Abnormal Elevated Connectivity During Language Processing is Associated with Poor Cognitive Performance in Children with Self-limited Epilepsy with Centrotemporal Spikes.

Self-Limited Epilepsy with Centrotemporal Spikes (SeLECTS) is associated with language impairments despite seizures originating in the motor cortex, suggesting aberrant cross-network interactions. Here we tested whether functional connectivity in SeLECTS during language tasks predicts language performance. We recorded high-density EEG from right-handed children with SeLECTS (n=31) and age-matched controls (n=32) during verb generation, repetition, and resting tasks. Phonological awareness was assessed using the Comprehensive Test of Phonological Processing-2. Connectivity between bilateral motor cortices and language regions (the left inferior frontal and superior temporal cortices and their right hemisphere homologues) was measured using weighted Phase Lag Index (wPLI). Children with SeLECTS demonstrated significantly elevated connectivity between motor and language regions during language processing. Motor-to-frontal connectivity was higher in SeLECTS during both verb generation and repetition tasks. Frontal-to-temporal connectivity was elevated specifically during verb generation. Higher interhemispheric connectivity (between the left and right hemispheres) during language tasks strongly predicted worse phonological awareness in children with SeLECTS (β= -40 to -61, all p<0.005), but not controls. Together, we found that children with SeLECTS exhibited pathologically elevated connectivity between motor and language networks that was strongly associated with impaired phonological awareness. These findings identify aberrant interhemispheric connectivity as a pathophysiological mechanism underlying language dysfunction and establish EEG-based connectivity measures as a potential biomarker for guiding targeted neuromodulation therapies to treat cognitive impairments in pediatric epilepsy.