Dec. 27, 2000 Researchers at Washington University School of Medicine in St. Louis have imaged language areas of the brain during recovery from stroke. This glimpse into the brain's natural rehabilitation pattern could lead to a better understanding of normal language processes and help optimize stroke therapy. The study is reported in the Dec. 26 issue of the journal Neurology.
Each year, 750,000 Americans suffer a temporary loss of blood flow to the brain, known as an ischemic stroke. Often, patients experience problems with speech and language, particularly after a stroke to the left side of the brain. Remarkably, many recover the majority of their language abilities within six to twelve months.
Although physical, occupational and speech therapies play key roles in recovery, scientists do not yet understand how the brain recovers and how different therapies influence rehabilitation. "We use many forms of therapy, but most of them are based on good common sense rather than on real, scientific evidence," explains Maurizio Corbetta, M.D., assistant professor of neurology, of radiology and of anatomy and neurobiology and the leader of this study.
When stroke patients regain some of their language abilities, their behavioral improvements may result from either of two mechanisms. The damaged area might recover its original functions or a different part of the brain might take over and compensate for the impaired region. Corbetta and colleagues set out to distinguish between these two possibilities. "We were interested in imaging areas potentially involved in language recovery to examine the underlying mechanisms," Corbetta says. "We also would like to find markers to distinguish between successful and unsuccessful recovery."
Recent advances in imaging techniques provide researchers with a window into the brain. To date, imaging studies of language recovery after stroke have examined patients on the basis of clinical symptoms. Scientists measure brain activity in patients with a specific language deficit in the hope of correlating that symptom with decreased activity in a particular area of the brain or capturing an image of how the brain reorganizes itself after injury.
But there is a great deal of variability in how clinical symptoms relate to lesion location and how the brain recovers after different lesions. From these methods alone, it has been difficult to determine a relationship between brain recovery and symptoms.
For this reason, Corbetta and colleagues began at the other side of the equation. They examined the long-term effects of damage to a well-defined region called the left inferior frontal gyrus — located on the left side, towards the front of the brain — known to be critical for language performance. Steven E. Petersen, Ph.D., and his colleagues at the School of Medicine have previously found that this region is very active in healthy volunteers during slightly challenging language tasks. For example, participants were asked to form a word that starts with "cou". When they think of a response, such as "cousin", this frontal area of the brain is active. However, the area does not appear to be involved when healthy individuals perform easy, fairly automatic tasks like reading words.
By screening 350 stroke patients Corbetta and colleagues identified six people whose damage was localized around this particular region. They tested these patients on the same language tasks used with healthy individuals.
All six patients performed poorly on the same tasks that activated this region in eight healthy participants, but performed normally on the easier task of word reading. "This is a good behavioral control," says Corbetta. "It confirms that this region is necessary for normal language performance, specifically on the more demanding verbal task."
The patients appeared to have a recovery plateau roughly 6 months after their stroke. At this point, the researchers studied the relationship between brain activity and verbal performance using positron emission tomography (PET) and functional magnetic resonance imaging (fMRI). These techniques allowed them to watch the pattern of brain activity as each patient performed these language tasks.
Surprisingly, PET images revealed that the area on the right side of the brain corresponding to the one damaged on the left side was significantly active during the difficult language tasks. In contrast, this region became only minimally active in the healthy participants.
When using PET, researchers must average the results from all the subjects in a group. In order to examine changes in brain activation in each patient, Corbetta and colleagues used fMRI. This is the first published account of changes in individual patients after stroke-induced frontal lobe damage. Again, the six patients had greater activity in the right side of the brain than the healthy participants. However, the level of activation on the right side failed to correlate with the subjects’ verbal performance.
In two patients, the area surrounding the damaged part of the brain on the left side also was active during the tasks. These patients had the best clinical recovery of language performance and the smallest lesions.
From these findings, the researchers suggest there might be two different mechanisms that mediate functional recovery of language. Several factors could determine which mechanism is implemented by each individual patient, including the extent of the brain damage.
First, areas in the right side of the brain that correspond to the damaged area on the left side appear to contribute to language recovery. After complete destruction of the left language area, the right side is active in all patients who have some degree of clinical recovery.
However, recovery appears to be better when parts of the left language area resume their role, as was found in the two patients with smaller lesions. This could indicate a second mechanism of recovery. Corbetta and his colleagues plan to examine additional patients immediately after a stroke and again after six months, when spontaneous recovery is fairly complete. These long-term data should reveal more about how the brain recovers, identify factors that predict recovery and clarify the brain's own rehabilitation technique. This new project is supported by the National Institute of Neurological Disorders and Stroke as part of a $4.7 million grant awarded to a team of researchers led by Marcus E. Raichle, M.D., the Allen P. and Josephine B. Green Professor of Pediatric Neurology, and a professor of radiology, of biomedical engineering and of anatomy and neurobiology.
This study is in collaboration with Howard Rosen, M.D., previous fellow in neurology at the School of Medicine and current assistant professor of neurology at the University of California at San Francisco; Martin Linenweber, graduate student in computer science; Avi Snyder, M.D., research assistant professor of radiology; Desiree White, Ph.D., associate professor of psychology; Julie Fiez, Ph.D., assistant professor of psychology at the University of Pittsburgh/Carnegie Mellon; Alexander W. Dromerick, M.D., associate professor of neurology and of occupational therapy; and Steven E. Petersen, Ph.D., professor of neurology, of radiology, of psychology and of anatomy and neurobiology, associate professor of neurological surgery and biomedical engineering.
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