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 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.

The authors have declared no competing interest.

FP is supported by the Child Health Research Studentship funded by the Child Health Research Charitable Incorporated Organisation. FP spent 8 weeks at the Children National Hospital in Washington, DC, funded by The Charlotte and Yule Bogue Research Fellowships in Honour of Sir Charles Lovatt Evans and A.J. Clark. MHE is supported by the Child Health Research Studentship, funded by the National Institute for Health and Care Research Great Ormond Street Hospital Biomedical Research Centre (NIHR GOSH BRC) and the Sigrid Juselius Foundation. LNS is supported by a K23 grant (K23 NINDS NS093152).

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The details of the IRB/oversight body that provided approval or exemption for the research described are given below:

Ethical approval was granted by the Great Ormond Street Hospital clinical audit department as a service evaluation (No. 1443, extended), according to the guidelines set by NHS Research Ethics Committee Review. Participants from Children's National Hospital (CNH) were part of clinical or research protocols with different aims related to pediatric epilepsy and language development, but all were approved by the Institutional Review Board at CNH. Parents provided informed written consent and all children gave assent to participate.

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