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Martha Constantine-Paton wins lifetime achievement award

Anne Trafton |

Constantine-Paton, a leading figure in the field of developmental neuroscience, has been awarded the Society for Neuroscience’s Mika Salpeter Lifetime Achievement Award.

The award recognizes individuals with outstanding career achievements in neuroscience who have also actively promoted the professional advancement of women in neuroscience. Constantine-Paton will be recognized for her achievements during the Society for Neuroscience’s annual meeting this October.

Over the past 30 years, Constantine-Paton has established a reputation as a leading figure in the field of developmental neuroscience. In particular, her pioneering work on NMDA receptor-dependent plasticity laid the groundwork for our current understanding of how the brain becomes correctly wired in response to activity and experience.

She has also mentored many students and postdocs, among them several prominent women scientists, and she is very active in promoting the career development of her junior colleagues.

“Martha’s research contributions have been extremely influential within her field, and her influence has also been felt through her exemplary record of mentoring and service,” says McGovern Institute director Robert Desimone. “Martha’s career indeed represents a lifetime of achievement and I cannot imagine a more deserving recipient for this honor.”

Predicting how patients respond to therapy

Anne Trafton |

Social anxiety is usually treated with either cognitive behavioral therapy or medications. However, it is currently impossible to predict which treatment will work best for a particular patient. The team of researchers from MIT, Boston University (BU) and Massachusetts General Hospital (MGH) found that the effectiveness of therapy could be predicted by measuring patients’ brain activity as they looked at photos of faces, before the therapy sessions began.

The findings, published this week in the Archives of General Psychiatry, may help doctors more accurately choose treatments for social anxiety disorder, which is estimated to affect around 15 million people in the United States.

“Our vision is that some of these measures might direct individuals to treatments that are more likely to work for them,” says John Gabrieli, the Grover M. Hermann Professor of Brain and Cognitive Sciences at MIT, a member of the McGovern Institute for Brain Research and senior author of the paper.

Lead authors of the paper are MIT postdoc Oliver Doehrmann and Satrajit Ghosh, a research scientist in the McGovern Institute.

Choosing treatments

Sufferers of social anxiety disorder experience intense fear in social situations, interfering with their ability to function in daily life. Cognitive behavioral therapy aims to change the thought and behavior patterns that lead to anxiety. For social anxiety disorder patients, that might include learning to reverse the belief that others are watching or judging them.

The new paper is part of a larger study that MGH and BU recently ran on cognitive behavioral therapy for social anxiety, led by Mark Pollack, director of the Center for Anxiety and Traumatic Stress Disorders at MGH, and Stefan Hofmann, director of the Social Anxiety Program at BU.

“This was a chance to ask if these brain measures, taken before treatment, would be informative in ways above and beyond what physicians can measure now, and determine who would be responsive to this treatment,” Gabrieli says.

Currently doctors might choose a treatment based on factors such as ease of taking pills versus going to therapy, the possibility of drug side effects, or what the patients’ insurance will cover. “From a science perspective there’s very little evidence about which treatment is optimal for a person,” Gabrieli says.

The researchers used functional magnetic resonance imaging (fMRI) to image the brains of patients before and after treatment. There have been many imaging studies showing brain differences between healthy people and patients with neuropsychiatric disorders, but so far imaging has not been established as a way to predict patient response to particular treatments.

Measuring brain activity

In the new study, the researchers measured differences in brain activity as patients looked at images of angry or neutral faces. After 12 weeks of cognitive behavioral therapy, patients’ social anxiety levels were tested. The researchers found that patients who had shown a greater difference in activity in high-level visual processing areas during the face-response task showed the most improvement after therapy.

The findings are an important step towards improving doctors’ ability to choose the right treatment for psychiatric disorders, says Greg Siegle, associate professor of psychiatry at the University of Pittsburgh. “It’s really critical that somebody do this work, and they did it very well,” says Siegle, who was not part of the research team. “It moves the field forward, and brings psychology into more of a rigorous science, using neuroscience to distinguish between clinical cases that at first appear homogeneous.”

Gabrieli says it’s unclear why activity in brain regions involved with visual processing would be a good predictor of treatment outcome. One possibility is that patients who benefited more were those whose brains were already adept at segregating different types of experiences, Gabrieli says.

The researchers are now planning a follow-up study to investigate whether brain scans can predict differences in response between cognitive behavioral therapy and drug treatment.

“Right now, all by itself, we’re just giving somebody encouraging or discouraging news about the likely outcome of therapy,” Gabrieli says. “The really valuable thing would be if it turns out to be differentially sensitive to different treatment choices.”

The research was funded by the Poitras Center for Affective Disorders Research and the National Institute of Mental Health.

Stroke disrupts how brain controls muscle synergies

Anne Trafton |

The simple act of picking up a pencil requires the coordination of dozens of muscles: The eyes and head must turn toward the object as the hand reaches forward and the fingers grasp it. To make this job more manageable, the brain’s motor cortex has implemented a system of shortcuts. Instead of controlling each muscle independently, the cortex is believed to activate muscles in groups, known as “muscle synergies.” These synergies can be combined in different ways to achieve a wide range of movements.

A new study from MIT, Harvard Medical School and the San Camillo Hospital in Venice finds that after a stroke, these muscle synergies are activated in altered ways. Furthermore, those disruptions follow specific patterns depending on the severity of the stroke and the amount of time that has passed since the stroke.

The findings, published this week in the Proceedings of the National Academy of Sciences, could lead to improved rehabilitation for stroke patients, as well as a better understanding of how the motor cortex coordinates movements, says Emilio Bizzi, an Institute Professor at MIT and senior author of the paper.

“The cortex is responsible for motor learning and for controlling movement, so we want to understand what’s going on there,” says Bizzi, who is a member of the McGovern Institute for Brain Research at MIT. “How does the cortex translate an idea to move into a series of commands to accomplish a task?”

Coordinated control

One way to explore motor cortical functions is to study how motor patterns are disrupted in stroke patients who suffered damage to the motor areas.

In 2009, Bizzi and his colleagues first identified muscle synergies in the arms of people who had suffered mild strokes by measuring electrical activity in each muscle as the patients moved. Then, by utilizing a specially designed factorization algorithm, the researchers identified characteristic muscle synergies in both the stroke-affected and unaffected arms.

“To control, precisely, each muscle needed for the task would be very hard. What we have proven is that the central nervous system, when it programs the movement, makes use of these modules,” Bizzi says. “Instead of activating simultaneously 50 muscles for a single action, you will combine a few synergies to achieve that goal.”

In the 2009 study, and again in the new paper, the researchers showed that synergies in the affected arms of patients who suffered mild strokes in the cortex are very similar to those seen in their unaffected arms even though the muscle activation patterns are different. This shows that muscle synergies are structured within the spinal cord, and that cortical stroke alters the ability of the brain to activate these synergies in the appropriate combinations.

However, the new study found a much different pattern in patients who suffered more severe strokes. In those patients, synergies in the affected arm merged to form a smaller number of larger synergies. And in a third group of patients, who had suffered their stroke many years earlier, the muscle synergies of the affected arm split into fragments of the synergies seen in the unaffected arm.

This phenomenon, known as fractionation, does not restore the synergies to what they would have looked like before the stroke. “These fractionations appear to be something totally new,” says Vincent Cheung, a research scientist at the McGovern Institute and lead author of the new PNAS paper. “The conjecture would be that these fragments could be a way that the nervous system tries to adapt to the injury, but we have to do further studies to confirm that.”

This is the first time that fractionation of muscle synergies identified by factorization has been seen in chronic stroke patients, says Simon Giszter, a professor of neurobiology and anatomy at Drexel University. “It raises the question of how this occurs and if it’s a compensatory process. If it is, we can use this measurement to study how the recovery process can be accelerated,” says Giszter, who was not involved in this study.

Toward better rehabilitation

The researchers believe that these patterns of synergies, which are determined by both the severity of the deficit and the time since the stroke occurred, could be used as markers to more fully describe individual patients’ impaired status. “In some of the patients, we see a mixture of these patterns. So you can have severe but chronic patients, for instance, who show both merging and fractionation,” Cheung says.

The findings could also help doctors design better rehabilitation programs. The MIT team is now working with several hospitals to establish new therapeutic protocols based on the discovered markers.

About 700,000 people suffer strokes in the United States every year, and many different rehabilitation programs exist to treat them. Choosing one is currently more of an art than a science, Bizzi says. “There is a great deal of need to sharpen current procedures for rehabilitation by turning to principles derived from the most advanced brain research,” he says. “It is very likely that different strategies of rehabilitation will have to be used in patients who have one type of marker versus another.”

The research was funded by the National Institutes of Health and the Italian Ministry of Health.

Thinking about others is not child’s play

Anne Trafton |

When you try to read other people’s thoughts, or guess why they are behaving a certain way, you employ a skill known as theory of mind. This skill, as measured by false-belief tests, takes time to develop: In children, it doesn’t start appearing until the age of 4 or 5.

Several years ago, MIT neuroscientist Rebecca Saxe showed that in adults, theory of mind is seated in a specific brain region known as the right temporo-parietal junction (TPJ). Saxe and colleagues at MIT have now shown how brain activity in the TPJ changes as children learn to reason about others’ thoughts and feelings.

The findings suggest that the right TPJ becomes more specific to theory of mind as children age, taking on adult patterns of activity over time. The researchers also showed that the more selectively the right TPJ is activated when children listen to stories about other people’s thoughts, the better those children perform in tasks that require theory of mind.

The paper, published in the July 31 online edition of the journal Child Development, lays the groundwork for exploring theory-of-mind impairments in autistic children, says Hyowon Gweon, a graduate student in Saxe’s lab and lead author of the paper.

Given that we know this is what typically developing kids show, the next question to ask is how it compares to autistic children who exhibit marked impairments in their ability to think about other people’s minds,” Gweon says. “Do they show differences from typically developing kids in their neural activity?”

Saxe, an associate professor of brain and cognitive sciences and associate member of MIT’s McGovern Institute for Brain Research, is senior author of the Child Development paper. Other authors are Marina Bedny, a postdoc in Saxe’s lab, and David Dodell-Feder, a graduate student at Harvard University.

Tracking theory of mind

The classic test for theory of mind is the false-belief test, sometimes called the Sally-Anne test. Experimenters often use dolls or puppets to perform a short skit: Sally takes a marble and hides it in her basket, then leaves the room. Anne then removes the marble and puts it in her own box. When Sally returns, the child watching the skit is asked: Where will Sally look for her marble?

Children with well-developed theory of mind realize that Sally will look where she thinks the marble is: her own basket. However, before children develop this skill, they don’t realize that Sally’s beliefs may not correspond to reality. Therefore, they believe she will look for the marble where it actually is, in Anne’s box.

Previous studies have shown that children start making accurate predictions in the false belief test around age 4, but this happens much later, if ever, in autistic children.

In this study, the researchers used functional magnetic resonance imaging (fMRI) to look for a link between the development of theory of mind and changes in neural activity in the TPJ. They studied 20 children, ranging from 5 to 11 years old.

Each child participated in two sets of experiments. First, the child was scanned in the MRI machine as he or she listened to different types of stories. One type focused on people’s mental states, another also focused on people but only on their physical appearances or actions, and a third type of story focused on physical objects.

The researchers measured activity across the brain as the children listened to different stories. By subtracting neural activity as they listen to stories about physical states from activity as they listen to stories about people’s mental states, the researchers can determine which brain regions are exclusive to interpreting people’s mental states.

In younger children, both the left and right TPJ were active in response to stories about people’s mental states, but they were also active when the children listened to stories about people’s appearances or actions. However, in older children, both regions became more specifically tuned to interpreting people’s thoughts and emotions, and were no longer responsive to people’s appearances or actions.

For the second task, done outside of the scanner, the researchers gave children tests similar to the classic Sally-Anne test, as well as harder questions that required making moral judgments, to measure their theory-of-mind abilities. They found that the degree to which activity in the right TPJ was specific to others’ mental states correlated with the children’s performance in theory-of-mind tasks.

Kristin Lagattuta, an associate professor of psychology at the University of California at Davis, says the paper makes an important contribution to understanding how theory of mind develops in older children. “Getting more insight into the neural basis of the behavioral development we’re seeing at these ages is exciting,” says Lagattuta, who was not involved in the research.

In an ongoing study of autistic children undergoing the same type of tests, the researchers hope to learn more about the neural basis of the theory-of-mind impairments seen in autistic children.

“So little is known about differences in neural mechanisms that contribute to these kinds of impairments,” Gweon says. “Understanding the developmental changes in brain regions related to theory of mind is going to be critical to think of measures that can help them in the real world.”

The research was funded by the Ellison Medical Foundation, the Packard Foundation, the John Merck Scholars Program, a National Science Foundation Career Award and an Ewha 21st Century Scholarship.

Video Profile: H. Robert Horvitz

Anne Trafton |

H. Robert Horvitz has devoted much of his career to studying the nematode worm Caenorhabditis elegans. Only 1 mm long and containing fewer than 1000 cells, C. elegans has proved to be remarkably informative for studying many biological problems, including the genetic control of development and behavior and the mechanisms that underlie neurodegenerative disease.

Ann Graybiel wins Kavli Prize in Neuroscience

Anne Trafton |

Three MIT researchers including Ann Graybiel  are among seven pioneering scientists worldwide named today as this year’s recipients of the Kavli Prizes.

These prizes recognize scientists for their seminal advances in astrophysics, nanoscience and neuroscience, and include a cash award of $1 million in each field. This year’s laureates were selected for their fundamental contributions to our understanding of the outer solar system; the differences in material properties at the nanoscale and at larger scales; and how the brain receives and responds to sensations such as sight, sound and touch.

The Kavli Prizes, awarded biennially since 2008, are a partnership between the Norwegian Academy of Science and Letters, the Kavli Foundation and the Norwegian Ministry of Education and Research. Today’s announcement was made by Nils Christian Stenseth, president of the Norwegian Academy of Science and Letters, and transmitted live at the opening event of the World Science Festival in New York.

King Harald of Norway will present the Kavli Prizes to the laureates at an award ceremony in Oslo on Sept. 4. The ceremony will be hosted by Ã…se Kleveland, former minister of culture for Norway, and Alan Alda, the actor, director, writer and longtime supporter of science.

The Kavli Prize in Astrophysics

The 2012 Kavli Prize in Astrophysics is shared by Jane X. Luu, a technical staff member at MIT’s Lincoln Laboratory, along with David C. Jewitt of the University of California at Los Angeles and Michael E. Brown of the California Institute of Technology. They received the prize “for discovering and characterizing the Kuiper Belt and its largest members, work that led to a major advance in the understanding of the history of our planetary system.”

In 1992, Luu and Jewitt spotted the first known object in the Kuiper Belt, a region beyond Neptune’s orbit that is more than 30 times Earth’s distance from the sun. Since then, they and others have identified more than 1,000 Kuiper Belt objects. Astronomers are particularly interested in these objects because their composition may resemble the primordial material that coalesced around the sun during the formation of our solar system.

Brown followed in Luu and Jewitt’s footsteps by searching the Kuiper Belt for planet-sized bodies. In 2005, he found Eris, an object about the same size as Pluto but with 27 percent more mass. As a result, astronomers revisited the definition of planets; Pluto was subsequently relegated to “dwarf planet” status.

The Kavli Prize in Nanoscience

The 2012 Kavli Prize in Nanoscience is given to Mildred S. Dresselhaus, Institute Professor Emerita of Physics and Computer Science and Engineering at MIT, “for her pioneering contributions to the study of phonons, electron-phonon interactions, and thermal transport in nanostructures.”

Over five decades, Dresselhaus has made multiple advances explaining how the nanoscale properties of materials can vary from those of the same materials at larger dimensions. Her early work on carbon fibers and on compounds made up of different chemical species sandwiched between graphite layers — known as graphite intercalation compounds — laid the groundwork for later discoveries concerning buckyballs, carbon nanotubes and graphene.

The Kavli Prize in Neuroscience

The Kavli Prize in Neuroscience is shared by Ann M. Graybiel, Institute Professor in MIT’s Department of Brain and Cognitive Science, along with Cornelia Isabella Bargmann of Rockefeller University and Winfried Denk of the Max Planck Institute for Medical Research. They received the prize “for elucidating basic neuronal mechanisms underlying perception and decision.”

Graybiel, of MIT’s McGovern Institute for Brain Research, has identified and traced neural loops connecting the outer layer of the brain to a region called the striatum, revealing that these form the basis for linking sensory cues to actions involved in habitual behaviors. Her work has provided a deeper understanding of human ability to make or break habits, and of what goes wrong in disorders involving movement and repetitive behaviors.

Bargmann has used nematode worms to provide insights into the molecular controls of animal behavior, yielding important advances including the discovery of the first evidence that odor response is governed by neurons; of the intracellular signaling pathways between odorant receptors and sensory neurons; and of specific neurons, receptors and neurotransmitters involved in behavior adaption following experience.

Two techniques developed by Denk have answered major questions about how information is transmitted from the eye to the brain: His invention of two-photon laser scanning fluorescence microscopy allowed imaging of living tissue at greater depths and with less unwanted background fluorescence, and his development of serial block-face electron microscopy allowed detailed 3-D imaging of minute structures within tissue.

About the Kavli Prizes

Kavli Prize recipients are chosen biennially by committees of distinguished international scientists recommended by the Chinese Academy of Sciences, the French Academy of Sciences, the Max Planck Society, the National Academy of Sciences and the Royal Society. The recommendations of these prize committees are then confirmed by the Norwegian Academy of Science and Letters.

The Kavli Prizes were initiated by and named after Fred Kavli, founder and chairman of the Kavli Foundation, which is dedicated to advancing science for the benefit of humanity, promoting public understanding of scientific research, and supporting scientists and their work.

For more detailed information on each of the prizes including a video of the 2012 award ceremony, see the Kavli Prize website.

2012 Scolnick Prize Lecture: Roger Nicoll, MD

Anne Trafton |

Dr. Roger Nicoll of the University of California, San Francisco delivered the 2012 Scolnick Prize lecture, entitled “Deconstructing and reconstructing an excitatory synapse,” at the McGovern Institute for Brain Research at MIT on Thursday April 19. 2012.