The annual McGovern Institute symposium took place on May 8, 2013 and featured nine talks on the subject of motor control and the motor cortex. In this video, Larry Abbott of Columbia University presents his talk, entitled “Network Models of Motor Cortex.”
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2013 McGovern Institute Symposium
The annual McGovern Institute symposium, which took place on May 8, 2013, featured nine talks on the subject of motor control and the motor cortex. Motor commands represent the output of the brain and its evolutionary raison d’être. To produce useful movements the brain must select appropriate combinations of muscles from a vast range of possibilities, and must activate them with precise control of force and timing.
This symposium explored how the brain accomplishes this task: what computations does it perform to control movement, how and where in the brain does this happen, and how can this knowledge be exploited for rehabilitation and for the development of neural prosthetics.
2013 McGovern Institute Retreat
Compulsive no more
By activating a brain circuit that controls compulsive behavior, McGovern neuroscientists have shown that they can block a compulsive behavior in mice — a result that could help researchers develop new treatments for diseases such as obsessive-compulsive disorder (OCD) and Tourette’s syndrome.
About 1 percent of U.S. adults suffer from OCD, and patients usually receive antianxiety drugs or antidepressants, behavioral therapy, or a combination of therapy and medication. For those who do not respond to those treatments, a new alternative is deep brain stimulation, which delivers electrical impulses via a pacemaker implanted in the brain.
For this study, the MIT team used optogenetics to control neuron activity with light. This technique is not yet ready for use in human patients, but studies such as this one could help researchers identify brain activity patterns that signal the onset of compulsive behavior, allowing them to more precisely time the delivery of deep brain stimulation.
“You don’t have to stimulate all the time. You can do it in a very nuanced way,” says Ann Graybiel, an Institute Professor at MIT, a member of MIT’s McGovern Institute for Brain Research and the senior author of a Science paper describing the study.
The paper’s lead author is Eric Burguière, a former postdoc in Graybiel’s lab who is now at the Brain and Spine Institute in Paris. Other authors are Patricia Monteiro, a research affiliate at the McGovern Institute, and Guoping Feng, the James W. and Patricia T. Poitras Professor of Brain and Cognitive Sciences and a member of the McGovern Institute.
Controlling compulsion
In earlier studies, Graybiel has focused on how to break normal habits; in the current work, she turned to a mouse model developed by Feng to try to block a compulsive behavior. The model mice lack a particular gene, known as Sapap3, that codes for a protein found in the synapses of neurons in the striatum — a part of the brain related to addiction and repetitive behavioral problems, as well as normal functions such as decision-making, planning and response to reward.
For this study, the researchers trained mice whose Sapap3 gene was knocked out to groom compulsively at a specific time, allowing the researchers to try to interrupt the compulsion. To do this, they used a Pavlovian conditioning strategy in which a neutral event (a tone) is paired with a stimulus that provokes the desired behavior — in this case, a drop of water on the mouse’s nose, which triggers the mouse to groom. This strategy was based on therapeutic work with OCD patients, which uses this kind of conditioning.
After several hundred trials, both normal and knockout mice became conditioned to groom upon hearing the tone, which always occurred just over a second before the water drop fell. However, after a certain point their behaviors diverged: The normal mice began waiting until just before the water drop fell to begin grooming. This type of behavior is known as optimization, because it prevents the mice from wasting unnecessary effort.
This behavior optimization never appeared in the knockout mice, which continued to groom as soon as they heard the tone, suggesting that their ability to suppress compulsive behavior was impaired.
The researchers suspected that failed communication between the striatum, which is related to habits, and the neocortex, the seat of higher functions that can override simpler behaviors, might be to blame for the mice’s compulsive behavior. To test this idea, they used optogenetics, which allows them to control cell activity with light by engineering cells to express light-sensitive proteins.
When the researchers stimulated light-sensitive cortical cells that send messages to the striatum at the same time that the tone went off, the knockout mice stopped their compulsive grooming almost totally, yet they could still groom when the water drop came. The researchers suggest that this cure resulted from signals sent from the cortical neurons to a very small group of inhibitory neurons in the striatum, which silence the activity of neighboring striatal cells and cut off the compulsive behavior.
“Through the activation of this pathway, we could elicit behavior inhibition, which appears to be dysfunctional in our animals,” Burguière says.
The researchers also tested the optogenetic intervention in mice as they groomed in their cages, with no conditioning cues. During three-minute periods of light stimulation, the knockout mice groomed much less than they did without the stimulation.
Scott Rauch, president and psychiatrist-in-chief of McLean Hospital in Belmont, Mass., says the MIT study “opens the door to a universe of new possibilities by identifying a cellular and circuitry target for future interventions.”
“This represents a major leap forward, both in terms of delineating the brain basis of pathological compulsive behavior and in offering potential avenues for new treatment approaches,” adds Rauch, who was not involved in this study.
Graybiel and Burguière are now seeking markers of brain activity that could reveal when a compulsive behavior is about to start, to help guide the further development of deep brain stimulation treatments for OCD patients.
The research was funded by the Simons Initiative on Autism and the Brain at MIT, the National Institute of Child Health and Human Development, the National Institute of Mental Health, and the Simons Foundation Autism Research Initiative.
Compulsive no more
By activating a brain circuit that controls compulsive behavior, researchers in Ann Graybiel‘s lab have shown that they can block a compulsive behavior in mice — a result that could help researchers develop new treatments for diseases such as obsessive-compulsive disorder (OCD) and Tourette’s syndrome. Read the story >>
Neville Hogan: 2013 McGovern Institute Symposium
The annual McGovern Institute symposium took place on May 8, 2013 and featured nine talks on the subject of motor control and the motor cortex. In this video, Neville Hogan of MIT presents his talk entitled, “Modular dynamics in motor control and neuro-rehabilitation.”
Emile Bruneau: Tweaking the Empathy Gap
Emile Bruneau, a postdoctoral associate in Rebecca Saxe’s lab at the McGovern Institute, is interested in the psychology of human conflict. He is working with Saxe to figure out why empathy — the ability to feel compassion for another person’s suffering — often fails between members of opposing conflict groups. Bruneau is also trying to locate patterns of brain activity that correlate with empathy, in hopes of eventually using such measures to determine how well people respond to reconciliation programs aimed at boosting empathy between groups in conflict.
Read more about Emile Bruneau’s work in the New York Times magazine.
Ann Graybiel Meets the President of the United States
President Barack Obama greets the 2012 U.S. Kavli Prize Laureates in the Oval Office, March 28, 2013.
Obama hosts Dresselhaus, Graybiel and Luu in Oval Office
President Barack Obama met Thursday, March 28, in the Oval Office with the six U.S. recipients of the 2012 Kavli Prizes — including MIT’s Mildred S. Dresselhaus, Ann M. Graybiel and Jane X. Luu. Obama and his science and technology advisor, John P. Holdren, received the scientists to recognize their landmark contributions in nanoscience, neuroscience and astrophysics, respectively. [watch video]
“American scientists, engineers and innovators strengthen our nation every day and in countless ways, but the all-stars honored by the Kavli Foundation deserve special praise for the scale of their advances in some of the most important and exciting research disciplines today,” said Holdren, who also serves as director of the White House Office of Science and Technology Policy. “I am grateful not only for their profound accomplishments, but for the inspiration they are providing to a new generation of doers, makers and discoverers.”
The researchers received their Kavli Prizes for making fundamental contributions to our understanding of the outer solar system; of the differences in material properties at nano- and larger scales; and of how the brain receives and responds to sensations such as sight, sound and touch.
The 2012 Kavli Prize in Astrophysics was awarded to Luu, David C. Jewitt of the University of California at Los Angeles, and Michael E. Brown of the California Institute of Technology 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. The Kuiper Belt lies beyond the orbit of Neptune and is a disk of more than 70,000 small bodies made of rock and ice, and orbiting the sun. Jewitt and Luu discovered the Kuiper Belt, and Brown discovered and characterized many of its largest members.
The 2012 Kavli Prize in Nanoscience was awarded to Dresselhaus for her work explaining why the properties of materials structured at the nanoscale can vary so much from those of the same materials at larger dimensions. Her early work provided the foundation for later discoveries concerning the famous C60 buckyball, carbon nanotubes and graphene. Dresselhaus received the Kavli Prize for her research into uniform oscillations of elastic arrangements of atoms or molecules called phonons; phonon-electron interactions; and heat conductivity in nanostructures.
The 2012 Kavli Prize in Neuroscience was awarded to Graybiel, Cornelia Isabella Bargmann of Rockefeller University, and Winfried Denk of the Max Planck Institute for Medical Research, who have pioneered the study of how sensory signals pass from the point of sensation — whether the eye, the foot or the nose — to the brain, and how decisions are made to respond. Each working on different parts of the brain, and using different techniques and models, they have combined precise neuroanatomy with sophisticated functional studies to gain understanding of their chosen systems.
MIT researchers join Obama for brain announcement
Four MIT neuroscientists were among those invited to the White House on Tuesday, April 2, when President Barack Obama announced a new initiative to understand the human brain.
Professors Ed Boyden, Emery Brown, Robert Desimone and Sebastian Seung were among a group of leading researchers who joined Obama for the announcement, along with Francis Collins, director of the National Institutes of Health, and representatives of federal and private funders of neuroscience research.
In unveiling the BRAIN (Brain Research through Advancing Innovative Neurotechnologies) Initiative, Obama highlighted brain research as one of his administration’s “grand challenges” — ambitious yet achievable goals that demand new innovations and breakthroughs in science and technology.
A key goal of the BRAIN Initiative will be to accelerate the development of new technologies to visualize brain activity and to understand how this activity is linked to behavior and to brain disorders.
“There is this enormous mystery waiting to be unlocked,” Obama said, “and the BRAIN Initiative will change that by giving scientists the tools they need to get a dynamic picture of the brain in action and better understand how we think and how we learn and how we remember. And that knowledge could be — will be — transformative.”
To jump-start the initiative, the NIH, the Defense Advanced Research Projects Agency, and the National Science Foundation will invest some $100 million in research support beginning in the next fiscal year. Planning will be overseen by a working group co-chaired by Cornelia Bargmann PhD ’87, now at Rockefeller University, and William Newsome of Stanford University. Brown, an MIT professor of computational neuroscience and of health sciences and technology, will serve as a member of the working group.
Boyden, the Benesse Career Development Associate Professor of Research in Engineering, has pioneered the development of new technologies for studying brain activity. Desimone, the Doris and Don Berkey Professor of Neuroscience, is director of MIT’s McGovern Institute for Brain Research, which conducts research in many areas relevant to the new initiative. Seung, a professor of computational neuroscience and physics, is a leader in the field of “connectomics,” the effort to describe the wiring diagram of the brain.