Interictal spikes and evoked cortical potentials share common spatiotemporal constraints in human epilepsy

Interictal epileptiform discharges (IEDs) are pathologic hallmarks of epilepsy which frequently arise and spread through networks of functionally-connected brain regions. Recent studies demonstrate that the sequential recruitment of brain regions by propagating IEDs is highly conserved across repeated discharges, suggesting that IED propagation is spatiotemporally constrained by features of the underlying epileptic network. Understanding how repetitive IED sequences relate to the spatiotemporal organization of the epileptic network may reveal key insights into the pathophysiological role of IEDs during epileptogenesis. Delivery of exogenous electrical current allows for direct experimental probing of epileptic network circuitry and correlation with spontaneous epileptiform activity (e.g., IEDs). In this pilot study of human subjects with refractory epilepsy, we performed cortical stimulation via invasive depth electrodes to test whether spatiotemporal patterns observed during spontaneous IEDs are reproduced by evoked cortical potentials. We found that evoked potentials were accentuated following stimulation of early-activating "upstream" IED regions (anterograde) and attenuated with stimulation of late-activating "downstream" IED regions (retrograde). Concordance between IED latencies and evoked potentials suggests that these distinct network phenomena share common spatiotemporal constraints in the human epileptic brain.