In 2003, 19 years after a car accident left him in a minimally conscious state, 39-year-old Terry Wallis spontaneously started to speak. Now, using specialized MRI scans, researchers have examined Wallis’s brain and found remarkable changes in his white matter. The findings could one day help scientists understand what happens in the brains of minimally conscious patients and how new interventions might rouse them back to full awareness.
Minimal consciousness is not uncommon after a severe brain injury, affecting at least 25,000 people in the United States. But unlike a coma, which usually lasts only a few weeks after an accident, a minimally conscious state can be prolonged for months or years. Patients are for the most part unaware of their surroundings and unable to communicate, but they may occasionally utter words, reach for objects, or respond to questions. (This condition is distinct from the vegetative state, which can also last for months or years but is not characterized by such intermittent awareness.)
Scientists know very little about what happens in the brain during such long stretches of impaired consciousness. Both human and animal research in recent years has shown that the adult brain has some capacity for self-repair. Stroke patients, for example, can sometimes recover speech or motor function as neural pathways in the brain reorganize to compensate for injured areas. And some patients do regain consciousness after months or even years, as in Wallis’s remarkable case. But doctors don’t yet know how to predict who will get better, and few treatments exist to boost whatever innate reorganization takes place. New brain imaging techniques, such as those used to generate the scans of Wallis’s brain, could help change that.
Wallis’s recovery began with one word, “mom.” Though such utterances are not unknown in minimally conscious patients, his doctors and family were surprised when his speech continued to improve. To try to find out the source of Wallis’s rare return to consciousness, a team led by neurologist Nicholas Schiff, of the Weill Medical College of Cornell University in New York, used a new variation of magnetic resonance imaging called diffusion tensor imaging (DTI). This technique can give scientists a detailed picture of the brain’s fiber tracts – the neural processes that relay messages between different parts of the brain. (See TR10: Diffusion Tensor Imaging, March/April 2006.) It had never been used to examine a minimally conscious patient before.
The first DTI scan, recorded eight months after his first words, showed that Wallis had profound brain damage. Compared with the brains of 20 normal subjects, both the overall structure and the neural fibers of his brain showed severe degeneration. “That in itself is a major piece of knowledge – that he could have this much injury and still have this kind of recovery years later,” says Schiff.
But scientists also discovered that a large area in the back of his brain appeared to have more fibers than normal, all oriented in the same direction – hinting that new pathways had sprouted to connect different brain structures. This unusual pattern encompassed a part of the brain known as the precuneus, which is highly active during conscious wakefulness but less active during sleep or anesthesia, says Steven Laureys, a neurologist at the University of Liege in Belgium.
Eighteen months after the first scan, Wallis had improved even more – he could move his previously paralyzed lower limbs, a recovery that was “as unexpected as him recovering speech,” says Schiff. When the researchers imaged his brain a second time, they found that the unusual area in the back had normalized, while another region, in an area that regulates movement, seemed to have grown more connected. The findings were published this week in The Journal of Clinical Investigation.
The researchers theorize that the changes they saw in the brain images correspond to growth of new neuronal connections. This growth might spark the recovery of different functions, such as language and movement. “Why did he emerge? None of us can answer this,” says Joy Hirsch, a neuroscientist at Columbia University who was not involved in the current study but collaborates with the researchers on other projects. “But it suggests a biological underpinning to recovery.”
James Bernat, a neurologist at Dartmouth Medical School in Hanover, NH, cautions against drawing too broad a conclusion from Wallis’s recovery: people tend to enter a minimally conscious state after suffering diffuse injury to the neural processes in the brain rather than massive death of the neural cells themselves, and such injuries may be easier to recover from. But he says the fact that Wallis’s motor improvements correlate with a neural change in a brain area that controls movement is particularly exciting. “We need to find out how often it happens, and why it happens,” says Bernat.
Of course, it’s difficult in any case to extrapolate from this one extraordinary case. No one knows what Wallis’s brain looked like before the accident or before he began to speak again. And it’s unclear why these specific parts of the brain were able to regenerate, or how the particular patterns of growth helped Wallis recover. But the findings do emphasize how important it is to study minimally conscious patients. “I think this paper serves as a beacon – it suggests there are mechanisms for emergence into consciousness, even if we don’t understand them,” says Hirsch. “This is a very hopeful sign for a field that has not received much attention from the medical and scientific world.”
Laureys, who wrote a commentary accompanying the paper, adds that he hopes the findings will change the sense of hopelessness many doctors feel about minimally conscious or vegetative patients. Though doctors know that the brain can reorganize itself by forming new neural connections throughout life (a phenomenon called neuroplasticity), Laureys says they previously thought this process ran out of steam soon after an injury. But he hopes this case will make them reconsider. “After many years, there is still a lot of plasticity going on with very significant clinical consequences,” he says.
Ultimately, doctors hope to find specific signs in the brain that predict which patients will get better. They also hope to develop targeted treatments that could help that process along. “But we can’t answer those questions without proper control studies,” says Hirsch.
The Cornell researchers now hope to study a larger number of people in the minimally conscious state to try to get a more systematic picture of the mechanisms underlying recovery.
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