Is an earlier onset of focal epilepsy associated with atypical language lateralization? A systematic review, meta-analysis and new data

Right and bilateral language representation is common in focal epilepsy, possibly reflecting the influence of epileptogenic lesions and/or seizure activity in the left hemisphere. Atypical language lateralization is assumed to be more likely in cases of early seizure onset, due to greater language plasticity in childhood. However, evidence for this association is mixed, with most research based on small samples and heterogenous cohorts. In this preregistered meta-analysis we examined the association between age at seizure onset and fMRI-derived language lateralization in individuals with focal epilepsy. The pooled effect size demonstrated a correlation between an earlier onset and rightward language lateralization in the total sample (r = 0.1, p = .005, k = 58, n = 1240), with no difference in the correlation between age at seizure onset and language lateralization between left and right hemisphere epilepsy samples (Q=62.03, p = .302). In exploratory analyses of the individual participant data (n = 1157), we demonstrated strong evidence that a logarithmic model fits the data better than a linear (BF=350) or categorical model with 6 years of age as a cut-off (BF=36). These findings indicate that there is a small but significant relationship between age at seizure onset and language lateralization. The relationship was consistent with theories of language plasticity proposing an exponential decline in plasticity over early childhood. However, given that this effect was subtle and only found in larger sample sizes, an early age at seizure onset would not serve as a good indicator of atypical language lateralization on the individual patient level.