Sleep fragmentation drives local, network-specific epileptic activity in human epilepsy

Sleep has complex links with epileptic activity, yet the causal role of sleep instability in driving and modulating pathological discharges in the human brain remains incompletely understood. Here we directly examine this by characterising the fine-scale temporal coupling between experimentally induced sleep arousals and interictal epileptiform discharges (IEDs), using combined stereo-electroencephalography and polysomnography recordings in patients with epilepsy. Sleep arousals triggered rapid IED increases, with effects gated by anatomical region and sleep stage. Increases were confined to neocortical regions and occurred during both non-rapid eye movement stage 2 (N2) and stage 3 (N3) sleep, with a larger effect observed in N2. IED increases did not differ between the seizure-onset zone and surrounding regions. Despite elevating IED counts, arousals did not alter IED spatial propagation, indicating state-dependent enhancement of local cortical excitability without recruitment of broader epileptic networks. These findings establish a causal role for sleep instability in actively driving pathological activity on fine-grained spatiotemporal scales, and highlight sleep stabilisation as a promising therapeutic strategy to reduce epileptic burden and preserve cortical network function.