Laminar distribution of electrically evoked hippocampal short latency ripple activity highlights the importance of the subiculum in vivo in human epilepsy, an intraoperative study

Abstract

OBJECTIVE\nThe goal of this study was to define the pathology and anesthesia dependency of single pulse electrical stimulation (SPES) dependent high-frequency oscillations (HFOs, ripples, fast ripples) in the hippocampal formation.\n\n\nMETHODS\nLaminar profile of electrically evoked short latency (<100 ms) high-frequency oscillations (80-500 Hz) was examined in the hippocampus of therapy-resistant epileptic patients (6 female, 2 male) in vivo, under general anesthesia.\n\n\nRESULTS\nParahippocampal SPES evoked HFOs in all recorded hippocampal subregions (Cornu Ammonis 2-3, dentate gyrus, and subiculum) were not uniform, rather the combination of ripples, fast ripples, sharp transients, and multiple unit activities. Mild and severe hippocampal sclerosis (HS) differed in the probability to evoke fast ripples: it decreased with the severity of sclerosis in CA2-3 but increased in the subiculum. Modulation in the ripple spectrum was observed only in the subiculum with increased fast HFO rate and frequency in severe HS. Inhalational anesthetics (isoflurane) suppressed the chance to evoke HFOs compared to propofol.\n\n\nCONCLUSION\nThe presence of early HFOs in the dentate gyrus and early fast HFOs (>250 Hz) in the other subregions indicate the pathological nature of these evoked oscillations. Subiculum was found to be active producing HFOs in parallel with the cell loss in the hippocampus proper, which emphasize the role of this region in the generation of epileptic activity.