Variation in homotopic areas' activity and inter-hemispheric intrinsic connectivity with type of language lateralization: an FMRI study of covert sentence generation in 297 healthy volunteers.

We investigated the regional correlates of differences in hemispheric lateralization in 297 healthy volunteers [including 153 left-handers (LH)] previously classified into three types of language lateralization according to their hemispheric functional lateralization index measured with fMRI during covert sentence production versus word list production (PRODSENT-LIST): 250 leftward asymmetrical Typicals, 10 rightward asymmetrical Strong-atypicals (only LH), and 37 Ambilaterals with weak lateralization. Using a functionally driven homotopic atlas (AICHA), we compared patterns of regional asymmetry during PRODSENT-LIST in these three groups. Among the 192 homotopic regions of interest (hROIs) of the AICHA atlas, 58 exhibited a significant effect of the type of lateralization on their BOLD signal variation during PRODSENT-LIST. The analyses of patterns of asymmetry of these 58 hROIs showed that (1) hROIs asymmetries in Strong-atypicals were significantly negatively correlated with those observed in Typicals, which indicates that their regional pattern of rightward asymmetries was comparable to the regional pattern of leftward language asymmetries of Typicals; (2) right- and left-handed Typicals had identical profiles, whereas left-handed Ambilaterals exhibited reduced leftward asymmetry as compared either to right-handed Ambilaterals or to Typicals. Moreover, left-handed Ambilaterals pattern of hROIs asymmetries significantly positively correlated with those of both Typicals and Strong-atypicals. In 291 of the participants, we tested the hypothesis that differences in language lateralization were associated with differences in inter-hemispheric connectivity during resting state by measuring their regional homotopic inter-hemispheric intrinsic connectivity coefficient (rHIICC) in 36 of the 58 hROIs known to be connected via the corpus callosum. Mean rHIICCs were negatively correlated with task-induced functional asymmetries, suggesting that enhanced inter-hemispheric cooperation at rest translates into increased inter-hemispheric cooperation during language production. In addition, the left-handed Ambilaterals exhibited a significantly larger rHIICC compared with right-handed Ambilaterals and Typicals, confirming a difference in inter-hemispheric organization in this group.