The way sensory prediction changes under anesthesia tells us how conscious cognition works

Our brains constantly work to make predictions about what’s going on around us to ensure that we can attend to and consider the unexpected, for instance. A new study examines how this works during consciousness and also breaks down under general anesthesia. The results add evidence to the idea that conscious thought requires synchronized communication — mediated by brain rhythms in specific frequency bands — between basic sensory and higher-order cognitive regions of the brain.

Previously, members of the research team in The Picower Institute for Learning and Memory at MIT and at Vanderbilt University had described how brain rhythms enable the brain to remain prepared to attend to surprises. Cognition-oriented brain regions (generally at the front of the brain) use relatively low-frequency alpha and beta rhythms to suppress processing by sensory regions (generally toward the back of the brain) of stimuli that have become familiar and mundane in the environment (e.g., your co-worker’s music). When sensory regions detect a surprise (e.g., the office fire alarm), they use faster-frequency gamma rhythms to tell the higher regions about it, and the higher regions process that at gamma frequencies to decide what to do (e.g., exit the building).

The new results, published Oct. 7 in the Proceedings of the National Academy of Sciences, show that when animals were under propofol-induced general anesthesia, a sensory region retained the capacity to detect simple surprises but communication with a higher cognitive region toward the front of the brain was lost, making that region unable to engage in its “top-down” regulation of the activity of the sensory region and keeping it oblivious to simple and more complex surprises alike.

What we’ve got here is failure to communicate

“What we are doing here speaks to the nature of consciousness,” says co-senior author Earl K. Miller, Picower Professor in The Picower Institute for Learning and Memory and MIT’s Department of Brain and Cognitive Sciences. “Propofol general anesthesia deactivates the top-down processes that that underlie cognition. It essentially disconnects communication between the front and back halves of the brain.”

Co-senior author Andre Bastos, an assistant professor in the psychology department at Vanderbilt and a former member of Miller’s MIT lab, adds that the study results highlight the key role of frontal areas in consciousness.

“These results are particularly important given the newfound scientific interest in the mechanisms of consciousness, and how consciousness relates to the ability of the brain to form predictions,” Bastos says.

The brain’s ability to predict is dramatically altered during anesthesia. It was interesting that the front of the brain, areas associated with cognition, were more strongly diminished in their predictive abilities than sensory areas. This suggests that prefrontal areas help to spark an “ignition” event that allows sensory information to become conscious. Sensory cortex activation by itself does not lead to conscious perception. These observations help us narrow down possible models for the mechanisms of consciousness.

Yihan Sophy Xiong, a graduate student in Bastos’ lab who led the study, says the anesthetic reduces the times in which inter-regional communication within the cortex can occur.

“In the awake brain, brain waves give short windows of opportunity for neurons to fire optimally — the ‘refresh rate’ of the brain, so to speak,” Xiong says. “This refresh rate helps organize different brain areas to communicate effectively. Anesthesia both slows down the refresh rate, which narrows these time windows for brain areas to talk to each other and makes the refresh rate less effective, so that neurons become more disorganized about when they can fire. When the refresh rate no longer works as intended, our ability to make predictions is weakened.”

Learning from oddballs

To conduct the research, the neuroscientists measured the electrical signals, “or spiking,” of hundreds of individual neurons and the coordinated rhythms of their aggregated activity (at alpha/beta and gamma frequencies), in two areas on the surface, or cortex, of the brain of two animals as they listened to sequences of tones. Sometimes the sequences would all be the same note (e.g., AAAAA). Sometimes there’d be a simple surprise that the researchers called a “local oddball” (e.g., AAAAB). But sometimes the surprise would be more complicated, or a “global oddball.” For example, after seeing a series of AAAABs, there’d all of a sudden be AAAAA, which violates the global but not the local pattern.

Prior work has suggested that a sensory region (in this case the temporoparietal area, or Tpt) can spot local oddballs on its own, Miller says. Detecting the more complicated global oddball requires the participation of a higher order region (in this case the frontal eye fields, or FEF).

The animals heard the tone sequences both while awake and while under propofol anesthesia. There were no surprises about the waking state. The researchers reaffirmed that top-down alpha/beta rhythms from FEF carried predictions to the Tpt and that Tpt would increase gamma rhythms when an oddball came up, causing FEF (and the prefrontal cortex) to respond with upticks of gamma activity as well.

But by several measures and analyses, the scientists could see these dynamics break down after the animals lost consciousness.

Under propofol, for instance, spiking activity declined overall but when a local oddball came along, Tpt spiking still increased notably but now spiking in FEF didn’t follow suit as it does during wakefulness.

Meanwhile, when a global oddball was presented during wakefulness, the researchers could use software to “decode” representation of that among neurons in FEF and the prefrontal cortex (another cognition-oriented region). They could also decode local oddballs in the Tpt. But under anesthesia the decoder could no longer reliably detect representation of local or global oddballs in FEF or the prefrontal cortex.

Moreover, when they compared rhythms in the regions amid wakeful versus unconscious states they found stark differences. When the animals were awake, oddballs increased gamma activity in both Tpt and FEF and alpha/beta rhythms decreased. Regular, non-oddball stimulation increased alpha/beta rhythms. But when the animals lost consciousness the increase in gamma rhythms from a local oddball was even greater in Tpt than when the animal was awake.

“Under propofol-mediated loss of consciousness, the inhibitory function of alpha/beta became diminished and/or eliminated, leading to disinhibition of oddballs in sensory cortex,” the authors wrote.

Other analyses of inter-region connectivity and synchrony revealed that the regions lost the ability to communicate during anesthesia.

In all, the study’s evidence suggests that conscious thought requires coordination across the cortex, from front to back, the researchers wrote.

“Our results therefore suggest an important role for prefrontal cortex activation, in addition to sensory cortex activation, for conscious perception,” the researchers wrote.

In addition to Xiong, Miller, and Bastos, the paper’s other authors are Jacob Donoghue, Mikael Lundqvist, Meredith Mahnke, Alex Major, and Emery N. Brown.

The National Institutes of Health, The JPB Foundation, and The Picower Institute for Learning and Memory funded the study.

Mixing joy and resolve, event celebrates women in science and addresses persistent inequalities

For two days at The Picower Institute for Learning and Memory at MIT, participants in the Kuggie Vallee Distinguished Lectures and Workshops celebrated the success of women in science and shared strategies to persist through, or better yet dissipate, the stiff headwinds women still face in the field.

“Everyone is here to celebrate and to inspire and advance the accomplishments of all women in science,” said host Li-Huei Tsai, Picower Professor in the Department of Brain and Cognitive Sciences and director of the Picower Institute, as she welcomed an audience that included scores of students, postdocs, and other research trainees. “It is a great feeling to have the opportunity to showcase examples of our successes and to help lift up the next generation.”

Tsai earned the honor of hosting the event after she was named a Vallee Visiting Professor in 2022 by the Vallee Foundation. Foundation president Peter Howley, a professor of pathological anatomy at Harvard University, said the global series of lectureships and workshops were created to honor Kuggie Vallee, a former Lesley College professor who worked to advance the careers of women.

During the program Sept. 24-25, speakers and audience members alike made it clear that helping women succeed requires both recognizing their achievements and resolving to change social structures in which they face marginalization.

Inspiring achievements

Lectures on the first day featured two brain scientists who have each led acclaimed discoveries that have been transforming their fields.

Michelle Monje, a pediatric neuro-oncologist at Stanford University whose recognitions include a MacArthur Fellowship, described her lab’s studies of brain cancers in children, which emerge at specific times in development as young brains adapt to their world by wiring up new circuits and insulating neurons with a fatty sheathing called myelin. Monje has discovered that when the precursors to myelinating cells, called oligodendrocyte precursor cells, harbor cancerous mutations, the tumors that arise — called gliomas — can hijack those cellular and molecular mechanisms. To promote their own growth, gliomas tap directly into the electrical activity of neural circuits by forging functional neuron-to-cancer connections, akin to the “synapse” junctions healthy neurons make with each other. Years of her lab’s studies, often led by female trainees, have not only revealed this insidious behavior (and linked aberrant myelination to many other diseases as well), but also revealed specific molecular factors involved. Those findings, Monje said, present completely novel potential avenues for therapeutic intervention.

“This cancer is an electrically active tissue and that is not how we have been approaching understanding it,” she said.

Erin Schuman stands and gestures behnind a wooden lectern with the MIT logo on it. Her audience is in the foreground, sitting in rows of auditorium-style chairs.

Erin Schuman delivers her Kuggie Vallee Distinguished Lecture on Sept. 24.

Photo: David Orenstein/Picower Institute


Erin Schuman, who directs the Max Planck Institute for Brain Research in Frankfurt, Germany, and has won honors including the Brain Prize, described her groundbreaking discoveries related to how neurons form and edit synapses along the very long branches — axons and dendrites — that give the cells their exotic shapes. Synapses form very far from the cell body where scientists had long thought all proteins, including those needed for synapse structure and activity, must be made. In the mid-1990s, Schuman showed that the protein-making process can occur at the synapse and that neurons stage the needed infrastructure — mRNA and ribosomes — near those sites. Her lab has continued to develop innovative tools to build on that insight, cataloging the stunning array of thousands of mRNAs involved, including about 800 that are primarily translated at the synapse, studying the diversity of synapses that arise from that collection, and imaging individual ribosomes such that her lab can detect when they are actively making proteins in synaptic neighborhoods.

Persistent headwinds

While the first day’s lectures showcased examples of women’s success, the second day’s workshops turned the spotlight on the social and systemic hindrances that continue to make such achievements an uphill climb. Speakers and audience members engaged in frank dialogues aimed at calling out those barriers, overcoming them, and dismantling them.

Susan Silbey, the Leon and Anne Goldberg Professor of Humanities, Sociology and Anthropology at MIT and professor of behavioral and policy sciences in the MIT Sloan School of Management, told the group that as bad as sexual harassment and assault in the workplace are, the more pervasive, damaging, and persistent headwinds for women across a variety of professions are “deeply sedimented cultural habits” that marginalize their expertise and contributions in workplaces, rendering them invisible to male counterparts, even when they are in powerful positions. High-ranking women in Silicon Valley who answered the “Elephant in the Valley” survey, for instance, reported high rates of many demeaning comments and demeanor, as well as exclusion from social circles. Even U.S. Supreme Court justices are not immune, she noted, citing research showing that for decades female justices have been interrupted with disproportionate frequency during oral arguments at the court. Silbey’s research has shown that young women entering the engineering workforce often become discouraged by a system that appears meritocratic, but in which they are often excluded from opportunities to demonstrate or be credited for that merit and are paid significantly less.

“Women’s occupational inequality is a consequence of being ignored, having contributions overlooked or appropriated, of being assigned to lower-status roles, while men are pushed ahead, honored and celebrated, often on the basis of women’s work,” Silbey said.

Often relatively small in numbers, women in such workplaces become tokens — visible as different, but still treated as outsiders, Silbey said. Women tend to internalize this status, becoming very cautious about their work while some men surge ahead in more cavalier fashion. Silbey and speakers who followed illustrated the effect this can have on women’s careers in science. Kara McKinley, an assistant professor of stem cell and regenerative biology at Harvard, noted that while the scientific career “pipeline” in some areas of science is full of female graduate students and postdocs, only about 20 percent of natural sciences faculty positions are held by women. Strikingly, women are already significantly depleted in the applicant pools for assistant professor positions, she said. Those who do apply tend to wait until they are more qualified than the men they are competing against. 

McKinley and Silbey each noted that women scientists submit fewer papers to prestigious journals, with Silbey explaining that it’s often because women are more likely to worry that their studies need to tie up every loose end. Yet, said Stacie Weninger, a venture capitalist and president of the F-Prime Biomedical Research Initiative and a former editor at Cell Press, women were also less likely than men to rebut rejections from journal editors, thereby accepting the rejection even though rebuttals sometimes work.

Nine people eat lunch at a round table in a spacious atrium. Stacie Weninger smiles as she speaks to the group. Similar tables are in the background.

Attendees of the workshops ate lunch with the event speakers, sharing stories and getting advice. Here, Stacie Weninger meets with a group of trainees.

Photo: David Orenstein/Picower Institute


Several speakers, including Weninger and Silbey, said pedagogy must change to help women overcome a social tendency to couch their assertions in caveats when many men speak with confidence and are therefore perceived as more knowledgeable.

At lunch, trainees sat in small groups with the speakers. They shared sometimes harrowing personal stories of gender-related difficulties in their young careers and sought advice on how to persist and remain resilient. Schuman advised the trainees to report mistreatment, even if they aren’t confident that university officials will be able to effect change, to at least make sure patterns of mistreatment get on the record. Reflecting on discouraging comments she experienced early in her career, Monje advised students to build up and maintain an inner voice of confidence and draw upon it when criticism is unfair.

“It feels terrible in the moment, but cream rises,” Monje said. “Believe in yourself. It will be OK in the end.”

Lifting each other up

Speakers at the conference shared many ideas to help overcome inequalities. McKinley described a program she launched in 2020 to ensure that a diversity of well-qualified women and non-binary postdocs are recruited for, and apply for, life sciences faculty jobs: the Leading Edge Symposium. The program identifies and names fellows — 200 so far — and provides career mentoring advice, a supportive community, and a platform to ensure they are visible to recruiters. Since the program began, 99 of the fellows have gone on to accept faculty positions at various institutions.

In a talk tracing the arc of her career, Weninger, who trained as a neuroscientist at Harvard, said she left bench work for a job as an editor because she wanted to enjoy the breadth of science, but also noted that her postdoc salary didn’t even cover the cost of child care. She left Cell Press in 2005 to help lead a task force on women in science that Harvard formed in the wake of comments by then-president Lawrence Summers widely understood as suggesting that women lacked “natural ability” in science and engineering. Working feverishly for months, the task force recommended steps to increase the number of senior women in science, including providing financial support for researchers who were also caregivers at home so they’d have the money to hire a technician. That extra set of hands would afford them the flexibility to keep research running even as they also attended to their families. Notably, Monje said she does this for the postdocs in her lab.

Susan Silbey stands behind a lectern in a seminar room

Susan Silbey speaks during the Kuggie Vallee workshops on Sept. 25 at MIT.

Photo: David Orenstein/Picower Institute


A graduate student asked Silbey at the end of her talk how to change a culture in which traditionally male-oriented norms marginalize women. Silbey said it starts with calling out those norms and recognizing that they are the issue, rather than increasing women’s representation in, or asking them to adapt to, existing systems.

“To make change, it requires that you do recognize the differences of the experiences and not try to make women exactly like men, or continue the past practices and think, ‘Oh, we just have to add women into it’,” she said.

Silbey also praised the Kuggie Vallee event at MIT for assembling a new community around these issues. Women in science need more social networks where they can exchange information and resources, she said.

“This is where an organ, an event like this, is an example of making just that kind of change: women making new networks for women,” she said.

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Uplifting West African communities, one cashew at a time

Ever wonder how your favorite snack was sourced? Joshua Reed-Diawuoh thinks more people should.

Reed-Diawuoh MBA ’20 is the founder and CEO of GRIA Food Company, which partners with companies that ethically source and process food in West Africa to support local food economies and help communities in the region more broadly.

“It’s very difficult for these agribusinesses and producers to start sustainable businesses and build up that value chain in the area,” says Reed-Diawuoh, who started the company as a student in the MIT Sloan School of Management. “We want to support these companies that put in the work to build integrated businesses that are employing people and uplifting communities.”

GRIA, which stands for “Grown in Africa,” is currently selling six types of flavored cashews sourced from Benin, Togo, and Burkina Faso. All of the cashews are certified by Fairtrade International, which means in addition to offering sustainable wages, access to financing, and decent working conditions, the companies receive a “Fairtrade Premium” on top of the selling price that allows them to invest in the long-term health of their communities.

“That premium is transformational,” Reed-Diawuoh says. “The premium goes to the producer cooperatives, or the farmers working the land, and they can invest that in any way they choose. They can put it back into their business, they can start new community development projects, like building schools or improving wastewater infrastructure, whatever they want.”

Cracking the nut

Reed-Diawuoh’s family is from Ghana, and before coming to MIT Sloan, he worked to support agriculture and food manufacturing for countries in Sub-Saharan Africa, with particular focus on uplifting small-scale farmers. That’s where he learned about difficulties with financing and infrastructure constraints that held many companies back.

“I wanted to get my hands dirty and start my own business that contributed to improving agricultural development in West Africa,” Reed-Diawuoh says.

He entered MIT Sloan in 2018, taking entrepreneurship classes and exploring several business ideas before deciding to ethically source produce from farmers and sell directly to consumers. He says MIT Sloan’s Sustainability Business Lab offered particularly valuable lessons for how to structure his business.

In his second year, Reed-Diawuoh was selected for a fellowship at the Legatum Center, which connected him to other entrepreneurs working in emerging markets around the world.

“Legatum was a pivotal milestone for me,” he says. “It provided me with some structure and space to develop this idea. It also gave me an incredible opportunity to take risks and explore different business concepts in a way I couldn’t have done if I was working in industry.”

The business model Reed-Diawuoh settled on for GRIA sources product from agribusiness partners in West Africa that adhere to the strictest environmental and labor standards. Reed-Diawuoh decided to start with cashews because they have many manual processing steps — from shelling to peeling and roasting — that are often done after the cashews are shipped out of West Africa, limiting the growth of local food economies and taking wealth out of communities.

Each of GRIA’s partners, from the companies harvesting cashews to the processing facilities, works directly with farmer cooperatives and small-scale farmers and is certified by Fairtrade International.

“Without proper oversight and regulations, workers oftentimes get exploited, and child labor is a huge problem across the agriculture sector,” Reed-Diawuoh says. “Fairtrade certifications try and take a robust and rigorous approach to auditing all of the businesses and their supply chains, from producers to farmers to processors. They do on-site visits and they audit financial documents. We went through this over the course of a thorough three-month review.”

After importing cashew kernels, GRIA flavors and packages them at a production facility in Boston. Reed-Diawuoh started by selling to small independent retailers in Greater Boston before scaling up GRIA’s online sales. He started ramping up production in the beginning of 2023.

“Every time we sell our product, if people weren’t already familiar with Fairtrade or ethical sourcing, we provide information on our packaging and all of our collateral,” Reed-Diawuoh says. “We want to spread this message about the importance of ethical sourcing and the importance of building up food manufacturing in West Africa in particular, but also in rising economies throughout the world.”

Making ethical sourcing mainstream

GRIA currently imports about a ton of Fairtrade cashews and kernels each quarter, and Reed-Diawuoh hopes to double that number each year for the foreseeable future.

“For each pound, we pay premiums for the kernels, and that supports this ecosystem where producers get compensated fairly for their work on the land, and agribusinesses are able to build more robust and profitable business models, because they have an end market for these Fairtrade-certified products.”

Reed-Diawuoh is currently trying out different packaging and flavors and is in discussions with partners to expand production capacity and move into Ghana. He’s also exploring corporate collaborations and has provided MIT with product over the past two years for conferences and other events.

“We’re experimenting with different growth strategies,” Reed-Diawuoh says. “We’re very much still in startup mode, but really trying to ramp up our sales and production.”

As GRIA scales, Reed-Diawuoh hopes it pushes consumers to start asking more of their favorite food brands.

“It’s absolutely critical that, if we’re sourcing produce in markets like the U.S. from places like West Africa, we’re hyper-focused on doing it in an ethical manner,” Reed-Diawuoh says. “The overall goal of GRIA is to ensure we are adhering to and promoting strict sourcing standards and being rigorous and thoughtful about the way we import product.”

New 3D printing technique creates unique objects quickly and with less waste

Multimaterial 3D printing enables makers to fabricate customized devices with multiple colors and varied textures. But the process can be time-consuming and wasteful because existing 3D printers must switch between multiple nozzles, often discarding one material before they can start depositing another.

Researchers from MIT and Delft University of Technology have now introduced a more efficient, less wasteful, and higher-precision technique that leverages heat-responsive materials to print objects that have multiple colors, shades, and textures in one step.

Their method, called speed-modulated ironing, utilizes a dual-nozzle 3D printer. The first nozzle deposits a heat-responsive filament and the second nozzle passes over the printed material to activate certain responses, such as changes in opacity or coarseness, using heat.
 

Animation of rectangular iron sweeping top layer of printing block as infrared inset shows thermal activity.
In speed-modulated ironing, the first nozzle of a dual-nozzle 3D printer deposits a heat-responsive filament and then the second nozzle passes over the printed material to activate certain responses, such as changes in opacity or coarseness, using heat.

Credit: Courtesy of the researchers

By controlling the speed of the second nozzle, the researchers can heat the material to specific temperatures, finely tuning the color, shade, and roughness of the heat-responsive filaments. Importantly, this method does not require any hardware modifications.

The researchers developed a model that predicts the amount of heat the “ironing” nozzle will transfer to the material based on its speed. They used this model as the foundation for a user interface that automatically generates printing instructions which achieve color, shade, and texture specifications.

One could use speed-modulated ironing to create artistic effects by varying the color on a printed object. The technique could also produce textured handles that would be easier to grasp for individuals with weakness in their hands.

“Today, we have desktop printers that use a smart combination of a few inks to generate a range of shades and textures. We want to be able to do the same thing with a 3D printer — use a limited set of materials to create a much more diverse set of characteristics for 3D-printed objects,” says Mustafa Doğa Doğan PhD ’24, co-author of a paper on speed-modulated ironing.

This project is a collaboration between the research groups of Zjenja Doubrovski, assistant professor at TU Delft, and Stefanie Mueller, the TIBCO Career Development Professor in the Department of Electrical Engineering and Computer Science (EECS) at MIT and a member of the MIT Computer Science and Artificial Intelligence Laboratory (CSAIL). Doğan worked closely with lead author Mehmet Ozdemir of TU Delft; Marwa AlAlawi, a mechanical engineering graduate student at MIT; and Jose Martinez Castro of TU Delft. The research will be presented at the ACM Symposium on User Interface Software and Technology.

Modulating speed to control temperature

The researchers launched the project to explore better ways to achieve multiproperty 3D printing with a single material. The use of heat-responsive filaments was promising, but most existing methods use a single nozzle to do printing and heating. The printer always needs to first heat the nozzle to the desired target temperature before depositing the material.

However, heating and cooling the nozzle takes a long time, and there is a danger that the filament in the nozzle might degrade as it reaches higher temperatures.

To prevent these problems, the team developed an ironing technique where material is printed using one nozzle, then activated by a second, empty nozzle which only reheats it. Instead of adjusting the temperature to trigger the material response, the researchers keep the temperature of the second nozzle constant and vary the speed at which it moves over the printed material, slightly touching the top of the layer.

“As we modulate the speed, that allows the printed layer we are ironing to reach different temperatures. It is similar to what happens if you move your finger over a flame. If you move it quickly, you might not be burned, but if you drag it across the flame slowly, your finger will reach a higher temperature,” AlAlawi says.

The MIT team collaborated with the TU Delft researchers to develop the theoretical model that predicts how fast the second nozzle must move to heat the material to a specific temperature.

The model correlates a material’s output temperature with its heat-responsive properties to determine the exact nozzle speed which will achieve certain colors, shades, or textures in the printed object.

“There are a lot of inputs that can affect the results we get. We are modeling something that is very complicated, but we also want to make sure the results are fine-grained,” AlAlawi says.

The team dug into scientific literature to determine proper heat transfer coefficients for a set of unique materials, which they built into their model. They also had to contend with an array of unpredictable variables, such as heat that may be dissipated by fans and the air temperature in the room where the object is being printed.

They incorporated the model into a user-friendly interface that simplifies the scientific process, automatically translating the pixels in a maker’s 3D model into a set of machine instructions that control the speed at which the object is printed and ironed by the dual nozzles.

Faster, finer fabrication

They tested their approach with three heat-responsive filaments. The first, a foaming polymer with particles that expand as they are heated, yields different shades, translucencies, and textures. They also experimented with a filament filled with wood fibers and one with cork fibers, both of which can be charred to produce increasingly darker shades.

The researchers demonstrated how their method could produce objects like water bottles that are partially translucent. To make the water bottles, they ironed the foaming polymer at low speeds to create opaque regions and higher speeds to create translucent ones. They also utilized the foaming polymer to fabricate a bike handle with varied roughness to improve a rider’s grip.

Trying to produce similar objects using traditional multimaterial 3D printing took far more time, sometimes adding hours to the printing process, and consumed more energy and material. In addition, speed-modulated ironing could produce fine-grained shade and texture gradients that other methods could not achieve.

In the future, the researchers want to experiment with other thermally responsive materials, such as plastics. They also hope to explore the use of speed-modulated ironing to modify the mechanical and acoustic properties of certain materials.