Abstracts

Rationale: Interictal epileptic discharges (IEDs) are an established biomarker of epileptogenicity. Recent studies suggest that high-frequency oscillations (HFO), which often occur associated with IEDs, might have additional diagnostic value. Hypothesizing that a high-frequent component of IEDs is related to distinct neuronal networks, we aimed to characterize these networks at the single-neuron level. Methods: Hybrid depth electrodes were implanted into the anterior hippocampus of 9 patients for stereotactic electroencephalography (SEEG). IEDs and HFOs were visually identified in macroelectrode recordings. Single-unit activity was extracted from microelectrode recordings using a previously established spike classification algorithm (Wave_clus). Putative pyramidal cells and interneurons were distinguished using criteria from previous rodent studies. Statistical hypothesis testing was performed using non-parametric methods. To examine if a single unit’s firing rate (FR) differed significantly between IEDs associated with HFOs (HFO-IEDs) and IEDs not associated with HFOs (non-HFO-IEDs), we randomly shuffled group labels 1000 times and thus computed a distribution of surrogate FR ratios (FRHFO-IED / FRnon-HFO-IED). A single unit’s firing rate was considered significantly different if its observed FR ratio was greater than 97.5% or lower than 2.5% of the surrogate FR ratios. Results: We identified 38 single units, of which 33 were classified as putative pyramidal cells and 5 as putative interneurons. Single-unit firing rate was higher during HFO-IEDs than during non-HFO-IEDs (p < 0.001). 61% of all single units fired above baseline during HFO-associated IEDs (HFO-IEDs), whereas only 37% fired above baseline during IEDs without associated HFO (non-HFO-IEDs), (p < 0.05). Comparison with surrogate data revealed that six single units fired significantly more during HFO-IEDs than during non-HFO-IEDs, one unit fired significantly less (p < 0.05). Five of the six single units with higher firing rate during HFO-IEDs were classified as pyramidal cells and one as an interneuron. Conclusions: Our findings suggest that some neurons are specifically associated with HFO-IEDs. Networks underlying HFO-IEDs might consist of more cells, or cells might be in general more active than in non-HFO-IEDs. It may be assumed that both pyramidal cells and interneurons are involved in HFO-IEDs. Funding: J. J. was supported by the German Research Foundation (DFG; JA 1725/4-1). J. S. was supported by the Berta-Ottenstein-Program, Faculty of Medicine, University of Freiburg.