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Noninvasive Determination of Language Lateralization by Functional Transcranial Doppler Sonography

A Comparison With the Wada Test
Originally published 1998;29:82–86


    Background and Purpose—Functional transcranial Doppler ultrasonography (fTCD) can assess event-related changes in cerebral blood flow velocities and, by comparison between sides, can provide a measure of hemispheric perfusional lateralization. It is easily applicable, insensitive to movement artifacts, and can be used in patients with less than perfect cooperation. In the present study we investigated the validity of fTCD in determining the hemispheric dominance for language by direct comparison of fTCD with intracarotid amobarbital anesthesia (Wada test).

    Methods—fTCD and the Wada test were performed in 19 patients evaluated for epilepsy surgery. By the Wada test, 13 patients were classified as left-hemisphere dominant and 6 as right-hemisphere dominant for language. fTCD was based on the continuous bilateral measurements of blood flow velocities in the middle cerebral arteries and event-related averaging during a cued word generation task previously shown to activate lateralized language areas in normal adults.

    Results—In 4 patients fTCD assessment was not possible because of lack of an acoustic temporal bone window. In the remaining 15 candidates, determination of language dominance was concordant with the Wada test in every case. Moreover, the correlation of the lateralization measures from both procedures was highly significant (r=.92, P<.0001).

    Conclusions—This strong correlation validates fTCD as a noninvasive and practical tool for the determination of language lateralization that can be applied for clinical and investigative purposes.

    In most epilepsy surgery programs, hemispheric dominance for language is assessed by intra-arterial administration of amobarbital by means of a transfemoral catheter placed into the cerebral arteries (Wada test).12 Although of proven value in predicting the potential risk of language impairment after resective surgery, the Wada test has several inherent limitations, most importantly its invasiveness.34 Recently, fMRI has been used to measure cerebral perfusional changes noninvasively during language tasks in patients capable of avoiding movement artifacts during MRI scanning. The technique has been found to correlate closely with the outcome of the Wada test.56

    The changes in cerebral perfusion during cognitive tasks that underlie fMRI result in corresponding alterations of blood flow velocities in the feeding basal arteries. These alterations can be noninvasively and conveniently assessed by fTCD.789101112131415161718 The technique involves the continuous bilateral measurement of blood flow velocities in both MCAs during repeated performance of a task. Successive, event-related changes of blood flow in both arteries relative to the respective pre-event baseline are averaged, and averages from each hemisphere are then subtracted from each other. The calculation of mean relative blood flow differences makes the technique very robust, even allowing for intermittent moving and speaking. Moreover, it renders fTCD insensitive to global changes of perfusion due to modulations in Pco2 or Po2 that affect blood flow velocities in both insonated arteries equally.18 Thus, fTCD can even be applied in patients unsuitable for examinations by fMRI and can easily be repeated for follow-up. Its only limitation is that some subjects lack an acoustic temporal bone window for insonation of the MCA. In a previous study we demonstrated that fTCD during cued word generation in healthy right-handed subjects was associated with a significantly higher blood flow increase to the left relative to the right hemisphere in every subject.16 In the present study we directly compared fTCD with the Wada test in patients evaluated for epilepsy surgery to test the validity of fTCD as a tool for determination of language dominance.

    Subjects and Methods


    We studied 19 patients (12 males, 7 females) aged 17 to 45 years (mean age, 29 years) who underwent comprehensive evaluation for surgical treatment of medically intractable epilepsy at our department in Münster and the Epilepsie-Zentrum Bethel (Germany). The assessment included neurological examination, ictal semiology, video monitoring with continuous interictal and ictal electrophysiological recording, MRI, neuropsychological evaluation, fTCD, and the Wada test. Subjects gave informed consent to participate in the study. All were native German speakers. Thirteen were right handed and six left handed by the Edinburgh Handedness Inventory19 (Table). Wada and fTCD evaluations were performed by two different examiners blinded to the results obtained with either technique.

    Functional TCD

    Determination of hemispheric language dominance by fTCD was performed as previously described by our group.16 Subjects were seated in front of a computer screen where, 5 seconds after a cueing tone, a letter was presented for 2.5 seconds (Fig 1). Subjects silently had to find as many German words as possible starting with the displayed letter. To control the performance of the task, subjects were instructed to report the words after a second auditory signal 15 seconds after presentation of the letter. All words had to be reported within a 5-second time period. Afterward, a relaxation period of 60 seconds was given. Then the next letter was presented in the same way. Letters were presented in random order. Q,. X, and Y were excluded because very few German words have these letters as initials. No letter was displayed more than once.

    To measure CBFV changes in the basal arteries as an indicator of a downstream increase of regional metabolic activity during the language task, a commercially available dual TCD device (Multi-Dop T, DWL) was used. The MCAs were insonated at a depth of 50 mm with two 2-MHz transducer probes attached to a headband and placed at the temporal skull windows bilaterally (Fig 1). Details of the insonation technique, particularly the correct identification of the MCA, have been published elsewhere.20 The angles of insonation were adjusted to obtain the maximal signal intensity at the predetermined insonation depth. The spectral envelope curves of the Doppler signal were recorded with a rate of 28 sample points per second and stored for off-line analysis with custom-tailored software that had been programmed by one of the authors (M.D.). Artifacts like those elicited by probe displacement were automatically detected by comparison of the number of pulses per time unit of the entire recording session with the frequency of peaks in a given segment. Frames of recordings were rejected when these frequencies differed by more than one third. Additionally, epochs containing CBFV values outside the range of 30% to 200% of the mean flow velocity were rejected. The remaining data were integrated over the corresponding cardiac cycles, segmented into epochs that related to the cueing tone, and were then averaged. The epochs were set to begin 15 seconds before and to end 35 seconds after the cueing tone. The mean velocity in the 15-second precueing interval (Vpre.mean) was taken as the baseline value. The relative CBFV changes (dV) during cerebral activation were calculated by the formula dV=[V(t)−Vpre.mean]*100/Vpre.mean

    where V(t) is the CBFV over time. Relative CBFV changes from repeated presentations of letters (on the average 20 runs) were averaged time-locked to the cueing tone. Differences in the velocity changes in the two MCAs in every patient were statistically evaluated by the Wilcoxon test for each time point. This nonparametric test is less sensitive to outliers when only a limited number of epochs can be averaged. The number of repetitions was less than 22 because no letter was presented more than once during the word generation task. An fTCD LIfTCD was calculated by the following formula (the integral was substituted by the corresponding sum over the sampled data points representing the velocity curve):

    where ΔV(t)=dV(t)leftdV(t)right is the difference between the relative velocity changes of the left and right MCAs. tmax represents the latency of the absolute maximum of ΔV(t) during an interval of 7 to 27 seconds after cueing, ie, during verbal processing. For integration a time period of tint=2 seconds was chosen. The test-retest reproducibility of this procedure in determining hemispheric language lateralization based on the Pearson product moment correlation coefficient was r=.95, P<.0001 (S.K. et al, unpublished data, 1997). Results of the language lateralization by fTCD LIfTCD and Wada test LIWADA were compared by linear regression of the respective LIs.

    Wada Method

    The Wada procedure corresponded to the one described by Jokeit et al.2122 Briefly, angiography was performed by a transfemoral approach with patients in a supine position. A single bolus of 150 mg amobarbital was injected over a 4-second interval into the internal carotid artery under study. First the side of suspected seizure focus and, 30 minutes later, the contralateral side were assessed. Immediately after injection, numerical ratings were performed for the following language tasks. Following simple commands such as “Lift your arm” (maximal score, 4); reporting his/her first and second names (maximal score, 2); naming the days of the week (maximal score, 8; 1 point per day listed with an additional point for the correct sequence); reading simple words (maximal score, 15); reading complex words (maximal score, 10); naming colors, objects, and numbers presented visually (maximal score, 10 each); repeating sentences (maximal score, 10); describing concrete drawings (maximal score, 15); and explaining the meaning of words (maximal score, 10). The performance in tasks having maximal scores of 10 or 15 points was rated with the use of a scale between 0 and 5 for each of two or three items: 0 indicated no response, 1 meant that the response was unintelligible, 2 indicated that the response was incorrect, 3 that only repetition of an answer spoken aloud was possible, 4 that a correct response was possible only after verbal priming, and 5 that a correct answer was given spontaneously.

    A Wada LI (LI Wada) was calculated by the formula: LI Wada=(Pleft−Pright), where P is the language score after left and right internal carotid artery injection, respectively. This formula yields Wada indices between −104 for strong left-hemispheric language dominance and +104 for strong right-hemispheric language dominance.


    Of 19 patients who underwent successful Wada testing, fTCD could be performed in 15 patients. In the remaining 4 candidates no adequate acoustic temporal bone window for insonation of the MCAs could be found. There were no dropouts due to distress, movement artifacts, or lack of cooperation. The Table presents details of the patients, duration of epilepsy, handedness, and results on the Wada test and the fTCD.

    Functional TCD

    During the examined task, 8% (mean; range, 0% to 20%) of the recorded CBFV epochs were rejected because of artifacts. Mean CBFV data from the remaining epochs showed a bilateral biphasic CBFV augmentation. A first CBFV increase was seen approximately 1 second after the cueing tone but before letter presentation. This increase peaked on average at the time when the letter was expected, ie, 5 to 7 seconds later. A second CBFV augmentation began during letter presentation and, on average, peaked 4 seconds later. During actual word generation, ie, from letter presentation to the second tone, a significant (P≤.05, Wilcoxon test) relative predominance of CBFV increase in the left hemisphere was seen in 11 patients and in the right hemisphere in 4 patients. The extent of relative hemispheric CBFV predominance, ie, the difference between the mean CBFV increase from the baseline in one hemisphere relative to the other, varied from 1.3% to 6.3% (median, 3.2%; quartile, 2.6% to 4.0%) (left greater than right) in patients with left-hemisphere language dominance, and it varied from 1.3% to 5.7% (median, 3.6%; quartile, 2.2% to 4.9%) (right greater than left) in patients with right-hemisphere language dominance. In every case the determination of language lateralization by fTCD was concordant with the Wada test.

    While attending the screen for an upcoming letter, ie, after the first cueing tone and before the actual display of a letter on the screen occurred, patients with left-hemisphere language dominance often showed a relative right-hemispheric CBFV increase. Patients with right-hemisphere language dominance showed either a relative CBFV increase in the right hemisphere or, in one case, in the left hemisphere. In most cases, however, these attention-related activations did not reach significance.

    The LIs for language determined with the Wada test (LI Wada) revealed a highly significant correlation with the LIs measured by fTCD (LI fTCD) (r=.92, P<.0001) (Fig 2).


    The main finding of this study was that determination of hemispheric language dominance by fTCD was concordant with the result of the Wada test in every case. Moreover, even the quantitative measure of lateralization assessed by both techniques correlated closely (r=.92, P<.0001). Obviously, the activated cerebral areas during the employed word generation task, which led to a lateralization on fTCD, correspond closely to those areas underlying the hemispheric dominance as assessed by the Wada test. Unlike the Wada test, however, fTCD is without any risk or inconvenience to the patient. The statistical technique of averaging relative blood flow differences provides a very reliable indicator of the language lateralization and the extent of this lateralization in individual patients. The findings in the present study, obtained on this basis, corroborate the suggestion that language lateralization occurs along a graded continuum.6

    The Wada test, although a proven standard for determination of language dominance, has several substantial disadvantages.3423 The required intracarotid angiography necessitates hospitalization, is distressing to the patients, and has a morbidity risk reported as high as 5%.24 Obtundation after injection of amobarbital can make the distinction between attention-related and language-related deficits difficult. Results can be influenced by cross flow of anesthetic from the injected internal carotid artery to the contralateral hemisphere via the circle of Willis25 or by carryover effects from the first to the second injection when both carotid arteries are injected on the same day.26 The very restricted time for testing after amobarbital injection and the unavailability of test-retest reliability data constitute further limitations.

    Because of the risks and shortcomings associated with the Wada test, various attempts have been made to find alternatives to this technique. Speech localization has been performed with the use of repetitive transcranial magnetic stimulation.27 Repetitive magnetic stimulation of the brain, however, carries a small but definite risk for seizures, particularly in epileptic patients.28 Moreover, it can induce facial and laryngeal muscle contractions interfering with speech performance. Positron emission tomography is another technique that allows localization of cerebral language functions29303132 but is in itself invasive because of radiation exposure.

    Functional MRI offers another noninvasive alternative for the determination of hemispheric language dominance.56 In patients with refractory epilepsy, however, fMRI can be difficult to perform. It requires maximal cooperation because the technique is very sensitive to movement artifacts.33 It cannot be used in patients with claustrophobia, gross obesity, metallic implants near to or in the head, or cardiac pacemakers. Here fTCD holds promise as a complementary technique, since the perfusional changes assessed by fTCD are similar to those detected by fMRI but without the above restrictions.12

    The physiological information obtained by either fTCD or the Wada test depends on the arterial distribution under study. While the amobarbital injection during the Wada test impairs cerebral function within the territory of the internal carotid artery, fTCD operates more selectively by pinpointing the distribution of a specific pial artery, eg, the MCA. Functional TCD imposes no time or space restraints and is associated with no distress and little to no inconvenience to the patient. Furthermore, TCD is a mobile and comparatively inexpensive technique, available in most neurological departments. It can be performed on an outpatient basis and may easily be repeated for follow-up purposes. It allows control regarding patient cooperation during every task without jeopardizing the recording in toto due to movement artifact, as is sometimes the case in fMRI studies. This makes it a practical tool for the determination of language dominance in the clinical setting. Functional TCD is, however, dependent on its ability to acoustically penetrate the temporal bone. In our series this was not always feasible because 4 of 19 patients lacked a “window.” In these patients, determination of language dominance by fTCD was not possible with our technology. However, auxiliary techniques are now becoming available that allow TCD assessment even in the presence of thicker bones.34

    Full use of the potential of fTCD has in the past been hampered by the fact that the CBFV signal displays large fluctuations of the mean in the range of ±30% due to heart rate or changes in Pco2. This makes detection of small functional changes on the order of 2% to 5% difficult. During cognitive tasks, triphasic modulations of heart rate and cardiac ejection fraction add to fluctuations of CBFV.3536 It was not before the introduction of bilateral simultaneous TCD that mean lateralized increases of the CBFV relative to these global fluctuations could be assessed by comparison between sides. This comparison between sides also allows for detection of bilateral language representation characterized by CBFV increases in both MCAs with small differences, ie, a low LI. In some series the reported incidence of bilateral language function determined by multiple language tasks applied during Wada testing is almost 20%.37 In our series only one patient17 had a low LI by both the Wada test and fTCD. Given the limited sample size, this study does not lend itself to establish a representative incidence of hemispheric language dominance. Although patients had not been specifically selected for the purpose of our study, the 20% incidence of right-hemispheric dominance was far higher than in amobarbital studies based on several hundred patients.38

    The word generation task during fTCD corresponds to paradigms used in other studies involving functional imaging.394041 Conversely, the Wada test, as used in the present study, assesses a wider variety of language functions. Time restraints during the intracarotid amobarbital procedure did not allow us to perform an additional word generation task identical to the one used for fTCD. Thus, there were not only methodological differences between fTCD (involving activation) and the Wada test (involving anesthesia) but also differences in the behavioral task. In the literature, impairments in word generation capabilities are linked to damage in the left frontal lobe but can also be seen in nonfrontal lobe lesions.4243 Activation studies indicate that lexical retrieval involves multiple regions of one hemisphere, many of which are located outside the classic language areas.44 Moreover, many of the patients in this study had long-standing cerebral lesions. Thus, there was an increased likelihood of functional reorganization of language areas and involvement of atypical anatomic locations.45 However, the strong correlation between the results from fTCD based on the word generation task and from the Wada test based on multiple language tasks indicates that there was a substantial overlap of brain regions involved in the respective behavioral tasks. Nevertheless, further fTCD studies involving different activation paradigms and direct comparison with postoperative language performance should be performed to better delineate the potential role of this new technique in epilepsy surgery and in other investigational fields of language lateralization.

    Selected Abbreviations and Acronyms

    CBFV=cerebral blood flow velocity
    fMRI=functional magnetic resonance imaging
    fTCD=functional transcranial Doppler ultrasonography
    LI=laterality index
    MCA=middle cerebral artery
    TCD=transcranial Doppler ultrasonography

    Presented in part at the Third International Conference on Functional Mapping of the Human Brain, May 19–23, Copenhagen, Denmark.

          Figure 1.

    Figure 1. Experimental setup of language dominance assessment by fTCD. Displayed data represent the averaged results from 20 letter presentations in a single subject. Note the delay of approximately 4 to 7 seconds before the maximal hemispheric difference is reached. dV indicates relative CBFV changes.

          Figure 2.

    Figure 2. Correlation between lateralization by the Wada test and the fTCD (r=.92045, P<.0001) (Wada= −1.594+ 16.892*fTCD). Dashed lines indicate 95% confidence intervals; •, individual patients with right- or left-hemispheric dominance for language.

    Table 1. Patient Characteristics, Duration of Epilepsy, Handedness, and Results of Wada Test and fTCD

    PtAge, ySeizure Onset, ySexHandednessEEG FocusEtiologyLI WadaLI fTCD
     1216MR (95)L frontotemporalMRI: L parietooccipital lobe tumor76NBW
     22719FR (60)Bilateral temporalFebrile seizures433.25
     33517MR (100)No lateralizationMRI: Lesion R temporal543.16
     43210FR (100)L temporalMRI: atrophy of R temporal lobe522.5
     5188MR (100)L parieto-occipitalMRI: atrophy of L temporal lobe−49NBW
     63010MR (100)R temporal and frontoparietalTrauma, MRI: atrophy of R hippocampus902.68
     7249ML (−100)R temporalMRI: R temporal mesial gangliogliom613.16
     81814ML (−95)R temporalCongenital malformation585.58
     9293FR (100)L parietocentralUnknown492.12
    10171FR (100)R frontal and generalizedMRI: R frontal cortical dysplasia526.33
    11306FL (−100)L temporalMRI: hippocampal atrophy, unknown etiology−78NBW
    122713MR (100)L temporalIntraoperative diagnosis: hemangioma482.95
    133431MR (100)R frontalMRI: atrophy of R hemisphere954.14
    144515MR (80)R temporalMRI: R temporal basal lesion884.14
    15437MR (100)L frontocentralMRI: L frontocentral cortical dysplasia77NBW
    162618FL (−100)L temporalFebrile seizures, MRI: L hemiatrophy−75−4.15
    171814MAmbidextrous (0)R frontocentralMRI: R central lesion−18−1.32
    18301ML (−100)L frontalTrauma (R arm atrophy)−104−5.69
    19191FR (80)Bilateral temporalMRI: hippocampal sclerosis, unknown etiology−86−3.08

    PT indicates patient; R, right; L, left; and NBW, no bone window.

    1Scores according to the Oldfield’s Edinburgh Handedness Inventory are provided in parentheses.

    This study was supported by the Bennigsen-Foerder grant from the Ministry of Science and Research of Nordrhein-Westfalen, Germany.


    Correspondence to Stefan Knecht, MD, Department of Neurology, University of Münster, Albert-Schweitzer-Straβe 33, D-48129 Münster, Germany. E-mail


    • 1 Wada J. A new method for determination of the side of cerebral speech dominance: a preliminary report on the intracarotid injection of sodium amytal in man. Igaku Seibutsugaku.1949; 4:221–222.Google Scholar
    • 2 Wada J, Rasmussen T. Intracarotid injection of sodium amytal for the lateralization of cerebral speech dominance. J Neurosurg.1960; 17:266–282.CrossrefGoogle Scholar
    • 3 Loring D, Meador K, Lee G, King D. Amobarbital Effects and Lateralized Brain Function: The Wada Test. New York, NY: Springer-Verlag; 1992.Google Scholar
    • 4 Woods R, Dodrill C, Ojemann G. Brain injury, handedness, and speech lateralization in a series of amobarbital studies. Ann Neurol.1988; 23:510–518.CrossrefMedlineGoogle Scholar
    • 5 Desmond J, Sum J, Wagner A, Demb J, Shear P, Glover G, Gabrieli J, Morrell M. Functional MRI measurement of language lateralization in Wada-tested patients. Brain.1995; 118:1411–1419.CrossrefMedlineGoogle Scholar
    • 6 Binder J, Swanson S, Hammeke T, Morris G, Mueller W, Fischer M, Benbadis S, Frost B, Rao S, Haughton W. Determination of language dominance using functional MRI: a comparison with the Wada test. Neurology.1996; 49:978–984.Google Scholar
    • 7 Bishop CCR, Powell S, Rutt D, Browse NL. Transcranial Doppler measurements of middle cerebral artery blood flow velocity: a validation study. Stroke.1986; 5:913–915.LinkGoogle Scholar
    • 8 Droste D, Harders A, Liberti G. Bilateral simultaneous transcranial Doppler monitoring during the performance of a verbal fluency task and a face recognition task. J Psychophysiol.1996; 10:303–309.Google Scholar
    • 9 Gomez SM, Gomez CR, Hall IS. Transcranial Doppler ultrasonographic assessment of intermittent light stimulation at different frequencies. Stroke.1990; 21:1746–1748.CrossrefMedlineGoogle Scholar
    • 10 Hartje W, Ringelstein E-B, Kistinger B, Fabianek K, Willmes K. Transcranial Doppler ultrasonic assessment of middle cerebral artery blood flow velocity changes during verbal and visuospatial cognitive tasks. Neuropsychology.1994; 12:1443–1452.Google Scholar
    • 11 Kelley RE, Chang JY, Scheinman NJ, Levin BE, Duncan RC, Lee SC. Transcranial Doppler assessment of cerebral flow velocity during cognitive tasks. Stroke.1992; 23:9–14.CrossrefMedlineGoogle Scholar
    • 12 Sitzer M, Knorr U, Seitz R. Cerebral hemodynamics during sensorimotor activation in humans. J Appl Physiol.1994; 77:2804–2811.CrossrefMedlineGoogle Scholar
    • 13 Njemanze PC, Gomez CR, Horenstein S. Cerebral lateralization and color perception: a transcranial Doppler study. Cortex.1992; 28:69–75.CrossrefMedlineGoogle Scholar
    • 14 Rihs F, Gutbrod K, Gutbrod B, Steiger H, Sturzenegger M, Mattle H. Determination of cognitive hemispheric dominance by ‘stereo’ transcranial Doppler sonography. Stroke.1995; 26:70–73.CrossrefMedlineGoogle Scholar
    • 15 Bulla-Hellwig M, Vollmer J, Götzen A, Skreczek W, Hartje W. Hemispheric asymmetry of arterial blood flow velocity changes during verbal and visuospatial tasks. Neuropsychologia.1996; 34:987–991.CrossrefMedlineGoogle Scholar
    • 16 Knecht S, Henningsen H, Deppe M, Huber T, Ebner A, Ringelstein E-B. Successive activation of both cerebral hemispheres during cued word generation. Neuroreport.1996; 7:820–824.CrossrefMedlineGoogle Scholar
    • 17 Knecht S, Deppe M, Bäcker M, Ringelstein E-B, Henningsen H. Regional cerebral blood flow increases during preparation for and processing of sensory stimuli. Exp Brain Res..1997; 116:309-314.CrossrefMedlineGoogle Scholar
    • 18 Deppe M, Knecht S, Henningsen H, Ringelstein E-B. Average: a Windows program for automated analysis of event related cerebral blood flow. J Neurosci Methods.1997; 75:147–154.CrossrefMedlineGoogle Scholar
    • 19 Oldfield RC. The assessment and analysis of handedness: the Edinburgh inventory. Neuropsychologia.1971; 9:97–113.CrossrefMedlineGoogle Scholar
    • 20 Ringelstein E-B, Kahlscheuer B, Niggemeyer E, Otis SM. Transcranial Doppler sonography: anatomical landmarks and normal velocity values. Ultrasound Med Biol.1990; 16:745–761.CrossrefMedlineGoogle Scholar
    • 21 Jokeit H, Ebner A, Holthausen H, Markowitsch H, Tuxhorn I. Reorganization of memory functions after human temporal lobe damage. Neuroreport.1996; 7:1627–1630.CrossrefMedlineGoogle Scholar
    • 22 Jokeit H, Ebner A, Holthausen H, Markowitsch H, Moch A, Pannek H, Schulz R, Tuxhorn I. Individual prediction of change in delayed recall of prose passages after left-sided anterior temporal lobectomy. Neurology.1997; 49:481–487.CrossrefMedlineGoogle Scholar
    • 23 Loring DW, Meador KJ, Lee GP, King DW, Nichols ME, Park YD, Murro AM, Gallagher BB, Smith JR. Wada memory asymmetries predict verbal memory decline after anterior temporal lobectomy. Neurology.1995; 45:1329–1333.CrossrefMedlineGoogle Scholar
    • 24 Rausch R, Silfvenius H, Wieser H, Dodrill C, Meador K, Jones-Gotman M. Intraarterial amobarbital procedures. In: Engel J, ed. Surgical Treatment of the Epilepsies. New York, NY: Raven Press; 1993:341–357.Google Scholar
    • 25 Hietala S, 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; 16:683–686.CrossrefMedlineGoogle Scholar
    • 26 Dinner D. Intracarotid amobarbital test to define language lateralization. In: Lüders H, ed. Epilepsy Surgery. New York, NY: Raven Press; 1992:503–506.Google Scholar
    • 27 Jennum P, Friberg L, Fuglsang-Frederiksen A, Dam M. Speech localization using repetitive transcranial magnetic stimulation. Neurology.1994; 44:269–273.CrossrefMedlineGoogle Scholar
    • 28 Hömberg V, Netz J. Generalised seizures induced by transcranial magnetic stimulation of the motor cortex. Lancet.1989; 334:1223. Letter.CrossrefGoogle Scholar
    • 29 Liotti M, Gay CT, Fox PT. Functional imaging and language: evidence from positron emission tomography. J Clin Neurophysiol.1994; 11:175–190.CrossrefMedlineGoogle Scholar
    • 30 Roland PE, Lassen NA, Friberg L. Regional cortical blood flow changes during fluent speech in subjects with verified hemispheric dominance. J Cereb Blood Flow Metab.1985; 5:205–206.Google Scholar
    • 31 Roland P. Brain Activation. New York, NY: Wiley Liss; 1993.Google Scholar
    • 32 Demonet J, Wise R, Frackowiak R. Language functions explored in normal subjects by positron emission tomography. Hum Brain Map.1994; 1:39–47.Google Scholar
    • 33 Glover G, Lee A. Motion artifacts in fMRI: comparison of 2DFT with PR and spiral scan methods. Magn Reson Med.1995; 33:624–635.CrossrefMedlineGoogle Scholar
    • 34 Kaps M, Schaffer P, Beller KD, Seidel G, Bliesath H, Wurst W. Phase I: transcranial echo contrast studies in healthy volunteers. Stroke.1995; 26:2048–2052.CrossrefMedlineGoogle Scholar
    • 35 Damen E, Brunia C. Changes in heart rate and slow brain potential related to motor preparation and stimulus anticipation in a time estimation task. Psychophysiology.1987; 24:700–713.CrossrefMedlineGoogle Scholar
    • 36 Pagani M, Mazzuero G, Ferrari A, Liberati D, Cerutti S, Vaitl D, Tavazzi L, Malliani A. Sympathovagal interaction during mental stress: a study using spectral analysis of heart rate variability in healthy control subjects and patients with prior myocardial infarction. Circulation. 1991;83(suppl 4):II43–II51.Google Scholar
    • 37 Loring DW, Meador KJ, Lee GP, Murro AM, Smith JR, Flanigin HF, Gallagher BB, King DW. Cerebral language lateralization: evidence from intracarotid amobarbital testing. Neuropsychologia.1990; 28:831–838.CrossrefMedlineGoogle Scholar
    • 38 Risse GL, Gates JR, Fangman MC. A reconsideration of bilateral language representation based on the intracarotid amobarbital procedure. Brain Cogn.1997; 33:118–132.CrossrefMedlineGoogle Scholar
    • 39 Petersen SE, Fox P, Posner M, Mintum M, Raichle M. Positron emission tomographic studies of the cortical anatomy of single-word processing. Nature.1988; 331:585–589.CrossrefMedlineGoogle Scholar
    • 40 Frith C, Friston KJ, Liddle PF, Frackowiak RS. A PET study of word finding. Neuropsychologia.1991; 29:1137–1148.CrossrefMedlineGoogle Scholar
    • 41 Cuenod CA, Bookheimer SY, Hertz-Pannier L, Zeffiro TA, Theodore WH, Le Bihan D. Functional MRI during word generation using conventional equipment. Neurology.1995; 45:1821–1827.CrossrefMedlineGoogle Scholar
    • 42 Borowski JG, Benton AL, Spreen O. Word fluency and brain damage. Neuropsychologia.1967; 5:135–140.CrossrefGoogle Scholar
    • 43 Ruff RM, Light RH, Parker SB, Levin HS. The psychological construct of word fluency. Brain Lang.1997; 57:394–405.CrossrefMedlineGoogle Scholar
    • 44 Damasio H, Grabowski TJ, Tranel D, Hichwa RD, Damasio AR. A neural basis for lexical retrieval. Nature.1996; 380:499–505.CrossrefMedlineGoogle Scholar
    • 45 Rasmussen T, Milner B. The role of early left-brain injury in determining lateralization of cerebral speech functions. Ann N Y Acad Sci.1977; 29:299–355Google Scholar


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