Human neocortical interictal epileptiform discharges are initiated by a low-voltage negative polarity wave

Purpose In between seizures, the brain of a patient with epilepsy will generate isolated, sporadic discharges (interictal epileptiform discharges [IEDs]). IED identification enables clinicians to diagnose epilepsy, and an understanding of IED waveforms may yield new insights into basic epilepsy mechanisms. I show that intracranial EEGs disclose a previously unreported negative polarity, low-voltage pre-potential at IED onset (i.e., a negative wave [n-wave]). I describe the features of n-waves and propose a plausible mechanism of their generation. Method In intracranial EEGs of the human neocortex, I assessed n-waves’ occurrence, anatomical location, amplitude, kinetics, and association with the subsequent positive pre-potential. I computed a model simulation of IED onset to identify plausible mechanisms behind n-wave generation. Results N-waves manifested in 40% of patients, in zones with and without seizures, and without a statistically significant prevalence in their anatomical location. These waveforms exhibited voltages of 140 + 42 μV and durations of 39.9 + 12.2 msec and were coupled with a positive pre-potential. In simulations of IED onset, n-waves can be generated by sequential recruitment of distinct microfoci over superficial cortical laminae. Conclusions N-waves represent an overlooked component of IED waveforms. They prolong the duration of IED onset and can facilitate synaptic hypersynchrony. They may also be associated with chronic epilepsy.