Using MRI, engineers have found a way to detect light deep in the brain

Scientists often label cells with proteins that glow, allowing them to track the growth of a tumor, or measure changes in gene expression that occur as cells differentiate.

A man stands with his arms crossed in front of a board with mathematical equations written on it.
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

While this technique works well in cells and some tissues of the body, it has been difficult to apply this technique to image structures deep within the brain, because the light scatters too much before it can be detected.

MIT engineers have now come up with a novel way to detect this type of light, known as bioluminescence, in the brain: They engineered blood vessels of the brain to express a protein that causes them to dilate in the presence of light. That dilation can then be observed with magnetic resonance imaging (MRI), allowing researchers to pinpoint the source of light.

“A well-known problem that we face in neuroscience, as well as other fields, is that it’s very difficult to use optical tools in deep tissue. One of the core objectives of our study was to come up with a way to image bioluminescent molecules in deep tissue with reasonably high resolution,” says Alan Jasanoff, an MIT professor of biological engineering, brain and cognitive sciences, and nuclear science and engineering.

The new technique developed by Jasanoff and his colleagues could enable researchers to explore the inner workings of the brain in more detail than has previously been possible.

Jasanoff, who is also an associate investigator at MIT’s McGovern Institute for Brain Research, is the senior author of the study, which appears today in Nature Biomedical Engineering. Former MIT postdocs Robert Ohlendorf and Nan Li are the lead authors of the paper.

Detecting light

Bioluminescent proteins are found in many organisms, including jellyfish and fireflies. Scientists use these proteins to label specific proteins or cells, whose glow can be detected by a luminometer. One of the proteins often used for this purpose is luciferase, which comes in a variety of forms that glow in different colors.

Jasanoff’s lab, which specializes in developing new ways to image the brain using MRI, wanted to find a way to detect luciferase deep within the brain. To achieve that, they came up with a method for transforming the blood vessels of the brain into light detectors. A popular form of MRI works by imaging changes in blood flow in the brain, so the researchers engineered the blood vessels themselves to respond to light by dilating.

“Blood vessels are a dominant source of imaging contrast in functional MRI and other non-invasive imaging techniques, so we thought we could convert the intrinsic ability of these techniques to image blood vessels into a means for imaging light, by photosensitizing the blood vessels themselves,” Jasanoff says.

“We essentially turn the vasculature of the brain into a three-dimensional camera.” – Alan Jasanoff

To make the blood vessels sensitive to light, the researcher engineered them to express a bacterial protein called Beggiatoa photoactivated adenylate cyclase (bPAC). When exposed to light, this enzyme produces a molecule called cAMP, which causes blood vessels to dilate. When blood vessels dilate, it alters the balance of oxygenated and deoxygenated hemoglobin, which have different magnetic properties. This shift in magnetic properties can be detected by MRI.

BPAC responds specifically to blue light, which has a short wavelength, so it detects light generated within close range. The researchers used a viral vector to deliver the gene for bPAC specifically to the smooth muscle cells that make up blood vessels. When this vector was injected in rats, blood vessels throughout a large area of the brain became light-sensitive.

“Blood vessels form a network in the brain that is extremely dense. Every cell in the brain is within a couple dozen microns of a blood vessel,” Jasanoff says. “The way I like to describe our approach is that we essentially turn the vasculature of the brain into a three-dimensional camera.”

Once the blood vessels were sensitized to light, the researchers implanted cells that had been engineered to express luciferase if a substrate called CZT is present. In the rats, the researchers were able to detect luciferase by imaging the brain with MRI, which revealed dilated blood vessels.

Tracking changes in the brain

The researchers then tested whether their technique could detect light produced by the brain’s own cells, if they were engineered to express luciferase. They delivered the gene for a type of luciferase called GLuc to cells in a deep brain region known as the striatum. When the CZT substrate was injected into the animals, MRI imaging revealed the sites where light had been emitted.

This technique, which the researchers dubbed bioluminescence imaging using hemodynamics, or BLUsH, could be used in a variety of ways to help scientists learn more about the brain, Jasanoff says.

For one, it could be used to map changes in gene expression, by linking the expression of luciferase to a specific gene. This could help researchers observe how gene expression changes during embryonic development and cell differentiation, or when new memories form. Luciferase could also be used to map anatomical connections between cells or to reveal how cells communicate with each other.

The researchers now plan to explore some of those applications, as well as adapting the technique for use in mice and other animal models.

The research was funded by the U.S. National Institutes of Health, the G. Harold and Leila Y. Mathers Foundation, Lore Harp McGovern, Gardner Hendrie, a fellowship from the German Research Foundation, a Marie Sklodowska-Curie Fellowship from the European Union, and a Y. Eva Tan Fellowship and a J. Douglas Tan Fellowship, both from the McGovern Institute for Brain Research.

Reevaluating an approach to functional brain imaging

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.

A man stands with his arms crossed in front of a board with mathematical equations written on it.
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.”

For people who speak many languages, there’s something special about their native tongue

A new study of people who speak many languages has found that there is something special about how the brain processes their native language.

In the brains of these polyglots — people who speak five or more languages — the same language regions light up when they listen to any of the languages that they speak. In general, this network responds more strongly to languages in which the speaker is more proficient, with one notable exception: the speaker’s native language. When listening to one’s native language, language network activity drops off significantly.

The findings suggest there is something unique about the first language one acquires, which allows the brain to process it with minimal effort, the researchers say.

“Something makes it a little bit easier to process — maybe it’s that you’ve spent more time using that language — and you get a dip in activity for the native language compared to other languages that you speak proficiently,” 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.

Saima Malik-Moraleda, a graduate student in the Speech and Hearing Bioscience and Technology Program at Harvard University, and Olessia Jouravlev, a former MIT postdoc who is now an associate professor at Carleton University, are the lead authors of the paper, which appears today in the journal Cerebral Cortex.

Many languages, one network

McGovern Investivator Ev Fedorenko in the Martinos Imaging Center at MIT. Photo: Caitlin Cunningham

The brain’s language processing network, located primarily in the left hemisphere, includes regions in the frontal and temporal lobes. In a 2021 study, Fedorenko’s lab found that in the brains of polyglots, the language network was less active when listening to their native language than the language networks of people who speak only one language.

In the new study, the researchers wanted to expand on that finding and explore what happens in the brains of polyglots as they listen to languages in which they have varying levels of proficiency. Studying polyglots can help researchers learn more about the functions of the language network, and how languages learned later in life might be represented differently than a native language or languages.

“With polyglots, you can do all of the comparisons within one person. You have languages that vary along a continuum, and you can try to see how the brain modulates responses as a function of proficiency,” Fedorenko says.

For the study, the researchers recruited 34 polyglots, each of whom had at least some degree of proficiency in five or more languages but were not bilingual or multilingual from infancy. Sixteen of the participants spoke 10 or more languages, including one who spoke 54 languages with at least some proficiency.

Each participant was scanned with functional magnetic resonance imaging (fMRI) as they listened to passages read in eight different languages. These included their native language, a language they were highly proficient in, a language they were moderately proficient in, and a language in which they described themselves as having low proficiency.

They were also scanned while listening to four languages they didn’t speak at all. Two of these were languages from the same family (such as Romance languages) as a language they could speak, and two were languages completely unrelated to any languages they spoke.

The passages used for the study came from two different sources, which the researchers had previously developed for other language studies. One was a set of Bible stories recorded in many different languages, and the other consisted of passages from “Alice in Wonderland” translated into many languages.

Brain scans revealed that the language network lit up the most when participants listened to languages in which they were the most proficient. However, that did not hold true for the participants’ native languages, which activated the language network much less than non-native languages in which they had similar proficiency. This suggests that people are so proficient in their native language that the language network doesn’t need to work very hard to interpret it.

“As you increase proficiency, you can engage linguistic computations to a greater extent, so you get these progressively stronger responses. But then if you compare a really high-proficiency language and a native language, it may be that the native language is just a little bit easier, possibly because you’ve had more experience with it,” Fedorenko says.

Brain engagement

The researchers saw a similar phenomenon when polyglots listened to languages that they don’t speak: Their language network was more engaged when listening to languages related to a language that they could understand, than compared to listening to completely unfamiliar languages.

“Here we’re getting a hint that the response in the language network scales up with how much you understand from the input,” Malik-Moraleda says. “We didn’t quantify the level of understanding here, but in the future we’re planning to evaluate how much people are truly understanding the passages that they’re listening to, and then see how that relates to the activation.”

The researchers also found that a brain network known as the multiple demand network, which turns on whenever the brain is performing a cognitively demanding task, also becomes activated when listening to languages other than one’s native language.

“What we’re seeing here is that the language regions are engaged when we process all these languages, and then there’s this other network that comes in for non-native languages to help you out because it’s a harder task,” Malik-Moraleda says.

In this study, most of the polyglots began studying their non-native languages as teenagers or adults, but in future work, the researchers hope to study people who learned multiple languages from a very young age. They also plan to study people who learned one language from infancy but moved to the United States at a very young age and began speaking English as their dominant language, while becoming less proficient in their native language, to help disentangle the effects of proficiency versus age of acquisition on brain responses.

The research was funded by the McGovern Institute for Brain Research, MIT’s Department of Brain and Cognitive Sciences, and the Simons Center for the Social Brain.

Imaging method reveals new cells and structures in human brain tissue

Using a novel microscopy technique, MIT and Brigham and Women’s Hospital/Harvard Medical School researchers have imaged human brain tissue in greater detail than ever before, revealing cells and structures that were not previously visible.

McGovern Institute Investigator Edward Boyden. Photo: Justin Knight

Among their findings, the researchers discovered that some “low-grade” brain tumors contain more putative aggressive tumor cells than expected, suggesting that some of these tumors may be more aggressive than previously thought.

The researchers hope that this technique could eventually be deployed to diagnose tumors, generate more accurate prognoses, and help doctors choose treatments.

“We’re starting to see how important the interactions of neurons and synapses with the surrounding brain are to the growth and progression of tumors. A lot of those things we really couldn’t see with conventional tools, but now we have a tool to look at those tissues at the nanoscale and try to understand these interactions,” says Pablo Valdes, a former MIT postdoc who is now an assistant professor of neuroscience at the University of Texas Medical Branch and the lead author of the study.

Edward Boyden, the Y. Eva Tan Professor in Neurotechnology at MIT; a professor of biological engineering, media arts and sciences, and brain and cognitive sciences; a Howard Hughes Medical Institute investigator; and a member of MIT’s McGovern Institute for Brain Research and Koch Institute for Integrative Cancer Research; and E. Antonio Chiocca, a professor of neurosurgery at Harvard Medical School and chair of neurosurgery at Brigham and Women’s Hospital, are the senior authors of the study, which appears today in Science Translational Medicine.

Making molecules visible

The new imaging method is based on expansion microscopy, a technique developed in Boyden’s lab in 2015 based on a simple premise: Instead of using powerful, expensive microscopes to obtain high-resolution images, the researchers devised a way to expand the tissue itself, allowing it to be imaged at very high resolution with a regular light microscope.

The technique works by embedding the tissue into a polymer that swells when water is added, and then softening up and breaking apart the proteins that normally hold tissue together. Then, adding water swells the polymer, pulling all the proteins apart from each other. This tissue enlargement allows researchers to obtain images with a resolution of around 70 nanometers, which was previously possible only with very specialized and expensive microscopes such as scanning electron microscopes.

In 2017, the Boyden lab developed a way to expand preserved human tissue specimens, but the chemical reagents that they used also destroyed the proteins that the researchers were interested in labeling. By labeling the proteins with fluorescent antibodies before expansion, the proteins’ location and identity could be visualized after the expansion process was complete. However, the antibodies typically used for this kind of labeling can’t easily squeeze through densely packed tissue before it’s expanded.

So, for this study, the authors devised a different tissue-softening protocol that breaks up the tissue but preserves proteins in the sample. After the tissue is expanded, proteins can be labelled with commercially available fluorescent antibodies. The researchers then can perform several rounds of imaging, with three or four different proteins labeled in each round. This labeling of proteins enables many more structures to be imaged, because once the tissue is expanded, antibodies can squeeze through and label proteins they couldn’t previously reach.

The technique works by embedding the tissue into a polymer that swells when water is added, and then softening up and breaking apart the proteins that normally hold tissue together.

“We open up the space between the proteins so that we can get antibodies into crowded spaces that we couldn’t otherwise,” Valdes says. “We saw that we could expand the tissue, we could decrowd the proteins, and we could image many, many proteins in the same tissue by doing multiple rounds of staining.”

Working with MIT Assistant Professor Deblina Sarkar, the researchers demonstrated a form of this “decrowding” in 2022 using mouse tissue.

The new study resulted in a decrowding technique for use with human brain tissue samples that are used in clinical settings for pathological diagnosis and to guide treatment decisions. These samples can be more difficult to work with because they are usually embedded in paraffin and treated with other chemicals that need to be broken down before the tissue can be expanded.

In this study, the researchers labeled up to 16 different molecules per tissue sample. The molecules they targeted include markers for a variety of structures, including axons and synapses, as well as markers that identify cell types such as astrocytes and cells that form blood vessels. They also labeled molecules linked to tumor aggressiveness and neurodegeneration.

Using this approach, the researchers analyzed healthy brain tissue, along with samples from patients with two types of glioma — high-grade glioblastoma, which is the most aggressive primary brain tumor, with a poor prognosis, and low-grade gliomas, which are considered less aggressive.

“We wanted to look at brain tumors so that we can understand them better at the nanoscale level, and by doing that, to be able to develop better treatments and diagnoses in the future. At this point, it was more developing a tool to be able to understand them better, because currently in neuro-oncology, people haven’t done much in terms of super-resolution imaging,” Valdes says.

A diagnostic tool

To identify aggressive tumor cells in gliomas they studied, the researchers labeled vimentin, a protein that is found in highly aggressive glioblastomas. To their surprise, they found many more vimentin-expressing tumor cells in low-grade gliomas than had been seen using any other method.

“This tells us something about the biology of these tumors, specifically, how some of them probably have a more aggressive nature than you would suspect by doing standard staining techniques,” Valdes says.

When glioma patients undergo surgery, tumor samples are preserved and analyzed using immunohistochemistry staining, which can reveal certain markers of aggressiveness, including some of the markers analyzed in this study.

“These are incurable brain cancers, and this type of discovery will allow us to figure out which cancer molecules to target so we can design better treatments. It also proves the profound impact of having clinicians like us at the Brigham and Women’s interacting with basic scientists such as Ed Boyden at MIT to discover new technologies that can improve patient lives,” Chiocca says.

The researchers hope their expansion microscopy technique could allow doctors to learn much more about patients’ tumors, helping them to determine how aggressive the tumor is and guiding treatment choices. Valdes now plans to do a larger study of tumor types to try to establish diagnostic guidelines based on the tumor traits that can be revealed using this technique.

“Our hope is that this is going to be a diagnostic tool to pick up marker cells, interactions, and so on, that we couldn’t before,” he says. “It’s a practical tool that will help the clinical world of neuro-oncology and neuropathology look at neurological diseases at the nanoscale like never before, because fundamentally it’s a very simple tool to use.”

Boyden’s lab also plans to use this technique to study other aspects of brain function, in healthy and diseased tissue.

“Being able to do nanoimaging is important because biology is about nanoscale things — genes, gene products, biomolecules — and they interact over nanoscale distances,” Boyden says. “We can study all sorts of nanoscale interactions, including synaptic changes, immune interactions, and changes that occur during cancer and aging.”

The research was funded by K. Lisa Yang, the Howard Hughes Medical Institute, John Doerr, Open Philanthropy, the Bill and Melinda Gates Foundation, the Koch Institute Frontier Research Program, the National Institutes of Health, and the Neurosurgery Research and Education Foundation.

How the brain responds to reward is linked to socioeconomic background

MIT neuroscientists have found that the brain’s sensitivity to rewarding experiences — a critical factor in motivation and attention — can be shaped by socioeconomic conditions.

In a study of 12 to 14-year-olds whose socioeconomic status (SES) varied widely, the researchers found that children from lower SES backgrounds showed less sensitivity to reward than those from more affluent backgrounds.

Using functional magnetic resonance imaging (fMRI), the research team measured brain activity as the children played a guessing game in which they earned extra money for each correct guess. When participants from higher SES backgrounds guessed correctly, a part of the brain called the striatum, which is linked to reward, lit up much more than in children from lower SES backgrounds.

The brain imaging results also coincided with behavioral differences in how participants from lower and higher SES backgrounds responded to correct guesses. The findings suggest that lower SES circumstances may prompt the brain to adapt to the environment by dampening its response to rewards, which are often scarcer in low SES environments.

“If you’re in a highly resourced environment, with many rewards available, your brain gets tuned in a certain way. If you’re in an environment in which rewards are more scarce, then your brain accommodates the environment in which you live. Instead of being overresponsive to rewards, it seems like these brains, on average, are less responsive, because probably their environment has been less consistent in the availability of rewards,” says John Gabrieli, the Grover Hermann Professor of Health Sciences and Technology, a professor of brain and cognitive sciences, and a member of MIT’s McGovern Institute for Brain Research.

Gabrieli and Rachel Romeo, a former MIT postdoc who is now an assistant professor in the Department of Human Development and Quantitative Methodology at the University of Maryland, are the senior authors of the study. MIT postdoc Alexandra Decker is the lead author of the paper, which appears today in the Journal of Neuroscience.

Reward response

Previous research has shown that children from lower SES backgrounds tend to perform worse on tests of attention and memory, and they are more likely to experience depression and anxiety. However, until now, few studies have looked at the possible association between SES and reward sensitivity.

In the new study, the researchers focused on a part of the brain called the striatum, which plays a significant role in reward response and decision-making. Studies in people and animal models have shown that this region becomes highly active during rewarding experiences.

To investigate potential links between reward sensitivity, the striatum, and socioeconomic status, the researchers recruited more than 100 adolescents from a range of SES backgrounds, as measured by household income and how much education their parents received.

Each of the participants underwent fMRI scanning while they played a guessing game. The participants were shown a series of numbers between 1 and 9, and before each trial, they were asked to guess whether the next number would be greater than or less than 5. They were told that for each correct guess, they would earn an extra dollar, and for each incorrect guess, they would lose 50 cents.

Unbeknownst to the participants, the game was set up to control whether the guess would be correct or incorrect. This allowed the researchers to ensure that each participant had a similar experience, which included periods of abundant rewards or few rewards. In the end, everyone ended up winning the same amount of money (in addition to a stipend that each participant received for participating in the study).

Previous work has shown that the brain appears to track the rate of rewards available. When rewards are abundant, people or animals tend to respond more quickly because they don’t want to miss out on the many available rewards. The researchers saw that in this study as well: When participants were in a period when most of their responses were correct, they tended to respond more quickly.

“If your brain is telling you there’s a really high chance that you’re going to receive a reward in this environment, it’s going to motivate you to collect rewards, because if you don’t act, you’re missing out on a lot of rewards,” Decker says.

Brain scans showed that the degree of activation in the striatum appeared to track fluctuations in the rate of rewards across time, which the researchers think could act as a motivational signal that there are many rewards to collect. The striatum lit up more during periods in which rewards were abundant and less during periods in which rewards were scarce. However, this effect was less pronounced in the children from lower SES backgrounds, suggesting their brains were less attuned to fluctuations in the rate of reward over time.

The researchers also found that during periods of scarce rewards, participants tended to take longer to respond after a correct guess, another phenomenon that has been shown before. It’s unknown exactly why this happens, but two possible explanations are that people are savoring their reward or that they are pausing to update the reward rate. However, once again, this effect was less pronounced in the children from lower SES backgrounds — that is, they did not pause as long after a correct guess during the scarce-reward periods.

“There was a reduced response to reward, which is really striking. It may be that if you’re from a lower SES environment, you’re not as hopeful that the next response will gain similar benefits, because you may have a less reliable environment for earning rewards,” Gabrieli says. “It just points out the power of the environment. In these adolescents, it’s shaping their psychological and brain response to reward opportunity.”

Environmental effects

The fMRI scans performed during the study also revealed that children from lower SES backgrounds showed less activation in the striatum when they guessed correctly, suggesting that their brains have a dampened response to reward.

The researchers hypothesize that these differences in reward sensitivity may have evolved over time, in response to the children’s environments.

“Socioeconomic status is associated with the degree to which you experience rewards over the course of your lifetime,” Decker says. “So, it’s possible that receiving a lot of rewards perhaps reinforces behaviors that make you receive more rewards, and somehow this tunes the brain to be more responsive to rewards. Whereas if you are in an environment where you receive fewer rewards, your brain might become, over time, less attuned to them.”

The study also points out the value of recruiting study subjects from a range of SES backgrounds, which takes more effort but yields important results, the researchers say.

“Historically, many studies have involved the easiest people to recruit, who tend to be people who come from advantaged environments. If we don’t make efforts to recruit diverse pools of participants, we almost always end up with children and adults who come from high-income, high-education environments,” Gabrieli says. “Until recently, we did not realize that principles of brain development vary in relation to the environment in which one grows up, and there was very little evidence about the influence of SES.”

The research was funded by the William and Flora Hewlett Foundation and a Natural Sciences and Engineering Research Council of Canada Postdoctoral Fellowship.

Tuning the mind to benefit mental health

This story also appears in the Winter 2024 issue of BrainScan.

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llustration of woman sitting at end of a dock with head down, arms wrapped around her knees.
Mental health is the defining public health crisis of our time, according to U.S. Surgeon General Vivek Murthy, and the nation’s youth is at the
center of this crisis.

Psychiatrists and pediatricians have sounded an alarm. The mental health of youth in the United States is worsening. Youth visits to emergency departments related to depression, anxiety, and behavioral challenges have been on the rise for years. Suicide rates among young people have escalated, too. Researchers have tracked these trends for more than a decade, and the Covid-19 pandemic only exacerbated the situation.

“It’s all over the news, how shockingly common mental health difficulties are,” says John Gabrieli, the Grover Hermann Professor of Health Sciences and Technology at MIT and an investigator at the McGovern Institute. “It’s worsening by every measure.”

Experts worry that our mental health systems are inadequate to meet the growing need. “This has gone from bad to catastrophic, from my perspective,” says Susan Whitfeld-Gabrieli, a professor of psychology at Northeastern University and a research affiliate at the McGovern Institute.

“We really need to come up with novel interventions that target the neural mechanisms that we believe potentiate depression and anxiety.”

Training the brain

One approach may be to help young people learn to modulate some of the relevant brain circuitry themselves. Evidence is accumulating that practicing mindfulness — focusing awareness on the present, typically through meditation — can change patterns of brain activity associated with emotions and mental health.

“There’s been a steady flow of moderate-size studies showing that when you help people gain mindfulness through training programs, you get all kinds of benefits in terms of people feeling less stress, less anxiety, fewer negative emotions, and sometimes more positive ones as well,” says Gabrieli, who is also a professor of brain and cognitive sciences at MIT. “Those are the things you wish for people.”

“If there were a medicine with as much evidence of its effectiveness as mindfulness, it would be flying off the shelves of every pharmacy.”
– John Gabrieli

Researchers have even begun testing mindfulness-based interventions head-to-head against standard treatments for psychiatric disorders. The results of recent studies involving hundreds of adults with anxiety disorders or depression are encouraging. “It’s just as good as the best medicines and the best behavioral treatments that we know a ton about,” Gabrieli says.

Much mindfulness research has focused on adults, but promising data about the benefits of mindfulness training for children and adolescents is emerging as well. In studies supported by the McGovern Institute’s Poitras Center for Psychiatric Disorders Research in 2019 and 2020, Gabrieli and Whitfield-Gabrieli found that sixth-graders in a Boston middle school who participated in eight weeks of mindfulness training experienced reductions in feelings of stress and increases in sustained attention. More recently, Gabrieli and Whitfeld-Gabrieli’s teams have shown how new tools can support mindfulness training and make it accessible to more children and their families — from a smartphone app that can be used anywhere to real-time neurofeedback inside an MRI scanner.

Three people practicing mindfulness in MIT Building 46. Woman on left is leaning on a railing, wearing headphones with eyes closed. Man seated in the center holds a bowl and a wooden spoon. Woman on right is seated with legs crossed and eyes closed.
Isaac Treves (center), a PhD student in the lab of John Gabrieli, is the lead author of two studies which found that mindfulness training may improve children’s mental health. Treves and his co-authors Kimberly Wang (left) and Cindy Li (right) also practice mindfulness in their daily lives. Photo: Steph Stevens

Mindfulness and mental health

Mindfulness is not just a practice, it is a trait — an open, non-judgmental way of attending to experiences that some people exhibit more than others. By assessing individuals’ mindfulness with questionnaires that ask about attention and awareness, researchers have found the trait associates with many measures of mental health. Gabrieli and his team measured mindfulness in children between the ages of eight and ten and found it was highest in those who were most emotionally resilient to the stress they experienced during the Covid-19 pandemic. As the team reported this year in the journal PLOS One, children who were more mindful rated the impact of the pandemic on their own lives lower than other participants in the study. They also reported lower levels of stress, anxiety, and depression.

Illustration of a finger tracing the outline of a hand. There is a circle next to the hand with text that says, "Breathe In, Breathe Out. Children enrolled in John Gabrieli’s mindfulness study learned to trace the outline of their fingers in rhythm with their in-andout breathing pattern. This multisensory breathing technique has been shown to relieve anxiety and relax the body."

Mindfulness doesn’t come naturally to everyone, but brains are malleable, and both children and adults can cultivate mindfulness with training and practice. In their studies of middle schoolers, Gabrieli and Whitfeld-Gabrieli showed that the emotional effects of mindfulness training corresponded to measurable changes in the brain: Functional MRI scans revealed changes in regions involved in stress, negative feelings, and focused attention.

Whitfeld-Gabrieli says if mindfulness training makes kids more resilient, it could be a valuable tool for managing symptoms of anxiety and depression before they become severe. “I think it should be part of the standard school day,” she says. “I think we would have a much happier, healthier society if we could be doing this from the ground up.”

Data from Gabrieli’s lab suggests broadly implementing mindfulness training might even pay off in terms of academic achievement. His team found in a 2019 study that middle school students who reported greater levels of mindfulness had, on average, better grades, better scores on standardized tests, fewer absences, and fewer school suspensions than their peers.

Some schools have begun making mindfulness programs available to their students. But those programs don’t reach everyone, and their type and quality vary tremendously. Indeed, not every study of mindfulness training in schools has found the program to significantly benefit participants, which may be because not every approach to mindfulness training is equally effective.

“This is where I think the science matters,” Gabrieli says. “You have to find out what kinds of supports really work and you have to execute them reasonably. A recent report from Gabrieli’s lab offers encouraging news: mindfulness training doesn’t have to be in-person. Gabrieli and his team found that children can benefit from practicing mindfulness at home with the help of an app.

When the pandemic closed schools in 2020, school-based mindfulness programs came to an abrupt halt. Soon thereafter, a group called Inner Explorer had developed a smartphone app that could teach children mindfulness at home. Gabrieli and his team were eager to find out if this easy-access tool could effectively support children’s emotional well-being.

In October of this year, they reported in the journal Mindfulness that after 40 days of app use, children between the ages of eight and ten reported less stress than they had before beginning mindfulness training. Parents reported that their children were also experiencing fewer negative emotions, such as loneliness and fear.

The outcomes suggest a path toward making evidence-based mindfulness training for children broadly accessible. “Tons of people could do this,” says Gabrieli. “It’s super scalable. It doesn’t cost money; you don’t have to go somewhere. We’re very excited about that.”

Visualizing healthy minds

Mindfulness training may be even more effective when practitioners can visualize what’s happening in their brains. In Whitfeld-Gabrieli’s lab, teenagers have had a chance to slide inside an MRI scanner and watch their brain activity shift in real time as they practiced mindfulness meditation. The visualization they see focuses on the brain’s default mode network (DMN), which is most active when attention is not focused on a particular task. Certain patterns of activity in the DMN have been linked to depression, anxiety, and other psychiatric conditions, and mindfulness training may help break these patterns.

McGovern research affiliate Susan Whitfield-Gabrieli in the Martinos Imaging Center. Photo: Caitlin Cunningham

Whitfeld-Gabrieli explains that when the mind is free to wander, two hubs of the DMN become active. “Typically, that means we’re engaged in some kind of mental time travel,” she says. That might mean reminiscing about the past or planning for the future, but can be more distressing when it turns into obsessive rumination or worry. In people with anxiety, depression, and psychosis, these network hubs are often hyperconnected.

“It’s almost as if they’re hijacked,” Whitfeld-Gabrieli says. “The more they’re correlated, the more psychopathology one might be experiencing. We wanted to unlock that hyperconnectivity for kids who are suffering from depression and anxiety.” She hoped that by replacing thoughts of the past and the future with focus on the present, mindfulness meditation would rein in overactive DMNs, and she wanted a way to encourage kids to do exactly that.

The neurofeedback tool that she and her colleagues created focuses on the DMN as well as separate brain region that is called on during attention-demanding tasks. Activity in those regions is monitored with functional MRI and displayed to users in a game-like visualization. Inside the scanner, participants see how that activity changes as they focus on a meditation or when their mind wanders. As their mind becomes more focused on the present moment, changes in brain activity move a ball toward a target.

Whitfeld-Gabrieli says the real-time feedback was motivating for adolescents who participated in a recent study, who all had histories of anxiety or depression. “They’re training their brain to tune their mind, and they love it,” she says.

MRI images of two brains, one showing an active DMN and the other showing a healthy DMN.
The default mode network (DMN) is a large-scale brain network that is active when a person is not focused on the outside world and the brain is at wakeful rest. The DMN is often over-engaged in adolescents with depression and anxiety, as well as teens at risk for these affective disorders (left). DMN activation and connectivity can be “tuned” to a healthier state through the practice of mindfulness (right).

In March, she and her team reported in Molecular Psychiatry that the neurofeedback tool helped those study participants reduce connectivity in the DMN and engage a more desirable brain state. It’s not the first success the team has had with the approach. Previously, they found that the decreases in DMN connectivity brought about by mindfulness meditation with neurofeedback were associated with reduced hallucinations for patients with schizophrenia. Testing the clinical benefits of the approach in teens is on the horizon; Whitfeld-Gabrieli and her collaborators plan to investigate how mindfulness meditation with real-time neurofeedback affects depression symptoms in an upcoming clinical trial.

Whitfeld-Gabrieli emphasizes that the neurofeedback is a training tool, helping users improve mindfulness techniques they can later call on anytime, anywhere. While that training currently requires time inside an MRI scanner, she says it may be possible create an EEG-based version of the approach, which could be deployed in doctors’ offices and other more accessible settings.

Both Gabrieli and Whitfeld-Gabrieli continue to explore how mindfulness training impacts different aspects of mental health, in both children and adults and with a range of psychiatric conditions. Whitfeld-Gabrieli expects it will be one powerful tool for combating a youth mental health crisis for which there will be no single solution. “I think it’s going to take a village,” she says. “We are all going to have to work together, and we’ll have to come up some really innovative ways to help.”

Re-imagining our theories of language

Over a decade ago, the neuroscientist Ev Fedorenko asked 48 English speakers to complete tasks like reading sentences, recalling information, solving math problems, and listening to music. As they did this, she scanned their brains using functional magnetic resonance imaging to see which circuits were activated. If, as linguists have proposed for decades, language is connected to thought in the human brain, then the language processing regions would be activated even during nonlinguistic tasks.

Fedorenko’s experiment, published in 2011 in the Proceedings of the National Academy of Sciences, showed that when it comes to arithmetic, musical processing, general working memory, and other nonlinguistic tasks, language regions of the human brain showed no response. Contrary to what many linguistists have claimed, complex thought and language are separate things. One does not require the other. “We have this highly specialized place in the brain that doesn’t respond to other activities,” says Fedorenko, who is an associate professor at the Department of Brain and Cognitive Sciences (BCS) and the McGovern Institute for Brain Research. “It’s not true that thought critically needs language.”

The design of the experiment, using neuroscience to understand how language works, how it evolved, and its relation to other cognitive functions, is at the heart of Fedorenko’s research. She is part of a unique intellectual triad at MIT’s Department of BCS, along with her colleagues Roger Levy and Ted Gibson. (Gibson and Fedorenko have been married since 2007). Together they have engaged in a years-long collaboration and built a significant body of research focused on some of the biggest questions in linguistics and human cognition. While working in three independent labs — EvLab, TedLab, and the Computational Psycholinguistics Lab — the researchers are motivated by a shared fascination with the human mind and how language works in the brain. “We have a great deal of interaction and collaboration,” says Levy. “It’s a very broadly collaborative, intellectually rich and diverse landscape.”

Using combinations of computational modeling, psycholinguistic experimentation, behavioral data, brain imaging, and large naturalistic language datasets, the researchers also share an answer to a fundamental question: What is the purpose of language? Of all the possible answers to why we have language, perhaps the simplest and most obvious is communication. “Believe it or not,” says Ted Gibson, “that is not the standard answer.”

Gibson first came to MIT in 1993 and joined the faculty of the Linguistics Department in 1997. Recalling the experience today, he describes it as frustrating. The field of linguistics at that time was dominated by the ideas of Noam Chomsky, one of the founders of MIT’s Graduate Program in Linguistics, who has been called the father of modern linguistics. Chomsky’s “nativist” theories of language posited that the purpose of language is the articulation of thought and that language capacity is built-in in advance of any learning. But Gibson, with his training in math and computer science, felt that researchers didn’t satisfyingly test these ideas. He believed that finding the answer to many outstanding questions about language required quantitative research, a departure from standard linguistic methodology. “There’s no reason to rely only on you and your friends, which is how linguistics has worked,” Gibson says. “The data you can get can be much broader if you crowdsource lots of people using experimental methods.” Chomsky’s ascendancy in linguistics presented Gibson with what he saw as a challenge and an opportunity. “I felt like I had to figure it out in detail and see if there was truth in these claims,” he says.

Three decades after he first joined MIT, Gibson believes that the collaborative research at BCS is persuasive and provocative, pointing to new ways of thinking about human culture and cognition. “Now we’re at a stage where it is not just arguments against. We have a lot of positive stuff saying what language is,” he explains. Levy adds: “I would say all three of us are of the view that communication plays a very import role in language learning and processing, but also in the structure of language itself.”

Levy points out that the three researchers completed PhDs in different subjects: Fedorenko in neuroscience, Gibson in computer science, Levy in linguistics. Yet for years before their paths finally converged at MIT, their shared interests in quantitative linguistic research led them to follow each other’s work closely and be influenced by it. The first collaboration between the three was in 2005 and focused on language processing in Russian relative clauses. Around that time, Gibson recalls, Levy was presenting what he describes as “lovely work” that was instrumental in helping him to understand the links between language structure and communication. “Communicative pressures drive the structures,” says Gibson. “Roger was crucial for that. He was the one helping me think about those things a long time ago.”

Levy’s lab is focused on the intersection of artificial intelligence, linguistics, and psychology, using natural language processing tools. “I try to use the tools that are afforded by mathematical and computer science approaches to language to formalize scientific hypotheses about language and the human mind and test those hypotheses,” he says.

Levy points to ongoing research between him and Gibson focused on language comprehension as an example of the benefits of collaboration. “One of the big questions is: When language understanding fails, why does it fail?” Together, the researchers have applied the concept of a “noisy channel,” first developed by the information theorist Claude Shannon in the 1950s, which says that information or messages are corrupted in transmission. “Language understanding unfolds over time, involving an ongoing integration of the past with the present,” says Levy. “Memory itself is an imperfect channel conveying the past from our brain a moment ago to our brain now in order to support successful language understanding.” Indeed, the richness of our linguistic environment, the experience of hundreds of millions of words by adulthood, may create a kind of statistical knowledge guiding our expectations, beliefs, predictions, and interpretations of linguistic meaning. “Statistical knowledge of language actually interacts with the constraints of our memory,” says Levy. “Our experience shapes our memory for language itself.”

All three researchers say they share the belief that by following the evidence, they will eventually discover an even bigger and more complete story about language. “That’s how science goes,” says Fedorenko. “Ted trained me, along with Nancy Kanwisher, and both Ted and Roger are very data-driven. If the data is not giving you the answer you thought, you don’t just keep pushing your story. You think of new hypotheses. Almost everything I have done has been like that.” At times, Fedorenko’s research into parts of the brain’s language system has surprised her and forced her to abandon her hypotheses. “In a certain project I came in with a prior idea that there would be some separation between parts that cared about combinatorics versus words meanings,” she says, “but every little bit of the language system is sensitive to both. At some point, I was like, this is what the data is telling us, and we have to roll with it.”

The researchers’ work pointing to communication as the constitutive purpose of language opens new possibilities for probing and studying non-human language. The standard claim is that human language has a drastically more extensive lexicon than animals, which have no grammar. “But many times, we don’t even know what other species are communicating,” says Gibson. “We say they can’t communicate, but we don’t know. We don’t speak their language.” Fedorenko hopes that more opportunities to make cross-species linguistic comparisons will open up. “Understanding where things are similar and where things diverge would be super useful,” she says.

Meanwhile, the potential applications of language research are far-reaching. One of Levy’s current research projects focuses on how people read and use machine learning algorithms informed by the psychology of eye movements to develop proficiency tests. By tracking the eye movements of people who speak English as a second language while they read texts in English, Levy can predict how good they are at English, an approach that could one day replace the Test of English as a Foreign Language. “It’s an implicit measure of language rather than a much more game-able test,” he says.

The researchers agree that some of the most exciting opportunities in the neuroscience of language lies with large language models that provide new opportunities for asking new questions and making new discoveries. “In the neuroscience of language, the kind of stories that we’ve been able to tell about how the brain does language were limited to verbal, descriptive hypotheses,” says Fedorenko. Computationally implemented models are now amazingly good at language and show some degree of alignment to the brain, she adds. Now, researchers can ask questions such as: what are the actual computations that cells are doing to get meaning from strings of words? “You can now use these models as tools to get insights into how humans might be processing language,” she says. “And you can take the models apart in ways you can’t take apart the brain.”

New Spanish-language neuroscience podcast flourishes in third season

A Spanish version of this news story can be found here. (Una versión en español de esta noticia se puede encontrar aquí.)

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Sylvia Abente, a clinical neurologist at the Universidad Nacional de Asunción in Paraguay, investigates the range of symptoms that characterize epilepsy. She works with indigenous peoples in Paraguay, and her fluency in Spanish and Guarni—the two official languages of Paraguay—allows her to help patients find the words to describe their epilepsy symptoms so she can treat them.

Juan Carlos Caicedo Mera, a neuroscientist at the Universidad Externado de Colombia, uses rodent models to research the neurobiological effects of early life stress. He has been instrumental in raising public awareness about the biological and behavioral effects of early-age physical punishment, leading to policy changes aimed at reducing its prevalence as a cultural practice in Colombia.

Woman interviews a man at a table with a camera recording the interview in the foreground.
Jessica Chomik-Morales (right) interviews Pedro Maldonado at the Biomedical Neuroscience Institute of Chile at the University of Chile. Photo: Jessica Chomik-Morales

Those are just two of the 33 neuroscientists in seven Latin American countries that Jessica Chomik-Morales interviewed over 37 days for the expansive third season of her Spanish-language podcast, “Mi Ultima Neurona” (“My Last Neuron”), which launches Sept. 18 at 5 p.m. on YouTube. Each episode runs between 45 and 90 minutes.

“I wanted to shine a spotlight on their stories to dispel the misconception that excellent science can only be done in America and Europe,” says Chomik-Morales, “or that it isn’t being produced in South America because of financial and other barriers.”

A first-generation college graduate who grew up in Asunción, Paraguay and Boca Raton, Florida, Chomik-Morales is now a postbaccalaureate research scholar at MIT. Here she works with Laura Schulz, professor of cognitive science, and Nancy Kanwisher, McGovern Institute investigator and the Walter A. Rosenblith Professor of Cognitive Neuroscience, using functional brain imaging to investigate how the brain explains the past, predicts the future, and intervenes on the present.

“The podcast is for the general public and is suitable for all ages,” she says. “It explains neuroscience in a digestable way to inspire young people that they, too, can become scientists and to show the rich variety of reseach that is being done in listeners’ home countries.”

Journey of a lifetime

“Mi Ultima Neurona” began as an idea in 2021 and grew rapidly into a collection of conversations with prominent Hispanic scientists, including L. Rafael Reif, a Venezuelan-American electrical engineer and the 17th president of MIT.

Woman interviews man at a table while another man adjusts microphone.
Jessica Chomik-Morales (left) interviews the 17th president of MIT, L. Rafael Reif (right), for her podcast while Héctor De Jesús-Cortés (center) adjusts the microphone. Photo: Steph Stevens

Building upon the professional relationships she built in seasons one and two, Chomik-Morales broadened her vision, and assembled a list of potential guests in Latin America for season three.  With research help from her scientific advisor, Héctor De Jesús-Cortés, an MIT postdoc from Puerto Rico, and financial support from the McGovern Institute, the Picower Institute for Learning and Memory, the Department of Brain and Cognitive Sciences, and MIT International Science and Technology Initiatives, Chomik-Morales lined up interviews with scientists in Mexico, Peru, Colombia, Chile, Argentina, Uruguay, and Paraguay during the summer of 2023.

Traveling by plane every four or five days, and garnering further referrals from one leg of the trip to the next through word of mouth, Chomik-Morales logged over 10,000 miles and collected 33 stories for her third season. The scientists’ areas of specialization run the gamut— from the social aspects of sleep/wake cycles to mood and personality disorders, from linguistics and language in the brain to computational modeling as a research tool.

“This is the most fulfilling thing I’ve ever done.” – Jessica Chomik-Morales

“If somebody studies depression and anxiety, I want to touch on their opinions regarding various therapies, including drugs, even microdosing with hallucinogens,” says Chomik-Morales. “These are the things people are talking about.” She’s not afraid to broach sensitive topics, like the relationship between hormones and sexual orientation, because “it’s important that people listen to experts talk about these things,” she says.

The tone of the interviews range from casual (“the researcher and I are like friends,” she says) to pedagogic (“professor to student”). The only constants are accessibility—avoiding technical terms—and the opening and closing questions in each one. To start: “How did you get here? What drew you to neuroscience?” To end: “What advice would you give a young Latino student who is interested in STEM?”

She lets her listeners’ frame of reference be her guide. “If I didn’t understand something or thought it could be explained better, I’d say, ‘Let’s pause. ‘What does this word mean?’ ” even if she knew the definition herself. She gives the example of the word “MEG” (magnetoencephalography)—the measurement of the magnetic field generated by the electrical activity of neurons, which is usually combined with magnetic resonance imaging to produce magnetic source imaging. To bring the concept down to Earth, she’d ask: “How does it work? Does this kind of scan hurt the patient?’ ”

Paving the way for global networking

Chomik-Morales’s equipment was spare: three Yeti microphones and a Canon video camera connected to her laptop computer. The interviews took place in classrooms, university offices, at researchers’ homes, even outside—no soundproof studios were available. She has been working with sound engineer David Samuel Torres, from Puerto Rico, to clarify the audio.

No technological limitations could obscure the significance of the project for the participating scientists.

Two women talking at a table in front of a camera.
Jessica Chomik-Morales (left) interviews Josefina Cruzat (right) at Adolfo Ibañez University in Chile. Photo: Jessica Chomik-Morales

“‘Mi Ultima Neurona’ showcases our diverse expertise on a global stage, providing a more accurate portrayal of the scientific landscape in Latin America,” says Constanza Baquedano, who is from Chile. “It’s a step toward creating a more inclusive representation in science.” Baquendano is an assistant professor of psychology at Universidad Adolfo Ibáñez, where she uses electrophysiology and electroencephalographic and behavioral measurements to investigate meditation and other contemplative states. “I was eager to be a part of a project that aimed to bring recognition to our shared experiences as Latin American women in the field of neuroscience.”

“Understanding the challenges and opportunities of neuroscientists working in Latin America is vital,”says Agustín Ibañez, professor and director of the Latin American Brain Health Institute (BrainLat) at Universidad Adolfo Ibáñez in Chile. “This region, characterized by significant inequalities affecting brain health, also presents unique challenges in the field of neuroscience,” says Ibañez, who is primarily interested in the intersection of social, cognitive, and affective neuroscience. “By focusing on Latin America, the podcast brings forth the narratives that often remain untold in the mainstream. That bridges gaps and paves the way for global networking.”

For her part, Chomik-Morales is hopeful that her podcast will generate a strong following in Latin America. “I am so grateful for the wonderful sponsorship from MIT,” says Chomik-Morales. “This is the most fulfilling thing I’ve ever done.”

Real-time feedback helps adolescents with depression quiet the mind

Real-time feedback about brain activity can help adolescents with depression or anxiety quiet their minds, according to a new study from MIT scientists. The researchers, led by McGovern research affiliate Susan Whitfield-Gabrieli, have used functional magnetic resonance imaging (fMRI) to show patients what’s happening in their brain as they practice mindfulness inside the scanner and to encourage them to focus on the present. They report in the journal Molecular Psychiatry that doing so settles down neural networks that are associated with symptoms of depression.

McGovern research affiliate Susan Whitfield-Gabrieli in the Martinos Imaging Center.

“We know this mindfulness meditation is really good for kids and teens, and we think this real-time fMRI neurofeedback is really a way to engage them and provide a visual representation of how they’re doing,” says Whitfield-Gabrieli. “And once we train people how to do mindfulness meditation, they can do it on their own at any time, wherever they are.”

The approach could be a valuable tool to alleviate or prevent depression in young people, which has been on the rise in recent years and escalated alarmingly during the Covid-19 pandemic. “This has gone from bad to catastrophic, in my perspective,” Whitfield-Gabrieli says. “We have to think out of the box and come up some really innovative ways to help.”

Default mode network

Mindfulness meditation, in which practitioners focus their awareness on the present moment, can modulate activity within the brain’s default mode network, which is so named because it is most active when a person is not focused on any particular task. Two hubs within the default mode network, the medial prefrontal cortex and the posterior cingulate cortex, are of particular interest to Whitfield-Gabrieli and her colleagues, due to a potential role in the symptoms of depression and anxiety.

“These two core hubs are very engaged when we’re thinking about the past or the future and we’re not really engaged in the present moment,” she explains. “If we’re in a healthy state of mind, we may be reminiscing about the past or planning for the future. But if we’re depressed, that reminiscing may turn into rumination or obsessively rehashing the past. If we’re particularly anxious, we may be obsessively worrying about the future.”

Whitfield-Gabrieli explains that these key hubs are often hyperconnected in people with anxiety and depression. The more tightly correlated the activity of the two regions are, the worse a person’s symptoms are likely to be. Mindfulness, she says, can help interrupt that hyperconnectivity.

“Mindfulness really helps to focus on the now, which just precludes all of this mind wandering and repetitive negative thinking,” she explains. In fact, she and her colleagues have found that mindfulness practice can reduce stress and improve attention in children. But she acknowledges that it can be difficult to engage young people and help them focus on the practice.

Tuning the mind

To help people visualize the benefits of their mindfulness practice, the researchers developed a game that can be played while an MRI scanner tracks a person’s brain activity. On a screen inside the scanner, the participant sees a ball and two circles. The circle at the top of the screen represents a desirable state in which the activity of the brain’s default mode network has been reduced, and the activity of a network the brain uses to focus on attention-demanding tasks—the frontal parietal network—has increased. An initial fMRI scan identifies these networks in each individual’s brain, creating a customized mental map on which the game is based.

“They’re training their brain to tune their mind. And they love it.” – Susan Whitfield-Gabrieli

As the person practices mindfulness meditation, which they learn prior to entering the scanner, the default mode network in the brain quiets while the frontal parietal mode activates. When the scanner detects this change, the ball moves and eventually enters its target. With an initial success, the target shrinks, encouraging even more focus. When the participant’s mind wanders from their task, the default mode network activation increases (relative to the frontal parietal network) and the ball moves down towards the second circle, which represents an undesirable state. “Basically, they’re just moving this ball with their brain,” Whitfield-Gabrieli says. “They’re training their brain to tune their mind. And they love it.”

Nine individuals between the ages of 17 and 19 with a history of major depression or anxiety disorders tried this new approach to mindfulness training, and for each of them, Whitfield-Gabrieli’s team saw a reduction in connectivity within the default mode network. Now they are working to determine whether an electroencephalogram, in which brain activity is measured with noninvasive electrodes, can be used to provide similar neurofeedback during mindfulness training—an approach that could be more accessible for broad clinical use.

Whitfield-Gabrieli notes that hyperconnectivity in the default mode network is also associated with psychosis, and she and her team have found that mindfulness meditation with real-time fMRI feedback can help reduce symptoms in adults with schizophrenia. Future studies are planned to investigate how the method impacts teens’ ability to establish a mindfulness practice and its potential effects on depression symptoms.

Partnership with MIT Museum explores relationship between neuroscience and society

What does a healthy relationship between neuroscience and society look like? How do we set the conditions for that relationship to flourish? Researchers and staff at the McGovern Institute and the MIT Museum have been exploring these questions with a five-month planning grant from the Dana Foundation.

Between October 2022 and March 2023, the team tested the potential for an MIT Center for Neuroscience and Society through a series of MIT-sponsored events that were attended by students and faculty of nearby Cambridge Public Schools. The goal of the project was to learn more about what happens when the distinct fields of neuroscience, ethics, and public engagement are brought together to work side-by-side.

Researchers assist volunteer in mock MRI scanner
Gabrieli lab members Sadie Zacharek (left) and Shruti Nishith (right) demonstrate how the MRI mock scanner works with a student volunteer from the Cambridge Public Schools. Photo: Emma Skakel, MIT Museum

Middle schoolers visit McGovern

Over four days in February, more than 90 sixth graders from Rindge Avenue Upper Campus (RAUC) in Cambridge, Massachusetts, visited the McGovern Institute and participated in hands-on experiments and discussions about the ethical, legal, and social implications of neuroscience research. RAUC is one of four middle schools in the city of Cambridge with an economically, racially, and culturally diverse student population. The middle schoolers interacted with an MIT team led by McGovern Scientific Advisor Jill R. Crittenden, including seventeen McGovern neuroscientists, three MIT Museum outreach coordinators, and neuroethicist Stephanie Bird, a member of the Dana Foundation planning grant team.

“It is probably the only time in my life I will see a real human brain.” – RAUC student

The students participated in nine activities each day, including trials of brain-machine interfaces, close-up examinations of preserved human brains, a tour of McGovern’s imaging center in which students watched as their teacher’s brain was scanned, and a visit to the MIT Museum’s interactive Artificial Intelligence Gallery.

Imagine-IT, a brain-machine interface designed by a team of middle school students during a visit to the McGovern Institute.

To close out their visit, students worked in groups alongside experts to invent brain-computer interfaces designed to improve or enhance human abilities. At each step, students were introduced to ethical considerations through consent forms, questions regarding the use of animal and human brains, and the possible impacts of their own designs on individuals and society.

“I admit that prior to these four days, I would’ve been indifferent to the inclusion of children’s voices in a discussion about technically complex ethical questions, simply because they have not yet had any opportunity to really understand how these technologies work,” says one researcher involved in the visit. “But hearing the students’ questions and ideas has changed my perspective. I now believe it is critically important that all age groups be given a voice when discussing socially relevant issues, such as the ethics of brain computer interfaces or artificial intelligence.”

 

For more information on the proposed MIT Center for Neuroscience and Society, visit the MIT Museum website.