Author: Julie Pryor

New gift expands mental illness studies at Poitras Center for Psychiatric Disorders Research

by Julie Pryor |

One in every eight people—970 million globally—live with mental illness, according to the World Health Organization, with depression and anxiety being the most common mental health conditions worldwide. Existing therapies for complex psychiatric disorders like depression, anxiety, and schizophrenia have limitations, and federal funding to address these shortcomings is growing increasingly uncertain.

Jim and Pat Poitras
James and Patricia Poitras at an event co-hosted by the McGovern Institute and Autism Speaks. Photo: Justin Knight

Patricia and James Poitras ’63 have committed $8 million to the Poitras Center for Psychiatric Disorders Research to launch pioneering research initiatives aimed at uncovering the brain basis of major mental illness and accelerating the development of novel treatments.

“Federal funding rarely supports the kind of bold, early-stage research that has the potential to transform our understanding of psychiatric illness. Pat and I want to help fill that gap—giving researchers the freedom to follow their most promising leads, even when the path forward isn’t guaranteed,” says James Poitras, who is chair of the McGovern Institute Board.

Their latest gift builds upon their legacy of philanthropic support for psychiatric disorders research at MIT, which now exceeds $46 million.

“With deep gratitude for Jim and Pat’s visionary support, we are eager to launch a bold set of studies aimed at unraveling the neural and cognitive underpinnings of major mental illnesses,” says Robert Desimone, director of the McGovern Institute, home to the Poitras Center. “Together, these projects represent a powerful step toward transforming how we understand and treat mental illness.”

A legacy of support

Soon after joining the McGovern Institute Leadership Board in 2006, the Poitrases made a $20 million commitment to establish the Poitras Center for Psychiatric Disorders Research at MIT. The center’s goal, to improve human health by addressing the root causes of complex psychiatric disorders, is deeply personal to them both.

“We had decided many years ago that our philanthropic efforts would be directed towards psychiatric research. We could not have imagined then that this perfect synergy between research at MIT’s McGovern Institute and our own philanthropic goals would develop,” recalls Patricia.

The center supports research at the McGovern Institute and collaborative projects with institutions such as the Broad Institute, McLean Hospital, Mass General Brigham and other clinical research centers. Since its establishment in 2007, the center has enabled advances in psychiatric research including the development of a machine learning “risk calculator” for bipolar disorder, the use of brain imaging to predict treatment outcomes for anxiety, and studies demonstrating that mindfulness can improve mental health in adolescents.

A scientist speaks at a podium with an image of DNA on the wall behind him.
Feng Zhang, the James and Patricia Poitras Professor of Neuroscience at MIT, delivers a lecture at the Poitras Center’s 10th anniversary celebration in 2017. Photo: Justin Knight

For the past decade, the Poitrases have also fueled breakthroughs in McGovern Investigator Feng Zhang’s lab, backing the invention of powerful CRISPR systems and other molecular tools that are transforming biology and medicine. Their support has enabled the Zhang team to engineer new delivery vehicles for gene therapy, including vehicles capable of carrying genetic payloads that were once out of reach. The lab has also advanced innovative RNA-guided gene engineering tools such as NovaIscB, published in Nature Biotechnology in May 2025. These revolutionary genome editing and delivery technologies hold promise for the next generation of therapies needed for serious psychiatric illness.

In addition to fueling research in the center, the Poitras family has gifted two endowed professorships—the James and Patricia Poitras Professor of Neuroscience at MIT, currently held by Feng Zhang, and the James W. (1963) and Patricia T. Poitras Professor of Brain and Cognitive Sciences at MIT, held by Guoping Feng—and an annual postdoctoral fellowship at the McGovern Institute.

New initiatives at the Poitras Center

The Poitras family’s latest commitment to the Poitras Center will launch an ambitious set of new projects that bring together neuroscientists, clinicians, and computational experts to probe underpinnings of complex psychiatric disorders including schizophrenia, anxiety, and depression. These efforts reflect the center’s core mission: to speed scientific discovery and therapeutic innovation in the field of psychiatric brain disorders research.

McGovern cognitive neuroscientists Evelina Fedorenko PhD ‘07 and Nancy Kanwisher ’80, PhD ’86, the Walter A. Rosenblith Professor of Cognitive Neuroscience—in collaboration with psychiatrist Ann Shinn of McLean Hospital—will explore how altered inner speech and reasoning contribute to the symptoms of schizophrenia. They will collect functional MRI data from individuals diagnosed with schizophrenia and matched controls as they perform reasoning tasks. The goal is to identify the brain activity patterns that underlie impaired reasoning in schizophrenia, a core cognitive disruption in the disorder.

Three women wearing name tags smile for hte camera.
Patricia Poitras (center) with McGovern Investigators Nancy Kanwisher ’80, PhD ’86 (left) and Martha Constantine-Paton (right) at the Poitras Center’s 10th anniversary celebration in 2017. Photo: Justin Knight

A complementary line of investigation will focus on the role of inner speech—the “voice in our head” that shapes thought and self-awareness. The team will conduct a large-scale online behavioral study of neurotypical individuals to analyze how inner speech characteristics correlate with schizophrenia-spectrum traits. This will be followed by neuroimaging work comparing brain architecture among individuals with strong or weak inner voices and people with schizophrenia, with the aim of discovering neural markers linked to self-talk and disrupted cognition.

A different project led by McGovern neuroscientist Mark Harnett and 2024–2026 Poitras Center Postdoctoral Fellow Cynthia Rais focuses on how ketamine—an increasingly used antidepressant—alters brain circuits to produce rapid and sustained improvements in mood. Despite its clinical success, ketamine’s mechanisms of action remain poorly understood. The Harnett lab is using sophisticated tools to track how ketamine affects synaptic communication and large-scale brain network dynamics, particularly in models of treatment-resistant depression. By mapping these changes at both the cellular and systems levels, the team hopes to reveal how ketamine lifts mood so quickly—and inform the development of safer, longer-lasting antidepressants.

Guoping Feng is leveraging a new animal model of depression to uncover the brain circuits that drive major depressive disorder. The new animal model provides a powerful system for studying the intricacies of mood regulation. Feng’s team is using state-of-the-art molecular tools to identify the specific genes and cell types involved in this circuit, with the goal of developing targeted treatments that can fine-tune these emotional pathways.

“This is one of the most promising models we have for understanding depression at a mechanistic level,” says Feng, who is also associate director of the McGovern Institute. “It gives us a clear target for future therapies.”

Another novel approach to treating mood disorders comes from the lab of James DiCarlo, the Peter de Florez Professor of Neuroscience at MIT, who is exploring the brain’s visual-emotional interface as a therapeutic tool for anxiety. The amygdala, a key emotional center in the brain, is heavily influenced by visual input. DiCarlo’s lab is using advanced computational models to design visual scenes that may subtly shift emotional processing in the brain—essentially using sight to regulate mood. Unlike traditional therapies, this strategy could offer a noninvasive, drug-free option for individuals suffering from anxiety.

Together, these projects exemplify the kind of interdisciplinary, high-impact research that the Poitras Center was established to support.

“Mental illness affects not just individuals, but entire families who often struggle in silence and uncertainty,” adds Patricia. “Our hope is that Poitras Center scientists will continue to make important advancements and spark novel treatments for complex mental health disorders and most of all, give families living with these conditions a renewed sense of hope for the future.”

Learning from punishment

by Jennifer Michalowski |

From toddlers’ timeouts to criminals’ prison sentences, punishment reinforces social norms, making it known that an offender has done something unacceptable. At least, that is usually the intent—but the strategy can backfire. When a punishment is perceived as too harsh, observers can be left with the impression that an authority figure is motivated by something other than justice.

It can be hard to predict what people will take away from a particular punishment, because everyone makes their own inferences not just about the acceptability of the act that led to the punishment, but also the legitimacy of the authority who imposed it. A new computational model developed by scientists at MIT’s McGovern Institute makes sense of these complicated cognitive processes, recreating the ways people learn from punishment and revealing how their reasoning is shaped by their prior beliefs.

Their work, reported August 4 in the journal PNAS, explains how a single punishment can send different messages to different people and even strengthen the opposing viewpoints of groups who hold different opinions about authorities or social norms.

Modeling punishment

“The key intuition in this model is the fact that you have to be evaluating simultaneously both the norm to be learned and the authority who’s punishing,” says McGovern Investigator and John W. Jarve Professor of Brain and Cognitive Sciences Rebecca Saxe, who led the research. “One really important consequence of that is even where nobody disagrees about the facts—everybody knows what action happened, who punished it, and what they did to punish it—different observers of the same situation could come to different conclusions.”

For example, she says, a child who is sent to timeout after biting a sibling might interpret the event differently than the parent. One might see the punishment as proportional and important, teaching the child not to bite. But if the biting, to the toddler, seemed a reasonable tactic in the midst of a squabble, the punishment might be seen as unfair, and the lesson will be lost.

People draw on their own knowledge and opinions when they evaluate these situations—but to study how the brain interprets punishment, Saxe and graduate student Setayesh Radkani wanted to take those personal ideas out of the equation. They needed a clear understanding of the beliefs that people held when they observed a punishment, so they could learn how different kinds of information altered their perceptions. So Radkani set up scenarios in imaginary villages where authorities punished individuals for actions that had no obvious analog in the real world.

Woman in red sweater smiling to camera
Graduate student Setayesh Radkani uses tools from psychology, cognitive neuroscience and machine learning to understand the social and moral mind. Photo: Caitlin Cunningham

Participants observed these scenarios in a series of experiments, with different information offered in each one. In some cases, for example, participants were told that the person being punished was either an ally or competitor of the authority, whereas in other cases, the authority’s possible bias was left ambiguous.

“That gives us a really controlled setup to vary prior beliefs,” Radkani explains. “We could ask what people learn from observing punitive decisions with different severities, in response to acts that vary in their level of wrongness, by authorities that vary in their level of different motives.”

For each scenario, participants were asked to evaluate four factors: how much the authority figure cared about justice; the selfishness of the authority; the authority’s bias for or against the individual being punished; and the wrongness of the punished act. The research team asked these questions when participants were first introduced to the hypothetical society, then tracked how their responses changed after they observed the punishment. Across the scenarios, participants’ initial beliefs about the authority and the wrongness of the act shaped the extent to which those beliefs shifted after they observed the punishment.

Radkani was able to replicate these nuanced interpretations using a cognitive model framed around an idea that Saxe’s team has long used to think about how people interpret the actions of others. That is, to make inferences about others’ intentions and beliefs, we assume that people choose actions that they expect will help them achieve their goals.

To apply that concept to the punishment scenarios, Radkani developed a model that evaluates the meaning of a punishment (an action aimed at achieving a goal of the authority) by considering the harm associated with that punishment; its costs or benefits to the authority; and its proportionality to the violation. By assessing these factors, along with prior beliefs about the authority and the punished act, the model was able to predict people’s responses to the hypothetical punishment scenarios, supporting the idea that people use a similar mental model. “You need to have them consider those things, or you can’t make sense of how people understand punishment when they observe it,” Saxe says.

Even though the team designed their experiments to preclude preconceived ideas about the people and actions in their imaginary villages, not everyone drew the same conclusions from the punishments they observed. Saxe’s group found that participants’ general attitudes toward authority influenced their interpretation of events. Those with more authoritarian attitudes—assessed through a standard survey—tended to judge punished acts as more wrong and authorities as more motivated by justice than other observers.

“If we differ from other people, there’s a knee-jerk tendency to say, ‘either they have different evidence from us, or they’re crazy,’” Saxe says. Instead, she says, “It’s part of the way humans think about each other’s actions.”

“When a group of people who start out with different prior beliefs get shared evidence, they will not end up necessarily with shared beliefs. That’s true even if everybody is behaving rationally,” says Saxe.

This way of thinking also means that the same action can simultaneously strengthen opposing viewpoints. The Saxe lab’s modeling and experiments showed that when those viewpoints shape individuals’ interpretations of future punishments, the groups’ opinions will continue to diverge. For instance, a punishment that seems too harsh to a group who suspects an authority is biased can make that group even more skeptical of the authority’s future actions. Meanwhile, people who see the same punishment as fair and the authority as just will be more likely to conclude that the authority figure’s future actions are also just. “You will get a vicious cycle of polarization, staying and actually spreading to new things,” says Radkani.

The researchers say their findings point toward strategies for communicating social norms through punishment. “It is exactly sensible in our model to do everything you can to make your action look like it’s coming out of a place of care for the long-term outcome of this individual, and that it’s proportional to the norm violation they did,” Saxe says. “That is your best shot at getting a punishment interpreted pedagogically, rather than as evidence that you’re a bully.”

Nevertheless, she says that won’t always be enough. “If the beliefs are strong the other way, it’s very hard to punish and still sustain a belief that you were motivated by justice.”

This study was funded, in part, by the Patrick J McGovern Foundation.

How the brain distinguishes oozing fluids from solid objects

Anne Trafton |

Imagine a ball bouncing down a flight of stairs. Now think about a cascade of water flowing down those same stairs. The ball and the water behave very differently, and it turns out that your brain has different regions for processing visual information about each type of physical matter.

In a new study, MIT neuroscientists have identified parts of the brain’s visual cortex that respond preferentially when you look at “things” — that is, rigid or deformable objects like a bouncing ball. Other brain regions are more activated when looking at “stuff” — liquids or granular substances such as sand.

This distinction, which has never been seen in the brain before, may help the brain plan how to interact with different kinds of physical materials, the researchers say.

“When you’re looking at some fluid or gooey stuff, you engage with it in different way than you do with a rigid object. With a rigid object, you might pick it up or grasp it, whereas with fluid or gooey stuff, you probably are going to have to use a tool to deal with it,” says Nancy Kanwisher, the Walter A. Rosenblith Professor of Cognitive Neuroscience; a member of the McGovern Institute for Brain Research and MIT’s Center for Brains, Minds, and Machines; and the senior author of the study.

MIT postdoc Vivian Paulun, who is joining the faculty of the University of Wisconsin at Madison this fall, is the lead author of the paper, which appears today in the journal Current Biology. RT Pramod, an MIT postdoc, and Josh Tenenbaum, an MIT professor of brain and cognitive sciences, are also authors of the study.

Stuff vs. things

Decades of brain imaging studies, including early work by Kanwisher, have revealed regions in the brain’s ventral visual pathway that are involved in recognizing the shapes of 3D objects, including an area called the lateral occipital complex (LOC). A region in the brain’s dorsal visual pathway, known as the frontoparietal physics network (FPN), analyzes the physical properties of materials, such as mass or stability.

Although scientists have learned a great deal about how these pathways respond to different features of objects, the vast majority of these studies have been done with solid objects, or “things.”

“Nobody has asked how we perceive what we call ‘stuff’ — that is, liquids or sand, honey, water, all sorts of gooey things. And so we decided to study that,” Paulun says.

These gooey materials behave very differently from solids. They flow rather than bounce, and interacting with them usually requires containers and tools such as spoons. The researchers wondered if these physical features might require the brain to devote specialized regions to interpreting them.

To explore how the brain processes these materials, Paulun used a software program designed for visual effects artists to create more than 100 video clips showing different types of things or stuff interacting with the physical environment. In these videos, the materials could be seen sloshing or tumbling inside a transparent box, being dropped onto another object, or bouncing or flowing down a set of stairs.

The researchers used functional magnetic resonance imaging (fMRI) to scan the visual cortex of people as they watched the videos. They found that both the LOC and the FPN respond to “things” and “stuff,” but that each pathway has distinctive subregions that respond more strongly to one or the other.

“Both the ventral and the dorsal visual pathway seem to have this subdivision, with one part responding more strongly to ‘things,’ and the other responding more strongly to ‘stuff,’” Paulun says. “We haven’t seen this before because nobody has asked that before.”

Roland Fleming, a professor of experimental psychology at Justus Liebig University of Geissen, described the findings as a “major breakthrough in the scientific understanding of how our brains represent the physical properties of our surrounding world.”

“We’ve known the distinction exists for a long time psychologically, but this is the first time that it’s been really mapped onto separate cortical structures in the brain. Now we can investigate the different computations that the distinct brain regions use to process and represent objects and materials,” says Fleming, who was not involved in the study.

Physical interactions

The findings suggest that the brain may have different ways of representing these two categories of material, similar to the artificial physics engines that are used to create video game graphics. These engines usually represent a 3D object as a mesh, while fluids are represented as sets of particles that can be rearranged.

“The interesting hypothesis that we can draw from this is that maybe the brain, similar to artificial game engines, has separate computations for representing and simulating ‘stuff’ and ‘things.’ And that would be something to test in the future,” Paulun says.

Portrait of smiling woman wearing a grey sweater.
McGovern Institute postdoc Vivian Paulun, who is joining the faculty of the University of Wisconsin at Madison in the fall of 2025, is the lead author of the “things vs. stuff” paper, which appears today in the journal Current Biology. Photo: Steph Stevens

The researchers also hypothesize that these regions may have developed to help the brain understand important distinctions that allow it to plan how to interact with the physical world. To further explore this possibility, the researchers plan to study whether the areas involved in processing rigid objects are also active when a brain circuit involved in planning to grasp objects is active.

They also hope to look at whether any of the areas within the FPN correlate with the processing of more specific features of materials, such as the viscosity of liquids or the bounciness of objects. And in the LOC, they plan to study how the brain represents changes in the shape of fluids and deformable substances.

The research was funded by the German Research Foundation, the U.S. National Institutes of Health, and a U.S. National Science Foundation grant to the Center for Brains, Minds, and Machines.

 

Adolescents’ willingness to explore is shaped by socioeconomic status

by Jennifer Michalowski |

Exploration is essential to learning—and a new study from scientists at MIT’s McGovern Institute suggests that students may be less willing to explore if they come from a low socioeconomic environment. The study, which focused on adolescents and was published July 9, 2025, in the journal Nature Communications, shows how differences in learning strategies might contribute to socioeconomic-related disparities in academic achievement.

Students with low socioeconomic status (SES)—a measure that takes into account parents’ income levels and educational attainment—tend to lag behind their higher-SES peers academically. Limited resources at home can restrict access to educational tools and experiences, likely contributing to these disparities. But the new study, led by McGovern Institute Investigator John Gabrieli, shows that students from low-SES backgrounds may approach learning differently, too.

“We often think about external factors when we think about socioeconomic differences in learning, but kids’ mindsets and internal factors can also play a role,” says Alexandra Decker, a postdoctoral fellow in Gabrieli’s lab who ran the study. Understanding such differences can help educators develop strategies to reduce disparities and help all students succeed.

The value of exploration

Exploration is a vital part of development, particularly during adolescence. By trying new things and testing limits, children begin to find their way in the world, discovering the subjects and experiences that motivate them. That’s important for obtaining new knowledge, both in and out of school. “There’s a lot of research suggesting that exploration is a really important mechanism that children use for learning,” Decker says. “Exploring their environment really broadly and making mistakes helps them get the feedback that they need for learning,” she says.

Because the outcomes of exploration are unknown, this way of interacting with the world involves risk. “If you try something new, the outcome is uncertain, and it could lead to a bad outcome before things get better. You might lose out, at least in the short term. ” Decker says.

At school, students can explore in a variety of ways, such as by asking questions in class or taking on courses in unfamiliar subjects. Both are opportunities to learn something new, though they may seem less safe than sitting quietly and sticking to more comfortable coursework. Decker points out that this kind of exploration might feel particularly risky when students feel they lack the resources to compensate if things don’t go well.

“If you’re in an environment that’s really enriching, you have resources to compensate for challenges that might be accrued through exploring. If you take a new course and you struggle, you can use your resources to get a tutor and overcome these challenges. Your environment can support exploration and its costs,” she says. “But if you’re in an environment where you don’t have resources to compensate for bad outcomes, you might not take that course that could lead to unknown outcomes.”

Risk-benefit analysis

To investigate the relationship between SES and exploration, Gabrieli’s team had students play a computer game in which they earned points for pumping up balloons as much as possible without popping them. The most successful strategy was to explore the limits early on by pumping the first balloons until they popped, thereby learning when to stop with future balloons. A less exploratory approach could keep all the balloons intact, but earn fewer points over the course of the game.

The students who participated in the study were between the ages of 12 and 14 and came from families with a wide range of SES. Those from lower-SES backgrounds were less likely to explore in the balloon pumping task, resulting in lower outcomes in the game. What’s more, the researchers found a relationship between students’ exploration in the game and their real-world academic performance. Those who explored the least in the balloon-popping game had lower grades than students who explored more. For students at lower-SES levels, reduced exploration also correlated to lower scores on standardized tests of academic skills.

The researchers took a closer look at the data to investigate why some students explored more than others in their game. Their analysis indicated that students who were reluctant to explore were more strongly motivated by avoiding losses than students who had pushed the limits as they pumped their balloons.

The finding suggests that potential losses might be particularly distressing to lower-SES students, says Gabrieli, who is also the Grover Hermann Professor of Health Sciences and Technology and a professor of brain and cognitive sciences at MIT. Decker adds students from less affluent backgrounds may have found losses to be more consequential than they are for students whose families have more resources, so it makes sense that those students might take greater pains to avoid them.

This is not the first time Gabrieli’s group has found that evidence of differences in the ways students from different socioeconomic backgrounds make decisions. In a brain imaging study published last year, they found that the brains of adolescents from low-SES backgrounds respond less to rewards than the brains of their higher-SES peers. “How you think about the world—in terms of what’s rewarding, risks worth taking or not taking—seems strongly influenced by the environment that you’re growing up in,” he says.

Decker notes that regardless of SES, students in the study were generally more willing to explore when they had experienced more recent successes in the task. This finding, along with what the team learned about how loss aversion curtails exploration, suggest strategies that educators might use to encourage more exploration in the classroom. “Low-stakes opportunities for kids to engage in exploratory risk-taking with positive feedback could go a long way to helping kids feel more comfortable exploring,” Decker says.

 

MIT’s McGovern Institute and Department of Brain and Cognitive Sciences welcome new faculty member Sven Dorkenwald

by Julie Pryor |

The McGovern Institute and the Department of Brain and Cognitive Sciences are pleased to announce the appointment of Sven Dorkenwald as an assistant professor starting in January 2026. A trailblazer in the field of computational neuroscience, Dorkenwald is recognized for his leadership in connectomics—an emerging discipline focused on reconstructing and analyzing neural circuitry at unprecedented scale and detail. 

“We are thrilled to welcome Sven to MIT” says McGovern Institute Director Robert Desimone. “He brings visionary science and a collaborative spirit to a rapidly advancing area of brain and cognitive sciences and his appointment strengthens MIT’s position at the forefront of brain research.” 

Dorkenwald’s research is driven by a bold vision: to develop and apply cutting-edge computational methods that reveal how brain circuits are organized and how they give rise to complex computations. His innovative work has led to transformative advances in the reconstruction of connectomes (detailed neural maps) from nanometer-scale electron microscopy images. He has championed open team science and data sharing and played a central role in producing the first connectome of an entire fruit fly brain—a groundbreaking achievement that is reshaping our understanding of sensory processing and brain circuit function. 

“Sven is a rising leader in computational neuroscience who has already made significant contributions toward advancing our understanding of the brain,” says Michale Fee, the Glen V. and Phyllis F. Dorflinger Professor of Neuroscience, and Department Head of Brain and Cognitive Sciences. “He brings a combination of technical expertise, a collaborative mindset, and a strong commitment to open science that will be invaluable to our department. I’m pleased to welcome him to our community and look forward to the impact he will have.” 

Dorkenwald earned his BS in physics in 2014 and MS in computer engineering in 2017 from the University of Heidelberg, Germany. He began his research in connectomics as an undergraduate in the group of Winfried Denk at the Max Planck Institute for Medical Research and Max Planck Institute of Neurobiology.  Dorkenwald went on to complete his PhD at Princeton University in 2023, where he studied both computer science and neuroscience under the mentorship of Sebastian Seung and Mala Murthy. 

All 139,255 neurons in the brain of an adult fruit fly reconstructed by the FlyWire Consortium, with each neuron uniquely color-coded. Render by Tyler Sloan. Image: Sven Dorkenwald

As a PhD student at Princeton, Dorkenwald spearheaded the FlyWire Consortium, a group of more than 200 scientists, gamers, and proofreaders who combined their skills to create the fruit fly connectome. More than 20 million scientific images of the adult fruit fly brain  were added to an AI model that traced each neuron and synapse in exquisite detail. Members of the consortium then checked the results produced by the AI model and pieced them together into a complete, three-dimensional map. With over 140,000 neurons, it is the most complex brain completely mapped to date. The findings were published in a special issue of Nature in 2024. 

Dorkenwald’s work also played a key role in the MICrONS’ consortium effort to reconstruct a cubic millimeter connectome of the mouse visual cortex. Within the MICrONS effort, he co-lead the development of the software infrastructure, CAVE, that enables scientists to collaboratively edit and analyze large connectomics datasets, including FlyWire’s. The findings of the MICrONS consortium were published in a special issue of Nature in 2025. 

Dorkenwald is currently a Shanahan Fellow at the Allen Institute and the University of Washington. He also serves as a visiting faculty researcher at Google Research, where he has been developing machine learning approaches for the annotation of cell reconstructions as part of the Neuromancer team led by Viren Jain.  

As an investigator at the McGovern Institute and an assistant professor in the department of brain and cognitive sciences at MIT, Dorkenwald  plans to develop computational approaches to overcome challenges in scaling connectomics to whole mammalian brains with the goal of advancing our mechanistic understanding of neuronal circuits and analyzing how they compare across regions and species. 

 

Feng Zhang elected to EMBO membership

by Julie Pryor |

The European Molecular Biology Organization (EMBO), a professional non-profit organization dedicated to promoting international research in life sciences, announced its new members today. Among the 69 new members recognized for their outstanding achievements is Feng Zhang, the James and Patricia Poitras Professor of Neuroscience at MIT and an investigator at the McGovern Institute.

Zhang, who is also a core member of the Broad Institute, a professor of brain and cognitive sciences and biological engineering at MIT, and a Howard Hughes Medical Institute investigator, is a molecular biologist focused on improving human health. He played an integral role in pioneering the use of CRISPR-Cas9 for genome editing in human cells, including working with Stuart Orkin to develop Casgevy, the first CRISPR-based therapeutic approved for clinical use. His team is currently discovering new ways to modify cellular function and activity—including the restoration of diseased, stressed, or aged cells to a more healthful state.

Zhang has been elected to EMBO as an associate member, where he joins a community of more than 2,100 international life scientists that have demonstrated research excellence in their fields.

“A major strength of EMBO lies in the excellence and dedication of its members,” says EMBO Director Fiona Watt. “Science thrives on global collaboration, and the annual election of the new EMBO members and associate members brings fresh energy and inspiration to our community. We are honoured to welcome this remarkable group of scientists to the EMBO Membership. Their ideas and contributions will enrich the organization and help advance the life sciences internationally.”

The 60 new EMBO members in 2025 are based in 18 member states of the EMBC, the intergovernmental organization that funds the main EMBO programs and activities. The nine new EMBO associate members, including Zhang, are based in six countries outside Europe. In total, 29 (42%) of the new members are women and 40 (58%) are men.

The new members will be formally welcomed at the next EMBO Members’ Meeting in Heidelberg, Germany, on 22-24 October 2025.

Rational engineering generates a compact new tool for gene therapy

by Jennifer Michalowski |

Scientists at the McGovern Institute and the Broad Institute of MIT and Harvard have reengineered a compact RNA-guided enzyme they found in bacteria into an efficient, programmable editor of human DNA. The protein they created, called NovaIscB, can be adapted to make precise changes to the genetic code, modulate the activity of specific genes, or carry out other editing tasks. Because its small size simplifies delivery to cells, NovaIscB’s developers say it is a promising candidate for developing gene therapies to treat or prevent disease.

The study was led by McGovern Institute investigator Feng Zhang, who is also the James and Patricia Poitras Professor of Neuroscience at MIT, a Howard Hughes Medical Institute investigator, and a core member of the Broad Institute. Zhang and his team reported their work today in the journal Nature Biotechnology.

Compact tools

NovaIscB is derived from a bacterial DNA cutter that belongs to a family of proteins called IscBs, which Zhang’s lab discovered in 2021. IscBs are a type of OMEGA system, the evolutionary ancestors to Cas9, which is part of the bacterial CRISPR system that Zhang and others have developed into powerful genome-editing tools. Like Cas9, IscB enzymes cut DNA at sites specified by an RNA guide. By reprogramming that guide, researchers can redirect the enzymes to target sequences of their choosing.

IscBs had caught the team’s attention not only because they share key features of CRISPR’s DNA-cutting Cas9, but also because they are a third of its size. That would be an advantage for potential gene therapies: Compact tools are easier to deliver to cells, and with a small enzyme, researchers would have more flexibility to tinker, potentially adding new functionalities without creating tools that were too bulky for clinical use.

From their initial studies of IscBs, researchers in Zhang’s lab knew that some members of the family could cut DNA targets in human cells. None of the bacterial proteins worked well enough to be deployed therapeutically, however: The team would have to modify an IscB to ensure it could edit targets in human cells efficiently without disturbing the rest of the genome.

To begin that engineering process, Soumya Kannan, a graduate student in Zhang’s lab who is now a junior fellow at the Harvard Society of Fellows, and postdoctoral fellow Shiyou Zhu first searched for an IscB that would make good starting point. They tested nearly 400 different IscB enzymes that can be found in bacteria. Ten were capable of editing DNA in human cells.

Even the most active of those would need to be enhanced to make it a useful genome editing tool. The challenge would be increasing the enzyme’s activity, but only at the sequences specified by its RNA guide. If the enzyme became more active, but indiscriminately so, it would cut DNA in unintended places. “The key is to balance the improvement of both activity and specificity at the same time,” explains Zhu.

Zhu notes that bacterial IscBs are directed to their target sequences by relatively short RNA guides, which makes it difficult to restrict the enzyme’s activity to a specific part of the genome. If an IscB could be engineered to accommodate a longer guide, it would be less likely to act on sequences beyond its intended target.

To optimize IscB for human genome editing, the team leveraged information that graduate student Han Altae-Tran, who is now a postdoctoral fellow at the University of Washington, had learned about the diversity of bacterial IscBs and how they evolved. For instance, the researchers noted that IscBs that worked in human cells included a segment they called REC, which was absent in other IscBs. They suspected the enzyme might need that segment to interact with the DNA in human cells. When they took a closer look at the region, structural modeling suggested that by slightly expanding part of the protein, REC might also enable IscBs to recognize longer RNA guides.

Based on these observations, the team experimented with swapping in parts of REC domains from different IscBs and Cas9s, evaluating how each change impacted the protein’s function. Guided by their understanding of how IscBs and Cas9s interact with both DNA and their RNA guides, the researchers made additional changes, aiming to optimize both efficiency and specificity.

In the end, they generated a protein they called NovaIscB, which was over 100 times more active in human cells than the IscB they had started with and that had demonstrated good specificity for its targets.

Kannan and Zhu constructed and screened hundreds of new IscBs before arriving at NovaIscB—and every change they made to the original protein was strategic. Their efforts were guided by their team’s knowledge of IscBs’ natural evolution as well as predictions of how each alteration would impact the protein’s structure, made using an artificial intelligence tool called AlphaFold2. Compared to traditional methods of introducing random changes into a protein and screening for their effects, this rational engineering approach greatly accelerated the team’s ability to identify a protein with the features they were looking for.

The team demonstrated that NovaIscB is a good scaffold for a variety of genome editing tools. “It biochemically functions very similarly to Cas9, and that makes it easy to port over tools that were already optimized with the Cas9 scaffold,” Kannan says. With different modifications, the researchers used NovaIscB to replace specific letters of the DNA code in human cells and to change the activity of targeted genes.

Importantly, the NovaIscB-based tools are compact enough to be easily packaged inside a single adeno-associated virus (AAV)—the vector most commonly used to safely deliver gene therapy to patients. Because they are bulkier, tools developed using Cas9 can require a more complicated delivery strategy.

Demonstrating NovaIscB’s potential for therapeutic use, Zhang’s team created a tool called OMEGAoff that adds chemical markers to DNA to dial down the activity of specific genes. They programmed OMEGAoff to repress a gene involved in cholesterol regulation, then used AAV to deliver the system to the livers of mice, leading to lasting reductions in cholesterol levels in the animals’ blood.

The team expects that NovaIscB can be used to target genome editing tools to most human genes, and look forward to seeing how other labs deploy the new technology. They also hope others will adopt their evolution-guided approach to rational protein engineering. “Nature has such diversity and its systems have different advantages and disadvantages,” Zhu says. “By learning about that natural diversity, we can make the systems we are trying to engineer better and better.”

This study was funded in part by the K. Lisa Yang and Hock E. Tan Center for Molecular Therapeutics at MIT, Broad Institute Programmable Therapeutics Gift Donors, Pershing Square Foundation, William Ackman, Neri Oxman, the Phillips family, and J. and P. Poitras.

Daily mindfulness practice reduces anxiety for autistic adults

by Jennifer Michalowski |

Just ten to 15 minutes of mindfulness practice a day led to reduced stress and anxiety for autistic adults who participated in a study led by scientists at MIT’s McGovern Institute. Participants in the study used a free smartphone app to guide their practice, giving them the flexibility to practice when and where they chose.

Mindfulness is a state in which the mind is focused only on the present moment. It is a way of thinking that can be cultivated with practice, often through meditation or breathing exercises—and evidence is accumulating that practicing mindfulness has positive effects on mental health. The new study, reported April 8, 2025, in the journal Mindfulness, adds to that evidence, demonstrating clear benefits for autistic adults.

“Everything you want from this on behalf of somebody you care about happened: reduced reports of anxiety, reduced reports of stress, reduced reports of negative emotions, and increased reports of positive emotions,” says McGovern Investigator John Gabrieli, who led the research with Liron Rozenkrantz, an investigator at the Azrieli Faculty of Medicine at Bar-Ilan University in Israel and a research affiliate in Gabrieli’s lab. “Every measure that we had of well-being moved in significantly in a positive direction,” adds Gabrieli, who is also the Grover Hermann Professor of Health Sciences and Technology and a professor of brain and cognitive sciences at MIT.

One of the reported benefits of practicing mindfulness is that it can reduce the symptoms of anxiety disorders. This prompted Gabrieli and his colleagues to wonder whether it might benefit adults with autism, who tend to report above average levels of anxiety and stress, which can interfere with daily living and quality of life. As many as 65 percent of autistic adults may also have an anxiety disorder.

Gabrieli adds that the opportunity for autistic adults to practice mindfulness with an app, rather than needing to meet with a teacher or class, seemed particularly promising. “The capacity to do it at your own pace in your own home, or any environment you like, might be good for anybody,” he says. “But maybe especially for people for whom social interactions can sometimes be challenging.”

The research team, including first author Cindy Li, the Autism Recruitment and Outreach Coordinator in Gabrieli’s lab, recruited 89 autistic adults to participate in their study. Those individuals were split into two groups: One would try the mindfulness practice for six weeks, while the others would wait and try the intervention later.

Participants were asked to practice daily using an app called Healthy Minds, which guides participants through seated or active mediations, each lasting 10 to 15 minutes. Participants reported that they found the app easy to use and had little trouble making time for the daily practice.

After six weeks, participants reported significant reductions in anxiety and perceived stress. These changes were not experienced by the wait-list group, which served as a control. However, after their own six weeks of practice, people in the wait-list group reported similar benefits. “We replicated the result almost perfectly. Every positive finding we found with the first sample we found with the second sample,” Gabrieli says.

The researchers followed up with study participants after another six weeks. Almost everyone had discontinued their mindfulness practice—but remarkably, their gains in well-being had persisted. Based on this finding, the team is eager to further explore the long-term effects of mindfulness practice in future studies. “There’s a hypothesis that a benefit of gaining mindfulness skills or habits is they stick with you over time—that they become incorporated in your daily life,” Gabrieli says. “If people are using the approach to being in the present and not dwelling on the past or worrying about the future, that’s what you want most of all. It’s a habit of thought that’s powerful and helpful.”

Even as they plan future studies, the researchers say they are already convinced that mindfulness practice can have clear benefits for autistic adults. “It’s possible mindfulness would be helpful at all kinds of ages,” Gabrieli says. But he points out the need is particularly great for autistic adults, who usually have fewer resources and support than autistic children have access to through their schools. Gabrieli is eager for more people with autism to try the Healthy Minds app. “Having scientifically proven resources for adults who are no longer in school systems might be a valuable thing,” he says.

This research was funded in part by The Hock E. Tan and K. Lisa Yang Center for Autism Research at MIT and the Yang Tan Collective.

Twenty-five years after its founding, the McGovern Institute is shaping brain science and improving human lives at a global scale

by Julie Pryor |

In 2000, Patrick J. McGovern ’59 and Lore Harp McGovern made an extraordinary gift to establish the McGovern Institute for Brain Research at MIT, driven by their deep curiosity about the human mind and their belief in the power of science to change lives. Their $350 million pledge began with a simple yet audacious vision: to understand the human brain in all its complexity and to leverage that understanding for the betterment of humanity.

Twenty-five years later, the McGovern Institute stands as a testament to the power of interdisciplinary collaboration, continuing to shape our understanding of the brain and improve the quality of life for people worldwide.

In the Beginning

“This is by any measure a truly historic moment for MIT,” said MIT’s 15th President Charles M. Vest during his opening remarks at an event in 2000 to celebrate the McGovern gift agreement. “The creation of the McGovern Institute will launch one of the most profound and important scientific ventures of this century in what surely will be a cornerstone of MIT scientific contributions from the decades ahead.”

Vest tapped Phillip A. Sharp, MIT Institute Professor Emeritus of Biology and Nobel laureate, to lead the institute and appointed six MIT professors — Emilio Bizzi, Martha Constantine-Paton, Ann Graybiel PhD ’71, H. Robert Horvitz ’68, Nancy Kanwisher ’80, PhD ’86, and Tomaso Poggio — to represent its founding faculty.  Construction began in 2003 on Building 46, a 376,000 square foot research complex at the northeastern edge of campus. MIT’s new “gateway from the north” would eventually house the McGovern Institute, the Picower Institute for Learning and Memory, and MIT’s Department of Brain and Cognitive Sciences.

Group photo in front of construction sign.
Patrick J. McGovern ’59 and Lore Harp McGovern gather with faculty members and MIT administration at the groundbreaking of MIT Building 46 in 2003. Photo: Donna Coveney

Robert Desimone, the Doris and Don Berkey Professor of Neuroscience at MIT,  succeeded Sharp as director of the McGovern Institute in 2005, and assembled a distinguished roster of 22 faculty members, including a Nobel laureate, a Breakthrough Prize winner, two National Medal of Science/Technology awardees, and 15 members of the American Academy of Arts and Sciences.

A Quarter Century of Innovation

On April 11, 2025, the McGovern Institute celebrated its 25th anniversary with a half day symposium featuring presentations by MIT Institute Professor Robert Langer, alumni speakers from various McGovern labs, and Desimone, who is in his twentieth year as director of the institute.

Desimone highlighted the institute’s recent discoveries, including the development of the CRISPR genome-editing system, which has culminated in the world’s first CRISPR gene therapy approved for humans — a remarkable achievement that is ushering in a new era of transformative medicine. In other milestones, McGovern researchers developed the first prosthetic limb fully controlled by the body’s nervous system; a flexible probe that taps into gut-brain communication; an expansion microscopy technique that paves the way for biology labs around the world to perform nanoscale imaging; and advanced computational models that demonstrate how we see, hear, use language, and even think about what others are thinking. Equally transformative has been the McGovern Institute’s work in neuroimaging, uncovering the architecture of human thought and establishing markers that signal the early emergence of mental illness, before symptoms even appear.

Synergy and Open Science

“I am often asked what makes us different from other neuroscience institutes and programs around the world,” says Desimone. “My answer is simple. At the McGovern Institute, the whole is greater than the sum of its parts.”

Many discoveries at the McGovern Institute have depended on collaborations across multiple labs, ranging from biological engineering to human brain imaging and artificial intelligence. In modern brain research, significant advances often require the joint expertise of people working in neurophysiology, behavior, computational analysis, neuroanatomy, and molecular biology. More than a dozen different MIT departments are represented by McGovern faculty and graduate students, and this synergy has led to insights and innovations that are far greater than what any single discipline could achieve alone.

Also baked into the McGovern ethos is a spirit of open science, where newly developed technologies are shared with colleagues around the world. Through hospital partnerships for example, McGovern researchers are testing their tools and therapeutic interventions in clinical settings, accelerating their discoveries into real-world solutions.

The McGovern Legacy  

Hundreds of scientific papers have emerged from McGovern labs over the past 25 years, but most faculty would argue that it’s the people, the young researchers, that truly define the McGovern Institute. Award-winning faculty often attract the brightest young minds, but many McGovern faculty also serve as mentors, creating a diverse and vibrant scientific community that is setting the global standard for brain research and its applications. Nancy Kanwisher ’80 PhD ’86, for example, has guided more than 70 doctoral students and postdocs who have gone on to become leading scientists around the world. Three of her former students, Evelina Fedorenko PhD ‘07, Josh McDermott PhD ‘06, and the John W. Jarve (1978) Professor of Brain and Cognitive Sciences, Rebecca Saxe PhD ‘03, are now her colleagues at the McGovern Institute. Other McGovern alumni shared stories of mentorship, science, and real-world impact at the 25th anniversary symposium.

Group photo of four smiling scientists.
Nancy Kanwisher (center) with former students-turned-colleagues Evelina Fedorenko (left), Josh McDermott, and Rebecca Saxe (right). Photo: Steph Stevens

Looking to the future, the McGovern community is more committed than ever to unraveling the mysteries of the brain and making a meaningful difference in lives of individuals at a global scale.

“By promoting team science, open communication, and cross-discipline partnerships,” says institute co-founder Lore Harp McGovern, “our culture demonstrates how individual expertise can be amplified through collective effort. I am honored to be the co-founder of this incredible institution – onward to the next 25 years!”

To the brain, Esperanto and Klingon appear the same as English or Mandarin

by Anne Trafton |

Within the human brain, a network of regions has evolved to process language. These regions are consistently activated whenever people listen to their native language or any language in which they are proficient.

A new study by MIT researchers finds that this network also responds to languages that are completely invented, such as Esperanto, which was created in the late 1800s as a way to promote international communication, and even to languages made up for television shows such as “Star Trek” and “Game of Thrones.”

To study how the brain responds to these artificial languages, MIT neuroscientists convened nearly 50 speakers of these languages over a single weekend. Using functional magnetic resonance imaging (fMRI), the researchers found that when participants listened to a constructed language in which they were proficient, the same brain regions lit up as those activated when they processed their native language.

“We find that constructed languages very much recruit the same system as natural languages, which suggests that the key feature that is necessary to engage the system may have to do with the kinds of meanings that both kinds of languages can express,” says Evelina Fedorenko, an associate professor of neuroscience at MIT, a member of MIT’s McGovern Institute for Brain Research and the senior author of the study.

The findings help to define some of the key properties of language, the researchers say, and suggest that it’s not necessary for languages to have naturally evolved over a long period of time or to have a large number of speakers.

“It helps us narrow down this question of what a language is, and do it empirically, by testing how our brain responds to stimuli that might or might not be language-like,” says Saima Malik-Moraleda, an MIT postdoc and the lead author of the paper, which appears this week in the Proceedings of the National Academy of Sciences.

Convening the conlang community

Unlike natural languages, which evolve within communities and are shaped over time, constructed languages, or “conlangs,” are typically created by one person who decides what sounds will be used, how to label different concepts, and what the grammatical rules are.

Esperanto, the most widely spoken conlang, was created in 1887 by L.L. Zamenhof, who intended it to be used as a universal language for international communication. Currently, it is estimated that around 60,000 people worldwide are proficient in Esperanto.

In previous work, Fedorenko and her students have found that computer programming languages, such as Python — another type of invented language — do not activate the brain network that is used to process natural language. Instead, people who read computer code rely on the so-called multiple demand network, a brain system that is often recruited for difficult cognitive tasks.

Fedorenko and others have also investigated how the brain responds to other stimuli that share features with language, including music and nonverbal communication such as gestures and facial expressions.

“We spent a lot of time looking at all these various kinds of stimuli, finding again and again that none of them engage the language-processing mechanisms,” Fedorenko says. “So then the question becomes, what is it that natural languages have that none of those other systems do?”

That led the researchers to wonder if artificial languages like Esperanto would be processed more like programming languages or more like natural languages. Similar to programming languages, constructed languages are created by an individual for a specific purpose, without natural evolution within a community. However, unlike programming languages, both conlangs and natural languages can be used to convey meanings about the state of the external world or the speaker’s internal state.

To explore how the brain processes conlangs, the researchers invited speakers of Esperanto and several other constructed languages to MIT for a weekend conference in November 2022. The other languages included Klingon (from “Star Trek”), Na’vi (from “Avatar”), and two languages from “Game of Thrones” (High Valyrian and Dothraki). For all of these languages, there are texts available for people who want to learn the language, and for Esperanto, Klingon, and High Valyrian, there is even a Duolingo app available.

“It was a really fun event where all the communities came to participate, and over a weekend, we collected all the data,” says Malik-Moraleda, who co-led the data collection effort with former MIT postbac Maya Taliaferro, now a PhD student at New York University.

During that event, which also featured talks from several of the conlang creators, the researchers used fMRI to scan 44 conlang speakers as they listened to sentences from the constructed language in which they were proficient. The creators of these languages — who are co-authors on the paper — helped construct the sentences that were presented to the participants.

While in the scanner, the participants also either listened to or read sentences in their native language, and performed some nonlinguistic tasks for comparison. The researchers found that when people listened to a conlang, the same language regions in the brain were activated as when they listened to their native language.

Common features

The findings help to identify some of the key features that are necessary to recruit the brain’s language processing areas, the researchers say. One of the main characteristics driving language responses seems to be the ability to convey meanings about the interior and exterior world — a trait that is shared by natural and constructed languages, but not programming languages.

“All of the languages, both natural and constructed, express meanings related to inner and outer worlds. They refer to objects in the world, to properties of objects, to events,” Fedorenko says. “Whereas programming languages are much more similar to math. A programming language is a symbolic generative system that allows you to express complex meanings, but it’s a self-contained system: The meanings are highly abstract and mostly relational, and not connected to the real world that we experience.”

Some other characteristics of natural languages, which are not shared by constructed languages, don’t seem to be necessary to generate a response in the language network.

“It doesn’t matter whether the language is created and shaped over time by a community of speakers, because these constructed languages are not,” Malik-Moraleda says. “It doesn’t matter how old they are, because conlangs that are just a decade old engage the same brain regions as natural languages that have been around for many hundreds of years.”

To further refine the features of language that activate the brain’s language network, Fedorenko’s lab is now planning to study how the brain responds to a conlang called Lojban, which was created by the Logical Language Group in the 1990s and was designed to prevent ambiguity of meanings and promote more efficient communication.

The research was funded by MIT’s McGovern Institute for Brain Research, Brain and Cognitive Sciences Department, the Simons Center for the Social Brain, the Frederick A. and Carole J. Middleton Career Development Professorship, and the U.S. National Institutes of Health.