The effect of interictal epileptiform discharges on single unit activity in the hippocampus

Abstract-Text (inklusive Referenzen und Bildunterschriften)

Background

Interictal epileptiform discharges (IED) are brief abortive events of pathological hypersynchronous neuronal activity in an epileptic network that occur in the interval between two successive seizures. It is well established, that IED interfere with neuronal activity. However, their pathological role and significance in the epilepsies remain subject of ongoing research. We identified and localized IED and detected single unit activity (SUA) in the hippocampus to investigate the effect that IED in different locations relative to the hippocampus might have on hippocampal neuronal activity.

Methods

We included ten patients who underwent stereotactic electroencephalography (SEEG) for preoperative assessment in drug resistant epilepsy. Among regular depth electrodes, patients were implanted with combined macro-micro electrodes in the hippocampus featuring 9 high impedance microwires (AD-TECH®, Neuralynx Inc.). After preprocessing, we detected hippocampal single unit activity (SUA) in continuous recordings of 4 hours using 5σ threshold crossing, followed by sorting and clustering via principle component analysis and feature extraction to differentiate putative pyramidal cells and interneurons. IED were visually identified in all macro electrodes and differentiated according to their maxima by an experienced epileptologists. Throughout the data, IED detection was carried out using a template search in BESA® (BESA GmbH). Subsequently, we matched IED and SUA data to analyse how mesiotemporal, temporal and extratemporal IED affect firing patterns of hippocampal pyramidal cells and interneurons. Random non-IED samples served as control.

Results

Disrupted SUA in the hippocampus was associated most prominently associated with mesiotemporal IED, followed by IED in the Amygdala and entorhinal cortex. In contrast, neocortical temporopolar, -lateral or -basal IED were associated less with disrupted activity and seemed to rather affect synchronization of larger formations of neurons in the hippocampus. Also putative pyramidal cells and interneurons were associated with a different firing frequency around IED.

Conclusion

The fact that IED disrupt SUA is already well established. However, spatial distribution of epileptiform activity might be an important determinant of functional disruption in the hippocampus in epilepsy. While IED maxima in the proximity of and with direct connection to the hippocampal formation seemed to have a putative causal effect on the activity of individual neurons, more distant IED arising in the temporal and extratemporal cortex seem to affect larger formations of neurons.