FMRI-Determined Language Lateralization in Patients with Unilateral or Mixed Language Dominance According to the Wada Test

Abstract

Due to the reported variability of the language laterality index (LI) across fMRI studies, reliable distinction between patients with unilateral and mixed language dominance is currently not possible, preventing clinical implementation of fMRI as a replacement for the invasive Wada test. Variability of the LI may be related to differences in experimental and control tasks, and statistical methodology. The goal of this study was to improve detection power of fMRI for hemispheric language dominance by using a combined analysis of four different language tasks (CTA), that has previously shown more reliable and robust LIs in groups of normal volunteers than individual task analyses (see Ramsey et al.). The CTA targets brain areas that are common to different language tasks, thereby focusing on areas that are critical for language processing. Further advantage of the CTA is that it is relatively independent of specific task and control conditions. 18 patients with typical (i.e., left-sided, n = 11) and atypical (i.e., right-sided or mixed, respectively, n = 3 and n = 4) language dominance according to the Wada test underwent fMRI (groups respectively denoted as Wada L, Wada R, and Wada M patients). Statistical methodology (including thresholding of activity maps) was fixed to assure a user-independent approach. CTA yielded better results than any of the individual task analyses: it was more robust (on average 2.5 times more brain activity was detected due to its higher statistical power) and more reliable (concordance for Wada L, Wada M and Wada R patients was respectively 10/11 (91%), 3/4 (75%), and 2/3 patients (67%)). Overall, a significant correlation was observed between frontal and temporoparietal LIs. Remarkably, brain activity for Wada M patients was significantly lower than for Wada L or Wada R patients, and a dissociation in lateralization was observed between frontal (right-sided) and temporoparietal (left-sided) activity in three of four patients. Of the individual task analyses, the verb generation task yielded best results for patients with unilateral language dominance (same concordance as CTA). However, in contrast to CTA results, the verb generation task was unable to identify Wada M patients (concordance in one of four patients). In conclusion, the CTA is a promising approach for clinical implementation of fMRI for the prediction of hemispheric language dominance.