Predictors of atypical language lateralization in focal epilepsy: A mega-analysis of fMRI evidence

OBJECTIVE: To identify predictors of language lateralization derived from functional magnetic resonance imaging (fMRI) in children and adults with left- and right-sided focal epilepsy. METHODS: We conducted a mega-analysis of data from 914 individuals from 24 samples. We used multilevel models to identify predictors of language lateralization in left and right hemisphere epilepsy groups. We assigned each participant a clinical predictor score to explore whether there was a cumulative influence of predictors on increasing atypical language lateralization. RESULTS: Left hemisphere epilepsy was a predictor of greater atypical language lateralization in the combined sample. Additional predictors of atypical language lateralization included left/ambidextrous handedness in both the left and right hemisphere groups, and longer duration of epilepsy, frontal lobe involvement, and history of a stroke or other precipitating injury in the left hemisphere group only. There was a cumulative effect of predictors in the left hemisphere groups. Eighty percent of individuals with four or more predictors had atypical language lateralization, compared to 19% of individuals with no predictors, other than left hemisphere epilepsy. SIGNIFICANCE: Consistent with theories of language plasticity, we demonstrated a robust effect of early acquired left hemisphere injury on language lateralization. There was also a subtle effect of duration of epilepsy, perhaps reflecting increasing bilaterality with age in adulthood. The association between left/ambidextrous handedness and atypical language lateralization in the left and right hemisphere groups likely reflects both genetic and epilepsy-associated effects. The total number of predictors identified for an individual could serve as an indication for presurgical language fMRI, when surgical management is considered.