Spatiotemporal dynamics between interictal epileptiform discharges and ripples during associative memory processing

We describe the spatiotemporal course of cortical high-gamma activity (HGA), hippocampal ripple activity and interictal epileptiform discharges (IEDs) during an associative memory task in 15 epilepsy patients undergoing invasive electroencephalography (iEEG). Successful encoding trials were significantly greater HGA in hippocampus and frontal regions. Successful recall trials manifested sustained HGA in occipital pole and hippocampus compared to failed responses. Hippocampal ripple rates were greater during successful encoding and retrieval trials. IEDs during encoding were associated with decreased odds of remembering in hippocampus (-19%), temporal pole (-18%) or middle temporal gyrus (-15%). Hippocampal IEDs during retrieval predicted 33% decreased odds of remembering. Odds of remembering were further reduced if IEDs occurred during the 500-2000 ms window of encoding or retrieval. Hippocampal IEDs were followed by a transient decrease in ripple rate. We hypothesize that IEDs impair associative memory in a regionally and temporally specific manner by decreasing physiologic hippocampal ripples necessary for effective encoding and recall. Because dynamic memory impairment arises from pathological IED events competing with physiological ripples, IEDs represent a promising therapeutic target for memory remediation in patients with epilepsy.