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

Abstract

We describe the spatiotemporal course of cortical high-gamma activity, hippocampal ripple activity and interictal epileptiform discharges during an associative memory task in 15 epilepsy patients undergoing invasive EEG. Successful encoding trials manifested significantly greater high-gamma activity in hippocampus and frontal regions. Successful cued recall trials manifested sustained high-gamma activity in hippocampus compared to failed responses. Hippocampal ripple rates were greater during successful encoding and retrieval trials. Interictal epileptiform discharges during encoding were associated with 15% decreased odds of remembering in hippocampus (95% confidence interval 6–23%). Hippocampal interictal epileptiform discharges during retrieval predicted 25% decreased odds of remembering (15–33%). Odds of remembering were reduced by 25–52% if interictal epileptiform discharges occurred during the 500–2000-ms window of encoding or by 41% during retrieval. During encoding and retrieval, hippocampal interictal epileptiform discharges were followed by a transient decrease in ripple rate. We hypothesize that interictal epileptiform discharges impair associative memory in a regionally and temporally specific manner by decreasing physiological hippocampal ripples necessary for effective encoding and recall. Because dynamic memory impairment arises from pathological interictal epileptiform discharge events competing with physiological ripples, interictal epileptiform discharges represent a promising therapeutic target for memory remediation in patients with epilepsy.

Hippocampal ripples signal contextually-mediated episodic recall

“…This stricter algorithm yields lower ripple rates with a wider distribution of durations and a peak ripple frequency ~90 Hz ( Extended Data Figs. 1c&5a ), all similar to previous work 8, 10, 11 . Despite the lower ripple rates, the PRE is significant for ≥2nd recalls compared to 1st recalls in CA1 and in the same direction for DG ( Extended Data Fig.…”

“…1c ), durations, spatial proximity, and rates ( Extended Data Figs. 1–2 ) are similar to previous work 7,8,10 . Anatomical localization of electrodes was performed by a combination of neuroradiologist labels and automated segmentation via separate processes for hippocampal subfields 21 and entorhinal and parahippocampal cortices 22, 23 .…”

“…2a ). The raster suggests that ripple rates rise several hundred ms prior to vocalization onset, as shown in recent work 7, 8, 10 .…”

“…Whereas previous work has grouped these events as they differ only in frequency and relative amplitudes between subfields 28, 29 , we ask if ripples detected using algorithms with narrower ranges still reliably show a PRE . For a first check, we implement a ripple detection algorithm with a narrower range (80-120 Hz) that was recently used to identify ripples in MTL 8, 10, 11 . This stricter algorithm yields lower ripple rates with a wider distribution of durations and a peak ripple frequency ~90 Hz ( Extended Data Figs.…”

“…Finally, we address the possibility that PRE is related to seizurogenic tissue in epileptic participants, even though recent work suggests epileptiform tissue should show a weaker link between ripples and memory than healthy tissue 8 . For those participants with a clinically-defined seizure onset zone (SOZ), we take all trials from bipolar pairs in the SOZ and compare them to all trials from bipolar pairs not in the SOZ.…”