Study reveals how an anesthesia drug induces unconsciousness

There are many drugs that anesthesiologists can use to induce unconsciousness in patients. Exactly how these drugs cause the brain to lose consciousness has been a longstanding question, but MIT neuroscientists have now answered that question for one commonly used anesthesia drug.

Using a novel technique for analyzing neuron activity, the researchers discovered that the drug propofol induces unconsciousness by disrupting the brain’s normal balance between stability and excitability. The drug causes brain activity to become increasingly unstable, until the brain loses consciousness.

“The brain has to operate on this knife’s edge between excitability and chaos.” – Earl K. Miller

“It’s got to be excitable enough for its neurons to influence one another, but if it gets too excitable, it spins off into chaos. Propofol seems to disrupt the mechanisms that keep the brain in that narrow operating range,” says Earl K. Miller, the Picower Professor of Neuroscience and a member of MIT’s Picower Institute for Learning and Memory.

The new findings, reported today in Neuron, could help researchers develop better tools for monitoring patients as they undergo general anesthesia.

Miller and Ila Fiete, a professor of brain and cognitive sciences, the director of the K. Lisa Yang Integrative Computational Neuroscience Center (ICoN), and a member of MIT’s McGovern Institute for Brain Research, are the senior authors of the new study. MIT graduate student Adam Eisen and MIT postdoc Leo Kozachkov are the lead authors of the paper.

Losing consciousness

Propofol is a drug that binds to GABA receptors in the brain, inhibiting neurons that have those receptors. Other anesthesia drugs act on different types of receptors, and the mechanism for how all of these drugs produce unconsciousness is not fully understood.

Miller, Fiete, and their students hypothesized that propofol, and possibly other anesthesia drugs, interfere with a brain state known as “dynamic stability.” In this state, neurons have enough excitability to respond to new input, but the brain is able to quickly regain control and prevent them from becoming overly excited.

Woman gestures with her hand in front of a glass wall with equations written on it.
Ila Fiete in her lab at the McGovern Institute. Photo: Steph Stevens

Previous studies of how anesthesia drugs affect this balance have found conflicting results: Some suggested that during anesthesia, the brain shifts toward becoming too stable and unresponsive, which leads to loss of consciousness. Others found that the brain becomes too excitable, leading to a chaotic state that results in unconsciousness.

Part of the reason for these conflicting results is that it has been difficult to accurately measure dynamic stability in the brain. Measuring dynamic stability as consciousness is lost would help researchers determine if unconsciousness results from too much stability or too little stability.

In this study, the researchers analyzed electrical recordings made in the brains of animals that received propofol over an hour-long period, during which they gradually lost consciousness. The recordings were made in four areas of the brain that are involved in vision, sound processing, spatial awareness, and executive function.

These recordings covered only a tiny fraction of the brain’s overall activity, so to overcome that, the researchers used a technique called delay embedding. This technique allows researchers to characterize dynamical systems from limited measurements by augmenting each measurement with measurements that were recorded previously.

Using this method, the researchers were able to quantify how the brain responds to sensory inputs, such as sounds, or to spontaneous perturbations of neural activity.

In the normal, awake state, neural activity spikes after any input, then returns to its baseline activity level. However, once propofol dosing began, the brain started taking longer to return to its baseline after these inputs, remaining in an overly excited state. This effect became more and more pronounced until the animals lost consciousness.

This suggests that propofol’s inhibition of neuron activity leads to escalating instability, which causes the brain to lose consciousness, the researchers say.

Better anesthesia control

To see if they could replicate this effect in a computational model, the researchers created a simple neural network. When they increased the inhibition of certain nodes in the network, as propofol does in the brain, network activity became destabilized, similar to the unstable activity the researchers saw in the brains of animals that received propofol.

“We looked at a simple circuit model of interconnected neurons, and when we turned up inhibition in that, we saw a destabilization. So, one of the things we’re suggesting is that an increase in inhibition can generate instability, and that is subsequently tied to loss of consciousness,” Eisen says.

As Fiete explains, “This paradoxical effect, in which boosting inhibition destabilizes the network rather than silencing or stabilizing it, occurs because of disinhibition. When propofol boosts the inhibitory drive, this drive inhibits other inhibitory neurons, and the result is an overall increase in brain activity.”

The researchers suspect that other anesthetic drugs, which act on different types of neurons and receptors, may converge on the same effect through different mechanisms — a possibility that they are now exploring.

If this turns out to be true, it could be helpful to the researchers’ ongoing efforts to develop ways to more precisely control the level of anesthesia that a patient is experiencing. These systems, which Miller is working on with Emery Brown, the Edward Hood Taplin Professor of Medical Engineering at MIT, work by measuring the brain’s dynamics and then adjusting drug dosages accordingly, in real-time.

“If you find common mechanisms at work across different anesthetics, you can make them all safer by tweaking a few knobs, instead of having to develop safety protocols for all the different anesthetics one at a time,” Miller says. “You don’t want a different system for every anesthetic they’re going to use in the operating room. You want one that’ll do it all.”

The researchers also plan to apply their technique for measuring dynamic stability to other brain states, including neuropsychiatric disorders.

“This method is pretty powerful, and I think it’s going to be very exciting to apply it to different brain states, different types of anesthetics, and also other neuropsychiatric conditions like depression and schizophrenia,” Fiete says.

The research was funded by the Office of Naval Research, the National Institute of Mental Health, the National Institute of Neurological Disorders and Stroke, the National Science Foundation Directorate for Computer and Information Science and Engineering, the Simons Center for the Social Brain, the Simons Collaboration on the Global Brain, the JPB Foundation, the McGovern Institute, and the Picower Institute.

What is language for?

Language is a defining feature of humanity, and for centuries, philosophers and scientists have contemplated its true purpose. We use language to share information and exchange ideas—but is it more than that? Do we use language not just to communicate, but to think?

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

In the June 19, 2024, issue of the journal Nature, McGovern Institute neuroscientist Evelina Fedorenko and colleagues argue that we do not. Language, they say, is primarily a tool for communication.

Fedorenko acknowledges that there is an intuitive link between language and thought. Many people experience an inner voice that seems to narrate their own thoughts. And it’s not unreasonable to expect that well-spoken, articulate individuals are also clear thinkers. But as compelling as these associations can be, they are not evidence that we actually use language to think.

 “I think there are a few strands of intuition and confusions that have led people to believe very strongly that language is the medium of thought,” she says.

“But when they are pulled apart thread by thread, they don’t really hold up to empirical scrutiny.”

Separating language and thought

For centuries, language’s potential role in facilitating thinking was nearly impossible to evaluate scientifically. But neuroscientists and cognitive scientists now have tools that enable a more rigorous consideration of the idea. Evidence from both fields, which Fedorenko, MIT cognitive scientist and linguist Edward Gibson, and University of California Berkeley cognitive scientist Steven Piantadosi review in their Nature Perspective, supports the idea that language is a tool for communication, not for thought.

“What we’ve learned by using methods that actually tell us about the engagement of the linguistic processing mechanisms is that those mechanisms are not really engaged when we think,” Fedorenko says. Also, she adds, “you can take those mechanisms away, and it seems that thinking can go on just fine.”

Over the past 20 years, Fedorenko and other neuroscientists have advanced our understanding of what happens in the brain as it generates and understands language. Now, using functional MRI to find parts of the brain that are specifically engaged when someone reads or listens to sentences or passages, they can reliably identify an individual’s language-processing network. Then they can monitor those brain regions while the person performs other tasks, from solving a sudoku puzzle to reasoning about other people’s beliefs.

“Your language system is basically silent when you do all sorts of thinking.” – Ev Fedorenko

“Pretty much everything we’ve tested so far, we don’t see any evidence of the engagement of the language mechanisms,” Fedorenko says. “Your language system is basically silent when you do all sorts of thinking.”

That’s consistent with observations from people who have lost the ability to process language due to an injury or stroke. Severely affected patients can be completely unable to process words, yet this does not interfere with their ability to solve math problems, play chess, or plan for future events. “They can do all the things that they could do before their injury. They just can’t take those mental representations and convert them into a format which would allow them to talk about them with others,” Fedorenko says. “If language gives us the core representations that we use for reasoning, then…destroying the language system should lead to problems in thinking as well, and it really doesn’t.”

Conversely, intellectual impairments do not always associate with language impairment; people with intellectual disability disorders or neuropsychiatric disorders that limit their ability to think and reason do not necessarily have problems with basic linguistic functions. Just as language does not appear to be necessary for thought, Fedorenko and colleagues conclude that it is also not sufficient to produce clear thinking.

Language optimization

In addition to arguing that language is unlikely to be used for thinking, the scientists considered its suitability as a communication tool, drawing on findings from linguistic analyses. Analyses across dozens of diverse languages, both spoken and signed, have found recurring features that make them easy to produce and understand. “It turns out that pretty much any property you look at, you can find evidence that languages are optimized in a way that makes information transfer as efficient as possible,” Fedorenko says.

That’s not a new idea, but it has held up as linguists analyze larger corpora across more diverse sets of languages, which has become possible in recent years as the field has assembled corpora that are annotated for various linguistic features. Such studies find that across languages, sounds and words tend to be pieced together in ways that minimize effort for the language producer without muddling the message. For example, commonly used words tend to be short, while words whose meanings depend on one another tend to cluster close together in sentences. Likewise, linguists have noted features that help languages convey meaning despite potential “signal distortions,” whether due to attention lapses or ambient noise.

“All of these features seem to suggest that the forms of languages are optimized to make communication easier,” Fedorenko says, pointing out that such features would be irrelevant if language was primarily a tool for internal thought.

“Given that languages have all these properties, it’s likely that we use language for communication,” she says. She and her coauthors conclude that as a powerful tool for transmitting knowledge, language reflects the sophistication of human cognition—but does not give rise to it.

What is consciousness?

In the hit T.V. show “Westworld,” Dolores Abernathy, a golden-tressed belle, lives in the days when Manifest Destiny still echoed in America. She begins to notice unusual stirrings shaking up her quaint western town—and soon discovers that her skin is synthetic, and her mind, metal. She’s a cyborg meant to entertain humans. The key to her autonomy lies in reaching consciousness.

Shows like “Westworld” and other media probe the idea of consciousness, attempting to nail down a definition of the concept. However, though humans have ruminated on consciousness for centuries, we still don’t have a solid definition (even the Merriam-Webster dictionary lists five). One framework suggests that consciousness is any experience, from eating a candy bar to heartbreak. Another argues that it is how certain stimuli influence one’s behavior.

MIT graduate student Adam Eisen.

While some search for a philosophical explanation, MIT graduate student Adam Eisen seeks a scientific one.

Eisen studies consciousness in the labs of Ila Fiete, an associate investigator at the McGovern Institute, and Earl Miller, an investigator at the Picower Institute for Learning and Memory. His work melds seemingly opposite fields, using mathematical models to quantitatively explain, and thereby ground, the loftiness of consciousness.

In the Fiete lab, Eisen leverages computational methods to compare the brain’s electrical signals in an awake, conscious state to those in an unconscious state via anesthesia—which dampens communication between neurons so people feel no pain or become unconscious.

“What’s nice about anesthesia is that we have a reliable way of turning off consciousness,” says Eisen.

“So we’re now able to ask: What’s the fluctuation of electrical activity in a conscious versus unconscious brain? By characterizing how these states vary—with the precision enabled by computational models—we can start to build a better intuition for what underlies consciousness.”

Theories of consciousness

How are scientists thinking about consciousness? Eisen says that there are four major theories circulating in the neuroscience sphere. These theories are outlined below.

Global workspace theory

Consider the placement of your tongue in your mouth. This sensory information is always there, but you only notice the sensation when you make the effort to think about it. How does this happen?

“Global workspace theory seeks to explain how information becomes available to our consciousness,” he says. “This is called access consciousness—the kind that stores information in your mind and makes it available for verbal report. In this view, sensory information is broadcasted to higher-level regions of the brain by a process called ignition.” The theory proposes that widespread jolts of neuronal activity or “spiking” are essential for ignition, like how a few claps can lead to an audience applause. It’s through ignition that we reach consciousness.

Eisen’s research in anesthesia suggests, though, that not just any spiking will do. There needs to be a balance: enough activity to spark ignition, but also enough stability such that the brain doesn’t lose its ability to respond to inputs and produce reliable computations to reach consciousness.

Higher order theories

Let’s say you’re listening to “Here Comes The Sun” by The Beatles. Your brain processes the medley of auditory stimuli; you hear the bouncy guitar, upbeat drums, and George Harrison’s perky vocals. You’re having a musical experience—what it’s like to listen to music. According to higher-order theories, such an experience unlocks consciousness.

“Higher-order theories posit that a conscious mental state involves having higher-order mental representations of stimuli—usually in the higher levels of the brain responsible for cognition—to experience the world,” Eisen says.

Integrated information theory

“Imagine jumping into a lake on a warm summer day. All components of that experience—the feeling of the sun on your skin and the coolness of the water as you submerge—come together to form your ‘phenomenal consciousness,’” Eisen says. If the day was slightly less sunny or the water a fraction warmer, he explains, the experience would be different.

“Integrated information theory suggests that phenomenal consciousness involves an experience that is irreducible, meaning that none of the components of that experience can be separated or altered without changing the experience itself,” he says.

Attention schema theory

Attention schema theory, Eisen explains, says ‘attention’ is the information that we are focused on in the world, while ‘awareness’ is the model we have of our attention. He cites an interesting psychology study to disentangle attention and awareness.

In the study, the researchers showed human subjects a mixed sequence of two numbers and six letters on a computer. The participants were asked to report back what the numbers were. While they were doing this task, faintly detectable dots moved across the screen in the background. The interesting part, Eisen notes, is that people weren’t aware of the dots—that is, they didn’t report that they saw them. But despite saying they didn’t see the dots, people performed worse on the task when the dots were present.

“This suggests that some of the subjects’ attention was allocated towards the dots, limiting their available attention for the actual task,” he says. “In this case, people’s awareness didn’t track their attention. The subjects were not aware of the dots, even though the study shows that the dots did indeed affect their attention.”

The science behind consciousness

Eisen notes that a solid understanding of the neural basis of consciousness has yet to be cemented. However, he and his research team are advancing in this quest. “In our work, we found that brain activity is more ‘unstable’ under anesthesia, meaning that it lacks the ability to recover from disturbances—like distractions or random fluctuations in activity—and regain a normal state,” he says.

He and his fellow researchers believe this is because the unconscious brain can’t reliably engage in computations like the conscious brain does, and sensory information gets lost in the noise. This crucial finding points to how the brain’s stability may be a cornerstone of consciousness.

There’s still more work to do, Eisen says. But eventually, he hopes that this research can help crack the enduring mystery of how consciousness shapes human existence. “There is so much complexity and depth to human experience, emotion, and thought. Through rigorous research, we may one day reveal the machinery that gives us our common humanity.”

A new computational technique could make it easier to engineer useful proteins

To engineer proteins with useful functions, researchers usually begin with a natural protein that has a desirable function, such as emitting fluorescent light, and put it through many rounds of random mutation that eventually generate an optimized version of the protein.

This process has yielded optimized versions of many important proteins, including green fluorescent protein (GFP). However, for other proteins, it has proven difficult to generate an optimized version. MIT researchers have now developed a computational approach that makes it easier to predict mutations that will lead to better proteins, based on a relatively small amount of data.

Using this model, the researchers generated proteins with mutations that were predicted to lead to improved versions of GFP and a protein from adeno-associated virus (AAV), which is used to deliver DNA for gene therapy. They hope it could also be used to develop additional tools for neuroscience research and medical applications.

Woman gestures with her hand in front of a glass wall with equations written on it.
MIT Professor of Brain and Cognitive Sciences Ila Fiete in her lab at the McGovern Institute. Photo: Steph Stevens

“Protein design is a hard problem because the mapping from DNA sequence to protein structure and function is really complex. There might be a great protein 10 changes away in the sequence, but each intermediate change might correspond to a totally nonfunctional protein. It’s like trying to find your way to the river basin in a mountain range, when there are craggy peaks along the way that block your view. The current work tries to make the riverbed easier to find,” says Ila Fiete, a professor of brain and cognitive sciences at MIT, a member of MIT’s McGovern Institute for Brain Research, director of the K. Lisa Yang Integrative Computational Neuroscience Center, and one of the senior authors of the study.

Regina Barzilay, the School of Engineering Distinguished Professor for AI and Health at MIT, and Tommi Jaakkola, the Thomas Siebel Professor of Electrical Engineering and Computer Science at MIT, are also senior authors of an open-access paper on the work, which will be presented at the International Conference on Learning Representations in May. MIT graduate students Andrew Kirjner and Jason Yim are the lead authors of the study. Other authors include Shahar Bracha, an MIT postdoc, and Raman Samusevich, a graduate student at Czech Technical University.

Optimizing proteins

Many naturally occurring proteins have functions that could make them useful for research or medical applications, but they need a little extra engineering to optimize them. In this study, the researchers were originally interested in developing proteins that could be used in living cells as voltage indicators. These proteins, produced by some bacteria and algae, emit fluorescent light when an electric potential is detected. If engineered for use in mammalian cells, such proteins could allow researchers to measure neuron activity without using electrodes.

While decades of research have gone into engineering these proteins to produce a stronger fluorescent signal, on a faster timescale, they haven’t become effective enough for widespread use. Bracha, who works in Edward Boyden’s lab at the McGovern Institute, reached out to Fiete’s lab to see if they could work together on a computational approach that might help speed up the process of optimizing the proteins.

“This work exemplifies the human serendipity that characterizes so much science discovery,” Fiete says.

“This work grew out of the Yang Tan Collective retreat, a scientific meeting of researchers from multiple centers at MIT with distinct missions unified by the shared support of K. Lisa Yang. We learned that some of our interests and tools in modeling how brains learn and optimize could be applied in the totally different domain of protein design, as being practiced in the Boyden lab.”

For any given protein that researchers might want to optimize, there is a nearly infinite number of possible sequences that could generated by swapping in different amino acids at each point within the sequence. With so many possible variants, it is impossible to test all of them experimentally, so researchers have turned to computational modeling to try to predict which ones will work best.

In this study, the researchers set out to overcome those challenges, using data from GFP to develop and test a computational model that could predict better versions of the protein.

They began by training a type of model known as a convolutional neural network (CNN) on experimental data consisting of GFP sequences and their brightness — the feature that they wanted to optimize.

The model was able to create a “fitness landscape” — a three-dimensional map that depicts the fitness of a given protein and how much it differs from the original sequence — based on a relatively small amount of experimental data (from about 1,000 variants of GFP).

These landscapes contain peaks that represent fitter proteins and valleys that represent less fit proteins. Predicting the path that a protein needs to follow to reach the peaks of fitness can be difficult, because often a protein will need to undergo a mutation that makes it less fit before it reaches a nearby peak of higher fitness. To overcome this problem, the researchers used an existing computational technique to “smooth” the fitness landscape.

Once these small bumps in the landscape were smoothed, the researchers retrained the CNN model and found that it was able to reach greater fitness peaks more easily. The model was able to predict optimized GFP sequences that had as many as seven different amino acids from the protein sequence they started with, and the best of these proteins were estimated to be about 2.5 times fitter than the original.

“Once we have this landscape that represents what the model thinks is nearby, we smooth it out and then we retrain the model on the smoother version of the landscape,” Kirjner says. “Now there is a smooth path from your starting point to the top, which the model is now able to reach by iteratively making small improvements. The same is often impossible for unsmoothed landscapes.”

Proof-of-concept

The researchers also showed that this approach worked well in identifying new sequences for the viral capsid of adeno-associated virus (AAV), a viral vector that is commonly used to deliver DNA. In that case, they optimized the capsid for its ability to package a DNA payload.

“We used GFP and AAV as a proof-of-concept to show that this is a method that works on data sets that are very well-characterized, and because of that, it should be applicable to other protein engineering problems,” Bracha says.

The researchers now plan to use this computational technique on data that Bracha has been generating on voltage indicator proteins.

“Dozens of labs having been working on that for two decades, and still there isn’t anything better,” she says. “The hope is that now with generation of a smaller data set, we could train a model in silico and make predictions that could be better than the past two decades of manual testing.”

The research was funded, in part, by the U.S. National Science Foundation, the Machine Learning for Pharmaceutical Discovery and Synthesis consortium, the Abdul Latif Jameel Clinic for Machine Learning in Health, the DTRA Discovery of Medical Countermeasures Against New and Emerging threats program, the DARPA Accelerated Molecular Discovery program, the Sanofi Computational Antibody Design grant, the U.S. Office of Naval Research, the Howard Hughes Medical Institute, the National Institutes of Health, the K. Lisa Yang ICoN Center, and the K. Lisa Yang and Hock E. Tan Center for Molecular Therapeutics at MIT.

Researchers reveal roadmap for AI innovation in brain and language learning

One of the hallmarks of humanity is language, but now, powerful new artificial intelligence tools also compose poetry, write songs, and have extensive conversations with human users. Tools like ChatGPT and Gemini are widely available at the tap of a button — but just how smart are these AIs?

A new multidisciplinary research effort co-led by Anna (Anya) Ivanova, assistant professor in the School of Psychology at Georgia Tech, alongside Kyle Mahowald, an assistant professor in the Department of Linguistics at the University of Texas at Austin, is working to uncover just that.

Their results could lead to innovative AIs that are more similar to the human brain than ever before — and also help neuroscientists and psychologists who are unearthing the secrets of our own minds.

The study, “Dissociating Language and Thought in Large Language Models,” is published this week in the scientific journal Trends in Cognitive Sciences. The work is already making waves in the scientific community: an earlier preprint of the paper, released in January 2023, has already been cited more than 150 times by fellow researchers. The research team has continued to refine the research for this final journal publication.

“ChatGPT became available while we were finalizing the preprint,” explains Ivanova, who conducted the research while a postdoctoral researcher at MIT’s McGovern Institute. “Over the past year, we’ve had an opportunity to update our arguments in light of this newer generation of models, now including ChatGPT.”

Form versus function

The study focuses on large language models (LLMs), which include AIs like ChatGPT. LLMs are text prediction models, and create writing by predicting which word comes next in a sentence — just like how a cell phone or email service like Gmail might suggest what next word you might want to write. However, while this type of language learning is extremely effective at creating coherent sentences, that doesn’t necessarily signify intelligence.

Ivanova’s team argues that formal competence — creating a well-structured, grammatically correct sentence — should be differentiated from functional competence — answering the right question, communicating the correct information, or appropriately communicating. They also found that while LLMs trained on text prediction are often very good at formal skills, they still struggle with functional skills.

“We humans have the tendency to conflate language and thought,” Ivanova says. “I think that’s an important thing to keep in mind as we’re trying to figure out what these models are capable of, because using that ability to be good at language, to be good at formal competence, leads many people to assume that AIs are also good at thinking — even when that’s not the case.

It’s a heuristic that we developed when interacting with other humans over thousands of years of evolution, but now in some respects, that heuristic is broken,” Ivanova explains.

The distinction between formal and functional competence is also vital in rigorously testing an AI’s capabilities, Ivanova adds. Evaluations often don’t distinguish formal and functional competence, making it difficult to assess what factors are determining a model’s success or failure. The need to develop distinct tests is one of the team’s more widely accepted findings, and one that some researchers in the field have already begun to implement.

Creating a modular system

While the human tendency to conflate functional and formal competence may have hindered understanding of LLMs in the past, our human brains could also be the key to unlocking more powerful AIs.

Leveraging the tools of cognitive neuroscience while a postdoctoral associate at Massachusetts Institute of Technology (MIT), Ivanova and her team studied brain activity in neurotypical individuals via fMRI, and used behavioral assessments of individuals with brain damage to test the causal role of brain regions in language and cognition — both conducting new research and drawing on previous studies. The team’s results showed that human brains use different regions for functional and formal competence, further supporting this distinction in AIs.

“Our research shows that in the brain, there is a language processing module and separate modules for reasoning,” Ivanova says. This modularity could also serve as a blueprint for how to develop future AIs.

“Building on insights from human brains — where the language processing system is sharply distinct from the systems that support our ability to think — we argue that the language-thought distinction is conceptually important for thinking about, evaluating, and improving large language models, especially given recent efforts to imbue these models with human-like intelligence,” says Ivanova’s former advisor and study co-author Evelina Fedorenko, a professor of brain and cognitive sciences at MIT and a member of the McGovern Institute for Brain Research.

Developing AIs in the pattern of the human brain could help create more powerful systems — while also helping them dovetail more naturally with human users. “Generally, differences in a mechanism’s internal structure affect behavior,” Ivanova says. “Building a system that has a broad macroscopic organization similar to that of the human brain could help ensure that it might be more aligned with humans down the road.”

In the rapidly developing world of AI, these systems are ripe for experimentation. After the team’s preprint was published, OpenAI announced their intention to add plug-ins to their GPT models.

“That plug-in system is actually very similar to what we suggest,” Ivanova adds. “It takes a modularity approach where the language model can be an interface to another specialized module within a system.”

While the OpenAI plug-in system will include features like booking flights and ordering food, rather than cognitively inspired features, it demonstrates that “the approach has a lot of potential,” Ivanova says.

The future of AI — and what it can tell us about ourselves

While our own brains might be the key to unlocking better, more powerful AIs, these AIs might also help us better understand ourselves. “When researchers try to study the brain and cognition, it’s often useful to have some smaller system where you can actually go in and poke around and see what’s going on before you get to the immense complexity,” Ivanova explains.

However, since human language is unique, model or animal systems are more difficult to relate. That’s where LLMs come in.

“There are lots of surprising similarities between how one would approach the study of the brain and the study of an artificial neural network” like a large language model, she adds. “They are both information processing systems that have biological or artificial neurons to perform computations.”

In many ways, the human brain is still a black box, but openly available AIs offer a unique opportunity to see the synthetic system’s inner workings and modify variables, and explore these corresponding systems like never before.

“It’s a really wonderful model that we have a lot of control over,” Ivanova says. “Neural networks — they are amazing.”

Along with Anna (Anya) Ivanova, Kyle Mahowald, and Evelina Fedorenko, the research team also includes Idan Blank (University of California, Los Angeles), as well as Nancy Kanwisher and Joshua Tenenbaum (Massachusetts Institute of Technology).

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.

School of Science announces 2024 Infinite Expansion Awards

The MIT School of Science has announced nine postdocs and research scientists as recipients of the 2024 Infinite Expansion Award, which highlights extraordinary members of the MIT community.

The following are the 2024 School of Science Infinite Expansion winners:

  • Sarthak Chandra, a research scientist in the Department of Brain and Cognitive Sciences, was nominated by Professor Ila Fiete, who wrote, “He has expanded the research abilities of my group by being a versatile and brilliant scientist, by drawing connections with a different area that he was an expert in from his PhD training, and by being a highly involved and caring mentor.”
  • Michal Fux, a research scientist in the Department of Brain and Cognitive Sciences, was nominated by Professor Pawan Sinha, who wrote, “She is one of those figurative beams of light that not only brilliantly illuminate scientific questions, but also enliven a research team.”
  • Andrew Savinov, a postdoc in the Department of Biology, was nominated by Associate Professor Gene-Wei Li, who wrote, “Andrew is an extraordinarily creative and accomplished biophysicist, as well as an outstanding contributor to the broader MIT community.”
  • Ho Fung Cheng, a postdoc in the Department of Chemistry, was nominated by Professor Jeremiah Johnson, who wrote, “His impact on research and our departmental community during his time at MIT has been outstanding, and I believe that he will be a worldclass teacher and research group leader in his independent career next year.”
  • Gabi Wenzel, a postdoc in the Department of Chemistry, was nominated by Assistant Professor Brett McGuire, who wrote, “In the one year since Gabi joined our team, she has become an indispensable leader, demonstrating exceptional skill, innovation, and dedication in our challenging research environment.”
  • Yu-An Zhang, a postdoc in the Department of Chemistry, was nominated by Professor Alison Wendlandt, who wrote, “He is a creative, deep-thinking scientist and a superb organic chemist. But above all, he is an off-scale mentor and a cherished coworker.”
  • Wouter Van de Pontseele, a senior postdoc in the Laboratory for Nuclear Science, was nominated by Professor Joseph Formaggio, who wrote, “He is a talented scientist with an intense creativity, scholarship, and student mentorship record. In the time he has been with my group, he has led multiple facets of my experimental program and has been a wonderful citizen of the MIT community.”
  • Alexander Shvonski, a lecturer in the Department of Physics, was nominated by Assistant Professor Andrew Vanderburg, who wrote, “… I have been blown away by Alex’s knowledge of education research and best practices, his skills as a teacher and course content designer, and I have been extremely grateful for his assistance.”
  • David Stoppel, a research scientist in The Picower Institute for Learning and Memory, was nominated by Professor Mark Bear and his research group, who wrote, “As impressive as his research achievements might be, David’s most genuine qualification for this award is his incredible commitment to mentorship and the dissemination of knowledge.”

Winners are honored with a monetary award and will be celebrated with family, friends, and nominators at a later date, along with recipients of the Infinite Mile Award.

Exposure to different kinds of music influences how the brain interprets rhythm

When listening to music, the human brain appears to be biased toward hearing and producing rhythms composed of simple integer ratios — for example, a series of four beats separated by equal time intervals (forming a 1:1:1 ratio).

However, the favored ratios can vary greatly between different societies, according to a large-scale study led by researchers at MIT and the Max Planck Institute for Empirical Aesthetics and carried out in 15 countries. The study included 39 groups of participants, many of whom came from societies whose traditional music contains distinctive patterns of rhythm not found in Western music.

“Our study provides the clearest evidence yet for some degree of universality in music perception and cognition, in the sense that every single group of participants that was tested exhibits biases for integer ratios. It also provides a glimpse of the variation that can occur across cultures, which can be quite substantial,” says Nori Jacoby, the study’s lead author and a former MIT postdoc, who is now a research group leader at the Max Planck Institute for Empirical Aesthetics in Frankfurt, Germany.

The brain’s bias toward simple integer ratios may have evolved as a natural error-correction system that makes it easier to maintain a consistent body of music, which human societies often use to transmit information.

“When people produce music, they often make small mistakes. Our results are consistent with the idea that our mental representation is somewhat robust to those mistakes, but it is robust in a way that pushes us toward our preexisting ideas of the structures that should be found in music,” says Josh McDermott, an associate professor of brain and cognitive sciences at MIT and a member of MIT’s McGovern Institute for Brain Research and Center for Brains, Minds, and Machines.

McDermott is the senior author of the study, which appears today in Nature Human Behaviour. The research team also included scientists from more than two dozen institutions around the world.

A global approach

The new study grew out of a smaller analysis that Jacoby and McDermott published in 2017. In that paper, the researchers compared rhythm perception in groups of listeners from the United States and the Tsimane’, an Indigenous society located in the Bolivian Amazon rainforest.

pitch perception study
Nori Jacoby, a former MIT postdoc now at the Max Planck Institute for Empirical Aesthetics, runs an experiment with a member of the Tsimane’ tribe, who have had little exposure to Western music. Photo: Josh McDermott

To measure how people perceive rhythm, the researchers devised a task in which they play a randomly generated series of four beats and then ask the listener to tap back what they heard. The rhythm produced by the listener is then played back to the listener, and they tap it back again. Over several iterations, the tapped sequences became dominated by the listener’s internal biases, also known as priors.

“The initial stimulus pattern is random, but at each iteration the pattern is pushed by the listener’s biases, such that it tends to converge to a particular point in the space of possible rhythms,” McDermott says. “That can give you a picture of what we call the prior, which is the set of internal implicit expectations for rhythms that people have in their heads.”

When the researchers first did this experiment, with American college students as the test subjects, they found that people tended to produce time intervals that are related by simple integer ratios. Furthermore, most of the rhythms they produced, such as those with ratios of 1:1:2 and 2:3:3, are commonly found in Western music.

The researchers then went to Bolivia and asked members of the Tsimane’ society to perform the same task. They found that Tsimane’ also produced rhythms with simple integer ratios, but their preferred ratios were different and appeared to be consistent with those that have been documented in the few existing records of Tsimane’ music.

“At that point, it provided some evidence that there might be very widespread tendencies to favor these small integer ratios, and that there might be some degree of cross-cultural variation. But because we had just looked at this one other culture, it really wasn’t clear how this was going to look at a broader scale,” Jacoby says.

To try to get that broader picture, the MIT team began seeking collaborators around the world who could help them gather data on a more diverse set of populations. They ended up studying listeners from 39 groups, representing 15 countries on five continents — North America, South America, Europe, Africa, and Asia.

“This is really the first study of its kind in the sense that we did the same experiment in all these different places, with people who are on the ground in those locations,” McDermott says. “That hasn’t really been done before at anything close to this scale, and it gave us an opportunity to see the degree of variation that might exist around the world.”

A grid of nine different photos showing a researcher working with an individual at a table. The individuals are wearing headphones.
Example testing sites. a, Yaranda, Bolivia. b, Montevideo, Uruguay. c, Sagele, Mali. d, Spitzkoppe, Namibia. e, Pleven, Bulgaria. f, Bamako, Mali. g, D’Kar, Botswana. h, Stockholm, Sweden. i, Guizhou, China. j, Mumbai, India. Verbal informed consent was obtained from the individuals in each photo.

Cultural comparisons

Just as they had in their original 2017 study, the researchers found that in every group they tested, people tended to be biased toward simple integer ratios of rhythm. However, not every group showed the same biases. People from North America and Western Europe, who have likely been exposed to the same kinds of music, were more likely to generate rhythms with the same ratios. However, many groups, for example those in Turkey, Mali, Bulgaria, and Botswana showed a bias for other rhythms.

“There are certain cultures where there are particular rhythms that are prominent in their music, and those end up showing up in the mental representation of rhythm,” Jacoby says.

The researchers believe their findings reveal a mechanism that the brain uses to aid in the perception and production of music.

“When you hear somebody playing something and they have errors in their performance, you’re going to mentally correct for those by mapping them onto where you implicitly think they ought to be,” McDermott says. “If you didn’t have something like this, and you just faithfully represented what you heard, these errors might propagate and make it much harder to maintain a musical system.”

Among the groups that they studied, the researchers took care to include not only college students, who are easy to study in large numbers, but also people living in traditional societies, who are more difficult to reach. Participants from those more traditional groups showed significant differences from college students living in the same countries, and from people who live in those countries but performed the test online.

“What’s very clear from the paper is that if you just look at the results from undergraduate students around the world, you vastly underestimate the diversity that you see otherwise,” Jacoby says. “And the same was true of experiments where we tested groups of people online in Brazil and India, because you’re dealing with people who have internet access and presumably have more exposure to Western music.”

The researchers now hope to run additional studies of different aspects of music perception, taking this global approach.

“If you’re just testing college students around the world or people online, things look a lot more homogenous. I think it’s very important for the field to realize that you actually need to go out into communities and run experiments there, as opposed to taking the low-hanging fruit of running studies with people in a university or on the internet,” McDermott says.

The research was funded by the James S. McDonnell Foundation, the Canadian National Science and Engineering Research Council, the South African National Research Foundation, the United States National Science Foundation, the Chilean National Research and Development Agency, the Austrian Academy of Sciences, the Japan Society for the Promotion of Science, the Keio Global Research Institute, the United Kingdom Arts and Humanities Research Council, the Swedish Research Council, and the John Fell Fund.

The brain runs an internal simulation to keep track of time

Clocks, computers, and metronomes can keep time with exquisite precision. But even in the absence of an external time keeper, we can track time on our own. We know when minutes or hours have elapsed, and we can maintain a rhythm when we dance, sing, or play music. Now, neuroscientists at the National Autonomous University of Mexico and MIT’s McGovern Institute and have discovered one way the brain keeps a beat: It runs an internal simulation, mentally recreating the perception of an external rhythm and preparing an appropriately timed response.

The discovery, reported January 10, 2024, in the journal Science Advances, illustrates how animals can think about imaginary events and use an internal model to guide their interactions with the world. “It’s a real indication of mental states as an independent driver of behavior,” says neuroscientist Mehrdad Jazayeri, an investigator at the McGovern Institute and an associate professor of brain and cognitive sciences at MIT.

Predicting the future

Jazayeri teamed up with Victor de Lafuente, a neuroscientist at the National Autonomous University of Mexico, to investigate the brain’s time-keeping ability. De Lafuente, who led the study, says they were motivated by curiosity about how the brain makes predictions and prepares for future states of the world.

De Lafuente and his team used a visual metronome to teach monkeys a simple rhythm, showing them a circle that moved between two positions on a screen to set a steady tempo. Then the metronome stopped. After a variable and unpredictable pause, the monkeys were asked to indicate where the dot would be if the metronome had carried on.

Monkeys do well at this task, successfully keeping time after the metronome stops. After the waiting period, they are usually able to identify the expected position of the circle, which they communicate by reaching towards a touchscreen.

To find out how the animals were keeping track of the metronome’s rhythm, de Lafuente’s group monitored their brain activity. In several key brain regions, they found rhythmic patterns of activity that oscillated at the same frequency as the metronome. This occurred while the monkeys watched the metronome. More remarkably, it continued after the metronome had stopped.

“The animal is seeing things going and then things stop. What we find in the brain is the continuation of that process in the animal’s mind,” Jazayeri says. “An entire network is replicating what it was doing.”

That was true in the visual cortex, where clusters of neurons respond to stimuli in specific spots within the eyes’ field of view. One set of cells in the visual cortex fired when the metronome’s circle was on the left of the screen; another set fired when the dot was on the right. As a monkey followed the visual metronome, the researchers could see these cells’ activity alternating rhythmically, tracking the movement. When the metronome stopped, the back-and-forth neural activity continued, maintaining the rhythm. “Once the stimulus was no longer visible, they were seeing the stimulus within their minds,” de Lafuente says.

They found something similar in the brain’s motor cortex, where movements are prepared and executed. De Lafuente explains that the monkeys are motionless for most of their time-keeping task; only when they are asked to indicate where the metronome’s circle should be do they move a hand to touch the screen. But the motor cortex was engaged even before it was time to move. “Within their brains there is a signal that is switching from the left to the right,” he says. “So the monkeys are thinking ‘left, right, left, right’—even when they are not moving and the world is constant.”

While some scientists have proposed that the brain may have a central time-keeping mechanism, the team’s findings indicate that entire networks can be called on to track the passage of time. The monkeys’ model of the future was surprisingly explicit, de Lafuente says, representing specific sensory stimuli and plans for movement. “This offers a potential solution to mentally tracking the dynamics in the world, which is to basically think about them in terms of how they actually would have happened,” Jazayeri says.

 

Complex, unfamiliar sentences make the brain’s language network work harder

With help from an artificial language network, MIT neuroscientists have discovered what kind of sentences are most likely to fire up the brain’s key language processing centers.

The new study reveals that sentences that are more complex, either because of unusual grammar or unexpected meaning, generate stronger responses in these language processing centers. Sentences that are very straightforward barely engage these regions, and nonsensical sequences of words don’t do much for them either.

For example, the researchers found this brain network was most active when reading unusual sentences such as “Buy sell signals remains a particular,” taken from a publicly available language dataset called C4. However, it went quiet when reading something very straightforward, such as “We were sitting on the couch.”

“The input has to be language-like enough to engage the system,” says Evelina Fedorenko, Associate Professor of Neuroscience at MIT and a member of MIT’s McGovern Institute for Brain Research. “And then within that space, if things are really easy to process, then you don’t have much of a response. But if things get difficult, or surprising, if there’s an unusual construction or an unusual set of words that you’re maybe not very familiar with, then the network has to work harder.”

Fedorenko is the senior author of the study, which appears today in Nature Human Behavior. MIT graduate student Greta Tuckute is the lead author of the paper.

Processing language

In this study, the researchers focused on language-processing regions found in the left hemisphere of the brain, which includes Broca’s area as well as other parts of the left frontal and temporal lobes of the brain.

“This language network is highly selective to language, but it’s been harder to actually figure out what is going on in these language regions,” Tuckute says. “We wanted to discover what kinds of sentences, what kinds of linguistic input, drive the left hemisphere language network.”

The researchers began by compiling a set of 1,000 sentences taken from a wide variety of sources — fiction, transcriptions of spoken words, web text, and scientific articles, among many others.

Five human participants read each of the sentences while the researchers measured their language network activity using functional magnetic resonance imaging (fMRI). The researchers then fed those same 1,000 sentences into a large language model — a model similar to ChatGPT, which learns to generate and understand language from predicting the next word in huge amounts of text — and measured the activation patterns of the model in response to each sentence.

Once they had all of those data, the researchers trained a mapping model, known as an “encoding model,” which relates the activation patterns seen in the human brain with those observed in the artificial language model. Once trained, the model could predict how the human language network would respond to any new sentence based on how the artificial language network responded to these 1,000 sentences.

The researchers then used the encoding model to identify 500 new sentences that would generate maximal activity in the human brain (the “drive” sentences), as well as sentences that would elicit minimal activity in the brain’s language network (the “suppress” sentences).

In a group of three new human participants, the researchers found these new sentences did indeed drive and suppress brain activity as predicted.

“This ‘closed-loop’ modulation of brain activity during language processing is novel,” Tuckute says. “Our study shows that the model we’re using (that maps between language-model activations and brain responses) is accurate enough to do this. This is the first demonstration of this approach in brain areas implicated in higher-level cognition, such as the language network.”

Linguistic complexity

To figure out what made certain sentences drive activity more than others, the researchers analyzed the sentences based on 11 different linguistic properties, including grammaticality, plausibility, emotional valence (positive or negative), and how easy it is to visualize the sentence content.

For each of those properties, the researchers asked participants from crowd-sourcing platforms to rate the sentences. They also used a computational technique to quantify each sentence’s “surprisal,” or how uncommon it is compared to other sentences.

This analysis revealed that sentences with higher surprisal generate higher responses in the brain. This is consistent with previous studies showing people have more difficulty processing sentences with higher surprisal, the researchers say.

Another linguistic property that correlated with the language network’s responses was linguistic complexity, which is measured by how much a sentence adheres to the rules of English grammar and how plausible it is, meaning how much sense the content makes, apart from the grammar.

Sentences at either end of the spectrum — either extremely simple, or so complex that they make no sense at all — evoked very little activation in the language network. The largest responses came from sentences that make some sense but require work to figure them out, such as “Jiffy Lube of — of therapies, yes,” which came from the Corpus of Contemporary American English dataset.

“We found that the sentences that elicit the highest brain response have a weird grammatical thing and/or a weird meaning,” Fedorenko says. “There’s something slightly unusual about these sentences.”

The researchers now plan to see if they can extend these findings in speakers of languages other than English. They also hope to explore what type of stimuli may activate language processing regions in the brain’s right hemisphere.

The research was funded by an Amazon Fellowship from the Science Hub, an International Doctoral Fellowship from the American Association of University Women, the MIT-IBM Watson AI Lab, the National Institutes of Health, the McGovern Institute, the Simons Center for the Social Brain, and MIT’s Department of Brain and Cognitive Sciences.