Prolongation of cortical sleep spindles during hippocampal interictal epileptiform discharges in epilepsy patients

• Published in: Epilepsia (Copenhagen) Vol. 63; no. 9; pp. 2256 - 2268
• Main Authors: Sákovics, Anna, Csukly, Gábor, Borbély, Csaba, Virág, Márta, Kelemen, Anna, Bódizs, Róbert, Erőss, Loránd, Fabó, Dániel
• Format: Journal Article
• Language: English
• Published: United States Wiley Subscription Services, Inc 01.09.2022
• Subjects: Activity patterns; Electrodes; Epilepsy; Epilepsy - complications; Firing pattern; Hippocampus; Humans; interictal epileptiform discharges; Memory Disorders; Scalp; Sleep; sleep spindle; Temporal Lobe; Thalamus; Therapeutic targets; epilepsy; interictal epileptiform discharges; hippocampus; sleep spindle
• ISSN: 0013-9580; 1528-1167; 1528-1167
• DOI: 10.1111/epi.17337

Objective Memory deficits are frequent among patients with epilepsies affecting the temporal lobe. Hippocampal interictal epileptic discharges (hIEDs), the presumed epileptic exaggeration of sharp wave‐ripples (SWRs), are known to contribute to memory dysfunction, but the potential underlying mechanism is unknown. The precise temporal coordination between hippocampal SWRs and corticothalamic spindles during sleep is critical for memory consolidation. Moreover, previous investigation indicated that hIEDs induce neocortical spindlelike oscillation. In the present study, we aimed to assess the influence of hIEDs on neocortical spindles. Methods We analyzed the spindle characteristics (duration, amplitude, frequency) of 21 epilepsy patients implanted with foramen ovale (FO) electrodes during a whole night sleep. Scalp sleep spindles were categorized based on their temporal relationship to hIEDs detected on the FO electrodes. Three groups were created: (1) spindles coinciding with hIEDs, (2) spindles “induced” by hIEDs, and (3) spindles without hIED co‐occurrence. Results We found that spindles co‐occurring with hIEDs had altered characteristics in all measured properties, lasted longer by 126 ± 48 ms (mean ± SD), and had higher amplitude by 3.4 ± 3.2 μV, and their frequency range shifted toward the higher frequencies within the 13–15‐Hz range. Also, hIED‐induced spindles had identical oscillatory properties to spindles without any temporal relationships with hIEDs. In more than half of our subjects, clear temporal coherence was revealed between hIEDs and spindles, but the direction of the coupling was patient‐specific. Significance We investigated the effect of hippocampal IEDs on neocortical spindle activity and found spindle alterations in cases of spindle–hIED co‐occurrence, but not in cases of hIED‐initiated spindles. We propose that this is a marker of a pathologic process, where IEDs may have direct effect on spindle generation. It could mark a potential mechanism whereby IEDs disrupt memory processes, and also provide a potential therapeutic target to treat memory disturbances in epilepsy.