Dopamine signals when a fear can be forgotten

Study shows how a dopamine circuit between two brain regions enables mice to extinguish fear after a peril has passed

Picower Institute at MIT

Facebook

WeChatBlueskyMessageWhatsAppEmail

 

image: 

An edited version of a figure from the research shows the ventral tegmental area, highlighting dopamine-associated neurons in green and one that connects to the posterior amygdala (magnified in inset) in red

view more 

Credit: Tonegawa Lab/MIT Picower Institute

Dangers come but dangers also go and when they do, the brain has an “all-clear” signal that teaches it to extinguish its fear. A new study in mice by MIT neuroscientists shows that the signal is the release of dopamine along a specific interregional brain circuit. The research therefore pinpoints a potentially critical mechanism of mental health, restoring calm when it works, but prolonging anxiety or even post-traumatic stress disorder when it doesn’t.

“Dopamine is essential to initiate fear extinction,” said Michele Pignatelli di Spinazzola, co-author of the new study from the lab of senior author Susumu Tonegawa, Picower Professor of biology and neuroscience at the RIKEN-MIT Laboratory for Neural Circuit Genetics in The Picower Institute for Learning and Memory and an HHMI Investigator.

In 2020 Tonegawa’s lab showed that learning to be afraid, and then learning when that’s no longer necessary, result from a competition between populations of cells in the brain’s amygdala region. When a mouse learns that a place is “dangerous” (because it gets a little foot shock there), the fear memory is encoded by neurons in the anterior of the basolateral amygdala (aBLA) that express the gene Rspo2. When the mouse then learns that a place is no longer associated with danger (because they wait there and the zap doesn’t recur), neurons in the posterior basolateral amygdala (pBLA) that express the gene Ppp1r1b encode a new fear extinction memory that overcomes the original dread. Notably those same neurons encode feelings of reward, helping to explain why it feels so good when we realize that an expected danger has dwindled.

In the new study, the lab, led by former members Xiangyu Zhang and Katelyn Flick, sought to determine what prompts these amygdala neurons to encode these memories. The rigorous set of experiments the team reports in the Proceedings of the National Academy of Sciences show that it’s dopamine sent to the different amygdala populations from distinct groups of neurons in the ventral tegmental area (VTA).

“Our study uncovers a precise mechanism by which dopamine helps the brain unlearn fear,” said Zhang, who also led the 2020 study and is now Senior Associate at Orbimed, a healthcare investment firm. “We found that dopamine activates specific amygdala neurons tied to reward, which in turn drive fear extinction. We now see that unlearning fear isn’t just about suppressing it—it’s a positive learning process powered by the brain’s reward machinery. This opens up new avenues for understanding and potentially treating fear-related disorders like PTSD.”

Forgetting fear

The VTA was the lab’s prime suspect to be the source of the signal because the region is well known for encoding surprising experiences and instructing the brain, with dopamine, to learn from them. The first set of experiments in the paper used multiple methods for tracing neural circuits to see whether and how cells in the VTA and the amygdala connect. They found a clear pattern: Rspo2 neurons were targeted by dopaminergic neurons in the anterior and left and right sides of the VTA. Ppp1r1b neurons received dopaminergic input from neurons in the center and posterior sections of the VTA. The density of connections was greater on the Ppp1r1b neurons than for the Rspo2 ones.

The circuit tracing showed that dopamine is available to amygdala neurons that encode fear and its extinction, but do those neurons care about dopamine? The team showed that indeed they express “D1” receptors for the neuromodulator. Commensurate with the degree of dopamine connectivity, Ppp1r1b cells had more receptors than Rspo2 neurons.

Dopamine does a lot of things, so the next question was whether its activity in the amygdala actually correlated with fear encoding and extinction. Using a method to track and visualize it in the brain, the team watched dopamine in the amygdala as mice underwent a three-day experiment. On day one they went to an enclosure where they experienced three little zaps on the feet. On day two they went back to the enclosure for 45 minutes where they didn’t experience any new shocks –at first the mice froze in fear but then relaxed after about 15 minutes. On day 3 they returned again to test whether they had indeed extinguished the fear they showed at the beginning of day 2.

The dopamine activity tracking revealed that during the shocks on day 1, Rspo2 neurons had the larger response to dopamine, but in the early moments of day 2 when the anticipated shocks didn’t come and the mice eased up on freezing in fear, the Ppp1r1b neurons showed the stronger dopamine activity. More strikingly, the mice that learned to extinguish their fear most strongly also showed the greatest dopamine signal at those neurons.

Causal connections

The final sets of experiments sought to show that dopamine is not just available and associated with fear encoding and extinction, but also actually causes them. In one set, they turned to optogenetics, a technology that enables scientists to activate or quiet neurons with different colors of light. Sure enough, when they quieted VTA dopaminergic inputs in the pBLA, doing so impaired fear extinction. When they activated those inputs, it accelerated fear extinction. The researchers were surprised that when they activated VTA dopaminergic inputs into the aBLA they could reinstate fear even without any new foot shocks, impairing fear extinction.

The other way they confirmed a causal role for dopamine in fear encoding and extinction was to manipulate the amygdala neurons’ dopamine receptors. In Ppp1r1b neurons, overexpressing dopamine receptors impaired fear recall and promoted extinction, whereas knocking the receptors down impaired fear extinction. Meanwhile in the Rspo2 cells, knocking down receptors reduced the freezing behavior.

“We showed that fear extinction requires VTA dopaminergic activity in the pBLA Ppp1r1b neurons by using optogenetic inhibition of VTA terminals and cell-type-specific knockdown of D1 receptors in these neurons,” the authors wrote.

The scientists are careful in the study to note that while they’ve identified the “teaching signal” for fear extinction learning, the broader phenomenon of fear extinction occurs brainwide, rather than in just this single circuit.

But the circuit seems to be a key node to consider as drug developers and psychiatrists work to combat anxiety and PTSD, Pignatelli di Spinazzola said.

“Fear learning and fear extinction provide a strong framework to study generalized anxiety and PTSD,” he said. “Our study investigates the underlying mechanisms suggesting multiple targets for a translational approach such as pBLA and use of dopaminergic modulation.”

Marianna Rizzo is also a co-author of the study. Support for the research came from the RIKEN Center for Brain Science, the Howard Hughes Medical Institute, the Freedom Together Foundation and The Picower Institute for Learning and Memory.

---

Journal

Proceedings of the National Academy of Sciences

DOI

10.1073/pnas.2501331122 

Method of Research

Experimental study

Subject of Research

Animals

Article Title

Dopamine induces fear extinction by activating the reward-responding amygdala neurons

Article Publication Date

28-Apr-2025

 

Anatomy of a “zombie” volcano: investigating the cause of unrest inside Uturuncu

University of Oxford

Facebook

XLinkedInWeChatBlueskyMessageWhatsAppEmail

 

image: 

Gravimeter and GPS station with Cerro Uturuncu in the background. Photo credit Duncan Muir, Cardiff University.

view more 

Credit: Duncan Muir, Cardiff University.

Images available via the link in the notes section

Scientists from China, the UK and the USA have collaborated to analyse the inner workings of Bolivia’s “zombie” volcano, Uturuncu. By combining seismology, physics models and analysis of rock composition, researchers identify the causes of Uturuncu’s unrest, alleviating fears of an imminent eruption. The findings have been published today (28 April) in the journal PNAS.

Deep in the Central Andes lies Uturuncu, Bolivia’s “zombie” volcano -so called because despite being technically dead (last erupting 250 thousand years ago), it still shows signs of unrest, including earthquakes and plumes of gases. This unrest manifests itself in a “sombrero” pattern of deformation, with the land in the centre of the volcanic system rising up, and surrounding areas sinking down.

For the local population, it is vitally important to assess the potential start and severity of an eruption from Uturuncu, which could cause widespread damage and threat to life. However, up to now there was no explanation for the continued volcanic unrest. Scientists believed that the key to understanding this was to visualise the way that magma and gases move around underneath the volcano.

This new study, which drew upon expertise from University of Science and Technology of China, the University of Oxford and Cornell University, used signals detected from more than 1,700 earthquake events to perform high-resolution imaging of the plumbing system in the shallow crust beneath Uturuncu. According to the findings, the “zombie”-like unrest of Uturuncu is due to the movement of liquid and gas beneath the crater, with a low likelihood of an imminent eruption.

Volcanic plumbing systems are a complex mixture of fluids and gases in magmatic reservoirs and hydrothermal systems. Previous studies have shown that Uturuncu sits above the world’s largest known magma body in the Earth’s crust, the Altiplano-Puna Volcanic Complex, and that an active hydrothermal system connects this body and the surface. But it was unknown how fluids may be moving through this underground system.

The research team made use of seismic tomography, a way of imaging the interior of the volcano, similar to methods used in medical imaging of the human body.  Seismic waves travel at different speeds through different materials, thereby providing high-resolution insights into the inner workings of Uturuncu in three dimensions. They combined this with analysis of the physical properties of the system, including rock composition, to better understand the subterranean volcanic system. This detailed analysis picked out possible upward migration pathways of geothermally heated fluids and showed how liquids and gases accumulate in reservoirs directly below the volcano’s crater. The research team believe that this is the most likely cause for the deformation in the centre of the volcanic system, and that the risk of a real eruption is low.

Co-author Professor Mike Kendall (Department of Earth Sciences, University of Oxford) said: “I am very pleased to be involved in this truly international collaboration. Our results show how linked geophysical and geological methods can be used to better understand volcanoes, and the hazards and potential resources they present.”

Co-author Professor Haijiang Zhang (School of Earth and Space Sciences, University of Science and Technology of China) said: “Understanding the anatomy of the Uturuncu volcanic system was only possible thanks to the expertise within the research team. This enabled us to combine various advanced geophysical imaging tools with modelling of the rock properties and their interactions with fluids.”

Co-author Professor Matthew Pritchard (Cornell University) added: "The methods in this paper could be applied to the more than 1400 potentially active volcanoes and to the dozens of volcanoes like Uturuncu that aren't considered active but that show signs of life — other potential zombie volcanoes." 

The research team hope that similar studies using the joint analysis of seismological and petrological properties can be used to view the anatomy of other volcanic systems in the future.

Notes to editors:

For media enquiries and interview requests, contact communications@earth.ox.ac.uk

The paper ‘Anatomy of magmatic hydrothermal system beneath Uturuncu volcano, Bolivia, by joint seismological and petrophysical analysis’ will be published in PNAS at 20:00 BST / 15:00 ET Monday 28 April, DOI 10.1073/pnas.2420996122

A pre-embargo copy of the paper can be viewed on the PNAS tipsheet on EurekAlert.

Images relating to the study which can be used in articles can be found at https://drive.google.com/drive/folders/1TXieDDIKOsfEp8imld9qpZRCtrYJ-p85?usp=sharing  These images are for editorial purposes relating to this press release ONLY and MUST be credited (see file name). They MUST NOT be sold on to third parties.

Cerro Uturuncu, one of many volcanoes on the Bolivian Altiplano that lie above the Altiplano-Puna Magma Body. Photo credit Jon Blundy, University of Oxford.

Cerro Uturuncu, right, and Cerro San Antonio, left, volcanoes above the small town of Quetena Chico on the Bolivian Altiplano. Photo Credit: Jon Blundy, University of Oxford.

About the University of Oxford

Oxford University has been placed number 1 in the Times Higher Education World University Rankings for the ninth year running, and ​number 3 in the QS World Rankings 2024. At the heart of this success are the twin-pillars of our ground-breaking research and innovation and our distinctive educational offer.

Oxford is world-famous for research and teaching excellence and home to some of the most talented people from across the globe. Our work helps the lives of millions, solving real-world problems through a huge network of partnerships and collaborations. The breadth and interdisciplinary nature of our research alongside our personalised approach to teaching sparks imaginative and inventive insights and solutions.

Through its research commercialisation arm, Oxford University Innovation, Oxford is the highest university patent filer in the UK and is ranked first in the UK for university spinouts, having created more than 300 new companies since 1988. Over a third of these companies have been created in the past five years. The university is a catalyst for prosperity in Oxfordshire and the United Kingdom, contributing £15.7 billion to the UK economy in 2018/19, and supports more than 28,000 full time jobs.

---

Journal

Proceedings of the National Academy of Sciences

DOI

10.1073/pnas.2420996122 

Article Title

Anatomy of the magmatic hydrothermal system beneath Uturuncu volcano, Bolivia, by joint seismological and petrophysical analysis

Article Publication Date

28-Apr-2025

 

Some dogs, cats bred to evolve same ‘smushed’ faces

Cornell University

For the first time, scientists at Cornell University and Washington University have uncovered examples of how selection pressures from breeding cats and dogs have led to “convergence” – the tendency of unrelated animals and plants to evolve similar characteristics under similar environmental conditions.

In this case, the researchers found remarkable examples of convergence both within these two domesticated species and also between them. The convergence showed up in breeds with short faces, technically referred to as brachycephalic or “smushed” faces.

As a result of artificial selection from breeding, certain breeds of these two species – which shared a common ancestor but have been evolutionarily separated for 50 million years – have converged to such an extreme that they are more similar to each other than they are to most members of their own species or their ancestors. This phenomenon hadn’t previously been observed in domesticated species, according to the paper, which is under embargo until 3pm ET on Monday, April 28 in PNAS.

When the researchers measured the skulls of brachycephalic dogs and cats, they found strikingly similar overlap between these breeds from two different species.

“Persian cats and pug and Pekingese dogs all have skull shapes that are very similar to each other, with flat and short faces, and their muzzles and palettes are tilted up in the same way,” said Abby Drake, senior lecturer at Cornell. Drake is a corresponding author on the paper along with Jonathan Losos, professor of biology at Washington University.

The same pattern of convergence has occurred multiple times within each species. In dogs, it occurred in bulldog breeds, but then separately in Asian dog breeds such as Pekingese and Shih Tzu. In cats, the same traits can be seen in Persian, Himalayan and Burmese breeds.

When convergence occurs through natural selection – such as in the development of wings in birds, bats and insects – it is usually a sign of a successful trait. In the case of domesticated species, evolution happens so rapidly, it can offer insight into evolutionary processes, Drake said.

The researchers mapped the skull shapes, compared them and discovered these similarities, even though the ancestors of cats and dogs looked quite different. Dogs descended from wolves, a larger animal with a long muzzle, while cats descended from wildcats, which are smaller animals with a shorter face and a snout.

“They start off in different places,” Drake said, “but because humans applied the same selection pressures, they evolved to look almost identical to each other.”

Artificial selection from breeding has led to a remarkable diversity of both cats and dogs, though dog diversity is even more extreme. It turns out dogs as a species are more diverse than the entire order of Carnivora.

“We’re seeing this very large evolutionary variation within a species that’s only been evolving for a relatively very short amount of time,” Drake said. “That’s a remarkable thing to see in evolution, which takes millions of years, but we did it with dogs by pushing them to the extremes.”

In this study, the team similarly found that cats are more diverse as a species than the entire family of Felidae, which has 41 species.

Unfortunately, Drake said, humans have pushed brachycephalic breeds to such extremes that they’re susceptible to breathing, eating and birthing issues and wouldn’t survive in the wild.

In the study, the researchers collected three-dimensional measurements of skull morphology from CT scans of domestic cats, dogs, wildcats, wolves, species within the Canidae (dog) family and from the Felidae (cat) family, and additional species such as weasels and walruses from the order Carnivora. These were acquired from veterinary institutions, museum collections and MorphoSource, a natural history digital archive.

-30-

---

Journal

Proceedings of the National Academy of Sciences

Article Title

Copy-Cat Evolution: Divergence and Convergence Within and Between Cat and Dog Breeds

Article Publication Date

28-Apr-2025

 

Sexism undermines teams by disrupting emotional synchrony’s role in performance

Groundbreaking research highlights the hidden cost of sexual harassment on collaboration and innovation

Bar-Ilan University

Facebook

XLinkedInWeChatBlueskyMessageWhatsAppEmail

In a world where innovation and progress depend on effective teamwork, a new study reveals how sexist behavior within teams sabotages not just individuals, but the very fabric of collaboration.

Researchers found that exposure to sexist comments significantly alters how women interact emotionally during teamwork, increasing a key ingredient of successful collaboration: emotional synchrony. Emotional synchrony—shared, temporally aligned facial expressions among team members—has long been known to enhance trust, coordination, and performance. But this study, published in the Proceedings of the National Academy of Sciences, shows that under threat of sexism, synchrony is repurposed from driving performance to simply fostering social bonding potentially as a defense mechanism.

“Sexism doesn’t just harm individuals—it actively rewires how teams function,” said one of the study’s authors, Prof. Ilanit Gordon, from the Department of Psychology and Gonda (Goldschmied) Multidisciplinary Brain Research Center at Bar-Ilan University and the Child Study Center at the Yale University School of Medicine. “We saw that emotional alignment, which usually helps people work better together, loses its impact for performance when women are subjected to sexist remarks.” Gordon collaborated on the study with Bar-Ilan University PhD student Alon Burns, Prof. Sharon Toker from Tel Aviv University and Prof. Yair Berson from McMaster University.

The research involved 177 all-women dyads collaborating on a task via video conferencing. Participants were randomly assigned to a control group or a sexism condition, in which they received subtle sexist comments from an actor posing as an experimenter leading the study. Advanced facial recognition software tracked the emotional expressions of each participant throughout the task.

The results were striking: While emotional synchrony predicted improved team performance in the control condition, it had no such benefit when teams were exposed to sexism. In fact, synchrony increased in the sexism condition—signaling greater social bonding—but this did not translate into better outcomes.

“Our findings suggest that emotional synchrony under sexism threat is heightened yet redirected toward social coping, rather than collaborating,” Gordon noted. “This shift might weaken the ability or willingness of teams to stay focused on shared goals.”

The implications are clear: creating environments where women feel safe is not only a moral imperative, but also a strategic one. The researchers emphasize that zero-tolerance policies for sexual harassment are essential for maintaining the integrity and effectiveness of team-based work.

---

Journal

Proceedings of the National Academy of Sciences

DOI

10.1073/pnas.2409708122 

Article Title

Sexism in Teams: Exposure to sexist comments increases emotional 5 synchrony but eliminates its benefits for team performance

 

‘Extremely rare event’: bone analysis suggests ancient echidnas lived in water

University of New South Wales

FacebookXLinkedInWeChatBluesky

MessageWhatsAppEmail

MODERN ECHINDA

A

A small bone found 30 years ago at Dinosaur Cove in south eastern Australia could turn what we know about the evolution of echidnas and platypuses on its head.

Up until now, the accepted understanding about these egg-laying monotremes – arguably the most unusual mammals on the planet – was that they were both descended from a land-bound ancestor. And while the platypus ancestors became semiaquatic, the echidnas stayed on the land, or so the story went.

But following a UNSW-led analysis of the bone – which was discovered by a team from Museums Victoria – it now looks like echidnas and platypuses evolved from a water-dwelling ancestor.

Lead author and palaeontologist, Emeritus Professor Suzanne Hand from UNSW’s School of Biological, Earth and Environmental Sciences (School of BEES), says there are about 30 instances where mammals evolved from land-dwelling to live wholly or partly in water, for example, whales, dolphins, dugongs, seals, walruses, otters and beavers. But it’s virtually unheard of to see mammals evolve in the opposite direction.

“We’re talking about a semiaquatic mammal that gave up the water for a terrestrial existence, and while that would be an extremely rare event, we think that’s what happened with echidnas,” she says.

Something funny about this humerus

In a study published today in the science journal PNAS, the researchers describe how a single humerus bone discovered in Victoria in the early 1990s challenges the terrestrial ancestor theory. The humerus bone – which is the upper arm bone between the shoulder and elbow – is the only bone known that belongs to the extinct species, Kryoryctes cadburyi, named in 2005.

Outwardly, the single humerus looked more similar to those found in echidnas than in platypuses, and led some scientists to conclude it may have been an ancestor of modern echidnas. But other scientists have suggested it was an early common ancestor to the platypus and echidna, known as a stem-monotreme. Whether Kryoryctes lived life solely on land like modern echidnas, or were amphibious like the living platypus, has been debated.

To answer these questions, Prof. Hand and colleagues decided to have a closer look at the fossil, including the internal microstructure of the bone using CT and other scanning techniques.

“While the external structure of a bone allows you to directly compare it with similar animals to help work out the animal’s relationships, the internal structure tends to reveal clues about its lifestyle and ecology,” she says.

“So the internal structure doesn't necessarily give you information about what that animal actually is, but it can tell you about its environment and how it lived.”

When Kryoryctes cadburyi lived in southern Victoria around 108 million years ago, during the Age of Dinosaurs (or Mesozoic), monotremes and monotreme-relatives dominated Australia’s mammal faunas.

“Australian Mesozoic mammals are rare and are known mostly only from their teeth and jaws. Kryoryctes cadburyi is so far the only one known from a limb bone,” says co-author Professor Michael Archer, also from UNSW School of BEES.

“This humerus has provided an exceptional opportunity to gain insights into how early Australian mammals lived, and it tells quite a story–perhaps not one we expected to discover.”

When the researchers looked at the internal structure of the ancient humerus bone, they were surprised to discover it didn’t match the light bones of echidnas.

“The internal structure revealed platypuses have very thick bone walls and a very reduced cavity within the bone for the bone marrow, while echidnas have very thin bone walls,” says Prof. Hand.

“The microstructure of the fossil Kryoryctes humerus is more like the internal bone structure seen in platypuses, in which their heavy bones act like ballast allowing them to easily dive to forage for food. You see this in other semiaquatic mammals.”

The researchers have concluded that this analysis adds far more weight to the idea that stem-monotremes started off as semi-aquatic animals. Somewhere along the line, they argue, ancestors of echidnas moved onto the land where their bones became lighter as they adapted to a new way of life. But unfortunately, the fossil record of platypus and echidna ancestors is sparse, and it’s not possible yet to say exactly when this happened.

“This is one of the reasons why we’re increasing our efforts to help investigate the Mesozoic opalised fossils of Lightning Ridge, NSW, which are about the same age as the Victorian fossil deposits,” Prof. Archer says.

“We’re hoping we’ll discover other ancestral monotremes that will help unravel the early history of this most fascinating group of mammals.”

 

Come to think of it…

There are other oddities about modern echidnas that could be further clues that speak to their semi-aquatic, ancient past.

“The bill of the platypus is well known to have lots of highly sensitive receptors that detect tiny electrical currents generated by prey,” Prof. Hand says.

“And while the beak of the echidnas has fewer receptors, people have suggested that these receptors are a leftover of their platypus-heritage, as are remnants of the platypus bill that can be found in the beak of echidna embryos.”

Another feature that could’ve been inherited from an aquatic ancestor, says Prof. Hand, is that the echidnas’ hind feet are turned backwards, much like a platypus’s hind feet which it uses as rudders when swimming.

“But in echidnas, this feature is used when burrowing, something not seen in other mammals except platypuses.”

Echidnas have also been found to have a diving reflex triggered when immersed in water that helps conserve oxygen and prolong breath-holding, and a study of a respiratory protein called myoglobin in mammals also suggests a semi-aquatic ancestry for echidnas.

“A positive charge on the surface of myoglobin is associated with increased capacity of the muscles in the body to store oxygen and increase the length of time a mammal can spend diving. This is high in the platypus, but is also higher than expected in echidnas, even as burrowers.”

Case closed?

Next up for the researchers is to further examine the microscopic anatomy – known as histology – of the Kryoryctes humerus using other methods.

“We know that bone histology can say a lot about how an animal lives. This kind of investigation typically requires destructive sectioning of a bone, which is not possible to do with a unique fossil like Kryoryctes. Instead, we are applying powerful scanning techniques, including non-destructive synchrotron imaging of the fossil, in order to gather even more information to help unravel this ancient mystery,” says Prof. Hand.

The research was carried out in collaboration with the Australian National University and other local institutions along with international organisations from Canada, Colombia, France and the UK.

---

Journal

Proceedings of the National Academy of Sciences

DOI

10.1073/pnas.2413569122 

Method of Research

Imaging analysis

Subject of Research

Animals

Article Title

Bone microstructure supports a Mesozoic origin for a semiaquatic burrowing lifestyle in monotremes (Mammalia)

Article Publication Date

28-Apr-2025

 

New non-invasive brain stimulation technique shows significant reduction in depression, anxiety and PTSD symptoms

University of Texas at Austin

Facebook

XLinkedInWeChaBlueskyMessageWhatsAppEmail

AUSTIN, Texas — Patients suffering from depression, anxiety and trauma-related disorders experienced significant relief from their symptoms after a new treatment that uses sound waves to modulate deep brain activity, according to new research from Dell Medical School at The University of Texas at Austin. The study, published this month in Molecular Psychiatry, demonstrates that low-intensity focused ultrasound technology can safely and effectively target the amygdala — a brain region known to be hyperactive in mood and anxiety disorders — without surgery or invasive procedures.

"Participants showed marked improvements across a range of symptoms after just three weeks of daily treatments," said Gregory Fonzo, Ph.D., senior author of the study and assistant professor in the Department of Psychiatry & Behavioral Sciences at Dell Med. "What makes this approach revolutionary is that it's the first time we've been able to directly modulate deep brain activity without invasive procedures or medications."

In the double-blind study, 29 patients with various mood and anxiety disorders received MRI-guided focused ultrasound to the left amygdala. The results showed both immediate reductions in amygdala activity, and after three weeks of daily sessions, patients experienced clinically significant improvements in negative affect and symptoms of depression, anxiety and PTSD.

"For decades, the amygdala has been a target of interest, but access has required either brain surgery or indirect approaches through cortical stimulation," said Fonzo. "This technology opens a new frontier in psychiatric treatment, potentially offering relief to patients who haven't responded to traditional therapies."

The treatment was well tolerated with no serious adverse events, suggesting a promising safety profile as researchers move toward larger clinical trials.

---

Journal

Molecular Psychiatry

DOI

10.1038/s41380-025-03033-w 

Article Title

Low-intensity transcranial focused ultrasound amygdala neuromodulation: a double-blind sham-controlled target engagement study and unblinded single-arm clinical trial

Article Publication Date

28-Apr-2025