Skip to main content
Advertisement
  • Neurology.org
  • Journals
    • Neurology
    • Clinical Practice
    • Education
    • Genetics
    • Neuroimmunology & Neuroinflammation
  • Online Sections
    • Neurology Video Journal Club
    • Inclusion, Diversity, Equity, Anti-racism, & Social Justice (IDEAS)
    • Innovations in Care Delivery
    • Practice Buzz
    • Practice Current
    • Residents & Fellows
    • Without Borders
  • Collections
    • COVID-19
    • Disputes & Debates
    • Health Disparities
    • Infographics
    • Neurology Future Forecasting Series
    • Null Hypothesis
    • Patient Pages
    • Topics A-Z
    • Translations
  • Podcast
  • CME
  • About
    • About the Journals
    • Contact Us
    • Editorial Board
  • Authors
    • Submit a Manuscript
    • Author Center

Advanced Search

Main menu

  • Neurology.org
  • Journals
    • Neurology
    • Clinical Practice
    • Education
    • Genetics
    • Neuroimmunology & Neuroinflammation
  • Online Sections
    • Neurology Video Journal Club
    • Inclusion, Diversity, Equity, Anti-racism, & Social Justice (IDEAS)
    • Innovations in Care Delivery
    • Practice Buzz
    • Practice Current
    • Residents & Fellows
    • Without Borders
  • Collections
    • COVID-19
    • Disputes & Debates
    • Health Disparities
    • Infographics
    • Neurology Future Forecasting Series
    • Null Hypothesis
    • Patient Pages
    • Topics A-Z
    • Translations
  • Podcast
  • CME
  • About
    • About the Journals
    • Contact Us
    • Editorial Board
  • Authors
    • Submit a Manuscript
    • Author Center
  • Home
  • Latest Articles
  • Current Issue
  • Past Issues
  • Neurology Video Journal Club
  • Residents & Fellows

User menu

  • Subscribe
  • My Alerts
  • Log in
  • Log out

Search

  • Advanced search
Neurology
Home
The most widely read and highly cited peer-reviewed neurology journal
  • Subscribe
  • My Alerts
  • Log in
  • Log out
Site Logo
  • Home
  • Latest Articles
  • Current Issue
  • Past Issues
  • Neurology Video Journal Club
  • Residents & Fellows

Share

April 01, 1996; 46 (4) ARTICLES

Determination of language dominance using functional MRI

A comparison with the Wada test

J. R. Binder, S. J. Swanson, T. A. Hammeke, G. L. Morris, W. M. Mueller, M. Fischer, S. Benbadis, J.A. Frost, S. M. Rao, V. M. Haughton
First published April 1, 1996, DOI: https://doi.org/10.1212/WNL.46.4.978
J. R. Binder
  • Find this author on Google Scholar
  • Find this author on PubMed
  • Search for this author on this site
S. J. Swanson
  • Find this author on Google Scholar
  • Find this author on PubMed
  • Search for this author on this site
T. A. Hammeke
  • Find this author on Google Scholar
  • Find this author on PubMed
  • Search for this author on this site
G. L. Morris
  • Find this author on Google Scholar
  • Find this author on PubMed
  • Search for this author on this site
W. M. Mueller
  • Find this author on Google Scholar
  • Find this author on PubMed
  • Search for this author on this site
M. Fischer
  • Find this author on Google Scholar
  • Find this author on PubMed
  • Search for this author on this site
S. Benbadis
  • Find this author on Google Scholar
  • Find this author on PubMed
  • Search for this author on this site
J.A. Frost
  • Find this author on Google Scholar
  • Find this author on PubMed
  • Search for this author on this site
S. M. Rao
  • Find this author on Google Scholar
  • Find this author on PubMed
  • Search for this author on this site
V. M. Haughton
  • Find this author on Google Scholar
  • Find this author on PubMed
  • Search for this author on this site
Full PDF
Citation
Determination of language dominance using functional MRI
A comparison with the Wada test
J. R. Binder, S. J. Swanson, T. A. Hammeke, G. L. Morris, W. M. Mueller, M. Fischer, S. Benbadis, J.A. Frost, S. M. Rao, V. M. Haughton
Neurology Apr 1996, 46 (4) 978-984; DOI: 10.1212/WNL.46.4.978

Citation Manager Formats

  • BibTeX
  • Bookends
  • EasyBib
  • EndNote (tagged)
  • EndNote 8 (xml)
  • Medlars
  • Mendeley
  • Papers
  • RefWorks Tagged
  • Ref Manager
  • RIS
  • Zotero
Permissions

Make Comment

See Comments

Downloads
2817

Share

  • Article
  • Figures & Data
  • Info & Disclosures
Loading

Abstract

We performed functional MRI (FMRI) in 22 consecutive epilepsy patients undergoing intracarotid amobarbital (Wada) testing and compared language lateralization measures obtained with the two procedures.FMRI used a single-word semantic decision task previously shown to activate lateralized language areas in normal adults. Correlation between the two tests was highly significant (r equals 0.96; 95% CIs 0.90 to 0.98; p less than 0.0001). These results validate the FMRI technique and suggest that ``active'' areas observed with this semantic processing task correspond to those underlying hemispheric dominance for language. The strong correlation observed supports the view that language lateralization is a continuous rather than a dichotomous variable. In addition to lateralization information, FMRI consistently demonstrated focal regions of activity in lateral frontal and temporo-parieto-occipital cortex. These functional maps may be helpful in defining the boundaries of surgical excisions.

NEUROLOGY 1996;46: 978-984.

Localization of cortical functions in patients undergoing excisional brain surgery is useful in three ways: to predict the general level of risk should the planned excision proceed, to guide the surgeon in limiting the boundaries of the excision, and to help determine the location of abnormal brain areas (e.g., seizure foci) preoperatively. One commonly used localization technique is the intracarotid amobarbital, or Wada, test, which measures the relative lateralization of language and memory functions across the two hemispheres. [1,2] Preoperative determination of language lateralization is important in selecting patients for more invasive and specific localization procedures, such as intraoperative stimulation mapping. [3] Determination of language lateralization is particularly important in the preoperative evaluation of epilepsy patients, because this population may have a higher incidence of atypical language dominance than does the normal population. [4,5] Although there are several alternative methods for determining language dominance, [6,7] the Wada test remains the only method used routinely for this purpose.

The Wada test, although a proven measure of language lateralization, has several important limitations. First, the required angiographic procedure is invasive, with reported complication rates of up to 3%. [8] Second, the test measures only the relative distribution of language across the two hemispheres. More specific information about localization within a hemisphere, which might be useful for tailoring an excision, must be obtained by other means, such as intraoperative stimulation mapping. Third, validity of the test depends on demonstration of relatively separate and symmetric arterial supply routes for the two hemispheres. Thus, interpretation of the test may not be straightforward or possible in patients with azygous supply patterns or arterial crossflow. [9] Other methodologic drawbacks of the Wada test are limitations on the time available for testing distinct functions during the procedure, the occurrence of excessive sedation that limits the validity of language and memory tests, occasional difficulty obtaining adequate hemisphere anesthetization, and the unavailability of test-retest reliability data. [10-12]

Functional MRI (FMRI) may provide a noninvasive alternative to the Wada test. FMRI produces detailed brain images showing the location of MR signal changes associated with cerebral activity. Previous reports described applications of FMRI in mapping motor, [13-15] visual, [16-18] auditory, [19,20] and somatosensory [21] systems. Other investigators reported preliminary FMRI observations in neurologic patients. [22,23] Several groups observed lateralized FMRI responses during performance of linguistic tasks. [24-27] In previous reports, we described such responses during a single-word semantic decision task with appropriate controls for auditory processing and attentional activation. [28,29] What remains unclear from these studies is whether these lateralized regions observed in normal subjects actually correspond to systems underlying language dominance, as measured with the Wada test. A powerful argument in favor of such an interpretation would be the demonstration that Wada results can be predicted on the basis of FMRI lateralization patterns. In this article, we compare language lateralization data obtained with FMRI and with the Wada test in a series of epilepsy patients undergoing preoperative evaluation. Language laterality scores are calculated under the assumption that lateralization is a graded rather than a dichotomous or otherwise discrete phenomenon. [30] We test the hypothesis that a correlation exists between these laterality measures and describe the anatomic pattern of FMRI activation typically observed.

Methods.

Subjects.

Subjects were consecutive patients with full-scale Wechsler Adult Intelligence Scale-Revised IQ scores more than equals 80 who were undergoing comprehensive evaluation at the Medical College of Wisconsin for surgical treatment of epilepsy. Patients selected for surgical evaluation met the following criteria: medically intractable epilepsy, restricted lifestyle because of recurrent seizures, and probable focal onset of seizures. All patients had neurologic examinations, continuous 16-channel inpatient video-EEG monitoring, preoperative neuropsychological testing, interictal and postictal single-photon emission CT, a standardized Wada test, and routine brain MRI. Subjects gave written informed consent for FMRI. All completed the Edinburgh Handedness Inventory (EHI). [31]

Wada methods.

Baseline language and memory tests were administered 2 hours before the Wada test, using alternate forms of the same tests used in the Wada. The Wada procedure was similar to that described by Loring et al. [32] With the patient in the supine position with arms elevated and outstretched, 125 mg of sodium amytal was injected by hand over a 4- to 5-second interval into the internal carotid artery while the patient counted aloud by ones. The side of suspected seizure focus was injected first. Simultaneous EEG was conducted during the procedure to monitor the onset and cessation of slowing in both hemispheres. If contralateral flaccid hemiplegia was not present, an additional 25- or 50-mg bolus of sodium amytal was injected. Counting disruption was numerically rated, as well as ability to follow two simple midline commands just after injection. Between 30 and 60 seconds postinjection, objects and line drawings were presented for later memory testing. Numerical ratings were then made on four language tasks: (1) comprehension of three one- and two-step commands of increasing difficulty (the most difficulty including inverted syntax), (2) naming objects or parts of objects depicted in line drawings, (3) phrase repetition, and (4) sentence reading. All ratings used a 0 to 3 scale, with lower scores reflecting poorer performance. Language tasks were repeated until the patient performed at base-line levels. Only the first two presentations of the four language tasks were scored. Also included in the scoring was a rating of paraphasic errors, based on the total number of errors during each series of language tests (0, more than 5 errors; 1, 3 to 5 errors; 2, 1 to 2 errors; and 3, no errors). Only trials conducted before return of motor functioning were included in final language calculations. A total score of 33 on the language measures was possible unless there was early return of motor function.

Approximately 30 minutes after the first injection, the identical procedure was repeated with 100 mg injected into the contralateral hemisphere. A Wada laterality index (Wada LI) was calculated for each patient as the difference [PL minus PR], where PL and PR are the percentage scores (of the total possible) from the language tasks for the right (test left) injection and the left (test right) injection. This approach yields LIs ranging between plus 100 (strong left hemisphere dominance) and minus 100 (strong right hemisphere dominance). Wada calculations were performed by a neuropsychologist blind to the FMRI results.

FMRI image acquisition.

MRI studies were conducted on a 1.5-T GE Signa scanner (General Electric, Milwaukee, WI) equipped with custom gradient and rf coils designed for whole-brain echoplanar imaging. FMRI used a blipped gradient-echo echoplanar sequence (TE 40 ms, TR 4 sec, matrix 64 times 64, slice thickness 8 mm, and field of view 24 cm). Ten sagittal slices were acquired, with 5 contiguous slices in the left hemisphere and 5 in the right hemisphere. Slices were positioned to cover the central two-thirds (40 mm) of each hemisphere, excluding the most medial and most lateral 10 to 20 mm. Care was taken to place slices symmetrically in the left and right hemisphere in each case. Series of 100 consecutive images were acquired simultaneously at each slice location during eight cycles of task activation. High-resolution anatomic reference images were obtained through the entire brain using either a T2-weighted fast spin-echo or T1-weighted spoiled gradient-echo sequence.

FMRI activation tasks.

Subjects were scanned with eyes closed and room lights dimmed. Stimuli were digitally recorded as pure tones and speech sound s presented at precise intervals using a computer playback system. Characteristics of the sound delivery apparatus have been described elsewhere. [29] Each 100-image echoplanar series consisted of multiple periods of baseline, during which subjects performed a tone discrimination control task, alternating with periods of activation, during which a contrasting semantic decision task was performed. [28,29] Each series began with four resting images (16 seconds) during which MR signal equilibrium was reached, followed by 96 images during which the semantic task alternated with the tone task every 24 seconds (48 s/cycle, 12 images per cycle, eight cycles). In the tone task, subjects heard brief sequences of three to seven tones. Each constituent tone had either a low (500 Hz) or high (750 Hz) pitch. A button press response (using the nondominant hand) was required for any sequence containing two high-pitch tones. In the semantic task, subjects heard spoken English nouns designating animals (e.g., ``squirrel'') and responded according to specified semantic criteria. Target words were animals that are both ``native to the United States'' and ``commonly used by humans.'' The two tasks were matched for stimulus intensity, average stimulus duration per trial (0.75 seconds), average trial duration (3 seconds), and frequency of positive targets (one target per 8 seconds). Subjects received instructions and brief practice sessions with each task before entering the scanner. The tone discrimination task has been shown to control for activation of superior temporal auditory processors as well as nonlinguistic lateral frontal lobe attentional systems. [28] The semantic decision-tone discrimination combination has been demonstrated to produce strongly lateralized activation in lateral frontal and temporoparietal heteromodal cortex of the dominant hemisphere in normal subjects. [29,33]

FMRI data analysis.

Identification of event-related MR signal changes used the correlation approach of Bandettini et al. [34] In brief, this method correlates the time-series MRI signal data (excluding signal equilibration images at the beginning of the series) with a reference vector on a voxel-by-voxel basis. A threshold value for the correlation coefficient is chosen to eliminate those voxels not significantly correlated with the activation procedure. The final functional image is created by superimposing significantly activated voxels on corresponding anatomic images of the same brain tissue.

Reference vectors were derived directly from each data set using a two-step method that selects voxels strongly correlated (r more than equals 0.70) with a simple mathematical model of the activation procedure (the model used for this study was a discontinuous square wave function; see reference 29), and then computes a data set-specific reference vector as the mean vector of this selected group of voxels. The eight activation cycles comprising this mean vector are then averaged across time to produce a mean activation waveform, which is repeated eight times to obtain the final reference vector. The correlation test was then performed again for each voxel using this empirically derived reference vector, with a correlation threshold of r more than equals 0.40. The probability that any given voxel will exceed this threshold by chance is approximately p less than 0.0001 [34] or p less than 0.05 for a set of 500 voxels. As a check on the validity of this threshold, thresholds were also determined empirically for each patient by correlating each data set with an aperiodic reference vector (a random number series). The distribution of resulting r values describes the range of correlations that occur by chance at a given probability level. When the desired probability is p less than 0.05 that any brain voxel in a slice will exceed the threshold by chance, empiric thresholds derived by this method ranged from r more than equals 0.35 to r more than equals 0.43, with a mean of 0.39 for the entire group of patients. Thus, the average probability of a false-positive voxel is less than 0.05 per slice using a threshold of 0.40, or approximately one false-positive voxel for each 20 brain slices. Because the average number of active voxels per slice was 14.6, the statistically estimated proportion of false-positive voxels was approximately 1 in 292, or less than 0.4%.

Activation volumes were determined in each patient by counting the significantly activated voxels in each hemisphere. An FMRI LI was calculated for each patient as the ratio ([VL minus VR]/[VL plus VR]) times 100, where VL and VR are activation volumes for the left and right hemispheres. This approach yields LIs ranging between plus 100 (strong left hemisphere dominance) and minus 100 (strong right hemisphere dominance). Despite differences in appearance, the formulae for Wada and FMRI LIs are hypothesized to be equivalent, because the percentage correct scores for the Wada test are thought to reflect the ratio of unanesthetized to total ``language tissue,'' that is, PL is hypothesized to reflect VL/[VL plus VR] and PR is hypothesized to reflect VR/[VL plus VR]. Thus, the Wada LI, [PL minus PR], is hypothetically equivalent to [V sub L minus VR]/[VL plus VR], which is the formula for the FMRI LI. FMRI analysis was automated and was performed by a research technician blind to the Wada results.

Results.

Patients.

Twenty-seven patients met entry criteria and underwent successful Wada testing. Of these, 24 patients were available for FMRI before surgery and agreed to participate in the FMRI procedure. One became claustrophobic soon after entering the scanner and was unable to complete the test. In one other case, the data were unusable because of a scanner malfunction. The remaining 22 patients included 14 women and 8 men, ranging in age from 17 to 64 years. Age at seizure onset ranged from birth to 32 years, with seizures beginning before age 10 years in 9 of 22 patients. Two patients were left-handed, 1 ambidextrous, and the others right-handed. Thirteen patients had normal routine MRIs, whereas the others had left temporal lobe atrophic or sclerotic changes (4 patients), temporal lobe cavernous angiomas (2 patients), or left hemisphere encephalomalacia (3 patients). For detailed information regarding the patients, including side of seizure focus and EHI scores, please see the Note at the end of this article.

Language dominance.

The Wada and FMRI tests were concordant in all cases in determining the hemisphere with greater language representation. Eighteen patients (16 right-handed, 1 ambidextrous, and 1 left-handed) had strong left hemisphere dominance for language as judged by the Wada test, with LIs ranging from plus 56 to plus 100. These same 18 patients also showed clear left hemisphere dominance by FMRI, with LIs ranging from plus 35 to plus 81. The four remaining patients (three right-handed and one left-handed) had atypical language distributions as judged by both Wada and FMRI. Wada LIs in these patients ranged from minus 60 to plus 25, and corresponding FMRI LIs ranged from minus 52 to plus 12.

Correlation between the two tests Figure 1 was very high (r equals 0.96; 95% CIs 0.90 to 0.98; p less than 0.0001). This correlation also held for the 18 patients with strong left hemisphere dominance (r equals 0.61; p less than 0.007), indicating a continuum of language lateralization even within this narrower range of values. There was no significant correlation in this sample of patients between a laterality index derived from the EHI and the Wada test LI (r equals 0.29; p equals 0.194) nor between the EHI and FMRI LIs (r equals 0.30; p equals 0.178). Although average LIs were more positive (indicating relatively stronger left dominance) in the group of patients with right hemisphere seizure foci than in patients with left hemisphere foci on all three lateralization measures, a one-factor ANOVA revealed that these group mean differences were not statistically significant.

Figure
  • Download figure
  • Open in new tab
  • Download powerpoint

Figure 1. FMRI laterality index plotted against Wada laterality index for 22 epilepsy patients. The regression function, y equals 0.764x plus 4.3, is shown as a dashed line. The correlation coefficient is 0.96.

Regional language localization by FMRI.

Figure 2 illustrates the location of active pixels in three representative subjects, one with strong left hemisphere dominance (patient 14), one with mixed primarily left language dominance (patient 16), and one with mixed primarily right language dominance (patient 18). ``Active'' voxels are those demonstrating relatively increased levels of MRI signal during the semantic decision task compared with the control task (tone discrimination). The main foci of activity were in the lateral frontal lobe and temporal-parietal-occipital junction in all subjects. Specific active structures included, in roughly descending order of frequency, the inferior and middle frontal gyri (Brodmann areas [BA] 9 and 44 to 46), the superior precentral sulcus (BA 6), the superior frontal gyrus and sulcus (BA 8 and 9), the angular gyrus (BA 39), the posterior inferior temporal gyrus and fusiform gyrus (BA 37), and the posterior superior temporal sulcus and middle temporal gyrus (BA 21/22). Although the supramarginal gyrus (BA 40) is usually considered to be a language area, there was relatively little activation in this region.

Figure
  • Download figure
  • Open in new tab
  • Download powerpoint

Figure 2. FMRI activation maps from three representative patients, illustrating the continuum of language lateralization across individuals. Areas demonstrating significant signal increase during the semantic decision task are highlighted using a qualitative red-yellow scale, with red indicating smaller absolute signal changes and yellow larger changes. Left and right slices are symmetrically placed in each patient; slices differ across patients because of differences in brain size and shape. Patient 14 had strong left hemisphere lateralization by FMRI (LI equals 72), whereas patient 16 had more symmetric language distribution with left dominance (LI equals 35) and patient 18 had relative right dominance (LI equals minus 20). Areas prominently activated include the inferior frontal sulcus, middle frontal gyrus, and lateral orbital sulcus (long black arrows); the angular gyrus (black arrowheads); the superior precentral sulcus (long blue arrow); the superior frontal sulcus and gyrus (blue arrowheads); the posterior ventrolateral temporal lobe (short black arrow); and the superior temporal sulcus (short blue arrow). Small foci are demonstrated in the cerebellum bilaterally and in the dorsal temporal pole.

Discussion.

Measures of language lateralization obtained by the Wada test and by FMRI were highly correlated in this series of patients with epilepsy. As expected, most patients (18/22) were strongly left hemisphere dominant, whereas the remainder had more symmetric language or right hemisphere dominance. Lateralization indexes varied continuously over a range from strong left to strong right dominance on both tests. A common approach in previous Wada test research has been to divide this continuum into categories such as ``exclusive left dominance,'' ``bilateral language,'' and ``exclusive right dominance.'' Even studies using quantitative language ratings like those used here have incorporated thresholds for abnormal performance to exclude deficits resulting from nonspecific effects of sedation, thereby defining most subjects as ``exclusively'' left dominant. [30] The present results demonstrate that even within a range that would typically be defined as exclusive left dominance, there is variation among subjects on the Wada test that is correlated with similar variation in FMRI activation maps. These data emphasize that language lateralization occurs along a graded continuum, even though most individuals have relatively strong left lateralization. Two anatomic mechanisms could explain this gradation in language lateralization. It may be that the phonologic, semantic, working memory, attentional, motor, and other component functions used in language are each located in one or the other hemisphere, with the number of these functional ``modules'' in each hemisphere varying from person to person. Alternatively, each linguistic component might be represented to some extent in both hemispheres, with the distribution varying across individuals. These two proposals are not mutually exclusive. Although our data do not test these models directly, the continuous variation we observed in language lateralization across individuals could be taken as indirect evidence for the latter model.

This is the first FMRI study to demonstrate validation of this technique through intrasubject comparisons with another functional localization method. (See ``Note added in proofs'' on page 983.) The close similarity between Wada and FMRI results suggests that the areas of activation observed using this FMRI procedure are, or at least largely include, those underlying language dominance. This correspondence may seem surprising at first, given the differences between the semantic decision task used for FMRI and the naming and auditory comprehension tasks emphasized in the Wada test. We propose that the semantic processing network activated in the FMRI procedure is also crucial for comprehension of spoken speech and for linguistic identification of visual stimuli. Although these latter tasks also place demands on auditory and visual perceptual systems and on motor response systems, it is the semantic component that is lateralized and forms the basis of hemispheric language dominance on both FMRI and Wada tests.

These results therefore support FMRI as a promising alternative to the Wada test for the determination of language lateralization. In contrast to the Wada test, FMRI is entirely noninvasive and without significant health risks. FMRI is not affected by underlying arterial supply patterns, can be easily repeated if necessary without additional risk, and affords the examiner sufficient time to test a range of cortical functions. Because the entire brain is assayed simultaneously, results are not confounded by difficulties in reproducing test conditions separately for each hemisphere as in the Wada test. For example, the Wada test may occasionally overestimate language symmetry because of inadequate anesthetization of the dominant hemisphere or because of arterial crossflow after nondominant hemisphere injection. [9,11,35] Unlike the Wada test, FMRI provides detailed information about the spatial localization of functions within each hemisphere, potentially offering the neurosurgeon useful data for minimizing the adverse effects of an excision.

Several factors could limit the general applicability of FMRI. We observed claustrophobic reactions in one patient and in a small percentage of normal volunteers. A small proportion of patients are unsuitable for MRI scanning because of cardiac pacemakers, metallic substances in the skull, or extreme obesity. Movement during scanning is a potential problem that introduces large artifacts in the time-series data. Methods of dealing with this problem include head restraints, discarding portions of the time-series contaminated by movement, and spatial registration of data during postprocessing. Although we did note extensive movement artifacts in this series of patients, the problem is likely to be worse in patients with more compromised cognitive abilities, particularly in those with attentional deficits. Automated image registration methods may be capable of correcting some or all of these motion problems. [36,37] Finally, the specific FMRI tasks used in this study are unsuitable for neurologic patients with moderate cognitive deficits. To achieve the broadest application of FMRI, it will be necessary to develop a standardized collection of qualitatively similar tasks covering a range of difficulty levels and to assign patients to suitable test forms based on results of standardized pre-scan screening tests.

The LIs calculated for both Wada and FMRI tests will depend on a number of procedural variables and on the adequacy of experimental controls. One important factor is the choice of a control task for FMRI. It must be assumed, for example, that some of the component functions activated during a complex language task are bilaterally represented or represented in the ``nondominant'' hemisphere. Examples of such functions are the processing of auditory information in speech sounds, which occurs bilaterally in the superior temporal gyri, [19,38] and the systems specialized for maintenance and distribution of attention, which are located primarily in the right hemisphere. [39,40] If activation of these functions is not ``subtracted'' using a suitable control task, then task-induced activity that is unrelated to the linguistic functions of interest will occur in the nondominant hemisphere, resulting in LIs that are closer to symmetry than they should be. A similar error would result from using a control task with linguistic features (e.g., repetition of words), which could have the effect of nullifying some of the language-associated activity in the dominant hemisphere.

The FMRI LI is dependent on the correlation threshold used to identify active voxels. At low correlation thresholds (i.e., r less than 0.30 in this study), the occurrence of false-positive correlations in both hemispheres moves the LI toward zero. At high thresholds (i.e., r more than 0.50), the number of active voxels becomes small--potentially affecting reliability--and many ``truly'' activated voxels are excluded. In plotting the LI as a function of correlation threshold, we observed, in most cases, a deviation away from zero as the r threshold is increased from 0 to 0.30, with the LI reaching a plateau by r equals 0.40. Above r equals 0.50, there is usually instability and erratic fluctuation of the LI due to the small number of voxels passing the threshold. These ranges of r are, of course, specific to the present study, because the statistical power of r depends on the number of data points (i.e., the number of images) considered in each correlation [34] and, to a lesser extent, on the interscan interval, or TR, that affects the degree of autocorrelation present in the data. [41]

The main areas of activation observed during our semantic processing task included the lateral and superior frontal lobe, the angular gyrus, and the posterior ventrolateral temporal lobe. Our imaging methods omitted lateral portions of gyri in the perisylvian region as well as entire gyri on the medial brain surface. We thus cannot comment on possible activation in these areas. The observed pattern of frontal and posterior heteromodal activation replicates our previous findings using the same procedure in normals [29] and is in accordance with PET data obtained using a similar task. [42] We interpreted this pattern as indicating a distributed neural network for linguistic comprehension, governing access and retrieval from semantic memory. [29] Although the activation maps produced by FMRI may prove useful in tailoring the boundaries of surgical resections--and may eventually supplant intraoperative stimulation mapping for this purpose--the validity of this application will require formal demonstration. Specifically, it will be necessary to test whether removal of areas ``active'' on FMRI is correlated with postoperative changes in neuropsychological test performance and whether such correlations are as good as or better than those obtained using intraoperative mapping techniques. [43-45]

In addition to its application in language testing, the Wada test is often used to determine lateralization of memory functions. [46] Memory lateralization data may assist in determining the hemisphere of seizure origin and appear to be important in predicting seizure control after surgery. [47,48] If FMRI is to replace the Wada test in clinical use, it will be necessary to develop and validate FMRI procedures for localizing verbal memory systems. The language task used in this study can be viewed as an index of long-term semantic memory, which is likely to be one of the component systems activated during typical declarative verbal memory tasks such as those used in the Wada test. Several investigators emphasized involvement of the lateral temporal neocortex in such tasks; [49,50] these areas are similar in location to the posterior ventrolateral temporal areas (BA 37 and 21/22) activated in the present study. It may also be possible to use FMRI to map medial temporal structures (parahippocampus and hippocampus) that are believed to play a dominant role in the consolidation of long-term declarative memories, although this possibility remains at present an open question.

Note.

Readers can obtain 1 page of supplementary material from the National Auxiliary Publications Service, c/o Microfiche Publications, PO Box 3513, Grand Central Station, New York, NY 10163-3513. Request document no. 05261. Remit with your order (not under separate cover), in US funds only, $7.75 for photocopies or $4.00 for microfiche. Outside the United States and Canada, add postage of $4.50 for the first 20 pages and $1.00 for each 10 pages of material thereafter, or $1.75 for the first microfiche and $.50 for each fiche thereafter. There is a $5.00 invoicing charge on all orders filled before payment.

Note added in proofs.

We recently learned of a similar study by Desmond et al. (Brain, in press) that reports close agreement between FMRI and Wada language results in 7 patients.

Acknowledgments

We thank P. Bandettini, R. Cox, J. Hyde, A. Jesmanowicz, T. Prieto, E. Wong, and other colleagues at the Medical College of Wisconsin for advice and support.

  • Copyright 1996 by Advanstar Communications Inc.

REFERENCES

  1. 1.↵
    Wada J, Rasmussen T. Intracarotid injection of sodium amytal for the lateralization of cerebral speech dominance. J Neurosurg 1960;17:266-282.
    OpenUrl
  2. 2.
    Loring DW, Meador KJ, Lee GP, King DW. Amobarbital effects and lateralized brain function: the Wada test. New York: Springer-Verlag, 1992.
  3. 3.↵
    Penfield W, Jasper H. Epilepsy and the functional anatomy of the human brain. New York: Little, Brown, 1954.
  4. 4.↵
    Rasmussen T, Milner B. The role of early left-brain injury in determining lateralization of cerebral speech functions. Ann N Y Acad Sci 1977;299:355-369.
    OpenUrl
  5. 5.
    Woods RP, Dodrill CB, Ojemann GA. Brain injury, handedness, and speech lateralization in a series of amobarbital studies. Ann Neurol 1988;23:510-518.
    OpenUrl
  6. 6.↵
    Pardo JV, Fox PT. Preoperative assessment of the cerebral hemispheric dominance for language with CBF PET. Human Brain Map 1993;1:57-68.
    OpenUrlPubMed
  7. 7.
    Jennum P, Friberg L, Fuglsang-Frederiksen A, Dam M. Speech localization using repetitive transcranial magnetic stimulation. Neurology 1994;44:269-273.
    OpenUrl
  8. 8.↵
    Dion JE, Gates PC, Fox AJ, Barnett HJ, Blom RJ. Clinical events following neuroangiography: a prospective study. Stroke 1987;18:997-1004.
    OpenUrl
  9. 9.↵
    Hietala S-O, Silfvenius H, Aasly J, Olivecrona M, Jonsson L. Brain perfusion with intracarotid injection of 99mTc-HM-PAO in partial epilepsy during amobarbital testing. Eur J Nucl Med 1990;16:683-687.
    OpenUrl
  10. 10.↵
    Malmgren K, Bilting M, Hagberg I, Hedstrom A, Silfvenius H, Starmark JE. A compound score for estimating the influence of inattention and somnolence during the intracarotid amobarbital test. Epilepsy Res 1992;12:253-259.
    OpenUrl
  11. 11.
    Rausch R, Silfvenius H, Wieser H-G, Dodrill CB, Meador KJ, Jones-Gotman M. Intraarterial amobarbital procedures. In: Engel J, ed. Surgical treatment of the epilepsies. New York: Raven Press, 1993;341-357.
  12. 12.
    Bouwer MS, Jones-Gotman M, Gotman J. Duration of sodium amytal effect: behavioral and EEG measures. Epilepsia 1993;34:61-68.
    OpenUrl
  13. 13.↵
    Bandettini PA, Wong EC, Hinks RS, Tikofsky RS, Hyde JS. Time course EPI of human brain function during task activation. Magn Reson Med 1992;25:390-397.
    OpenUrl
  14. 14.
    Rao SM, Binder JR, Bandettini PA, et al. Functional magnetic resonance imaging of complex human movements. Neurology 1993;43:2311-2318.
    OpenUrl
  15. 15.
    Kim S-G, Ashe J, Georgopoulos AP, et al. Functional imaging of human motor cortex at high magnetic field. J Neurophysiol 1993;69:297-302.
    OpenUrl
  16. 16.↵
    Kwong KK, Belliveau JW, Chesler DA, et al. Dynamic magnetic resonance imaging of human brain activity during primary sensory stimulation. Proc Natl Acad Sci USA 1992;89:5675-5679.
    OpenUrl
  17. 17.
    Ogawa S, Tank DW, Menon R, et al. Intrinsic signal changes accompanying sensory stimulation: functional brain mapping using MRI. Proc Natl Acad Sci USA 1992;89:5951-5955.
    OpenUrl
  18. 18.
    Turner R, Jezzard P, Wen H, et al. Functional mapping of the human visual cortex at 4 tesla and 1.5 tesla using deoxygenation contrast EPI. Magn Reson Med 1993;29:277-279.
    OpenUrlPubMed
  19. 19.↵
    Binder JR, Rao SM, Hammeke TA, et al. Functional magnetic resonance imaging of human auditory cortex. Ann Neurol 1994;35:662-672.
    OpenUrlPubMed
  20. 20.
    Binder JR, Rao SM, Hammeke TA, Frost JA, Bandettini PA, Hyde JS. Effects of stimulus rate on signal response during functional magnetic resonance imaging of auditory cortex. Cogn Brain Res 1994;2:31-38.
    OpenUrl
  21. 21.↵
    Hammeke TA, Yetkin FZ, Mueller WM, et al. Functional magnetic resonance imaging of somatosensory stimulation. Neurosurgery 1994;35:677-681.
    OpenUrlPubMed
  22. 22.↵
    Jack CR, Thompson RM, Butts RK, et al. Sensory motor cortex: correlation of presurgical mapping with functional MR imaging and invasive cortical mapping. Radiology 1994;190:85-92.
    OpenUrl
  23. 23.
    Morris GL, Mueller WM, Yetkin FZ, et al. Functional magnetic resonance imaging in partial epilepsy. Epilepsia 1994;35:1194-1198.
    OpenUrlPubMed
  24. 24.↵
    Hinke RM, Hu X, Stillman AE, et al. Functional magnetic resonance imaging of Broca's area during internal speech. Neuroreport 1993;4:675-678.
    OpenUrl
  25. 25.
    Binder JR, Rao SM, Hammeke TA, et al. Functional magnetic resonance imaging (FMRI) of auditory semantic processing [abstract]. Neurology 1993;43(suppl 2):A189.
  26. 26.
    Cuenod CA, Bookheimer S, Pannier L, et al. Functional imaging during word generation using a conventional MRI scanner [abstract]. Proc Soc Magn Reson Med 1993;3:1414.
    OpenUrl
  27. 27.
    Benson RR, Kwong KK, Buchbinder BR, et al. Noninvasive evaluation of language dominance using functional MRI [abstract]. Proc Soc Magn Reson Med 1994;2:684.
    OpenUrl
  28. 28.↵
    Binder JR, Rao SM, Hammeke TA, et al. Identification of auditory, linguistic, and attention systems with task subtraction functional MRI [abstract]. Proc Soc Magn Reson Med 1994;2:681.
    OpenUrl
  29. 29.↵
    Binder JR, Rao SM, Hammeke TA, et al. Lateralized human brain language systems demonstrated by task subtraction functional magnetic resonance imaging. Arch Neurol 1995;52:593-601.
    OpenUrl
  30. 30.↵
    Loring DW, Meador KJ, Lee GP, et al. Cerebral language lateralization: evidence from intracarotid amobarbital testing. Neuropsychologia 1990;28:831-838.
    OpenUrl
  31. 31.↵
    Oldfield RC. The assessment and analysis of handedness: the Edinburgh inventory. Neuropsychologia 1971;9:97-113.
    OpenUrl
  32. 32.↵
    Loring DW, Murro AM, Meador KJ, et al. Wada memory testing and hippocampal volume measurements in the evaluation for temporal lobectomy. Neurology 1993;43:1789-1793.
    OpenUrlAbstract/FREE Full Text
  33. 33.
    Binder JR, Rao SM, Hammeke TA, et al. A lateralized, distributed network for semantic processing demonstrated with whole brain functional MRI [abstract]. Proc Soc Magn Reson Med 1994;2:695.
    OpenUrl
  34. 34.↵
    Bandettini PA, Jesmanowicz A, Wong EC, Hyde JS. Processing strategies for time-course data sets in functional MRI of the human brain. Magn Reson Med 1993;30:161-173.
    OpenUrlPubMed
  35. 35.
    Snyder PJ, Novelly RA, Harris LJ. Mixed speech dominance in the intracarotid sodium amytal procedure: validity and criteria issues. J Clin Exp Neuropsychol 1990;12:629-643.
    OpenUrlPubMed
  36. 36.↵
    Woods RP, Cherry SR, Mazziotta JC. Rapid automated algorithm for aligning and reslicing PET images. J Comput Assist Tomogr 1992;16:620-633.
    OpenUrl
  37. 37.
    Risinger R, Hertz-Pannier L, Schmidt M, Maisog JM, Cuenod CA, Le Bihan D. Evaluation of image registration in functional brain MRI [abstract]. Proc Soc Magn Reson Med 1994;2:649.
    OpenUrl
  38. 38.
    Wise R, Chollet F, Hadar U, Friston K, Hoffner E, Frackowiak R. Distribution of cortical neural networks involved in word comprehension and word retrieval. Brain 1991;114:1803-1817.
    OpenUrlAbstract/FREE Full Text
  39. 39.↵
    Deutsch G, Papanicolaou AC, Bourbon T, Eisenberg HM. Cerebral blood flow evidence of right cerebral activation in attention demanding tasks. Int J Neurosci 1988;36:23-28.
    OpenUrl
  40. 40.
    Pardo JV, Fox PT, Raichle ME. Localization of a human system for sustained attention by positron emission tomography. Nature 1991;349:61-64.
    OpenUrlPubMed
  41. 41.↵
    Friston KJ, Jezzard P, Turner R. Analysis of functional MRI time-series. Human Brain Map 1994;1:153-171.
    OpenUrlPubMed
  42. 42.↵
    Demonet J-F, Chollet F, Ramsay S, et al. The anatomy of phonological and semantic processing in normal subjects. Brain 1992;115:1753-1768.
    OpenUrlAbstract/FREE Full Text
  43. 43.↵
    Ojemann GA, Dodrill CB. Verbal memory deficits after left temporal lobectomy for epilepsy. J Neurosurg 1985;62:101-107.
    OpenUrlPubMed
  44. 44.
    Hermann BP, Wyler AR. Comparative results of temporal lobectomy under local or general anesthesia: language outcome. J Epilepsy 1988;1:127-134.
    OpenUrl
  45. 45.
    Ojemann GA, Sutherling WW, Lesser RP, Dinner DS, Jayakar P, Saint-Hilaire J-M. Cortical stimulation. In: Engel J, ed. Surgical treatment of the epilepsies. New York: Raven Press, 1993:399-414.
  46. 46.↵
    Loring DW, Lee GP, Meador KJ, Flanigin HF, Figueroa RE, Martin RC. The intracarotid amobarbital procedure as a predictor of memory failure following unilateral temporal lobectomy. Neurology 1990;40:605-610.
    OpenUrl
  47. 47.↵
    Loring DW, Meador KJ, Lee GP, et al. Wada memory performance predicts seizure outcome following anterior temporal lobectomy. Neurology 1994;44:2322-2324.
    OpenUrl
  48. 48.
    Sperling MR, Saykin AJ, Glosser G, et al. Predictors of outcome after anterior temporal lobectomy: the intracarotid amobarbital test. Neurology 1994;44:2325-2330.
    OpenUrl
  49. 49.↵
    Hart J, Lewis PJ, Lesser RP, et al. Anatomic correlates of memory from intracarotid amobarbital injections with technetium Tc 99m hexamethylpropyleneamine oxime SPECT. Arch Neurol 1993;50:745-750.
    OpenUrl
  50. 50.
    Perrine K, Uysal S, Dogali M, Luciano DJ, Devinski O. Functional mapping of memory and other nonlinguistic cognitive abilities in adults. Adv Neurol 1993;63:165-177.
    OpenUrlPubMed

Letters: Rapid online correspondence

No comments have been published for this article.
Comment

REQUIREMENTS

If you are uploading a letter concerning an article:
You must have updated your disclosures within six months: http://submit.neurology.org

Your co-authors must send a completed Publishing Agreement Form to Neurology Staff (not necessary for the lead/corresponding author as the form below will suffice) before you upload your comment.

If you are responding to a comment that was written about an article you originally authored:
You (and co-authors) do not need to fill out forms or check disclosures as author forms are still valid
and apply to letter.

Submission specifications:

  • Submissions must be < 200 words with < 5 references. Reference 1 must be the article on which you are commenting.
  • Submissions should not have more than 5 authors. (Exception: original author replies can include all original authors of the article)
  • Submit only on articles published within 6 months of issue date.
  • Do not be redundant. Read any comments already posted on the article prior to submission.
  • Submitted comments are subject to editing and editor review prior to posting.

More guidelines and information on Disputes & Debates

Compose Comment

More information about text formats

Plain text

  • No HTML tags allowed.
  • Web page addresses and e-mail addresses turn into links automatically.
  • Lines and paragraphs break automatically.
Author Information
NOTE: The first author must also be the corresponding author of the comment.
First or given name, e.g. 'Peter'.
Your last, or family, name, e.g. 'MacMoody'.
Your email address, e.g. higgs-boson@gmail.com
Your role and/or occupation, e.g. 'Orthopedic Surgeon'.
Your organization or institution (if applicable), e.g. 'Royal Free Hospital'.
Publishing Agreement
NOTE: All authors, besides the first/corresponding author, must complete a separate Publishing Agreement Form and provide via email to the editorial office before comments can be posted.
CAPTCHA
This question is for testing whether or not you are a human visitor and to prevent automated spam submissions.

Vertical Tabs

You May Also be Interested in

Back to top
  • Article
    • Abstract
    • Methods.
    • Results.
    • Discussion.
    • Note.
    • Note added in proofs.
    • Acknowledgments
    • REFERENCES
  • Figures & Data
  • Info & Disclosures
Advertisement

Hemiplegic Migraine Associated With PRRT2 Variations A Clinical and Genetic Study

Dr. Robert Shapiro and Dr. Amynah Pradhan

► Watch

Related Articles

  • No related articles found.

Alert Me

  • Alert me when eletters are published
Neurology: 100 (6)

Articles

  • Ahead of Print
  • Current Issue
  • Past Issues
  • Popular Articles
  • Translations

About

  • About the Journals
  • Ethics Policies
  • Editors & Editorial Board
  • Contact Us
  • Advertise

Submit

  • Author Center
  • Submit a Manuscript
  • Information for Reviewers
  • AAN Guidelines
  • Permissions

Subscribers

  • Subscribe
  • Activate a Subscription
  • Sign up for eAlerts
  • RSS Feed
Site Logo
  • Visit neurology Template on Facebook
  • Follow neurology Template on Twitter
  • Visit Neurology on YouTube
  • Neurology
  • Neurology: Clinical Practice
  • Neurology: Education
  • Neurology: Genetics
  • Neurology: Neuroimmunology & Neuroinflammation
  • AAN.com
  • AANnews
  • Continuum
  • Brain & Life
  • Neurology Today

Wolters Kluwer Logo

Neurology | Print ISSN:0028-3878
Online ISSN:1526-632X

© 2023 American Academy of Neurology

  • Privacy Policy
  • Feedback
  • Advertise