Resting-state functional connectivity of the sensorimotor network in medication-naïve Chinese children with ADHD: cross-sectional associations with hyperactivity/impulsivity and executive function

BackgroundAttention-deficit/hyperactivity disorder (ADHD) is a prevalent neurodevelopmental disorder, often—but not always—characterized by inattention, hyperactivity/impulsivity, and deficits in executive functions (EFs); some individuals may also exhibit sensorimotor dysfunction. While SMN dysfunction has been implicated in ADHD, the patterns of SMN functional connectivity (FC) and their relationships with clinical symptoms and EFs remain inconsistent, partly due to methodological heterogeneity.MethodsThe study included 62 medication-naïve patients with ADHD (aged 6–15 years) and 46 healthy controls matched for age, sex, and IQ. Clinical symptoms and EFs were assessed using CPRS, IVA-CPT, and Stroop tests. Resting-state fMRI data were acquired, and ROIs within SMN, SN, DMN, and FPN were selected from the Dosenbach atlas. FC was analyzed using Network-Based Statistics (NBS). Partial correlations explored FC–behavior relationships in the ADHD group, controlling for age, sex, and IQ.ResultsThe ADHD group showed significantly higher CPRS hyperactivity/impulsivity scores and poorer IVA-CPT and Stroop performance. Compared to controls, ADHD showed increased FC within SMN (right posterior insula to left precentral gyrus/parietal lobe), between SMN–DMN (precentral gyrus, dorsal frontal cortex, temporal lobe, angular gyrus, posterior cingulate cortex, and precuneus), and SMN–SN (middle insula, superior parietal lobule, superior temporal gyrus, basal ganglia, and fusiform gyrus). Enhanced intra-SMN FC was negatively correlated with impulsivity/hyperactivity and hyperactivity index scores. Enhanced SMN–DMN FC was negatively correlated with hyperactivity symptoms and positively correlated with control quotients in IVA-CPT. Enhanced SMN–SN FC was negatively correlated with Stroop correct responses and positively correlated with omission errors.ConclusionsIn this medication-naïve pediatric sample, distinct SMN connectivity patterns differentially related to ADHD symptoms and executive function. However, given the cross-sectional design and modest sample size, these associations cannot establish causality; they require replication in longitudinal studies and larger cohorts to clarify whether they reflect developmental variation, neurobiological subtypes, or epiphenomena.

Autism-Like Traits in Mice Improved After Single Rapamycin Dose

The results of a preclinical study led by UCLA Health researchers suggest that inflammation during pregnancy in mice can trigger autism-like brain and behavior changes in offspring, and that the effects may be rapidly but temporarily reversible in adulthood with a short-term dose of the immunosuppressive drug rapamycin.

The study showed that a single dose of rapamycin rapidly improved changes including brain overactivity, seizure risk, sensory sensitivity, repetitive behaviors, and abnormal brain functional network organization. Rapamycin itself is not considered a viable candidate for human therapy, as the effects of the drug were found to be temporary, with repeated dosing losing efficacy, and repeated use also having the potential for toxicity. However, the researchers said the study findings indicate that some autism-related brain changes may still be treatable in adulthood, and point to possible therapeutic approaches that target the underlying pathway rather than only symptoms.

“These results reframe how autism-associated symptoms might be treated,” said Janel Le Belle, PhD, an associate professor in the UCLA Department of Neurosurgery. “If the adult brain remains capable of functional normalization, then some features of autism may be successfully addressed without needing to correct underlying structural differences.” Le Belle is first author of the researchers’ published paper in Nature Communications, titled “Acute rapamycin treatment reveals distinct mechanisms of dysfunction in a maternal inflammation mouse model.”

Neurodevelopmental disorders result from the disruption of brain development in utero or in early life, with genetic, environmental, epigenetic, and immunological factors all potential contributors to complex pathogenesis, the authors wrote. Previous studies have shown that offspring of mothers who experience inflammation while pregnant have a higher likelihood of developing autism-associated traits such as repetitive behaviors and difficulty with social interaction, as well as brain overgrowth and disrupted sensory processing that continue into adulthood. “Maternal inflammatory response (MIR) during early mouse gestation induces a cascade of physiological and behavioral changes associated with autism spectrum disorder (ASD),” they stated.

Rapamycin has been shown in previous mouse autism studies to improve symptoms by suppressing an overactive mTOR pathway that signals cell growth and proliferation. What has been less clear is whether these brain changes could still be modifiable in adulthood, and whether rapamycin’s benefits came from long-term structural repair or faster functional changes. “We wanted to understand the mechanisms that underlie the effects of adult mTOR inhibition, where treatment isn’t aimed at preventing or reversing structural brain abnormalities,” the team stated.

For their newly reported study the scientists exposed pregnant mice to a mild inflammatory trigger early in gestation at a dose that was too low to make the mothers significantly ill. The resulting offspring went on to develop chronic brain and body-wide inflammation, mild brain overgrowth, overactive cell-signaling in the mTOR pathway, disorganized brain functional network connectivity and behaviors associated with autism.

When researchers gave adult offspring a single dose of rapamycin they found rapid improvement across nearly every measure. Neurons that had been firing abnormally calmed down, susceptibility to seizures dropped, brain regions that had been miscommunicating reorganized into more typical patterns and repetitive behaviors and sensory over-responsivity eased. These changes occurred within roughly two hours of drug administration, which was too rapid to be explained by the kind of physical rewiring of brain synapses that typically takes longer.

“The level of functional normalization achieved over this short time suggests new mechanisms by which possible treatments may act,” said the study’s senior author Harley Kornblum, MD, PhD, director of the UCLA Intellectual and Developmental Disabilities Research Center in the Semel Institute for Neuroscience and Human Behavior. “It suggests the adult brain may be more adaptable than we assumed, even when the underlying structural changes from early development are still there. This points us toward the brain’s functional circuitry, not just its physical structure, as a target for future treatment approaches.”

To understand the mechanisms of rapid rapamycin effects, researchers examined gene activity in brain cells before and after treatment. They found that rapamycin reversed abnormal expression of genes tied to autism, epilepsy and ion channel function, particularly in excitatory neurons, suggesting the drug works by quickly rebalancing brain cell excitability rather than by repairing structural brain differences.

The findings suggest that mTOR pathway activity, brain network organization and neuronal excitation levels as potential targets for future therapies aimed at specific autism symptoms such as sensory over-responsivity, a common but difficult-to-treat symptom of autism. “Our findings demonstrate that mTOR dysregulation drives dysfunctional brain development in MIR offspring but the adult brain remains amenable to rapid functional normalization, rescuing core and comorbid ASD associated brain and behavior phenotypes,” the authors stated.

Co-senior author and professor in the UCLA Department of Neurosurgery, Neil Harris, PhD, cautioned that the results showed the treatment effects to be temporary and that daily dosing produced tolerance over several weeks. This, along with rapamycin’s high potential for toxicity and the fact that these studies were performed in mice, makes it unsuitable for broad use in humans. “This points toward new therapeutic targets like sensory circuit neuromodulation or balancing neuronal inhibition and excitation, rather than toward rapamycin itself as a treatment,” Harris said. As the authors further commented in their paper, “Restoring excitatory/inhibitory imbalance and sensory functional network modularity may be important targets for therapeutically addressing multiple ASD phenotypes.”

The post Autism-Like Traits in Mice Improved After Single Rapamycin Dose appeared first on GEN – Genetic Engineering and Biotechnology News.

Curvature-guided anisotropic noise injection for robust multimodal data processing in neuroscience and perception science

IntroductionLarge-batch training is widely used to scale multimodal neural networks that integrate heterogeneous inputs such as visual, textual, and physiological signals. However, increasing the batch size suppresses the stochastic fluctuations of mini-batch sampling, which can trap multimodal models in sharp, modality-dominant minima and produce a persistent generalization gap.MethodsTo address this problem, we propose Geometric Anisotropic Noise Injection (GANI), a curvature-aware optimization framework inspired by information geometry and multisensory integration. GANI decouples deterministic large-batch descent from stochastic geometric exploration. It approximates local curvature through an exponential moving average of first-order gradients and injects structured anisotropic noise during parameter updates, thereby restoring the geometry-aware exploration dynamics of small-batch stochastic gradient descent with linear computational complexity.ResultsTheoretical analysis shows that curvature-aligned stochasticity can accelerate escape from sharp modality-specific basins and guide parameters toward flatter regions. Experimental evaluations across multimodal benchmark settings and stress tests demonstrate that GANI reduces the generalization gap, improves convergence stability, bounds the maximum Hessian eigenvalue, and maintains stronger performance under visual noise and missing textual information than standard large-batch SGD and common adaptive optimizers.DiscussionBy linking optimization geometry with multimodal representation dynamics, GANI provides an efficient and interpretable mechanism for robust heterogeneous data processing. The framework offers potential value for uncertainty-aware multisensory integration, brain-inspired perception science, and scalable multimodal learning under noisy or incomplete sensory conditions.

Gene Therapy Restores Brain Function and Behavior in Fragile X Syndrome

A University of California, Riverside-led research team has developed a gene therapy that restored production of a missing brain protein, corrected abnormalities in brain circuitry, and improved behavior in a mouse model of Fragile X syndrome (FXS). The study, published in the journal Molecular Therapy Nucleic Acids, tested an adeno-associated virus (AAV)-based therapy carrying a normal human version of the FMR1 gene to produce the Fragile X messenger ribonucleoprotein (FMRP) and found that early treatment normalized several measures of brain activity while improving social behavior, exploratory behavior, and cognitive flexibility.

“In a typical brain, FMRP acts like a brake or a volume control,” said senior author Iryna Ethell, PhD, a professor of biomedical sciences at the UC Riverside School of Medicine. “Without it, neural circuits become overactive and less efficient, which contributes to many of the developmental and behavioral challenges associated with FXS.”

FXS is the most common single-gene cause of autism spectrum disorder. According to the researchers, the disorder typically manifests from expansion of CGG repeats in the 5′ untranslated region of FMR1. The mutation causes methylation and silencing of the gene, leading to a major reduction or complete loss of FMRP, an RNA-binding protein that regulates numerous messenger RNAs involved in synapse formation, maturation, and function. Loss of the protein can lead to abnormal synaptic activity and increased cortical hyperexcitability.

FXS can produce sensory hypersensitivity, seizures, anxiety, intellectual disability, developmental delays, repetitive behaviors, and social communication difficulty. Current treatments for this syndrome don’t seek to cure it, rather they are aimed at managing the associated symptoms of anxiety, hyperactivity, irritability, aggression, depression, and seizures.

The therapy developed by the research team was designed to replace missing FMRP rather than repair the original mutation. To do this, the researchers used an AAV9 viral vector to deliver human FMR1 isoform 7, one of the most abundant forms of the protein found in the brain. The therapy was tested in newborn mice lacking FMRP via intracerebroventricular injections at either a low or high doses.

The work built on earlier research that explored the potential of AAV-mediated restoration of FMRP in rodent models. These prior studies used a range of viral serotypes, promoters, delivery routes, and FMRP isoforms and showed they could partially or completely correct specific biochemical, physiological, and behavioral abnormalities. The researchers noted that studies involving mouse and rat FMRP homologs had shown that restoring the protein could improve a range of Fragile X-related deficits.

The current study showed that high-dose treatment produced the strongest positive effects in the mouse models. Electroencephalography showed normalization of baseline gamma power, improvements in responses to sound, reduced background neural activity, and improved habituation to repeated auditory stimuli. The therapy also restored abnormal patterns of brain-wave coupling that have been associated with Fragile X-related dysfunction.

Behavioral testing showed that these improvements persisted into adulthood. Mice receiving the higher dose displayed normalized exploratory behavior, improved social preference, and better performance in probabilistic reversal learning, a measure of cognitive flexibility that requires adapting when previously rewarded behaviors stop producing rewards.

“Fragile X mice tend to persist with an old solution even after the rules change,” Ethell said. “After treatment, they became much better at adapting, performing similarly to mice with normal FMR1 function.”

The researchers noted that their work showed the importance of delivering at therapy for FXS early in its development. They said that widespread distribution of the potential new gene therapy throughout the brain was necessary to achieve a therapeutic benefit. There was a clear relationship between the proportion of neurons expressing the therapeutic gene and the degree of functional recovery, which indicated that restoring FMRP in a sufficient number of cortical cells is critical for correcting any behavioral deficits.

While a promising step, the investigators said that the work was a preclinical study and that future research will now focus on developing delivery methods that can of have broad distribution across the human brain. The team also believes their approach could have broader applications.

“Beyond FXS, the findings may provide a roadmap for treating other genetic neurodevelopmental disorders caused by the loss of a single critical protein,” Ethell said. “Our study shows it may be possible to restore function across complex brain networks by replacing a missing gene. That gives us reason to be optimistic about the future of genetic medicine.”

The post Gene Therapy Restores Brain Function and Behavior in Fragile X Syndrome appeared first on Inside Precision Medicine.

Vibrating Pill Predicts Anorexia Relapse

A vibrating capsule that assesses how nerve signals from the stomach are registered by the brain could help identify patients with anorexia at risk of relapse, a clinical trial suggests.

The findings, in JAMA Psychiatry, offers an insight into how the eating disorder affects the nervous system as well as a way to personalize and assess the success of treatment.

The results suggest that disruptions in gastrointestinal (GI) interoception—involving the detection, transmission, and processing of signals in the digestive tract—can increase the risk of anorexia returning, even if weight has normalized.

Gastric signals could therefore act as scalable biomarkers to identify who is at increased risk of relapse and track whether treatment is improving gut-brain signaling.

“People with anorexia nervosa do not simply ignore signals from the body,” explained researcher Sahib Khalsa, PhD, at the University of California, Los Angeles.

“Rather, their nervous system may process gut sensations differently, making those signals harder to detect, trust and learn from. Over time, that may contribute to the persistence of symptoms even after weight is restored.”

Khalsa and co-workers asked 62 girls and women with anorexia nervosa whose weight had been restored to healthy levels to swallow the vibrating capsule in their crossover trial.

The capsule could be remotely controlled by the researchers to produce mechanosensory stimulation of different intensities in the stomach.

Participants were asked to press a button upon sensing a vibration, with 54 patients followed up at six months after discharge from hospital and their results compared with 57 healthy control individuals.

Computational modeling was used to estimate how strongly participants anticipated feeling sensations in their stomachs, how heavily their brains depended on body signals, and how quickly they adjusted their expectations as to the presence or absence of signals.

The researchers found that participants with anorexia had abnormal GI interoception across behavioral and computational domains compared with healthy participants, despite having intact neural and physiological responses.

Participants with anorexia were less able to detect subtle stomach sensations and were more likely than others to believe there were no sensations when the pill was vibrating. They were also less likely to update those expectations when gastric signals occurred.

Patients who were more likely to ignore the stomach signals were also at increased likelihood of relapsing to the eating disorder.

“One of the most striking findings was that these differences persisted even after weight restoration,” said Khalsa.

“Recovery from anorexia nervosa isn’t just about restoring body weight. The underlying brain–body communication problems may remain and could contribute to relapse.”

The researchers conclude that their results support the use of ingestible mechanosensory probes and computer modeling as scalable tools to monitor treatment response and guide relapse prevention in eating disorders.

The post Vibrating Pill Predicts Anorexia Relapse appeared first on Inside Precision Medicine.

The Download: a reality check for geoengineering and the science of interoception

This is today’s edition of The Download, our weekday newsletter that provides a daily dose of what’s going on in the world of technology.

Hacking the atmosphere: geoengineering gets a reality check

Solar geoengineering, the controversial idea that we could deliberately intervene in the climate system to counteract global warming, is moving beyond computer simulations and into the practical engineering challenges required to make it real.

Researchers are now working on aircraft, materials, and other systems for solar geoengineering. But as they delve into these details, they’re finding that even early deployment would require significant new infrastructure, time, and investment.

Find out what happens when solar geoengineering encounters the realities of trying to cool the planet.

—James Temple

MIT Technology Review Narrated: inside interoception, the hidden sense of how you feel inside

Scientists have a word for how we sense ourselves from the inside: interoception. Today, thanks to a 2021 Nobel Prize and new tools that can map internal signaling across the body, research into interoception is taking off.

As researchers decode how signals move between body and brain, a clearer picture is starting to take shape—with implications for how we treat conditions from obesity to anxiety.

—Katherine W. Isaacs

This is our latest story to be turned into an MIT Technology Review Narrated podcast, which we publish each week on Spotify and Apple Podcasts. Just navigate to MIT Technology Review Narrated on either platform, and follow us to get all our new content as it’s released.

The must-reads

I’ve combed the internet to find you today’s most fun/important/scary/fascinating stories about technology.

1 SpaceX is now valued higher than Amazon 
Its market value hit $2.659 trillion yesterday. (Axios)
+ A post-IPO stock surge also briefly pushed it above Microsoft’s. (Quartz)
+ It’s now the world’s fifth most valuable company. (Guardian)
+ SpaceX is acquiring AI coding startup Cursor for $60 billion. (CNBC)

2 G7 leaders want access to top US AI models
They’re pushing to escape restrictions on the likes of Fable 5. (Reuters $)
+ The Mythos shutdown has sparked a global scramble for sovereign AI. (Fortune)
+ The world is looking to ditch US AI models. (MIT Technology Review)

3 Trump’s AI export strategy has run into Trump’s export controls
His administration risks undermining its own AI plans. (Axios)
+ It now effectively has a licensing regime for frontier AI. (Fortune)
+ Here’s how a top Chinese AI model overcame US sanctions. (MIT Technology Review) 

4 Huawei’s big comeback has exposed the limits of US chip controls
It’s overcome restrictions on advanced chipmaking gear. (Financial Times $)
+ The AI boom has ignited Asia’s chip companies. (NYT $)

5 AI fears are pushing Silicon Valley toward gene-editing startups
They want smarter babies to counter superintelligent AI. (Mother Jones)
+ The pursuit of perfect babies is an ethical mess. (MIT Technology Review)

6 A brain implant has enabled a speechless ALS patient to work full-time
The system translates his brain activity into speech. (The Register)
+ He’s become the first “power user” of a BCI. (MIT Technology Review)

7 A leak has revealed details of Peter Thiel’s secret society
Its program ranges from cult-building to prepping for World War III. (Wired $)

8 ChatGPT’s market share has slipped below 50% for the first time
Thanks to the rise of Gemini and Claude. (TechCrunch)

9 A quantum state that lasts forever may finally be within our grasp
Experiments suggest that quantum “eternity” is possible. (New Scientist $)

10 Commodore has made a digital detox phone that isn’t dumb
The Callback combines gadget nostalgia with modern needs. (The Verge)

Quote of the day

“The Entity List is like whack-a-mole and you’ve got to ‌keep whacking ⁠the moles.” 

—Philip Luck, who studies global supply chains at the Center for Strategic and International Studies, tells Reuters that a lack of new blacklistings is likely leading American innovations to adversaries who could use them against the US.

One More Thing

A model generated by AlphaFold shows how amino acids fold to form a protein.

COURTESY OF DEEPMIND


This is the reason Demis Hassabis started DeepMind

Watching DeepMind’s AI master the ancient board game Go, Demis Hassabis realized that his company was ready to take on one of the most important and complicated puzzles in biology: predicting the structure of proteins. 

The result was AlphaFold2, an AI that could predict the shape of proteins down to the nearest atom. “It’s the most complex thing we’ve ever done,” Hassabis told MIT Technology Review.

Taking on scientific problems is the culmination of what Hassabis set out to achieve, and it’s what he wants to be known for.  “This is the reason I started DeepMind,” he says. “In fact, it’s why I’ve worked my whole career in AI.”

Discover how he plans to transform science with AI. 

—Will Douglas Heaven

We can still have nice things

A place for comfort, fun, and distraction to brighten up your day. (Got any ideas? Drop me a line.)

+ This mesmerising footage of wind rolling through grass looks like CGI.
+ The glorious early days of internet discovery have been revived by the return of StumbleUpon.
+ A German subway entrance has been delightfully designed as an old tram car crashing into the pavement.
+ The Last Museum lets you search across 5.8 million museum artworks spanning from 3000 BC to the present day.

The Download: “reprogramming” aging, and the hidden sense of interoception

This is today’s edition of The Download, our weekday newsletter that provides a daily dose of what’s going on in the world of technology.

Why “reprogramming” is the buzziest approach to reversing aging right now

Earlier this week, Life Biosciences, a biotech company focused on reversing age-related diseases, announced that it had dosed its first volunteer. A person with glaucoma has had an experimental treatment injected straight into their eyeball.

The idea is to treat the disease by regenerating healthy nerves in the eye—but the company already hopes to go further. If the treatment can reverse glaucoma, similar treatments could reverse other diseases of aging. Maybe, just maybe, they could reverse aging altogether.

The approach relies on “reprogramming” cells to a younger state. It’s one of many strategies being explored by biotech companies looking to slow and reverse aging. But of all of them, it seems to be the one that is truly taking off.

Read the full story on the pursuit of reprogramming for rejuvenation.

—Jessica Hamzelou

This story is from The Checkup, our weekly newsletter giving you the inside track on all things biotech. Sign up to receive it in your inbox every Thursday.

Inside Interoception: The hidden sense of how you feel inside

Scientists have a word for how we sense ourselves from the inside: interoception. Today, thanks to a 2021 Nobel Prize and new tools that can map internal signaling across the body, research into interoception is taking off.

As researchers decode how signals move between body and brain, a clearer picture is starting to take shape—with implications for how we understand and treat conditions from obesity to chronic pain to anxiety.

Find out how it’s leading to a “new continent of awareness.”

—Katherine W. Isaacs

This story is part of MIT Technology Review Explains, our series untangling the complex, messy world of technology to help you understand what’s coming next. You can read more from the series here. 

The must-reads

I’ve combed the internet to find you today’s most fun/important/scary/fascinating stories about technology.

1 SpaceX has officially delivered the largest IPO in history
It’s raised a record $75 billion at a $1.77 trillion valuation. (Axios)
+ Making Elon Musk the world’s first trillionaire (on paper). (Reuters $)
+ The IPO will now put his “extreme ownership” to the test. (Wired $)
+ While China attempts to build a Starlink rival. (Rest of World)
+ And other challenges to SpaceX emerge. (MIT Technology Review)

2 Jeff Bezos wants to build an “artificial general engineer”
Through his new industrial AI startup, Prometheus. (NYT $)
+ Which just raised $12 billion, valuing it at $41 billion. (TechCrunch)
+ Meanwhile, OpenAI is building a fully automated researcher. (MIT Technology Review)

3 Chinese regulators are dramatically intensifying tech enforcement
A spell of relative restraint has ended. (SCMP)
+ Regulators have admonished e-commerce giants Alibaba and JD.com. (FT $)
+ And blocked Meta’s acquisition of Chinese AI startup Manus. (BBC)

4 Google says Chinese cybercriminals used Gemini to scam Americans
It’s suing the network over the alleged AI-powered scams.(NYT $)
+ “Supercharged scams” are one of our 10 Things That Matter in AI Right Now. (MIT Technology Review)

5 Ukraine’s defense AI chief predicts a “new paradigm” of warfare
He expects AI systems to unify into a single battlefield network. (Reuters $)
+ AI chatbots could be used for targeting decisions. (MIT Technology Review)

6 Anthropic has rankled users with its safety-first Fable model
Stringent safety rules and refusals to help have sparked a backlash. (NBC)
+ Anthropic has backtracked on some policies. (Wired $)

7 Pokémon Go data trained AI that could assist military drones
It could help them locate themselves in war zones. (Guardian)
+ Pokémon Go data is also training delivery robots. (MIT Technology Review)

8 Orbital data centers are harder than Silicon Valley thinks
Shedding heat in space requires ingenious new designs. (IEEE Spectrum)
+ We need a few things to put data centers in space. (MIT Technology Review)

9 A toy universe shows time could be a quantum illusion
It could emerge from quantum interactions, rather than just existing by default. (New Scientist $)

10 Chatbots keep telling stories about a lighthouse keeper called Ella
And now we may finally know why. (404 Media)

Quote of the day

“People are paying a trillion dollars for Elon.” 

—Ross Gerber, the CEO of Gerber Kawasaki, which owns SpaceX stock, tells the New York Times why he believes the company’s IPO is overvalued.

One More Thing

a knight standing in a virtual space

GEORGE WYLESOL


How generative AI could reinvent what it means to play

I was immediately attracted to open-world games, in which you’re free to explore a vast simulated world and choose what challenges to accept. To make them feel alive, these games are inhabited by crowds of “nonplayer characters” (NPCs). But the illusion starts to weaken when you spend enough time with them.

It may not always be like that. Just as it’s upending other industries, generative AI is opening the door to entirely new kinds of in-game interactions that are open-ended, creative, and unexpected. The game may not always have to end.

Discover how generative AI could make games—and other worlds—deeply immersive.

—Niall Firth

We can still have nice things

A place for comfort, fun, and distraction to brighten up your day. (Got any ideas? Drop me a line.)

+ My feet have fallen for the Crocs x Super Mario collection.
+ Denmark’s 2026 Mullet Championship is the hottest hairdo contest of the year.
+ Hungry at half-time? Here are seven mouth-watering international recipes inspired by the World Cup.
+ Feast your eyes on a helicopter bound for Mars and a flowery Milky Way frame in Nature’s top images from last month.

Inside interoception: The hidden sense of how you feel inside

MIT Technology Review Explains: Let our writers untangle the complex, messy world of science and technology to help you understand what’s coming next. You can read more from the series here.

Your brain lives in the dark space of your skull. Yet it knows when the wind lifts the hairs on your skin, when your heart is racing, when your gut tightens with fear.

It’s also, right now, predicting what you’ll read next as your eyes move across this page. It’s picking up signals that help it make sense of what’s happening around you and prepare you to act if you need to stay safe. You aren’t usually aware that your brain is doing all that.

Our senses take in information at a staggering rate—roughly 11 million bits flood in every second from our skin, eyes, ears, and more. That’s nearly three paperback novels’ worth of data every second. Only a sliver reaches our conscious awareness.  Researchers estimate that our conscious minds can process roughly 10 to 60 bits of information per second, about the rate at which you’re reading this sentence. That’s a ratio of about one conscious bit to hundreds of thousands of unconscious bits.

And that’s a mercy. As Moriah Thomason, a neuroscientist at NYU Langone, says, “Thank goodness we’re built like this. There’s a layer of what we have access to in conscious awareness. And then we have a right-under-the-surface amount. There is only a certain amount we are meant to ‘hold in mind’ in order to function successfully.” 

What you are aware of: Your stomach growling when you’re hungry. Your palms sweating before you speak in public. The breath you just took, if you pay attention to it. Even your heartbeat, which some people can sense from the inside without feeling their pulse in their wrist.

Scientists have a word for how we sense ourselves from the inside: interoception. 

The term was coined in 1906 by the British neurophysiologist Charles Sherrington. For most of the 20th century it remained largely confined to textbooks. Today, thanks to a 2021 Nobel Prize and new tools that can map the interoceptive system across the body, the study of this facility is suddenly quite hot. As researchers decode how signals move between body and brain, a clearer picture is starting to take shape—with implications for how we understand and treat conditions from obesity to chronic pain to anxiety.

The field began to take off in the 1990s. In 1994, the neurologist Antonio Damasio published a book with a pointed title: Descartes’ Error. He challenged the historical separation of thinking and feeling, arguing that our ability to choose and act is driven by feelings, and those feelings in turn are shaped by the body’s signals, such as your gut clenching or your skin going clammy. When we lose that connection between feeling and thinking, as one of Damasio’s patients did after surgery to treat a brain tumor, we may still be able to reason with perfect logic about the pros and cons of traveling on a Tuesday or a Wednesday. But without the emotional signals that help us predict what a choice will feel like, our reason spins and circles, and we cannot decide.

A contemporary of Damasio’s, the neuroscientist Bud Craig, spent his career asking one question: How do you feel? He charted how the brain builds an inner map of the body and updates it in real time every moment you are alive.

Think of the captain’s bridge on the USS Enterprise, where a live map displays the status of the ship’s critical systems: oxygen levels, energy availability, hull integrity, shield strength. Another set of indicators senses things outside the ship: asteroid belts, enemy ships, radiation, life signs, and spatial anomalies not yet understood.

Your brain, only about the size of your two fists pressed together, creates a map like this for your entire body, along with a map of the outside world, from data streaming in through your five senses. Together, they feed into your brain’s working model of you in the world, now and across time—where you are, who you are, your expectations for what’s about to happen (based on everything you know), and what all that means for you.

When someone asks “How are you doing?” we consult our maps and report back on our status. We might say we’re happy, depleted, anxious, or energetic. These feelings are always a braid of emotional and physical sensations. They’re what your interoceptive navigational system serves up to your awareness when you sense yourself from the inside.

As we grow up, we learn to interpret what these sensations mean—interpretations that, in turn, can alter our physiology, emotions, and behavior. Research by the psychologist Alia Crum shows that people who embrace a “stress is enhancing” mindset produce more growth hormones than people who have a “stress is debilitating” mindset. They also experience more positive emotions and greater cognitive flexibility.

Language also matters. We learn words for the textures of our feelings—words that then shape how we feel and act. People low in emotional “granularity”—as the psychologist Marc Brackett calls the ability to distinguish between closely related feelings—react more impulsively under stress and are less able to find meaning in difficult experiences. But mindsets and emotional intelligence are malleable. We can learn that “anxious” is different from “terrified,” and we can even reframe how we interpret our body’s sensations. Instead of thinking of the butterflies in our bellies as annoying, we can welcome them as our body’s way of preparing us for a peak performance.

Scientists have long understood that the interoceptive information informing these lived experiences travels via two major systems: nerves and humors (blood and lymph). Now they’re actively studying a third system—the “interstitium,” a network of fluid-filled spaces woven throughout the body’s connective fascia that may also play a role in communication.

But until recently, scientific understanding of this interoceptive system looked like a high-level schematic that left out vital details—how information travels from the outside environment in, how it moves from your body to your brain, and how it is integrated and interpreted within your brain. Researchers are now racing to explore what the neuroscientist Catherine Tallon-Baudry calls this “new continent of awareness.”

The wandering highway

One of the most active areas of research centers on the vagus nerve, the main component of the parasympathetic nervous system and an information highway carrying news from your organs up to your brain and back down to your body. The vagus has become a celebrity nerve, ubiquitous in wellness podcasts and trauma therapy. “Tone your vagus nerve.” “Activate your parasympathetic system.” The language suggests a single thing you can target, like a muscle. The reality, as Steve Liberles at Harvard Medical School is discovering, is far more interesting.

Liberles has spent most of his career mapping what he calls “the great wide unknown” of one of our largest and longest nerves. He speaks the way he works—methodically, without overselling. But the questions driving him are huge. How do we sense our body’s inner state? What information flows through which channels? And how does the brain decide what to do with it?

“When I’m nervous giving a talk in front of a thousand people,” he says, “my heart might race. I might get butterflies in my stomach. I might get goosebumps on my skin.” We all know what he’s talking about.

“It’s bizarre,” he muses. “Your brain has to send a signal to the gut, and then the gut back to the brain, to tell you you’re nervous?” He pauses. “This just shows there is this intimate connectivity between the brain and the body that’s real.”

The vagus is often called the calming nerve, because it controls “rest and digest” functions that quiet our body after the sympathetic nervous system revs us up with “fight or flight” impulses to handle danger or stress. 

But it is also doing something else: It’s listening to us inside. Anatomists have known for over a century that roughly 80% of its fibers carry information upward, from body to brain. Think of it as a two-lane highway with far more traffic headed north. What scientists are just beginning to understand in detail is what those signals are saying. 

Liberles is decoding the vagus with molecular precision and finding that its messaging system is unexpectedly diverse. So far, his research has uncovered dozens of types of vagus nerve cells, each wired to a specific organ. Team Red relays information about the heart; Team Blue, the gut.

Within those teams, each courier has a unique job that’s different from those all its teammates perform. Liberles found 10 types in the lungs alone. Until then, only one lung reflex had ever been identified, in 1868. One nerve courier carries information about breathing rate; another the stretch of your lungs; yet another information about airway threats, like food going down the wrong pipe.

“It’s super exciting to think about what each of these neurons is doing,” he told me in a conversation last fall, a flash of intensity breaking through the calm. “Where does it go in the body? What is it sensing? What is it controlling?”

The doors of the cell

Liberles is mapping the vagus information highways. But highways need on-ramps for signals to enter. For years, one of neurobiology’s biggest mysteries was the molecular on-ramp for our sense of touch.

Somewhere, something in our bodies was converting physical force into an electrical signal that the nervous system could understand. But no one knew how. 

Solving that mystery required a scientist willing to trust a hunch when the data couldn’t show the way. 

Ardem Patapoutian grew up in Lebanon and fled the country’s civil war at 18, landing in Los Angeles, where he delivered pizzas and wrote horoscopes for a local newspaper before falling in love with science at UCLA.

In the 1990s, as a postdoc at the University of California, San Francisco, he became fascinated with our sense of touch—the last of the five major senses not yet understood at the molecular level. The lung stretch signal that Liberles’s vagus neurons carry to the brain? No one had ever figured out how that signal began.

“How do you feel the embrace of a loved one? How do your fingers distinguish one texture of hair from another?” Patapoutian invites us to wonder in his 2021 Nobel Prize lecture. The problem: Most cellular communication works through chemistry. But mechanical force offers no molecule to bind. How does the body translate physical pressure into the electrochemical language that neurons speak?

Scientists knew that the answer had to be an ion channel—a protein gate embedded in cell membranes that opens to let electrically charged particles into the cell. But tracking down the one responsible for touch turned out to be absurdly difficult. Ion channels are a hundred thousandth the size of a cell, invisible to ordinary microscopes. Worse, they don’t resemble each other. You can’t recognize one by its shape or its sequence of amino acids. Even with one right in front of you, nothing would tell you it was there.

At Scripps, where he works now, Patapoutian decided to try an unusual approach. He’d try to find cells that showed sensitivity to touch and destroy their internal genetic blueprint one gene at a time—hunting for the move that would make the cell go numb. It was tedious, expensive, and possibly a dead end. “A lot of people made fun of us,” he says.

Two years in, Patapoutian’s collaborator Bertrand Coste had burned through half his postdoctoral appointment with no results. Patapoutian said: Another 30 genes, and then we decide whether to continue.

What kept them going, Patapoutian told me, was informed intuition. “As you gain more experience, you have this sense of what’s going to work, what’s not going to work. Sometimes the data cannot answer the question of when to stop or when to continue. There has to be another process. If you start trusting it, it gives you an avenue to continue.”

Coste knocked out candidate gene 72. Flatline. The cell had gone numb.

They’d found it—the mechanism behind something you feel every day.

They named the protein they identified PIEZO, from the Greek piezi, meaning pressure. There are two variations, PIEZO1 and PIEZO2, each responsible for sensing different kinds of pressure in the body. They’re elegant in their design—over 2,500 amino acids folded into a three-bladed propeller-shaped gate embedded in cell membranes. When pressure stretches the membrane, the gate opens and electrically charged ions flood through, translating physical pressure into an electrical signal that the brain can understand—all within milliseconds.

Patapoutian calls scientific discovery a dream that survives reality. He won the Nobel Prize in medicine in 2021 for his discovery of PIEZO, sharing the award with David Julius of UCSF for his work on how cells sense temperature. Now researchers are finding PIEZO proteins everywhere—skin, organs, blood vessels, and even red blood cells, where they help the cells squeeze through narrow capillaries. They’re how your brain knows where your hand is in space without looking at it, a sense called proprioception. They’re in plants too, enabling roots to sense pressure as they push down into the earth.

PIEZO was just the beginning. With a $14.5 million grant from the US National Institutes of Health, Patapoutian and his collaborators are now mapping the body’s entire interoceptive system—as many internal senses as he can find, he says.8

Patapoutian has translated his discovery into a unique form of public outreach. At scientific conferences, he sometimes rolls up his sleeve mid-lecture to reveal half his arm covered in ink—a gigantic PIEZO protein in exquisite anatomical detail, its blades spreading across his biceps. Then he flexes. The tattoo flexes with him, the structure bending exactly as the real protein does when pressure opens the gate.

“At a pub or a party,” he explains, smiling, “how else would I demonstrate this beautiful structure?”

Orchestrating the field

Steve Liberles is mapping a major interoception highway. Ardem Patapoutian discovered the gates of touch. Meanwhile, Wen Chen at the National Institutes of Health is pulling the field together, putting neuroscientists, immunologists, physiologists, and clinicians into the same room. The demand, she says, has been enormous.

She tested her pitch at a dinner party with NIH colleagues a few years ago. You’re hungry right now—that’s interoception. You’re thirsty—that’s interoception. Heads nodded as she pointed around the table.

“We can’t have just the brain or just the body,” she told me. “We need to look at the whole person.”

In 2018 she organized a symposium on interoception where Liberles was one of the invitees, along with researchers and practitioners of meditation and yoga. “It was not their thing,” she says, laughing as she recalls how uncomfortable some of the researchers looked. But the practitioners were excited to finally meet scientists who were studying the inner mechanisms of what they did.

That was followed by a series of NIH workshops on interoception that spanned topics from basic science to clinical practice. Patapoutian was the keynote speaker for the first one. 

The NIH began funding scientists to chart the neural circuits of interoception and bringing them together to talk about their findings. Partway through one of these meetings, the equipment failed for an hour. More than 1,000 people stayed online, waiting for it to come back.

“We were shocked at the turnout,” she says. “There was much bigger interest than we could have imagined.”

Chen is now building infrastructure to match the demand: a formal community, funding mechanisms, a venue where cardiologists and neuroscientists and clinicians can all find each other. And she’s redefining the field as she goes; interoception is not a one-way signal from body to brain but a continuous two-way communication system, each direction shaping the other in real time.10   

Liberles’s nervousness on stage is that two-way loop in action. Signals from his racing heart and belly butterflies travel up to the brain, which weaves them into an interpretation: This is anxiety, and this is what to do to handle it. His actions produce fresh signals that the brain reads in light of its ongoing predictions about what will happen next. In the body-brain communication loop, each player constantly updates the other.

I asked Wen what her work on interoception might mean for another inner sense: intuition. “People talk about ‘gut feelings,’” I said. “How does that relate to interoception?”

 “Intuition might be the bridge where interoception moves from unconscious processing to conscious awareness,” she answered. “If that’s true, then intuition is not magic. It’s physiology.”

But it depends on how we read the signals. Intuition is like pain. It tells you something, but it’s not always clear what. “Perhaps we can treat intuition as a source of data,” she says. “Meaningful, but probably not complete.”

“Maybe we can be grounded in both—in feeling and fact.”

Which raises a more personal question: What do you do with the signals your body is sending?

One avenue for exploration is therapeutic intervention—both pharmacological and neural stimulation. Vagal nerve stimulation has treated epilepsy and depression for four decades, but as Liberles puts it, it’s like pressing all the keys on the piano to hit one note. Weight-loss drugs like Ozempic act in part through vagal pathways but can cause nausea as a side effect, because the targeting isn’t precise enough. Map the body’s circuits with enough accuracy and you might hit the note you actually want.

Another area of active research is psychological and behavioral—teaching people how to detect and even shape interoceptive signals. Low interoceptive awareness is linked to mental-health disorders and stress-related physical conditions.11 But like emotional intelligence, it’s not fixed. Researchers are finding that people can boost their body awareness by, for example, learning to detect their heartbeats from the inside—now a common measure of interoceptive awareness.12 Other interventions focus on body-based therapies and conscious activation of the parasympathetic “rest and digest” system to improve emotional and physical well-being. The placebo effect is another example of the mind acting on the body through expectation alone.

The signals we once dismissed as vague feelings—when your gut tightens before you know why, when your body says yes or no before your mind catches up—those are real. How we interpret them and whether we act on them is another frontier.

It’s clear that gut feelings play a role in scientific research, especially when the path forward looks foggy. Patapoutian’s informed intuition kept him and his colleagues going long enough to find PIEZO, a reminder that major discoveries often start with a hunch that is later tested against evidence. Chen puts it well: Maybe we can be grounded in both feeling and fact.

Katherine W. Isaacs is a writer and senior lecturer at the MIT Sloan School of Management. Her teaching and research focus on the intersection of psychology, technology, and innovation. Originally trained as a biologist and later as a social psychologist, she is currently working on a book called Gut Feel, about intuition, interoception, and embodied decision-making.