team accounted for these different rates, the associations between attention problems and brain structure disappeared.

"That's what made the whole house of cards topple," Albaugh said. Earlier studies had accounted for the differences between boys and girls at single snapshots, but not over time, he noted. As kids dropped out of these smaller studies, their carefully balanced analyses may have swung to disproportionately reflect boys’ lower rate of cortical thinning.

Digging further into the data, the team split the cohort into just boys and just girls. In both sexes individually, there was no relationship between cortical thickness and attention.

The replication crisis rolls on

Dr. Max Wiznitzer, a pediatric neurologist at Case Western Reserve University who was not involved with the new study, said it was "well designed" and "asked the right questions." The new findings were based on parent-reported attention problems rather than ADHD diagnoses, so Albaugh's team conducted a series of follow-up studies looking at subsets of the patients who were diagnosed clinically, which produced similar results.

The new findings add to the overall replication crisis affecting neuroscience. New, powerful datasets and more precise imaging techniques have undermined, rather than strengthened, notable neuroscience studies that have guided the field. Albaugh said these new datasets suggest that many of these early findings "may have been flukes."

Notably, the influence of sex differences has been largely overlooked in neuroscience, and this research highlights how acknowledging sex as a factor can refine a study's conclusions.

Albaugh was quick to emphasize that the findings don't change the underlying knowledge that ADHD is a biological condition that has a strong genetic component. But it does leave the field lacking reliable biological signatures for the condition, Wiznitzer said.

The study should encourage researchers in the field to seek biological signatures that can be used to guide the diagnosis and treatment of individual patients rather than groups, he added. Cortical thickness was never used in those ways.

"If I put someone on medication and their behavior improves, in a way, it doesn't matter what their cortical thickness is," Wiznitzer said. "Clinically, there's the improvement, which is what you're after."

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At the Alcor facility in Arizona, more than 150 disembodied heads reportedly lie in cryogenic chambers, preserved in hopes that future medical advances can bring these brains back to life in new bodies. Given that scientists still cannot revive a cryogenically preserved brain, why do patients bother with cryonics at all? Why couldn't these heads just be stitched onto new bodies in the present day, when they're still fresh? In other words, why isn't a brain transplant possible?

Dr. Max Krucoff, an assistant professor of neurosurgery at the Medical College of Wisconsin, would rather describe such a procedure as a body transplant. Unlike a patient who receives a donor heart or liver, transplanting a brain into a patient's body would make them "a completely new human being," he told Live Science. "Your agency, your identity, is contained within your brain."

Semantics aside, Krucoff said this transplant is currently impossible because surgeons cannot yet forge signaling connections between nerves in the central nervous system, which includes the brain and spinal cord. Transplanted peripheral nerves, or the nerves that branch off throughout the body beyond the brain and spinal cord, can eventually communicate with their new neighbors, since these nerve cells can regenerate. There is less evidence that the adult human central nervous system can generate fresh neurons, and if it does, it's to a limited degree. Neurons can form new connections throughout a person's lifetime, which is how learning is encoded, but scientists do not understand this pathway well enough to exploit it for a transplant.

Even a partial brain transplant, such as a cerebellum swap, is out of the question for now. In the case of the cerebellum, the structure is home to millions of specialized neurons called Purkinje cells, each of which receives signals from thousands of other neurons. "The number of connections is exponential," Krucoff said. "That's way beyond our capacity."

Fusing brain and body at the spinal cord would be the simplest theoretical brain transplant, since connections between spinal nerves are more straightforward than neurons in the brain. The surgeon performing this head transplant could connect the skin, muscle, vessels and bones in the neck, and even align the nerves of the spinal cord, "but to get those cells to communicate, we just haven't figured out how to do that yet," Krucoff said.

Has a brain transplant ever been attempted?

Scientists began attempting head transplants on animals with the advent of new blood vessel suturing techniques in the early 1900s. Most of the dogs and monkeys involved in those experiments survived a few days at most, as researchers struggled to create a working vascular system or to manage host rejection of the transplanted head with immunosuppressive agents.

Starting in 1970, Dr. Robert J. White transplanted the heads of monkeys onto new host bodies. The animals could chew and swallow food after surgery, and postsurgical electroencephalogram readouts suggested that their brains were awake, though none survived more than nine days.

Inspired by this work, Italian surgeon Dr. Sergio Canavero laid out his vision for the first human head transplant in 2013, attracting widespread pushback from colleagues on ethical and scientific grounds. Canavero's 2017 announcement that he had performed the first head transplant on a human cadaver was described at the time as "the continuation of a despicable fraud" by New York University bioethicist Arthur Caplan, who pointed out the likelihood of immune rejection and the challenge of linking a brain with all-new nervous inputs.

Can any tissue be transplanted into the central nervous system?

Although a surgeon can't switch one brain out for another, stem cell or organoid grafts could one day replenish damaged or diseased brain tissue.

Stem cells programmed to develop into neurons may have better odds of integrating into existing circuitry than mature neurons do, said Ruslan Rust, an assistant professor of research physiology and neuroscience at the University of Southern California Keck School of Medicine.

Ideally, these stem cells could be derived from the patient's own tissue, to lower the odds of immune rejection, but standardized donor cell lines reduce the need for quality control on individual tissue samples. In this way, neurons originating from one person's tissue could populate another person's brain.

Stem cell therapies have been tested in clinical trials for Parkinson's disease, stroke, spinal cord injury and epilepsy, but none of these treatments for these conditions are approved by the U.S. Food and Drug Administration for commercial use.

Rust told Live Science that future research will need to address the potential risks of these techniques, such as incompletely differentiated stem cells forming a tumor after transplant, or cells that do become neurons disrupting signaling pathways.

"The billion dollar question is, how do we make [transplanted cells] the cells that we want them to be, and how do we make sure that they integrate into those local circuitries where we want them to go?" he said.

Stem cells are also used to create lab-grown models of nervous tissues, called organoids, that can be transplanted into the brain. A 2023 study reported that human brain organoids could repair injured rat cortex, though therapies based on organoid transplant are still years away. Rust said such procedures could be more invasive than transplanting individual stem cells, and would need to account for vascular supply to the new tissue.

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Scientists have created a comprehensive map of smell receptors in the mouse nose, revealing a few surprises about this fundamental sense.

Smell receptors, or olfactory receptors, were previously thought to be randomly distributed within the lining of the nasal cavity. But now, the first-of-its-kind map shows that they are highly organized, with different types separated into tight bands.

The study, published Tuesday (April 28) in the journal Cell, provides new clues about how the sense of smell works.

Smells are detected by olfactory sensory neurons in the nasal cavity. Each neuron expresses one of 1,172 different receptors encoded in mouse DNA, with each receptor detecting a different type of smell.

Other senses ‪—‬ such as touch, vision and hearing ‪—‬ are known to use sensory maps. For example, for hearing, different frequencies are encoded at different positions in the cochlea of the inner ear, and from there, that information is relayed to the brain. Smell was not thought to use such mapping, but in the past six or seven years, newer techniques have enabled scientists to examine around 5.5 million neurons in over 300 individual mice and better understand which genes are active in different nose cells.

One of these techniques is called single-cell sequencing, said senior study author Dr. Sandeep Datta, a neurobiologist at Harvard Medical School. It enabled the researchers to look at each mature olfactory sensory neuron "one at a time, to identify which receptor is being expressed," he explained. Then, a technique called spatial transcriptomics helped the researchers locate those receptors.

Using this data, the team created a "beautiful map" of the over 1,100 smell receptors in the mouse nose. The map showed "a thousand separate stripes of odor receptor expression that overlap with each other but are very organized," Datta said.

Neurons that express the same receptor in the nose target the same spot within the olfactory bulb, the brain's primary processing center for smell, the team found. "The map in the nose is precisely aligned with the map in the brain," Datta said.

The degree of complexity within the lining of the nose is remarkable, he added. "Mice, for example, have around 20 million olfactory neurons that express more than a thousand types of smell receptors, compared with only three main types of visual receptors for color vision," he said.

Interestingly, the positions of the roughly 1,100 types of receptors were essentially the same across every lab mouse the researchers examined. The work also identified a molecule called retinoic acid (RA) that likely guides each neuron to express the correct receptor based on the location. Adding or removing RA resulted in the receptor map shifting up or down, suggesting the molecule may help control the position and influence of the neurons.

Alyssa Brewer, a neuroscientist at the University of California, Irvine, said that these findings are very exciting, as they completely overturn the existing idea of how olfactory receptors are organized.

The work "beautifully resolves a long-standing question about the peripheral olfactory system in mice," Brewer, who was not involved in the study, told Live Science in an email. "But it opens up an equally exciting set of questions about what happens next, both upstream in the brain and across species."

Brewer would like to know how well these findings translate to humans, something Datta and his team are already looking into. Datta's team is also interested in understanding why the stripes in mice are arranged in that specific order.

"The human olfactory system is, in many respects, similar to the mouse olfactory system [though we] have fewer odor receptors," Datta noted. "But we don't know much about whether these basic principles we're learning about in the mouse apply to humans." Understanding this could help develop treatments for loss of smell and its consequences, including an increased risk of depression.

Editor's note: This article was updated on April 29, 2026, to add comments from Alyssa Brewer.

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Engineers have printed tiny, artificial neurons that can "talk" to mouse brain cells, and the development could pave the way to innovations in computing and medicine.

The work, published April 15 in the journal Nature Nanotechnology, adds to a growing field that aims to build computers that mimic the inner workings of the brain.

The hope is that better artificial neurons could lead to "neuromorphic computers," a new type of computing that could substantially improve the energy efficiency of artificial intelligence (AI).

"We are trying to mimic the brain as faithfully as possible," said study co-author Mark Hersam, a professor of materials science and engineering at Northwestern University. "What motivates us is to come up with an alternative to conventional digital computing to handle large amounts of data in a more energy-efficient way," he told Live Science.

The work could also usher in new brain-computer interfaces, which enable electronic devices to be controlled with brain activity. Brain-computer interfaces can be used to control prosthetic limbs or assistive communication devices, for example.

Because neuromorphic computers are designed to emulate the brain, they should be well suited to interact with brain tissue. Additionally, some scientists have suggested that artificial neurons could replace damaged nerve cells or restore lost brain function in degenerative diseases such as Alzheimer's.

Bottling the brain in a chip

To recapitulate brain tissue, you can't use traditional silicon chips, which are rigid and built from repeating transistors arranged in two-dimensional structures. They have fixed connections that can't evolve.

That's a far cry from the delicate infrastructure of the brain. Brain cells are physically flexible, vary depending on their location, and communicate in a 3D matrix that changes over time. Connections between neurons can grow stronger if they are used consistently, or they can fade if they are underused. All of these properties are necessary to create the intricate processors that are constantly making sense of the complex world around us.

Because of these discrepancies between the brain and machinery, most brain-computer interfaces fail to slot seamlessly into the brain; instead, they rely on relatively crude pulses to communicate with neurons. Making efficient artificial neurons means finding materials that feel and act like neurons, in that they mimic neural firing patterns and adjust those signals as needed.

Artificial neurons designed prior to the new study tend to use either soft, organic materials, such as gels or tissues that can pass electricity and chemical signals, or hard metal oxides. Each approach has drawbacks: While the soft materials' spiking patterns tend to be too slow, the hard materials' tend to be too fast, Hersam explained.

To better replicate neurons, Hersam and his team used printable inks laced with tiny flakes of molybdenum disulfide, an inorganic compound that acts as a semiconductor, and graphene, an electrical conductor. The inks are printed on a flexible polymer substrate.

Historically, such substrates have been viewed as a hindrance because the polymers interfere with electrical currents. But as Hersam and his colleagues discovered, this can be a boon for artificial neurons, as the team found that the polymers can be manipulated to control how electricity flows through the lab-made brain cell.

"The key innovation was this partial decomposition of the polymer," Hersam said.

By carefully tailoring how the polymer heats up and breaks down, the engineers can create tiny filaments of energy. Rather than increasing steadily, the current running through the neuron increases and then falls back, enabling a sudden release of energy akin to a neuron spiking. That action is called a "snap back negative differential resistance."

And by tuning the parameters of the device, the team was able to generate more complex signaling patterns, including a series of spikes spaced out in time or sudden flurries of spikes. "We can achieve all different types of spiking responses that mimic biology," Hersam said.

To prove this, the scientists placed their artificial neurons next to slices of a mouse's brain in a lab dish. They found that the mouse neurons fired at the same pace as the artificial neurons, suggesting the tissue could decode the artificial signal as if it were born from real tissue.

Artificial neurons of the future

Timothée Levi, a professor of bioelectronics who works on artificial neurons at the University of Bordeaux in France, praised the new type of artificial neuron, noting that it can "fit the normal frequency of neurons," he said.

Levi, who was not involved in the research, said the work adds to a series of recent studies showing that artificial neurons can communicate with biological neurons. These developments have unfolded alongside a slew of advances improving how artificial neurons are built, how they connect with each other, and how they are programmed, Levi said.

He emphasized, however, that artificial neurons are still far from fully communicating with biological neurons in a significant manner. "We can control them for a short time but not yet for a long time," he said, so they're not yet fit to be permanent additions to a human brain, for instance.

There's still a lot of work to be done in understanding how the brain works so it can be faithfully reproduced by a computer, Levi and Hersam noted. Moreover, artificial neurons aren't enough — you need to link them together at artificial synapses.

"The frontier problem," Hersam said, "is that we have a series of devices that mimic different elements of the brain, but we need to integrate them together into circuits that achieve the full functionality."

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On April 18, 1861, a doctor in Paris cut open the brain of a patient who had died the day before — and unwittingly identified a brain region that's key to spoken language.

The patient, Louis Victor Leborgne, was nicknamed "Tan" by doctors at Bicêtre Hospital because it was one of the only words he could say. By the time he died at age 51, he had spent 21 years living in the psychiatric ward of the hospital.

Leborgne was reportedly healthy at birth but began having epileptic seizures in early childhood. At age 30, he lost his ability to speak. For a while, he avoided getting treatment, but he was eventually admitted to Bicêtre Hospital.

Doctors found that he could understand language well and he would use gestures to convey his needs. Rarely, he could utter a swear word.

A decade after he was admitted to the hospital, he began to experience right-sided paralysis that grew steadily worse, as well as mental difficulties. Eventually, he lost the ability to walk. He spent the last seven years of his life in bed.

During these last few years, Dr. Paul Broca, a surgeon at the hospital, began to see Leborgne as a patient.

"The numerical responses were the ones he made best, by opening or closing his fingers. He would indicate, without error, the time on a watch to the second. He knew exactly how many years he had been in Bicêtre, etc," Broca said of his patient, according to a translation.

"However, many questions to which a man of normal intelligence would have found the means to respond by gesture, remained without intelligible response; other times the response was clear, but did not answer the question," Broca observed. "Undoubtedly, then, the intelligence of the patient had been affected to a great degree, but he maintained certainly more of it than was needed for talking."

On April 17, 1861, Leborgne died of gangrene — likely a result of a bedsore in his leg. The next day, Broca began an autopsy and noted a pocket of clear fluid about the size of a "chicken's egg" in the perisylvian region of the brain's left hemisphere; this region surrounds a deep groove called the lateral sulcus, which marks the upper boundary of the temporal lobe. Several areas surrounding the fluid exhibited a "softness." And there were other abnormalities: Leborgne's brain was lighter than normal, and several brain regions had a smaller volume than expected.

That same day, Broca presented his autopsy findings at the Anthropological Society Meeting in Paris. At the time, there was an ongoing debate between scientists who believed all of the brain's functions were diffused throughout the organ's tissues and those who believed certain regions performed specific functions.

Broca's autopsy was strong evidence for the latter idea.

"The principal home and the original seat of the softness is the middle part of the frontal lobe of the left hemisphere; it is there that one finds the most extensive lesions — the most advanced and the oldest," he said in his presentation.

This suggested that "in the present case, the lesion of the frontal lobe was the cause of the loss of speech," Broca added.

At the meeting, however, his peers didn't immediately recognize the finding's significance; most of the meeting was taken up with now-discredited race "science" focused on supposed links between skull measurements and intelligence. But by August 1861, Broca had studied the brains of multiple patients with what would later be termed aphasia. The research reinforced his conviction that speech was localized to the frontal lobe, and he would later narrow the region to the left frontal lobe.

Over the course of his life, Broca would not only identify the region tied to aphasia but also note that speech therapy could occasionally help patients regain speech.

Since Broca's time, researchers have confirmed that discrete brain regions perform specific cognitive functions and have zeroed in on a much more precise region of the brain that is key for speech than Broca identified. That area is now named Broca's area and is recognized as important to Broca's aphasia, in which patients can understand language but have trouble producing spoken, written or sign language.

We now know that other regions and networks beyond Broca's area play a big role in speech. For instance, damage to Wernicke's area, discovered in 1874, can trigger a form of aphasia in which patients speak in long, complete sentences that have little meaning.

For decades, Leborgne's intact brain, which Broca never cut into sections but only examined superficially, could be viewed at the Dupuytren Museum in Paris, which closed to the public in 2016.

Steve Fleming’s research is definitely “meta” — a Greek prefix indicating self-reference. He’s a cognitive neuroscientist at University College London who studies metacognition: what we know about what we know, think about what we think, believe about what we believe. While this may seem quite philosophical and well-nigh impossible to study in the lab, he has made it his mission to measure and model it and understand where in the brain it manifests itself.

Fleming explored these issues in his 2021 book, Know Thyself: The Science of Self-Awareness. In the 2024 Annual Review of Psychology, he further examined the link between metacognition and confidence: our sense of whether we have made the right decision, whether we are successful at the tasks presented to us, and whether our worldview is likely correct.

Fleming’s work is casting new light on why some people seem chronically underconfident even when they’re doing just fine, and why others are entirely convinced they’re right about everything, even when there is overwhelming evidence to the contrary. In the following discussion, which has been edited for length and clarity, Fleming shared his thoughts on some of the questions that inevitably come up when our brains assess their own activity.

Metacognition is quite an uncommon research topic. How did you end up studying this?

I studied experimental psychology in Oxford, where I had the opportunity to work with psychologist Paul Azzopardi. He studies blindsight, a condition where, due to certain types of brain damage, people are subjectively blind but still able to perform various tasks using visual information. This presents a fascinating dissociation between conscious experience and actual functionality.

At that point, I hadn’t figured out how to connect the more philosophical ideas about conscious experience to something we can actually measure and study in the lab. But ever since then, my career has been inching towards achieving the original goal of using mathematical models from psychology to explain aspects of self-awareness. These are things that psychologists and philosophers have always been interested in, but that are quite difficult to pin down in practice.

How do you measure something like metacognition in the lab?

The standard approach is to measure people’s objective performance on a task as well as their subjective assessment of their own performance, usually in the form of confidence ratings. For example, we might be asking whether a visual stimulus known as a grating is tilted to the left or to the right, or to compare the brightness of two gratings shown one after the other. That would be a judgment about the outside world. We can then also ask them a metacognitive question, to evaluate their confidence in their decision about the world.

When we have lots of these kinds of judgments over time, we can observe the extent to which confidence is tracking performance, on a trial-by-trial basis. If someone has high confidence when they’re right and lower confidence when they’re wrong, they can be ascribed a high degree of what we call metacognitive efficiency. We can use that as a way of quantifying differences in metacognition between individuals or groups.

Can you link these differences to what is happening in people’s brains?

One popular way of doing this has been to look at differences in brain activity and structure between people, using brain imaging techniques like fMRI and magnetoencephalography to try and find out what aspects of brain function gives some people better metacognition than others. But we’ve realized that approach is limited.

So the field has shifted. More recently, we’re instead looking at the relationship between patterns of brain activity and trial-by-trial variation in how confident individual people feel about decisions we ask them to make in experiments.

Essentially, what’s been found is that there are different stages of tracking uncertainty about our own performance when we’re performing a particular task.

For example, if you’re trying to discriminate the orientation of a line, neurons in the part of the brain that are sensitive to different possible line orientations will be firing to different extents, reflecting any uncertainty in what you see. Studies show that if there is conflicting information at that level, that affects people’s confidence estimates in the tests.

There are also data suggesting another higher-level stage of assessment: There are brain areas in the prefrontal cortex signaling confidence in a more general fashion, one that is not tied to the specific input we receive when conducting a particular task. This process continues after you’ve made a decision, and the brain is then also considering information that wasn’t initially available. It’s as if it is still trying to figure out whether it got it right or wrong.

That seems to happen pretty much automatically. It doesn’t require any external instruction or conscious effort. When we do ask people to consciously engage in metacognition and report how they feel about their performance, they seem to engage yet another stage of processing, which involves the frontopolar areas of the human brain: regions right towards the front of the cortex that are particularly well-developed in humans compared to other primates. These areas are activated when metacognitive estimates are used to communicate to others or to consciously control behavior, like we asked them to do in these experiments.

What happens if metacognition does not work the way it should?

A pervasive sense of underconfidence has been regularly linked to symptoms of anxiety and depression. We know that individuals who suffer from this general sense of underconfidence are not necessarily performing the tasks any worse than the next person. So one of the puzzles we are interested in trying to solve is why some people are not learning from their own performance. Why is it that they’re unable to realize that they’re actually doing quite well, and then update their beliefs about their skills and abilities appropriately?

What we’ve found is that at a trial-by-trial level, people with anxiety and depression are just as likely as others to show instances of high confidence. But there is an asymmetry in how they learn from these. They sometimes are very confident that they are doing well, but they don’t incorporate those signals into their more global estimates of how well they are doing in these experiments, and presumably daily life as well. At the same time, they are perfectly able to incorporate evidence from trials in which they weren’t very confident about performing well.

Interestingly, this isn’t the case when we give them explicit feedback about their performance. When we tell them that they are right, they realize that they are actually performing quite well.

How could this be applied to help people who struggle with underconfidence?

In a recent study, we’ve shown that underconfidence in people with greater anxiety symptoms is exacerbated with time. If we probe their confidence immediately after they make a decision, they’ll be a bit underconfident. But if we wait a few seconds, they’re even more underconfident about that previous decision, everything else being equal. And it only gets worse.

What we think is happening is that they’re engaging all these brain mechanisms that I talked about earlier to reflect on their own decisions and actions. Now, as time elapses, if you tend to be a more anxious person, those processes lead you to become even more underconfident than you would otherwise be. You’re spending too much time ruminating on your performance.

So one concrete piece of advice that we can extract out of those findings is that if you know that you are prone to that kind of bias, it’s better not to think too much after you’ve made a choice. If immediately after, you think, "All right, yeah, that was a reasonable thing to do," leave it be.

What about people who are, perhaps, a bit more confident than they should be? It appears that can be quite helpful in today’s society.

It's very interesting to think about what is adaptive, on a societal level, for future success. One hypothesis I advance in the book is that if you have a slightly overconfident worldview as well as good metacognitive sensitivity that helps you realize when you're really wrong, that can be quite a powerful mix. Because, as you say, there is a lot of research suggesting that people who are perhaps a little overconfident do well socially. People tend to like them and want them in positions of power because they seem decisive.

At the same time, you don't want someone without proper self-awareness to be able to bluff their way to the top and reach a position of power.

So I think there is a sweet spot where you do need to project a bit of overconfidence to be perceived as competent, yet you also want to make sure you're not too seduced by self-confidence, whether it’s your own or someone else's.

We've found that people with a more open-minded worldview, who are willing to acknowledge that their view might not be the only valid one and believe it's important to listen to the views of people who disagree with them, also tend to have more accurate metacognition in the kinds of tasks we can study in the lab. Accurate metacognition prompts them to seek out new information and update their beliefs if they might be inaccurate. There is a solid body of evidence to suggest that in this way, these signals can help us, over time, to develop a more accurate worldview.

Might it be possible to train metacognition using these kinds of tasks, and do you think that might help us to reduce the societal tensions we experience today?

I think a lack of metacognition is far from the only reason we see polarization in society today. But our research does offer some tools that we could use to try and cultivate people’s ability to think critically about their own thinking, knowledge and decisions, without getting into politics.

The obvious place to do this would be in education, which I believe has a lot of potential. Parents and teachers implicitly encourage children to be more self-aware, but they rarely do so explicitly.

We don’t teach metacognition in the same way we teach math or history or physics. I think that might be a really powerful way of developing more open-minded ways of thinking.

This article originally appeared in Knowable Magazine, a nonprofit publication dedicated to making scientific knowledge accessible to all. Sign up for Knowable Magazine’s newsletter.

For researcher Lynnette Averill, the quest to find a treatment for post-traumatic stress disorder (PTSD) is deeply personal. Averill's father served as an enlisted infantryman with the U.S. Marine Corps in Vietnam and struggled to cope with his war experiences when he returned home. After years of ineffective treatments, he died by suicide when Averill was three.

Driven by a mission to support veterans' mental health, Averill trained as a psychologist and began working with people with PTSD — a condition that affects more than 12 million Americans in any given year. Victims of violence, abuse and accidents can experience post-traumatic symptoms such as persistent flashbacks, hypervigilance, and entrenched negative beliefs about themselves and their environment.

"People can be very stuck in black-and-white thinking, such as, 'I'm a bad person,' 'I deserve this,' 'the world is dangerous," Averill, a clinical research psychologist at the Baylor College of Medicine in Texas, said during a panel discussion at the Psychedelic Science conference in Denver in June 2025.

The root of these symptoms lie in how trauma shapes changes in the brain in the weeks and months after a frightening event. The brain's fear center — the amygdala — becomes hyperactive, constantly signaling danger, while the brain regions responsible for contextualizing memories and managing emotional responses become less active and less able to counterbalance those fear signals. Traditional therapies, such as antidepressant medications and trauma-focused psychotherapies, help only a fraction of patients and can take months to be effective.

"For many people with PTSD, they simply aren't enough, " Averill told Live Science.

Consequently, Averill is one of a group of researchers who are exploring a new potential avenue for treating PTSD: psychedelics. Psychedelic-assisted psychotherapy, using MDMA or psilocybin, may act on the brain systems disrupted in PTSD, rather than simply treating the symptoms.

The early findings have been positive: A recent clinical trial showed that 67% of patients who received MDMA-assisted therapy no longer met PTSD criteria after treatment, compared with 32% in the placebo group, and clinical trials investigating psilocybin's potential to treat the condition are showing promise.

Averill is currently leading a pioneering Texas state-funded clinical trial investigating psilocybin for veterans with PTSD and has seen how quickly the drugs can act.

"There's potential for people to feel that the needle has moved in hours," Averill said. "And that is just quite literally lifesaving."

How trauma changes the brain

PTSD shares symptoms with depression and anxiety. Yet it is characterized by a response to a single trauma or set of traumatic events. Such experiences spark fear and often challenge an individual's core beliefs that the world is a just, safe and predictable place. People with PTSD can feel helpless and without agency.

It's normal for people who have endured traumatic events to experience these symptoms for a short time, and for most people, they resolve within a week or two, clinical psychologist Gregory Fonzo, a co-director of the Charmaine and Gordon McGill Center for Psychedelic Research and Therapy at the University of Texas at Austin's Dell Medical School, told Live Science. But a subset of people get stuck.

"PTSD is essentially a disorder of nonrecovery," Fonzo said.

During the instigating event, trauma activates the brain's fear alarm system, including the amygdala, and signals a rapid release of stress hormones and neurotransmitters, such as norepinephrine (noradrenaline). The higher levels of norepinephrine increase arousal and the physiological “fight or flight” response. The interaction of norepinephrine and corticotropin-releasing hormone modulates increases activity between the amygdala and hippocampus, reinforcing the synaptic connections that help store fear and vivid details of the event.

For the majority of people who recover quickly, this powerful fear response is successfully extinguished. The prefrontal cortex, the brain's regulatory control system, and the hippocampus, the brain's center for memory, exert top-down control and file the event as a past memory and no longer dangerous, which restores normal signaling in the amygdala.

For people who develop PTSD, however, the trauma creates more persistent changes in the brain, Dr. Jerrold Rosenbaum, a psychiatrist and director of the Center for Neuroscience of Psychedelics at Massachusetts General Hospital, told Live Science.

In PTSD, the amygdala remains stuck in an overactive state, causing symptoms like hyperarousal, irritability and being easily startled. At the same time, the prefrontal cortex, which normally calms those alarms, becomes underactive, leaving the amygdala's overreactive fear response unchecked.

Neuroimaging has shown that PTSD is associated with a reduced volume of the hippocampus, which is the brain region that processes the context — the where, when and circumstances — of an event. In normal circumstances the hippocampus can discriminate between real and perceived danger. For example, it will categorize the sound of a car backfiring in an everyday environment differently than the blast of gunshot, which occurred specifically in a war zone. But a diminished hippocampus could make it harder for patients to distinguish between the two.

There's also evidence that PTSD is associated with changes in the connectivity of the default mode network (DMN), a set of interconnected brain regions that are highly active when a person is resting, their mind is wandering, or they are engaged in thinking about themselves or their memories rather than the outside world. Researchers hypothesize that heightened connectivity within the DMN is a neurobiological abnormality that pushes the system into overdrive, potentially leading to rumination or the involuntary re-experiencing of negative events (or flashbacks), which are characteristic symptoms of PTSD. In PTSD, the DMN also appears to be abnormally disconnected from the executive control regions and simultaneously abnormally connected with lower-level emotional systems, such as the amygdala. Scientists believe this increased coupling may drive intense, automatic emotions such as shame and guilt.

In a healthy brain, the prefrontal cortex can evaluate and change upsetting thoughts, but PTSD compromises this ability. PTSD is also associated with reduced levels of brain-derived neurotrophic factor (BDNF), a signaling protein that is critical for neural plasticity — the formation of new synapses and the strengthening or pruning of existing neural connections. The deficit in BDNF effectively "locks" the trauma response in place and can prevent the brain from integrating new, non-fearful thinking, scientists theorize.

The result is a system trapped in fearful thinking and the past.

"PTSD can definitely manifest in rigidity and entrenchment of ways of thinking about oneself and others in the world," Brandon Weiss, a psychologist at the Johns Hopkins Medical Center for Psychedelic and Consciousness Research, told Live Science.

Treatment challenges

Physicians have used trauma-focused psychotherapy, such as cognitive processing therapy (CPT) and prolonged exposure (PE), to treat PTSD. In CPT, therapists guide patients to examine and change distorted thinking, such as the belief that they are to blame for events outside of their control. PE focuses on teaching the patient to reduce their fear by gradually confronting the traumatic memories in a controlled environment.

But these treatments are difficult for people to go through because they have to face the stuff that is really bothering them, Fonzo said. "So a lot of people drop out before they finish the treatment."

Access to specialized, trauma-focused therapists can be challenging, and not everyone benefits from such treatments, Fonzo said. Other treatment options include SSRIs, like sertraline (Zoloft) or paroxetine (Paxel), but only 20% to 30% of patients experience a remission on these drugs.

Most importantly, many patients feel like the medication hasn't addressed the root cause of their trauma, Rosenbaum said.

Creating a safe space to process trauma

For Jennifer Mitchell, a neuroscientist and the associate chief of staff for research and development at San Francisco Veterans Affairs Medical Center, it was imperative to find effective treatments for military veterans suffering from PTSD.

"I see how debilitating it is for individuals that have served and have experienced combat," Mitchell told Live Science. "And we absolutely owe them to come up with better treatments."

Nearly a decade ago, Mitchell and her colleagues began to investigate whether MDMA (3,4-methylenedioxymethamphetamine), commonly known as ecstasy or molly, could treat PTSD when used in conjunction with psychotherapy. In 2023, the team published their findings on a diverse group of 104 participants with PTSD from the general population, 80% of whom had a history of contemplating suicide. By the end of the study, 71% of the participants who'd received MDMA no longer met the criteria for PTSD, and another 15% still had symptoms but had what the researchers termed a "clinically meaningful benefit."

MDMA's effectiveness hinges partly on its ability to act as a neuroplastogen — a compound that harnesses the brain's ability to form new connections and strengthen and reorganize existing connections. In the past few years, scientists have begun to explore the potential for another neuroplastogen to treat PTSD: psilocybin.

Clinical trials have found psilocybin, the main psychoactive ingredient in magic mushrooms, to be a promising therapy for treatment-resistant anxiety and depression, and studies conducted on animals have pointed to its potential for treating PTSD.

A study on mature adult mice demonstrated that MDMA temporarily reopens a critical period for where the brain is sensitive to learning that social behaviors are beneficial by inducing structural and functional changes in the brain’s reward circuits. Specifically the drug makes the nucleus accumbens reward circuitry more sensitive to the social hormone oxytocin. This enhanced sensitivity allows the adult brain to re-encode social cues as intrinsically rewarding and safe, facilitating the re-learning of trust and attachment for up to two weeks after a single dose, the researcher theorize.

Mitchell has witnessed similar responses in humans and hypothesizes that the drug creates a neurobiological state in which patients can form a strong, trusting bond with a therapist. "There's a therapeutic window where people feel renewed energy, they don't feel so stuck, and they can actually work on the psychological side of their issues," Mitchell said.

Simultaneously, functional neuroimaging data points to MDMA's impacts on the fear circuitry of the brain. The drug decreases activity in the amygdala while increasing activity in the prefrontal cortex. MDMA also restores normal levels of BDNF in the amygdala, hippocampus and prefrontal cortex, theoretically leading to the formation of new synapses and structural changes that enable greater plasticity in these regions.

Researchers hypothesize that the dampening of the fear response, the enhancement of the prefrontal cortex's regulatory role, and the restoration of flexibility in key brain regions set the scene for patients to revisit and reprocess memories without being overwhelmed by fear. By entering therapy with this more regulated perspective, recovery can happen quickly.

"By the end of a treatment session, you can see that something has shifted. The subject will be holding themselves differently and look hopeful," Mitchell said. "I've been doing this type of research for 35 years, and it is the most remarkable thing that I've seen."

Once the patients have analyzed and processed their trauma, they are less likely to slip back into their PTSD symptoms after MDMA, Mitchell said. The researchers collected data on the patients in increments over the two years after their treatment ended, and the positive benefits appear to be durable, Mitchell said.

Breaking free

When a single dose of psilocybin was injected into chronically stressed mice that had developed learned helplessness and avoidance behaviors, for example, researchers could see immediate and enduring structural changes in the rodents' brains. The rapid increase in dendritic spines — the tiny protrusions that form synapses, the connections between brain cells —suggests that psilocybin may directly reverse the loss of neuronal connections observed in the frontal cortex of rodents subjected to chronic stress, the authors suggest. And the changes could prepare the brain for fear extinction and emotional processing —key elements of overcoming trauma.

Consequently, several trials are underway to investigate psilocybin as a treatment option for PTSD. In August 2025, biotechnology company Compass Pathways published its findings on a trial designed to test the safety of psilocybin for PTSD. The small safety study wasn't designed to measure effectiveness. Nevertheless, participants seemed to show an immediate reduction in PTSD symptoms after a single 25-milligram dose of the company's synthetic psilocybin. Clinicians reported the improvements had endured when tested 12 weeks later.

In the study Averill is leading, clinicians started dosing seven participants who had experienced PTSD symptoms for an average of 19 years at the start of the trial in February. The early findings "have been incredible," Averill said during a panel discussion at the Psychedelic Science conference in Denver in June 2025.

Within a few hours of the first dose of psilocybin, every single veteran reported positive changes in their beliefs and perceptions. After the treatment effects subsided, participants underwent therapy and said the drug enabled them to reevaluate their original traumatic experiences from a nonjudgmental perspective, without the shame and guilt, Averill said.

So how does psilocybin bring about these changes?

Studies in mice have demonstrated that, in a similar vein to MDMA, psilocybin helps brain cells grow new dendritic spines. These new branches appear in the prefrontal cortex and the hippocampus, the key regions responsible for learning, planning and memory.

But brain scans from people have shown that psilocybin simultaneously disrupts and desynchronizes, or dissolves, connectivity within the DMN for three weeks. Scientists hypothesize that this desynchronization of the brain system involved in self-referential processing results in a mind that is less constrained, more flexible and less consumed by self-reproach. They propose that the disruption of rigid cognitive patterns and negative thought loops may promote psychological flexibility and self-compassion.

"It has been surprising to see these maladaptive beliefs shift when I'd learned that change would only come about through longer term talk therapy," Weiss said.

Dissolving rigid thinking can open up the mind to new possibilities, including the idea that the patient wasn't responsible for the original trauma, Weiss said. Weiss is currently carrying out a clinical trial examining the effect of psilocybin therapy on the cognitive beliefs related to PTSD and is witnessing participants' experiences of the treatment.

"Many are endorsing less guilt and are able to let go of the sense that they were to blame for this happening," he said.

Proceeding cautiously, with haste

When Fonzo first reviewed the data on psychedelics as a treatment option in mental health, he was excited by what he found. But he pointed out that there haven't yet been any large, controlled studies evaluating psilocybin for PTSD. The research is still in its early stages with small pilot studies or clinical trials still assessing the safety of the drug. "There needs to be a sober perspective on what the evidence does, and does not show," Fonzo said, "because these treatments aren't necessarily going to be suitable for everyone."

Fonzo believes the answer lies in the expansion of funding for clinical trials, but research in psychedelics still faces steep hurdles. Both MDMA and psilocybin are listed as Schedule I substances in the U.S. — a federal classification reserved for drugs considered to have a high potential for abuse and no accepted medical use. That label makes studying them a bureaucratic nightmare, as researchers must navigate complex regulatory approvals and secure special licenses just to handle the compounds.

On top of that, every trial demands careful screening to find participants who meet the strict inclusion and exclusion criteria. Also, due to the profound and unmistakable psychoactive effects of psychedelics, in trials, it can be hard to hide who is and isn't getting the drug and thus create a robust placebo group.

Despite these challenges, new clinical trials are underway to explore variations in dosage, psychotherapy pairing and long-term outcomes. Weiss and his colleagues are investigating administering combinations of MDMA and psilocybin — so-called psychedelic stacking — and comparing the effectiveness of each treatment separately. "We're still learning about what is the most efficient and rapid-acting approach to helping people," Weiss said.

For veterans who are experiencing suicidal thoughts as part of their PTSD, finding interventions that spur rapid change could be key, Weiss said. Despite the compelling findings, the regulatory approval of psychedelic treatments for PTSD is moving slowly. In August 2024, the U.S. Food and Drug Administration declined to approve MDMA-assisted therapy for PTSD, citing concerns over the study design and blinding procedures. Mitchell has been frustrated about the decision not to approve the treatment with guardrails, or for a subset of people who really need it.

"My own brain gets cranky when I hear people not consider PTSD a life-threatening condition — because it is," Mitchell said. In the United States in 2024, an average of 17 veterans died each day by suicide.

"That's why speed matters. We can't wait months for treatments that barely work," Mitchell said.

Averill has witnessed PTSD patients liberated by psychedelic therapy, but she cautioned that the psychedelic experience is not a "silver bullet" but rather one that opens the doors to healing. One veteran in the clinical trial she'd been leading described feeling like he'd been locked in a cage and said every movement felt painful. The psilocybin removed the cage, and he was able to revisit his traumatic experiences.

Averill's goal is to continue exploring how psychedelic-assisted therapy can help PTSD sufferers move beyond merely tolerating their existence. "We want to help people move forward and build lives they really want to be living," Averill said.

An experimental treatment uses specialized neurons derived from stem cells to "soak up" triggers of pain and inflammation in the arthritic knees of mice.

This lab-mouse experiment suggests the therapy could potentially help with chronic pain in people, caused by conditions like osteoarthritis, for example. The hope is that the "pain sponge" could enable patients to stop relying on opioid medications for pain relief, the researchers say.

And as a bonus side effect, the engineered neurons also promoted bone and cartilage repair in the mice they were tested in, the researchers reported in a preprint posted to the server bioRxiv in December 2025. The work has not yet been peer-reviewed.

"The possibility that the therapy could both relieve pain and slow cartilage degeneration is particularly compelling for osteoarthritis," Chuan-Ju Liu, an orthopedics professor at Yale University who wasn't involved in the study, told Live Science.

How the pain sponge works

The therapy, known as SN101, uses human pluripotent stem cells (hPSC), which can differentiate into any type of cell in the body. In the study, led by Gabsang Lee, a neurology professor at the Johns Hopkins School of Medicine, researchers engineered the hPSC to differentiate into specialized sensory neurons.

These neurons effectively worked as a sponge for inflammatory pain signals. They sequestered the signals before they could be transmitted to the brain and cause pain.

Theoretically, the therapy could work for any kind of chronic pain, said Daniel Saragnese, co-founder of SereNeuro Therapeutics, the biotech company developing SN101. That said, the researchers have so far tested its effectiveness for only osteoarthritis, the most common form of arthritis.

The degenerative condition is characterized by inflammation and chronic pain that affects the joints, mainly the hips, knees, lower back and neck. It causes pain and stiffness, as well as inflammation driven by the breakdown of bone, cartilage and other tissues. There is no cure.

Currently, osteoarthritis symptoms are managed with lifestyle changes, including physical therapy, and various pain relievers, such as over-the-counter and topical painkillers, opioids, and steroid injections.

In the context of neurodegenerative diseases — such as multiple sclerosis, Alzheimer's disease, and Parkinson's disease — scientists have been working on using hPSCs to replace or repair damaged neurons. With SN101, though, the researchers are taking an alternative approach. The new hPSC-derived neurons are injected at the site of inflammation and exist alongside other pain-sensing neurons, rather than replacing them.

The new neurons serve as biological decoys, binding nearby inflammatory factors before they can be picked up by the body's original neurons.

Potential pros of SN101

Chronic pain, which is defined as pain that lasts three months or more, is often managed with opioid drugs that bind to receptors in the body to reduce the intensity of pain. However, opioids cause unwanted side effects, such as nausea and vomiting, and carry a risk of addiction.

Despite their downsides, it is estimated that about 9% of patients with knee osteoarthritis turn to opioids, which can lead to excessive, long-term use. As such, scientists are always on the lookout for safer and more efficient pain-management techniques.

By using biologically complex cells that naturally express multiple pain receptors, SN101 may more closely reflect the way pain and inflammation manifest in living tissues, Liu said. This could help snuff out pain at its source. Opioids, on the other hand, bind to receptors in the brain to temporarily block painful sensations, so they don't get at the signals at the root of pain.

"However, this work remains at a preclinical stage," Liu emphasized.

The research will need to pass significant milestones before human use, including formal toxicology studies, long-term safety assessments, and first-in-human clinical trials, he said. Nonetheless, he called the idea behind the therapy "innovative."

The researchers pointed out several limitations in their recent study that would need investigation before SN101 could be deemed safe for humans. One is the treatment's immunogenicity — that is, whether it triggers a harmful immune response in the body. Another limitation is that human and mouse knee joints are very different, so some results from the arthritic mouse study might not translate to people.

"Human joints are larger [than mouse joints], more mechanically complex, and subject to decades of cumulative stress," Liu noted. Additionally, "pain processing and immune-neuronal interactions can differ substantially between mice and humans, which may affect both therapeutic efficacy and durability."

Destroying "undead" cells in the brain may help to relieve a common form of epilepsy, a new lab study suggests.

In the research, published in the journal Annals of Neurology, researchers found that clearing away damaged-but-undying brain cells in mouse models of epilepsy improved the rodents' memory and reduced their number of seizures. The research focused on temporal lobe epilepsy (TLE), the world's most common seizure disorder, which affects roughly 50 million people globally.

The findings could help researchers develop the first disease-modifying medications for TLE, meaning drugs that actually get at the condition's drivers, rather than just treating the symptoms, the study authors say. Available antiseizure drugs reduce the number and severity of seizures but don't address their root cause, and patients who don't benefit much from the drugs may require brain surgery or nerve-stimulation devices.

Slaying zombies

TLE can arise after head trauma or infection, and more rarely, it can have genetic causes. But exactly how these factors are linked to seizures and memory loss is still unclear.

Meanwhile, a new idea has emerged around the role of "zombified" cells in epilepsy.

When cells are damaged, they often undergo programmed cell death, which causes them to self-destruct. But some cells instead enter a stage called senescence, in which they no longer divide like healthy cells do but still refuse to die.

Study co-author Patrick Forcelli, a pharmacologist at Georgetown University, told Live Science that these cells' influence has been a hot topic among neuroscientists. "There's been an increasing appreciation that cellular senescence might play an important role in a range of brain disorders," he said.

His team noticed that these zombie cells behaved similarly to how brain cells do at the very start of a seizure. Both the zombies and pre-epileptic brain areas develop tissue scarring, called fibrosis. In their new paper, Forcelli and his colleagues asked whether removing senescent cells from the brain might alter the symptoms of TLE.

The team began by looking for signs of senescence in TLE-affected brains. Some patients with TLE have parts of their brains removed to help reduce or eliminate their seizures. The scientists compared brain tissue samples from these patients with autopsied samples from people without TLE.

Notably, the non-TLE group was significantly older than the TLE group, Forcelli said. Despite this, the epilepsy group had five times as many senescent cells in their tissue samples, on average.

Next, in mouse models of TLE, the team showed that the animals also had more signs of senescence in their brains than did mice without seizures. These signs of senescence were most strongly linked to microglia, cells that form part of the brain's in-house immune system. Dysfunctional microglia have been increasingly implicated in brain diseases, including dementia.

The team then tried removing senescent cells from the mice. They gave some of the mice a combination of the leukemia drug dasatinib and the anti-inflammatory plant pigment quercetin. This unusual cocktail has been repeatedly shown in previous research to deplete senescent cell numbers; such treatments are known as senolytics.

James Kirkland, a gerontologist at Cedars-Sinai Medical Center who first identified the two compounds' senolytic effects, told Live Science that they target the pathways that senescent cells use to resist normal cell death.

Dasatinib has been approved as a cancer treatment by the U.S. Food and Drug Administration (FDA), while quercetin is currently regulated as a supplement and food ingredient and is recognized as safe for human use. Trials would be needed to evaluate this treatment combo as a senolytic in humans.

A delicate balance

The dual treatment improved several symptoms in the mice. "We were able to normalize memory function of the mice" and significantly reduce their seizures, Forcelli said. "We also protected a large population of animals from developing seizures at all, so this is a disease-modifying approach in that respect."

In a separate experiment, Forcelli's team tried eliminating all of the microglia — both healthy and senescent — from the mice with TLE. This broad removal didn't help the animals, in part because the senescent cells proved resistant to the wide-spectrum treatment.

"We got rid of lots and lots of healthy microglia, and we left the senescent microglia," Forcelli said. Previous studies have suggested microglia have both damaging and protective roles in epilepsy, he added. The influence of a small population of senescent cells working against a larger population of healthy microglia could explain this inconsistency. It also suggests that any treatment aimed at microglia would need to carefully target the senescent ones.

Forcelli plans to conduct further research to find the best time to administer potential senolytic treatments for TLE. For instance, should the drug be given immediately after someone experiences head trauma, or could it still be effective a week or month afterward?

In addition, Kirkland said that targeting senescence and other aging-related processes could have applications across many different conditions. But he warned that the wider public should wait for the results of formal clinical trials rather than taking commercially available supplements with marketed senolytic properties.

He noted that these supplements may contain ingredients not listed on their labels or dangerously high levels of the active compound.

"There's an issue with quality control because there's a lack of regulation," Kirkland said. In the U.S., supplements do not undergo the rigorous safety, efficacy and quality testing that pharmaceutical drugs do, so claims about what they do in the body are often untested or undertested.

Luckily, rigorous clinical trials are now investigating various types of senolytics. Kirkland said preclinical work has identified some "60 or 70" conditions in which senolytics might delay or prevent disease. "There's a whole new world coming," he concluded.

This article is for informational purposes only and is not meant to offer medical advice.

The patient: A 25-year-old man in Germany

The symptoms: The man was on a ski trip in November 2008 when an avalanche knocked him unconscious and left him buried under snow for 15 minutes. His body tissues were starved of oxygen while he was trapped, leading him to develop a condition called hypoxia. His friend rescued him and immediately began CPR upon releasing him from the snow, Berend Feddersen, a neurologist at the University of Munich in Germany, and the lead author of a report on the case, previously told Live Science. He was then taken to a hospital.

The hypoxia left the man with a movement disorder that caused uncontrollable twitching in the muscles of his legs and mouth when he walked and talked, respectively. He didn't experience these muscle jerks in his arms.

What happened next: After a stint in the hospital, the man was moved to a rehabilitation facility. While at this center, he started a sudoku puzzle — a regular pastime of his prior to the injury.

As he solved the sudoku, the muscles in his left arm repeatedly jerked. But these movements immediately ceased when he stopped work on the puzzle.

The diagnosis: The man appeared to be having clonic seizures — repeated jerking movements — in his arm while solving sudoku, so the medical team ran brain scans to better understand what was happening.

An electroencephalogram, which measures activity on the brain's surface, revealed the patient was experiencing a right centroparietal seizure pattern — meaning the seizures stemmed from the central and parietal regions in the right hemisphere of his brain. MRI did not show any evidence of disease or abnormality that might be driving this seizure activity.

The medical team then performed a functional MRI (fMRI) on the patient while he solved a sudoku; this type of scan tracks activity throughout the brain via blood flow. The scan revealed "widespread activation," although activity in the centroparietal cortex was particularly high, the doctors wrote in a report of the case. A closer inspection using a form of MRI called diffusion tensor imaging, which creates maps of the brain's white-matter fibers, showed fewer inhibitory fibers in this brain region.

The loss of those inhibitory fibers — which help keep the activity of brain cells in check — resulted in a three-fold increase in activity of the nerve running down the patient's left arm. The doctors wrote that the hypoxia the man experienced during the avalanche is the "most likely" cause of this damage.

In turn, the over-activation of the right centroparietal cortex resulted in focal epileptic seizures, which are seizures focused in one discrete region of the brain. Specifically, the patient had developed reflex epilepsy, in which seizures are triggered by certain stimuli, like particular lights or music.

In this case, the three-dimensional image the patient imagined while solving sudoku triggered the seizures, Feddersen said. The patient did not experience clonic seizures when reading, writing or calculating. But the doctors could prompt a seizure by giving the man other visual-spatial tasks, such as placing a random string of numbers in order from smallest to largest.

The treatment: The patient was prescribed anti-epileptic medication, which stopped his seizures; he was more than five years seizure-free as of 2015, the report says. He also received physical therapy, which helped ease the twitches he experienced when walking and talking.

He also gave up solving sudoku puzzles.

What makes the case unique: About 3.8% of people will develop epilepsy in their life, with around 4% to 7% of those patients experiencing reflex seizures. Although this was the first known case of a sudoku puzzle triggering seizures, a common type of reflex epilepsy is called "praxis induction," in which visual-motor tasks — like playing chess or cards — set off muscle jerks.

For instance, in 2015, doctors reported the cases of five men with epilepsy in China who had seizures induced by playing the ancient Chinese game of Zipai. These men, ages 19 to 44 years old, stopped having seizures when they avoided playing Zipai. Similarly, in January 2025, doctors in Taiwan reported on 30 patients who had reflex seizures triggered by playing Mah-Jong.

For more intriguing medical cases, check out our Diagnostic Dilemma archives.

This article is for informational purposes only and is not meant to offer medical advice.

Supplying nerves with a fresh supply of mitochondria could curb chronic nerve pain, a new study hints.

The research, conducted with mouse cells, live mice, and human tissues, reveals a previously unsung role of mitochondria, the powerhouses of cells. It shows that support cells within the nervous system can ship mitochondria to the nerves that respond to pressure, temperature and pain. But problems with that shipping process can deplete the nerves' energy reserves, causing them to malfunction.

Whereas nerves would normally send a signal to the brain in response to some stimulus, dysfunctional nerves "fire sometimes spontaneously, even without stimulation," said senior study author Ru-Rong Ji, director of the Duke University School of Medicine's Center for Translational Pain Medicine and a professor of anesthesiology and neurobiology.

"That will drive chronic pain and also will lead to neurodegeneration," Ji told Live Science, "because if you fire like crazy, eventually, that neuron probably will degenerate."

The new study, published Wednesday (Jan. 7) in the journal Nature, points to potential new ways of heading off that neuronal breakdown — and one strategy could involve transferring mitochondria directly into nerves.

Fresh mitochondria reduce pain

The research zoomed in on satellite glial cells, unique cells that physically wrap themselves around the "roots" of nerve cells located near the spinal cord. The bodies of these nerve cells cluster together near the spine, and from each cluster, bundles of long fibers extend to different parts of the body, from head to toe. The longest of these fiber bundles belong to the sciatic nerve, which measures just over 3 feet (1 meter) long.

The sheer length of the fibers poses a "real challenge," because for a nerve to function properly, mitochondria made in the nerve's root must travel down to the end of each fiber, and that in itself requires energy to do, Ji said. That raises a question of how nerves maintain this power-hungry supply chain.

Scientists once thought that cells had to make all of their own mitochondria, but in recent years, they have uncovered evidence that cells swap mitochondria. This can occur between cells of the same type or between cells of different types, such as between a stem cell and an immune cell, for example. To facilitate the swap, cells construct tiny structures called tunneling nanotubes for the mitochondria to travel through, like spitballs sliding from one end of a straw to another.

Ji and his team wondered whether satellite glial cells might be able to send mitochondria to the nerve cells they encircle — and it turns out that they can.

"We demonstrate that these cells actually extend these tunneling nanotubes to deliver in the mitochondria. This [finding] is unique in this study," Ji said.

In a series of experiments with mouse cells and human tissues, the researchers took snapshots of the tiny tubes that formed between glia and nerve cells, noting distinct "bulges" that appeared in the tubes as materials traveled through them. By tacking a fluorescent tag onto mitochondria, they were able to track instances in which powerhouses from glial cells made their way into the nerves.

The nanotubes were transient structures that broke down soon after a given transfer was complete. Experiments showed that a protein called MYO10 was critical to the tubes' construction, helping to extend them out from the glia. But additionally, the mitochondria could sometimes be transferred without the tubes, either inside tiny bubbles released by glia or through special channels that formed between the membranes of the donor and recipient cells.

In healthy lab mice, the researchers found that disrupting these different modes of mitochondria shipment made the mice more sensitive to pain. That's because it spurred damage in the nerves and caused them to fire abnormally.

They also looked at mice with various types of nerve damage, such as from exposure to chemotherapy drugs or from diabetes. These nerve-damaging conditions also disrupted the mitochondrial exchange from glia to some degree, and this contributed to nerve pain in the lab mice. Transferring healthy glia into the mice alleviated the pain, though, by providing them with a fresh source of healthy mitochondria.

A new view on glia

Notably, nerve damage from diabetes and chemotherapy tends to hit the smallest nerve fibers the hardest, whereas medium and large fibers show more resilience. In the team's experiments, they found that the larger nerve fibers appeared to receive a higher volume of mitochondria from glia, while small fibers got fewer by comparison. In short, it seems that glia have a "preference" toward lending their mitochondria to larger fibers, the study authors wrote.

"That is still a puzzle. We don't know why that's the case," Ji said. But nonetheless, it might begin to explain why small fibers are more vulnerable to damage in these conditions, triggering symptoms of numbness, painful tingling or burning in the feet and hands.

More studies are needed to fully understand how mitochondria are shuttled from glia to nerve cells in health and disease. This fundamental research could pave the way to future treatments for nerve pain, the team thinks. In theory, treatments could be aimed at boosting the activity of satellite glial cells, so they produce and transfer more mitochondria.

Or alternatively, mitochondria could be harvested from cells grown in the lab, purified, and then injected straight into nerves as a treatment, he added.

Historically, glia were solely thought of as the glue of the nervous system, providing structural support to neurons by binding them together. But scientists have since uncovered that glia are involved in processes once thought to be handled only by neurons, like memory. And the new study suggests glia may actually be physically plugged into neuronal networks, Ji said.

"If they can transport mitochondria, such a very large organelle, in that tube, then you can transport many other things, right?" he suggested. "That means the neurons and the glial cells, they are much more connected than we thought."

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A new brain-machine interface (BMI) uses light to "speak" to the brain, mouse experiments show.

The minimally invasive wireless device, which is placed under the scalp, receives inputs in the form of light patterns, which are then conveyed to genetically modified neurons in brain tissue.

In the new study, these neurons activated as if they were responding to sensory information from the mice's eyes. The mice learned to match these different patterns of brain activity to perform specific tasks — namely, to uncover the locations of tasty snacks in a series of lab experiments.

The device marks a step toward a new generation of BMIs that will be capable of receiving artificial inputs — in this case, LED light — independent of typical sensory channels the brain relies on, such as the eyes. This would help scientists build devices that interface with the brain, without requiring trailing wires or bulky external parts.

"The technology is a very powerful tool for doing fundamental research," and it could address human health challenges in the longer term, said John Rogers, a bioelectronics researcher at Northwestern University and senior author of the study, which was published Dec. 8 in the journal Nature Neuroscience.

Bypassing the sensory system

The device, which is smaller than a human index finger, is soft and flexible, so it conforms to the curvature of the skull. It includes 64 tiny LEDs, an electronic circuit that powers the lights, and a receiver antenna. Additionally, an external antenna controls the LEDs using near-field-communications (NFC) — electromagnetic fields for short-range communications as is done for contactless card payments.

The compact device is designed to be placed under the skin, rather than being implanted directly into the brain. "It projects light directly onto the brain [through the skull], and the response of the brain to that light is generated by a genetic modification in the neurons," Rogers told Live Science.

Brain cells don't normally respond to light that is shone on them, so gene editing is required to make that happen.

"The genetic modification creates light-sensitive ion channels," Rogers explained. When activated by light, these channels allow charged particles to flow into brain cells, tripping a signal that then gets sent to other cells. "Through that mechanism, we create light sensitivity directly in the brain tissue itself," he said. The genetic modification of the brain cells was done using a viral vector, a harmless virus made to deliver the desired genetic tweak into specific cells in different regions of the brain.

The use of light to control the activity of genetically modified cells is called optogenetics, and it's a relatively new science. In past work, the researchers used a similar approach to activate just one group of brain cells, but the new device enabled them to toggle the activity of many neurons across the brain.

"[The genetic modification] is not just stimulating the part of the brain that's naturally responsible for visual perception, but across the entire surface of the cortex," Rogers said. Thus, sending different patterns of illumination creates a corresponding distribution of neural activity. "It's like we can project a series of images — almost like play a movie — directly into the brain by controlling [the] sequence of patterns."

The researchers tested the implant in the mice by wirelessly instructing it to produce various patterned bursts of light. The mice were trained to respond to each pattern with a specific behavior, indicating that they could distinguish between the patterns transmitted. With each type of signal, they had to go to a specific cavity in a wall, and for choosing correctly, they'd get sugar water as a reward.

Bin He, a neuroengineering researcher at Carnegie Mellon University who wasn't involved in the study, called it a novel technique for using light to tune circuits across the brain. "It may have various applications in neuroscience research using animal models … and beyond," he said.

For instance, the researchers see potential for this device in future prosthetics. Applications could include adding sensations, like touch or pressure, to prosthetic limbs, or sending visual or auditory signals to vision or hearing prostheses.

"Optogenetic techniques are just beginning to be used with humans," Rogers said. "There are tremendous advantages [to using light] because you don't need to disrupt the brain tissues. You can use different wavelengths of light to control different regions of the brain."

Rogers said that from a technology standpoint, the platform could scale to cover much larger areas of the brain and contain more micro-LEDs. However, they would have to rethink the power-supply requirements to support a larger device. It should technically work in humans as it does in mice, but further research will be needed before any tests are attempted in humans.

"The biggest hurdle is around the regulatory approval for the genetic modification," he said.

Brain quiz: Test your knowledge of the most complex organ in the body

Scientists have identified a "dial" in the human brain that ramps up when we explore a new area — and the finding could help us understand why getting lost is often an early symptom of dementia, such as Alzheimer's disease.

Imagine you're walking a well-worn route home, but you accidentally take a wrong turn. It doesn't take long for your brain to sound alarms to tell you that you've gotten lost.

The new study, published Dec. 4 in the journal Nature Communications, combined high-powered brain imaging and virtual reality (VR) to reveal what happens in the brain when we explore both familiar and unfamiliar environments.

"When you move to a new city or travel somewhere, it doesn't happen that you just become familiar," study co-author Deniz Vatansever, a neuroscientist at Fudan University in China, told Live Science. "You have to explore your environment to become familiar with it." Vatansever and his team aimed to re-create this experience in VR.

They recruited 56 healthy volunteers ages 20 to 37, each of whom navigated a virtual world while inside a scanner. They explored the virtual environment — a grassy field surrounded by mountains — while looking for six "items" hidden throughout it. Vatansever's team monitored the volunteers' brain activity with functional MRI, a technique that tracks blood flow through the brain, as they explored familiar and unfamiliar areas of this world.

The team zoomed in on the hippocampus, a brain region that's important for memory and navigation. The seahorse-shaped hippocampus is rich with place cells, which light up in response to specific locations. Previous research had shown that one end of the hippocampus contains cells that fire when we think about location in a broad sense, such as where landmarks are in a nearby city. At the other end, place cells activate when we think about specific locations, like where we keep a box of cereal in our kitchen.

Between the "head" and "tail" of the hippocampus seahorse is a gradient of activity linking these broad and fine-tuned representations of locations. But no one had previously examined the organization of cells that respond to the newness or familiarity of a place.

Vatansever's team found that the head of the hippocampus contains cells that fired when their participants explored areas they had been in previously. Cells at the tail responded to new locations. And the whole region was arranged in a gradient, from familiar to unfamiliar.

"You could see that there's this shift in level of novelty versus familiarity as you go from one end to the other," Vatansever said.

Previous research produced mixed results on which areas of the hippocampus respond to novelty or familiarity in the environment, said Zita Patai, a cognitive neuroscientist at University College London who was not involved with the research. "What they're showing is that [the discrepancy] might partially be due to the fact that it's a gradient," she told Live Science.

Other brain areas also responded differently to new and familiar locations. A region in the cortex — the brain's higher-thinking hub — had a cone-shaped gradient. "At the very center of it are bits that 'prefer' more familiarity. And as you move out, then there is greater and greater preference for being active for novelty," Vatansever said.

The team also probed whether navigating familiar and unfamiliar areas activated broader brain networks, or groups of cells spread throughout the brain that often activate in sync. Familiar areas activated networks previously linked to motor control and memory, whereas novel areas activated networks associated with focus and perception.

This division may help the brain adapt to new environments by focusing on and absorbing relevant details, Vatansever said. Then, memory and motor control combine to help navigate familiar areas, he proposed.

The findings may explain some of the earliest signs of dementia, Vatansever suggested. The cells within the gradients in the cortex and hippocampus happen to be among the first brain areas affected by Alzheimer's disease. Both the front and rear regions of the hippocampus are equally vulnerable in the condition's early stages.

Louis Renoult, a cognitive neuroscientist at the University of East Anglia who was not involved with the research, said the paper demonstrated the strong links between navigation and memory.

The brain areas that help us navigate are also key for episodic memory, which relates to specific events in our lives rather than to factual knowledge, Renoult told Live Science. Episodic memory is also especially vulnerable in the early stages of Alzheimer's.

A better understanding of how navigation is encoded in the brain could reveal measurable signs of dementia's earliest stages, when the ability to navigate begins to falter.

"If you wanted to enhance people's ability to be independent, you'd want them to be able to go to new places and understand new things," Patai said. "In that sense, the link between spatial novelty and memory is really interesting."

In his book "One Hand Clapping: Unraveling the Mystery of the Human Mind" (Prometheus/Swift Press, 2025), New York University neuroscientist Nikolay Kukushkin traces the evolution of human consciousness. He starts the story with the emergence of the first DNA on Earth and then highlights key evolutionary landmarks that paved the way to us — namely, modern-day humans. In the following excerpt, Kukushkin describes the "social brain hypothesis," which posits that human intelligence arose, in part, to help us keep track of our increasingly complex social groups.

What made us human

In the past, many explanations of human uniqueness focused on what gave us the ability to become as intelligent as we are, rather than why we would want to be so intelligent. We often take it for granted that intelligence is what every animal obviously wants, and we just figured out a better evolutionary path toward it. One classic explanation for this involves, for example, walking on two legs, caused by a transition from trees to grasslands, which freed the hands from climbing and allowed us to do more complicated things. Another explanation focuses on our increasingly meat-based diet, which allowed for larger brain sizes. These factors certainly played critical roles in allowing us to become who we are. But they alone don't necessarily explain what is so good about being intelligent in the first place. We just assume that to be self-evident.

I think it's a bit of a self-serving assumption, like jellyfish wondering why no one else has managed to evolve stinging cells. We like to believe that we somehow won evolution — a notion we discussed in chapter 3 when talking about complexity and perfection. We have this image of an ape standing up, picking up a stick, and being rewarded for this achievement with a massive brain.

But the truth is, intelligence comes at a price, and for many species, the benefits just aren't worth it. A brain such as our own takes prodigious amounts of energy away from a body already burning through its fuel: a gram of brain tissue uses ten times the amount of nutrients as an average gram of the human body. Besides, a bigger brain is heavier and easier to damage. So there are considerable evolutionary costs to an enlarged brain. For any given species, these costs eventually outweigh the diminishing returns of brain enlargement. All brains have an evolutionary stage at which they are large enough. If a double-sized brain provided rhinos with a survival advantage, over millions of years their brain would have certainly doubled in size — you have to have very little awareness of evolutionary history to believe that we alone cracked some code that eluded everybody for eons. For rhinos, there wasn't any extra advantage in larger brains, so their brains turned out just as they did. The question is not why humans succeeded where others failed — as we tend to think — but why we needed supercomputers when others were fine with calculators.

There's an interesting pattern that may explain it. If you measure the size of the cerebral cortex — the brain's "machine of understanding"— in different primate species relative to the rest of their brain and plot it against the number of group members typical for each of those species, the two numbers fall on a straight line: the more members, the bigger the cortex. Humans are number one on both accounts — our cortex is the largest relative to the rest of the brain, as is our typical group size, estimated around 150 — that's the number of people in a typical hunter-gatherer society and a typical cap on the number of active social acquaintances that we moderns can maintain. For example, corporate organizations often naturally fragment into units of about 150 people.

Why would that be? This is far from a resolved question, but the proponents of the so-called social brain hypothesis say that reason is that social behavior is a uniquely demanding task, putting unprecedented strain on our brain's capacities. All mammals, to some extent, use their brain as a mirror, understanding others' behavior by modeling it inside their own mind. But primates, whose defensive groups swell into the tens and even hundreds, had to contend with tens and hundreds of these complex, interconnected models of other group members — their personalities, their emotions, their mutual relationships — which one of them did what to whom at what point and so on, a tremendous trove of complex data that we, humans, take to be as natural as eating dinner but that would befuddle even the smartest non-primate. In short, the social brain hypothesis states that social life is what pushed us to become intelligent.

The way this explanation differs from others is by offering an incentive rather than simply means to achieve it: yes, free hands, meat diet, and many other factors made our brain possible, but the reason we needed it in the first place was to remember all our friends who helped us fight monsters.

As cheesy as it sounds, I think about it all the time. There have been many different fables told about the birth of the human species: that it was work that made us human (this was the communist narrative — an ape picking up a tool) or maybe that it was violence (this is the narrative from "2001: A Space Odyssey" — an ape picking up a weapon). Those were not just scientific theories — they were origin stories, as important for a modern mind to make sense of itself as myths were to an ancient mind. An origin story is told to explain what you are really about, and in doing so, it doesn't simply describe the past but provides a template for the present. If you are about work, then work is the pillar on which your life should naturally stand. If you are about violence, then there is no sense trying to avoid it. But the more we learn about ourselves, the clearer it becomes that we are really about others. Our entire essence is to carry tens and even hundreds of peers inside our brains, to navigate the vicissitudes of their emotions and relationships, to derive both meaning and joy from living life together. It has long been recognized, for example, that happiness depends far less on individual well-being than on the richness of social contacts. Social life has a profound effect on us, and not just mentally but physically: for example, the Harvard Study of Adult Development, which began in 1938 and tracked hundreds of people for several decades, famously showed that close relationships are better predictors of long and happy lives than social class, IQ, or even genes. Too often, modern lives let us forget a firmly established fact: friends are worth living for. The social brain hypothesis puts an origin story behind this simple truth.

It also puts the birth of our species in a broader context. Our brains started swelling in size long before the first Homo sapiens. All primates share the relationship between group size and the cerebral cortex, which means that it always took a large brain to handle many peers.

And that, in turn, means that sooner or later, something like a human was inevitable.

When eukaryotes first started extracting energy from other organisms, this set the trajectory toward the human species — eventually there was bound to be someone who could control fire and even nuclear fission. There's something similar that the social brain hypothesis points to, at the deepest level. Once primates were swept in a drive to enlarge their groups and brains, eventually there was bound to be someone with groups large enough and with brains advanced enough to start talking to each other, inventing symbols and abstract categories — and from that, finally, there was bound to arise some form of culture, art, and civilization.

It is this final essence — an abstract, symbolic language passed from person to person by cultural transmission — that completes the design of a human being that we had seen gradually crystallize over billions of years. But to understand why language was so important for our species, we must now take a detour. Most books about human evolution begin right about here and proceed through the past few million years to the present, during which apes gradually evolved into several species of Homo, of which today only one survives — the "wise" one, or sapiens. But our quest instead takes us inward, into the human brain, into the sea of electrical signals pulsing through this astounding machine that runs our conscious minds.

Researchers think they may have found a way to reverse "lazy eye," even in adults who've typically had the condition since childhood.

The technique has so far been tested only in animals, though, so it needs further study before it can be used in human patients.

A lazy eye, or amblyopia, develops when the brain favors one eye over the other in early childhood, causing vision in the less-favored eye to decline. The standard treatment involves placing a patch over the stronger eye to force the brain to rely on the weaker one. However, this method is effective only during infancy and early childhood, when the neural connections that regulate vision are still being formed.

Now, a mouse study published Nov. 25 in the journal Cell Reports introduces a method for temporarily shutting down the weak eye, which can lead to recovery from amblyopia, even after long-term vision issues. "Rebooting" the lazy eye seems to come from a burst of activity in neurons that pass visual signals from the retina to the visual cortex, a hub for processing visual information in the brain.

"The finding that inactivation of the amblyopic eye enables vision recovery in a mouse model of amblyopia is encouraging," said Ben Thompson, a professor and the director of the School of Optometry and Vision Science at the University of Waterloo in Canada, who was not involved in the study.

But more research is needed to see whether the method will be safe and effective in humans, too, Thompson told Live Science in an email.

Dr. Dennis Levi, a professor of optometry and vision science at the University of California, Berkeley who was not involved in the study, was also cautiously optimistic about the findings. Historically, scientists have tried various methods of reversing lazy eye in mice, but they "failed to produce significant improvements in humans with amblyopia," he told Live Science in an email. But this new technique seems to hold promise.

So, how might temporarily shutting down the weak eye help to restore its vision?

Earlier work from MIT neuroscientist Mark Bear and colleagues showed that anesthetizing the non-lazy eye triggered visual recovery in the lazy eye in older animals, including cats and mice. Similar results have been found in monkeys, which may spell good news for humans, Levi noted.

In the new study, the team hypothesized that blocking input from one retina causes neurons to fire in synchronized bursts in the thalamus, a part of the brain that handles incoming sensory information. Specifically, these bursts are seen in the lateral geniculate nucleus (LGN), part of the brain that relays information from the eyes to the visual cortex.

Similar bursts happen in the LGN before birth and help the visual system develop in the womb. That led the team to wonder whether re-creating this early activity pattern could help treat amblyopia.

They tried injecting a local anesthetic called tetrodotoxin (TTX) into the retinas of mice and then monitored the rodents' LGN neurons. TTX is a neurotoxin found in animals like pufferfish, but it also has potential therapeutic uses, including anesthesia and the treatment of severe pain. Research into these uses in humans is ongoing, but in the context of this study, TTX was useful for rebooting the retinas of mice.

The researchers found that shutting down either eye triggered the same burst pattern in the LGN. In a second experiment, they genetically modified the mice so their LGN neurons couldn't produce this burst firing. The activity stopped, and the anesthetic treatment no longer improved amblyopia. That showed that the bursts themselves were crucial for recovery.

Next, the team tested whether they could treat amblyopia by inactivating only the weak eye. They ran an experiment in which some mice with amblyopia got an injection in their weak eye while others did not. The injection stopped the retina from sending signals for about two days.

A week after the injection, the scientists measured how much each eye influenced activity in the visual cortex and found that the treated mice had a much more balanced input from both eyes than the untreated mice did. This showed that shutting down the weak eye for a short time helped it "catch up" with the other eye.

Thompson said this result is encouraging "because the fellow eye does not have to be exposed to any risks of the treatment." But he emphasized that "more work is needed to assess whether tetrodotoxin will be safe and effective in humans."

Previous studies suggest that the effects of TTX on amblyopia generalize to cats and monkeys, raising hope that the approach may one day help humans as well.

The discovery that burst firing can help boost the brain's ability to rewire and form new networks is "extremely interesting," Thompson said. Noninvasive tools used to stimulate the brain might eventually be harnessed to trigger similar neural responses, without the need for TTX injections, he added.

This article is for informational purposes only and is not meant to offer medical advice.

"Consciousness," although challenging to define, can be thought of as a first-person awareness of one's surroundings and oneself. You sense the world through your eyes, nose, ears and hands, and track your internal bodily states via interactions between your cells. These data streams collide to give rise to your personal perception of the world, your place within it, and your motivations for moving through it.

An enduring question about consciousness is how this state of awareness comes about. Is consciousness simply the result of a bunch of chemical reactions? Or is there some extra "secret ingredient"?

In the book "One Hand Clapping: Unraveling the Mystery of the Human Mind" (Prometheus/Swift Press, 2025), New York University neuroscientist Nikolay Kukushkin explores these questions. To do so, he traces the evolutionary history of human consciousness from the formation of Earth's first DNA molecules to present-day Homo sapiens. Kukushkin studies memory in non-brain biological systems, such as human kidney cells, as well as in simple organisms such as sea slugs. He also considers himself a "molecular philosopher."

"I like to think about mental processes, philosophical questions of life and existence from the ground up," Kukushkin told Live Science. Originally published in Russian, a new edition of "One Hand Clapping" has now been released in English. Live Science spoke with Kukushkin about the book and his views on the nature of human consciousness.

Nicoletta Lanese: In this book, what is your working definition of "consciousness"?

Nikolay Kukushkin: It can be defined from the top down, from our personal experience, or you can attempt, as I do, to define it from the ground up.

The top-down description would be consciousness is the first-personness of it all — the fact that to me, experience feels different than looking at someone else's experience, that internally, there is something else than just "facts of life" [meaning biological systems].

I was having this debate with a philosopher colleague [who questioned], "How can the directionality of consciousness arise from the physical facts of the brain being there?" But to me, it's not a problem. Physics is directional — a rock "wants" to fall down. This potential energy is the gravitation of a system towards an energy minimum, and I think everything is that. It's just a level of complexity. A rock gravitates towards an energy minimum; for a rock, it just means falling down. A cell gravitates towards an energy minimum; for the cell, it might mean predicting the environment in some way. You get to a brain, you form these predictive expectations — millions of neurons talking to one another.

I think what puzzles them [proponents of the top-down definition] is the very directionality of a system towards some state, because they think the default is no directionality. I don't think there is such a default. I think physics, the entire universe, is directionality. Time is this unit of one thing leading to another, this unit of causality. So, if everything consists of these grains of causality, then I don't think it's that puzzling that we are driven towards anything, that there is some sort of drive of the system towards a state.

My ground-up definition of consciousness would be this particular form of causality as it plays out in our brain. And the reason why we think of it as "different" is because it's circular. We have this circulation of causality through the networks of our brain. We form predictions that affect how we perceive new data. That affects our predictions; that affects how we perceive new data.

There's this circular motion of causality that makes us constantly reevaluate our beliefs, including our beliefs about what we are and who we are, and what does it all mean and where we're currently present. And that rolling motion is consciousness, in my definition. I guess I challenge the top-down people to say, what else is missing?

NL: You note that this feedback loop helps set humans apart from computers — how so?

NK: The difference is that they [computers] form their perception — we could call it "the model" — before they start inferring. Basically, first they form their "beliefs," and then they start generating predictions based on those beliefs. What we do is we constantly circulate those things. Every prediction, every belief, everything we perceive, affects the model — and then the model feeds back on what we perceive, and it's a constant motion.

I think it's [consciousness is] possible to achieve in an artificial computer, but it requires a different microchip, because we currently have memory and processing separated. That's just the constraint of a silicon chip. If we had a more biologically similar chip that simultaneously memorizes and infers, and that would be constantly generating its own new beliefs — well, that I think is how AI starts really thinking for itself. Because then it can not just act upon what it was trained on, but it can train itself on its own inferences.

NL: In the book, you discuss stages in our primate ancestors' evolution that laid the groundwork for the human brain. What, then, introduced that next level of intelligence, what we think of as "humanness"?

NK: There's a couple of answers to this. First, what we often perceive as this unique humanness that's categorically different is not necessarily such a categorical difference. It's much more of a smooth transition.

There's a general trend that the size of the primate cortex — the "thinking part" of your brain — correlates with the size of the social group. And we humans are number one on both counts. The more friends you have, the bigger your brain has to be, because it's a really uniquely complicated operation to perceive the intentions and the motivations and the emotions of this large group of people. It becomes exponentially more complex as you add more people, because you have to take into account not just what each individual person thinks but then what each individual person thinks about each other.

What I'm describing is basically the "social brain hypothesis," though I would call it a theory. It's an explanation for why we're so smart, and it says that we are so smart because we are social. Traditionally, it was believed to be the other way: We are social because we have such a great brain. But this hypothesis is the other way around. We were forced to become social because of all this collective protection, and that is so complicated to handle for the brain that we had to become smarter, and we have to grow these larger and larger and larger brains. Eventually, you hit the point when you're a human.

NL: Are there other theories?

NK: So far, I've talked about this gradual progression, but there is a second answer. I think there is also something categorically different about humans, and that is language. It's not to say that Homo sapiens is necessarily the only species that has ever spoken any language — there's some debate about that. But I do think there's something categorical about language in this transition between animal communication and human communication.

That's the fact that our language is infinitely generative. There is no equivalent, as far as we know, in the animal kingdom of an infinitely generative system of communication. It's passed from human to human, like this cognitive virus, and there must have been a moment when this passage has become stable — when it took off, essentially. We have this natural tendency to create a language and pass it on.

NL: Do you see that as an extension of humans' theory of mind — being able to acknowledge and understand others' viewpoints?

NK: Absolutely, yes, I would agree with that. I think that the reason why we developed this language is fundamentally social. We wouldn't have developed it if we were solitary creatures.

There's this idea that language and the brain co-evolved together. You have to think of them as flowers and pollinators. It's not that flowers were caused by pollinators or pollinators were caused by the flowers; they both evolved together, mutually reinforcing each other, and I think the same is true for language in the human brain.

NL: You also raise this idea in the book that it was basically inevitable that humans — or some similar organism — would evolve on Earth. Why is that?

NK: When eukaryotes appear [in the history of life on Earth], I think that is this key moment in our history that sets in motion a trajectory that will eventually, like you said, almost predictably lead to the human species.

Why do I believe that? In this moment, what was created is this new type of organism, this "supercell" consisting of both bacteria and archaea that fused together. What this new cell is able to do that nobody else could do before is eat other organisms whole and steal energy away from them. It has a special membrane that it can bend and form vesicles inside, these bubbles in which it can contain its prey. And it has this powerhouse of the cell — mitochondria, the bacteria that entered this archaeal host.

That gives eukaryotes access to unprecedented quantities of energy and sets in motion this evolutionary arms race. They get greedy on this energy; they build up these massive, impressive, energetically expensive cells. But now these cells depend on a constant supply of prey, of somebody to eat. It will perish unless you keep adding more energy, and everybody else around you has the same problem. They need to eat and not be eaten. That sets in motion this evolution of even more complicated cells, of even more convoluted defense or offense, and then teeth and claws and shells.

As you get more complex, you become more vulnerable, too. Bacteria barely care about these mass extinctions; for them, an environmental cataclysm is easy to recover from. But as your organisms become more complex, they become really vulnerable. We started investing into more ways for these organisms to avoid danger, to be self-guided. Maybe to prevent their accidental death, give them a brain to make sure that it can tell where danger is, and so it can avoid that death.

Once you have a brain, well, you can't possibly include everything about that brain into the genetic instructions that you pass from generation to generation. The whole point of a brain is that it needs to learn for itself. Once you create that, this organism starts thinking for itself. It starts acquiring its own motivations that are not prescribed in genes. It starts developing its own thoughts, and that's how you eventually get to us.

We are a culmination of this trajectory. There wasn't anything special about our lineage, our line of evolution, compared to everything else. Eukaryotes compared to bacteria and archaea are special in precisely the same way as humans are special amongst all the creatures around us.

Editor's note: This interview has been lightly edited for length and clarity.

The brain disease chronic traumatic encephalopathy (CTE) has been linked to physical trauma to the head — and it turns out that those head impacts may trigger inflammation and DNA damage that accumulates in brain cells over time, a new study finds.

That DNA damage, which can eventually lead to cell dysfunction and death, resembles the damage seen in the brains of people with Alzheimer's disease, the research suggests.

CTE is a brain disease linked to repetitive head impacts. Football players, soldiers, boxers and others who experience repeated blows to the head are at higher risk of developing CTE than the general population. The disease, which for now can only be definitively diagnosed postmortem, comes with a particular pattern of protein buildup in the brain and neuron death. During life, CTE can cause memory loss, impulsivity, motor problems and mood changes.

The scientists behind the new study decided to dig into the link between DNA damage and CTE after they showed that they found that mature neurons, which don't divide, nonetheless accumulate mutations throughout life. In a 2015 study, the team found that these mutations build up even faster in the context of brain diseases, such as Alzheimer's.

"We used to think neurons had the most stable genomes in the body," said Dr. Christopher Walsh, a geneticist at Boston's Children's Hospital who was a co-author on both that prior study and the new one. "But it turns out, they pick up mutations year after year, and those mutations accelerate in neurodegenerative disease," he told Live Science.

That discovery raised a question: If DNA damage builds up in other brain disorders, could it also be driving the neuron loss seen in CTE?

In the new study, published Oct. 30 in the journal Science, researchers analyzed the genomes of individual neurons sampled from 15 people who had been diagnosed with CTE after death, as well as those from four people with a history of repetitive head impacts but no CTE. The team compared these neurons with cells from healthy brains and with cells from people with Alzheimer's disease. They did this using single-cell whole-genome sequencing, which analyzes all of the DNA in each cell sampled.

The results showed that neurons from CTE brains carried more DNA mutations than those from healthy brains. On average, they carried about 114 additional single-letter changes in the DNA code per neuron. But neurons from people who had repeated head impacts but no CTE showed no increase in mutations, compared with healthy brains.

The pattern of mutations seen in CTE seems to be very similar to what happens in Alzheimer's disease, the researchers observed. Both have an increased number of mutations and similar types of DNA alterations.

In the team's prior study, they "discovered that neurons, which don't replicate, actually accumulate mutations at a steady rate throughout life," Walsh said. "Even in healthy brains, that clock ticks forward about 17 new mutations per year from birth to old age. But in disease, that clock speeds up."

The researchers also identified another kind of genetic damage: short insertions and deletions, known as indels, in which letters are added or subtracted from DNA's code. These tiny DNA breaks were more abundant in neurons from both CTE and Alzheimer's brains than in healthy ones. In some of the CTE cases, neurons contained more than a thousand indels — equivalent to what might be seen in more than a century of normal aging.

"These indels have increased," Walsh said. "They're probably numerous enough to cause serious dysfunction or death in the affected cells."

Although the study did not directly test for inflammation in the neurons, earlier work by study co-authors Dr. Ann McKee, a neuropathologist at Boston University (BU) CTE Center, and John Cherry, a neuroscientist at BU, has shown that inflammation is widespread activation of microglia — the brain's immune cells — in CTE brains.

"We think CTE might be a combination of repeated head trauma and inflammation," Walsh said. "That combination may bombard the genome with the same kinds of damaging processes that ultraviolet light causes in skin or tobacco smoke in the lungs," as both UV and tobacco exposure trigger DNA damage.

In summary, repeated head impacts may trigger inflammation in the brain, which can promote the accumulation of DNA mutations in neurons and contribute to cell dysfunction and death. These findings suggest that while head trauma remains a key trigger of CTE, the long-term harm is likely driven by inflammation-driven DNA damage.

The team is now investigating whether similar processes happen in other neurodegenerative diseases, such as amyotrophic lateral sclerosis (ALS) and Huntington's disease.

"This could be a common final pathway across diseases," Walsh said. "We'd like to trace the biochemical steps from inflammation to neuron death and figure out where we can intervene."

Exercise has big benefits for the brain, but the exact reasons why have been mysterious. Now, new studies suggest that exercised muscles release brain-boosting substances into the blood — and at least in lab animals, that boost can be transferred from one individual to another via an injection of those substances.

Previously, common explanations for why regular physical activity is good for the brain pointed to better blood flow, less stress and a stronger heart. But those ideas didn't fully explain how movement directly affected neurons.

Clues are emerging from animal research. In a study published in October in the journal Brain Research, one group of young adult mice ran freely on wheels for four weeks while others stayed sedentary. Scientists then isolated extracellular vesicles — molecular "packages" that carry proteins and genetic material — from the runners' blood and injected them into the sedentary mice.

After getting these injections twice a week for four weeks, these treated sedentary mice grew about 50% more new brain cells in a memory-related region called the hippocampus, compared with untreated sedentary mice. Most of the new cells developed into mature neurons, a process known as neurogenesis. (For humans, there's ongoing debate around whether neurogenesis occurs in meaningful amounts in the adult brain.)

First study author Meghan Connolly, a postdoctoral researcher at the University of Alberta, told Live Science in an email that she was struck by how specific the effect was — vesicles isolated from running mice boosted neuron growth, while those from sedentary animals did not. The researchers don't yet know whether the vesicles entered the brain or acted indirectly through other bodily signals. But Connolly explained that the vesicles themselves carried many proteins linked to antioxidant defenses and neurogenesis.

Notably, this surge in new brain cells may matter only if those cells survive long enough to fully integrate into the brain's existing structure, said Paul Lucassen, a neuroscientist at the University of Amsterdam who was not part of the study. The study zoomed in on "newborn neurons that still need weeks to grow and wire themselves into the brain's existing circuits," he told Live Science in an email. "Only when they find their place in the network can they help shape learning and memory."

Connolly said the next step is to test whether these vesicles can restore neurogenesis and improve memory in laboratory models of brain diseases — avenues that some researchers are already exploring.

In another study, published earlier this year in the journal iScience, scientists used a well-established mouse model of Alzheimer's disease (AD). In AD, neurons malfunction and die off over time in part due to a buildup of abnormal proteins, including amyloid and tau. In the experiment, one set of mice ran voluntarily on wheels for six months while another group was sedentary; the active mice showed less amyloid buildup in the cortex and better metabolism and memory than their counterparts.

In another part of that study, the researchers gave vesicles from mice that had just exercised to sedentary Alzheimer's-model animals. The vesicles, delivered through the nose, reproduced the metabolic benefits but didn't improve memory or clearly reduce amyloid levels, they found.

Mark Febbraio, a professor at Monash University and a member of the research team, explained that the intranasal delivery method may have affected memory outcomes because it requires light anesthesia. He told Live Science in an email that his group is now running follow-up experiments with human participants, comparing vesicles heading to and from the brain during exercise. Preliminary results hint that the vesicles heading toward the brain may be enriched for proteins affecting cognition.

But vesicles may be only one piece of this puzzle. Other recent studies in humans suggest that regular exercise likely helps the brain via multiple biological pathways. As Joram Mul, an exercise neurobiologist at the University of Amsterdam, put it, exercise stirs the entire body — muscles, nerves, and even gut microbes — into motion.

"It's a whole-body effect," Mul said, "not a single factor explaining all, but a symphony of multiple factors and processes," playing in perfect harmony.

Brain quiz: Test your knowledge of the most complex organ in the body

Can we change bad memories? In this adapted excerpt from "How to Change a Memory" (Princeton University Press, 2025), author and neuroscientist Steve Ramirez recounts the events that led him and his colleagues to discover memories could be artificially controlled in rodents, by tapping directly into the brain.

Feelings like anxiety are hard to understand because they're often invisible to everyone else. But they're part of everyday life. We all regularly experience bouts of stress and anxiety. What if the job interviewer doesn't like me? Should I cram tonight for my exam tomorrow? What should I say on my first date?

Our biology often forces us to be prepared for multiple outcomes in the midst of uncertainty. It's healthy to care about these multiple outcomes because it encourages us to put in the work, to adequately prep for a given stressful event. And yet, sometimes the scales of stress become tilted to such an extreme that pathologies of the brain begin to emerge.

The tremendous variation in how any individual arrives at a state of anxiety, for example, highlights that our brain contains many winding roads that can ultimately converge on the same feeling. We all have our triggers in life, but what those triggers are depends on experience — on memory. When these differences impair our mood, thinking, behavior and overall daily functioning, then they get lumped into a category. What's more, if observed impairments share similar features, then this category itself falls within a broader classification — that of a mental disorder.

As I was entering my last year of graduate school, I was just beginning to understand how omnipresent an anxious feeling can truly be. Just as my own stressors in life began accumulating — finishing my thesis, writing grants and job applications, continuing the seemingly never-ending search for purpose as a scientist and person — my mom too had a sudden resurgence of anxious moments that ultimately culminated in frequent panic attacks. Once I learned about her lifelong experience with the erratic thing that anxiety was for her, I started to appreciate the on-again, off-again and on-again nature of these feelings. I couldn’t stop thinking about her panic attacks and how frustrating it was to not be able to press "off" on some of the most debilitating moments one can endure.

My last project in graduate school would attempt to artificially activate positive memories to suppress the symptoms associated with anxiety and depression. It would be my most personal scientific endeavor, a very direct way for me to join the fight at my mom's side and to thank her for being my superhero. If my research could somehow inspire new therapeutic strategies that might be useful for alleviating these kinds of debilitating conditions, then my work will have gained an even deeper, more personally meaningful purpose.

My lab partner Xu Liu and I wanted to take a brain-centric approach to our newest project. Could memory itself be artificially controlled in rodents, by tapping directly into the brain to restore neuronal and behavioral balance in a therapeutic name?

Luckily, our project had a scientific precedent in humans — in an influential paper by psychologist Barbara Fredrickson and colleagues called "The undoing effect of positive emotions." This study highlighted the capacity of positive emotions to undo the physiological effects that negative emotions have on the brain and body.

The undoing hypothesis proposes that positive emotions can be used for more than just feeling good. They can be used to help us get out of bed in the morning; pursue happiness; change how we think about and interact with ourselves and others; and counteract, or at least regulate, negative emotions. When human subjects were stressed and then watched movie clips that elicited contentment and amusement, their bodies rebounded in beneficial ways: their stress-induced increases in cardiovascular activity, for instance, returned to baseline faster than when they watched neutral or sad movie clips. Excitingly, this reveals a very real physical connection between feelings of positivity and their direct effects on our biology.

Xu and I wanted to further this work by testing for a potential therapeutic capacity of positive memories by jump-starting their biology from within the brain. We placed our animals in a box that had two small valves on separate ends: one that delivered sugar water when the animals licked it and another that delivered regular water. This is known as the sucrose preference test. Rodents normally prefer sugar water over regular water, the same way humans will typically find sugary liquids preferable to a bland liquid. On the other hand, rodents with depression-and anxiety-related behaviors tend to show a 50:50 preference. They show no preference at all.

As expected, the animals displaying anxiety-and depression-related behavior licked at each of the valves randomly over the course of 15 minutes. As with Project X — our first successful attempt at MIT to artificially control memories in the rodent brain — all we had to do was hit a button that would turn our lasers on and optogenetically awaken a memory from within.

Click.

The deep-blue laser flickered throughout the mouse’s hippocampus, waking up — activating — cells that held onto a positive memory. I remember thinking that our optogenetic stimulation was a fancy, high-tech Proustian madeleine, one capable of triggering the rich remembrance of things past. If you'll entertain my romanticization of the moment: the mouse perked up immediately, as if a shudder ran from its brain to its body, and it began scanning the environment to decide which valve to visit first.

An extraordinary thing was happening. I imagine that the mouse felt the memory invade all its senses, strangely detached and with no suggestion of an origin, since the essence of these sensations was in the mouse as much as it was the mouse. And once the positive memory fully revealed itself within seconds, the now-motivated mouse inspected each valve with some sniffing, followed by a taste test.

When it found the valve with the sugar water, the mouse started licking vigorously, so much so that it consumed as much sugar water as our control animals. In under an hour, Xu and I saw that reactivating positive memories restored our mice's behavior to a healthy baseline. Just as exciting, reactivating positive memories also turned on many areas of the brain involved in rewarding experiences and motivation.

The key to reversing abnormal behavior was embedded within their positive memories all along. For as long as the laser was shining its sapphire radiance in their brains, the mice were motivated to keep consuming their sugar water reward. All this from stimulating cells in the hippocampus. Or to say this with less novelistic flare: the mice got a sugary treat.

In the following weeks, one of my gifted undergraduates Briana Chen collected a large empirical dataset for the project, and it came with an exciting plot twist: when she artificially reactivated positive memories twice a day, or "chronically," for about a week, not only did this permanently ameliorate symptoms we believed were associated with depression and anxiety, but it also promoted the growth of new cells in the brain. Positive memories had both short- and long-term benefits, all the way from cells to behavior.

Inspired by the neuro-centric Research Domain Criteria (RDoC) approach to treating the brain, our hope was that the biological potency of positive memories — like medications — could inform cognitive-behavioral approaches to treating disorders of the brain. This project was meaningful to me on a personal level: I thought of my mom's panic attacks and the idea that she might never have to experience the kind of crippling anxiety that robs someone of peace.

Positive memories are some of the most powerful biological tools available in our brains. At home, my mom and I shared a treasure trove of them — one that we both remember is from the time when I was a teenager, and we were visiting her parents in El Salvador.

One morning, my cousins, parents and grandparents all walked down a hill behind the house my mom grew up in to go swimming in the village pond. My cousins kept egging me on to jump from a cliff into the pond, and my mom kept telling me I didn't have to.

Like her, I was the opposite of an adrenaline-seeker because, oh I don't know, maybe my innate biology was onto something, as "please do not free-fall to Earth" kept repeating in my mind. She could see that I was scared, and after a few minutes she suggested, much to my surprise, that we jump together. We held hands and tiptoed to the edge — uno, dos, tres — we were in the air! Moments later, we emerged from the water laughing in delightful disbelief at our newfound courage.

Neuroscience tells us that this memory has all the ingredients of life's dessert that make us feel good. From an RDoC perspective, my cognitive and valence systems are all interacting to produce the riches from this experience: the cognitive system enables the memory of jumping off of a cliff, which at first generated feelings of fear via the negative valence systems, which are now almost immediately counteracted by feelings of reward via the positive valence systems.

What was once a moment of fear is now a memory of triumph with my mom. It's the only time I can remember when we both took a literal leap of faith, so we cherish the memory as an example of what our brains can achieve together. A million little life moments like these, packaged neatly into a million memories that we hold onto constitute the good stuff in life.

Adapted from "How To Change a Memory: One Neuroscientist's Quest To Alter The Past". Copyright © 2025 by Steve Ramirez. Reprinted by permission of Princeton University Press.

Bowerbirds create stages that make them look bigger to potential partners. Fish and butterflies can flash what looks like a large, staring eye to intimidate predators or deflect attacks. Male peacock spiders raise their legs as part of a courtship ritual to make them seem much larger than they actually are.

These are just some of the strategies that help these animals survive and reproduce. They raise a fascinating question: Are animals fooled by optical illusions?

Researchers are finding that many of them do experience these perceptual quirks, though not always in the same way. "Illusions show that animals, as well as humans, can misinterpret visual information," Jennifer Kelley, an evolutionary biologist at the University of Western Australia, told Live Science in an email. "Information processing is expensive and costly, and since there is a limit on how much information can be obtained, brains take shortcuts."

Optical illusions are an important scientific tool because they reveal these shortcuts that brains use to turn raw sensory input into perceptions of reality. When something unexpected happens, scientists gain deeper insight into the rules that govern perception. If nonhuman animals are the subjects of these illusions, scientists can start to better understand how evolution has crafted similar rules to improve survival and aid reproduction.

"Many animals use visual strategies such as size exaggeration or camouflage because perception is not about reproducing reality faithfully, but about survival," Maria Santacà, a researcher into animal behavior and cognition at the University of Vienna, told Live Science in an email.

Size illusions are perhaps the best-known visual tricks. Humans fall for them all the time. A classic of the genre is the Ebbinghaus illusion, which shows how one circle surrounded by smaller circles looks a lot larger than the same circle surrounded by bigger circles.

Guppies fall for this illusion, too. Santacà was lead author on a 2025 study, which demonstrated that when a circle of food flakes was surrounded by smaller disks, the fish chose them more often, as if there were genuinely more food in the circle. Contrastingly, ring doves, when tested with the same setup using millet seeds, didn't consistently fall for the illusion.

The likely explanation lies in the two species' respective ecosystems, Santacà said. "Guppies live in dynamic underwater habitats with variable light and complex backgrounds, so their visual system emphasizes global processing, integrating the whole scene. Doves, by contrast, feed on small seeds against textured ground surfaces, which requires precise local discrimination. Their perception could therefore be optimized for detail rather than context, making them less prone to this particular illusion."

Context matters

It turns out that who an animal hangs around with can amplify these illusions. Female fiddler crabs prefer males with large claws, but attractiveness is relative. A male flanked by two smaller-clawed rivals is more attractive to a female than the same male surrounded by bigger neighbors. This context effect mirrors the Ebbinghaus illusion and suggests that males can boost their perceived appeal simply by courting near less-imposing neighbors.

"These strategies exploit the way visual systems interpret context, helping animals appear larger to rivals, smaller to predators." Santancà argued. "In nature, what matters is not to be seen accurately, but to be perceived in the most advantageous way."

Not all species follow the same script: Pigeons are subject to the Ebbinghaus effect, but in reverse, while baboons are completely unaffected by the illusion. Kelley argued that "this suggests that brains are wired differently across species, which is not surprising due to variations in physiology and because the information that is most relevant may differ among species."

Not only do animals perceive illusions, but some are masters of creating these tricks. "Males may not only use features of their body to appear large (and therefore more attractive) but may utilise and/or modify their physical or social environment to alter the female’s perception of size," Kelley said.

Male great bowerbirds, for instance, arrange pebbles from small to large along the floor of their bower (an area they build to impress females as part of a courtship ritual) to create a forced perspective illusion, a 2010 study found. Objects that are farther away should take up less room in the field of vision than closer objects of the same size do. From the female's perspective, the fact that this isn't true makes the bower look shorter and thus the male appear larger.

Others are tricked by illusions about their own bodies. Octopuses can be fooled by a version of the "rubber hand illusion," a trick long thought to be unique to humans. In experiments, researchers stroked a real octopus arm hidden from view and a visible fake octopus arm at the same time. When the fake arm was pinched, the octopus reacted as if its own arm had been attacked — changing color or pulling back. A similar experiment found that mice were also duped by this illusion. The fact that octopus and rodent nervous systems evolved completely separately from ours makes it all the more surprising that they should also be subject to the illusion.

Camouflage as illusion

Camouflage offers another example. Disruptive coloration uses high-contrast patches toward the edges of prey bodies to create false boundaries that confuse predators' edge-detection systems. Countershading — which is common in fish, reptiles and mammals — grades color from dark on top to light below. Because the sun comes from above, light bellies are thought to make prey harder to spot from below. Similarly, a 2013 study found that dark prey backs are thought to blend in better with darker ground or the depths of the ocean, which confuses predators that are hunting from above.

"Countershading is probably so widespread because it solves a very fundamental problem — how to avoid being detected by predators when directional light produces regions of brightness/darkness across the body," Kelley said.

In the same way the surroundings can distort size in the Ebbinghaus illusion, context also warps brightness and color. A gray patch looks darker against a pale background — a phenomenon called simultaneous brightness contrast. Similar effects occur for color. Insects, fish and birds all show these biases, which suggests a common mechanism for processing contrasting colors and shades. The illusion might be useful to courting males to help make themselves look brighter or for animals that change color to stand out from the background.

Illusions demonstrate that perception is not about perfect accuracy; it is about what works in a given environment. As Kelley told Live Science: "It’s always ultimately about survival and reproduction!"

For guppies, integrating context may help gauge rivals or mates in a flickering stream. For doves, precision trumps context when pecking seeds. When animals themselves deploy illusions, they exploit these neural shortcuts as survival strategies. The gap between reality and perception is a rich space for evolution to do some of its most creative work.

Brain inflammation may be fueled by a gene on the X chromosome, a new study in mice suggests.

And in female mice, who carry two X chromosomes, a diabetes drug called metformin may work to counteract that inflammation.

If these findings bear out in later studies, they could help to unravel the long-standing mystery of why women, who have two copies of this inflammation-driving gene, are more prone to certain autoimmune diseases, particularly after menopause.

A disparity between the sexes

Our bodies are patrolled by immune cells that provide protection against bacteria and viruses, but sometimes, these defenses turn on us. In the autoimmune disorder multiple sclerosis (MS), for instance, the immune system attacks myelin, the fatty insulation surrounding the nerve fibers in the brain and spinal cord. This leads to symptoms such as muscle weakness and difficulty walking, as well issues with memory and thinking.

The disease is two to three times more common in women than in men, and symptoms often become more debilitating after menopause. But until recently, scientists didn't know why.

Dr. Rhonda Voskuhl, a neurologist and neuroscientist at UCLA, has been investigating that mystery for decades. Clinical patterns showing higher disease rates in women are "a really valuable clue" that the difference may be driven by an X-linked gene, Voskuhl told Live Science.

That's because women typically inherit an X chromosome from each parent, while men inherit only one from their mothers. Normally, one set of X-linked genes in women is silenced, leaving only one active gene from either the mother or the father. But a handful of genes escape this "X inactivation," Voskuhl told Live Science, giving women an enhanced dose of X-linked gene activity.

To see if X-linked genes might explain women's higher rates of MS, Voskuhl and her colleagues looked at existing data for human microglia, the primary immune cells in the brain. They looked at cells from both men and women with MS.

Compared with those from men, women’s microglia had higher levels of a protein called KDM6A, which is encoded by the KDM6A gene on the X chromosome. Women's cells also showed higher levels of immune-related gene activity.

To investigate the role of KDM6A gene in the brain, Voskuhl and colleagues used techniques to "knock out" the activity of the gene in lab mice — specifically in the rodents' microglia. Then, they induced an MS-like condition in the mice using established methods.

Female knockout mice walked better, and their brain tissue had less nerve damage and more intact, myelin-covered nerve fibers compared with female mice with a functional KDM6A gene. Knockout female mice also showed less infiltration by immune cells, called T cells, compared with female mice with working KDM6A genes.

But deleting the KDM6A gene had no effect in male mice, the researchers reported in the new study, published Oct. 15 in the journal Science Translational Medicine. The finding hints that the KDM6A gene may fuel brain inflammation in females because they have two copies of it and one copy "escapes" silencing. Thus, females may get an increased dose of the KDM6A protein.

The researchers then looked for a drug that could mimic the effects of deleting KDM6A. Earlier studies had shown that metformin can block the KDM6A enzyme in other cell types, so Voskuhl wondered whether it would have the same effect in microglia. Her team found that metformin calmed brain inflammation and improved symptoms in female mice while having little effect in male mice.

This points to the potential for sex-specific treatments, given that both KDM6A activity and metformin's effects differ between men and women. If such a treatment were only tested in men or in a mixed pool of study participants, its effectiveness in women may not be noticeable, Voskuhl explained; so data from women would need to be gathered and analyzed in isolation.

"It's a brilliant study," said Dr. Lawrence Steinman, a neurologist at Stanford University who was not involved in the new work, because it identifies one of the key genes that make women more susceptible to MS. It's "another step forward" in understanding how KDM6A shapes immune activity in the brain and keeps microglia "on the quiet side," Steinman told Live Science.

Follow-up studies and clinical trials are still needed to pinpoint the most clinically effective ways to block KDM6A in women's microglia, and to confirm that such a drug would be therapeutically beneficial.

These findings also hint at an interplay between hormones and chromosome-linked inflammation. Past work has shown that estrogen generally counteracts the inflammation in the body, helping balance immune activity that defends the female brain against pathogens and excess inflammation during the reproductive years, Voskuhl said.

"So when estrogen levels go down in menopause," she said, "you lose that protection."

This article is for informational purposes only and is not meant to offer medical advice.

Brain quiz: Test your knowledge of the most complex organ in the body

Scientists may be closer to understanding why time seems to pass more quickly as we age — and brain scans of people watching an old Alfred Hitchcock show helped them address this enduring question.

In a study published Sept. 30 in the journal Communications Biology, scientists pulled data from the Cambridge Centre for Ageing and Neuroscience (Cam-CAN), a long-term brain-aging research project. In total, 577 people had previously watched an excerpt from the old television series "Alfred Hitchcock Presents" — specifically, eight minutes of an episode called "Bang! You're Dead." As the study participants watched the clip, functional MRI (fMRI) scans were recorded; these scans would provide a measure of how the participants' brain activity changed over time.

This particular clip was chosen because previous research showed that, compared with other video clips, it elicits the most synchronous patterns of brain activity in a wide variety of viewers. That makes it ideal for studying how the brain divides and tracks unfolding events.

At the time the brain scans were taken, the participants were between 18 and 88 years old. The researchers got access to these existing fMRI recordings and used the so-called Greedy State Boundary Search (GSBS) to analyze them.

As the name suggests, this computer algorithm detects transitions between stable patterns of brain activity. It does so "greedily" — that is, it identifies these shifts moment by moment, without taking into account the overall structure of the narrative on a longer time scale.

During the eight-minute clip, the brains of older participants shifted to new activity states less frequently, and those brain states lasted longer for them than they did for younger participants. This pattern was consistent across the full age range of 18 to 88 years.

"This suggests that longer [and, therefore, fewer] neural states within the same period may contribute to older adults experiencing time as passing more quickly," the researchers wrote in their report. This aligns with an idea of time that dates back to Aristotle: The more notable events occur in a given time period, the longer it subjectively seems. The new results raise the possibility that if older adults' brains are logging fewer "events" in a given time frame, maybe that's why time seems to fly by.

Although this is only a hypothesis so far, "the idea that this may affect perception and memory in everyday life, including the feeling that subjective time seems to pass faster with age, looks very plausible to me," said Giorgio Vallortigara, a neuroscientist at the University of Trento in Italy who wasn't involved in the new study.

The authors attributed their observations that older adults show fewer transitions between neural states to a phenomenon known as age-related neural dedifferentiation. In this process, the activity of different areas of the brain becomes less specific with age. For example, in young people, groups of neurons in face-selective regions respond more selectively to faces as a category, but in older people, these neuron groups light up more often for objects that aren't faces. This generalization — at the level of broader groups of neurons rather than individual neurons — may be true for the brain as a whole and may make it harder to recognize where one event ends and another begins, the study authors proposed.

However, neural dedifferentiation may not wholly explain why time flies when you're older.

Joanna Szadura, a linguist at Maria Curie-Skłodowska University in Poland, studies how language shapes our perception of time. She told Live Science that the scientists' hypothesis is well-founded but added that we must also take into account that each of us has two time scales.

Society divides time linearly into hours, days and years, while our internal scale follows logarithmic laws. For example, a year is 20% of a 5-year-old's life so far but only 2% of a 50-year-old's. Therefore, the perception of time depends on not only the number of neural "events" in the brain but also the internal nonlinear way in which we measure time.

The researchers noted that older adults may still be able to make time feel subjectively fuller.

"Learning new things, traveling, and engaging in novel activities may help make time feel more expansive in retrospect," study co-author Linda Geerligs, a researcher at Radboud University in the Netherlands, told Live Science in an email. "Maybe even more important though, are meaningful social interactions and activities that bring joy, which can also contribute to a fuller sense of time."

Brain quiz: Test your knowledge of the most complex organ in the body

When you wake up in the morning, it might feel like your brain just switched on at the ring of an alarm, although you still might feel groggy for a while. But the actual process the brain goes through to wake up is a gradual, coordinated event. So exactly how does it happen?

First, let's define what it means to be awake. "Being awake means the brain is in a state that supports awareness, movement and thinking," Rachel Rowe, a professor of integrative physiology at the University of Colorado Boulder, told Live Science in an email. "Unlike sleep, where brain waves are slow and synchronized, wakefulness is marked by faster, more flexible activity that lets us respond to the world around us."

There isn't a single moment when the brain flips from asleep to awake, however, said Aurélie Stephan, a sleep researcher at the University of Lausanne in Switzerland. Research has shown that the subcortical regions of the brain — a group of neural formations located below the cerebral cortex — are responsible for waking us up. The reticular activating system (RAS) first acts like the "starter switch," Rowe explained, sending signals to activate the thalamus, a structure that relays sensory information to other parts of the brain, and then the cerebral cortex, the wrinkled outer layer of the brain.

In a 2025 study, Stephan and her colleagues also found that the brain executes a signature pattern of activity upon waking. When the study participants woke up from non-REM sleep, which comprises different stages of sleep ranging from light to deep sleep — their brain activity first showed a short burst in slower, sleep-like waves, followed by faster waves linked to wakefulness.

When they woke up from REM sleep — a sleep stage characterized by vivid dreams and rapid eye movements — their brain waves went straight to faster activity. Overall, regardless of which stage of sleep participants were in, their brain activity appeared to start from the front and central regions of the brain and move to the back of the brain as they woke up, the researchers found.

Why we feel so groggy in the morning

Once we're awake, our brains still need time to reach their full cognitive capacity. This period, called sleep inertia, can last anywhere from 15 to 30 minutes — sometimes even an hour, Stephan said. Researchers don't know why this morning grogginess happens, but the time we wake up can play an important role in how we feel. And ditching the alarm clock could help.

"When your brain [naturally] wakes up, it will send a signal in a moment that makes sense" to end your slumber, Stephan explained. There are many regions taking internal and external signals into account that are discussing with each other when to transition to different stages of sleep and also, ultimately, when to wake you up spontaneously, she explained.

Our arousal system is listening for these internal and external inputs and creating cycles in which we're more alert about every 50 seconds. Our level of alertness fluctuates within those 50 second periods, growing and diminishing over and over.

"During the buildup phase … it is harder to be woken up," Stephan said. But when the cycle wanes, "our sleep is more fragile and it is easier to wake up," she said. "So basically within this 50 seconds period we have a period of sleep continuity and a period of sleep fragility."

That's why Stephan advises her friends to always wake up at the same time, without the help of an alarm.

"Your brain will wait for the right 50-second moment, and you'll feel less sleepy upon awakening," she said. "If you have an alarm clock, it's kind of random. It could wake you up in the worst moment ever, and then you will have a strong sleep inertia."

Still, much of what we know about waking up remains a mystery. Scientists still aren't sure why the same amount of sleep feels refreshing one day but not the next. Some research has suggested that diet and length of sleep can impact morning alertness, or how the brain switches from awake to asleep.

"What pushes our brain to wake up spontaneously actually remains an open question," Stephan said.

Sleep quiz: How much do you know about sleep and dreams?

The patient: A 31-year-old woman

The symptoms: The woman visited a clinic because she had long experienced bursts of uncontrollable laughter, which doctors described as "mirthless" in a report of her case. According to the patient, she had been having these intermittent bursts of involuntary laughter since infancy, but her condition had never been formally investigated or diagnosed.

She said that before each episode started, she would experience a "feeling of dread" in her neck and chest. During the involuntary laughing incidents, she could not speak or swallow, and she had difficulty breathing. Each outburst lasted a few seconds and typically occurred about once per day, usually shortly after the woman awoke in the morning.

The woman noted that, when she was a child, each episode would last several minutes and occurred more frequently — about six or seven times a day, and sometimes while she was asleep. Her parents did not recognize the laughter as being beyond her control. Rather, they thought her laughing was deliberate and would ask her to stop, the patient reported. As she grew older, the bouts of laughter became shorter and happened less frequently.

What happened next: Prior to the patient's visit to the clinic, MRI and electroencephalography (EEG) of her brain showed no abnormalities. However, when the clinicians examined videos of her laughing episodes, they noted that they closely resembled gelastic seizures. This type of seizure commonly triggers uncontrolled laughing, giggling or smirking, but it can also cause grunting, mumbling or lip smacking. It is named after the Greek word for laughter ("gelastikos").

Gelastic seizures are typically focal, meaning they're caused by abnormal electrical activity in one specific part of the brain. On a second MRI, doctors discovered an area of abnormality in the hypothalamus, a key structure for maintaining homeostasis. The abnormality measured about 0.2 inches (5 millimeters) wide.

The diagnosis: They identified the lesion as a hypothalamic hamartoma, a noncancerous lesion that occurs during fetal development. Gelastic seizures that provoke bursts of involuntary laughter, during which the individual is aware of their actions but can't control them, are a hallmark of this lesion. The exact reason these lesions trigger giggling fits isn't fully understood.

The treatment: The patient had previously taken trial doses of the anti-seizure drugs levetiracetam and lamotrigine, which are used to treat epilepsy, with no effect. Because her episodes were not severe, the woman decided that she did not want medication.

She was not experiencing any other behavioral or cognitive issues and the attacks had declined in severity and frequency over time, so the doctors at the clinic determined that no additional treatment was required.

What makes the case unique: Hypothalamic hamartomas are rare, but when they do occur, they are typically accompanied by cognitive and behavioral impairment. In children, the growths can cause developmental delays or trigger the early onset of puberty, because the hypothalamus helps regulate hormones. Patients that have gelastic seizures triggered by these lesions often develop more severe forms of epilepsy and experience other types of seizures down the line.

The woman's case is highly unusual because her symptoms naturally declined to a manageable level. This benign outcome of epilepsy associated with hypothalamic hamartomas, "to our knowledge, has not been previously reported," the doctors wrote.

For more intriguing medical cases, check out our Diagnostic Dilemma archives.

This article is for informational purposes only and is not meant to offer medical advice.

Using a ChatGPT-like AI model, scientists have created a new map of the mouse brain that captures previously uncharted areas of the organ in unprecedented detail.

The map, published Tuesday (Oct. 7) in the journal Nature Communications, captures 1,300 regions of the brain and is the first to detail brain regions without requiring manual input from humans. The study authors, from the University of California, San Francisco (UCSF) and the Allen Institute for Cell Science, hope that the project will enable researchers to sketch such tissue maps across the entire body.

Advances in genomics have produced a vast amount of information about the cells across the nervous system, revealing the cells' identities and functions. One technique that has produced this data deluge is spatial transcriptomics, which reveals how cells use genetic information to produce proteins, thereby connecting the information in the genome with the body's functions.

The approach also shows the positions of individual cells in the space within tissues. This information has informed previous cell atlases of the mouse brain. However, arranging the information from such experiments into a comprehensive brain map poses a significant challenge. For previous maps of the brain, researchers had to manually annotate each piece of the map to demarcate specific areas of the brain and where the recorded cells fit within them. The new study sidestepped this laborious task.

The spatial transcriptomics data used for the new map included information on the activity of 500 to 1,000 genes in each analyzed cell. At this level of complexity, the data analysis is challenging, said study co-author Reza Abbasi-Asl, a professor of neurology and bioengineering at UCSF. Moreover, marking brain regions using the raw spatial transcriptomics data — a process called parcellation — produces fuzzy maps, Abbasi-Asl said.

That's where the team's AI-based approach paid off.

Large language models (LLMs), such as ChatGPT, have captivated and excited millions of users with their ability to generate text output from prompts. At their core, these systems work by mathematically predicting the relationships between individual words. Abbasi-Asl, alongside his doctoral student Alex Lee, created the AI system, named CellTransformer, which instead analyzes how individual cells sit next to each other in the brain based on spatial transcriptomics information.

The AI system transforms the spatial data, enhancing it with new information. "We build a missing piece between spatial transcriptomics data and parcellation of the brain that connects the two," Abbasi-Asl told Live Science. The new dataset generated by CellTransformer produces much sharper maps that are more similar to known brain regions than manual annotation could, according to Abbasi-Asl, and also identifies previously uncataloged, finer-grained regions.

The new map covers approximately 1,300 sections of the mouse brain, resulting in a total dataset of over 9 million cells. The team coordinated their data with the Allen Institute’s Common Coordinate Framework (CCF), a high-resolution map of the mouse brain previously constructed using manual annotation. There was strong coherence between the AI-generated output and the gold-standard CCF, which gave the team confidence that their findings were highly accurate.

CellTransformer successfully mapped known brain regions, such as the hippocampus, a key memory center. The tool also charted brain areas that other mapping efforts had struggled to obtain data on, such as the midbrain reticular nucleus, (CK)which is located in the topmost part of the brainstem and processes sensory and motor information, while also regulating sleep.

The data processing behind CellTransformer doesn't work only for brain tissue, the authors emphasized.

"A similar pipeline could be used with data sets that are now emerging from the heart, from other body parts, and also from tissues that are collected in disease models as opposed to healthy models," Abbasi-Asl said.

The team also wants to test CellTransformer on human brain data — but while the mouse brain contains tens of millions of cells, our brains have around 170 billion cells, including 86 billion neurons. The human brain's sheer size, as well as its more complex structure, will make it harder to provide a sufficient amount of spatial data to feed the AI.

If such data can be brought to CellTransformer, Abbasi-Asl reckons the tools could process it, though. "We do believe that it could work on human data too," he said. "That's another really important next step."

Until Homo floresiensis was discovered, scientists assumed that the evolution of the human lineage was defined by bigger and bigger brains. Via a process called encephalization, human brains evolved to be relatively more massive than would be expected based on corresponding body size.

This proportionally bigger brain is what anthropologists argued enabled us and our relatives to perform more complex tasks such as using fire, forging and wielding tools, making art and domesticating animals.

But these theories had to be thrown out the window when archaeologists announced our fossil cousins Homo floresiensis via scientific publication in 2004. Homo floresiensis lived from about 700,000 to 60,000 years ago in the rainforests of Indonesia, partially contemporaneous with our own species.

Aptly nicknamed Hobbits, Homo floresiensis were short-statured, at just over 3 feet (1 meter) tall, and had a chimp-size brain. This discovery upended the assumption that brains have been increasing in size over the past several million years and generated confusion about what separates recent human relatives in our genus Homo from our more ancient ancestors.

Our new research on the skulls and teeth provides a novel theory for how the Hobbits evolved to be small.

We are professors of anthropology at Western Washington University. After attending a 2023 workshop for biological anthropologists studying juveniles in the fossil record, we began looking at brain size changes across human evolution.

Related: Archaic human 'hobbits' were even shorter than we thought, 700,000-year-old teeth and bone reveal

Our previous work on the proportions of molar teeth generated new insights into the evolution of pregnancy by demonstrating that fetal growth rates are tightly linked to molar proportions in primates. Now, we wanted to see whether we could uncover a relationship between tooth proportions and brain size among our fossil relatives.

Paleontologists have only limited skeletal materials, sometimes only a few teeth, for many fossil species, including Homo floresiensis. If tooth proportions can provide information about fossil brain size, it opens up a world of possibilities for assessing past changes in encephalization.

Reconstructing brain size using teeth

We collated data on tooth and brain size for 15 fossil species on the human family tree, spanning about 5 million years of evolution. Somewhat oxymoronically, the third molars — otherwise known as wisdom teeth — have gotten proportionally smaller as brain size has gotten larger throughout human evolution, for most species.

Overall, human relatives with relatively larger wisdom teeth are more ancient and had smaller brains. More recent taxa, like Homo neanderthalensis, had relatively smaller third molars, compared to their other teeth, and larger brains.

This relationship allows researchers to figure out something about brain size for fossils that are incomplete, perhaps existing only as a few lone teeth. Since teeth are predominately made of inorganic matter, they survive in the fossil record much more often than other parts of the body, making up the vast majority of paleontological materials recovered. Being able to know more about brain size from just a few teeth is a truly useful tool.

Scientists recognize now that the formation of the brain and the teeth are inextricably connected during gestation. And for most species, larger brains are correlated with smaller wisdom teeth.

The one exception in genus Homo is Homo floresiensis, the Hobbit. The wisdom teeth of the Hobbits are small proportional to the other molars — the typical pattern for members of genus Homo. But their brains are also small, which is quite unusual.

There are two primary ways for brain size to decrease: by slowing down growth during gestation before birth or by slowing down growth after birth, during childhood. Because teeth develop early in gestation, slowing down growth rates during pregnancy tends to affect tooth shape and size, or even whether the teeth develop at all. Slowing growth later, during childhood, influences skeletal shape and size in other ways, because different parts of the body develop at different times.

Our new research provides evidence that the body size of Homo floresiensis likely shrank from a larger-bodied Homo ancestor by slowing down growth during childhood. The Hobbits' small wisdom teeth suggest that, at least in utero, they were on track for the proportionally bigger brains that are the trademark of humans and their relatives. Any brake that slowed down brain growth likely occurred after birth.

In fact, this is the same mechanism through which some short-statured modern human populations have adapted to their local ecological conditions.

Getting small on islands

The small body size of Homo floresiensis was likely an adaptation to the unique conditions of their island environment on Flores.

Evolving small body size as an adaptation to living on an isolated island is known as insular nanism. There are many examples of other mammals becoming small on islands over the past 60 million years. But one of the most relevant examples is the dwarf elephant, Stegodon sondaarii, that lived on Flores and was hunted by H. floresiensis for food.

Both Homo floresiensis and Homo luzonensis, another short, island hominin from Southeast Asia, likely evolved very short stature because of the ecological effects of limited food availability and lack of large predators, which tends to characterize island habitats.

Because brain size and body size are tightly linked, body size evolution inherently affects brain evolution. Among modern humans, larger people have larger brains, and smaller people have smaller brains.

But people with smaller brains are certainly no less intelligent than people with larger brains. Variation in body size dictates brain size; it is not a measure of cognitive ability. The island Hobbits crafted tools, hunted large-for-them game in the form of pygmy elephants, and likely made and used fire.

Our research supports that their small body size originated from a slowdown in growth during childhood. But this process would likely have had little impact on brain function or cognitive ability. We hypothesize that the Hobbits were small but highly capable.

Understanding the evolution of us

New research, including our study, continues to reinforce the importance of understanding how pregnancy and child growth and development evolved. If we want to know what distinguishes humans from our evolutionary ancestors, and how we evolved, we must understand how the earliest moments of life have changed and why.

Our work also encourages the reevaluation of endless attention on increasing brain size as the predominant force in human evolution. Other species in genus Homo had small brains but were likely not much different from us.

This edited article is republished from The Conversation under a Creative Commons license. Read the original article.

In a groundbreaking first, a gene therapy in clinical trials has slowed the progression of Huntington's disease, a rare genetic disorder in which toxic bits of protein cause brain cells to malfunction and die.

To date, approved treatments for Huntington's disease aim to manage its symptoms, which most often emerge in a person's 30s or 40s. The progressive condition injures and kills key neurons involved in controlling mood, cognition and motor control. Various drugs can help to offset the depression, hallucinations and poorly coordinated movements that arise from that destruction.

However, no available treatments have been shown to slow the underlying drivers of Huntington's, and patients typically die within 10 to 25 years of their symptoms starting.