Ann M. Graybiel, the Walter A. Rosenblith Professor of Brain and Cognitive Sciences, last week was named the 2002 recipient of the James R. Killian Faculty Achievement Award. Established in 1971 as a tribute to MIT's 10th president and former chair of the MIT Corporation, the award recognizes extraordinary professional accomplishment by full-time members of the MIT faculty.
The committee's citation said, "Professor Graybiel has had a profound impact on research on the functional anatomy and physiology of the brain. She and her group made the pioneering discovery of the fundamental architecture of the large forebrain region known as the basal ganglia, and delineated the neurochemical organization of the system of neurotransmitters there. This work is of great significance because it represents the first time that a mechanism for directed neurochemical control of complex brain circuits was demonstrated." The decision was read at last week's faculty meeting by Paul E. Gray, professor of electrical engineering and computer science and president emeritus, who stood in for committee chair Jerry Hausman, professor of economics.
On May 9, the White House announced that Graybiel, an investigator at the McGovern Institute for Brain Research, was one of 15 people to receive the 2001 National Medal of Science from President Bush. Graybiel will be presented the medal at a ceremony in Washington, D.C., on June 13. She will deliver the Killian lecture in the fall.
Deborah Halber, science writer in the MIT News Office, interviewed Graybiel in her office in Building E25.
Halber: You have been awarded the National Medal of Science and now the Killian award. How do you feel about each of these?
Graybiel: I am honored and touched and moved. The Killian Award is given by the faculty of MIT. I consider it an honor even to be a member of the faculty of MIT. The faculty are extraordinary people. So I hold this honor dear. It is very, very special to me.
The National Medal of Science is a wonderful honor, our nation's highest honor in science, and receiving it just inspires me to do more. And most of all it makes me think of all the people with whom I've worked in the lab, and how lucky I am to have such colleagues. We always try to work as a team in our lab, and I am truly grateful to my colleagues.
How did you feel about being the only woman in the 2001 group?
When I first heard about this, I didn't notice that. Someone said, "Ann, do you realize you're the only woman?" I was so surprised. I couldn't believe it. So I looked at the list, and sure enough, I was.
I am very optimistic about the future. Things are changing. I grew up in northern Florida, and at the time, science was first taught in ninth grade. Girls weren't allowed to take the course. We had to take home economics. We learned how to make a collar and an apron, but we couldn't take science! Now young girls are trained, and conditions are better.
A real key is self-confidence. I try to build the self-confidence of students, including the young women. I want them to be confident, as well as competent. I certainly can say that there are wonderful women in our lab.
I do think it's still very difficult for most women in science. It's a very tough thing to pull it all off--a career and family. I'm just so grateful that I am able to be a woman and enjoy it, and yet to have a very serious career. I feel dedicated to being a role model. I don't know whether I have succeeded, but I sure try.
When did you first become interested in studying the human brain?
I'm truly fortunate. My father was a physician and a research scientist, and he taught me very early about the joy of doing research. And my mother was passionately interested in medicine.
I first got interested in nature and in learning about nature. I wanted to start in math and physics and then go to chemistry and then do biology and then psychology and then finally philosophy. That was my eighth-grade dream. I didn't do all that. I didn't know that I'd work on the brain. So I went into chemistry and then biology at Harvard. At that time, psychology and biology were quite separate things. I asked whether I could do a joint degree, but it was too early.
It is a huge privilege to work on these subjects--the biology of cognition, the biology of human behavior--so my interest has grown and grown, and is still growing.
Did you think, from your first involvement, that we would have come as far as we have?
When I went into neuroscience, all the great questions were thought to be unsolvable. How do we think? How do we feel? What is consciousness? How do we generate an emotion? So what people concentrated on is: 'what is it about the nervous system that allows us to coordinate our muscles?' or 'what happens when light comes in our eyes?' or 'what are the early stages of seeing or feeling or hearing?'
But the big questions at a more cognitive level were considered unapproachable. Now I think it's evident that those questions are approachable. So in that sense, I'm thrilled. I think we've come a long way. I don't think, though, that we really know the code used by the brain to do its computations. The field of brain science is very young, very dynamic and absolutely wide open. It's probably like physics in the early days, and I don't know whether we've had our Einstein yet.
Why study the basal ganglia when so many people say the cortex is the brain's "executive"?
The cerebral cortex is a fabulous organ--a thin sheet of cells on the outside of the brain that probably underlies most of our cognitive abilities. But it is my belief that the neocortex requires the deeper structures of the brain, like the basal ganglia, to carry out its cognitive functions. As we perceive and think and plan, the neocortex moves from one state to another, and the hunch I have is that the basal ganglia help the neocortex go into a new state. As we develop routines of behavior or habits, we are beginning to think that the basal ganglia act to put the behavioral routines together so they can be expressed as "chunks." This then frees up the neocortex to carry out cognitive operations.
Are habits a good thing or a bad thing?
They're both, of course. We all have good habits and bad habits. The interesting questions are how can we develop good ones, and how can we avoid the bad ones? One of the things that intrigues us in the lab is that if you look at many habits, they are triggered by some context, either in the environment or internally. You get up in the morning and have a cup of coffee and read the paper or go to the computer. Ordinarily, it's context that triggers a habit.
Understanding these triggers is important, as is understanding how just entering into a context can make us, without thinking, do one thing or another. As I've worked on this experimentally, the thing that's surprised me the most is the cells in the part of the brain that respond to a certain stimulus only do it if the behavior is in one context. If you suddenly turn the room lights on, or move the animal to another place, the response is gone and the cells don't fire. So context is profoundly interesting. This is true of the neocortex and it's true of the basal ganglia.
What do habits and addictions have in common?
Anyone who has tried to stop smoking or kick any other habit knows how terrible it is to go, for example, to where the cigarettes used to be kept. So again, context is important. But I think you've asked the $64,000 question--no one knows exactly what happens in the physiological sense when someone is addicted. There are some changes in the brain. In the case of addiction, we get a real surge in dopamine, a reward signal in the brain, at least early on in the addictive phase. This really turns the brain on. In a habit, we probably do, too, early on, but after a while the behavior becomes autonomous. Then even if the reward rush isn't there, we do it anyway.
Now, the interesting thing is that some of the mechanisms that lead to repetitive behaviors in an addicted state may be similar to the ones that lead to abnormal movements in some neurological disorders. For example, in Parkinson's disease, after a few years of L-dopa therapy, the patient may develop a condition in which he develops abnormal movements. The patient was unable to move, then the L-dopa lets him move, but then he develops abnormal, unwanted movements that are almost the opposite of Parkinson's. They're almost like the abnormal movements in Huntington's disease. So it's a wretched, horrible situation.
We are very actively engaged in trying to understand this, because I really hope that if we study habit and the basis of repetitive behaviors, we can help to understand the brain mechanisms involved in Parkinson's disease and Huntington's disease and disorders such as obsessive-compulsive disorder and Tourette syndrome.
Do you have any habits that you don't like?
Yes, do I have to say what they are? (laughing) I think we all do.
What are some of the biggest potential payoffs in brain research?
I think we have enormous undeveloped potential to use our brain more fully. How do we learn to motivate ourselves? I feel very, very strongly that we really might help everyone if we could understand how we become motivated and how we develop these patterns of behavior. Think about what it would be like if it were perfectly normal for us to do many different things that we never thought we were capable of doing. This potential is lurking in there, and we don't tap it.
Are we close to curing brain disorders?
I think fundamental progress toward curing or at least treating a number of neurodegenerative disorders is coming, and I don't think help is a century away. I work with many people and organizations with a sense of mission and a sense of hurry about helping patients with disorders such as Parkinson's disease, Alzheimer's disease, Huntington's disease, Tourette syndrome and obsessive-compulsive disorder--and the energy and talent and new discoveries are there.
I feel the same sense of mission about also helping normal people. I have the same passion to help us have happier, more fulfilling lives. I want to understand the brain well enough so someone can apply this knowledge to help us be everything we could be, and I mean this in a scientifically well-founded sense. No one would deny that it's a good idea to exercise. I believe we should exercise our brains. I believe we should exercise in every way we can. But we need to know more about how to do that. And we need to know how to help people want to do it. Most people laugh at the idea that neuroscience could ever help with societal issues. So at the risk of being laughed at, I say it can. Knowledge is a good thing.
A version of this article appeared in MIT Tech Talk on May 22, 2002.
