The numbers of left, bilateral, and right dominant cases, grouped by language lateralization method and language dominance category are displayed in , along with a breakdown of the number of patients with each possible combination of results from the two tests. Most of the disagreements in categorization (38 of 42) involved patients who were labeled as bilateral by one of the tests but not by the other. In four extreme cases, Wada indicated left dominance while fMRI indicated right dominance. There were no cases with the reverse pattern.
Number of Left, Bilateral, and Right Dominant Cases Based on a Wada Categorization Cut Score of 50 and an fMRI Categorization Cut Score of 25 (N=229)
and show the Wada/fMRI LI discordance rates, using the dual criteria requiring discordant categorization and an LI difference score of at least 50 units. Discordance was observed in 32 patients, or 14% of the total sample. Using Wada as the measure of reference, discordance rates ranged from 8–40%, depending on language dominance category (see ). The difference in rate of discordance as a function of Wada dominance category was highly significant (chi-square = 26.8, p < .0001). Rates for both the bilateral category (p < .0001, Fisher exact test) and the right dominant category (p = .0083, Fisher exact test) were higher than for the left dominant category. The discordance rate was numerically higher in patients with bilateral language than in those with right dominance, though this difference did not reach statistical significance.
Language Discordance Rates when Wada is Left, Right, and Bilateral using a Wada Categorization Cut Score of 50 and an fMRI Categorization Cut Score of 25
Language Discordance Rates when fMRI is Left, Right, and Bilateral using a Wada Categorization Cut Score of 50 and an fMRI Categorization Cut Score of 25 – fMRI as Reference
Using fMRI as the measure of reference, discordance rates ranged from 6–57%, depending on language dominance category (see ). Differences between the dominance categories were highly significant (chi-square = 55.3, p < .0001). The discordance rate was higher when fMRI indicated bilateral dominance (p < .0001, Fisher exact test) or right dominance (p = .0085, Fisher exact test) than when fMRI indicated left dominance. The rate was also higher when fMRI indicated bilateral dominance than when fMRI indicated right dominance (p = .028, Fisher exact test).
Overall, these data indicate high levels of concordance (92%–94%) when a result indicates left dominant language. Discordance was much more likely when either test indicated atypical language dominance. The highest rates of discordance were observed when fMRI LIs indicated bilateral language.
Predictors of Discordance
Summary statistics for the concordant and discordant groups are shown in . T-tests and chi-square analyses were performed to compare discordant and concordant groups. The discordant and concordant groups did not differ with regard to any subject variables, Wada quality indices, or fMRI quality indices after Bonferroni correction for multiple comparisons (all p values > .04). Significant differences were observed between the concordant group and the discordant group with regard to Wada LIs and fMRI LIs, with much lower mean LIs on both tests in the discordant group.
Comparisons Between Concordant and Discordant Groups
Categorical comparisons between concordant and discordant groups may not be optimally sensitive, given that discordance varies along a continuum. We therefore conducted Pearson correlations with selected continuous variables to test for relationships between these variables and the absolute values of the Wada-fMRI LI difference score. No significant relationships were observed except for the Wada and fMRI LIs (). In both cases, the more atypical the LI, the larger the absolute Wada-fMRI LI difference.
Correlations Between Continuous Variables and Wada-fMRI LI Difference Scores
Given the non-Gaussian LI distributions, we also examined the same variables with Spearman correlations (, right columns). The only significant relationship was observed for the fMRI LI. Again, the more atypical the LI, the larger the absolute Wada-fMRI difference.
Next, a series of simple regression analyses were performed to examine the relationship between selected groups of predictor variables and the absolute value of the LI difference scores. Although most variables of interest were not correlated with the LI difference score, we hypothesized that they might collectively explain a significant amount of variance in the LI difference score. First, we entered subject variables that were hypothesized to have a relationship with discordance due to their association with atypical language organization in previous studies (handedness, age at seizure onset, mesial temporal sclerosis or hippocampal atrophy, full scale IQ). This model did not account for any significant variance in the LI difference score (Adjusted R2 = .01, F(4, 221) = 1.82, p =.13). In a separate regression analysis, we entered the Wada quality indices described above, which also did not account for a significant amount of the variance in LI difference scores (Adjusted R2 = -.01, F(7, 199) = .74, p =.64). Likewise, the fMRI quality indices did not predict a significant amount of the variance in LI difference scores (Adjusted R2 = .02, F(6, 208) = 1.77, p =.11).
Finally, because the Wada LI and the fMRI LI were both significantly correlated with LI difference score, we used a hierarchical regression analysis to explore the relative predictive value of each LI. When the Wada LI was entered in block one followed by the fMRI LI in block two, the Wada LI accounted for 5% of the variance in Wada-fMRI LI difference scores (R2 change = .05, p =.001), and fMRI LI accounted for an additional 22% of the variance (R2change = .22, p < .0001). When the fMRI LI was entered first in block one followed by the Wada LI in block two, the fMRI LI accounted for 26% of the variance in Wada-fMRI LI difference scores (R2change = .26, p < .0001) and the Wada LI accounted for only an additional 2% of the variance (R2change = .02, p = .03). Thus most of the variance in LI difference scores is accounted for by the fMRI LI. The negative sign of this relationship () indicates that as the fMRI LI becomes more negative (meaning more atypical language), the LI discrepancy tends to increase.
Cases of Extreme Discordance
As mentioned above, there were four extreme cases of discordance, in which Wada indicated left dominance and fMRI indicated right dominance. Although comprising less than 2% of the sample, these cases are potentially informative with respect to causes of discordance. These patients were all right handed with right hemisphere seizure foci. Close examination of the Wada results for these patients did not reveal any potential quality issues. However, when the fMRI data were examined, one of the patients had extremely small number of activated voxels (76 total voxels, in contrast to a median activation of 12,299 voxels in the entire patient sample). In a post hoc analysis, we did not find a systematic statistical relationship between discordance and total activation volume. There was a numerically greater rate of discordance in the decile of the sample with the smallest activation volume (22% discordant) compared to the rest of the sample (13% discordant), but this difference did not approach significance (chi-square = 1.28, p = .26).