ARTICLE IN BRIEF
A new study suggests that an increase in gray matter volume in the right hemisphere leads to better language outcomes in stroke patients with aphasia, providing the rationale for targeting the right hemisphere during aphasia rehabilitation.
When a left hemisphere stroke leaves a patient with significant aphasia, does the right hemisphere contribute to or impede recovery? That question remains a subject of debate in the world of stroke rehabilitation. Now, a new study, published in the October 31 online edition of Brain, strongly suggests that an increase in gray matter volume in the right hemisphere leads to better language outcomes, providing the rationale for targeting the right hemisphere during aphasia rehabilitation.
The stroke literature is inconsistent on the contribution of the right hemisphere to recovery, said lead study author Peter Turkeltaub, MD, PhD, an assistant professor of neurology and director of the Cognitive Recovery Lab at Georgetown University in Washington, DC. The inconsistency is due in part to the differential effects of small versus large strokes, he said.
With a small stroke and less severe aphasia, the left hemisphere may be able to compensate on its own through recruitment of other “language-capable” areas. But with a larger stroke and more severe aphasia, the right hemisphere may be called on to a greater degree, he explained. Thus, right hemisphere involvement will be associated with worse outcomes, but potentially as a consequence, not a cause, of those outcomes.
To determine the actual contribution of the right hemisphere to aphasia recovery, Dr. Turkeltaub performed a multistep evaluation of gray matter and language performance in 32 patients with aphasia following a left hemisphere stroke.
“The main factor that determines how well a person does after stroke is how severe the stroke is,” he said, “so we first estimated how severe a person's deficit should be based on the size of stroke and the location relative to left hemisphere language areas,” as well as age and gender.
That analysis took advantage of a relatively new technique, called support vector regression-based lesion-symptom mapping (SVR-LSM), which correlates lesion burden with aphasia symptoms, as measured by the Western Aphasia Battery-Revised (WAB-R). The SVR-LSM technique is an advance over standard lesion-symptom mapping, Dr. Turkeltaub explained, because it takes into account the known anatomic patterns of stroke damage, and it includes the effects of lesions on known language networks, rather than just focal brain areas, in assessing lesion burden.
“SVR-LSM identifies the specific areas of the brain in which damage causes behavioral deficits,” Dr. Turkeltaub said. “Whereas prior lesion-symptom mapping methods have examined each location in the brain one at a time, SVR-LSM examines every area simultaneously. This makes it more resistant to certain types of error in localization compared to prior techniques.”
Using the technique “allowed us to estimate how severe each person's deficit should be based on the size of stroke, the amount of damage in critical left hemisphere language areas, and demographic factors, like age and gender,” he said.
For each patient, Dr. Turkeltaub generated a prediction of aphasia severity based on right hemisphere damage alone, which could be compared to the WAB-R score. Next, he used voxel-based morphometry to measure gray matter density and volume, to see whether differences in right hemisphere gray matter could account for any discrepancies between the predicted and actual aphasia severity.
Dr. Turkeltaub found that an area in the right temporal parietal cortex, specifically the posterior-superior temporal gyrus and the supramarginal gyrus, was larger in those patients whose WAB-R scores were better than predicted based on their left hemisphere damage. The effect was significant for both the total score and on the subsections of spontaneous speech, repetition, and naming/word finding, but not auditory-verbal comprehension. “People with more gray matter volume are doing better than expected on each outcome, and those with less are doing worse than expected,” he said.
But were the increases in volume in the right hemisphere a result of the stroke, or did they simply represent the natural variation in gray matter volume among the population? To address this question, Dr. Turkeltaub compared the aphasia group as a whole to a group of 30 non-stroke controls.
He found that patients had a higher average volume than controls specifically in the areas correlated with improved aphasia. “That implies there was growth in these areas after the stroke, and the amount of growth related to outcome,” he said.
Finally, he compared the aphasia patients to 10 stroke patients with no aphasia. Again, the same regions were larger in the aphasia patients than the non-aphasia patients, suggesting the increased gray matter volume was not a general response to stroke but a specific consequence of language area damage.
The study was small, Dr. Turkeltaub emphasized, and needs to be repeated in a larger cohort, work he is beginning. But if the findings hold up, they may have important implications for aphasia treatment, he said.
Current experimental approaches include transcranial stimulation, either magnetic or electrical, applied to the right hemisphere. “In order to optimize those treatments, we need to have a thorough understanding of the brain changes that occur after stroke,” he said. A common approach is to stimulate over the right hemisphere homolog of Broca's area in order to suppress its activity. “Data such as ours suggest there may be other targets, and that perhaps we should be trying to facilitate activity in some parts of the right hemisphere,” Dr. Turkeltaub said. “The first successful brain stimulation studies of aphasia used right Broca's area suppression, and so much of the research to date has adopted that approach. But there have been no head-to-head trials demonstrating that right Broca's area inhibition provides the maximum benefit compared to other approaches, such as right hemisphere excitation. It's also important to recognize that no current approach has proven clinically significant benefits. More research is needed both to determine the most effective strategy for brain stimulation and to determine whether effects are clinically meaningful.”
Commenting on the study, Roy Hamilton, MD, an assistant professor of neurology at the University of Pennsylvania, said: “We know that the right hemisphere gets engaged after a stroke in persons with aphasia. We know it does something, but there has been a debate about whether the role of the right hemisphere is inhibitory or facilitative with respect to language recovery. This debate is important for determining how existing and novel aphasia therapies could be targeted.”
The results from this study, especially the comparison with age-matched controls, are compelling, Dr. Hamilton said. “This is pretty strong evidence that increased volume of these areas likely plays a compensatory role with respect to language recovery in patients with stroke and aphasia. This gives us the wherewithal to create novel hypotheses about where and how we should use stimulation in these patients.”
Gottfried Schlaug, MD, PhD, an associate professor of neurology at Harvard Medical School and Beth Israel Deaconess Medical Center, agreed. “This study makes a strong case that the nondominant side of the brain potentially contributes to recovery,” he said. “For patients with significant aphasia, the only way to recovery may be through the right hemisphere. We have to identify those critical regions in the right hemisphere that are involved naturally and figure out if there are behavioral techniques to facilitate their recovery further.”
One strategy being pursued by Dr. Schlaug and others is melodic intonation therapy, which uses musical speech to recruit the right hemisphere's language capabilities. An alternative or supplemental approach uses rhythmic activity of the left hand to engage the right side of the brain, potentially facilitating activation of language networks.
“Natural recovery shows us the way that the brain already engages in recovery,” Dr. Schlaug said. “Our task is to do better than nature.”
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