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From Molecules to Mind

MIT’s new McGovern Institute for Brain Research hopes to connect the dots between brain cell activity and behavior changes.

Tangled neural fibers, knotted proteins, and clumps of degenerating neurons ravage the brains of Alzheimer’s sufferers. What causes these abnormalities? Why do they lead to dementia? Despite decades of research, very little is known about the brain, from the mechanisms of normal cognition and emotion to the causes of depression, addiction, and other diseases.

But since the 1990s, designated by the National Institute of Mental Health as the Decade of the Brain, there has been a global push to synthesize knowledge about the brain being gleaned by physiologists, computer modelers, imaging experts, and molecular biologists and to foster collaborations between these groups. The most recent example of this trend is MIT’s McGovern Institute for Brain Research, which officially opened on November 4.

When fully staffed, the Institute will house 16 principal investigators. One group of scientists will work to develop more sensitive and accurate imaging technologies, which can probe the activities of single neurons. Another team will investigate the impact of genetics on normal mental processes and disease. A third will use computational techniques to interpret large quantities of physiological data from live organisms in order to understand the neuronal bases of behavior.

Technology Review’s Assistant Editor Katherine Bourzac spoke with Robert Desimone, the Institute’s director, on the eve of its grand opening on November 4. Desimone studies the activity of neurons in the cortex in non-human primates, for example, how the brain decides which visual stimuli to privilege and which to ignore. Desimone hopes these studies will lead to insights about the neural mechanisms of perception, memory, and attention that characterize debilitating brain diseases such as Alzheimer’s.

Technology Review: What is the biggest challenge in brain science right now?

Robert Desimone: There’ve been tremendous advances in understanding the genetic basis of life, on the one hand, and also tremendous advances in brain images in intact human beings engaged in cognitive tests on the other hand. The challenge for neuroscience is bridging that gap – bridging from what goes on inside one cell in your brain to something that through a complex chain results in either normal cognition, thought, language, perception of beauty, on the one hand, or a terrible brain disorder on the other hand. That’s the challenge, understanding how you go from A to B.

TR: How do you plan to get there?

RD: The McGovern Institute was formed with faculty that have their research directed at all the things in between, going from molecules to mind, from Bob Horvitz who works on the genetics of the behavior of worms up through people like John Gabrieli and Nancy Kanwisher who do brain imaging studies in human beings and cognitive tests. And we have everyone in between: people doing computer modeling, people doing neurophysiology, people doing neuroanatomy, people looking at molecules and so on…People are willing to roll up their sleeves and collaborate with people who have expertise at different levels to make progress in understanding the mind.

TR: What have been the Institute’s most important recent accomplishments in the field?

RD: We have a paper coming out from Ann Graybiel this month in Nature reporting how habits are formed and how habits are reinstated through the operations of neurons in the basal ganglia. This has tremendous importance for understanding how addictions form – for example, where people might become addicted to something, whether it’s a drug, cigarettes, or whatever. Then they give it up. But then through a new stimulus in the future they might have renewed cravings and reactivate that habit easily. Graybiel has discovered the neural basis for this in animal studies in the basal ganglia – the reactivation of habits that you thought might have been lost. A very important study.

We have another very important study that’s coming out in Science that’s based on the collaboration between two McGovern faculty members that I think really epitomizes the fact that you need people working at different levels of analysis. It’s between Jim DiCarlo and Tommy Poggio. Jim and Tommy are taking the data from Jim’s neural recordings in monkeys as they recognize patterns and using Tommy’s fantastic computer analytical methods for finding patterns and data. They have developed algorithms for figuring out what the monkey sees from the recordings in his brain.

This is the kind of thing that scientists really love to see. We have all these ideas about how a given neural system works, but it’s when you implement it in a real software system to show that it actually works, it works the way you think it might work, that you really have a strong test. Those are two core findings this month.

TR: What are some of the new or upcoming technologies being used for brain research?

RD: We’re opening the Martinos Imaging Center at the McGovern Institute with the building opening. We have the imaging center set up for three large instruments. The third [space] is being purposely left empty so that we can develop the technology of the future. We allow for future development based on work that will go on at MIT.

Even using the machines that we have, we have faculty like Alan Jasanoff, who’s in nuclear engineering. He’s working on not just imaging activity of brain cells, but imaging certain molecules that are trafficking between cells. He’ll be able to implement that work on the scanners that we have here.

TR: What about functional magnetic resonance imaging (fMRI)? It shows activity in various parts of the brain by measuring blood flow, but there’s debate among scientists about what this activity really represents.’

RD: Functional MRI is going to be a very important component of the research here. But what we’re hoping to do is have a better understanding of the neural basis of these fMRI signals. We know that there are hemodynamic (blood flow) changes that are induced by neural activity. What aspect of neural activity induced these changes? We’re still not entirely clear. By the combination of animal and human work that we can do here, we’re hoping to be one of the leading sites in figuring out what that relationship is.

TR: Where is the field with respect to understanding brain diseases such as Parkinson’s and Alzheimer’s?

RD: I think the public wants honest answers to those questions, even though there’s always the temptation to imagine that we’re going to have important diseases cured in five or ten years. It’s like the IT field. No one predicted Google before Google happened. This is what science is like – if it’s a true breakthrough, something that’s really revolutionary, you don’t know it in advance of it happening.

All I can say is that the pieces are in place for making these really significant advances. The recent announcement of the human haplotype map that’s just been finished by the Human Genome Sequencing Center involving the Broad Institute across the street (from the McGovern Institute) is a very important advance in the genetics field (see “A New Map for Health”). It’s this kind of advance that we want to be able to capitalize on here in our neuroscience work.

The pieces are there. I think there’s going to be very significant progress in some of these brain disorders, but we’re not going to lay out false hope either – they’re very difficult problems.

TR: The McGovern website suggests that a better understanding of the brain can lead to an improvement in social relations. That sounds creepy.

RD: It may sound a little, but let me give you an example I think everyone can relate to. Research into heart disease has led to a revolution in how people live their lives. People have changed how they eat because they understand the impact that eating different things can have on the heart and the development of cancer. People have changed the way they eat, the way they exercise – the whole country is running differently because of what we’ve now understood about basic biology.

I think the same thing is going to happen from neuroscience. As we understand brain plasticity, as we understand brain development, this is going to be incorporated more and more into how we educate our children in an effective way. If we understand the brain mechanisms that control emotion or anger and impulsivity, this is going to affect how we teach children to control their angry emotions and their impulses.

These are the basic elements of human social life [for which] we’re going to understand something about the biology. It’s not that we’re going to be able to influence these things by taking a pill. You’re not going to take a pill and learn things better, or take a pill and not be angry anymore. We’re going to change the way we live based on this biological knowledge.

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