How music lessons can improve language skills

Many studies have shown that musical training can enhance language skills. However, it was unknown whether music lessons improve general cognitive ability, leading to better language proficiency, or if the effect of music is more specific to language processing.

A new study from MIT has found that piano lessons have a very specific effect on kindergartners’ ability to distinguish different pitches, which translates into an improvement in discriminating between spoken words. However, the piano lessons did not appear to confer any benefit for overall cognitive ability, as measured by IQ, attention span, and working memory.

“The children didn’t differ in the more broad cognitive measures, but they did show some improvements in word discrimination, particularly for consonants. The piano group showed the best improvement there,” says Robert Desimone, director of MIT’s McGovern Institute for Brain Research and the senior author of the paper.

The study, performed in Beijing, suggests that musical training is at least as beneficial in improving language skills, and possibly more beneficial, than offering children extra reading lessons. The school where the study was performed has continued to offer piano lessons to students, and the researchers hope their findings could encourage other schools to keep or enhance their music offerings.

Yun Nan, an associate professor at Beijing Normal University, is the lead author of the study, which appears in the Proceedings of the National Academy of Sciences the week of June 25.

Other authors include Li Liu, Hua Shu, and Qi Dong, all of Beijing Normal University; Eveline Geiser, a former MIT research scientist; Chen-Chen Gong, an MIT research associate; and John Gabrieli, the Grover M. Hermann Professor in Health Sciences and Technology, a professor of brain and cognitive sciences, and a member of MIT’s McGovern Institute for Brain Research.

Benefits of music

Previous studies have shown that on average, musicians perform better than nonmusicians on tasks such as reading comprehension, distinguishing speech from background noise, and rapid auditory processing. However, most of these studies have been done by asking people about their past musical training. The MIT researchers wanted to perform a more controlled study in which they could randomly assign children to receive music lessons or not, and then measure the effects.

They decided to perform the study at a school in Beijing, along with researchers from the IDG/McGovern Institute at Beijing Normal University, in part because education officials there were interested in studying the value of music education versus additional reading instruction.

“If children who received music training did as well or better than children who received additional academic instruction, that could a justification for why schools might want to continue to fund music,” Desimone says.

The 74 children participating in the study were divided into three groups: one that received 45-minute piano lessons three times a week; one that received extra reading instruction for the same period of time; and one that received neither intervention. All children were 4 or 5 years old and spoke Mandarin as their native language.

After six months, the researchers tested the children on their ability to discriminate words based on differences in vowels, consonants, or tone (many Mandarin words differ only in tone). Better word discrimination usually corresponds with better phonological awareness — the awareness of the sound structure of words, which is a key component of learning to read.

Children who had piano lessons showed a significant advantage over children in the extra reading group in discriminating between words that differ by one consonant. Children in both the piano group and extra reading group performed better than children who received neither intervention when it came to discriminating words based on vowel differences.

The researchers also used electroencephalography (EEG) to measure brain activity and found that children in the piano group had stronger responses than the other children when they listened to a series of tones of different pitch. This suggest that a greater sensitivity to pitch differences is what helped the children who took piano lessons to better distinguish different words, Desimone says.

“That’s a big thing for kids in learning language: being able to hear the differences between words,” he says. “They really did benefit from that.”

In tests of IQ, attention, and working memory, the researchers did not find any significant differences among the three groups of children, suggesting that the piano lessons did not confer any improvement on overall cognitive function.

Aniruddh Patel, a professor of psychology at Tufts University, says the findings also address the important question of whether purely instrumental musical training can enhance speech processing.

“This study answers the question in the affirmative, with an elegant design that directly compares the effect of music and language instruction on young children. The work specifically relates behavioral improvements in speech perception to the neural impact of musical training, which has both theoretical and real-world significance,” says Patel, who was not involved in the research.

Educational payoff

Desimone says he hopes the findings will help to convince education officials who are considering abandoning music classes in schools not to do so.

“There are positive benefits to piano education in young kids, and it looks like for recognizing differences between sounds including speech sounds, it’s better than extra reading. That means schools could invest in music and there will be generalization to speech sounds,” Desimone says. “It’s not worse than giving extra reading to the kids, which is probably what many schools are tempted to do — get rid of the arts education and just have more reading.”

Desimone now hopes to delve further into the neurological changes caused by music training. One way to do that is to perform EEG tests before and after a single intense music lesson to see how the brain’s activity has been altered.

The research was funded by the National Natural Science Foundation of China, the Beijing Municipal Science and Technology Commission, the Interdiscipline Research Funds of Beijing Normal University, and the Fundamental Research Funds for the Central Universities.

How the brain performs flexible computations

Humans can perform a vast array of mental operations and adjust their behavioral responses based on external instructions and internal beliefs. For example, to tap your feet to a musical beat, your brain has to process the incoming sound and also use your internal knowledge of how the song goes.

MIT neuroscientists have now identified a strategy that the brain uses to rapidly select and flexibly perform different mental operations. To make this discovery, they applied a mathematical framework known as dynamical systems analysis to understand the logic that governs the evolution of neural activity across large populations of neurons.

“The brain can combine internal and external cues to perform novel computations on the fly,” says Mehrdad Jazayeri, the Robert A. Swanson Career Development Professor of Life Sciences, a member of MIT’s McGovern Institute for Brain Research, and the senior author of the study. “What makes this remarkable is that we can make adjustments to our behavior at a much faster time scale than the brain’s hardware can change. As it turns out, the same hardware can assume many different states, and the brain uses instructions and beliefs to select between those states.”

Previous work from Jazayeri’s group has found that the brain can control when it will initiate a movement by altering the speed at which patterns of neural activity evolve over time. Here, they found that the brain controls this speed flexibly based on two factors: external sensory inputs and adjustment of internal states, which correspond to knowledge about the rules of the task being performed.

Evan Remington, a McGovern Institute postdoc, is the lead author of the paper, which appears in the June 6 edition of Neuron. Other authors are former postdoc Devika Narain and MIT graduate student Eghbal Hosseini.

Ready, set, go

Neuroscientists believe that “cognitive flexibility,” or the ability to rapidly adapt to new information, resides in the brain’s higher cortical areas, but little is known about how the brain achieves this kind of flexibility.

To understand the new findings, it is useful to think of how switches and dials can be used to change the output of an electrical circuit. For example, in an amplifier, a switch may select the sound source by controlling the input to the circuit, and a dial may adjust the volume by controlling internal parameters such as a variable resistance. The MIT team theorized that the brain similarly transforms instructions and beliefs to inputs and internal states that control the behavior of neural circuits.

To test this, the researchers recorded neural activity in the frontal cortex of animals trained to perform a flexible timing task called “ready, set, go.” In this task, the animal sees two visual flashes — “ready” and “set” — that are separated by an interval anywhere between 0.5 and 1 second, and initiates a movement — “go” — some time after “set.” The animal has to initiate the movement such that the “set-go” interval is either the same as or 1.5 times the “ready-set” interval. The instruction for whether to use a multiplier of 1 or 1.5 is provided in each trial.

Neural signals recorded during the “set-go” interval clearly carried information about both the multiplier and the measured length of the “ready-set” interval, but the nature of these representations seemed bewilderingly complex. To decode the logic behind these representations, the researchers used the dynamical systems analysis framework. This analysis is used in the study of a wide range of physical systems, from simple electrical circuits to space shuttles.

The application of this approach to neural data in the “ready, set, go” task enabled Jazayeri and his colleagues to discover how the brain adjusts the inputs to and initial conditions of frontal cortex to control movement times flexibly. A switch-like operation sets the input associated with the correct multiplier, and a dial-like operation adjusts the state of neurons based on the “ready-set” interval. These two complementary control strategies allow the same hardware to produce different behaviors.

David Sussillo, a research scientist at Google Brain and an adjunct professor at Stanford University, says a key to the study was the research team’s development of new mathematical tools to analyze huge amounts of data from neuron recordings, allowing the researchers to uncover how a large population of neurons can work together to perform mental operations related to timing and rhythm.

“They have very rigorously brought the dynamical systems approach to the problem of timing,” says Sussillo, who was not involved in the research.

“A bridge between behavior and neurobiology”

Many unanswered questions remain about how the brain achieves this flexibility, the researchers say. They are now trying to find out what part of the brain sends information about the multiplier to the frontal cortex, and they also hope to study what happens in these neurons as they first learn tasks that require them to respond flexibly.

“We haven’t connected all the dots from behavioral flexibility to neurobiological details. But what we have done is to establish an algorithmic understanding based on the mathematics of dynamical systems that serves as a bridge between behavior and neurobiology,” Jazayeri says.

The researchers also hope to explore whether this type of model could help to explain behavior of other parts of the brain that have to perform computations flexibly.

The research was funded by the National Institutes of Health, the Sloan Foundation, the Klingenstein Foundation, the Simons Foundation, the McKnight Foundation, the Center for Sensorimotor Neural Engineering, and the McGovern Institute.

Ed Boyden and Feng Zhang named Howard Hughes Medical Institute Investigators

Two members of the MIT faculty were named Howard Hughes Medical Institute (HHMI) investigators today. Ed Boyden and Feng Zhang join a community of 300 HHMI scientists who are “transforming biology and medicine, one discovery at a time.” Both researchers have been instrumental in recognizing, developing, and sharing robust tools with broad utility that have revolutionized the life sciences.

“We are thrilled that Ed and Feng are being recognized in this way” says Robert Desimone, director of the McGovern Institute for Brain Research at MIT. “Being named to the investigator program recognizes their previous achievements and allows them to follow the innovative path that is a trait of their research.”

HHMI selects new Investigators to join its flagship program through periodic competitions. In choosing researchers to join its investigator program, HHMI specifically aims to select ‘people, not projects’ and identifies trail blazers in the biomedical sciences. The organization provides support for an unusual length of time, seven years with a renewal process at the end of that period, thus giving selected scientists the time and freedom to tackle difficult and important biological questions. HHMI-affiliated scientists continue to work at their home institution. The HHMI Investigator program currently funds 300 scientists at 60 research institutions across the United States.

Ed Boyden, the Y. Eva Tan Professor in Neurotechnology at MIT, has pioneered a number of technologies that allow visualization and manipulation of complex biological systems. Boyden worked, along with Karl Deisseroth and Feng Zhang, on optogenetics, a system that leverages microbial opsins to manipulate neuronal activity using light. This technology has transformed our ability to examine neuronal function in vivo. Boyden’s work initiated optogenetics, then extended it into a multicolor, high-speed, and noninvasive toolbox. Subsequent technological advances developed by Boyden and his team include expansion microscopy, an imaging strategy that overcomes the limits of light microscopy by expanding biological specimens in a controlled fashion. Boyden’s team also recently developed a directed evolution system that is capable of robotically screening hundreds of thousands of mutated proteins for specific properties within hours. He and his team recently used the system to develop a high-performance fluorescent voltage indicator.

“I am honored and excited to become an HHMI investigator,” says Boyden, who is also a member of MIT’s McGovern Institute for Brain Research and Koch Institute for Integrative Cancer Research and an associate professor in the Program in Media Arts and Sciences at the MIT Media Lab; the MIT Department of Brain and Cognitive Sciences; and the MIT Department of Biological Engineering. “This will give my group the ability to open up completely new areas of science, in a way that would not be possible with traditional funding.”

Feng Zhang is a molecular biologist focused on building new tools for probing the human brain. As a graduate student, Zhang was part of the team that developed optogenetics. Zhang went on to develop other innovative tools. These achievements include the landmark deployment of the microbial CRISPR-Cas9 system for genome engineering in eukaryotic cells. The ease and specificity of the system has led to its widespread use. Zhang has continued to mine bacterial CRISPR systems for additional enzymes with useful properties, leading to the discovery of Cas13, which targets RNA, rather than DNA. By leveraging the unique properties of Cas13, Zhang and his team created a precise RNA editing tool, which may potentially be a safer way to treat genetic diseases because the genome does not need to be cut, as well as a molecular detection system, termed SHERLOCK, which can sense trace amounts of genetic material, such as viruses.

“It is so exciting to join this exceptional scientific community,” says Zhang, “and be given this opportunity to pursue our research into engineering natural systems.”

Zhang is the James and Patricia Poitras Professor of Neuroscience at MIT, an associate professor in the MIT departments of Brain and Cognitive Sciences and Biological Engineering, an investigator at the McGovern Institute for Brain Research, and a core member of the Broad Institute of MIT and Harvard.

The MIT Media Lab, Broad Institute of MIT and Harvard, and MIT departments of Brain and Cognitive Sciences and Biological Engineering contributed to this article.

Biologists discover function of gene linked to familial ALS

MIT biologists have discovered a function of a gene that is believed to account for up to 40 percent of all familial cases of amyotrophic lateral sclerosis (ALS). Studies of ALS patients have shown that an abnormally expanded region of DNA in a specific region of this gene can cause the disease.

In a study of the microscopic worm Caenorhabditis elegans, the researchers found that the gene has a key role in helping cells to remove waste products via structures known as lysosomes. When the gene is mutated, these unwanted substances build up inside cells. The researchers believe that if this also happens in neurons of human ALS patients, it could account for some of those patients’ symptoms.

“Our studies indicate what happens when the activities of such a gene are inhibited — defects in lysosomal function. Certain features of ALS are consistent with their being caused by defects in lysosomal function, such as inflammation,” says H. Robert Horvitz, the David H. Koch Professor of Biology at MIT, a member of the McGovern Institute for Brain Research and the Koch Institute for Integrative Cancer Research, and the senior author of the study.

Mutations in this gene, known as C9orf72, have also been linked to another neurodegenerative brain disorder known as frontotemporal dementia (FTD), which is estimated to affect about 60,000 people in the United States.

“ALS and FTD are now thought to be aspects of the same disease, with different presentations. There are genes that when mutated cause only ALS, and others that cause only FTD, but there are a number of other genes in which mutations can cause either ALS or FTD or a mixture of the two,” says Anna Corrionero, an MIT postdoc and the lead author of the paper, which appears in the May 3 issue of the journal Current Biology.

Genetic link

Scientists have identified dozens of genes linked to familial ALS, which occurs when two or more family members suffer from the disease. Doctors believe that genetics may also be a factor in nonfamilial cases of the disease, which are much more common, accounting for 90 percent of cases.

Of all ALS-linked mutations identified so far, the C9orf72 mutation is the most prevalent, and it is also found in about 25 percent of frontotemporal dementia patients. The MIT team set out to study the gene’s function in C. elegans, which has an equivalent gene known as alfa-1.

In studies of worms that lack alfa-1, the researchers discovered that defects became apparent early in embryonic development. C. elegans embryos have a yolk that helps to sustain them before they hatch, and in embryos missing alfa-1, the researchers found “blobs” of yolk floating in the fluid surrounding the embryos.

This led the researchers to discover that the gene mutation was affecting the lysosomal degradation of yolk once it is absorbed into the cells. Lysosomes, which also remove cellular waste products, are cell structures which carry enzymes that can break down many kinds of molecules.

When lysosomes degrade their contents — such as yolk — they are reformed into tubular structures that split, after which they are able to degrade other materials. The MIT team found that in cells with the alfa-1 mutation and impaired lysosomal degradation, lysosomes were unable to reform and could not be used again, disrupting the cell’s waste removal process.

“It seems that lysosomes do not reform as they should, and material accumulates in the cells,” Corrionero says.

For C. elegans embryos, that meant that they could not properly absorb the nutrients found in yolk, which made it harder for them to survive under starvation conditions. The embryos that did survive appeared to be normal, the researchers say.

Robert Brown, chair of the Department of Neurology at the University of Massachusetts Medical School, describes the study as a major contribution to scientists’ understanding of the normal function of the C9orf72 gene.

“They used the power of worm genetics to dissect very fully the stages of vesicle maturation at which this gene seems to play a major role,” says Brown, who was not involved in the study.

Neuronal effects

The researchers were able to partially reverse the effects of alfa-1 loss in the C. elegans embryos by expressing the human protein encoded by the C9orf72 gene. “This suggests that the worm and human proteins are performing the same molecular function,” Corrionero says.

If loss of C9orf72 affects lysosome function in human neurons, it could lead to a slow, gradual buildup of waste products in those cells. ALS usually affects cells of the motor cortex, which controls movement, and motor neurons in the spinal cord, while frontotemporal dementia affects the frontal areas of the brain’s cortex.

“If you cannot degrade things properly in cells that live for very long periods of time, like neurons, that might well affect the survival of the cells and lead to disease,” Corrionero says.

Many pharmaceutical companies are now researching drugs that would block the expression of the mutant C9orf72. The new study suggests certain possible side effects to watch for in studies of such drugs.

“If you generate drugs that decrease C9orf72 expression, you might cause problems in lysosomal homeostasis,” Corrionero says. “In developing any drug, you have to be careful to watch for possible side effects. Our observations suggest some things to look for in studying drugs that inhibit C9orf72 in ALS/FTD patients.”

The research was funded by an EMBO postdoctoral fellowship, an ALS Therapy Alliance grant, a gift from Rose and Douglas Barnard ’79 to the McGovern Institute, and a gift from the Halis Family Foundation to the MIT Aging Brain Initiative.

McGovern Institute awards 2018 Scolnick Prize to David Anderson

The McGovern Institute for Brain Research at MIT announced today that David J. Anderson of Caltech is the winner of the 2018 Edward M. Scolnick Prize in Neuroscience. He was awarded the prize for his contributions to the isolation and characterization of neural stem cells and for his research on neural circuits that control emotional behaviors in animal models. The Scolnick Prize is awarded annually by the McGovern Institute to recognize outstanding advances in any field of neuroscience.

“We congratulate David Anderson on being selected for this award,” says Robert Desimone, director of the McGovern Institute and chair of the selection committee. “His work has provided fundamental insights into neural development and the structure and function of neural circuits.”

Anderson is the Seymour Benzer Professor of Biology at Caltech, where he has been on the faculty since 1986, and is currently the director of the Tianqiao and Chrissy Chen Institute for Neuroscience. He is also an investigator of the Howard Hughes Medical Institute. He received his PhD in cell biology from Rockefeller University, where he trained with the late Günter Blobel, and he received his postdoctoral training in molecular biology with Richard Axel at Columbia University.

For the first 20 years of his career, Anderson focused his research on the biology of neural stem cells and was the first to isolate a multipotent stem cell from the mammalian nervous system. He subsequently identified growth factors and master transcriptional regulators that control their differentiation into neurons and glial cells. Anderson also made the unexpected and fundamental discovery that arteries and veins are genetically distinct even before the heart begins to beat. Combining this discovery with his interest in neural development, Anderson went on to contribute to the expanding field of vessel identity and the study of molecular cross-talk between developing nerves and blood vessels.

More recently, Anderson has shifted his focus from neural development to the study of neural circuits that control emotional behaviors, such as fear, anxiety, and aggression, in animal models. Anderson has employed various technologies for neural circuit manipulation including optogenetics, pharmacogenetics, electrophysiology, in vivo imaging, and quantitative behavior analysis using machine vision-based approaches. He developed and applied powerful genetic methods to identify and manipulate cells and circuits involved in emotional behaviors in mice — including ways to inactivate neurons reversibly and to trace their synaptic targets. In addition to this work on vertebrate neural circuitry, Anderson mounted a parallel inquiry that dissects the genes and circuits underlying aggressive behavior in the fruitfly Drosophila melanogaster, and has become an international leader in this rapidly developing field.

Among his many honors and awards, Anderson is a Perl-UNC Neuroscience Prize recipient, a fellow of the American Academy of Arts and Sciences and a member of the National Academy of Sciences. Anderson also played a key role in the foundation of the Allen Institute for Brain Sciences and the Allen Brain Atlas, a comprehensive open-source atlas of gene expression in the mouse brain.

Anderson will deliver the Scolnick Prize lecture at the McGovern Institute on Friday, Sept. 21 at 4 p.m. in the Singleton Auditorium of MIT’s Brain and Cognitive Sciences Complex (Room 46-3002). The event is free and open to the public.

National Academy of Sciences elects four MIT professors for 2018

Four MIT faculty members have been elected to the National Academy of Sciences (NAS) in recognition of their “distinguished and continuing achievements in original research.”

MIT’s four new NAS members are: Amy Finkelstein, the John and Jennie S. MacDonald Professor of Economics; Mehran Kardar, the Francis Friedman Professor of Physics; Xiao-Gang Wen, the Cecil and Ida Green Professor of Physics; and Feng Zhang, the Patricia and James Poitras ’63 Professor in Neuroscience at MIT, associate professor of brain and cognitive sciences and of biological engineering, and member of the McGovern Institute for Brain Research and the Broad Institute

The group was among 84 new members and 21 new foreign associates elected to the NAS. Membership in the NAS is one of the most significant honors given to academic researchers.

Amy Finkelstein

Finkelstein is the co-scientific director of J-PAL North America, the co-director of the Public Economics Program at the National Bureau of Economic Research, a member of the Institute of Medicine and the American Academy of Arts and Sciences, and a fellow of the Econometric Society.

She has received numerous awards and fellowships including the John Bates Clark Medal (2012), the American Society of Health Economists’ ASHEcon Medal (2014), a Presidential Early Career Award for Scientists and Engineers (2009), the American Economic Association’s Elaine Bennett Research Prize (2008) and a Sloan Research Fellowship (2007). She has also received awards for graduate student teaching (2012) and graduate student advising (2010) at MIT.

She is one of the two principal investigators for the Oregon Health Insurance Experiment, a randomized evaluation of the impact of extending Medicaid coverage to low income, uninsured adults.

Mehran Kardar

Kardar obtained a BA from Cambridge University in 1979 and a PhD in physics from MIT in 1983. He was a junior fellow of the Harvard Society of Fellows from 1983 to 1986 before returning to MIT as an assistant professor, and was promoted to full professor in 1996. He has been a visiting professor at a number of institutions including Catholic University in Belgium, Oxford University, the University of California at Santa Barbara, the University of California at Berkeley, and Ecole Normale Superieure in Paris.

His expertise is in statistical physics, and he has lectured extensively on this topic at MIT and in workshops at universities and institutes in France, the U.K., Switzerland, and Finland. He is the author of two books based on these lectures. In 2018 he was recognized by the American Association of Physics Teachers with the John David Jackson Excellence in Graduate Physics Education Award.

Kardar is a member of the founding board of the New England Complex Science Institute and the editorial board of Journal of Statistical Physics, and has helped organize Gordon Conference and KITP workshops. His awards include the Bergmann memorial research award, the A. P. Sloan Fellowship, the Presidential Young Investigator award, the Edgerton award for junior faculty achievements (MIT), and the Guggenheim Fellowship. He is a fellow of the American Physical Society and the American Academy of Arts and Sciences.

Xiao-Gang Wen

Wen received a BS in physics from University of Science and Technology of China in 1982 and a PhD in physics from Princeton University in 1987.

He studied superstring theory under theoretical physicist Edward Witten at Princeton University and later switched his research field to condensed matter physics while working with theoretical physicists Robert Schrieffer, Frank Wilczek, and Anthony Zee in the Institute for Theoretical Physics at the University of California at Santa Barbara (1987–1989). He became a five-year member of the Institute for Advanced Study at Princeton University in 1989 and joined MIT in 1991. Wen is the Cecil and Ida Green professor of Physics at MIT, a Distinguished Moore Scholar at Caltech, and a Distinguished Research Chair at the Perimeter Institute. In 2017 he received the Oliver E. Buckley Condensed Matter Physics Prize of the American Physical Society.

Wen’s main research area is condensed matter theory. His interests include strongly correlated electronic systems, topological order and quantum order, high-temperature superconductors, the origin and unification of elementary particles, and the Quantum Hall Effect and non-Abelian statistics.

Feng Zhang

Zhang is a bioengineer focused on developing tools to better understand nervous system function and disease. His lab applies these novel tools to interrogate gene function and study neuropsychiatric disorders in animal and stem cell models. Since joining MIT and the Broad Institute in January 2011, Zhang has pioneered the development of genome editing tools for use in eukaryotic cells — including human cells — from natural microbial CRISPR systems. He also developed a breakthrough technology called optogenetics with Karl Deisseroth at Stanford University and Edward Boyden, now of MIT.

Zhang joined MIT and the Broad Institute in 2011 and was awarded tenure in 2016. He received his BA in chemistry and physics from Harvard College and his PhD in chemistry from Stanford University. Zhang’s award include the Perl/UNC Prize in Neuroscience (2012, shared with Karl Deisseroth and Ed Boyden), the National Institutes of Health Director’s Pioneer Award (2012), the National Science Foundation’s Alan T. Waterman Award (2014), the Jacob Heskel Gabbay Award in Biotechnology and Medicine (2014, shared with Jennifer Doudna and Emmanuelle Charpentier), the Society for Neuroscience Young Investigator Award (2014), the Okazaki award, the Canada Gairdner International Award (shared with Doudna and Charpentier along with Philippe Horvath and Rodolphe Barrangou) and the 2016 Tang Prize (shared with Doudna and Charpentier).

Zhang is a founder of Editas Medicine, a genome editing company founded by world leaders in the fields of genome editing, protein engineering, and molecular and structural biology.

Calcium-based MRI sensor enables more sensitive brain imaging

MIT neuroscientists have developed a new magnetic resonance imaging (MRI) sensor that allows them to monitor neural activity deep within the brain by tracking calcium ions.

Because calcium ions are directly linked to neuronal firing — unlike the changes in blood flow detected by other types of MRI, which provide an indirect signal — this new type of sensing could allow researchers to link specific brain functions to their pattern of neuron activity, and to determine how distant brain regions communicate with each other during particular tasks.

“Concentrations of calcium ions are closely correlated with signaling events in the nervous system,” says Alan Jasanoff, an MIT professor of biological engineering, brain and cognitive sciences, and nuclear science and engineering, an associate member of MIT’s McGovern Institute for Brain Research, and the senior author of the study. “We designed a probe with a molecular architecture that can sense relatively subtle changes in extracellular calcium that are correlated with neural activity.”

In tests in rats, the researchers showed that their calcium sensor can accurately detect changes in neural activity induced by chemical or electrical stimulation, deep within a part of the brain called the striatum.

MIT research associates Satoshi Okada and Benjamin Bartelle are the lead authors of the study, which appears in the April 30 issue of Nature Nanotechnology. Other authors include professor of brain and cognitive sciences and Picower Institute for Learning and Memory member Mriganka Sur, Research Associate Nan Li, postdoc Vincent Breton-Provencher, former postdoc Elisenda Rodriguez, Wellesley College undergraduate Jiyoung Lee, and high school student James Melican.

Tracking calcium

A mainstay of neuroscience research, MRI allows scientists to identify parts of the brain that are active during particular tasks. The most commonly used type, known as functional MRI, measures blood flow in the brain as an indirect marker of neural activity. Jasanoff and his colleagues wanted to devise a way to map patterns of neural activity with specificity and resolution that blood-flow-based MRI techniques can’t achieve.

“Methods that are able to map brain activity in deep tissue rely on changes in blood flow, and those are coupled to neural activity through many different physiological pathways,” Jasanoff says. “As a result, the signal you see in the end is often difficult to attribute to any particular underlying cause.”

Calcium ion flow, on the other hand, can be directly linked with neuron activity. When a neuron fires an electrical impulse, calcium ions rush into the cell. For about a decade, neuroscientists have been using fluorescent molecules to label calcium in the brain and image it with traditional microscopy. This technique allows them to precisely track neuron activity, but its use is limited to small areas of the brain.

The MIT team set out to find a way to image calcium using MRI, which enables much larger tissue volumes to be analyzed. To do that, they designed a new sensor that can detect subtle changes in calcium concentrations outside of cells and respond in a way that can be detected with MRI.

The new sensor consists of two types of particles that cluster together in the presence of calcium. One is a naturally occurring calcium-binding protein called synaptotagmin, and the other is a magnetic iron oxide nanoparticle coated in a lipid that can also bind to synaptotagmin, but only when calcium is present.

Calcium binding induces these particles to clump together, making them appear darker in an MRI image. High levels of calcium outside the neurons correlate with low neuron activity; when calcium concentrations drop, it means neurons in that area are firing electrical impulses.

Detecting brain activity

To test the sensors, the researchers injected them into the striatum of rats, a region that is involved in planning movement and learning new behaviors. They then gave the rats a chemical stimulus that induces short bouts of neural activity, and found that the calcium sensor reflected this activity.

They also found that the sensor picked up activity induced by electrical stimulation in a part of the brain involved in reward.

This approach provides a novel way to examine brain function, says Xin Yu, a research group leader at the Max Planck Institute for Biological Cybernetics in Tuebingen, Germany, who was not involved in the research.

“Although we have accumulated sufficient knowledge on intracellular calcium signaling in the past half-century, it has seldom been studied exactly how the dynamic changes in extracellular calcium contribute to brain function, or serve as an indicator of brain function,” Yu says. “When we are deciphering such a complicated and self-adapted system like the brain, every piece of information matters.”

The current version of the sensor responds within a few seconds of the initial brain stimulation, but the researchers are working on speeding that up. They are also trying to modify the sensor so that it can spread throughout a larger region of the brain and pass through the blood-brain barrier, which would make it possible to deliver the particles without injecting them directly to the test site.

With this kind of sensor, Jasanoff hopes to map patterns of neural activity with greater precision than is now possible. “You could imagine measuring calcium activity in different parts of the brain and trying to determine, for instance, how different types of sensory stimuli are encoded in different ways by the spatial pattern of neural activity that they induce,” he says.

The research was funded by the National Institutes of Health and the MIT Simons Center for the Social Brain.

Nancy Kanwisher receives 2018 Heineken Prize

Nancy Kanwisher, the Walter A. Rosenblith Professor of Cognitive Neuroscience at MIT, has been named a recipient of the 2018 Heineken Prize — the Netherlands’ most prestigious scientific prize — for her work on the functional organization of the human brain.

Kanwisher, who is a professor of brain and cognitive sciences and a member of MIT’s McGovern Institute for Brain Research, uses neuroimaging to study the functional organization of the human brain. Over the last 20 years her lab has played a central role in the identification of regions of the human brain that are engaged in particular components of perception and cognition. Many of these regions are very specifically engaged in a single mental function such as perceiving faces, places, bodies, or words, or understanding the meanings of sentences or the mental states of others. These regions form a “neural portrait of the human mind,” according to Kanwisher, who has assembled dozens of videos for the general public on her website, NancysBrainTalks.

“Nancy Kanwisher is an exceptionally innovative and influential researcher in cognitive neuropsychology and the neurosciences,” according to the Royal Netherlands Academy of Arts and Sciences, the organization that selects the prizewinners. “She is being recognized with the 2018 C.L. de Carvalho-Heineken Prize for Cognitive Science for her highly original, meticulous and cogent research on the functional organization of the human brain.”

Kanwisher is among five international scientists who have been recognized by the academy with the biennial award. The other winners include biomedical scientist Peter Carmeliet  of the University of Leuven, biologist Paul Hebert of the University of Guelph, historian John R. McNeill of Georgetown University, and biophysicist Xiaowei Zhuang of Harvard University.

The Heineken Prizes, each worth $200,000, are named after Henry P. Heineken (1886-1971); Alfred H. Heineken (1923-2002) and Charlene de Carvalho-Heineken (1954), chair of the Dr H.P. Heineken Foundation and the Alfred Heineken Fondsen Foundation, which fund the prizes. The laureates are selected by juries assembled by the academy and made up of leading Dutch and foreign scientists and scholars.

The Heineken Prizes will be presented at an award ceremony on Sept. 27 in Amsterdam.

Eight from MIT elected to American Academy of Arts and Sciences for 2018

Eight MIT faculty members are among 213 leaders from academia, business, public affairs, the humanities, and the arts elected to the American Academy of Arts and Sciences, the academy announced today.

One of the nation’s most prestigious honorary societies, the academy is also a leading center for independent policy research. Members contribute to academy publications, as well as studies of science and technology policy, energy and global security, social policy and American institutions, the humanities and culture, and education.

Those elected from MIT this year are:

  • Alexei Borodin, professor of mathematics;
  • Gang Chen, the Carl Richard Soderberg Professor of Power Engineering and head of the Department of Mechanical Engineering;
  • Larry D. Guth; professor of mathematics;
  • Parag A. Pathak, the Jane Berkowitz Carlton and Dennis William Carlton Professor of Microeconomics;
  • Nancy L. Rose, the Charles P. Kindleberger Professor of Applied Economics and head of the Department of Economics;
  • Leigh H. Royden, professor of earth, atmostpheric, and planetary sciences;
  • Sara Seager, the Class of 1941 Professor in the Department of Earth, Atmospheric and Planetary Sciences with a joint appointment in the Department of Physics; and
  • Feng Zhang, the James and Patricia Poitras Professor of Neuroscience within the departments of Brain and Cognitive Sciences and Biological Engineering, and an investigator at the McGovern Institute for Brain Research at MIT.

“This class of 2018 is a testament to the academy’s ability to both uphold our 238-year commitment to honor exceptional individuals and to recognize new expertise,” said Nancy C. Andrews, chair of the board of the American Academy.

“Membership in the academy is not only an honor, but also an opportunity and a responsibility,” added Jonathan Fanton, president of the American Academy. “Members can be inspired and engaged by connecting with one another and through academy projects dedicated to the common good. The intellect, creativity, and commitment of the 2018 class will enrich the work of the academy and the world in which we live.”

The new class will be inducted at a ceremony in October in Cambridge, Massachusetts.

Since its founding in 1780, the academy has elected leading “thinkers and doers” from each generation, including George Washington and Benjamin Franklin in the 18th century, Maria Mitchell and Daniel Webster in the 19th century, and Toni Morrison and Albert Einstein in the 20th century. The current membership includes more than 200 Nobel laureates and 100 Pulitzer Prize winners.

School of Science announces Infinite Mile Awards for 2018

The MIT School of Science has announced seven winners of the Infinite Mile Award for 2018. The award will be presented at a luncheon this May in recognition of staff members whose accomplishments and contributions to their departments, laboratories, and centers far exceed expectations.

The 2018 Infinite Mile Award winners are:

Hristina Dineva, Department of Biology;

Theresa Cummings, Department of Mathematics;

Mary Gallagher, Department of Biology;

Jack McGlashing, Laboratory for Nuclear Science;

Sydney Miller, Department of Physics;

Miroslava Parsons, Department of Earth, Atmospheric and Planetary Sciences; and

Alexandra Sokhina, Simons Center for the Social Brain.

The awards luncheon will also honor winners of last fall’s Infinite Kilometer Award, which was established to highlight and reward the extraordinary — but often underrecognized — work of the school’s research staff and postdoctoral researchers.

The 2017 Infinite Kilometer winners are:

Rodrigo Garcia, McGovern Institute for Brain Research;

Lydia Herzel, Department of Biology;

Yutaro Iiyama, Laboratory for Nuclear Science;

Kendrick Jones, Picower Institute for Learning and Memory;

Matthew Musgrave, Laboratory for Nuclear Science;

Cody Siciliano, Picower Institute for Learning and Memory;

Peter Sudmant, Department of Biology; and

Ashley Watson, Picower Institute for Learning and Memory.