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Determination of Cognitive Hemispheric Lateralization by “Functional” Transcranial Doppler Cross-Validated by Functional MRI

Originally published 1999;30:2491–2492

    To the Editor:

    In their article on functional transcranial Doppler sonography (fTCD), Schmidt et al1 conclude the fTCD can lateralize higher cognitive functions reliably. They suggest that it may be used in patients in the preoperative evaluation before brain surgery. But because “data to validate fTCD…are still lacking,” they caution that fTCD should be cross-checked with well established techniques (presumably the Wada test), particularly with regard to language dominance. Stroke published such a study (“Noninvasive Determination of Hemispheric Language Dominance Using Functional Transcranial Doppler Sonography: A Comparison With the Wada Test”)2 1 year ago.

    Schmidt et al base their suggestions on group averages. Again, it was this very journal that published a study on the feasibility and reproducibility of single-subject assessment by fTCD.3 A full account of the present state of single-case fTCD analysis has already been published by Deppe et al.4

    Schmidt et al state that “concordant differences between the female and the male subgroup could be visualized.”1 To us, this sentence is somewhat misleading. Changes in lateralization “concordant” in fMRI and fTCD have a 50% chance of occurring in each sex. The authors provide no statistical evidence for sex differences in their paper. Such differences cannot be established by finding significant (P=0.022) lateralization only in females and not in males, particularly as long as no correction for multiple comparisons (eg, Bonferroni) was performed. Even then, they found significant sex differences of cerebral blood flow velocity within neither the left nor the right middle cerebral arteries (figure 7).1

    We agree with Schmidt et al that fTCD has a clinical potential. This is why the same rigid methodological requirements should be applied to fTCD as to other functional imaging techniques. The methodological tools for single-case studies are available.


    • 1 Schmidt P, Kings T, Willmes K, Roessler F, Reul J, Thron A. Determination of cognitive hemispheric lateralization by “functional” transcranial Doppler cross-validated by functional MRI. Stroke..1999; 30:939–945.CrossrefMedlineGoogle Scholar
    • 2 Knecht S, Deppe M, Ebner A, Henningsen H, Huber T, Jokeit H, Ringelstein E. Noninvasive determination of hemispheric language dominance using functional transcranial Doppler sonography: A comparison with the Wada test. Stroke..1998; 29:82–86.CrossrefMedlineGoogle Scholar
    • 3 Knecht S, Deppe M, Ringelstein E-B, Wirtz M, Lohmann H, Dräger B, Huber T, Henningsen H. Reproducibility of functional transcranial Doppler-sonography in determining hemispheric language lateralization. Stroke..1998; 29:1155–1159.CrossrefMedlineGoogle Scholar
    • 4 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
    strokeahaStrokeStrokeStroke0039-24991524-4628Lippincott Williams & Wilkins
    ResponseSchmidt Peter, MDR1, Krings Timo, MDR1R2, Willmes Klaus, PhDR2R3, and Thron Armin, MDR1R2111999cerebral blood flowmagnetic resonance imagingultrasonography

    In accord with our colleagues Knecht and coworkers, we are glad that Stroke offers a platform for publishing and discussing the latest results of fTCD research.

    Despite these promising research findings, fTCD still is not routinely used in the majority of hospitals. To promote this clinical application, we thought our confirmatory findings to be worth publishing. To our knowledge, our study was the first in which the potentials of fTCD and fMRI in identifying cognitive lateralization were compared directly. We could show for the group of subjects that with both methods one can detect a significant blood flow shift to the right hemisphere induced by a complex cognitive visuospatial task.

    Our statement concerning the comparison of female and male subjects (“fTCD shows a higher VMCA increase of the rMCA in the male subgroup compared with the female subgroup, corresponding to the larger area of activation found in the fMRI results in the male subgroup”) was purely descriptive. It was meant to be an additional surprising yet possibly accidental finding that we thought to be worth mentioning. A 2-factorial repeated measures ANOVA with hemisphere (left, right) as repeated measures factor and gender as the second factor revealed no significant interaction between both factors (P=0.62), indicating that there was no significant gender difference in the degree of discrepancy between VMCA increases in both hemispheres. So our initial statement must either be considered accidental, or a much larger study would be required to detect a small interaction effect with sufficient statistical power. We have been aware of the work by Knecht and his colleaguesR1R2R3 quoted in their letter to Stroke, but because we did not utilize their method of evaluation we did not quote these papers.

    With both fMRI as well as fTCD we could show the adequacy of both methods in detecting cognitive lateralization in a visuospatial task. In case of an absent temporal skull window, when fTCD fails to be useful for studying lateralization, fMRI might be a future alternative to the Wada test without any known side effects. Therefore, Knecht and coworkers must be credited for having pointed out that every new noninvasive technique must be studied closely for individual patient reproducibility of lateralization effects in cognitive paradigms.


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