New hope for the damaged brain

Brain plasticity — the ability of the brain to renew itself — is a hot research topic for good reason: The Centers for Disease Control and Prevention predicts an epidemic of brain-related health problems as our society ages.

A major cause of such problems is stroke, the fourth leading cause of death in the United States and a major cause of long-term disability. In a groundbreaking effort to improve people's recovery after one of these devastating events, Georgetown University Medical Center has partnered with MedStar National Rehabilitation Hospital in Washington, D.C., to create the Center for Brain Plasticity and Recovery, which will apply new thinking and state-of-the-art research methods to improve recovery from stroke and, in the future, from other neurological disorders as well.

In July, Georgetown tapped cognitive psychologist Elissa Newport, PhD, of the University of Rochester's department of brain and cognitive sciences to head the new center, a post she assumed with Alexander Dromerick, MD, a Georgetown neurologist and stroke specialist, as its co-director.

"Elissa is an articulate spokesperson for the power of the interdisciplinary approach, and she lives and breathes science in a way that energizes [medical and psychology] students and fellows to pursue their work collaboratively and with great rigor," says Georgetown Medical Center's executive vice president, Howard Federoff, MD, PhD. "I'm confident that in future years, great young trainees will want to be part of the center because of her charisma and leadership."

At the center, scientists from a range of disciplines will study a variety of interventions that have the potential to enhance recovery after stroke, from cellular mechanisms that may facilitate healing to brain stimulation techniques that might optimize brain functioning. The Monitor spoke with Newport about the center's direction, the promise of plasticity research and the importance of interdisciplinary collaboration in addressing a public health problem that is bound to worsen as we face a "silver tsunami" of aging citizens.

How long has brain plasticity work been going on, and why is it vital to the new center's work?

Scientists have been interested in brain plasticity since at least the 1930s. Early work suggested that there are critical periods for the development and reorganization of brain function, and showed that the brain's ability to change and learn declines with age. For example, when children experience damage to the left hemisphere, they reorganize language to the right hemisphere, but that no longer happens in adulthood. As a result, we used to think that extensive plasticity was not possible in the adult brain.

But in the last 10 or 15 years, researchers have begun to see evidence of residual plasticity in the adult brain, with a wave of research suggesting that the adult brain can still demonstrate plasticity in structure and function. So now, you see paper after paper in Nature and Science saying that taxi drivers in London have bigger hippocampi than those of other people, or that you can enlarge the areas of the brain dealing with sensory motor control by putting people in experiments where they learn to juggle.

These findings hint that there might be ways to harness such mechanisms after injury or disease — hints that we hope to exploit in our work at the center.

Why is interdisciplinary work so important when studying stroke recovery?

Stroke recovery is a complex process that involves the reduction of injury and the repair of damaged circuits, as well as the restoration or retraining of impaired physical, sensory and cognitive processes. So it requires the input of many disciplines. One of these disciplines is represented by cellular-molecular people — scientists who study gene expression and cellular-molecular approaches to stimulating the formation of new synapses and circuits.

Then of course there are neurologists, who provide our clinical understanding of stroke and stroke recovery. This group includes pediatric and adult stroke neurologists, as well as neurologists who specialize in rehabilitation medicine and in clinical trials research.

A third group is cognitive neuroscientists, people like me who do basic research on learning, development and memory. We believe that rehabilitation involves many of the same mechanisms that underlie basic learning and memory, so if we understand how to control and enhance learning and memory, we'll also understand how to make rehabilitation work better at the times we need it.

What are some particularly promising directions the center will explore in studying stroke recovery and brain plasticity?

There are a few areas we're very interested in. One is something my colleague Alex Dromerick was already investigating at the National Rehabilitation Hospital that is related to my own interests in "critical periods" — windows of time where the brain shows more plasticity than others. In the case of stroke, the literature suggests there is a short period of time after the event where the brain tries to repair itself through processes such as sprouting new synaptic connections. We don't know whether these processes are actually functional, but they happen pretty early on after a stroke, usually not at a time when people are well enough to undergo rehabilitation. So one promising direction is to test whether we can catch that very early period using appropriate rehabilitation methods, or, by manipulating the underlying molecular mechanisms, even push those processes to occur later, when patients are better able to work on rehabilitation training.

Several of our scientists, including Peter Turkeltaub, MD, PhD, and Michelle Harris-Love, PhD, are also using brain stimulation techniques to study whether stimulating or inhibiting specific parts of the brain can aid in recovery. In these techniques, you give participants magnetic resonance imaging that provides pictures of their brain and skull, then load the images into software that enables you to direct a stimulator on the skull to very precise areas of the brain.

Alex Dromerick, William Gaillard, MD, and I are also interested in examining ways to enhance language reorganization in the brains of adult stroke patients. Children who have had a stroke or other brain disorder are able to shift language over to the right hemisphere. In adults, this inter-hemispheric relationship has changed: Each hemisphere inhibits the other so they're not competing to perform the same functions. Peter Turkeltaub has been doing research with aphasic patients — those who have lost language capabilities — in which he alters the relationships between the hemispheres by using stimulation techniques, thus enabling the uninjured portions of the left hemisphere to work better. You can also combine stimulation techniques with behavioral training to enhance activity that is relevant to impaired cognitive functions.

What unique attributes does your background in psychological science bring to your new role?

Scientists are not going to solve the problem of recovery from damage to the brain with cellular, molecular or pharmaceutical treatments alone. We're going to have to figure out how to get learning to occur in combination with that, whether it is cognitive, sensory or motor learning.

Take an extreme example. Let's say that after a neurological injury, stem cell techniques allowed us to give people a new piece of a brain. That approach would work fine for repairing the heart or kidney or bladder. But what would I do with a new brain? What you want back are the things you've learned and the memories your brain holds — the networks that represent what you've learned and remember. That's what psychologists bring to the future of brain recovery.

You seem to be a model of brain plasticity yourself, taking over this whole new role and area.

It seems to be a habit of mine to take on a new field every 10 years. For example, some time ago I took on the study of sign languages as a way of understanding the biology of language learning and constraints on language structure. I did the same thing when I became chair of the department of brain and cognitive sciences at Rochester, devoting a chunk of my time to building a new department. I have always stayed focused on the same big questions — the nature of learning and developmental change — but find it continually stimulating to find new areas to learn about within that domain.

That said, this is a bigger move than most. Moving into a medical setting, seeing patients, going on rounds, learning how to talk to patients and their families and hoping that some of the basic work on brain plasticity we're doing might change the future of stroke recovery — all of these activities are quite new for me. I'm dealing with many of the same questions I have been studying all along, but in a different way. Our field is on the brink of making real breakthroughs in understanding how the brain can recover. It's very exciting.

Tori DeAngelis is a writer in Syracuse, N.Y.