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Imaging Aphasia: The Coming Paradigm Shift
Brain and Cognition 42, 60–63 (2000) doi:10.1006/brcg.1999.1162, available online at http://www.idealibrary.com on
Imaging Aphasia: The Coming Paradigm Shift Pooja Khatri and Daniel B. Hier University of Illinois
Dating back to 1861, when Paul Broca correlated Leborgne’s left hemisphere lesion with his aphasia and right-sided hemiplegia, the dominant method in aphasia research has been clinical–anatomical correlation. With the advent of PET, followed by SPECT, and finally fMRI, will come a paradigm shift. Instead of correlating brain lesions with aphasic symptoms, we can now correlate brain function with language performance. Instead of asking, ‘‘What is injured?’’ we can now ask, ‘‘What is working?’’ Functional imaging can address a variety of questions including the locus of activation of a given brain function, the relative responsiveness among regions involved in the same function, and connecting pathways between regions. For instance, Raichle et al. (1997) showed an unexpected activation of the right cerebellum in practice-related learning of verb generation in normal subjects. In addition, Benson et al. (1999) have shown that verb-generation tasks, in contrast with naming and reading tasks, provide remarkably reliable activation of the dominant hemisphere. New patterns of connectivity have been suggested by Weiller et al. (1995), who showed that despite complete destruction of Wernicke’s area, increased activation in Broca’s area is seen on fMRI during word repetition. Aphasia occurs in eighty thousand new people each year. Prognostic indicators for this devastating condition are needed. Currently, the single most important predictor of long-term outcome is initial aphasia severity, which lacks the power to predict individual outcome. Another central goal is to understand the mechanisms of recovery. Theories such as compensation, redundancy, diaschisis, latent pathways, and restoration provide a theoretical framework for considering how recovery might occur. Empirical data is needed to know how recovery does occur. Eventually, a better understanding of recovery will lead to more effective clinical interventions. Several intriAddress correspondence and reprint requests to Pooja Khatri or Daniel B. Hier, Department of Neurology, University of Illinois, 912 S. Wood Street, Chicago IL 60612. E-mail: neuro@ uic.edu. 60 0278-2626/00 $35.00 Copyright 2000 by Academic Press All rights of reproduction in any form reserved.
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guing questions must be answered. What is the role of the right hemisphere? How does reorganization of the left hemisphere influence recovery? Do individual differences in organization of language influence recovery from aphasia? And how may therapy and retraining remap language in the brain after aphasia? The role of the right hemisphere in language function and recovery remains controversial. Weiller et al. (1995) have used functional imaging to show that the right hemisphere may play a crucial role in effective recovery from aphasia. They studied six patients with complete destruction of Wernicke’s area who subsequently recovered from Wernicke’s aphasia. Compared to controls, these recovered aphasics showed increased activation in right hemisphere areas homotopic to left hemisphere language areas. In addition, they found increased left frontal cortex activation, including Broca’s area, during a verb generation task. Similarly, Thulborn et al. (1999) followed the temporal course of two recovering aphasics with fMRI. They demonstrated progressive right hemisphere activation during silent sentence reading tasks when compared to controls. Other studies have suggested that recovery from aphasia depends on the sparing of left hemisphere language cortex or reactivation of language areas in the left hemisphere. Karbe et al. (1995) studied twenty-two aphasic patients with a variety of infarcts. They found that the best predictor of twoyear outcome after Wernicke’s or Broca’s aphasia was early activation of left Wernicke’s or Broca’s area, respectively. In their study, right hemisphere activation showed no correlation with recovery. Furthermore, some studies show that right hemisphere activation by language tasks after aphasia may actually predict poor recovery. For example, Heiss et al. (1999) divided twenty-two patients by left hemisphere infarcts into subcortical, frontal, and temporal groups, irrespective of aphasia type and severity. They demonstrated that a shift from right hemisphere to left hemisphere activation by language tasks corresponded with better recovery both within and between groups, with the best recovery corresponding to preserved and reactivated left temporal regions. They hypothesize ‘‘a hierarchy of strategies for recovery’’ with the preferred strategy being utilization of previous language zones in the left hemisphere. Synthesis of these studies into a cohesive theory of how recovery from aphasia occurs is difficult. It is complicated by variations in number of patients studied, locations and sizes of infarcts, types of aphasia, aphasia measurement, imaging activation tasks, time course of the studies, imaging analysis methods, and research designs. Specifically, why has right hemisphere activation by language been shown to correlate with good recovery from aphasia in some studies, and poor recovery in others? Closer examination of Weiller et al.’s study (1995) yields two speculative explanations. First, perilesional areas that would be unique to certain individuals and not apparent with group averaging were not assessed. Second, increased left hemi-
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sphere activation was present in these patients, possibly accounting for some of the recovery noted. In the study by Thulborn et al., the degree to which the two patients recovered is not known, as they were not assessed by objective measures. Variability in activation tasks alone cannot explain these differences, as conflicting results are seen between groups using the same tasks (Weiller, 1995; Wharburton, 1999). Thus, while this issue requires further study, the evidence appears to favor the dominant hemisphere language areas as the source of most recovery from aphasia. However, individual exceptions may occur. Functional brain imaging may help us understand whether individual differences explain differences in recovery from aphasia. Functional brain imaging also gives us an important tool to study the effectiveness of retraining and rehabilitation of aphasia. This may give more information about the recovery process generally as well. Belin et al. (1996) studied seven nonfluent aphasics with left hemisphere global hypoperfusion who had an absence of recovery despite standard speech therapies. These patients were trained with melodic intonation therapy (MIT), a modality of aphasia therapy, for two years and subsequently imaged by PET. Increased homotopic right hemisphere activation was visualized without MIT word repetition, while the same patient showed increased left hemisphere language area activation with MIT word repetition. The study by Belin et al. suggests that right hemisphere activation patterns may not be related to the recovery process. Instead they may represent the persistence of aphasia, a significant shift in the understanding of right hemisphere activation if supported by further studies. In conclusion, functional imaging allows us to address previously unanswerable questions including the role of the right hemisphere in recovery from aphasia, how the left hemisphere reorganizes itself for language after aphasia, how individual differences in organization for language contribute to recovery from aphasia, and how rehabilitation from aphasia alters brain organization for language. As answers to these questions lead to new and different understandings of the brain, the paradigm shift is on the way. REFERENCES Belin, P., Van Eeckhout, P., Zilbovicius, M., Remy, P., Francois, C., Guillaume, S., Chain, F., Rancurel, G., & Samson, Y. 1996. Recovery from nonfluent aphasia after melodic intonation therapy: A PET study. Neurology, 47, 1504–1511. Benson, R. R., Fitzgerald, D. B., LeSueur, L. L., Kennedy, D. N., Kwong, K. K., Buchbinder, B. R., Davis T. L., Weisskoff, R. M., Talavage, T. M., Logan, W. J., Cosgrove, G. R., Belliveau, J. W., & Rosen, B. R. 1999. Language dominance determined by whole brain functional MRI in patients with brain lesions. Neurology, 52, 798–809. Heiss, W-D., Kessler, J., Thiel, A., Ghaemi, M., & Karbe, H. 1999. Differential capacity of left and right hemispheric areas for compensation of poststroke aphasia. Annals of Neurology, 45, 430–438. Raichle, M. E. 1997. Functional imaging in behavioral neurology and neuropsychology. In
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T. E. Feinberg & M. J. Farrah (Eds.), Behavioral neurology and neuropsychology (pp. 83–100). New York: McGraw–Hill, . Thulborn, K. R., Carpenter, P. A., & Just, M. A. 1999. Plasticity of language-related brain function during recovery from stroke. Stroke, 30, 749–54. Warburton, E., Price, C. J., Swinburn, K., & Wise, R. J. 1999. Mechanisms of recovery from aphasia: Evidence from positron emission tomography studies. Journal of Neurology, Neurosurgery & Psychiatry, 66, 155–161. Weiller, C., Isensee, C., Rijntjes, M., Huber, W., Muller, S. P., Bier, D., Dutschka, K., Woods, R. P., Noth, J., & Diener, H. C. (1995). Recovery from Wernicke’s aphasia: A positron emission tomographic study. Annals of Neurology, 37, 723–732.
Imaging Aphasia: The Coming Paradigm Shift Pooja Khatri and Daniel B. Hier University of Illinois
Dating back to 1861, when Paul Broca correlated Leborgne’s left hemisphere lesion with his aphasia and right-sided hemiplegia, the dominant method in aphasia research has been clinical–anatomical correlation. With the advent of PET, followed by SPECT, and finally fMRI, will come a paradigm shift. Instead of correlating brain lesions with aphasic symptoms, we can now correlate brain function with language performance. Instead of asking, ‘‘What is injured?’’ we can now ask, ‘‘What is working?’’ Functional imaging can address a variety of questions including the locus of activation of a given brain function, the relative responsiveness among regions involved in the same function, and connecting pathways between regions. For instance, Raichle et al. (1997) showed an unexpected activation of the right cerebellum in practice-related learning of verb generation in normal subjects. In addition, Benson et al. (1999) have shown that verb-generation tasks, in contrast with naming and reading tasks, provide remarkably reliable activation of the dominant hemisphere. New patterns of connectivity have been suggested by Weiller et al. (1995), who showed that despite complete destruction of Wernicke’s area, increased activation in Broca’s area is seen on fMRI during word repetition. Aphasia occurs in eighty thousand new people each year. Prognostic indicators for this devastating condition are needed. Currently, the single most important predictor of long-term outcome is initial aphasia severity, which lacks the power to predict individual outcome. Another central goal is to understand the mechanisms of recovery. Theories such as compensation, redundancy, diaschisis, latent pathways, and restoration provide a theoretical framework for considering how recovery might occur. Empirical data is needed to know how recovery does occur. Eventually, a better understanding of recovery will lead to more effective clinical interventions. Several intriAddress correspondence and reprint requests to Pooja Khatri or Daniel B. Hier, Department of Neurology, University of Illinois, 912 S. Wood Street, Chicago IL 60612. E-mail: neuro@ uic.edu. 60 0278-2626/00 $35.00 Copyright 2000 by Academic Press All rights of reproduction in any form reserved.
MILLENNIUM ISSUE
61
guing questions must be answered. What is the role of the right hemisphere? How does reorganization of the left hemisphere influence recovery? Do individual differences in organization of language influence recovery from aphasia? And how may therapy and retraining remap language in the brain after aphasia? The role of the right hemisphere in language function and recovery remains controversial. Weiller et al. (1995) have used functional imaging to show that the right hemisphere may play a crucial role in effective recovery from aphasia. They studied six patients with complete destruction of Wernicke’s area who subsequently recovered from Wernicke’s aphasia. Compared to controls, these recovered aphasics showed increased activation in right hemisphere areas homotopic to left hemisphere language areas. In addition, they found increased left frontal cortex activation, including Broca’s area, during a verb generation task. Similarly, Thulborn et al. (1999) followed the temporal course of two recovering aphasics with fMRI. They demonstrated progressive right hemisphere activation during silent sentence reading tasks when compared to controls. Other studies have suggested that recovery from aphasia depends on the sparing of left hemisphere language cortex or reactivation of language areas in the left hemisphere. Karbe et al. (1995) studied twenty-two aphasic patients with a variety of infarcts. They found that the best predictor of twoyear outcome after Wernicke’s or Broca’s aphasia was early activation of left Wernicke’s or Broca’s area, respectively. In their study, right hemisphere activation showed no correlation with recovery. Furthermore, some studies show that right hemisphere activation by language tasks after aphasia may actually predict poor recovery. For example, Heiss et al. (1999) divided twenty-two patients by left hemisphere infarcts into subcortical, frontal, and temporal groups, irrespective of aphasia type and severity. They demonstrated that a shift from right hemisphere to left hemisphere activation by language tasks corresponded with better recovery both within and between groups, with the best recovery corresponding to preserved and reactivated left temporal regions. They hypothesize ‘‘a hierarchy of strategies for recovery’’ with the preferred strategy being utilization of previous language zones in the left hemisphere. Synthesis of these studies into a cohesive theory of how recovery from aphasia occurs is difficult. It is complicated by variations in number of patients studied, locations and sizes of infarcts, types of aphasia, aphasia measurement, imaging activation tasks, time course of the studies, imaging analysis methods, and research designs. Specifically, why has right hemisphere activation by language been shown to correlate with good recovery from aphasia in some studies, and poor recovery in others? Closer examination of Weiller et al.’s study (1995) yields two speculative explanations. First, perilesional areas that would be unique to certain individuals and not apparent with group averaging were not assessed. Second, increased left hemi-
62
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sphere activation was present in these patients, possibly accounting for some of the recovery noted. In the study by Thulborn et al., the degree to which the two patients recovered is not known, as they were not assessed by objective measures. Variability in activation tasks alone cannot explain these differences, as conflicting results are seen between groups using the same tasks (Weiller, 1995; Wharburton, 1999). Thus, while this issue requires further study, the evidence appears to favor the dominant hemisphere language areas as the source of most recovery from aphasia. However, individual exceptions may occur. Functional brain imaging may help us understand whether individual differences explain differences in recovery from aphasia. Functional brain imaging also gives us an important tool to study the effectiveness of retraining and rehabilitation of aphasia. This may give more information about the recovery process generally as well. Belin et al. (1996) studied seven nonfluent aphasics with left hemisphere global hypoperfusion who had an absence of recovery despite standard speech therapies. These patients were trained with melodic intonation therapy (MIT), a modality of aphasia therapy, for two years and subsequently imaged by PET. Increased homotopic right hemisphere activation was visualized without MIT word repetition, while the same patient showed increased left hemisphere language area activation with MIT word repetition. The study by Belin et al. suggests that right hemisphere activation patterns may not be related to the recovery process. Instead they may represent the persistence of aphasia, a significant shift in the understanding of right hemisphere activation if supported by further studies. In conclusion, functional imaging allows us to address previously unanswerable questions including the role of the right hemisphere in recovery from aphasia, how the left hemisphere reorganizes itself for language after aphasia, how individual differences in organization for language contribute to recovery from aphasia, and how rehabilitation from aphasia alters brain organization for language. As answers to these questions lead to new and different understandings of the brain, the paradigm shift is on the way. REFERENCES Belin, P., Van Eeckhout, P., Zilbovicius, M., Remy, P., Francois, C., Guillaume, S., Chain, F., Rancurel, G., & Samson, Y. 1996. Recovery from nonfluent aphasia after melodic intonation therapy: A PET study. Neurology, 47, 1504–1511. Benson, R. R., Fitzgerald, D. B., LeSueur, L. L., Kennedy, D. N., Kwong, K. K., Buchbinder, B. R., Davis T. L., Weisskoff, R. M., Talavage, T. M., Logan, W. J., Cosgrove, G. R., Belliveau, J. W., & Rosen, B. R. 1999. Language dominance determined by whole brain functional MRI in patients with brain lesions. Neurology, 52, 798–809. Heiss, W-D., Kessler, J., Thiel, A., Ghaemi, M., & Karbe, H. 1999. Differential capacity of left and right hemispheric areas for compensation of poststroke aphasia. Annals of Neurology, 45, 430–438. Raichle, M. E. 1997. Functional imaging in behavioral neurology and neuropsychology. In
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T. E. Feinberg & M. J. Farrah (Eds.), Behavioral neurology and neuropsychology (pp. 83–100). New York: McGraw–Hill, . Thulborn, K. R., Carpenter, P. A., & Just, M. A. 1999. Plasticity of language-related brain function during recovery from stroke. Stroke, 30, 749–54. Warburton, E., Price, C. J., Swinburn, K., & Wise, R. J. 1999. Mechanisms of recovery from aphasia: Evidence from positron emission tomography studies. Journal of Neurology, Neurosurgery & Psychiatry, 66, 155–161. Weiller, C., Isensee, C., Rijntjes, M., Huber, W., Muller, S. P., Bier, D., Dutschka, K., Woods, R. P., Noth, J., & Diener, H. C. (1995). Recovery from Wernicke’s aphasia: A positron emission tomographic study. Annals of Neurology, 37, 723–732.