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    Summer research offers a springboard to advanced studies

    Doctoral studies at MIT aren’t a calling for everyone, but they can be for anyone who has had opportunities to discover that science and technology research is their passion and to build the experience and skills to succeed. For Taylor Baum, Josefina Correa Menéndez, and Karla Alejandra Montejo, three graduate students in just one lab of The Picower Institute for Learning and Memory, a pivotal opportunity came via the MIT Summer Research Program in Biology and Neuroscience (MSRP-Bio). When a student finds MSRP-Bio, it helps them find their future in research. 

    In the program, undergraduate STEM majors from outside MIT spend the summer doing full-time research in the departments of Biology, Brain and Cognitive Sciences (BCS), or the Center for Brains, Minds and Machines (CBMM). They gain lab skills, mentoring, preparation for graduate school, and connections that might last a lifetime. Over the last two decades, a total of 215 students from underrepresented minority groups, who are from economically disadvantaged backgrounds, first-generation or nontraditional college students, or students with disabilities have participated in research in BCS or CBMM labs.  

    Like Baum, Correa Menéndez, and Montejo, the vast majority go on to pursue graduate studies, says Diversity and Outreach Coordinator Mandana Sassanfar, who runs the program. For instance, among 91 students who have worked in Picower Institute labs, 81 have completed their undergraduate studies. Of those, 46 enrolled in PhD programs at MIT or other schools such as Cornell, Yale, Stanford, and Princeton universities, and the University of California System. Another 12 have gone to medical school, another seven are in MD/PhD programs, and three have earned master’s degrees. The rest are studying as post-baccalaureates or went straight into the workforce after earning their bachelor’s degree. 

    After participating in the program, Baum, Correa Menéndez, and Montejo each became graduate students in the research group of Emery N. Brown, the Edward Hood Taplin Professor of Computational Neuroscience and Medical Engineering in The Picower Institute and the Institute for Medical Engineering and Science. The lab combines statistical, computational, and experimental neuroscience methods to study how general anesthesia affects the central nervous system to ultimately improve patient care and advance understanding of the brain. Brown says the students have each been doing “off-the-scale” work, in keeping with the excellence he’s seen from MSRP BIO students over the years. For example, on Aug. 10 Baum and Correa Menéndez were honored with MathWorks Fellowships.

    “I think MSRP is fantastic. Mandana does this amazing job of getting students who are quite talented to come to MIT to realize that they can move their game to the next level. They have the capacity to do it. They just need the opportunities,” Brown says. “These students live up to the expectations that you have of them. And now as graduate students, they’re taking on hard problems and they’re solving them.” 

    Paths to PhD studies 

    Pursuing a PhD is hardly a given. Many young students have never considered graduate school or specific fields of study like neuroscience or electrical engineering. But Sassanfar engages students across the country to introduce them to the opportunity MSRP-Bio provides to gain exposure, experience, and mentoring in advanced fields. Every fall, after the program’s students have returned to their undergraduate institutions, she visits schools in places as far flung as Florida, Maryland, Puerto Rico, and Texas and goes to conferences for diverse science communities such as ABRCMS and SACNAS to spread the word. 

    Taylor Baum

    Photo courtesy of Taylor Baum.

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    When Baum first connected with the program in 2017, she was finding her way at Penn State University. She had been majoring in biology and music composition but had just switched the latter to engineering following a conversation over coffee exposing her to brain-computer interfacing technology, in which detecting brain signals of people with full-body paralysis could improve their quality of life by enabling control of computers or wheelchairs. Baum became enthusiastic about the potential to build similar systems, but as a new engineering student, she struggled to find summer internships and research opportunities. 

    “I got rejected from every single progam except the MIT Center for Brains, Minds and Machines MSRP,” she recalls with a chuckle. 

    Baum thrived in MSRP-Bio, working in Brown’s lab for three successive summers. At each stage, she said, she gained more research skills, experience, and independence. When she graduated, she was sure she wanted to go to graduate school and applied to four of her dream schools. She accepted MIT’s offer to join the Department of Electrical Engineering and Computer Science, where she is co-advised by faculty members there and by Brown. She is now working to develop a system grounded in cardiovascular physiology that can improve blood pressure management. A tool for practicing anesthesiologists, the system automates the dosing of drugs to maintain a patient’s blood pressure at safe levels in the operating room or intensive care unit. 

    More than that, Baum not only is leading an organization advancing STEM education in Puerto Rico, but also is helping to mentor a current MSRP-Bio student in the Brown lab. 

    “MSRP definitely bonds everyone who has participated in it,” Baum says. “If I see anyone who I know participated in MSRP, we could have an immediate conversation. I know that most of us, if we needed help, we’d feel comfortable asking for help from someone from MSRP. With that shared experience, we have a sense of camaraderie, and community.” 

    In fact, a few years ago when a former MSRP-Bio student named Karla Montejo was applying to MIT, Baum provided essential advice and feedback about the application process, Montejo says. Now, as a graduate student, Montejo has become a mentor for the program in her own right, Sassanfar notes. For instance, Montejo serves on program alumni panels that advise new MSRP-Bio students. 

    Karla Alejandra Montejo

    Photo courtesy of Karla Alejandra Montejo.

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    Montejo’s family immigrated to Miami from Cuba when she was a child. The magnet high school she attended was so new that students were encouraged to help establish the school’s programs. She forged a path into research. 

    “I didn’t even know what research was,” she says. “I wanted to be a doctor, and I thought maybe it would help me on my resume. I thought it would be kind of like shadowing, but no, it was really different. So I got really captured by research when I was in high school.” 

    Despite continuing to pursue research in college at Florida International University, Montejo didn’t get into graduate school on her first attempt because she hadn’t yet learned how to focus her application. But Sassanfar had visited FIU to recruit students and through that relationship Montejo had already gone through MIT’s related Quantitative Methods Workshop (QMW). So Montejo enrolled in MSRP-Bio, working in the CBMM-affiliated lab of Gabriel Kreiman at Boston Children’s Hospital. 

    “I feel like Mandana really helped me out, gave me a break, and the MSRP experience pretty much solidified that I really wanted to come to MIT,” Montejo says. 

    In the QMW, Montejo learned she really liked computational neuroscience, and in Kreiman’s lab she got to try her hand at computational modeling of the cognition involved in making perceptual sense of complex scenes. Montejo realized she wanted to work on more biologically based neuroscience problems. When the summer ended, because she was off the normal graduate school cycle for now, she found a two-year post-baccalaurate program at Mayo Clinic studying the role a brain cell type called astrocytes might have in the Parkinson’s disease treatment deep brain stimulation. 

    When it came time to reapply to graduate schools (with the help of Baum and others in the BCS Application Assistance Program) Montejo applied to MIT and got in, joining the Brown lab. Now she’s working on modeling the role of  metabolic processes in the changing of brain rhythms under anesthesia, taking advantage of how general anesthesia predictably changes brain states. The effects anesthetic drugs have on cell metabolism and the way that ultimately affects levels of consciousness reveals important aspects of how metabolism affects brain circuits and systems. Earlier this month, for instance, Montejo co-led a paper the lab published in The Proceedings of the National Academy of Sciences detailing the neuroscience of a patient’s transition into an especially deep state of unconsciousness called “burst suppression.” 

    Josefina Correa Menendez

    Photo: David Orenstein

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    A signature of the Brown lab’s work is rigorous statistical analysis and methods, for instance to discern brain arousal states from EEG measures of brain rhythms. A PhD candidate in MIT’s Interdisciplinary Doctoral Program in Statistics, Correa Menéndez is advancing the use of Bayesian hierarchical models for neural data analysis. These statistical models offer a principled way of pooling information across datasets. One of her models can help scientists better understand the way neurons can “spike” with electrical activity when the brain is presented with a stimulus. The other’s power is in discerning critical features such as arousal states of the brain under general anesthesia from electrophysiological recordings. 

    Though she now works with complex equations and computations as a PhD candidate in neuroscience and statistics, Correa Menéndez was mostly interested in music art as a high school student at Academia María Reina in San Juan and then architecture in college at the University of Puerto Rico at Río Piedras. It was discussions at the intersection of epistemology and art during an art theory class that inspired Correa Menéndez to switch her major to biology and to take computer science classes, too. 

    When Sassanfar visited Puerto Rico in 2017, a computer science professor (Patricia Ordóñez) suggested that Correa Menéndez apply for a chance to attend the QMW. She did, and that led her to also participate in MSRP-Bio in the lab of Sherman Fairchild Professor Matt Wilson (a faculty member in BCS, CBMM, and the Picower Institute). She joined in the lab’s studies of how spatial memories are represented in the hippocampus and how the brain makes use of those memories to help understand the world around it. With mentoring from then-postdoc Carmen Varela (now a faculty member at Florida State University), the experience not only exposed her to neuroscience, but also helped her gain skills and experience with lab experiments, building research tools, and conducting statistical analyses. She ended up working in the Wilson lab as a research scholar for a year and began her graduate studies in September 2018.  

    Classes she took with Brown as a research scholar inspired her to join his lab as a graduate student. 

    “Taking the classes with Emery and also doing experiments made me aware of the role of statistics in the scientific process: from the interpretation of results to the analysis and the design of experiments,” she says. “More often than not, in science, statistics becomes this sort of afterthought — this ‘annoying’ thing that people need to do to get their paper published. But statistics as a field is actually a lot more than that. It’s a way of thinking about data. Particularly, Bayesian modeling provides a principled inference framework for combining prior knowledge into a hypothesis that you can test with data.” 

    To be sure, no one starts out with such inspiration about scientific scholarship, but MSRP-Bio helps students find that passion for research and the paths that opens up.   More

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    Drones navigate unseen environments with liquid neural networks

    In the vast, expansive skies where birds once ruled supreme, a new crop of aviators is taking flight. These pioneers of the air are not living creatures, but rather a product of deliberate innovation: drones. But these aren’t your typical flying bots, humming around like mechanical bees. Rather, they’re avian-inspired marvels that soar through the sky, guided by liquid neural networks to navigate ever-changing and unseen environments with precision and ease.

    Inspired by the adaptable nature of organic brains, researchers from MIT’s Computer Science and Artificial Intelligence Laboratory (CSAIL) have introduced a method for robust flight navigation agents to master vision-based fly-to-target tasks in intricate, unfamiliar environments. The liquid neural networks, which can continuously adapt to new data inputs, showed prowess in making reliable decisions in unknown domains like forests, urban landscapes, and environments with added noise, rotation, and occlusion. These adaptable models, which outperformed many state-of-the-art counterparts in navigation tasks, could enable potential real-world drone applications like search and rescue, delivery, and wildlife monitoring.

    The researchers’ recent study, published today in Science Robotics, details how this new breed of agents can adapt to significant distribution shifts, a long-standing challenge in the field. The team’s new class of machine-learning algorithms, however, captures the causal structure of tasks from high-dimensional, unstructured data, such as pixel inputs from a drone-mounted camera. These networks can then extract crucial aspects of a task (i.e., understand the task at hand) and ignore irrelevant features, allowing acquired navigation skills to transfer targets seamlessly to new environments.

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    Drones navigate unseen environments with liquid neural networks.

    “We are thrilled by the immense potential of our learning-based control approach for robots, as it lays the groundwork for solving problems that arise when training in one environment and deploying in a completely distinct environment without additional training,” says Daniela Rus, CSAIL director and the Andrew (1956) and Erna Viterbi Professor of Electrical Engineering and Computer Science at MIT. “Our experiments demonstrate that we can effectively teach a drone to locate an object in a forest during summer, and then deploy the model in winter, with vastly different surroundings, or even in urban settings, with varied tasks such as seeking and following. This adaptability is made possible by the causal underpinnings of our solutions. These flexible algorithms could one day aid in decision-making based on data streams that change over time, such as medical diagnosis and autonomous driving applications.”

    A daunting challenge was at the forefront: Do machine-learning systems understand the task they are given from data when flying drones to an unlabeled object? And, would they be able to transfer their learned skill and task to new environments with drastic changes in scenery, such as flying from a forest to an urban landscape? What’s more, unlike the remarkable abilities of our biological brains, deep learning systems struggle with capturing causality, frequently over-fitting their training data and failing to adapt to new environments or changing conditions. This is especially troubling for resource-limited embedded systems, like aerial drones, that need to traverse varied environments and respond to obstacles instantaneously. 

    The liquid networks, in contrast, offer promising preliminary indications of their capacity to address this crucial weakness in deep learning systems. The team’s system was first trained on data collected by a human pilot, to see how they transferred learned navigation skills to new environments under drastic changes in scenery and conditions. Unlike traditional neural networks that only learn during the training phase, the liquid neural net’s parameters can change over time, making them not only interpretable, but more resilient to unexpected or noisy data. 

    In a series of quadrotor closed-loop control experiments, the drones underwent range tests, stress tests, target rotation and occlusion, hiking with adversaries, triangular loops between objects, and dynamic target tracking. They tracked moving targets, and executed multi-step loops between objects in never-before-seen environments, surpassing performance of other cutting-edge counterparts. 

    The team believes that the ability to learn from limited expert data and understand a given task while generalizing to new environments could make autonomous drone deployment more efficient, cost-effective, and reliable. Liquid neural networks, they noted, could enable autonomous air mobility drones to be used for environmental monitoring, package delivery, autonomous vehicles, and robotic assistants. 

    “The experimental setup presented in our work tests the reasoning capabilities of various deep learning systems in controlled and straightforward scenarios,” says MIT CSAIL Research Affiliate Ramin Hasani. “There is still so much room left for future research and development on more complex reasoning challenges for AI systems in autonomous navigation applications, which has to be tested before we can safely deploy them in our society.”

    “Robust learning and performance in out-of-distribution tasks and scenarios are some of the key problems that machine learning and autonomous robotic systems have to conquer to make further inroads in society-critical applications,” says Alessio Lomuscio, professor of AI safety in the Department of Computing at Imperial College London. “In this context, the performance of liquid neural networks, a novel brain-inspired paradigm developed by the authors at MIT, reported in this study is remarkable. If these results are confirmed in other experiments, the paradigm here developed will contribute to making AI and robotic systems more reliable, robust, and efficient.”

    Clearly, the sky is no longer the limit, but rather a vast playground for the boundless possibilities of these airborne marvels. 

    Hasani and PhD student Makram Chahine; Patrick Kao ’22, MEng ’22; and PhD student Aaron Ray SM ’21 wrote the paper with Ryan Shubert ’20, MEng ’22; MIT postdocs Mathias Lechner and Alexander Amini; and Rus.

    This research was supported, in part, by Schmidt Futures, the U.S. Air Force Research Laboratory, the U.S. Air Force Artificial Intelligence Accelerator, and the Boeing Co. More

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    Neurodegenerative disease can progress in newly identified patterns

    Neurodegenerative diseases — like amyotrophic lateral sclerosis (ALS, or Lou Gehrig’s disease), Alzheimer’s, and Parkinson’s — are complicated, chronic ailments that can present with a variety of symptoms, worsen at different rates, and have many underlying genetic and environmental causes, some of which are unknown. ALS, in particular, affects voluntary muscle movement and is always fatal, but while most people survive for only a few years after diagnosis, others live with the disease for decades. Manifestations of ALS can also vary significantly; often slower disease development correlates with onset in the limbs and affecting fine motor skills, while the more serious, bulbar ALS impacts swallowing, speaking, breathing, and mobility. Therefore, understanding the progression of diseases like ALS is critical to enrollment in clinical trials, analysis of potential interventions, and discovery of root causes.

    However, assessing disease evolution is far from straightforward. Current clinical studies typically assume that health declines on a downward linear trajectory on a symptom rating scale, and use these linear models to evaluate whether drugs are slowing disease progression. However, data indicate that ALS often follows nonlinear trajectories, with periods where symptoms are stable alternating with periods when they are rapidly changing. Since data can be sparse, and health assessments often rely on subjective rating metrics measured at uneven time intervals, comparisons across patient populations are difficult. These heterogenous data and progression, in turn, complicate analyses of invention effectiveness and potentially mask disease origin.

    Now, a new machine-learning method developed by researchers from MIT, IBM Research, and elsewhere aims to better characterize ALS disease progression patterns to inform clinical trial design.

    “There are groups of individuals that share progression patterns. For example, some seem to have really fast-progressing ALS and others that have slow-progressing ALS that varies over time,” says Divya Ramamoorthy PhD ’22, a research specialist at MIT and lead author of a new paper on the work that was published this month in Nature Computational Science. “The question we were asking is: can we use machine learning to identify if, and to what extent, those types of consistent patterns across individuals exist?”

    Their technique, indeed, identified discrete and robust clinical patterns in ALS progression, many of which are non-linear. Further, these disease progression subtypes were consistent across patient populations and disease metrics. The team additionally found that their method can be applied to Alzheimer’s and Parkinson’s diseases as well.

    Joining Ramamoorthy on the paper are MIT-IBM Watson AI Lab members Ernest Fraenkel, a professor in the MIT Department of Biological Engineering; Research Scientist Soumya Ghosh of IBM Research; and Principal Research Scientist Kenney Ng, also of IBM Research. Additional authors include Kristen Severson PhD ’18, a senior researcher at Microsoft Research and former member of the Watson Lab and of IBM Research; Karen Sachs PhD ’06 of Next Generation Analytics; a team of researchers with Answer ALS; Jonathan D. Glass and Christina N. Fournier of the Emory University School of Medicine; the Pooled Resource Open-Access ALS Clinical Trials Consortium; ALS/MND Natural History Consortium; Todd M. Herrington of Massachusetts General Hospital (MGH) and Harvard Medical School; and James D. Berry of MGH.

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    MIT Professor Ernest Fraenkel describes early stages of his research looking at root causes of amyotrophic lateral sclerosis (ALS).

    Reshaping health decline

    After consulting with clinicians, the team of machine learning researchers and neurologists let the data speak for itself. They designed an unsupervised machine-learning model that employed two methods: Gaussian process regression and Dirichlet process clustering. These inferred the health trajectories directly from patient data and automatically grouped similar trajectories together without prescribing the number of clusters or the shape of the curves, forming ALS progression “subtypes.” Their method incorporated prior clinical knowledge in the way of a bias for negative trajectories — consistent with expectations for neurodegenerative disease progressions — but did not assume any linearity. “We know that linearity is not reflective of what’s actually observed,” says Ng. “The methods and models that we use here were more flexible, in the sense that, they capture what was seen in the data,” without the need for expensive labeled data and prescription of parameters.

    Primarily, they applied the model to five longitudinal datasets from ALS clinical trials and observational studies. These used the gold standard to measure symptom development: the ALS functional rating scale revised (ALSFRS-R), which captures a global picture of patient neurological impairment but can be a bit of a “messy metric.” Additionally, performance on survivability probabilities, forced vital capacity (a measurement of respiratory function), and subscores of ALSFRS-R, which looks at individual bodily functions, were incorporated.

    New regimes of progression and utility

    When their population-level model was trained and tested on these metrics, four dominant patterns of disease popped out of the many trajectories — sigmoidal fast progression, stable slow progression, unstable slow progression, and unstable moderate progression — many with strong nonlinear characteristics. Notably, it captured trajectories where patients experienced a sudden loss of ability, called a functional cliff, which would significantly impact treatments, enrollment in clinical trials, and quality of life.

    The researchers compared their method against other commonly used linear and nonlinear approaches in the field to separate the contribution of clustering and linearity to the model’s accuracy. The new work outperformed them, even patient-specific models, and found that subtype patterns were consistent across measures. Impressively, when data were withheld, the model was able to interpolate missing values, and, critically, could forecast future health measures. The model could also be trained on one ALSFRS-R dataset and predict cluster membership in others, making it robust, generalizable, and accurate with scarce data. So long as 6-12 months of data were available, health trajectories could be inferred with higher confidence than conventional methods.

    The researchers’ approach also provided insights into Alzheimer’s and Parkinson’s diseases, both of which can have a range of symptom presentations and progression. For Alzheimer’s, the new technique could identify distinct disease patterns, in particular variations in the rates of conversion of mild to severe disease. The Parkinson’s analysis demonstrated a relationship between progression trajectories for off-medication scores and disease phenotypes, such as the tremor-dominant or postural instability/gait difficulty forms of Parkinson’s disease.

    The work makes significant strides to find the signal amongst the noise in the time-series of complex neurodegenerative disease. “The patterns that we see are reproducible across studies, which I don’t believe had been shown before, and that may have implications for how we subtype the [ALS] disease,” says Fraenkel. As the FDA has been considering the impact of non-linearity in clinical trial designs, the team notes that their work is particularly pertinent.

    As new ways to understand disease mechanisms come online, this model provides another tool to pick apart illnesses like ALS, Alzheimer’s, and Parkinson’s from a systems biology perspective.

    “We have a lot of molecular data from the same patients, and so our long-term goal is to see whether there are subtypes of the disease,” says Fraenkel, whose lab looks at cellular changes to understand the etiology of diseases and possible targets for cures. “One approach is to start with the symptoms … and see if people with different patterns of disease progression are also different at the molecular level. That might lead you to a therapy. Then there’s the bottom-up approach, where you start with the molecules” and try to reconstruct biological pathways that might be affected. “We’re going [to be tackling this] from both ends … and finding if something meets in the middle.”

    This research was supported, in part, by the MIT-IBM Watson AI Lab, the Muscular Dystrophy Association, Department of Veterans Affairs of Research and Development, the Department of Defense, NSF Gradate Research Fellowship Program, Siebel Scholars Fellowship, Answer ALS, the United States Army Medical Research Acquisition Activity, National Institutes of Health, and the NIH/NINDS. More

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    Emery Brown wins a share of 2022 Gruber Neuroscience Prize

    The Gruber Foundation announced on May 17 that Emery N. Brown, the Edward Hood Taplin Professor of Medical Engineering and Computational Neuroscience at MIT, has won the 2022 Gruber Neuroscience Prize along with neurophysicists Laurence Abbott of Columbia University, Terrence Sejnowski of the Salk Institute for Biological Studies, and Haim Sompolinsky of the Hebrew University of Jerusalem.

    The foundation says it honored the four recipients for their influential contributions to the fields of computational and theoretical neuroscience. As datasets have grown ever larger and more complex, these fields have increasingly helped scientists unravel the mysteries of how the brain functions in both health and disease. The prize, which includes a total $500,000 award, will be presented in San Diego, California, on Nov. 13 at the annual meeting of the Society for Neuroscience.

    “These four remarkable scientists have applied their expertise in mathematical and statistical analysis, physics, and machine learning to create theories, mathematical models, and tools that have greatly advanced how we study and understand the brain,” says Joshua Sanes, professor of molecular and cellular biology and founding director of the Center for Brain Science at Harvard University and member of the selection advisory board to the prize. “Their insights and research have not only transformed how experimental neuroscientists do their research, but also are leading to promising new ways of providing clinical care.”

    Brown, who is an investigator in The Picower Institute for Learning and Memory and the Institute for Medical Engineering and Science at MIT, an anesthesiologist at Massachusetts General Hospital, and a professor at Harvard Medical School, says: “It is a pleasant surprise and tremendous honor to be named a co-recipient of the 2022 Gruber Prize in Neuroscience. I am especially honored to share this award with three luminaries in computational and theoretical neuroscience.”

    Brown’s early groundbreaking findings in neuroscience included a novel algorithm that decodes the position of an animal by observing the activity of a small group of place cells in the animal’s brain, a discovery he made while working with fellow Picower Institute investigator Matt Wilson in the 1990s. The resulting state-space algorithm for point processes not only offered much better decoding with fewer neurons than previous approaches, but it also established a new framework for specifying dynamically the relationship between the spike trains (the timing sequence of firing neurons) in the brain and factors from the outside world.

    “One of the basic questions at the time was whether an animal holds a representation of where it is in its mind — in the hippocampus,” Brown says. “We were able to show that it did, and we could show that with only 30 neurons.”

    After introducing this state-space paradigm to neuroscience, Brown went on to refine the original idea and apply it to other dynamic situations — to simultaneously track neural activity and learning, for example, and to define with precision anesthesia-induced loss of consciousness, as well as its subsequent recovery. In the early 2000s, Brown put together a team to specifically study anesthesia’s effects on the brain.

    Through experimental research and mathematical modeling, Brown and his team showed that the altered arousal states produced by the main classes of anesthesia medications can be characterized by analyzing the oscillatory patterns observed in the EEG along with the locations of their molecular targets, and the anatomy and physiology of the neural circuits that connect those locations. He has established, including in recent papers with Picower Professor Earl K. Miller, that a principal way in which anesthetics produce unconsciousness is by producing oscillations that impair how different brain regions communicate with each other.

    The result of Brown’s research has been a new paradigm for brain monitoring during general anesthesia for surgery, one that allows an anesthesiologist to dose the patient based on EEG readouts (neural oscillations) of the patient’s anesthetic state rather than purely on vital sign responses. This pioneering approach promises to revolutionize how anesthesia medications are delivered to patients, and also shed light on other altered states of arousal such as sleep and coma.

    To advance that vision, Brown recently discussed how he is working to develop a new research center at MIT and MGH to further integrate anesthesiology with neuroscience research. The Brain Arousal State Control Innovation Center, he said, would not only advance anesthesiology care but also harness insights gained from anesthesiology research to improve other aspects of clinical neuroscience.

    “By demonstrating that physics and mathematics can make an enormous contribution to neuroscience, doctors Abbott, Brown, Sejnowski, and Sompolinsky have inspired an entire new generation of physicists and other quantitative scientists to follow in their footsteps,” says Frances Jensen, professor and chair of the Department of Neurology and co-director of the Penn Medicine Translational Neuroscience Center within the Perelman School of Medicine at the University of Pennsylvania, and chair of the Selection Advisory Board to the prize. “The ramifications for neuroscience have been broad and profound. It is a great pleasure to be honoring each of them with this prestigious award.”

    This report was adapted from materials provided by the Gruber Foundation. More

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    Emery Brown earns American Institute for Medical and Biological Engineering Pierre Galletti Award

    The American Institute for Medical and Biological Engineering has awarded its highest honor this year to Emery N. Brown, the Edward Hood Taplin Professor of Computational Neuroscience and Health Sciences and Technology in The Picower Institute for Learning and Memory and the Institute for Medical Engineering and Science at MIT.

    Brown, who is also an anesthesiologist at Massachusetts General Hospital and the Warren M. Zapol Professor at Harvard Medical School, received the 2022 Pierre M. Galletti Award during the national organization’s Annual Event held on March 25.

    For decades, Brown’s lab has uniquely unified three fields: neuroscience, statistics, and anesthesiology. He is renowned for the development of statistical methods and signal-processing algorithms to enable and improve analysis of neural activity measurements. The work has had numerous applications including studies of learning and memory, brain-computer interfaces, and systems neuroscience. He has also pioneered investigations of how general anesthetic drugs work in the brain to induce and maintain simultaneous but reversible states of unconsciousness, amnesia, immobility, and analgesia. Building on these improvements in fundamental understanding, his lab engineers systems to improve monitoring of patient state and anesthetic dosing during surgery. Optimizing doses of general anesthetic drugs can improve patient care in many ways, including by minimizing side effects such as post-operative delirium and by improving post-operative pain management.

    AIMBE said Brown earned the award in recognition of his “significant contributions to neuroscience data analysis and for characterizing the neurophysiology of anesthesia-induced unconsciousness and demonstrating how it can be reliably monitored in real time using electroencephalogram recordings.”

    Brown, who is also a faculty member in MIT’s Department of Brain and Cognitive Sciences, is now working to develop a research center at MIT dedicated to taking neuroscience-based approaches to advance anesthesiology.

    “I am extremely honored and grateful to the AIMBE for choosing me to receive the 2022 Galletti Award in recognition of my research deciphering the neuroscience of how anesthetics work,” he says. “I would like to express my gratitude to my collaborators, post-doctoral fellows, students, research assistants, and clinical coordinators who have made this possible.” More

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    Can machine-learning models overcome biased datasets?

    Artificial intelligence systems may be able to complete tasks quickly, but that doesn’t mean they always do so fairly. If the datasets used to train machine-learning models contain biased data, it is likely the system could exhibit that same bias when it makes decisions in practice.

    For instance, if a dataset contains mostly images of white men, then a facial-recognition model trained with these data may be less accurate for women or people with different skin tones.

    A group of researchers at MIT, in collaboration with researchers at Harvard University and Fujitsu Ltd., sought to understand when and how a machine-learning model is capable of overcoming this kind of dataset bias. They used an approach from neuroscience to study how training data affects whether an artificial neural network can learn to recognize objects it has not seen before. A neural network is a machine-learning model that mimics the human brain in the way it contains layers of interconnected nodes, or “neurons,” that process data.

    The new results show that diversity in training data has a major influence on whether a neural network is able to overcome bias, but at the same time dataset diversity can degrade the network’s performance. They also show that how a neural network is trained, and the specific types of neurons that emerge during the training process, can play a major role in whether it is able to overcome a biased dataset.

    “A neural network can overcome dataset bias, which is encouraging. But the main takeaway here is that we need to take into account data diversity. We need to stop thinking that if you just collect a ton of raw data, that is going to get you somewhere. We need to be very careful about how we design datasets in the first place,” says Xavier Boix, a research scientist in the Department of Brain and Cognitive Sciences (BCS) and the Center for Brains, Minds, and Machines (CBMM), and senior author of the paper.  

    Co-authors include former MIT graduate students Timothy Henry, Jamell Dozier, Helen Ho, Nishchal Bhandari, and Spandan Madan, a corresponding author who is currently pursuing a PhD at Harvard; Tomotake Sasaki, a former visiting scientist now a senior researcher at Fujitsu Research; Frédo Durand, a professor of electrical engineering and computer science at MIT and a member of the Computer Science and Artificial Intelligence Laboratory; and Hanspeter Pfister, the An Wang Professor of Computer Science at the Harvard School of Enginering and Applied Sciences. The research appears today in Nature Machine Intelligence.

    Thinking like a neuroscientist

    Boix and his colleagues approached the problem of dataset bias by thinking like neuroscientists. In neuroscience, Boix explains, it is common to use controlled datasets in experiments, meaning a dataset in which the researchers know as much as possible about the information it contains.

    The team built datasets that contained images of different objects in varied poses, and carefully controlled the combinations so some datasets had more diversity than others. In this case, a dataset had less diversity if it contains more images that show objects from only one viewpoint. A more diverse dataset had more images showing objects from multiple viewpoints. Each dataset contained the same number of images.

    The researchers used these carefully constructed datasets to train a neural network for image classification, and then studied how well it was able to identify objects from viewpoints the network did not see during training (known as an out-of-distribution combination). 

    For example, if researchers are training a model to classify cars in images, they want the model to learn what different cars look like. But if every Ford Thunderbird in the training dataset is shown from the front, when the trained model is given an image of a Ford Thunderbird shot from the side, it may misclassify it, even if it was trained on millions of car photos.

    The researchers found that if the dataset is more diverse — if more images show objects from different viewpoints — the network is better able to generalize to new images or viewpoints. Data diversity is key to overcoming bias, Boix says.

    “But it is not like more data diversity is always better; there is a tension here. When the neural network gets better at recognizing new things it hasn’t seen, then it will become harder for it to recognize things it has already seen,” he says.

    Testing training methods

    The researchers also studied methods for training the neural network.

    In machine learning, it is common to train a network to perform multiple tasks at the same time. The idea is that if a relationship exists between the tasks, the network will learn to perform each one better if it learns them together.

    But the researchers found the opposite to be true — a model trained separately for each task was able to overcome bias far better than a model trained for both tasks together.

    “The results were really striking. In fact, the first time we did this experiment, we thought it was a bug. It took us several weeks to realize it was a real result because it was so unexpected,” he says.

    They dove deeper inside the neural networks to understand why this occurs.

    They found that neuron specialization seems to play a major role. When the neural network is trained to recognize objects in images, it appears that two types of neurons emerge — one that specializes in recognizing the object category and another that specializes in recognizing the viewpoint.

    When the network is trained to perform tasks separately, those specialized neurons are more prominent, Boix explains. But if a network is trained to do both tasks simultaneously, some neurons become diluted and don’t specialize for one task. These unspecialized neurons are more likely to get confused, he says.

    “But the next question now is, how did these neurons get there? You train the neural network and they emerge from the learning process. No one told the network to include these types of neurons in its architecture. That is the fascinating thing,” he says.

    That is one area the researchers hope to explore with future work. They want to see if they can force a neural network to develop neurons with this specialization. They also want to apply their approach to more complex tasks, such as objects with complicated textures or varied illuminations.

    Boix is encouraged that a neural network can learn to overcome bias, and he is hopeful their work can inspire others to be more thoughtful about the datasets they are using in AI applications.

    This work was supported, in part, by the National Science Foundation, a Google Faculty Research Award, the Toyota Research Institute, the Center for Brains, Minds, and Machines, Fujitsu Research, and the MIT-Sensetime Alliance on Artificial Intelligence. More

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    Professor Emery Brown has big plans for anesthesiology

    Emery N. Brown — the Edward Hood Taplin Professor of Medical Engineering and of Computational Neuroscience at MIT, an MIT professor of health sciences and technology, an investigator with The Picower Institute for Learning and Memory at MIT, and the Warren M. Zapol Professor of Anaesthesia at Harvard Medical School and Massachusetts General Hospital (MGH) — clearly excels at many roles. Renowned internationally for his anesthesia and neuroscience research, he embodies a unique blend of anesthesiologist, statistician, neuroscientist, educator, and mentor to both students and colleagues. Notably, Brown is one of the most decorated clinician-scientists in the country; he is one of only 25 people — and the first African-American, statistician, and anesthesiologist — to be elected to all three National Academies (Science, Engineering, and Medicine).

    Now, he is handing off one of his many key roles and responsibilities. After almost 10 years, Brown is stepping down as co-director of the Harvard-MIT Program in Health Sciences and Technology (HST). He will turn his energies toward working to develop a new joint center between MIT and MGH that uses the study of anesthesia to design novel approaches to controlling brain states. While a goal of the new center will be to improve anesthesia and intensive care unit management, according to Brown, it will also study related problems such as treating depression, insomnia, and epilepsy, as well as enhancing coma recovery.

    Founded in 1970, HST is one of the oldest interdisciplinary educational programs focused on training the next generation of clinician-scientists and engineers, who learn to translate science, engineering, and medical research into clinical practice, with the aim of improving human health. The MIT Institute for Medical Engineering and Science (IMES), where Brown is associate director, is HST’s home at MIT. Brown was the first HST co-director after the establishment of IMES in 2012; Wolfram Goessling is the Harvard University co-director of HST.

    “Emery has been an exemplary leader for HST during his tenure, and has helped it become a hub for the training of world-class scientists, engineers, and clinicians,” says Anantha Chandrakasan, dean of the MIT School of Engineering and the Vannevar Bush Professor of Electrical Engineering and Computer Science. “I am deeply grateful for his many years of service and wish him well as he moves on to new endeavors.”

    Elazer R. Edelman, director of IMES, calls Brown “a phenom who has been dedicated to our programs for years.”

    “With his thoughtful leadership and understated style, Emery made many contributions to the HST community,” Edelman continues. “On a personal note, this is bittersweet for me, as Emery has been a partner and mentor in my role as IMES director. And while I know that he will always be there for me, as he has been for all of us at IMES and HST, I will miss our late-night calls and midday conferences on matters of import for MIT, IMES, and HST.”

    Brown says “it was an honor and a privilege to co-direct HST with Wolfram.”

    “The students, staff, and faculty are simply amazing,” Brown continues. “Although, now more than 50 years old, HST remains at the vanguard for training PhD and MD students to work at the intersection between engineering, science, and medicine.”

    Goessling also thanks Brown for his leadership: “I truly valued Emery’s partnership and friendship, working together to deepen ties between the MIT and Harvard sides of HST. I am particularly grateful for working with Emery on our combined diversity efforts, leading to the HST Diversity Ambassadors initiative that made HST a better and stronger program.”

    According to Edelman, Brown was instrumental in the transition to new paradigms and relationships with HMS in the context of IMES. In 2014, he led the establishment of clear criteria for HST faculty membership, thereby strengthening the community of faculty experts who train students and provide research opportunities. More recently, he provided guidance through the turmoil of the ongoing Covid-19 pandemic, including the transition to online instruction and the return to the classroom. And Brown has always been a strong supporter of student diversity efforts, serving as an advocate and advisor to HST students.

    Brown holds BA, MA, and PhD degrees from Harvard University, and an MD from Harvard Medical School. He has been recognized with many awards, including the 2020 Swartz Prize in Theoretical and Computational Neuroscience, the 2018 Dickson Prize in Science, and an NIH Director’s Pioneer Award. Brown also served on President Barack Obama’s BRAIN Initiative Working Group. Among his many accomplishments, he has been cited for developing neural signal processing algorithms to characterize how neural systems represent and transmit information, and for unlocking the neurophysiology of how anesthetics produce the states of general anesthesia.

    Edelman says the process is underway to name a successor to Brown as co-director of HST at MIT. More

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    Taming the data deluge

    An oncoming tsunami of data threatens to overwhelm huge data-rich research projects on such areas that range from the tiny neutrino to an exploding supernova, as well as the mysteries deep within the brain. 

    When LIGO picks up a gravitational-wave signal from a distant collision of black holes and neutron stars, a clock starts ticking for capturing the earliest possible light that may accompany them: time is of the essence in this race. Data collected from electrical sensors monitoring brain activity are outpacing computing capacity. Information from the Large Hadron Collider (LHC)’s smashed particle beams will soon exceed 1 petabit per second. 

    To tackle this approaching data bottleneck in real-time, a team of researchers from nine institutions led by the University of Washington, including MIT, has received $15 million in funding to establish the Accelerated AI Algorithms for Data-Driven Discovery (A3D3) Institute. From MIT, the research team includes Philip Harris, assistant professor of physics, who will serve as the deputy director of the A3D3 Institute; Song Han, assistant professor of electrical engineering and computer science, who will serve as the A3D3’s co-PI; and Erik Katsavounidis, senior research scientist with the MIT Kavli Institute for Astrophysics and Space Research.

    Infused with this five-year Harnessing the Data Revolution Big Idea grant, and jointly funded by the Office of Advanced Cyberinfrastructure, A3D3 will focus on three data-rich fields: multi-messenger astrophysics, high-energy particle physics, and brain imaging neuroscience. By enriching AI algorithms with new processors, A3D3 seeks to speed up AI algorithms for solving fundamental problems in collider physics, neutrino physics, astronomy, gravitational-wave physics, computer science, and neuroscience. 

    “I am very excited about the new Institute’s opportunities for research in nuclear and particle physics,” says Laboratory for Nuclear Science Director Boleslaw Wyslouch. “Modern particle detectors produce an enormous amount of data, and we are looking for extraordinarily rare signatures. The application of extremely fast processors to sift through these mountains of data will make a huge difference in what we will measure and discover.”

    The seeds of A3D3 were planted in 2017, when Harris and his colleagues at Fermilab and CERN decided to integrate real-time AI algorithms to process the incredible rates of data at the LHC. Through email correspondence with Han, Harris’ team built a compiler, HLS4ML, that could run an AI algorithm in nanoseconds.

    “Before the development of HLS4ML, the fastest processing that we knew of was roughly a millisecond per AI inference, maybe a little faster,” says Harris. “We realized all the AI algorithms were designed to solve much slower problems, such as image and voice recognition. To get to nanosecond inference timescales, we recognized we could make smaller algorithms and rely on custom implementations with Field Programmable Gate Array (FPGA) processors in an approach that was largely different from what others were doing.”

    A few months later, Harris presented their research at a physics faculty meeting, where Katsavounidis became intrigued. Over coffee in Building 7, they discussed combining Harris’ FPGA with Katsavounidis’s use of machine learning for finding gravitational waves. FPGAs and other new processor types, such as graphics processing units (GPUs), accelerate AI algorithms to more quickly analyze huge amounts of data.

    “I had worked with the first FPGAs that were out in the market in the early ’90s and have witnessed first-hand how they revolutionized front-end electronics and data acquisition in big high-energy physics experiments I was working on back then,” recalls Katsavounidis. “The ability to have them crunch gravitational-wave data has been in the back of my mind since joining LIGO over 20 years ago.”

    Two years ago they received their first grant, and the University of Washington’s Shih-Chieh Hsu joined in. The team initiated the Fast Machine Lab, published about 40 papers on the subject, built the group to about 50 researchers, and “launched a whole industry of how to explore a region of AI that has not been explored in the past,” says Harris. “We basically started this without any funding. We’ve been getting small grants for various projects over the years. A3D3 represents our first large grant to support this effort.”  

    “What makes A3D3 so special and suited to MIT is its exploration of a technical frontier, where AI is implemented not in high-level software, but rather in lower-level firmware, reconfiguring individual gates to address the scientific question at hand,” says Rob Simcoe, director of MIT Kavli Institute for Astrophysics and Space Research and the Francis Friedman Professor of Physics. “We are in an era where experiments generate torrents of data. The acceleration gained from tailoring reprogrammable, bespoke computers at the processor level can advance real-time analysis of these data to new levels of speed and sophistication.”

    The Huge Data from the Large Hadron Collider 

    With data rates already exceeding 500 terabits per second, the LHC processes more data than any other scientific instrument on earth. Its future aggregate data rates will soon exceed 1 petabit per second, the biggest data rate in the world. 

    “Through the use of AI, A3D3 aims to perform advanced analyses, such as anomaly detection, and particle reconstruction on all collisions happening 40 million times per second,” says Harris.

    The goal is to find within all of this data a way to identify the few collisions out of the 3.2 billion collisions per second that could reveal new forces, explain how dark matter is formed, and complete the picture of how fundamental forces interact with matter. Processing all of this information requires a customized computing system capable of interpreting the collider information within ultra-low latencies.  

    “The challenge of running this on all of the 100s of terabits per second in real-time is daunting and requires a complete overhaul of how we design and implement AI algorithms,” says Harris. “With large increases in the detector resolution leading to data rates that are even larger the challenge of finding the one collision, among many, will become even more daunting.” 

    The Brain and the Universe

    Thanks to advances in techniques such as medical imaging and electrical recordings from implanted electrodes, neuroscience is also gathering larger amounts of data on how the brain’s neural networks process responses to stimuli and perform motor information. A3D3 plans to develop and implement high-throughput and low-latency AI algorithms to process, organize, and analyze massive neural datasets in real time, to probe brain function in order to enable new experiments and therapies.   

    With Multi-Messenger Astrophysics (MMA), A3D3 aims to quickly identify astronomical events by efficiently processing data from gravitational waves, gamma-ray bursts, and neutrinos picked up by telescopes and detectors. 

    The A3D3 researchers also include a multi-disciplinary group of 15 other researchers, including project lead the University of Washington, along with Caltech, Duke University, Purdue University, UC San Diego, University of Illinois Urbana-Champaign, University of Minnesota, and the University of Wisconsin-Madison. It will include neutrinos research at Icecube and DUNE, and visible astronomy at Zwicky Transient Facility, and will organize deep-learning workshops and boot camps to train students and researchers on how to contribute to the framework and widen the use of fast AI strategies.

    “We have reached a point where detector network growth will be transformative, both in terms of event rates and in terms of astrophysical reach and ultimately, discoveries,” says Katsavounidis. “‘Fast’ and ‘efficient’ is the only way to fight the ‘faint’ and ‘fuzzy’ that is out there in the universe, and the path for getting the most out of our detectors. A3D3 on one hand is going to bring production-scale AI to gravitational-wave physics and multi-messenger astronomy; but on the other hand, we aspire to go beyond our immediate domains and become the go-to place across the country for applications of accelerated AI to data-driven disciplines.” More