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Neuroscientists create a comprehensive map of the cerebral cortex

Anne Trafton |

By analyzing brain scans taken as people watched movie clips, MIT researchers have created the most comprehensive map yet of the functions of the brain’s cerebral cortex.

Using functional magnetic resonance imaging (fMRI) data, the research team identified 24 networks with different functions, which include processing language, social interactions, visual features, and other types of sensory input.

Many of these networks have been seen before but haven’t been precisely characterized using naturalistic conditions. While the new study mapped networks in subjects watching engaging movies, previous works have used a small number of specific tasks or examined correlations across the brain in subjects who were simply resting.

“There’s an emerging approach in neuroscience to look at brain networks under more naturalistic conditions. This is a new approach that reveals something different from conventional approaches in neuroimaging,” says Robert Desimone, director of MIT’s McGovern Institute for Brain Research. “It’s not going to give us all the answers, but it generates a lot of interesting ideas based on what we see going on in the movies that’s related to these network maps that emerge.”

The researchers hope that their new map will serve as a starting point for further study of what each of these networks is doing in the brain.

Desimone and John Duncan, a program leader in the MRC Cognition and Brain Sciences Unit at Cambridge University, are the senior authors of the study, which appears today in Neuron. Reza Rajimehr, a research scientist in the McGovern Institute and a former graduate student at Cambridge University, is the lead author of the paper.

Precise mapping

The cerebral cortex of the brain contains regions devoted to processing different types of sensory information, including visual and auditory input. Over the past few decades, scientists have identified many networks that are involved in this kind of processing, often using fMRI to measure brain activity as subjects perform a single task such as looking at faces.

In other studies, researchers have scanned people’s brains as they do nothing, or let their minds wander. From those studies, researchers have identified networks such as the default mode network, a network of areas that is active during internally focused activities such as daydreaming.

“Up to now, most studies of networks were based on doing functional MRI in the resting-state condition. Based on those studies, we know some main networks in the cortex. Each of them is responsible for a specific cognitive function, and they have been highly influential in the neuroimaging field,” Rajimehr says.

However, during the resting state, many parts of the cortex may not be active at all. To gain a more comprehensive picture of what all these regions are doing, the MIT team analyzed data recorded while subjects performed a more natural task: watching a movie.

“By using a rich stimulus like a movie, we can drive many regions of the cortex very efficiently. For example, sensory regions will be active to process different features of the movie, and high-level areas will be active to extract semantic information and contextual information,” Rajimehr says. “By activating the brain in this way, now we can distinguish different areas or different networks based on their activation patterns.”

The data for this study was generated as part of the Human Connectome Project. Using a 7-Tesla MRI scanner, which offers higher resolution than a typical MRI scanner, brain activity was imaged in 176 people as they watched one hour of movie clips showing a variety of scenes.

The MIT team used a machine-learning algorithm to analyze the activity patterns of each brain region, allowing them to identify 24 networks with different activity patterns and functions.

Some of these networks are located in sensory areas such as the visual cortex or auditory cortex, as expected for regions with specific sensory functions. Other areas respond to features such as actions, language, or social interactions. Many of these networks have been seen before, but this technique offers more precise definition of where the networks are located, the researchers say.

“Different regions are competing with each other for processing specific features, so when you map each function in isolation, you may get a slightly larger network because it is not getting constrained by other processes,” Rajimehr says. “But here, because all the areas are considered together, we are able to define more precise boundaries between different networks.”

The researchers also identified networks that hadn’t been seen before, including one in the prefrontal cortex, which appears to be highly responsive to visual scenes. This network was most active in response to pictures of scenes within the movie frames.

Executive control networks

Three of the networks found in this study are involved in “executive control,” and were most active during transitions between different clips. The researchers also observed that these control networks appear to have a “push-pull” relationship with networks that process specific features such as faces or actions. When networks specific to a particular feature were very active, the executive control networks were mostly quiet, and vice versa.

“Whenever the activations in domain-specific areas are high, it looks like there is no need for the engagement of these high-level networks,” Rajimehr says. “But in situations where perhaps there is some ambiguity and complexity in the stimulus, and there is a need for the involvement of the executive control networks, then we see that these networks become highly active.”

Using a movie-watching paradigm, the researchers are now studying some of the networks they identified in more detail, to identify subregions involved in particular tasks. For example, within the social processing network, they have found regions that are specific to processing social information about faces and bodies. In a new network that analyzes visual scenes, they have identified regions involved in processing memory of places.

“This kind of experiment is really about generating hypotheses for how the cerebral cortex is functionally organized. Networks that emerge during movie watching now need to be followed up with more specific experiments to test the hypotheses. It’s giving us a new view into the operation of the entire cortex during a more naturalistic task than just sitting at rest,” Desimone says.

The research was funded by the McGovern Institute, the Cognitive Science and Technology Council of Iran, the MRC Cognition and Brain Sciences Unit at the University of Cambridge, and a Cambridge Trust scholarship.

A cell protector collaborates with a killer

by Jennifer Michalowski |

From early development to old age, cell death is a part of life. Without enough of a critical type of cell death known as apoptosis, animals wind up with too many cells, which can set the stage for cancer or autoimmune disease. But careful control is essential, because when apoptosis eliminates the wrong cells, the effects can be just as dire, helping to drive many kinds of neurodegenerative disease.

Portrait of a scientist
McGovern Investigator Robert Horvitz poses for a photo in his laboratory. Photo: AP Images/Aynsley Floyd

By studying the microscopic roundworm Caenorhabditis elegans—which was honored with its fourth Nobel Prize last month—scientists at MIT’s McGovern Institute have begun to unravel a longstanding mystery about the factors that control apoptosis: how a protein capable of preventing programmed cell death can also promote it. Their study, led by McGovern Investigator Robert Horvitz and reported October 9, 2024, in the journal Science Advances, sheds light on the process of cell death in both health and disease.

“These findings, by graduate student Nolan Tucker and former graduate student, now MIT faculty colleague, Peter Reddien, have revealed that a protein interaction long thought to block apoptosis in C. elegans, likely instead has the opposite effect,” says Horvitz, who shared the 2002 Nobel Prize for discovering and characterizing the genes controlling cell death in C. elegans.

Mechanisms of cell death

Horvitz, Tucker, Reddien and colleagues have provided foundational insights in the field of apoptosis by using C. elegans to analyze the mechanisms that drive apoptosis as well as the mechanisms that determine how cells ensure apoptosis happens when and where it should. Unlike humans and other mammals, which depend on dozens of proteins to control apoptosis, these worms use just a few. And when things go awry, it’s easy to tell: When there’s not enough apoptosis, researchers can see that there are too many cells inside the worms’ translucent bodies. And when there’s too much, the worms lack certain biological functions or, in more extreme cases, can’t reproduce or die during embryonic development.

black and white microscopic image of worms
The nematode worm Caenorhabditis elegans has provided answers to many fundamental questions in biology. Image: Robert Horvitz

Work in the Horvitz lab defined the roles of many of the genes and proteins that control apoptosis in worms. These regulators proved to have counterparts in human cells, and for that reason studies of worms have helped reveal how human cells govern cell death and pointed toward potential targets for treating disease.

A protein’s dual role

Three of C. elegans’ primary regulators of apoptosis actively promote cell death, whereas just one, CED-9, reins in the apoptosis-promoting proteins to keep cells alive. As early as the 1990s, however, Horvitz and colleagues recognized that CED-9 was not exclusively a protector of cells. Their experiments indicated that the protector protein also plays a role in promoting cell death. But while researchers thought they knew how CED-9 protected against apoptosis, its pro-apoptotic role was more puzzling.

CED-9’s dual role means that mutations in the gene that encode it can impact apoptosis in multiple ways. Most ced-9 mutations interfere with the protein’s ability to protect against cell death and result in excess cell death. Conversely, mutations that abnormally activate ced-9 cause too little cell death, just like mutations that inactivate any of the three killer genes.

An atypical ced-9 mutation, identified by Reddien when he was a PhD student in Horvitz’s lab, hinted at how CED-9 promotes cell death. That mutation altered the part of the CED-9 protein that interacts with the protein CED-4, which is proapoptotic. Since the mutation specifically leads to a reduction in apoptosis, this suggested that CED-9 might need to interact with CED-4 to promote cell death.

The idea was particularly intriguing because researchers had long thought that CED-9’s interaction with CED-4 had exactly the opposite effect: In the canonical model, CED-9 anchors CED-4 to cells’ mitochondria, sequestering the CED-4 killer protein and preventing it from associating with and activating another key killer, the CED-3 protein —thereby preventing apoptosis.

To test the hypothesis that CED-9’s interactions with the killer CED-4 protein enhance apoptosis, the team needed more evidence. So graduate student Nolan Tucker used CRISPR gene editing tools to create more worms with mutations in CED-9, each one targeting a different spot in the CED-4-binding region. Then he examined the worms. “What I saw with this particular class of mutations was extra cells and viability,” he says—clear signs that the altered CED-9 was still protecting against cell death, but could no longer promote it. “Those observations strongly supported the hypothesis that the ability to bind CED-4 is needed for the pro-apoptotic function of CED-9,” Tucker explains. Their observations also suggested that, contrary to earlier thinking, CED-9 doesn’t need to bind with CED-4 to protect against apoptosis.

When he looked inside the cells of the mutant worms, Tucker found additional evidence that these mutations prevented CED-9’s ability to interact with CED-4. When both CED-9 and CED-4 are intact, CED-4 appears associated with cells’ mitochondria. But in the presence of these mutations, CED-4 was instead at the edge of the cell nucleus. CED-9’s ability to bind CED-4 to mitochondria appeared to be necessary to promote apoptosis, not to protect against it.

In wild-type worms CED-4 is localized to mitochondria. However, the introduction of CED-9-CED-4 binding mutations such as ced-4(n6703) or ced-9(n6704), causes CED-4 protein to localize to the outer edge of the nucleus. Image: Nolan Tucker, Robert Horvitz

Looking ahead

While the team’s findings begin to explain a long-unanswered question about one of the primary regulators of apoptosis, they raise new ones, as well. “I think that this main pathway of apoptosis has been seen by a lot of people as more or less settled science. Our findings should change that view,” Tucker says.

The researchers see important parallels between their findings from this study of worms and what’s known about cell death pathways in mammals. The mammalian counterpart to CED-9 is a protein called BCL-2, mutations in which can lead to cancer.  BCL-2, like CED-9, can both promote and protect against apoptosis. As with CED-9, the pro-apoptotic function of BCL-2 has been mysterious. In mammals, too, mitochondria play a key role in activating apoptosis. The Horvitz lab’s discovery opens opportunities to better understand how apoptosis is regulated not only in worms but also in humans, and how dysregulation of apoptosis in humans can lead to such disorders as cancer, autoimmune disease and neurodegeneration.

Adults’ brain activity appears unchanged after a year of medical use of cannabis

by Jennifer Michalowski |

In a study of adults who use cannabis because they are seeking relief from pain, depression, anxiety, or insomnia, scientists at MIT and Harvard found no changes in brain activity after one year of self-directed use. The study, reported September 18, 2024, in JAMA Network Open, is among the first to investigate how the real-world ways people use cannabis to treat medical symptoms might impact the brain in lasting ways.

While some studies have linked chronic cannabis use to changes in the brain’s structure and function, outcomes vary depending, in part, on how and when people use the substance. People who begin using cannabis during adolescence, while the brain is still developing, may be particularly vulnerable to brain changes. The potency of the products they use and how often they use them matter, too.

Participants in the research, who obtained medical cannabis cards at the outset of the study, tended to choose lower potency products and use them less than daily. This may be why the researchers’ analysis—which focused on the brain activity associated with three kinds of cognitive processes—showed no changes after a year of use.

“For most older adults, occasional cannabis will not dramatically affect brain activation,” says Harvard neuroscientist Jodi Gilman, who led the study. “However, there are some individuals who may be vulnerable to negative effects of cannabis on cognitive function, particularly those using higher potency products more frequently.”

Gilman cautions that in another study of the same medical cannabis users, her team found that the drug failed to alleviate patients’ pain, depression, or anxiety. “So it didn’t help their symptoms—but it wasn’t associated with significant changes in brain activation,” she says. She also cautioned that some adults in the study did develop problems with cannabis use, including cannabis use disorder.

Medical cannabis programs are currently established in 38 U.S. states and Washington, D.C., increasing access to a substance that many people hope might help them relieve distressing medical symptoms. But little is known about how this type of cannabis use affects neural circuits in the brain. “Cannabis has been legalized through ballot initiatives and by legislatures. Dispensary cannabis has not been tested through large, randomized, double-blind clinical trials,” Gilman says. With McGovern Principal Research Scientist Satrajit Ghosh and MD-PhD student Debbie Burdinski, she set out to see what neuroimaging data would reveal about the impacts of this type of cannabis use.

Participants in their study were all adults seeking relief from depression, anxiety, pain, or insomnia who, prior to obtaining their medical cannabis cards, had never used cannabis at high frequencies. The researchers wanted their study to reflect the ways people really use cannabis, so participants were free choose which types of products they used, as well as how much and how often. “We told people, “Get what you want, use it you as you wish, and we’re going to look at how it may affect the brain,” Gilman explains.

Participants reported using a variety of products, but generally, they tended to choose low-potency products. Their frequency of use also varied, from less than once a month to once or more each day. Fewer than 20 percent of participants were daily users.

At the start of the study and again one year later, the research team used functional MRI scans to watch what happened in the brain while participants used three key cognitive skills: working memory, inhibitory control, and reward processing. The activity revealed on the scans showed the researchers which parts of the brain were working to perform these tasks.

Alterations in activity patterns could indicate changes in brains function. But in the 54 participants who underwent both brain scans, Gilman, Ghosh, and Burdinski found that after one year of cannabis use, brain activity during these three cognitive tasks was unchanged. Burdinski notes that many facets of cognition were not followed in the study, so some changes to brain activity could have occurred without being evident in the team’s data.

The researchers acknowledge that their study cohort, whose members were mostly female, middle-aged, and well educated, was less diverse than the population of people who use cannabis for medical symptoms. In fact, Gilman says, groups that are most vulnerable to negative consequences of cannabis may not have been well represented in the study, and it’s possible that a study of a different subgroup would have found different results.

Ghosh points out that there is still a lot to learn about the impact of cannabis, and larger studies are needed to understand its effects on the brain, including how it impacts different populations. For some individuals, he stresses, its use can have severe, debilitating effects, including symptoms of psychosis, delusions, or cannabinoid hyperemesis syndrome.

Larger studies are needed to understand cannabis’s effects on the brain and how it impacts different populations, Ghosh says. “Science can help us understand how we should be thinking about the impact of various substances or various interventions on the brain, instead of just anecdotal considerations of how they work,” he says. “Maybe there are people for whom there are changes. Now we can start teasing apart those details.”

Brains, fashion, alien life, and more: Highlights from the Cambridge Science Festival

by Adam Conner-Simons | MIT Museum |

What is it like to give birth on Mars? Can bioengineer TikTok stars win at the video game “Super Smash Brothers” while also answering questions about science? How do sheep, mouse, and human brains compare? These questions and others were asked last month when more than 50,000 visitors from across Cambridge, Massachusetts, and Greater Boston participated in the MIT Museum’s annual Cambridge Science Festival, a week-long celebration dedicated to creativity, ingenuity, and innovation. Running Monday, Sept. 23 through Sunday, Sept. 29, the 2024 edition was the largest in its history, with a dizzyingly diverse program spanning more than 300 events presented in more than 75 different venues, all free and open to the public.

Presented in partnership with the City of Cambridge and more than 250 collaborators across Greater Boston, this year’s festival comprised a wide range of interactive programs for adults, children, and families, including workshops, demos, keynote lectures, walking tours, professional networking opportunities, and expert panels. Aimed at scientists and non-scientists alike, the festival also collaborated with several local schools to offer visits from an astronaut for middle- and high-school students.

With support from dozens of local organizations, the festival was the first iteration to happen under the new leadership of Michael John Gorman, who was appointed director of the MIT Museum in January and began his position in July.

“A science festival like this has an incredible ability to unite a diverse array of people and ideas, while also showcasing Cambridge as an internationally recognized leader in science, technology, engineering, and math,” says Gorman. “I’m thrilled to have joined an institution that values producing events that foster such a strong sense of community, and was so excited to see the enthusiastic response from the tens of thousands of people who showed up and made the festival such a success.”

The 2024 Cambridge Science Festival was broad in scope, with events ranging from hands-on 3D-printing demos to concerts from the MIT Laptop Ensemble to participatory activities at the MIT Museum’s Maker Hub. This year’s programming also highlighted three carefully curated theme tracks that each encompassed more than 25 associated events:

  1. “For the Win: Games, Puzzles, and the Science of Play” (Thursday) consisted of multiple evening events clustered around Kendall Square.
  2. “Frontiers: A New Era of Space Exploration” (Friday and Saturday) featured programs throughout Boston and was co-curated by The Space Consortium, organizers of Massachusetts Space Week.
  3. “Electric Skin: Wearable Tech and the Future of Fashion” (Saturday) offered both day and evening events at the intersection of science, fabric, and fashion, taking place at The Foundry and co-curated by Boston Fashion Week and Advanced Functional Fabrics of America.

One of the discussions tied to the games-themed “For the Win” track involved artist Jeremy Couillard speaking with MIT Lecturer Mikael Jakobsson about the larger importance of games as a construct for encouraging interpersonal interaction and creating meaningful social spaces. Starting this past summer, the List Visual Arts Center has been the home of Couillard’s first-ever institutional solo exhibition, which centers around “Escape from Lavender Island,” a dystopian third-person, open-world exploration game he released in 2023 on the Steam video-game platform.

For the “Frontiers” space theme, one of the headlining events, “Is Anyone Out There?”, tackled the latest cutting-edge research and theories related to the potential existence of extraterrestrial life. The panel of local astronomers and astrophysicists included Sara Seager, the Class of 1941 Professor of Planetary Science, professor of physics, and professor of aeronautics and astronautics at MIT; Kim Arcand, an expert in astronomic visualization at the Harvard-Smithsonian Center for Astrophysics; and Michael Hecht, a research scientist and associate director of research management at MIT’s Haystack Observatory. The researchers spoke about the tools they and their peers use to try to search for extraterrestrial life, and what discovering life beyond our planet might mean for humanity.

For the “Electric Skin” fashion track, events spanned a range of topics revolving around the role that technology will play in the future of the field, including sold-out workshops where participants learned how to laser-cut and engineer “structural garments.” A panel looking at generative technologies explored how designers are using AI to spur innovation in their companies. Onur Yüce Gün, director of computational design at New Balance, also spoke on a panel with Ziyuan “Zoey” Zhu from IDEO, MIT Media Lab research scientist and architect Behnaz Farahi, and Fiorenzo Omenetto, principal investigator and director of The Tufts Silk Lab and the Frank C. Doble Professor of Engineering at Tufts University and a professor in the Biomedical Engineering Department and in the Department of Physics at Tufts.

Beyond the three themed tracks, the festival comprised an eclectic mix of interactive events and panels. Cambridge Public Library hosted a “Science Story Slam” with high-school students from 10 different states competing for $5,000 in prize money. Entrants shared 5-minute-long stories about their adventures in STEM, with topics ranging from probability to “astro-agriculture.” Judges included several MIT faculty and staff, as well as New York Times national correspondent Kate Zernike.

Elsewhere, the MIT Museum’s Gorman moderated a discussion on AI and democracy that included Audrey Tang, the former minister of digital affairs of Taiwan. The panelists explored how AI tools could combat the polarization of political discourse and increase participation in democratic processes, particularly for marginalized voices. Also in the MIT Museum, the McGovern Institute for Brain Research organized a “Decoding the Brain” event with demos involving real animal brains, while the Broad Institute of MIT and Harvard ran a “Discovery After Dark” event to commemorate the institute’s 20th anniversary. Sunday’s Science Carnival featured more than 100 demos, events, and activities, including the ever-popular “Robot Petting Zoo.”

When it first launched in 2007, the Cambridge Science Festival was by many accounts the first large-scale event of its kind across the entire United States. Similar festivals have since popped up all over the country, including the World Science Festival in New York City, the USA Science and Engineering Festival in Washington, the North Carolina Science Festival in Chapel Hill, and the San Diego Festival of Science and Engineering.

More information about the festival is available online, including opportunities to participate in next year’s events.

Brain pathways that control dopamine release may influence motor control

Anne Trafton |

Within the human brain, movement is coordinated by a brain region called the striatum, which sends instructions to motor neurons in the brain. Those instructions are conveyed by two pathways, one that initiates movement (“go”) and one that suppresses it (“no-go”).

In a new study, MIT researchers have discovered an additional two pathways that arise in the striatum and appear to modulate the effects of the go and no-go pathways. These newly discovered pathways connect to dopamine-producing neurons in the brain — one stimulates dopamine release and the other inhibits it.

By controlling the amount of dopamine in the brain via clusters of neurons known as striosomes, these pathways appear to modify the instructions given by the go and no-go pathways. They may be especially involved in influencing decisions that have a strong emotional component, the researchers say.

“Among all the regions of the striatum, the striosomes alone turned out to be able to project to the dopamine-containing neurons, which we think has something to do with motivation, mood, and controlling movement,” says Ann Graybiel, an MIT Institute Professor, a member of MIT’s McGovern Institute for Brain Research, and the senior author of the new study.

Iakovos Lazaridis, a research scientist at the McGovern Institute, is the lead author of the paper, which appears today in the journal Current Biology.

New pathways

Graybiel has spent much of her career studying the striatum, a structure located deep within the brain that is involved in learning and decision-making, as well as control of movement.

Within the striatum, neurons are arranged in a labyrinth-like structure that includes striosomes, which Graybiel discovered in the 1970s. The classical go and no-go pathways arise from neurons that surround the striosomes, which are known collectively as the matrix. The matrix cells that give rise to these pathways receive input from sensory processing regions such as the visual cortex and auditory cortex. Then, they send go or no-go commands to neurons in the motor cortex.

However, the function of the striosomes, which are not part of those pathways, remained unknown. For many years, researchers in Graybiel’s lab have been trying to solve that mystery.

Their previous work revealed that striosomes receive much of their input from parts of the brain that process emotion. Within striosomes, there are two major types of neurons, classified as D1 and D2. In a 2015 study, Graybiel found that one of these cell types, D1, sends input to the substantia nigra, which is the brain’s major dopamine-producing center.

It took much longer to trace the output of the other set, D2 neurons. In the new Current Biology study, the researchers discovered that those neurons also eventually project to the substantia nigra, but first they connect to a set of neurons in the globus palladus, which inhibits dopamine output. This pathway, an indirect connection to the substantia nigra, reduces the brain’s dopamine output and inhibits movement.

The researchers also confirmed their earlier finding that the pathway arising from D1 striosomes connects directly to the substantia nigra, stimulating dopamine release and initiating movement.

“In the striosomes, we’ve found what is probably a mimic of the classical go/no-go pathways,” Graybiel says. “They’re like classic motor go/no-go pathways, but they don’t go to the motor output neurons of the basal ganglia. Instead, they go to the dopamine cells, which are so important to movement and motivation.”

Emotional decisions

The findings suggest that the classical model of how the striatum controls movement needs to be modified to include the role of these newly identified pathways. The researchers now hope to test their hypothesis that input related to motivation and emotion, which enters the striosomes from the cortex and the limbic system, influences dopamine levels in a way that can encourage or discourage action.

That dopamine release may be especially relevant for actions that induce anxiety or stress. In their 2015 study, Graybiel’s lab found that striosomes play a key role in making decisions that provoke high levels of anxiety; in particular, those that are high risk but may also have a big payoff.

“Ann Graybiel and colleagues have earlier found that the striosome is concerned with inhibiting dopamine neurons. Now they show unexpectedly that another type of striosomal neuron exerts the opposite effect and can signal reward. The striosomes can thus both up- or down-regulate dopamine activity, a very important discovery. Clearly, the regulation of dopamine activity is critical in our everyday life with regard to both movements and mood, to which the striosomes contribute,” says Sten Grillner, a professor of neuroscience at the Karolinska Institute in Sweden, who was not involved in the research.

Another possibility the researchers plan to explore is whether striosomes and matrix cells are arranged in modules that affect motor control of specific parts of the body.

“The next step is trying to isolate some of these modules, and by simultaneously working with cells that belong to the same module, whether they are in the matrix or striosomes, try to pinpoint how the striosomes modulate the underlying function of each of these modules,” Lazaridis says.

They also hope to explore how the striosomal circuits, which project to the same region of the brain that is ravaged by Parkinson’s disease, may influence that disorder.

The research was funded by the National Institutes of Health, the Saks-Kavanaugh Foundation, the William N. and Bernice E. Bumpus Foundation, Jim and Joan Schattinger, the Hock E. Tan and K. Lisa Yang Center for Autism Research, Robert Buxton, the Simons Foundation, the CHDI Foundation, and an Ellen Schapiro and Gerald Axelbaum Investigator BBRF Young Investigator Grant.

Seven with MIT ties elected to National Academy of Medicine for 2024

by Nina Tamburello | Koch Institute |

The National Academy of Medicine recently announced the election of more than 90 members during its annual meeting, including MIT faculty members Matthew Vander Heiden and Fan Wang, along with five MIT alumni.

Election to the National Academy of Medicine (NAM) is considered one of the highest honors in the fields of health and medicine and recognizes individuals who have demonstrated outstanding professional achievement and commitment to service.

Matthew Vander Heiden is the director of the Koch Institute for Integrative Cancer Research at MIT, a Lester Wolfe Professor of Molecular Biology, and a member of the Broad Institute of MIT and Harvard. His research explores how cancer cells reprogram their metabolism to fuel tumor growth and has provided key insights into metabolic pathways that support cancer progression, with implications for developing new therapeutic strategies. The National Academy of Medicine recognized Vander Heiden for his contributions to “the development of approved therapies for cancer and anemia” and his role as a “thought leader in understanding metabolic phenotypes and their relations to disease pathogenesis.”

Vander Heiden earned his MD and PhD from the University of Chicago and completed  his clinical training in internal medicine and medical oncology at the Brigham and Women’s Hospital and the Dana-Farber Cancer Institute. After postdoctoral research at Harvard Medical School, Vander Heiden joined the faculty of the MIT Department of Biology and the Koch Institute in 2010. He is also a practicing oncologist and instructor in medicine at Dana-Farber Cancer Institute and Harvard Medical School.

Fan Wang is a professor of brain and cognitive sciences, an investigator at the McGovern Institute, and director of the K. Lisa Yang and Hock E. Tan Center for Molecular Therapeutics at MIT.  Wang’s research focuses on the neural circuits governing the bidirectional interactions between the brain and body. She is specifically interested in the circuits that control the sensory and emotional aspects of pain and addiction, as well as the sensory and motor circuits that work together to execute behaviors such as eating, drinking, and moving. The National Academy of Medicine has recognized her body of work for “providing the foundational knowledge to develop new therapies to treat chronic pain and movement disorders.”

Before coming to MIT in 2021, Wang obtained her PhD from Columbia University and received her postdoctoral training at the University of California at San Francisco and Stanford University. She became a faculty member at Duke University in 2003 and was later appointed the Morris N. Broad Professor of Neurobiology. Wang is also a member of the American Academy of Arts and Sciences and she continues to make important contributions to the neural mechanisms underlying general anesthesia, pain perception, and movement control.

MIT alumni who were elected to the NAM for 2024 include:

  • Leemore Dafny PhD ’01 (Economics);
  • David Huang ’85 MS ’89  (Electrical Engineering and Computer Science) PhD ’93 Medical Engineering and Medical Physics);
  • Nola M. Hylton ’79 (Chemical Engineering);
  • Mark R. Prausnitz PhD ’94 (Chemical Engineering); and
  • Konstantina M. Stankovic ’92 (Biology and Physics) PhD ’98 (Speech and Hearing Bioscience and Technology)

Established originally as the Institute of Medicine in 1970 by the National Academy of Sciences, the National Academy of Medicine addresses critical issues in health, science, medicine, and related policy and inspires positive actions across sectors.

“This class of new members represents the most exceptional researchers and leaders in health and medicine, who have made significant breakthroughs, led the response to major public health challenges, and advanced health equity,” said National Academy of Medicine President Victor J. Dzau. “Their expertise will be necessary to supporting NAM’s work to address the pressing health and scientific challenges we face today.”

Model reveals why debunking election misinformation often doesn’t work

Anne Trafton |

When an election result is disputed, people who are skeptical about the outcome may be swayed by figures of authority who come down on one side or the other. Those figures can be independent monitors, political figures, or news organizations. However, these “debunking” efforts don’t always have the desired effect, and in some cases, they can lead people to cling more tightly to their original position.

Neuroscientists and political scientists at MIT and the University of California at Berkeley have now created a computational model that analyzes the factors that help to determine whether debunking efforts will persuade people to change their beliefs about the legitimacy of an election. Their findings suggest that while debunking fails much of the time, it can be successful under the right conditions.

For instance, the model showed that successful debunking is more likely if people are less certain of their original beliefs and if they believe the authority is unbiased or strongly motivated by a desire for accuracy. It also helps when an authority comes out in support of a result that goes against a bias they are perceived to hold: for example, Fox News declaring that Joseph R. Biden had won in Arizona in the 2020 U.S. presidential election.

“When people see an act of debunking, they treat it as a human action and understand it the way they understand human actions — that is, as something somebody did for their own reasons,” says Rebecca Saxe, the John W. Jarve Professor of Brain and Cognitive Sciences, a member of MIT’s McGovern Institute for Brain Research, and the senior author of the study. “We’ve used a very simple, general model of how people understand other people’s actions, and found that that’s all you need to describe this complex phenomenon.”

The findings could have implications as the United States prepares for the presidential election taking place on Nov. 5, as they help to reveal the conditions that would be most likely to result in people accepting the election outcome.

MIT graduate student Setayesh Radkani is the lead author of the paper, which appears today in a special election-themed issue of the journal PNAS Nexus. Marika Landau-Wells PhD ’18, a former MIT postdoc who is now an assistant professor of political science at the University of California at Berkeley, is also an author of the study.

Modeling motivation

In their work on election debunking, the MIT team took a novel approach, building on Saxe’s extensive work studying “theory of mind” — how people think about the thoughts and motivations of other people.

As part of her PhD thesis, Radkani has been developing a computational model of the cognitive processes that occur when people see others being punished by an authority. Not everyone interprets punitive actions the same way, depending on their previous beliefs about the action and the authority. Some may see the authority as acting legitimately to punish an act that was wrong, while others may see an authority overreaching to issue an unjust punishment.

Last year, after participating in an MIT workshop on the topic of polarization in societies, Saxe and Radkani had the idea to apply the model to how people react to an authority attempting to sway their political beliefs. They enlisted Landau-Wells, who received her PhD in political science before working as a postdoc in Saxe’s lab, to join their effort, and Landau suggested applying the model to debunking of beliefs regarding the legitimacy of an election result.

The computational model created by Radkani is based on Bayesian inference, which allows the model to continually update its predictions of people’s beliefs as they receive new information. This approach treats debunking as an action that a person undertakes for his or her own reasons. People who observe the authority’s statement then make their own interpretation of why the person said what they did. Based on that interpretation, people may or may not change their own beliefs about the election result.

Additionally, the model does not assume that any beliefs are necessarily incorrect or that any group of people is acting irrationally.

“The only assumption that we made is that there are two groups in the society that differ in their perspectives about a topic: One of them thinks that the election was stolen and the other group doesn’t,” Radkani says. “Other than that, these groups are similar. They share their beliefs about the authority — what the different motives of the authority are and how motivated the authority is by each of those motives.”

The researchers modeled more than 200 different scenarios in which an authority attempts to debunk a belief held by one group regarding the validity of an election outcome.

Each time they ran the model, the researchers altered the certainty levels of each group’s original beliefs, and they also varied the groups’ perceptions of the motivations of the authority. In some cases, groups believed the authority was motivated by promoting accuracy, and in others they did not. The researchers also altered the groups’ perceptions of whether the authority was biased toward a particular viewpoint, and how strongly the groups believed in those perceptions.

Building consensus

In each scenario, the researchers used the model to predict how each group would respond to a series of five statements made by an authority trying to convince them that the election had been legitimate. The researchers found that in most of the scenarios they looked at, beliefs remained polarized and in some cases became even further polarized. This polarization could also extend to new topics unrelated to the original context of the election, the researchers found.

However, under some circumstances, the debunking was successful, and beliefs converged on an accepted outcome. This was more likely to happen when people were initially more uncertain about their original beliefs.

“When people are very, very certain, they become hard to move. So, in essence, a lot of this authority debunking doesn’t matter,” Landau-Wells says. “However, there are a lot of people who are in this uncertain band. They have doubts, but they don’t have firm beliefs. One of the lessons from this paper is that we’re in a space where the model says you can affect people’s beliefs and move them towards true things.”

Another factor that can lead to belief convergence is if people believe that the authority is unbiased and highly motivated by accuracy. Even more persuasive is when an authority makes a claim that goes against their perceived bias — for instance, Republican governors stating that elections in their states had been fair even though the Democratic candidate won.

As the 2024 presidential election approaches, grassroots efforts have been made to train nonpartisan election observers who can vouch for whether an election was legitimate. These types of organizations may be well-positioned to help sway people who might have doubts about the election’s legitimacy, the researchers say.

“They’re trying to train to people to be independent, unbiased, and committed to the truth of the outcome more than anything else. Those are the types of entities that you want. We want them to succeed in being seen as independent. We want them to succeed as being seen as truthful, because in this space of uncertainty, those are the voices that can move people toward an accurate outcome,” Landau-Wells says.

The research was funded, in part, by the Patrick J. McGovern Foundation and the Guggenheim Foundation.

A new method makes high-resolution imaging more accessible

Anne Trafton |

A classical way to image nanoscale structures in cells is with high-powered, expensive super-resolution microscopes. As an alternative, MIT researchers have developed a way to expand tissue before imaging it — a technique that allows them to achieve nanoscale resolution with a conventional light microscope.

In the newest version of this technique, the researchers have made it possible to expand tissue 20-fold in a single step. This simple, inexpensive method could pave the way for nearly any biology lab to perform nanoscale imaging.

“This democratizes imaging,” says Laura Kiessling, the Novartis Professor of Chemistry at MIT and a member of the Broad Institute of MIT and Harvard and MIT’s Koch Institute for Integrative Cancer Research. “Without this method, if you want to see things with a high resolution, you have to use very expensive microscopes. What this new technique allows you to do is see things that you couldn’t normally see with standard microscopes. It drives down the cost of imaging because you can see nanoscale things without the need for a specialized facility.”

At the resolution achieved by this technique, which is around 20 nanometers, scientists can see organelles inside cells, as well as clusters of proteins.

“Twenty-fold expansion gets you into the realm that biological molecules operate in. The building blocks of life are nanoscale things: biomolecules, genes, and gene products,” says Edward Boyden, the Y. Eva Tan Professor in Neurotechnology at MIT; a professor of biological engineering, media arts and sciences, and brain and cognitive sciences; a Howard Hughes Medical Institute investigator; and a member of MIT’s McGovern Institute for Brain Research and Koch Institute for Integrative Cancer Research.

Boyden and Kiessling are the senior authors of the new study, which appears today in Nature Methods. MIT graduate student Shiwei Wang and Tay Won Shin PhD ’23 are the lead authors of the paper.

A single expansion

Boyden’s lab invented expansion microscopy in 2015. The technique requires embedding tissue into an absorbent polymer and breaking apart the proteins that normally hold tissue together. When water is added, the gel swells and pulls biomolecules apart from each other.

The original version of this technique, which expanded tissue about fourfold, allowed researchers to obtain images with a resolution of around 70 nanometers. In 2017, Boyden’s lab modified the process to include a second expansion step, achieving an overall 20-fold expansion. This enables even higher resolution, but the process is more complicated.

“We’ve developed several 20-fold expansion technologies in the past, but they require multiple expansion steps,” Boyden says. “If you could do that amount of expansion in a single step, that could simplify things quite a bit.”

With 20-fold expansion, researchers can get down to a resolution of about 20 nanometers, using a conventional light microscope. This allows them see cell structures like microtubules and mitochondria, as well as clusters of proteins.

In the new study, the researchers set out to perform 20-fold expansion with only a single step. This meant that they had to find a gel that was both extremely absorbent and mechanically stable, so that it wouldn’t fall apart when expanded 20-fold.

To achieve that, they used a gel assembled from N,N-dimethylacrylamide (DMAA) and sodium acrylate. Unlike previous expansion gels that rely on adding another molecule to form crosslinks between the polymer strands, this gel forms crosslinks spontaneously and exhibits strong mechanical properties. Such gel components previously had been used in expansion microscopy protocols, but the resulting gels could expand only about tenfold. The MIT team optimized the gel and the polymerization process to make the gel more robust, and to allow for 20-fold expansion.

To further stabilize the gel and enhance its reproducibility, the researchers removed oxygen from the polymer solution prior to gelation, which prevents side reactions that interfere with crosslinking. This step requires running nitrogen gas through the polymer solution, which replaces most of the oxygen in the system.

Once the gel is formed, select bonds in the proteins that hold the tissue together are broken and water is added to make the gel expand. After the expansion is performed, target proteins in tissue can be labeled and imaged.

“This approach may require more sample preparation compared to other super-resolution techniques, but it’s much simpler when it comes to the actual imaging process, especially for 3D imaging,” Shin says. “We document the step-by-step protocol in the manuscript so that readers can go through it easily.”

Imaging tiny structures

Using this technique, the researchers were able to image many tiny structures within brain cells, including structures called synaptic nanocolumns. These are clusters of proteins that are arranged in a specific way at neuronal synapses, allowing neurons to communicate with each other via secretion of neurotransmitters such as dopamine.

In studies of cancer cells, the researchers also imaged microtubules — hollow tubes that help give cells their structure and play important roles in cell division. They were also able to see mitochondria (organelles that generate energy) and even the organization of individual nuclear pore complexes (clusters of proteins that control access to the cell nucleus).

Wang is now using this technique to image carbohydrates known as glycans, which are found on cell surfaces and help control cells’ interactions with their environment. This method could also be used to image tumor cells, allowing scientists to glimpse how proteins are organized within those cells, much more easily than has previously been possible.

The researchers envision that any biology lab should be able to use this technique at a low cost since it relies on standard, off-the-shelf chemicals and common equipment such confocal microscopes and glove bags, which most labs already have or can easily access.

“Our hope is that with this new technology, any conventional biology lab can use this protocol with their existing microscopes, allowing them to approach resolution that can only be achieved with very specialized and costly state-of-the-art microscopes,” Wang says.

The research was funded, in part, by the U.S. National Institutes of Health, an MIT Presidential Graduate Fellowship, U.S. National Science Foundation Graduate Research Fellowship grants, Open Philanthropy, Good Ventures, the Howard Hughes Medical Institute, Lisa Yang, Ashar Aziz, and the European Research Council.

Tiny magnetic discs offer remote brain stimulation without transgenes

by David L. Chandler |

Novel magnetic nanodiscs could provide a much less invasive way of stimulating parts of the brain, paving the way for stimulation therapies without implants or genetic modification, MIT researchers report.

The scientists envision that the tiny discs, which are about 250 nanometers across (about 1/500 the width of a human hair), would be injected directly into the desired location in the brain. From there, they could be activated at any time simply by applying a magnetic field outside the body. The new particles could quickly find applications in biomedical research, and eventually, after sufficient testing, might be applied to clinical uses.

The development of these nanoparticles is described in the journal Nature Nanotechnology, in a paper by Polina Anikeeva, a professor in MIT’s departments of Materials Science and Engineering and Brain and Cognitive Sciences, graduate student Ye Ji Kim, and 17 others at MIT and in Germany.

Deep brain stimulation (DBS) is a common clinical procedure that uses electrodes implanted in the target brain regions to treat symptoms of neurological and psychiatric conditions such as Parkinson’s disease and obsessive-compulsive disorder. Despite its efficacy, the surgical difficulty and clinical complications associated with DBS limit the number of cases where such an invasive procedure is warranted. The new nanodiscs could provide a much more benign way of achieving the same results.

Over the past decade other implant-free methods of producing brain stimulation have been developed. However, these approaches were often limited by their spatial resolution or ability to target deep regions. For the past decade, Anikeeva’s Bioelectronics group as well as others in the field used magnetic nanomaterials to transduce remote magnetic signals into brain stimulation. However, these magnetic methods relied on genetic modifications and can’t be used in humans.

Since all nerve cells are sensitive to electrical signals, Kim, a graduate student in Anikeeva’s group, hypothesized that a magnetoelectric nanomaterial that can efficiently convert magnetization into electrical potential could offer a path toward remote magnetic brain stimulation. Creating a nanoscale magnetoelectric material was, however, a formidable challenge.

Kim synthesized novel magnetoelectric nanodiscs and collaborated with Noah Kent, a postdoc in Anikeeva’s lab with a background in physics who is a second author of the study, to understand the properties of these particles.

The structure of the new nanodiscs consists of a two-layer magnetic core and a piezoelectric shell. The magnetic core is magnetostrictive, which means it changes shape when magnetized. This deformation then induces strain in the piezoelectric shell which produces a varying electrical polarization. Through the combination of the two effects, these composite particles can deliver electrical pulses to neurons when exposed to magnetic fields.

One key to the discs’ effectiveness is their disc shape. Previous attempts to use magnetic nanoparticles had used spherical particles, but the magnetoelectric effect was very weak, says Kim. This anisotropy enhances magnetostriction by over a 1000-fold, adds Kent.

The team first added their nanodiscs to cultured neurons, which allowed then to activate these cells on demand with short pulses of magnetic field. This stimulation did not require any genetic modification.

They then injected small droplets of magnetoelectric nanodiscs solution into specific regions of the brains of mice. Then, simply turning on a relatively weak electromagnet nearby triggered the particles to release a tiny jolt of electricity in that brain region. The stimulation could be switched on and off remotely by the switching of the electromagnet. That electrical stimulation “had an impact on neuron activity and on behavior,” Kim says.

The team found that the magnetoelectric nanodiscs could stimulate a deep brain region, the ventral tegmental area, that is associated with feelings of reward.

The team also stimulated another brain area, the subthalamic nucleus, associated with motor control. “This is the region where electrodes typically get implanted to manage Parkinson’s disease,” Kim explains. The researchers were able to successfully demonstrate the modulation of motor control through the particles. Specifically, by injecting nanodiscs only in one hemisphere, the researchers could induce rotations in healthy mice by applying magnetic field.

The nanodiscs could trigger the neuronal activity comparable with conventional implanted electrodes delivering mild electrical stimulation. The authors achieved subsecond temporal precision for neural stimulation with their method yet observed significantly reduced foreign body responses as compared to the electrodes, potentially allowing for even safer deep brain stimulation.

The multilayered chemical composition and physical shape and size of the new multilayered nanodiscs is what made precise stimulation possible.

While the researchers successfully increased the magnetostrictive effect, the second part of the process, converting the magnetic effect into an electrical output, still needs more work, Anikeeva says. While the magnetic response was a thousand times greater, the conversion to an electric impulse was only four times greater than with conventional spherical particles.

“This massive enhancement of a thousand times didn’t completely translate into the magnetoelectric enhancement,” says Kim. “That’s where a lot of the future work will be focused, on making sure that the thousand times amplification in magnetostriction can be converted into a thousand times amplification in the magnetoelectric coupling.”

What the team found, in terms of the way the particles’ shapes affects their magnetostriction, was quite unexpected. “It’s kind of a new thing that just appeared when we tried to figure out why these particles worked so well,” says Kent.

Anikeeva adds: “Yes, it’s a record-breaking particle, but it’s not as record-breaking as it could be.” That remains a topic for further work, but the team has ideas about how to make further progress.

While these nanodiscs could in principle already be applied to basic research using animal models, to translate them to clinical use in humans would require several more steps, including large-scale safety studies, “which is something academic researchers are not necessarily most well-positioned to do,” Anikeeva says. “When we find that these particles are really useful in a particular clinical context, then we imagine that there will be a pathway for them to undergo more rigorous large animal safety studies.”

The team included researchers affiliated with MIT’s departments of Materials Science and Engineering, Electrical Engineering and Computer Science, Chemistry, and Brain and Cognitive Sciences; the Research Laboratory of Electronics; the McGovern Institute for Brain Research; and the Koch Institute for Integrative Cancer Research; and from the Friedrich-Alexander University of Erlangen, Germany. The work was supported, in part, by the National Institutes of Health, the National Center for Complementary and Integrative Health, the National Institute for Neurological Disorders and Stroke, the McGovern Institute for Brain Research, and the K. Lisa Yang and Hock E. Tan Center for Molecular Therapeutics in Neuroscience.

Finding some stability in adaptable brains

by Jennifer Michalowski |

One of the brain’s most celebrated qualities is its adaptability. Changes to neural circuits, whose connections are continually adjusted as we experience and interact with the world, are key to how we learn. But to keep knowledge and memories intact, some parts of the circuitry must be resistant to this constant change.

“Brains have figured out how to navigate this landscape of balancing between stability and flexibility, so that you can have new learning and you can have lifelong memory,” says neuroscientist Mark Harnett, an investigator at MIT’s McGovern Institute.

In the August 27, 2024 of the journal Cell Reports, Harnett and his team show how individual neurons can contribute to both parts of this vital duality. By studying the synapses through which pyramidal neurons in the brain’s sensory cortex communicate, they have learned how the cells preserve their understanding of some of the world’s most fundamental features, while also maintaining the flexibility they need to adapt to a changing world.

McGovern Institute Investigator Mark Harnett. Photo: Adam Glanzman

Visual connections

Pyramidal neurons receive input from other neurons via thousands of connection points. Early in life, these synapses are extremely malleable; their strength can shift as a young animal takes in visual information and learns to interpret it. Most remain adaptable into adulthood, but Harnett’s team discovered that some of the cells’ synapses lose their flexibility when the animals are less than a month old. Having both stable and flexible synapses means these neurons can combine input from different sources to use visual information in flexible ways.

Microscopic image of a mouse brain.
A confocal image of a mouse brain showing dLGN neurons in pink. Image: Courtney Yaeger, Mark Harnett.

Postdoctoral fellow Courtney Yaeger took a close look at these unusually stable synapses, which cluster together along a narrow region of the elaborately branched pyramidal cells. She was interested in the connections through which the cells receive primary visual information, so she traced their connections with neurons in a vision-processing center of the brain’s thalamus called the dorsal lateral geniculate nucleus (dLGN).

The long extensions through which a neuron receives signals from other cells are called dendrites, and they branch of from the main body of the cell into a tree-like structure. Spiny protrusions along the dendrites form the synapses that connect pyramidal neurons to other cells. Yaeger’s experiments showed that connections from the dLGN all led to a defined region of the pyramidal cells—a tight band within what she describes as the trunk of the dendritic tree.

Yaeger found several ways in which synapses in this region— formally known as the apical oblique dendrite domain—differ from other synapses on the same cells. “They’re not actually that far away from each other, but they have completely different properties,” she says.

Stable synapses

In one set of experiments, Yaeger activated synapses on the pyramidal neurons and measured the effect on the cells’ electrical potential. Changes to a neuron’s electrical potential generate the impulses the cells use to communicate with one another. It is common for a synapse’s electrical effects to amplify when synapses nearby are also activated. But when signals were delivered to the apical oblique dendrite domain, each one had the same effect, no matter how many synapses were stimulated. Synapses there don’t interact with one another at all, Harnett says. “They just do what they do. No matter what their neighbors are doing, they all just do kind of the same thing.”

Two rows of seven confocal microscope images of dendrites.
Representative oblique (top) and basal (bottom) dendrites from the same Layer 5 pyramidal neuron imaged across 7 days. Transient spines are labeled with yellow arrowheads the day before disappearance. Image: Courtney Yaeger, Mark Harnett.

The team was also able to visualize the molecular contents of individual synapses. This revealed a surprising lack of a certain kind of neurotransmitter receptor, called NMDA receptors, in the apical oblique dendrites. That was notable because of NMDA receptors’ role in mediating changes in the brain. “Generally when we think about any kind of learning and memory and plasticity, it’s NMDA receptors that do it,” Harnett says. “That is the by far most common substrate of learning and memory in all brains.”

When Yaeger stimulated the apical oblique synapses with electricity, generating patterns of activity that would strengthen most synapses, the team discovered a consequence of the limited presence of NMDA receptors. The synapses’ strength did not change. “There’s no activity-dependent plasticity going on there, as far as we have tested,” Yaeger says.

That makes sense, the researchers say, because the cells’ connections from the thalamus relay primary visual information detected by the eyes. It is through these connections that the brain learns to recognize basic visual features like shapes and lines.

“These synapses are basically a robust, high fidelity readout of this visual information,” Harnett explains. “That’s what they’re conveying, and it’s not context sensitive. So it doesn’t matter how many other synapses are active, they just do exactly what they’re going to do, and you can’t modify them up and down based on activity. So they’re very, very stable.”

“You actually don’t want those to be plastic,” adds Yaeger.

“Can you imagine going to sleep and then forgetting what a vertical line looks like? That would be disastrous.” – Courtney Yaeger

By conducting the same experiments in mice of different ages, the researchers determined that the synapses that connect pyramidal neurons to the thalamus become stable a few weeks after young mice first open their eyes. By that point, Harnett says, they have learned everything they need to learn. On the other hand, if mice spend the first weeks of their lives in the dark, the synapses never stabilize—further evidence that the transition depends on visual experience.

The team’s findings not only help explain how the brain balances flexibility and stability, they could help researchers teach artificial intelligence how to do the same thing. Harnett says artificial neural networks are notoriously bad at this: When an artificial neural network that does something well is trained to do something new, it almost always experiences “catastrophic forgetting” and can no longer perform its original task. Harnett’s team is exploring how they can use what they’ve learned about real brains to overcome this problem in artificial networks.