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‘Overdue’ debate unfurls over neuroimaging method

By Angie Voyles Askham When Shan Siddiqi arrived in Australia in February to speak at the 2026 Noosa Brain Workshop, he was still thinking about a paper published in Nature Neuroscience three weeks prior. The work had criticized lesion network mapping (LNM), a neuroimaging method that Siddiqi uses as the basis for much of his work. LNM uses the location of brain lesions in various health conditions to infer information about networks of brain activity altered in those conditions. But the January paper claimed the approach produces biased results, and points to largely the same brain networks no matter the condition. After reading the full paper, however, Siddiqi, associate professor of psychiatry at Harvard Medical School, decided the authors’ criticism was toothless—it highlighted issues that he and his colleagues were aware of, and had already developed methods to address. Yet to his dismay, in the following days and weeks the criticism kept coming, both on social media and in news articles, including one by The Transmitter. The issue hung over the conference, too. During a social event on the first night of the Noosa meeting, other attendees asked Siddiqi, as a leading proponent of the method, for his thoughts, and he decided he needed to address the criticism in his talk the following day. The next afternoon, he told the audience of senior neuroimaging researchers that he took the challenge raised in the paper seriously, and said it had caused him and his co-author Michael D. Fox to reanalyze their data in collaboration with neuroimaging statisticians. He then presented the two competing hypotheses to the audience—LNM findings are disease specific versus LNM is mathematically flawed—and explained how he and Fox tested both with real data. The results seemed to validate LNM, Siddiqi said, leading him to conclude that the critique rested on incorrect assumptions about how the method is implemented. © 2026 Simons Foundation

Related chapters from BN: Chapter 2: Functional Neuroanatomy: The Cells and Structure of the Nervous System
Related chapters from MM:Chapter 2: Neurophysiology: The Generation, Transmission, and Integration of Neural Signals
Link ID: 30205 - Posted: 04.18.2026

Colliding currents can target the deep brain without surgery

By Jennie Erin Smith In 2017, physicist Nir Grossman made a discovery that promised a versatile new way to manipulate the living brain. Working in mice, he and his collaborators applied two high-frequency electrical currents to the skull. At the spot in the rodents’ brains where the currents collided, the electric field altered neural activity. Other noninvasive methods typically reach no further than the cortex, the brain’s outer layer. The new approach, called temporal interference (TI) stimulation, offered access to deep-brain areas previously only targetable with surgery. Neuroscientists were quick to see TI’s potential for studying the brain and treating its disorders, and they are now testing it in a variety of human trials. Although the studies are still small and many have not been replicated, they hint that TI may have potential to ease epilepsy symptoms, help stroke patients recover movement, boost memory in people with Alzheimer’s disease, and treat psychiatric conditions. Many say TI—which uses two pairs of head-mounted electrodes linked to portable current generators—is nimbler and likely safer than transcranial focused ultrasound, another emerging technology that can modulate deep-brain regions without surgery. And because TI equipment is inexpensive and widely available, it’s been easy for labs to try out. “What [TI] should be is an open-source therapy,” says physicist and epilepsy researcher Adam Williamson of St. Anne’s University Hospital. This year, he and his colleagues showed in a pilot study of people with epilepsy that TI stimulation to the hippocampus, a deep-brain structure that is often the source of hard-to-treat seizures, could both suppress spikes of abnormal brain activity and improve participants’ sleep. His group and another at Duke University are collaborating on a larger clinical trial of the approach. In TI, two high-frequency electrical currents applied to the brain meet or interfere to form a low-frequency focal area, or “envelope,” that can boost or suppress the rate of neurons’ electrical signaling. “It’s a powerful way to entrain neuronal activity,” says Melanie Boly, an epilepsy researcher at the University of Wisconsin–Madison. © 2026 American Association for the Advancement of Science.

Fed on Reams of Cell Data, AI Maps New Neighborhoods in the Brain

By Amber Dance Real estate agents will tell you that a home’s most important feature is “location, location, location.” It’s similar in neuroscience: “Location is everything in the brain,” said Bosiljka Tasic (opens a new tab), a self-described “biological cartographer.” Brain injury in one spot could knock out memory; damage in another could interfere with personality. Neuroscientists and doctors are lost without a good map. Researchers have been mapping the brain for more than a century. By tracing cellular patterns that are visible under a microscope, they’ve created colorful charts and models that delineate regions and have been able to associate them with functions. In recent years, they’ve added vastly greater detail: They can now go cell by cell and define each one by its internal genetic activity. But no matter how carefully they slice and how deeply they analyze, their maps of the brain seem incomplete, muddled, inconsistent. For example, some large brain regions have been linked to many different tasks; scientists suspect that they should be subdivided into smaller regions, each with its own job. So far, mapping these cellular neighborhoods from enormous genetic datasets has been both a challenge and a chore. Recently, Tasic, a neuroscientist and genomicist at the Allen Institute for Brain Science, and her collaborators recruited artificial intelligence for the sorting and mapmaking effort. They fed genetic data from five mouse brains — 10.4 million individual cells with hundreds of genes per cell — into a custom machine learning algorithm. The program delivered maps that are a neuro-realtor’s dream, with known and novel subdivisions within larger brain regions. Humans couldn’t delineate such borders in several lifetimes, but the algorithm did it in hours. The authors published their methods (opens a new tab) in Nature Communications in October. © 2026 Simons Foundation

BRAIN Initiative researchers ‘dream big’ amid shifts in leadership, funding

By Claudia López Lloreda The U.S. Brain Research through Advancing Innovative Neurotechnologies (BRAIN) Initiative is kicking off a new phase. In a road map published in November, it identified four research priorities for the next decade: integrating its databases, informing precision circuit therapies, understanding human neuroscience and advancing NeuroAI. The plan shows a thoughtful effort to “protect a very important initiative,” says J. Anthony Movshon, professor of neural science and psychology at New York University—at a time when its future seems unsettled. The BRAIN Initiative is co-led by the directors of the National Institute of Mental Health and the National Institute for Neurological Disorders and Stroke. But the NIMH has had an acting director since June 2024. Last month, the Trump administration terminated the initiative’s other co-director—Walter Koroshetz—from his role as director of the National Institute for Neurological Disorders and Stroke. And it is not clear whether the initiative will have sufficient funding or support to undertake this decade-long effort, says Joshua Sanes, professor emeritus of molecular and cellular biology at Harvard University and contributing editor for The Transmitter. “My guess is that if things continue politically the way they’re going now, [these goals] would not be accomplished in the United States in the next 10 years.” Even if the BRAIN Initiative receives the amount of funding it is expecting, many neuroscientists are too busy grappling with the fallout of grant cancellations, hiring freezes and the loss of training programs to think about the future, says Eve Marder, university professor of biology at Brandeis University. “I’m talking to all these people who are struggling to keep their labs open.” “You can have all the dreams in the universe,” but these big-picture speculations, which may require vast resources, are hard to reconcile with the erosion and destruction of academic science and training programs for young investigators, she adds. “It is difficult to look at a 10-year horizon, and [it] may be a waste of time and effort when we don’t know what is happening to science funding in the next year.” © 2026 Simons Foundation

Methodological flaw may upend network mapping tool

By Angie Voyles Askham More than 200 published studies and at least seven ongoing clinical trials rely on potentially faulty brain network maps, according to a study published today in Nature Neuroscience. The findings cast doubt on a widely used method to generate brain network maps, says František Váša, senior lecturer in machine learning and computational neuroscience at King’s College London, who was not involved in the new study and has not used the approach in his own work. “I think it’s worth revisiting some of the literature critically,” he says. And for those who use the method or plan to, “proceed with caution,” he adds. The creators of the method, called lesion network mapping (LNM), say that the issues raised by the new study are not insurmountable. The study’s “results are often striking and tell an important cautionary point—that lesion network mapping can be prone to false-positive findings or nonspecific findings, and study designs need to be constructed carefully in a way that can account for this,” wrote LNM co-developer Aaron Boes, professor of pediatrics at the University of Iowa’s Carver College of Medicine, in an email to The Transmitter. Boes and his colleagues developed LNM in 2015 to identify the pattern of brain activity disrupted in a given neurological condition, whether obsessive-compulsive disorder, Parkinson’s disease or psychopathy. It spawned a new way to put functional MRI to practical use, offering a clear brain network to target for treatment, says Martijn van den Heuvel, professor of computational neuroimaging and brain systems at Vrije Universiteit Amsterdam and an investigator on the new study. © 2026 Simons Foundation

10 Most Mind-Blowing Discoveries About the Brain in 2025

By Allison Parshall The human brain has 86 billion neurons connected by roughly 100 trillion synapses, making it one of the most complex objects in the known universe. Each year neuroscientists make fascinating, important and downright strange discoveries about how this resilient structure works, and 2025 didn’t disappoint. Here are 10 of the most fascinating brain discoveries of this year for your own brain to noodle on. Brain scans of thousands of people revealed that the human brain has five distinct eras, with turning points in the way it is organized occurring at age nine, 32, 66 and 83. Across each of these stages—for example, the “adolescent” period between age nine and 32—people’s brains tend to experience the same types of changes. You don’t remember being a newborn or even a toddler. Adults’ earliest memories tend to start around preschool and no earlier. But recent research suggests that your brain was making memories back then; you just don’t have access to them now. A study of the infant hippocampus, a deep-brain structure crucial for memory formation, found that it can store memories once babies are around one year old—though it’s not clear why we can’t recall them once we grow up. Untangling Alzheimer’s Researchers also discovered another oddity of newborn babies’ brain: they have very high levels of a protein that, in adults, indicates Alzheimer’s disease. Tau proteins help to stabilize brain cells’ structure, but they can undergo chemical changes that lead them to become tangled up, a process linked to Alzheimer’s. The fact that healthy newborn brains have high levels of these proteins, which later decrease, suggests that these detrimental changes in adults could be avoided or reversed. Fluorescence light micrograph of neural progenitor cells. Astrocytes have been stained orange and neural progenitor cells green. Cell nuclei are blue © 2025 SCIENTIFIC AMERICAN,

Related chapters from BN: Chapter 1: Introduction: Scope and Outlook; Chapter 7: Life-Span Development of the Brain and Behavior
Related chapters from MM:Chapter 1: Cells and Structures: The Anatomy of the Nervous System; Chapter 13: Memory and Learning
Link ID: 30054 - Posted: 12.20.2025

Authors retract Science paper on controversial fMRI method

By Calli McMurray The authors behind a contentious 2022 Science paper that purported to measure neuronal activity using functional MRI (fMRI) retracted the work today. The retraction marks the end of the road for the method, called “direct imaging of neuronal activity,” or DIANA, says Noam Shemesh, principal investigator at the Champalimaud Centre for the Unknown, who was not involved in the now-retracted work. But many neuroimaging researchers still hope to one day use fMRI to capture neuronal activity. “MRI is such a rich modality. It has such rich physics, and not all of it has been exploited in the functional sense,” Shemesh says. DIANA collected fMRI data in a way that enabled the researchers to measure signal changes on the order of tens of milliseconds. The team, led by Jang-Yeon Park at Sungkyunkwan University, captured a signal peak in the somatosensory cortex of mice 25 milliseconds after shocking their whisker pads. Despite an initial flurry of excitement from the field, other labs could not replicate the results. As a result, the paper received an editorial expression of concern in August 2023 because “the methods described in the paper are inadequate to allow reproduction of the results and … the results may have been biased by subjective data selection,” the notice states. Following the editorial expression of concern, “we reanalyzed the data. Unfortunately, the additional results revealed unexpected MR signal characteristics and did not robustly support the original conclusions. We are therefore retracting the paper,” the retraction notice states. Science did not have any additional comment beyond what is outlined in the expression of concern and retraction notice. © 2025 Simons Foundation

Worms help untangle brain structure/function mystery

By Holly Barker When scientists produced the first map of all synaptic connections in the roundworm Caenorhabditis elegans in 1986, many hailed it as a blueprint for the flow of brain signals. As it turned out, though, models of neuronal activity based on this wiring diagram bore little resemblance to the functional maps of brain activity measured in living worms. This disconnect isn’t limited to worms. Mice, for instance, appear to have widespread silent synapses—wired connections that don’t send signals—and the actual responses of some cells in the fruit fly’s visual system do not match the responses the connectome predicts. A new preprint helps to explain why: Most network features, in C. elegans at least, are not conserved between the anatomical and functional connectomes. Yet the anatomical connectome can still forecast—albeit in a complex way—observed neuronal activity in the worms, according to a second preprint by the same team, because “most signaling is happening along the wires,” says Andrew Leifer, associate professor of physics and neuroscience at Princeton University and principal investigator on both preprints. The findings begin to address the long-standing challenge of reconciling structure and function, and show that “we weren’t entirely wrong” about the importance of synaptic connectivity, says Jihong Bai, professor of basic sciences at the Fred Hutchinson Cancer Center, who was not involved in the work. The debut of a color-coded map of cell types in the worm brain in 2021 split the neuroscience community. It made it possible to identify individual neurons in whole-brain recordings and compare annotated recordings with the connectome—an exercise that revealed no correlation between the two. © 2025 Simons Foundation

Longer fMRI brain scans boost reliability—but only to a point

By Claudia López Lloreda fMRI researchers have long faced a conundrum: Given finite resources and time to spend on scanning, is it better to scan lots of participants for a short time each, or a smaller number of people for a longer time? A new study quantifies this tradeoff for brain-wide association studies (BWAS), which aim to link brain differences to physical and cognitive traits. Using large-scale public fMRI datasets, the team found that their ability to accurately predict cognitive features from functional connectivity data increased with sample size and with scan length, up to 20 minutes. But accuracy began to plateau for longer scans, and beyond 30 minutes, the added length (and cost) provided diminishing returns. A half-hour seems to be the optimal scanning time, says Thomas Yeo, associate professor of electrical and computer engineering at the National University of Singapore and principal investigator of the study. Scan duration is “essentially providing a different knob for people to tune” to meet power requirements in their fMRI experiments, he says. Although the neuroimaging community already knew that scan time is important and five minutes is insufficient, “this is one of the first major studies in the past few years to really quantitatively map that out” for BWAS studies, says Brenden Tervo-Clemmens, assistant professor of psychiatry and behavioral sciences at the University of Minnesota, who was not involved with the study. Tervo-Clemmens and his colleagues had previously shown in a 2022 study the importance of sample size in BWAS, calculating that these analyses need thousands of participants to get meaningful associations. This new study adds another part of the equation, he says. Yeo’s team developed the Optimal Scan Time Calculator to help other neuroscientists design their own studies. “Democratizing these complex methodological issues into a usable package is really, really useful,” Tervo-Clemmens says. © 2025 Simons Foundation

Can portable headsets peer into the minds of hunter-gatherers and other understudied populations?

By Siddhant Pusdekar The food we eat, the air we breathe, and our daily activities all shape how our minds work. Yet most brain research focuses on a narrow slice of humanity: people in high-income countries in the Northern Hemisphere. That leaves a vast gap in our understanding of how neural activity varies across cultures, environments, and lifestyles. A team of researchers from Tanzania and India has taken a step toward closing that gap. In a study published this week in eNeuro, they describe a strategy for collecting data from the brains of diverse groups—from hunter-gatherers to urban dwellers—using electroencephalography (EEG). The technology relies on portable headsets, widely used in clinical settings, that record the brain’s electrical activity through electrodes placed on the scalp. The researchers trained trusted community members as “surveyors,” who visited participants where they live and work to gather EEG data and conduct surveys about their lifestyles and experiences. The initial effort, which involved nearly 8000 volunteers across Tanzania and India, shows that this kind of data collection in low- and middle-income countries is feasible and affordable, the researchers say. The work cost them $50 for each person studied, a fraction of equivalent, large-scale studies conducted in research labs. A: I think mental health is one of the defining health issues in India. When we survey 18- to 24-year-olds, 50% tell us that almost every other day of the month they don’t feel like going to work or college. India is a young country and is increasingly relying on its youth to grow its economy. If they can’t function in their daily activities, you can’t expect them to be productive and contribute to the economy.

New dopamine sensor powers three-color imaging in live animals

By Diana Kwon A new sensor makes it possible for the first time to simultaneously track dopamine and up to two additional molecules in the brains of living animals. The sensor, dubbed HaloDA1.0, uses a novel dopamine-tagging system that emits light at the far-red end of the color spectrum, according to the team behind the work. “There’s a real need to monitor multiple relevant molecules, as they’re doing here,” says Nicolas Tritsch, assistant professor of neuroscience at McGill University, who was not involved in the study. Because dopamine is involved in a range of key brain functions, when studying its effects on a cell it’s important to consider other neuromodulators that are released at the same time, as well as the signaling cascades these molecules may trigger, Tritsch says. Most dopamine-tracking strategies genetically encode a naturally occurring fluorescent protein into dopamine receptors; when dopamine attaches to the modified receptors, the fluorescent protein changes shape and emits light. But naturally occurring fluorescent proteins have a limited color palette, which has made it difficult to develop sensors that can go beyond two-color imaging, says study investigator Yulong Li, professor of life sciences at Peking University. Instead of genetically encoding a fluorescent protein, HaloDA1.0 attaches a synthetic molecule called HaloTag to dopamine receptors. This tag binds tightly to previously developed artificial dyes that change shape and fluoresce in the far-red spectrum when dopamine binds to its receptors. Because the dyes fluoresce at the far end of the red spectrum, it leaves room for other sensors to glow at different wavelengths. © 2025 Simons Foundation

Super-resolution microscopes showcase the inner lives of cells

By Katarina Zimmer Using a tiny, spherical glass lens sandwiched between two brass plates, the 17th century Dutch microscopist Antonie van Leeuwenhoek was the first to officially describe red blood cells and sperm cells in human tissues, and observe “animalcules” — bacteria and protists — in the water of a lake. Increasingly powerful light microscopes followed, revealing cell organelles like the nucleus and energy-producing mitochondria. But by 1873, scientists realized there was a limit to the level of detail. When light passes through a lens, the light gets spread out through diffraction. This means that two objects can’t be distinguished if they’re less than roughly 250 nanometers (250 billionths of a meter) apart — instead, they’ll appear as a blur. That put the inner workings of cell structures off limits. Electron microscopy, which uses electron beams instead of light, offers higher resolution. But the resulting black-and-white images make it hard tell proteins apart, and the method only works on dead cells. Now, however, optics engineers and physicists have developed sophisticated tricks to overcome the diffraction limit of light microscopes, opening up a new world of detail. These “super-resolution” light microscopy techniques can distinguish objects down to 100 nanometers and sometimes even less than 10 nanometers. Scientists attach tiny, colored fluorescent tags to individual proteins or bits of DNA, often in living cells where they can watch them in action. As a result, they are now filling in key knowledge gaps about how cells work and what goes wrong in neurological diseases and cancers, or during viral infections. “We can really see new biology — things that we were hoping to see but hadn’t seen before,” says molecular cell biologist Lothar Schermelleh, who directs an imaging center at the University of Oxford in the United Kingdom. Here’s some of what scientists are learning in this new age of light microscopy. Overcoming the diffraction limit

Giant map details nerves across a mouse’s body: see stunning pics

Mariana Lenharo A speedy imaging method can map the nerves running from a mouse’s brain and spinal cord to the rest of its body at micrometre-scale resolution, revealing details such as individual fibres travelling from a key nerve to distant organs1. Previous efforts have mapped the network of connections between nerve cells, known as the connectome, in the mouse brain. But tracing the complex paths of nerves through the rest of the body has been challenging. To do so, the creators of the new map used a custom-built microscope to scan exposed tissue, completing the process in just 40 hours. Nerves look blue in the reconstructed view of a genetically engineered mouse (left) whose neurons produce a fluorescent marker. In a separate animal (right), antibodies detail the sympathetic nerves (purple). Credit: M.-Y. Shi et al./Cell (CC-BY-4.0) The method, described today in Cell, is an important technical achievement, says Ann-Shyn Chiang, a neuroscientist at the National Tsing Hua University in Hsinchu, Taiwan, who was not involved with the research. “This work is a major step forward in expanding connectomics beyond the brain,” he says. To prepare a mouse’s body for the scan, researchers treat it with chemicals that make its tissues transparent by removing fat, calcium and other components that block light. This provides a clear view of the nerves, which have been labelled with fluorescent marker proteins. The see-through body is then placed into a device that combines a slicing tool and a microscope that takes 3D images. A piston gradually pushes the mouse towards the slicing blade, 400 micrometres at a time. After each slice, a microscope images the newly exposed surface of the mouse, capturing details up to 600 micrometres deep — roughly the thickness of six sheets of paper — below the surface. The body then advances for the next cut. The cycle repeats around 200 times without pause, to cover the entire body. The images are then combined. © 2025 Springer Nature Limited

Brain-reading devices raise ethical dilemmas — researchers propose protections

Kristel Tjandra For two decades, Ann Johnson has been unable to walk or talk after she experienced a stroke that impaired her balance and her breathing and swallowing abilities. But in 2022, Johnson was finally able to hear her voice through an avatar, thanks to a brain implant. The implant is an example of the neurotechnologies that have entered human trials during the past five years. These devices, developed by research teams and firms including entrepreneur Elon Musk’s Neuralink, can alter the nervous system’s activity to influence functions such as speech, touch and movement. Last month, they were the topic of a meeting in Paris, hosted by the United Nations scientific and cultural agency UNESCO, at which delegates finalized a set of ethical principles to govern neurotechnologies. The recommendations focus on protecting users from technology misuse that could infringe on their human rights, including their autonomy and freedom of thought. The delegates, who included scientists, ethicists and legal specialists, decided on nine principles. These include recommendations that technology developers disclose how neural information is collected and used, and that they ensure the long-term safety of a product on people’s mental states. “This document clarifies how to protect human rights, especially in relation to the nervous system,” says Pedro Maldonado, a neuroscientist at the University of Chile in Santiago who was one of 24 experts who drafted the recommendations in 2024. The principles are not legally binding, but nations and organizations can use them to develop their own policies. In November, UNESCO’s 194 member states will vote on whether to adopt the standards. The meeting considered a range of neurotechnology applications, including devices designed to be implanted into the body and non-invasive devices, which are being explored in medicine, entertainment and education. © 2025 Springer Nature Limited

Billy Joel Has Normal Pressure Hydrocephalus. What Is It?

By Maggie Astor Billy Joel has canceled his upcoming concerts because of a brain disorder affecting his hearing, vision and balance, the singer-songwriter announced on Friday. The condition, called normal pressure hydrocephalus, or N.P.H., is estimated to affect hundreds of thousands of older Americans. Here’s what to know about it. What is normal pressure hydrocephalus? N.P.H. occurs when excess cerebrospinal fluid accumulates in the brain, causing difficulty walking, trouble controlling one’s bladder and memory problems. Those symptoms together suggest the disorder. The bladder symptoms can include incontinence and waking up at night to urinate with increasing frequency, said Dr. Charles Matouk, a neurosurgeon at Yale University and director of the university’s Normal Pressure Hydrocephalus Program. A statement posted to Mr. Joel’s social media accounts on Friday said his condition had been “exacerbated by recent concert performances.” N.P.H. is rare, but risk increases with age. Dr. Matouk estimated that it might affect less than 1 percent of the population ages 65 to 80, but likely 5 percent or more of people over 80. Experts say the condition is likely underdiagnosed because its symptoms can easily be dismissed as normal effects of aging. Dr. Matouk urged people to see a doctor if they experienced trouble walking, controlling their bladder and remembering things. How is it diagnosed? When a patient shows up with gait, bladder and memory problems, the first test may be a CT scan or M.R.I. In patients with N.P.H., that imaging will show enlargement of the brain’s fluid-filled ventricles. But the conclusive test is a spinal tap: Because that procedure removes cerebrospinal fluid, patients with N.P.H. experience a temporary alleviation of symptoms, confirming the diagnosis, Dr. Matouk said. © 2025 The New York Times Company

Related chapters from BN: Chapter 2: Functional Neuroanatomy: The Cells and Structure of the Nervous System; Chapter 19: Language and Lateralization
Related chapters from MM:Chapter 2: Neurophysiology: The Generation, Transmission, and Integration of Neural Signals; Chapter 15: Language and Lateralization
Link ID: 29801 - Posted: 05.24.2025

Connectomics 2.0: Simulating the brain

By Laura Dattaro In 2012, neuroscientists Sebastian Seung and J. Anthony Movshon squared off at a Columbia University event over the usefulness of connectomes—maps of every connection between every cell in the brain of a living organism. Such a map, Seung argued, could crack open the brain’s computations and provide insight into processes such as sensory perception and memory. But Movshon, professor of neural science and psychology at New York University, countered that the relationship between structure and function was not so straightforward—that even if you knew how all of a brain’s neurons connect to one another, you still wouldn’t understand how the organ turns electrical signals into cognition and behavior. The debate in the field continues, even though Seung and his colleagues in the FlyWire Consortium completed the first connectome of a female Drosophila melanogaster in 2023, and even though a slew of new computational models built from that and other connectomes hint that structure does, in fact, reveal something about function. “This is just the beginning, and that’s what’s exciting,” says Seung, professor of neuroscience at the Princeton Neuroscience Institute. “These papers are kicking off a beginning to an entirely new field, which is connectome-based brain simulation.” A simulated fruit fly optic lobe, detailed in a September 2024 Nature paper, for example, accurately predicts which neurons in living fruit flies respond to different visual stimuli. “All the work that’s been done in the past year or two feels like the beginning of something new,” says John Tuthill, associate professor of neuroscience at the University of Washington. Tuthill was not involved in the optic lobe study but used a similar approach to identify a circuit that seems to control walking in flies. Most published models so far have made predictions about simple functions that were already understood from recordings of neural activity, Tuthill adds. But “you can see how this will build up to something that is eventually very insightful.” © 2025 Simons Foundation

Noninvasive technologies can map and target human brain with unprecedented precision

By Bruce Rosen The past two decades—and particularly the past 10 years, with the tool-focused efforts of the BRAIN Initiative—have delivered remarkable advances in our ability to study and manipulate the brain, both in exquisite cellular detail and across increasing swaths of brain territory. These advances resulted from improvements in tools such as optical imaging, chemogenetics and multiprobe electrodes, to name a few. Powerful as these technologies are, though, their invasive nature makes them ill-suited for widespread adoption in human brain research. Fortunately, our fundamental understanding of the physics and engineering behind noninvasive modalities—based largely on recording, generating and manipulating electromagnetic and acoustic fields in the human brain—has also progressed over the past decade. These advances are on the threshold of providing much more detailed recordings of electromagnetic activity, not only across the human cortex but at depth. And these same principles can improve our ability to precisely and noninvasively stimulate the human brain. Though these tools have limitations compared with their invasive counterparts, their noninvasive nature make them suitable for wide-scale investigation of the links between human behavior and action, as well as for individually understanding and treating an array of brain disorders. The most common method to assess brain electrophysiology is the electroencephalogram (EEG), first developed in the 1920s and now routinely used for both basic neuroscience and the clinical diagnosis of conditions ranging from epilepsy to sleep disorders to traumatic brain injury. It’s widely used, given its simplicity and low cost, but it has drawbacks. Understanding exactly where the EEG signals arise from in the brain is often difficult, for example; electric current from the brain must pass through multiple tissue layers (including overlying brain itself) before it can be detected with electrodes on the scalp surface, blurring the spatial resolution. Advanced computational methods combined with imaging data from MRI can partially mitigate these issues, but the analysis is complex, and results are imperfect. Still, because EEG can be readily combined with behavioral assessments and other

An Advance in Brain Research That Was Once Considered Impossible

By Carl Zimmer The human brain is so complex that scientific brains have a hard time making sense of it. A piece of neural tissue the size of a grain of sand might be packed with hundreds of thousands of cells linked together by miles of wiring. In 1979, Francis Crick, the Nobel-prize-winning scientist, concluded that the anatomy and activity in just a cubic millimeter of brain matter would forever exceed our understanding. “It is no use asking for the impossible,” Dr. Crick wrote. Forty-six years later, a team of more than 100 scientists has achieved that impossible, by recording the cellular activity and mapping the structure in a cubic millimeter of a mouse’s brain — less than one percent of its full volume. In accomplishing this feat, they amassed 1.6 petabytes of data — the equivalent of 22 years of nonstop high-definition video. “This is a milestone,” said Davi Bock, a neuroscientist at the University of Vermont who was not involved in the study, which was published Wednesday in the journal Nature. Dr. Bock said that the advances that made it possible to chart a cubic millimeter of brain boded well for a new goal: mapping the wiring of the entire brain of a mouse. “It’s totally doable, and I think it’s worth doing,” he said. More than 130 years have passed since the Spanish neuroscientist Santiago Ramón y Cajal first spied individual neurons under a microscope, making out their peculiar branched shapes. Later generations of scientists worked out many of the details of how a neuron sends a spike of voltage down a long arm, called an axon. Each axon makes contact with tiny branches, or dendrites, of neighboring neurons. Some neurons excite their neighbors into firing voltage spikes of their own. Some quiet other neurons. Human thought somehow emerges from this mix of excitation and inhibition. But how that happens has remained a tremendous mystery, largely because scientists have been able to study only a few neurons at a time. In recent decades, technological advances have allowed scientists to start mapping brains in their entirety. In 1986, British researchers published the circuitry of a tiny worm, made up of 302 neurons. In subsequent years, researchers charted bigger brains, such as the 140,000 neurons in the brain of a fly. © 2025 The New York Times Company

To make a meaningful contribution to neuroscience, fMRI must break out of its silo

Avram Holmes. Human thought and behavior emerge through complex and reciprocal interactions that link microscale molecular and cellular processes with macroscale functional patterns. Functional MRI (fMRI), one of the most common methods for studying the human brain, detects these latter patterns through the “blood oxygen level dependent,” or BOLD, signal, a composite measure of both neural and vascular signals that reflects an indirect measure of brain activity. Despite an enormous investment by scientific funders and the research community in the use of fMRI, though, researchers still don’t fully understand the underlying mechanisms that drive individual or population-level differences measured via in-vivo brain imaging, which limits our ability to interpret those data. For fMRI to meaningfully contribute to progress in neuroscience, we need to develop research programs that link phenomena across levels, from genes and molecules to cells, circuits, networks and behavior. Without a concerted effort in this direction, fMRI will remain a methodological spandrel, a byproduct of technological development rather than a tool explicitly designed to reveal neural mechanisms, generating isolated datapoints that are left unintegrated with broader scientific theory or progress. Recently, the human functional neuroimaging community has turned a critical eye toward its own methods and findings. These debates have led to field-wide initiatives calling for larger and more diverse study samples, better phenotypic reliability and findings that generalize across populations. But researchers have put relatively little emphasis on contextualizing the resulting work across levels of analysis or on deciphering the biological mechanism that may underpin changes to the BOLD signal across groups and individual people or over the lifespan. Appeals to better integrate the different levels of neuroscience are not new. But despite persuasive arguments, fMRI researchers have largely remained scientifically siloed, isolated by a nearly ubiquitous focus on a single level of analysis and a rigid adherence to a select set of imaging methods. Our work is typically presented inside of field-specific echo chambers—departmental or group seminars, topic-specific journals and society meetings—where our methodological and analytic choices go unchallenged. What progress can we expect to make if we remain isolated from other fields of study? © 2025 Simons Foundation

The Mysterious Flow of Fluid in the Brain

By Veronique Greenwood Encased in the skull, perched atop the spine, the brain has a carefully managed existence. It receives only certain nutrients, filtered through the blood-brain barrier; an elaborate system of protective membranes surrounds it. That privileged space contains a mystery. For more than a century, scientists have wondered: If it’s so hard for anything to get into the brain, how does waste get out? The brain has one of the highest metabolisms of any organ in the body, and that process must yield by-products that need to be removed. In the rest of the body, blood vessels are shadowed by a system of lymphatic vessels. Molecules that have served their purpose in the blood move into these fluid-filled tubes and are swept away to the lymph nodes for processing. But blood vessels in the brain have no such outlet. Several hundred kilometers of them, all told, seem to thread their way through this dense, busily working tissue without a matching waste system. However, the brain’s blood vessels are surrounded by open, fluid-filled spaces. In recent decades, the cerebrospinal fluid, or CSF, in those spaces has drawn a great deal of interest. “Maybe the CSF can be a highway, in a way, for the flow or exchange of different things within the brain,” said Steven Proulx, who studies the CSF system at the University of Bern. A recent paper in Cell contains a new report about what is going on around the brain (opens a new tab) and in its hidden cavities. A team at the University of Rochester led by the neurologist Maiken Nedergaard (opens a new tab) asked whether the slow pumping of the brain’s blood vessels might be able to push the fluid around, among, and in some cases through cells, to potentially drive a system of drainage. In a mouse model, researchers injected a glowing dye into CSF, manipulated the blood vessel walls to trigger a pumping action, and saw the dye concentration increase in the brain soon after. They concluded that the movement of blood vessels might be enough to move CSF, and possibly the brain’s waste, over long distances. © 2025 Simons Foundation.

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