Repetitive transcranial magnetic stimulation modulates brain connectivity in children with self-limited epilepsy with centrotemporal spikes

Objective: Self-limited epilepsy with centrotemporal spikes (SeLECTS) is a common pediatric syndrome in which interictal epileptiform discharges (IEDs) emerge from the motor cortex and children often develop language deficits. IEDs may induce these language deficits by pathologically enhancing brain connectivity. Using a shamcontrolled design, we test the impact of inhibitory low-frequency repetitive transcranial magnetic stimulation (rTMS) on connectivity and IEDs in SeLECTS. Methods: Nineteen children participated in a cross-over study comparing active vs. sham motor cortex rTMS. Single pulses of TMS combined with EEG (spTMS-EEG) were applied to the motor cortex before and after rTMS to probe connectivity. Connectivity was quantified by calculating the weighted phase lag index (wPLI) between six regions of interest: bilateral motor cortices (implicated in SeLECTS) and bilateral inferior frontal and superior temporal regions (important for language). IED frequency before and after rTMS was also quantified. Results: Active, but not sham, rTMS decreased wPLI connectivity between multiple regions, with the greatest reductions seen in superior temporal connections in the stimulated hemisphere. IED frequency decreased after active but not sham rTMS. Significance: Low-frequency rTMS reduces pathologic hyperconnectivity and IEDs in children with SeLECTS, making it a promising avenue for therapeutic interventions for SeLECTS and potentially other pediatric epilepsy syndromes.