Anikeeva, the Matoula S. Salapatas Professor in Materials Science and Engineering at MIT, works at the intersection of materials science, electronics, and neurobiology to improve our understanding of brain-body communication. She is head of MIT’s Materials Science and Engineering Department, and is also a professor of brain and cognitive sciences, director of the K. Lisa Yang Brain-Body Center, and associate director of the Research Laboratory of Electronics. Anikeeva’s lab has developed ultrathin, flexible fibers that probe the flow of information between the brain and peripheral organs in the body. Her ultimate goal is to develop novel technologies to achieve healthy minds in healthy bodies.
The Blavatnik National Awards for Young Scientists is the largest unrestricted scientific prize offered to America’s most promising, faculty-level scientific researchers under 42. The 2024 Blavatnik National Awards received 331 nominations from 172 institutions in 43 US states and selected three women scientists as laureates (Cigall Kadoch, Dana Farber Cancer Institute; Markita del Carpio Landry, UC Berkeley; and Britney Schmidt, Cornell University). An additional 15 finalists, including two from MIT: Anikeeva and Yogesh Surendranath will also receive monetary prizes.
“On behalf of the Blavatnik Family Foundation, I congratulate this year’s outstanding laureates and finalists for their exceptional research. They are among the preeminent leaders of the next generation of scientific innovation and discovery,” said Len Blavatnik, founder of Access Industries and the Blavatnik Family Foundation and a member of the President’s Council of The New York Academy of Sciences.
The Blavatnik National Awards for Young Scientists will celebrate the 2024 laureates and finalists in a gala ceremony on October 1, 2024, at the American Museum of Natural History in New York.
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.
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.”
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.
Placebos are inert treatments, generally not expected to impact biological pathways or improve a person’s physical health. But time and again, some patients report that they feel better after taking a placebo. Increasingly, doctors and scientists are recognizing that rather than dismissing placebos as mere trickery, they may be able to help patients by harnessing their power.
To maximize the impact of the placebo effect and design reliable therapeutic strategies, researchers need a better understanding of how it works. Now, with a new animal model developed by scientists at the McGovern Institute, they will be able to investigate the neural circuits that underlie placebos’ ability to elicit pain relief.
“The brain and body interaction has a lot of potential, in a way that we don’t fully understand,” says McGovern investigator Fan Wang. “I really think there needs to be more of a push to understand placebo effect, in pain and probably in many other conditions. Now we have a strong model to probe the circuit mechanism.”
Context-dependent placebo effect
McGovern Investigator Fan Wang. Photo: Caitliin Cunningham
In the September 5, 2024, issue of the journal Current Biology, Wang and her team report that they have elicited strong placebo pain relief in mice by activating pain-suppressing neurons in the brain while the mice are in a specific environment—thereby teaching the animals that they feel better when they are in that context. Following their training, placing the mice in that environment alone is enough to suppress pain. The team’s experiments, which were funded by the National Institutes of Health, the K. Lisa Yang Brain-Body Center and the K. Lisa Yang and Hock E. Tan Center for Molecular Therapeutics within MIT’s Yang Tan Collective show that this context-dependent placebo effect relieves both acute and chronic pain.
Context is critical for the placebo effect. While a pill can help a patient feel better when they expect it to, even if it is made only of sugar or starch, it seems to be not just the pill that sets up those expectations, but the entire scenario in which the pill is taken. For example, being in a hospital and interacting with doctors can contribute to a patient’s perception of care, and these social and environmental factors can make a placebo effect more probable.
Postdoctoral fellows Bin Chen and Nitsan Goldstein used visual and textural cues to define a specific place. Then they activated pain-suppressing neurons in the brain while the animals were in this “pain-relief box.” Those pain-suppressing neurons, which Wang’s lab discovered a few years ago, are located in an emotion-processing center of the brain called the central amygdala. By expressing light-sensitive channels in these neurons, the researchers were able to suppress pain with light in the pain-relief box and leave the neurons inactive when mice were in a control box.
Animals learned to prefer the pain-relief box to other environments. And when the researchers tested their response to potentially painful stimuli after they had made that association, they found the mice were less sensitive while they were there. “Just by being in the context that they had associated with pain suppression, we saw that reduced pain—even though we weren’t actually activating those [pain-suppressing] neurons,” Goldstein explains.
Acute and chronic pain relief
Some scientists have been able to elicit placebo pain relief in rodents by treating the animals with morphine, linking environmental cues to the pain suppression caused by the drugs similar to the way Wang’s team did by directly activating pain-suppressing neurons. This drug-based approach works best for setting up expectations of relief for acute pain; its placebo effect is short-lived and mostly ineffective against chronic pain. So Wang, Chen, and Goldstein were particularly pleased to find that their engineered placebo effect was effective for relieving both acute and chronic pain.
In their experiments, animals experiencing a chemotherapy-induced hypersensitivity to touch exhibited a preference for the pain relief box as much as animals who were exposed to a chemical that induces acute pain, days after their initial conditioning. Once there, their chemotherapy-induced pain sensitivity was eliminated; they exhibited no more sensitivity to painful stimuli than they had prior to receiving chemotherapy.
One of the biggest surprises came when the researchers turned their attention back to the pain-suppressing neurons in the central amygdala that they had used to trigger pain relief. They suspected that those neurons might be reactivated when mice returned to the pain-relief box. Instead, they found that after the initial conditioning period, those neurons remained quiet. “These neurons are not reactivated, yet the mice appear to be no longer in pain,” Wang says. “So it suggests this memory of feeling well is transferred somewhere else.”
Goldstein adds that there must be a pain-suppressing neural circuit somewhere that is activated by pain-relief-associated contexts—and the team’s new placebo model sets researchers up to investigate those pathways. A deeper understanding of that circuitry could enable clinicians to deploy the placebo effect—alone or in combination with active treatments—to better manage patients’ pain in the future.
When you arrive in a new city, every outing can be an exploration. You may know your way to a few places, but only if you follow a specific route. As you wander around a bit, get lost a few times, and familiarize yourself with some landmarks and where they are relative to each other, your brain develops a cognitive map of the space. You learn how things are laid out, and navigating gets easier.
It takes a lot to generate a useful mental map. “You have to understand the structure of relationships in the world,” says McGovern Investigator Mehrdad Jazayeri. “You need learning and experience to construct clever representations. The advantage is that when you have them, the world is an easier place to deal with.”
Indeed, Jazayeri says, internal models like these are the core of intelligent behavior.
Mehrdad Jazayeri (right) and graduate student Jack Gabel sit inside a rig designed to probe the brain’s ability to solve real-world problems with internal models. Photo: Steph Stevens
Many McGovern scientists see these cognitive maps as windows into their biggest questions about the brain: how it represents the external world, how it lets us learn and adapt, and how it forms and reconstructs memories. Researchers are learning that cells and strategies that the brain uses to understand the layout of a space also help track other kinds of structures in the world, too — from variations in sound to sequences of events. By studying how neurons behave as animals navigate their environments, McGovern researchers also expect to deepen their understanding of other important cognitive functions as well.
Decoding spatial maps
McGovern Investigator Ila Fiete builds theoretical models that help explain how spatial maps are formed in the brain. Previous research has shown that “place cells” and “grid cells” are place-sensitive neurons in the brain’s hippocampus and entorhinal cortex whose firing patterns help an animal map out a space. As an animal becomes familiar with its environment, subsets of these cells become tied to specific locations, firing only when the animal is in them.
The brain’s ability to navigate the world is made possible by a brain circuit that includes the hippocampus (above), entorhinal cortex, and retrosplenial cortex. The firing pattern of “grid cells” and “place cells” in this circuit help form mental representations, or cognitive maps, of the external world. These brain regions are also among the first areas to be affected in people with Alzheimer’s, who often have trouble navigating. Image: Qian Chen, Guoping Feng
Fiete’s models have shown how these circuits can integrate information about movement, like signals from the muscles and vestibular system that change as an animal moves around, to calculate and update its estimate of an animal’s position in space. Fiete suspects the cells that do this can use the same strategy to keep track of other kinds of movement or change.
Mapping a space is about understanding where things are in relationship to one another, says Jazayeri, and tracking relationships is useful for modeling many kinds of structure in the world. For example, the hippocampus and entorhinal cortex are also closely linked to episodic memory, which keeps track of the connections between events and experiences.
“These brain areas are thought to be critical for learning relationships,” Jazayeri says.
Navigating virtual worlds
A key feature of cognitive maps is that they enable us to make predictions and respond to new situations without relying on immediate sensory cues. In a study published in Nature this June, Jazayeri and Fiete saw evidence of the brain’s ability to call up an internal model of an abstract domain: they watched neurons in the brain’s entorhinal cortex register a sequence of images, even when they were hidden from view.
Ila Fiete and postdoc Sarthak Chandra (right) develop theoretical models to study the brain. Photo: Steph Stevens
We can remember the layout of our home from far away or plan a walk through the neighborhood without stepping outside — so it may come as no surprise that the brain can call up its internal model in the absence of movement or sensory inputs. Indeed, previous research has shown that the circuits that encode physical space also encode abstract spaces like auditory sound sequences. But these experiments were performed in the presence of the stimuli, and Jazayeri and his team wanted to know whether simply imagining movement through an abstract domain may also evoke the same cognitive maps.
To test the entorhinal cortex’s ability to do this, Jazayeri and his team designed an experiment where animals had to “mentally” navigate through a previously explored, but now invisible, sequence of images. Working with Fiete, they found that the neurons that had become responsive to particular images in the visible sequence would also fire when mentally navigating the sequence in which images were hidden from view — suggesting the animal was conjuring a representation of the image in its mind.
Ila Fiete has shown that the brain generates a one-dimensional ring of neural activity that acts as a compass. Here, head direction is indicated by color. Image: Ila Fiete
“You see these neurons in the entorhinal cortex undergo very clear dynamic patterns that are in correspondence with what we think the animal might be thinking at the time,” Jazayeri says. “They are updating themselves without any change out there in the world.”
The team then incorporated their data into a computational model to explore how neural circuits might form a mental model of abstract sequences. Their artificial circuit showed that the external inputs (eg., image sequences) become associated with internal models through a simple associative learning rule in which neurons that fire together, wire together. This model suggests that imagined movement could update the internal representations, and the learned association of these internal representations with external inputs might enable a recall of the corresponding inputs even when they are absent.
More broadly, Fiete’s research on cognitive mapping in the hippocampus is leading to some interesting predictions: “One of the conclusions we’re coming to in my group is that when you reconstruct a memory, the area that’s driving that reconstruction is the entorhinal cortex and hippocampus but the reconstruction may happen in the sensory periphery, using the representations that played a role in experiencing that stimulus in the first place,” Fiete explains. “So when I reconstruct an image, I’m likely using my visual cortex to do that reconstruction, driven by the hippocampal complex.” Signals from the entorhinal cortex to the visual cortex during navigation could help an animal visualize landmarks and find its way, even when those landmarks are not visible in the external world.
Landmark coding
Near the entorhinal cortex is the retrosplenial cortex, another brain area that seems to be important for navigation. It is positioned to integrate visual signals with information about the body’s position and movement through space. Both the retrosplenial cortex and the entorhinal cortex are among the first areas impacted by Alzheimer’s disease; spatial disorientation and navigation difficulties may be consequences of their degeneration.
Researchers suspect the retrosplenial cortex may be key to letting an animal know not just where something is, but also how to get there. McGovern Investigator Mark Harnett explains that to generate a cognitive map that can be used to navigate, an animal must understand not just where objects or other cues are in relationship to itself, but also where they are in relationship to each other.
In a study reported in eLife in 2020, Harnett and colleagues may have glimpsed both of these kinds of representations of space inside the brain. They watched neurons there light up as mice ran on a treadmill and tracked the passage of a virtual environment. As the mice became familiar with the landscape and learned where they were likely to find a reward, activity in the retrosplenial cortex changed.
Lukas Fischer, a Harnett lab postdoc, operates a rig designed to study how mice navigate a virtual environment. Photo: Justin Knight
“What we found was this representation started off sort of crude and mostly about what the animal was doing. And then eventually it became more about the task, the landscape, and the reward,” Harnett says.
Harnett’s team has since begun investigating how the retrosplenial cortex enables more complex spatial reasoning. They designed an experiment in which mice must understand many spatial relationships to access a treat. The experimental setup requires mice to consider the location of reward ports, the center of their environment, and their own viewing angle. Most of the time, they succeed. “They have to really do some triangulation, and the retrosplenial cortex seems to be critical for that,” Harnett says.
When the team monitored neural activity during the task, they found evidence that when an animal wasn’t quite sure where to go, its brain held on to multiple spatial hypotheses at the same time, until new information ruled one out.
Fiete, who has worked with Harnett to explore how neural circuits can execute this kind of spatial reasoning, points out that Jazayeri’s team has observed similar reasoning in animals that must make decisions based on temporarily ambiguous auditory cues. “In both cases, animals are able to hold multiple hypotheses in mind and do the inference,” she says. “Mark’s found that the retrosplenial cortex contains all the signals necessary to do that reasoning.”
Beyond spatial reasoning
As his team learns more about the how the brain creates and uses cognitive maps, Harnett hopes activity in the retrosplenial cortex will shed light on a fundamental aspect of the brain’s organization. The retrosplenial cortex doesn’t just receive information from the brain’s vision-processing center, it also sends signals back. He suspects these may direct the visual cortex to relay information that is particularly pertinent to forming or using a meaningful cognitive map.
“The brain’s navigation system is a beautiful playground.” – Ila Fiete
This kind of connectivity, where parts of the brain that carry out complex cognitive processing send signals back to regions that handle simpler functions, is common in the brain. Figuring out why is a key pursuit in Harnett’s lab. “I want to use that as a model for thinking about the larger cortical computations, because you see this kind of motif repeated in a lot of ways, and it’s likely key for understanding how learning works,” he says.
Fiete is particularly interested in unpacking the common set of principles that allow cell circuits to generate maps of both our physical environment and our abstract experiences. What is it about this set of brain areas and circuits that, on the one hand, permits specific map-building computations, and, on the other hand, generalizes across physical space and abstract experience?
“The brain’s navigation system is a beautiful playground,” she says, “and an amazing system in which to investigate all of these questions.”
The Howard Hughes Medical Institute (HHMI) has named McGovern Institute neuroscientist Mehrdad Jazayeri as one of 26 new HHMI investigators—a group of visionary scientists who HHMI will support with more than $300 million over the next seven years.
Support from HHMI is intended to give its investigators, who work at institutions across the United States, the time and resources they need to push the boundaries of the biological sciences. Jazayeri, whose work integrates neurobiology with cognitive science and machine learning, plans to use that support to explore how the brain enables rapid learning and flexible behavior—central aspects of intelligence that have been difficult to study using traditional neuroscience approaches.
Jazayeri says he is delighted and honored by the news. “This is a recognition of my lab’s past accomplishments and the promise of the exciting research we want to embark on,” he says. “I am looking forward to engaging with this wonderful community and making new friends and colleagues while we elevate our science to the next level.”
An unexpected path
Jazayeri, who has been an investigator at the McGovern Institute since 2013, has already made a series of groundbreaking discoveries about how physiological processes in the brain give rise to the abilities of the mind. “That’s what we do really well,” he says. “We expose the computational link between abstract mental concepts, like belief, and electrical signals in the brain,” he says.
Jazayeri’s expertise and enthusiasm for this work grew out a curiosity that was sparked unexpectedly several years after he’d abandoned university education. He’d pursued his undergraduate studies in electrical engineering, a path with good job prospects in Iran where he lived. But an undergraduate program at Sharif University of Technology in Tehran left him disenchanted. “It was an uninspiring experience,” he says. “It’s a top university and I went there excited, but I lost interest as I couldn’t think of a personally meaningful application for my engineering skills. So, after my undergrad, I started a string of random jobs, perhaps to search for my passion.”
A few years later, Jazayeri was trying something new, happily living and working at a banana farm near the Caspian Sea. The farm schedule allowed for leisure in the evenings, which he took advantage of by delving into boxes full of books that an uncle regularly sent him from London. The books were an unpredictable, eclectic mix. Jazayeri read them all—and it was those that talked about the brain that most captured his imagination.
Until then, he had never had much interest in biology. But when he read about neurological disorders and how scientists were studying the brain, he was captivated. The subject seemed to merge his inherent interest in philosophy with an analytical approach that he also loved. “These books made me think that you actually can understand this system at a more concrete level…you can put electrodes in the brain and listen to what neurons say,” he says. “It had never even occurred to me to think about those things.”
He wanted to know more. It took time to find a graduate program in neuroscience that would accept a student with his unconventional background, but eventually the University of Toronto accepted him into a master’s program after he crammed for and passed an undergraduate exam testing his knowledge of physiology. From there, he went on to earn a PhD in neuroscience from New York University studying visual perception, followed by a postdoctoral fellowship at the University of Washington where he studied time perception.
In 2013, Jazayeri joined MIT’s Department of Brain and Cognitive Sciences. At MIT, conversations with new colleagues quickly enriched the way he thought about the brain. “It is fascinating to listen to cognitive scientists’ ideas about the mind,” he says. “They have a rich and deep understanding of the mind but the language they use to describe the mind is not the language of the brain. Bridging this gap in language between neuroscience and cognitive science is at the core of research in my lab.”
His lab’s general approach has been to collect data on neural activity from humans and animals as they perform tasks that call on specific aspects of the mind. “We design tasks that are as simple as possible but get at the crux of the problems in cognitive science,” he explains. “Then we build models that help us connect abstract concepts and theories in cognitive science to signals and dynamics of neural activity in the brain.”
It’s an interdisciplinary approach that even calls on many of the engineering approaches that had failed to inspire him as a student. Students and postdocs in the lab bring a diverse set of knowledge and skills, and together the team has made significant contributions to neuroscience, cognitive science, and computational science.
With animals trained to reproduce a rhythm, they’ve shown how neurons adjust the speed of their signals to predict when something will occur, and what happens when the actual timing of a stimulus deviates from the brain’s expectations.
Studies of time interval predictions have also helped the team learn how the brain weighs different pieces of information as it assesses situations and makes decisions. This process, called Bayesian integration, shapes our beliefs and our confidence in those beliefs. “These are really fundamental concepts in cognitive sciences, and we can now say how neurons exactly do that,” he says.
More recently, by teaching animals to navigate a virtual environment, Jazayeri’s team has found activity in the brain that appears to call up a cognitive map of a space even when its features are not visible. The discovery helps reveal how the brain builds internal models and uses them to interact with the world.
A new paradigm
Jazayeri is proud of these achievements. But he knows that when it comes to understanding the power and complexity of cognition, something is missing.
“Two really important hallmarks of cognition are the ability to learn rapidly and generalize flexibly. If somebody can do that, we say they’re intelligent,” he says. It’s an ability we have from an early age. “If you bring a kid a bunch of toys, they don’t need several years of training, they just can play with the toys right away in very creative ways,” he says. In the wild, many animals are similarly adept at problem solving and finding uses for new tools. But when animals are trained for many months on a single task, as typically happens in a lab, they don’t behave as intelligently. “They become like an expert that does one thing well, but they’re no longer very flexible,” he says.
Figuring out how the brain adapts and acts flexibly in real-world situations in going to require a new approach. “What we have done is that we come up with a task, and then change the animal’s brain through learning to match our task,” he says. “What we now want to do is to add a new paradigm to our work, one in which we will devise the task such that it would match the animal’s brain.”
As an HHMI investigator, Jazayeri plans to take advantage of a host of new technologies to study the brain’s involvement in ecologically relevant behaviors. That means moving beyond the virtual scenarios and digital platforms that have been so widespread in neuroscience labs, including his own, and instead letting animals interact with real objects and environments. “The animal will use its eyes and hands to engage with physical objects in the real world,” he says.
To analyze and learn about animals’ behavior, the team plans detailed tracking of hand and eye movements, and even measurements of sensations that are felt through the hands as animals explore objects and work through problems. These activities are expected to engage the entire brain, so the team will broadly record and analyze neural activity.
Designing meaningful experiments and making sense of the data will be a deeply interdisciplinary endeavor, and Jazayeri knows working with a collaborative community of scientists will be essential. He’s looking forward to sharing the enormous amount of relevant data his lab expects to collect with the research community and getting others involved. Likewise, as a dedicated mentor, he is committed to training scientists who will continue and expand the work in the future.
He is enthusiastic about the opportunity to move into these bigger questions about cognition and intelligence, and support from HHMI comes at an opportune moment. “I think we have now built the infrastructure and conceptual frameworks to think about these problems, and technology for recording and tracking animals has developed a great deal, so we can now do more naturalistic experiments,” he says.
His passion for his work is one of many passions in his life. His love for family, friends, and art are just as deep, and making space to experience everything is a lifelong struggle. But he knows his zeal is infectious. “I think my love for science is probably one of the best motivators of people around me,” he says.
Some people, especially those in public service, perform admirable feats—healthcare workers fighting to keep patients alive or a first responder arriving at the scene of a car crash. But the emotional weight can become a mental burden. Research has shown that emergency personnel are at elevated risk for mental health challenges like post-traumatic stress disorder. How can people undergo such stressful experiences and also maintain their well-being?
A new study from the McGovern Institute reveals that a cognitive strategy focused on social good may be effective in helping people cope with distressing events. The research team found that the approach was comparable to another well-established emotion regulation strategy, unlocking a new tool for dealing with highly adverse situations.
“How you think can improve how you feel.”
– John Gabrieli
“This research suggests that the social good approach might be particularly useful in improving well-being for those constantly exposed to emotionally taxing events,” says John Gabrieli, the Grover Hermann Professor of Health Sciences and Technology and a professor of brain and cognitive sciences at MIT, who is a senior author of the paper.
The study, published today in PLOS ONE, is the first to examine the efficacy of this cognitive strategy. Nancy Tsai, a postdoctoral research scientist in Gabrieli’s lab at the McGovern Institute, is the lead author of the paper.
Emotion regulation tools
Emotion regulation is the ability to mentally reframe how we experience emotions—a skill critical to maintaining good mental health. Doing so can make one feel better when dealing with adverse events, and emotion regulation has been shown to boost emotional, social, cognitive, and physiological outcomes across the lifespan.
MIT postdoctoral researcher Nancy Tsai. Photo: Steph Stevens
One emotion regulation strategy is “distancing,” where a person copes with a negative event by imagining it as happening far away, a long time ago, or from a third-person perspective. Distancing has been well-documented as a useful cognitive tool, but it may be less effective in certain situations, especially ones that are socially charged—like a firefighter rescuing a family from a burning home. Rather than distancing themselves, a person may instead be forced to engage directly with the situation.
“In these cases, the ‘social good’ approach may be a powerful alternative,” says Tsai. “When a person uses the social good method, they view a negative situation as an opportunity to help others or prevent further harm.” For example, a firefighter experiencing emotional distress might focus on the fact that their work enables them to save lives. The idea had yet to be backed by scientific investigation, so Tsai and her team, alongside Gabrieli, saw an opportunity to rigorously probe this strategy.
A novel study
The MIT researchers recruited a cohort of adults and had them complete a questionnaire to gather information including demographics, personality traits, and current well-being, as well as how they regulated their emotions and dealt with stress. The cohort was randomly split into two groups: a distancing group and a social good group. In the online study, each group was shown a series of images that were either neutral (such as fruit) or contained highly aversive content (such as bodily injury). Participants were fully informed of the types of images they might see and could opt out of the study at any time.
Each group was asked to use their assigned cognitive strategy to respond to half of the negative images. For example, while looking at a distressing image, a person in the distancing group could have imagined that it was a screenshot from a movie. Conversely, a subject in the social good group might have responded to the image by envisioning that they were a first responder saving people from harm. For the other half of the negative images, participants were asked to only look at them and pay close attention to their emotions. The researchers asked the participants how they felt after each image was shown.
Social good as a potent strategy
The MIT team found that distancing and social good approaches helped diminish negative emotions. Participants reported feeling better when they used these strategies after viewing adverse content compared to when they did not and stated that both strategies were easy to implement.
The results also revealed that, overall, distancing yielded a stronger effect. Importantly, however, Tsai and Gabrieli believe that this study offers compelling evidence for social good as a powerful method better suited to situations when people cannot distance themselves, like rescuing someone from a car crash, “Which is more probable for people in the real world,” notes Tsai. Moreover, the team discovered that people who most successfully used the social good approach were more likely to view stress as enhancing rather than debilitating. Tsai says this link may point to psychological mechanisms that underlie both emotion regulation and how people respond to stress.
“The social good approach may be a potent strategy to combat the immense emotional demands of certain professions.”
– John Gabrieli
Additionally, the results showed that older adults used the cognitive strategies more effectively than younger adults. The team suspects that this is probably because, as prior research has shown, older adults are more adept at regulating their emotions likely due to having greater life experiences. The authors note that successful emotion regulation also requires cognitive flexibility, or having a malleable mindset to adapt well to different situations.
“This is not to say that people, such as physicians, should reframe their emotions to the point where they fully detach themselves from negative situations,” says Gabrieli. “But our study shows that the social good approach may be a potent strategy to combat the immense emotional demands of certain professions.”
The MIT team says that future studies are needed to further validate this work, and that such research is promising in that it can uncover new cognitive tools to equip individuals to take care of themselves as they bravely assume the challenge of taking care of others.
Language is a defining feature of humanity, and for centuries, philosophers and scientists have contemplated its true purpose. We use language to share information and exchange ideas—but is it more than that? Do we use language not just to communicate, but to think?
McGovern Investivator Ev Fedorenko in the Martinos Imaging Center at MIT. Photo: Caitlin Cunningham
In the June 19, 2024, issue of the journal Nature, McGovern Institute neuroscientist Evelina Fedorenko and colleagues argue that we do not. Language, they say, is primarily a tool for communication.
Fedorenko acknowledges that there is an intuitive link between language and thought. Many people experience an inner voice that seems to narrate their own thoughts. And it’s not unreasonable to expect that well-spoken, articulate individuals are also clear thinkers. But as compelling as these associations can be, they are not evidence that we actually use language to think.
“I think there are a few strands of intuition and confusions that have led people to believe very strongly that language is the medium of thought,” she says.
“But when they are pulled apart thread by thread, they don’t really hold up to empirical scrutiny.”
Separating language and thought
For centuries, language’s potential role in facilitating thinking was nearly impossible to evaluate scientifically. But neuroscientists and cognitive scientists now have tools that enable a more rigorous consideration of the idea. Evidence from both fields, which Fedorenko, MIT cognitive scientist and linguist Edward Gibson, and University of California Berkeley cognitive scientist Steven Piantadosi review in their Nature Perspective, supports the idea that language is a tool for communication, not for thought.
“What we’ve learned by using methods that actually tell us about the engagement of the linguistic processing mechanisms is that those mechanisms are not really engaged when we think,” Fedorenko says. Also, she adds, “you can take those mechanisms away, and it seems that thinking can go on just fine.”
Over the past 20 years, Fedorenko and other neuroscientists have advanced our understanding of what happens in the brain as it generates and understands language. Now, using functional MRI to find parts of the brain that are specifically engaged when someone reads or listens to sentences or passages, they can reliably identify an individual’s language-processing network. Then they can monitor those brain regions while the person performs other tasks, from solving a sudoku puzzle to reasoning about other people’s beliefs.
“Your language system is basically silent when you do all sorts of thinking.” – Ev Fedorenko
“Pretty much everything we’ve tested so far, we don’t see any evidence of the engagement of the language mechanisms,” Fedorenko says. “Your language system is basically silent when you do all sorts of thinking.”
That’s consistent with observations from people who have lost the ability to process language due to an injury or stroke. Severely affected patients can be completely unable to process words, yet this does not interfere with their ability to solve math problems, play chess, or plan for future events. “They can do all the things that they could do before their injury. They just can’t take those mental representations and convert them into a format which would allow them to talk about them with others,” Fedorenko says. “If language gives us the core representations that we use for reasoning, then…destroying the language system should lead to problems in thinking as well, and it really doesn’t.”
Conversely, intellectual impairments do not always associate with language impairment; people with intellectual disability disorders or neuropsychiatric disorders that limit their ability to think and reason do not necessarily have problems with basic linguistic functions. Just as language does not appear to be necessary for thought, Fedorenko and colleagues conclude that it is also not sufficient to produce clear thinking.
Language optimization
In addition to arguing that language is unlikely to be used for thinking, the scientists considered its suitability as a communication tool, drawing on findings from linguistic analyses. Analyses across dozens of diverse languages, both spoken and signed, have found recurring features that make them easy to produce and understand. “It turns out that pretty much any property you look at, you can find evidence that languages are optimized in a way that makes information transfer as efficient as possible,” Fedorenko says.
That’s not a new idea, but it has held up as linguists analyze larger corpora across more diverse sets of languages, which has become possible in recent years as the field has assembled corpora that are annotated for various linguistic features. Such studies find that across languages, sounds and words tend to be pieced together in ways that minimize effort for the language producer without muddling the message. For example, commonly used words tend to be short, while words whose meanings depend on one another tend to cluster close together in sentences. Likewise, linguists have noted features that help languages convey meaning despite potential “signal distortions,” whether due to attention lapses or ambient noise.
“All of these features seem to suggest that the forms of languages are optimized to make communication easier,” Fedorenko says, pointing out that such features would be irrelevant if language was primarily a tool for internal thought.
“Given that languages have all these properties, it’s likely that we use language for communication,” she says. She and her coauthors conclude that as a powerful tool for transmitting knowledge, language reflects the sophistication of human cognition—but does not give rise to it.
The Norwegian Academy of Science and Letters today announced the 2024 Kavli Prize Laureates in the fields of astrophysics, nanoscience, and neuroscience. The 2024 Kavli Prize in Neuroscience honors Nancy Kanwisher, the Walter A. Rosenblith Professor of Cognitive Neuroscience at MIT and an investigator at the McGovern Institute, along with UC Berkeley neurobiologist Doris Tsao, and Rockefeller University neuroscientist Winrich Freiwald for their discovery of a highly localized and specialized system for representation of faces in human and non-human primate neocortex. The neuroscience laureates will share $1 million USD.
“Kanwisher, Freiwald, and Tsao together discovered a localized and specialized neocortical system for face recognition,” says Kristine Walhovd, Chair of the Kavli Neuroscience Committee. “Their outstanding research will ultimately further our understanding of recognition not only of faces, but objects and scenes.”
Overcoming failure
As a graduate student at MIT in the early days of functional brain imaging, Kanwisher was fascinated by the potential of the emerging technology to answer a suite of questions about the human mind. But a lack of brain imaging resources and a series of failed experiments led Kanwisher consider leaving the field for good. She credits her advisor, MIT Professor of Psychology Molly Potter, for supporting her through this challenging time and for teaching her how to make powerful inferences about the inner workings of the mind from behavioral data alone.
After receiving her PhD from MIT, Kanwisher spent a year studying nuclear strategy with a MacArthur Foundation Fellowship in Peace and International Security, but eventually returned to science by accepting a faculty position at Harvard University where she could use the latest brain imaging technology to pursue the scientific questions that had always fascinated her.
Zeroing in on faces
Recognizing faces is important for social interaction in many animals. Previous work in human psychology and animal research had suggested the existence of a functionally specialized system for face recognition, but this system had not clearly been identified with brain imaging technology. It is here that Kanwisher saw her opportunity.
Using a new method at the time, called functional magnetic resonance imaging or fMRI, Kanwisher’s team scanned people while they looked at faces and while they looked at objects, and searched for brain regions that responded more to one than the other. They found a small patch of neocortex, now called the fusiform face area (FFA), that is dedicated specifically to the task of face recognition. She found individual differences in the location of this area and devised an analysis technique to effectively localize specialized functional regions in the brain. This technique is now widely used and applied to domains beyond the face recognition system. Notably, Kanwisher’s first FFA paper was co-authored with Josh McDermott, who was an undergrad at Harvard University at the time, and is now an associate investigator at the McGovern Institute and holds a faculty position alongside Kanwisher in MIT’s Department of Brain and Cognitive Sciences.
The Kanwisher lab at Harvard University circa 1996. From left to right: Nancy Kanwisher, Josh McDermott (then an undergrad), Marvin Chun (postdoc), Ewa Wojciulik (postdoc), and Jody Culham (grad student). Photo: Nancy Kanwisher
From humans to monkeys
Inspired by Kanwisher´s findings, Winrich Freiwald and Doris Tsao together used fMRI to localize similar face patches in macaque monkeys. They mapped out six distinct brain regions, known as the face patch system, including these regions’ functional specialization and how they are connected. By recording the activity of individual brain cells, they revealed how cells in some face patches specialize in faces with particular views.
Tsao proceeded to identify how the face patches work together to identify a face, through a specific code that enables single cells to identify faces by assembling information of facial features. For example, some cells respond to the presence of hair, others to the distance between the eyes. Freiwald uncovered that a separate brain region, called the temporal pole, accelerates our recognition of familiar faces, and that some cells are selectively responsive to familiar faces.
“It was a special thrill for me when Doris and Winrich found face patches in monkeys using fMRI,” says Kanwisher, whose lab at MIT’s McGovern Institute has gone on to uncover many other regions of the human brain that engage in specific aspects of perception and cognition. “They are scientific heroes to me, and it is a thrill to receive the Kavli Prize in neuroscience jointly with them.”
“Nancy and her students have identified neocortical subregions that differentially engage in the perception of faces, places, music and even what others think,” says McGovern Institute Director Robert Desimone. “We are delighted that her groundbreaking work into the functional organization of the human brain is being honored this year with the Kavli Prize.”
Together, the laureates, with their work on neocortical specialization for face recognition, have provided basic principles of neural organization which will further our understanding of how we perceive the world around us.
About the Kavli Prize
The Kavli Prize is a partnership among The Norwegian Academy of Science and Letters, The Norwegian Ministry of Education and Research, and The Kavli Foundation (USA). The Kavli Prize honors scientists for breakthroughs in astrophysics, nanoscience and neuroscience that transform our understanding of the big, the small and the complex. Three one-million-dollar prizes are awarded every other year in each of the three fields. The Norwegian Academy of Science and Letters selects the laureates based on recommendations from three independent prize committees whose members are nominated by The Chinese Academy of Sciences, The French Academy of Sciences, The Max Planck Society of Germany, The U.S. National Academy of Sciences, and The Royal Society, UK.
In the hit T.V. show “Westworld,” Dolores Abernathy, a golden-tressed belle, lives in the days when Manifest Destiny still echoed in America. She begins to notice unusual stirrings shaking up her quaint western town—and soon discovers that her skin is synthetic, and her mind, metal. She’s a cyborg meant to entertain humans. The key to her autonomy lies in reaching consciousness.
Shows like “Westworld” and other media probe the idea of consciousness, attempting to nail down a definition of the concept. However, though humans have ruminated on consciousness for centuries, we still don’t have a solid definition (even the Merriam-Webster dictionary lists five). One framework suggests that consciousness is any experience, from eating a candy bar to heartbreak. Another argues that it is how certain stimuli influence one’s behavior.
MIT graduate student Adam Eisen.
While some search for a philosophical explanation, MIT graduate student Adam Eisen seeks a scientific one.
Eisen studies consciousness in the labs of Ila Fiete, an associate investigator at the McGovern Institute, and Earl Miller, an investigator at the Picower Institute for Learning and Memory. His work melds seemingly opposite fields, using mathematical models to quantitatively explain, and thereby ground, the loftiness of consciousness.
In the Fiete lab, Eisen leverages computational methods to compare the brain’s electrical signals in an awake, conscious state to those in an unconscious state via anesthesia—which dampens communication between neurons so people feel no pain or become unconscious.
“What’s nice about anesthesia is that we have a reliable way of turning off consciousness,” says Eisen.
“So we’re now able to ask: What’s the fluctuation of electrical activity in a conscious versus unconscious brain? By characterizing how these states vary—with the precision enabled by computational models—we can start to build a better intuition for what underlies consciousness.”
Theories of consciousness
How are scientists thinking about consciousness? Eisen says that there are four major theories circulating in the neuroscience sphere. These theories are outlined below.
Global workspace theory
Consider the placement of your tongue in your mouth. This sensory information is always there, but you only notice the sensation when you make the effort to think about it. How does this happen?
“Global workspace theory seeks to explain how information becomes available to our consciousness,” he says. “This is called access consciousness—the kind that stores information in your mind and makes it available for verbal report. In this view, sensory information is broadcasted to higher-level regions of the brain by a process called ignition.” The theory proposes that widespread jolts of neuronal activity or “spiking” are essential for ignition, like how a few claps can lead to an audience applause. It’s through ignition that we reach consciousness.
Eisen’s research in anesthesia suggests, though, that not just any spiking will do. There needs to be a balance: enough activity to spark ignition, but also enough stability such that the brain doesn’t lose its ability to respond to inputs and produce reliable computations to reach consciousness.
Higher order theories
Let’s say you’re listening to “Here Comes The Sun” by The Beatles. Your brain processes the medley of auditory stimuli; you hear the bouncy guitar, upbeat drums, and George Harrison’s perky vocals. You’re having a musical experience—what it’s like to listen to music. According to higher-order theories, such an experience unlocks consciousness.
“Higher-order theories posit that a conscious mental state involves having higher-order mental representations of stimuli—usually in the higher levels of the brain responsible for cognition—to experience the world,” Eisen says.
Integrated information theory
“Imagine jumping into a lake on a warm summer day. All components of that experience—the feeling of the sun on your skin and the coolness of the water as you submerge—come together to form your ‘phenomenal consciousness,’” Eisen says. If the day was slightly less sunny or the water a fraction warmer, he explains, the experience would be different.
“Integrated information theory suggests that phenomenal consciousness involves an experience that is irreducible, meaning that none of the components of that experience can be separated or altered without changing the experience itself,” he says.
Attention schema theory
Attention schema theory, Eisen explains, says ‘attention’ is the information that we are focused on in the world, while ‘awareness’ is the model we have of our attention. He cites an interesting psychology study to disentangle attention and awareness.
In the study, the researchers showed human subjects a mixed sequence of two numbers and six letters on a computer. The participants were asked to report back what the numbers were. While they were doing this task, faintly detectable dots moved across the screen in the background. The interesting part, Eisen notes, is that people weren’t aware of the dots—that is, they didn’t report that they saw them. But despite saying they didn’t see the dots, people performed worse on the task when the dots were present.
“This suggests that some of the subjects’ attention was allocated towards the dots, limiting their available attention for the actual task,” he says. “In this case, people’s awareness didn’t track their attention. The subjects were not aware of the dots, even though the study shows that the dots did indeed affect their attention.”
The science behind consciousness
Eisen notes that a solid understanding of the neural basis of consciousness has yet to be cemented. However, he and his research team are advancing in this quest. “In our work, we found that brain activity is more ‘unstable’ under anesthesia, meaning that it lacks the ability to recover from disturbances—like distractions or random fluctuations in activity—and regain a normal state,” he says.
He and his fellow researchers believe this is because the unconscious brain can’t reliably engage in computations like the conscious brain does, and sensory information gets lost in the noise. This crucial finding points to how the brain’s stability may be a cornerstone of consciousness.
There’s still more work to do, Eisen says. But eventually, he hopes that this research can help crack the enduring mystery of how consciousness shapes human existence. “There is so much complexity and depth to human experience, emotion, and thought. Through rigorous research, we may one day reveal the machinery that gives us our common humanity.”
A new way of imaging the brain with magnetic resonance imaging (MRI) does not directly detect neural activity as originally reported, according to scientists at MIT’s McGovern Institute. The method, first described in 2022, generated excitement within the neuroscience community as a potentially transformative approach. But a study from the lab of McGovern Associate Investigator Alan Jasanoff, reported March 27, 2024, in the journal Science Advances, demonstrates that MRI signals produced by the new method are generated in large part by the imaging process itself, not neuronal activity.
Alan Jasanoff, associate member of the McGovern Institute, and a professor of brain and cognitive sciences, biological engineering, and nuclear science and engineering at MIT. Photo: Justin Knight
Jasanoff explains that having a noninvasive means of seeing neuronal activity in the brain is a long-sought goal for neuroscientists. The functional MRI methods that researchers currently use to monitor brain activity don’t actually detect neural signaling. Instead, they use blood flow changes triggered by brain activity as a proxy. This reveals which parts of the brain are engaged during imaging, but it cannot pinpoint neural activity to precise locations, and it is too slow to truly track neurons’ rapid-fire communications.
So when a team of scientists reported in Science a new MRI method called DIANA, for “direct imaging of neuronal activity,” neuroscientists paid attention. The authors claimed that DIANA detected MRI signals in the brain that corresponded to the electrical signals of neurons, and that it acquired signals far faster than the methods now used for functional MRI.
“Everyone wants this,” Jasanoff says. “If we could look at the whole brain and follow its activity with millisecond precision and know that all the signals that we’re seeing have to do with cellular activity, this would be just wonderful. It could tell us all kinds of things about how the brain works and what goes wrong in disease.”
Jasanoff adds that from the initial report, it was not clear what brain changes DIANA was detecting to produce such a rapid readout of neural activity. Curious, he and his team began to experiment with the method. “We wanted to reproduce it, and we wanted to understand how it worked,” he says.
Decoding DIANA
Recreating the MRI procedure reported by DIANA’s developers, postdoctoral researcher Valerie Doan Phi Van imaged the brain of a rat as an electric stimulus was delivered to one paw. Phi Van says she was excited to see an MRI signal appear in the brain’s sensory cortex, exactly when and where neurons were expected to respond to the sensation on the paw. “I was able to reproduce it,” she says. “I could see the signal.”
With further tests of the system, however, her enthusiasm waned. To investigate the source of the signal, she disconnected the device used to stimulate the animal’s paw, then repeated the imaging. Again, signals showed up in the sensory processing part of the brain. But this time, there was no reason for neurons in that area to be activated. In fact, Phi Van found, the MRI produced the same kinds of signals when the animal inside the scanner was replaced with a tube of water. It was clear DIANA’s functional signals were not arising from neural activity.
Phi Van traced the source of the specious signals to the pulse program that directs DIANA’s imaging process, detailing the sequence of steps the MRI scanner uses to collect data. Embedded within DIANA’s pulse program was a trigger for the device that delivers sensory input to the animal inside the scanner. That synchronizes the two processes, so the stimulation occurs at a precise moment during data acquisition. That trigger appeared to be causing signals that DIANA’s developers had concluded indicated neural activity.
It was clear DIANA’s functional signals were not arising from neural activity.
Phi Van altered the pulse program, changing the way the stimulator was triggered. Using the updated program, the MRI scanner detected no functional signal in the brain in response to the same paw stimulation that had produced a signal before. “If you take this part of the code out, then the signal will also be gone. So that means the signal we see is an artifact of the trigger,” she says.
Jasanoff and Phi Van went on to find reasons why other researchers have struggled to reproduce the results of the original DIANA report, noting that the trigger-generated signals can disappear with slight variations in the imaging process. With their postdoctoral colleague Sajal Sen, they also found evidence that cellular changes that DIANA’s developers had proposed might give rise to a functional MRI signal were not related to neuronal activity.
Jasanoff and Phi Van say it was important to share their findings with the research community, particularly as efforts continue to develop new neuroimaging methods. “If people want to try to repeat any part of the study or implement any kind of approach like this, they have to avoid falling into these pits,” Jasanoff says. He adds that they admire the authors of the original study for their ambition: “The community needs scientists who are willing to take risks to move the field ahead.”
