Functional MRI and Wada studies in patients with interhemispheric dissociation of language functions
Introduction
Measurement of language lateralization, using either the intracarotid amobarbital (Wada) test or functional magnetic resonance imaging (fMRI), is a routine part of the presurgical evaluation of patients with intractable epilepsy. Knowledge about language dominance can be useful for predicting cognitive morbidity from surgery. Patients with epilepsy have a higher incidence of atypical language representation than the healthy population [1], [2], [3]. Many factors are known to influence language lateralization. The role of early brain injury in language reorganization is well documented [1], [2], [3], [4], [5], [6]. Location of the seizure focus, seizure frequency, size of brain lesion, and handedness also influence language reorganization and shifting of language abilities [7], [8], [9], [10], [11].
Although atypical language representation is not uncommon among patients with chronic epilepsy, a strong difference in lateralization between different language skills is rare. Kurthen at al. [12] reported four cases of dissociation of language functions during Wada testing among 144 patients. These authors considered counting backward; speech production on tasks of naming, repetition, and reading; and dysphasic errors (paraphasias and perseveration) to reflect “expressive” linguistic capacities, whereas comprehension of spoken commands and questions was used to assess “receptive” language functions. Their findings demonstrated that in rare cases, the expressive language system can be located in one hemisphere and receptive language ability in the other. In a study examining bilateral language representation among patients with epilepsy, Risse and co-authors [2] mentioned that they found only two patients among more than 500 Wada studies whose results suggested interhemispheric dissociation of language skills. The Wada test used by these authors assessed automatic speech, naming, reading, and auditory comprehension. Dissociations in their two patients reportedly reflected differential lateralization on comprehension and overt speech production tasks. No further information is available about these patients because neither met criteria for inclusion in the study.
Although the Wada test has been the gold standard for many years for assessing language dominance, fMRI has recently emerged as a viable noninvasive alternative to the Wada. Many studies have examined the degree of concordance between these methods. Although several initial studies with small patient samples reported 100% concordance [13], [14], [15], [16], [17], [18], [19], [20], more recent, larger series show discordance rates in the range of 5–25% [21], [22], [23], [24]. The degree of discordance varies depending on region of interest (e.g., frontal vs temporal) over which the lateralization measure is computed, methods used to determine laterality (e.g., placement of cutoff scores), seizure location (e.g., temporal vs extratemporal), language (e.g., semantic judgment vs fluency), and control/contrast tasks (perceptual controls vs rest) employed during fMRI, and the Wada language tasks used.
Discrepancies between Wada and fMRI could arise from several factors, as each test has potential methodological limitations. The validity of the Wada test can be compromised by obtundation, insufficient anesthetization, interhemispheric arterial crossflow, and the relatively brief period available for testing. Functional MRI results can be affected by head motion, insufficient statistical power due to inadequate number of trials or image volumes [25], and poor task compliance. Functional MRI procedures also must be carefully designed to activate a wide range of language processes yet avoid activation of nonlanguage systems (e.g., attention, low-level audition, or vision) engaged by the language task(s). Functional MRI and Wada are fundamentally different in that one is an activation method and the other is a transient “lesion” paradigm. Discrepancies could thus arise when the fMRI lateralization score reflects activation that is not essential for performance.
Discordance might also arise when the fMRI protocol does not examine the same set of language processes assessed during Wada testing. During the Wada procedure, each hemisphere is tested on multiple language tasks (i.e., comprehension, naming, repetition, and reading), whereas fMRI protocols often use a single task or task contrast. Functional MRI protocols may thus be more sensitive to some language processes than others. Given this difference between the two techniques, discordance could arise in some cases as a result of differential lateralization of certain language capacities (e.g., speech production) relative to others (e.g., language comprehension). In such cases, the Wada lateralization score would be more likely to show bilateral language representation, whereas fMRI might suggest a more lateralized language system because of inability to detect particular language components.
We describe four patients who showed clear interhemispheric dissociation of language functions on Wada testing. For these patients, one type of language task (either production or comprehension) was supported exclusively by one hemisphere, whereas the other type was supported by the opposite hemisphere. All four patients underwent fMRI language mapping to determine if patients with this pattern of bilateral language would show discordance between Wada and fMRI and to examine several hypotheses about the underlying reason for this discordance. This study provides the first fMRI data on patients with clear signs of interhemispheric dissociations in language functions.
Section snippets
Patient selection and Wada testing
The patients were selected from 490 consecutive adults who underwent comprehensive evaluation for surgical treatment of medically intractable epilepsy. Of this sample, 269 patients underwent both Wada and fMRI tests, including all 4 of the patients described in this article. In addition to fMRI, the presurgical evaluation for epilepsy included long-term video/EEG monitoring, neuropsychological testing, structural brain MRI, and a standardized Wada test. The Wada procedure was similar to that
Results
Demographic and relevant epilepsy-related information for the four patients is summarized in Table 1. The differences between Wada LIs and fMRI LIs (absolute values) were relatively large for three patients (discordant cases: S1 = 93, S2 = 43, and S3 = 113), whereas the difference for the remaining patient was relatively small (concordant case: S4 = 14). Both S1 and S2 had Wada LIs showing relatively symmetric language representation (S1: −16, S2: +10) and had fMRI LIs showing clear left dominance (S1:
Discussion
Epilepsy surgery candidates provide a unique opportunity to examine the effects of a chronic focal abnormality on the cerebral organization of language. It is well documented that patients with early left hemisphere lesions, particularly non-right-handed patients, have a higher incidence of atypical (right or bilateral) representation of language functions. Atypical language representation is estimated to occur in 5 to 53% of right-handed epilepsy patients [1], [2], [3], [7], [33], whereas the
Acknowledgments
Our thanks to Linda Allen, George Morris, Romila Mushtaq, Conrad Nievera, and Manoj Raghavan for assistance with patient recruitment. This work was supported by National Institute of Neurological Diseases and Stroke Grant R01 NS35929, National Institutes of Health General Clinical Research Center Grant M01 RR00058, and the Charles A. Dana Foundation.
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