In a proof-of-concept study, researchers demonstrated the effectiveness of a potential new therapy for Timothy syndrome, an often life-threatening and rare genetic disorder that affects a wide range of bodily systems, leading to severe cardiac, neurological, and psychiatric symptoms as well as physical differences such as webbed fingers and toes. The treatment restored typical cellular function in 3D structures created from cells of people with Timothy syndrome, known as organoids, which can mimic the function of cells in the body. These results could serve as the foundation for new treatment approaches for the disorder. The study, supported by the National Institutes of Health (NIH), appears in the journal Nature.
“Not only do these findings offer a potential road map to treat Timothy syndrome, but research into this condition also offers broader insights into other rare genetic conditions and mental disorders,” said Joshua A. Gordon, M.D., Ph.D., director of the National Institute of Mental Health, part of NIH.
Sergiu Pasca, M.D., and colleagues at Stanford University, Stanford, California, collected cells from three people with Timothy syndrome and three people without Timothy syndrome and examined a specific region of a gene known as CACNA1C that harbors a mutation that causes Timothy syndrome. They tested whether they could use small pieces of genetic material that bind to gene products and promote the production of a protein not carrying the mutation, known as antisense oligonucleotides (ASOs), to restore cellular deficits underlying the syndrome.
In the lab, researchers applied the ASOs to human brain tissue structures grown from human cells, known as organoids, and tissue structures formed through the integration of multiple cell types, known as assembloids. They also analyzed organoids transplanted into the brains of rats. All of the methods were created using cells from people with Timothy syndrome. Applying the ASOs restored normal functioning in the cells, and the therapy’s effects were dose-dependent and lasted at least 90 days.
“Our study showed that we can correct cellular deficits associated with Timothy syndrome,” said Dr. Pasca. “We are now actively working towards translating these findings into the clinic, bringing hope that one day we may have an effective treatment for this devastating neurodevelopmental disorder.
The genetic mutation that causes Timothy syndrome affects the exon 8A region of the CACNA1C gene. The gene contains instructions for controlling calcium channels — pores in the cell critical for cellular communication. The CACNA1C gene in humans also contains another region (exon 8) that controls calcium channels but is not impacted in Timothy syndrome type 1. The ASOs tested in this study decreased the use of the mutated exon 8A and increased reliance on the nonaffected exon 8, restoring normal calcium channel functioning.

Cleveland Clinic researchers developed an artficial intelligence (AI) model that can determine the best combination and timeline to use when prescribing drugs to treat a bacterial infection, based solely on how quickly the bacteria grow given certain perturbations. A team led by Jacob Scott, MD, PhD, and his lab in the Theory Division of Translational Hematology and Oncology, recently published their findings in PNAS.
Antibiotics are credited with increasing the average US lifespan by almost ten years. Treatment lowered fatality rates for health issues we now consider minor — like some cuts and injuries. But antibiotics aren’t working as well as they used to, in part because of widespread use.
“Health agencies worldwide agree that we’re entering a post-antibiotic era,” explains Dr. Scott. “If we don’t change how we go after bacteria, more people will die from antibiotic-resistant infections than from cancer by 2050.”
Bacteria replicate quickly, producing mutant offspring. Overusing antibiotics gives bacteria a chance to practice making mutations that resist treatment. Over time, the antibiotics kill all the susceptible bacteria, leaving behind only the stronger mutants that the antibiotics can’t kill.
One strategy physicians are using to modernize the way we treat bacterial infections is antibiotic cycling. Healthcare providers rotate between different antibiotics over specific time periods. Changing between different drugs gives bacteria less time to evolve resistance to any one class of antibiotic. Cycling can even make bacteria more susceptible to other antibiotics.
“Drug cycling shows a lot of promise in effectively treating diseases,” says study first author and medical student Davis Weaver, PhD. “The problem is that we don’t know the best way to do it. Nothing’s standardized between hospitals for which antibiotic to give, for how long and in what order.”
Study co-author Jeff Maltas, PhD, a postdoctoral fellow at Cleveland Clinic, uses computer models to predict how a bacterium’s resistance to one antibiotic will make it weaker to another. He teamed up with Dr. Weaver to see if data-driven models could predict drug cycling regimens that minimize antibiotic resistance and maximize antibiotic susceptibility, despite the random nature of how bacteria evolve.

Dr. Weaver led the charge to apply reinforcement learning to the drug cycling model, which teaches a computer to learn from its mistakes and successes to determine the best strategy to complete a task. This study is among the first to apply reinforcement learning to antibiotic cycling regiments, Drs. Weaver and Maltas say.
“Reinforcement learning is an ideal approach because you just need to know how quickly the bacteria are growing, which is relatively easy to determine,” explains Dr. Weaver. “There’s also room for human variations and errors. You don’t need to measure the growth rates perfectly down to the exact millisecond every time.”
The research team’s AI was able to figure out the most efficient antibiotic cycling plans to treat multiple strains of E. coli and prevent drug resistance. The study shows that AI can support complex decision-making like calculating antibiotic treatment schedules, Dr. Maltas says.
Dr. Weaver explains that in addition to managing an individual patient’s infection, the team’s AI model can inform how hospitals treat infections across the board. He and his research team are also working to expand their work beyond bacterial infections into other deadly diseases.
“This idea isn’t limited to bacteria, it can be applied to anything that can evolve treatment resistance,” he says. “In the future we believe these types of AI can be used to to manage drug-resistant cancers, too.”

Conditions such as diabetes, heart attack and vascular diseases commonly diagnosed in people with spinal cord injuries can be traced to abnormal post-injury neuronal activity that causes abdominal fat tissue compounds to leak and pool in the liver and other organs, a new animal study has found.
After discovering the connection between dysregulated neuron function and the breakdown of triglycerides in fat tissue in mice, researchers found that a short course of the drug gabapentin, commonly prescribed for nerve pain, prevented the damaging metabolic effects of the spinal cord injury.
Gabapentin inhibits a neural protein that, after the nervous system is damaged, becomes overactive and causes communication problems — in this case, affecting sensory neurons and the abdominal fat tissue to which they’re sending signals.
“We believe there is maladaptive reorganization of the sensory system that causes the fat to undergo changes, initiating a chain of reactions — triglycerides start breaking down into glycerol and free fatty acids that are released in circulation and taken up by the liver, the heart, the muscles, and accumulating, setting up conditions for insulin resistance,” said senior author Andrea Tedeschi, assistant professor of neuroscience in The Ohio State University College of Medicine.
“Through administration of gabapentin, we were able to normalize metabolic function.”
The study is published today (April 24, 2024) in Cell Reports Medicine.
Previous research has found that cardiometabolic diseases are among the leading causes of death in people who have experienced a spinal cord injury. These often chronic disorders can be related to dysfunction in visceral white fat (or adipose tissue), which has a complex metabolic role of storing energy and releasing fatty acids as needed for fuel, but also helping keep blood sugar levels at an even keel.

Earlier investigations of these diseases in people with neuronal damage have focused on adipose tissue function and the role of the sympathetic nervous system — nerve activity known for its “fight or flight” response, but also a regulator of adipose tissue that surrounds the abdominal organs.
Instead, Debasish Roy — a postdoctoral researcher in the Tedeschi lab and first author on the paper — decided to focus on sensory neurons in this context. Tedeschi and colleagues have previously shown that a neuronal receptor protein called alpha2delta1 is overexpressed after spinal cord injury, and its increased activation interferes with post-injury function of axons, the long, slender extensions of nerve cell bodies that transmit messages.
In this new work, researchers first observed how sensory neurons connect to adipose tissue under healthy conditions, and created a spinal cord injury mouse model that affected only those neurons — without interrupting the sympathetic nervous system.
Experiments revealed a cascade of abnormal activity within seven days after the injury in neurons — though only in their communication function, not their regrowth or structure — and in visceral fat tissue. Expression of the alpha2delta1 receptor in sensory neurons increased as they over-secreted a neuropeptide called CGRP, all while communicating through synaptic transmission to the fat tissue — which, in a state of dysregulation, drove up levels of a receptor protein that engaged with the CGRP.
“These are quite rapid changes. As soon as we disrupt sensory processing as a result of spinal cord injury, we see changes in the fat,” Tedeschi said. “A vicious cycle is established — it’s almost like you’re pressing the gas pedal so your car can run out of gas but someone else continues to refill the tank, so it never runs out.”
The result is the spillover of free fatty acids and glycerol from fat tissue, a process called lipolysis, that has gone out of control. Results also showed an increase in blood flow in fat tissue and recruitment of immune cells to the environment.

“The fat is responding to the presence of CGRP, and it’s activating lipolysis,” Tedeschi said. “CGRP is also a potent vasodilator, and we saw increased vascularization of the fat — new blood vessels forming as a result of the spinal cord injury. And the recruitment of monocytes can help set up a chronic pro-inflammatory state.”
Silencing the genes that encode the alpha2delta1 receptor restored the fat tissue to normal function, indicating that gabapentin — which targets alpha2delta1 and its partner, alpha2delta2 — was a good treatment candidate. Tedeschi’s lab has previously shown in animal studies that gabapentin helped restore limb function after spinal cord injury and boosted functional recovery after stroke.
But in these experiments, Roy discovered something tricky about gabapentin: The drug prevented changes in abdominal fat tissue and lowered CGRP in the blood — and in turn prevented spillover of fatty acids into the liver a month later, establishing normal metabolic conditions. But paradoxically, the mice developed insulin resistance — a known side effect of gabapentin.
The team changed drug delivery tactics, starting with a high dose and tapering off — and stopping after four weeks.
“This way, we were able to normalize metabolism to a condition much more similar to control mice,” Roy said. “This suggests that as we discontinue administration of the drug, we retain beneficial action and prevent spillover of lipids in the liver. That was really exciting.”
Finally, researchers examined how genes known to regulate white fat tissue were affected by targeting alpha2delta1 genetically or with gabapentin, and found both of these interventions after spinal cord injury suppress genes responsible for disrupting metabolic functions.
Tedeschi said the combined findings suggest starting gabapentin treatment early after a spinal cord injury may protect against detrimental conditions involving fat tissue that lead to cardiometabolic disease — and could enable discontinuing the drug while retaining its benefits and lowering the risk for side effects.
This work was supported by grants from the National Institute of Neurological Disorders and Stroke and the National Institutes of Health, and by the Chronic Brain Injury program at Ohio State.
Co-authors, all from Ohio State, were Elliot Dion, Jesse Sepeda, Juan Peng, Sai Rishik Lingam, Kristy Townsend, Andrew Sas and Wenjing Sun.

A Ludwig Cancer Research study has discovered how a lipid molecule found at high levels within tumors undermines the anti-cancer immune response and compromises a recently approved immunotherapy known as adoptive cell therapy (ACT) using tumor infiltrating lymphocytes, or TIL-ACT. In this individualized cell therapy, TILs — CD8+ T cells that kill cancer cells — are expanded in culture from a patient’s tumor samples and reinfused into the patient as a treatment.
Researchers led by Ludwig Lausanne’s Matteo Morotti, Alizee Grimm, Denarda Dangaj Laniti and Director George Coukos report in the current issue of Nature their discovery — based on analyses of data and samples collected in TIL-ACT clinical trials — of the mechanism by which the lipid, prostaglandin E2 (PGE2), poisons TIL metabolism to serve as a checkpoint against their anti-tumor activity. They also show that disrupting that mechanism during the cell culture processes employed in TIL-ACT dramatically improves the therapeutic potential of transferred TILs in mouse models of cancer.
A companion study led by researchers at the Technical University of Munich, done using mouse models of cancer, confirms the Ludwig Lausanne team’s findings and appears in the same issue of Nature. Several researchers share authorship of both papers.
“These findings have important implications for cancer immunotherapy in general, as they identify a novel and eminently targetable checkpoint against the function of infiltrating cytotoxic T cells in the tumor microenvironment,” said Coukos. “More immediately, we can now complete the circle here at Lausanne: we have harnessed the data and materials obtained from TIL-ACT trials in humans to advance our understanding of tumor immunology and can now apply what we have learned to improve outcomes for patients undergoing such therapies. This is a key element of our strategy — and of Ludwig’s overall mission.”
The Ludwig Lausanne researchers began by examining gene expression data collected from T cells isolated from patients for TIL-ACT. Their analysis revealed that the TILs that already bore markers of response to interleukin-2 (IL-2) — a factor essential to functional vitality and proliferation of T cells — were the ones that expanded best in culture. The researchers also tracked the growth in culture of 215 individual tumor-reactive TILs that respond to IL-2, which is a key component of TIL cultures, and showed that this is indeed the case.
Further examination of gene expression data collected from clinical trial samples revealed that TILs that responded poorly to IL-2 expressed relatively large numbers of receptors for PGE2 on their surfaces. In line with that finding, anti-cancer TILs from tumor fragments that had high levels of PGE2 were found to expand poorly in culture.
To explore how PGE2 compromises TIL-ACT, the researchers began by identifying a signature of gene expression associated with PGE2’s effects on T cells.

“We found that patients’ tumor-reactive TILs that bore this PGE2 signature expanded very poorly in culture, and that these TILs were often in states that would otherwise be essential to therapeutic responses,” said Morotti. “Further, corresponding clinical trial data revealed that the melanoma patients whose TILs bore that signature had responded poorly to TIL-ACT therapy.”
The researchers next probed how PGE2 exerts its effects on TILs. They found that the lipid, acting through its receptors (EP2 and EP4), disrupts the ability of T cells to sense and respond to IL-2 by monkeywrenching the assembly of the IL-2 receptor’s component proteins. The resulting loss of IL-2 stimulation initiates a cascade of biochemical events in the cells that culminates in profound metabolic dysfunction, inducing a functional lethargy in the TILs known as “anergy” and ultimately triggering ferroptosis, a type of programmed cell death.
The researchers also examined whether blocking PGE2 could overcome these effects.
“By adding a drug that inhibits PGE2 production to the TIL culture medium we restored the ability of TILs to respond to IL-2 and improved the expansion of tumor-reactive TILs more than two-fold,” said Grimm. “Small molecules that block PGE2 interaction with its receptors had a similar effect. These studies not only confirmed our hypothesis but also identify a means to swiftly translate our findings for clinical application.”
The researchers show that, grown in the presence of PGE2 inhibitor, tumor-reactive TILs become responsive to IL-2 once again and show signs of renewed metabolic fitness and functional vitality. These TILs prevented cancer cells taken from the tumors they previously inhabited from forming new tumors in mice, while the same TILs grown sans PGE2-inhibitor did not. The revitalized TILs were also better agents of TIL-ACT therapy in a mouse model.
The companion study in Nature, led by the Jan Böttcher lab in Munich, confirms the findings of this study in mouse models of cancer. It also shows that the inhibition of IL-2 signaling in TILs occurs within the microenvironment of tumors. Engagement of the PD-1 checkpoint on T cells, which is currently targeted by several immunotherapies, is by contrast thought to occur mainly in the lymph nodes around tumors.
“When we learned we were working on essentially the same problem, we decided to combine our efforts and publish our shared discoveries as back-to-back publications in the same journal,” said Dangaj Laniti. “That spirit of cooperation, rather than the usual, fierce competition, has borne fruit in the discovery of a previously unknown immune checkpoint in tumors that is mechanistically distinct from the PD-1 checkpoint that cancers exploit to foil anti-tumor T cells. It has been very gratifying to be a part of this partnership, whose discoveries will surely be of great benefit to cancer patients.”
In addition to their posts at Ludwig Lausanne, George Coukos directs the Department of Oncology at the Lausanne University Hospital (UNIL CHUV) and codirects the Swiss Cancer Center Léman and Denarda Dangaj Laniti is the Head of the Tumor Microenvironment and Biomarker Discovery Lab at Ludwig Lausanne.
This study was supported by Ludwig Cancer Research, Swiss Cancer League Foundation, the German Research Foundation and grants from the Biltema Foundation, Paul Matson Foundation and Cancera Foundation.

Malaria is a mosquito-borne disease caused by a parasite that spreads from bites of infected female Anopheles mosquitoes. If left untreated in humans, malaria can cause severe symptoms, health complications and even death.
In tropical and subtropical regions where malaria is prevalent, scientists are concerned that climate warming might increase the risk of malaria transmission in certain areas and contribute to further spread. However, there is still much to learn about the relationship between temperature and the mosquito and parasite traits that influence malaria transmission.
In “Estimating the effects of temperature on transmission of the human malaria parasite, Plasmodium falciparum,” a groundbreaking study published in the journal Nature Communications, researchers at the University of Florida, Pennsylvania State University and Imperial College, combined novel experimental data within an innovative modeling framework to examine how temperature might affect transmission risk in different environments in Africa.
“In broad terms, scientists know that temperature affects key traits such as mosquito longevity, the time it takes for a mosquito to become infectious after feeding on an infected host, and the overall ability of the mosquito to transmit the disease” said Matthew Thomas, a UF/IFAS professor and UF/IFAS Invasion Science Research Institute (ISRI) director. “But what might seem surprising is that these temperature dependencies have not been properly measured for any of the primary malaria vectors in Africa.”
“Our findings provide novel insights into the effects of temperature on the ability of Anopheles gambiae mosquitoes — arguably the most important malaria mosquito in Africa — to transmit Plasmodium falciparum, the most prevalent species of human malaria in Africa,” said Eunho Suh, joint first-author with Isaac Stopard at Imperial College, and assistant research professor at Penn State, who conducted the empirical research as a post-doctoral student in Thomas’ previous lab.
The study involved several detailed laboratory experiments in which hundreds of mosquitoes were fed with Plasmodium falciparum-infected blood and then exposed at different temperatures to examine the progress of infection and development rate within the mosquitoes, as well as the survival of the mosquitoes themselves.
“The novel data were then used to explore the implications of temperature on malaria transmission potential across four locations in Kenya that represent diverse current environments with different intensities of baseline transmission, and that are predicted to experience different patterns of warming under climate change,” explained Thomas.

The study supports previous research results in demonstrating that various mosquito and parasite traits exhibit intermittent relationships with temperature and that under future warming temperatures, transmission potential is likely to increase in some environments but could reduce in others. However, the new data suggest that parasites can develop more quickly at cooler temperatures and that the rate of parasite development might be less sensitive to changes in temperature, than previously thought.
The data also indicate that the successful development of parasites in the mosquito, declines at thermal extremes, contributing to the upper and lower environmental bounds for transmission.
Combining these results into a simple transmission model suggests that contrary to earlier predictions, the anticipated surge in malaria transmission, attributed to climate warming, may be less severe than feared, particularly in cooler regions like the Kenyan Highlands.
“Some of the current assumptions on mosquito ecology and malaria transmission derive from work done in the early part of the last century. Our study is significant in highlighting the need to revisit some of this conventional understanding,” said Thomas.
“While the time it takes for a mosquito to become infectious is strongly dependent on environmental temperature, it also depends on the species and possibly strain of malaria and mosquito,” said Suh.
The comprehensive study and findings represent a significant step forward in understanding the intricacies of malaria transmission and paves the way for future research aimed at controlling malaria on a global scale.
“Our work focused on the malaria parasite Plasmodium falciparum in the African malaria vector, Anopheles gambiae. However, Plasmodium vivaxis another important parasite species responsible for most malaria in Asia, as well as the recently reported malaria cases in the U.S.,” said Suh. “Like Plasmodium falciparum, the established model describing the effects of temperature on development of Plasmodium vivaxremains poorly validated.”
The same is true for other vector-borne diseases, such as dengue or Zika virus, added Suh.
“We need more work of the type we present in the current paper, ideally using local mosquito and parasite or pathogen strains, to better understand the effects of climate and climate change on transmission risk,” he said.

Cells constantly navigate a dynamic environment, facing ever-changing conditions and challenges. But how do cells swiftly adapt to these environmental fluctuations? A new Moffitt Cancer Center study, published in iScience, is answering that question by challenging our understanding of how cells function. A team of researchers suggests that cells possess a previously unknown information processing system that allows them to make rapid decisions independent of their genes.
For decades, scientists have viewed DNA as the sole source of cellular information. This DNA blueprint instructs cells on how to build proteins and carry out essential functions. However, new research at Moffitt led by Dipesh Niraula, Ph.D., and Robert Gatenby, M.D., discovered a nongenomic information system that operates alongside DNA, enabling cells to gather information from the environment and respond quickly to changes.
The study focused on the role of ion gradients across the cell membrane. These gradients, maintained by specialized pumps, require large energy expenditure to generate varying transmembrane electrical potentials. The researchers proposed that the gradients represent an enormous reservoir of information that allows cells to monitor their environment continuously. When information is received at some point on the cell membrane, it interacts with specialized gates in ion-specific channels, which then open, allowing those ions to flow along the pre-existing gradients to form a communication channel. The ion fluxes trigger a cascade of events adjacent to the membrane, allowing the cell to analyze and rapidly respond to the information. When the ion fluxes are large or prolonged, they can cause self-assembly of the microtubules and microfilaments for the cytoskeleton.
Typically, the cytoskeleton network provides mechanical support for the cell and is responsible for cell shape and movement. However, the Moffitt researchers noted that proteins from the cytoskeleton are also excellent ion conductors. This allows the cytoskeleton to act as a highly dynamic intracellular wiring network to transmit ion-based information from the membrane to the intracellular organelles, including mitochondria, endoplasmic reticulum and the nucleus. The researchers suggested that this system, which allows for rapid and local responses to specific signals, can also generate coordinated regional or global responses to larger environmental changes.
“Our research reveals the capability of cells to harness transmembrane ion gradients as a means of communication, allowing them to sense and respond to changes in their surroundings rapidly,” said Niraula, an applied research scientist in the Department of Machine Learning. “This intricate network enables cells to make swift and informed decisions, critical for their survival and function.”
The researchers believe that this nongenomic information system is critical for forming and maintaining normal multicellular tissue and suggests the well described ion fluxes in neurons represent a specialized example of this broad information network. Disruption of these dynamics may also be a critical component of cancer development. They demonstrated their model was consistent with multiple experimental observations and highlighted several testable predictions arising from their model, hopefully paving the way for future experiments to validate their theory and shed light on the intricacies of cellular decision-making.
“This study challenges the implicit assumption in biology that the genome is the sole source of information, and that the nucleus acts as a kind of central processor. We present an entirely new network of information that allows rapid adaptation and sophisticated communication necessary for cell survival and probably deeply involved in the intercellular signaling that permits functioning multicellular organisms,” said Gatenby, co-director of the Center of Excellence for Evolutionary Therapy at Moffitt.
This work was supported by the National Institutes of Health (R01-CA233487).

A thin film that combines an electrode grid and LEDs can both track and produce a visual representation of the brain’s activity in real-time during surgery-a huge improvement over the current state of the art. The device is designed to provide neurosurgeons visual information about a patient’s brain to monitor brain states during surgical interventions to remove brain lesions including tumors and epileptic tissue.
Each LED in the device mirrors the activity of a few thousand neurons. In a series of proof-of-concept experiments in rodents and large non-primate mammals, researchers showed that the device can effectively track and display neural activity in the brain corresponding to different areas of the body. In this case, the LEDs developed by the team light up red in the areas that need to be removed by the surgeon. Surrounding areas that control critical functions and should be avoided show up in green.
The study also showed that the device can visualize the onset and map the propagation of an epileptic seizure on the surface of the brain. This would allow physicians to isolate the ‘nodes’ of the brain that are involved in epilepsy. It also would allow physicians to deliver necessary treatment by removing tissue or by using electrical pulses to stimulate the brain.
“Neurosurgeons could see and stop a seizure before it spreads, view what brain areas are involved in different cognitive processes, and visualize the functional extent of tumor spread. This work will provide a powerful tool for the difficult task of removing a tumor from the most sensitive brain areas,” said Daniel Cleary, one of the study’s coauthors, a neurosurgeon and assistant professor at Oregon Health and Science University. Cleary was a medical resident and a postdoctoral researcher at the University of California San Diego.
The device was conceived and developed by a team of engineers and physicians from University of California San Diego and Massachusetts General Hospital (MGH) and was led by Shadi Dayeh, the paper’s corresponding author and a professor in the Department of Electrical and Computer Engineering at UC San Diego. The team describes their work in the April 24 issue of the journal Science Translational Medicine.
During brain surgery, physicians need to map brain function to define which areas of the organ control critical functions and can’t be removed. Currently, neurosurgeons work with a team of electrophysiologists during the procedure. But that team and their monitoring equipment are located in a different part of the operating room. Brain areas that need to be protected and those that need to be operated on are either marked by electrophysiologists on a paper that is brought to the surgeon or communicated verbally to the surgeon, who then places sterile papers on the brain surface to mark these regions. “Both are inefficient ways of communicating critical information during a procedure, and could impact its outcomes,” said Dr. Angelique Paulk of MGH, who is a co-author and co-inventor of the technology.
In addition, the electrodes currently used to monitor brain activity during surgery do not produce detailed fine grained data. So surgeons need to keep a buffer zone, known as resection margin, of 5 to 7 millimeters (about ¼ of an inch) around the area they are removing inside the brain. This means that they might leave some harmful tissue in. The new device provides a level of detail that would shrink this buffer zone to less than a millimeter.

“We invented the brain microdisplay to display with precision critical cortical boundaries and to guide neurosurgery in a cost-effective device that simplifies and reduces the time of brain mapping procedures,” said Shadi Dayeh, the paper’s corresponding author and a professor in the Department of Electrical and Computer Engineering at the UC San Diego Jacobs School of Engineering.
Researchers installed the LEDs on top of another innovation from the Dayeh lab, the platinum nanorod electrode grid (PtNRGrid). Using the PtNRGrids since 2019, Dayeh’s team pioneered human brain and spinal cord mapping with thousands of channels to monitor brain neural activity. They reported early safety and effectiveness results in a series of articles in Science Translational Medicine in 2022 in tens of human subjects. (New sensor grids record human brain signals with record breaking resolution and Microelectrode array can enable safer spinal cord surgery) — ahead of Neuralink and other companies in this space.
The PtNRGrid also includes perforations, which enable physicians to insert probes to stimulate the brain with electrical signals, both for mapping and for therapy.
How it’s made
Dayeh and his team used their expertise in working with Gallium Nitride to develop a manufacturing technique for high-efficiency LEDs that do not heat up when they light up and do not damage brain tissues. The material itself is grown on a flat and rigid substrate called Qromis substrate technology. Dayeh’s team at UC San Diego was able to embed thousands of LEDs in flexible films and release them from the substrate in the form of a flexible display panel. Researchers then used inkjet printing to deposit quantum dot inks on the surface of the LEDs to convert their blue light to multiple other colors. “This enables richer and more nuanced visual representation of neural activity patterns,” said Dayeh.
“These Gallium nitride-based inorganic micro-LEDs, substantially brighter and power-efficient than organic LEDs, can maintain clear visibility under surgical lights that may exceed the brightness of direct sunlight. The iEEG microdisplay, just a few tens of microns thick, captures brain activity at 20,000 samples per second across thousands of channels and visualizes it at a video rate of 40 Hz. This enables precise and real-time displays of cortical dynamics during critical surgical interventions,” said Youngbin Tchoe, the first author and co-inventor, formerly a postdoc in the Dayeh group at UC San Diego and now an assistant professor at Ulsan National Institute of Science and Technology.

The microdisplays measure 5 by 5 square millimeters and 32 by 32 square millimeters and include either 1024 or 2048 of these LEDs, laminated on the back of the PtNRGrid. In addition to the LEDs, the device includes acquisition and control electronics as well as software drivers to analyze and project cortical activity directly from the surface of the brain.
“The brain iEEG-microdisplay can impressively both record the activity of the brain to a very fine degree and display this activity for a neurosurgeon to use in the course of surgery. We hope that this device will ultimately lead to better clinical outcomes for patients with its ability to both reveal and communicate the detailed activity of the underlying brain during surgery,” said study coauthor Jimmy Yang, a neurosurgeon and assistant professor at The Ohio State University.
Next steps
Dayeh’s team is working to build a microdisplay that will include 100,000 LEDs, with a resolution equivalent to that of a smartphone screen. Each LED in those displays would reflect the activity of a few hundred neurons. These brain microdisplays will cost a fraction of a high-end smartphone.
This brain microdisplay will also include a foldable portion. This would allow surgeons to operate within the foldable portion and monitor the impact of the procedure as the other, unfolded portion of the microdisplay shows the status of the brain in real time.
Researchers are also working on one limitation of the study. The close proximity of the LED sensors and the PtNRGrids led to a slight interference and noise in the data. The team plans to build customized hardware to change the frequency of the pulses that turn on the LEDs to make it easier to screen out that signal, which is not relevant to the brain’s electrical activity.
The work was supported by the National Institutes of Health primarily by Dayeh’s Director’s New Innovator Award No. NIBIB DP2-EB029757 titled “Bringing Light to Functional Mapping in Resective Neurosurgery.” The research was supported in part by the BRAIN® Initiative NIH grants R01NS123655, K99NS119291, UG3NS123723, and 5R01NS109553.
The brain microdisplay was fabricated in the Nano3 cleanroom facilities at UC San Diego’s Qualcomm Institute and was tested in large mammals at UC San Diego’s Center of the Future of Surgery.

The abortion case before the Supreme Court on Wednesday featured vigorous questioning and comments, particularly by the three liberal justices. At issue is whether Idaho’s near-total ban on abortion is so strict that it violates a federal law requiring emergency care for any patient, including providing abortions for pregnant women in dire situations.A ruling could reverberate beyond Idaho, to at least half a dozen other states that have similarly restrictive bans.The implications of the case could also extend beyond abortion, including whether states can legally restrict other types of emergency medical care and whether the federal law opens the door for claims of fetal personhood.Here are some takeaways:The case centers on whether Idaho’s abortion ban violates federal law.Idaho’s ban allows abortion to save the life of a pregnant woman, but not to prevent her health from deteriorating. The federal government says it therefore violates the Emergency Medical Treatment and Labor Act, or EMTALA, which was enacted nearly 40 years ago.EMTALA says that when a patient goes to an emergency room with an urgent medical issue, hospitals must either provide treatment to stabilize the patient or transfer the patient to a medical facility that can, regardless of the patient’s ability to pay. It says that if a state law conflicts with the federal law, the federal law takes precedence.A lawyer representing Idaho, Joshua Turner, told the Supreme Court that the state does not believe its abortion ban conflicts with the federal law. He said the ban allows emergency departments to provide abortions if a pregnant woman has a medical problem that is likely to lead to her death, not just if she is facing imminent death.We are having trouble retrieving the article content.Please enable JavaScript in your browser settings.Thank you for your patience while we verify access. If you are in Reader mode please exit and log into your Times account, or subscribe for all of The Times.Thank you for your patience while we verify access.Already a subscriber? Log in.Want all of The Times? Subscribe.

The abortion case before the Supreme Court on Wednesday featured vigorous questioning and comments, particularly by the three liberal justices. At issue is whether Idaho’s near-total ban on abortion is so strict that it violates a federal law requiring emergency care for any patient, including providing abortions for pregnant women in dire situations.A ruling could reverberate beyond Idaho, to at least half a dozen other states that have similarly restrictive bans.The implications of the case could also extend beyond abortion, including whether states can legally restrict other types of emergency medical care and whether the federal law opens the door for claims of fetal personhood.Here are some takeaways:The case centers on whether Idaho’s abortion ban violates federal law.Idaho’s ban allows abortion to save the life of a pregnant woman, but not to prevent her health from deteriorating. The federal government says it therefore violates the Emergency Medical Treatment and Labor Act, or EMTALA, which was enacted nearly 40 years ago.EMTALA says that when a patient goes to an emergency room with an urgent medical issue, hospitals must either provide treatment to stabilize the patient or transfer the patient to a medical facility that can, regardless of the patient’s ability to pay. It says that if a state law conflicts with the federal law, the federal law takes precedence.A lawyer representing Idaho, Joshua Turner, told the Supreme Court that the state does not believe its abortion ban conflicts with the federal law. He said the ban allows emergency departments to provide abortions if a pregnant woman has a medical problem that is likely to lead to her death, not just if she is facing imminent death.We are having trouble retrieving the article content.Please enable JavaScript in your browser settings.Thank you for your patience while we verify access. If you are in Reader mode please exit and log into your Times account, or subscribe for all of The Times.Thank you for your patience while we verify access.Already a subscriber? Log in.Want all of The Times? Subscribe.

Since a new form of bird flu arrived in 2022, federal officials have sought to reassure Americans that the threat to the public remained low.The Biden administration on Wednesday said that it would begin requiring dairy cows moving across state lines to be tested for bird flu, which has been spreading in herds for months. The new policy is part of a growing effort to stamp out the spread of a virus that federal health officials have sought to reassure Americans poses little risk to people so far.The new order, issued by the Department of Agriculture, says that lactating cows must test negative for influenza A viruses, a class that includes bird flu, before they are transported. The owners of herds with positive tests will need to provide data on the movements of the cattle to help investigators trace the disease.The testing will help protect the livestock industry, limit the spread of the virus and “better understand this disease,” Mike Watson, a senior Department of Agriculture official, told reporters in a press briefing Wednesday morning.Since a highly contagious form of bird flu was detected in the United States in 2022, federal officials have sought to reassure Americans that the threat to the public remained low, even as the virus infected a growing number of mammals. Federal regulators on Tuesday announced that inactive viral fragments had been found in pasteurized milk, a suggestion that the virus was likely spreading much more widely among cattle than previously known.Dr. Nirav Shah, the principal deputy director of the Centers for Disease Control and Prevention, told reporters on Wednesday that there were no changes in the genetic makeup of the virus that would allow it to spread easily among people. So far, Dr. Shah said, states have been monitoring 44 people who were exposed to the virus and are being monitored for infection.As of Wednesday, the outbreak had spread to 33 herds in eight states, according to the U.S.D.A. But just one human infection has been reported, in a dairy worker in Texas who had direct contact with sick cows. The case was mild.We are having trouble retrieving the article content.Please enable JavaScript in your browser settings.Thank you for your patience while we verify access. If you are in Reader mode please exit and log into your Times account, or subscribe for all of The Times.Thank you for your patience while we verify access.Already a subscriber? Log in.Want all of The Times? Subscribe.