S15. Shedding lights on interictal epliepyic spikes: An animal and patient study

Abstract

Many questions concerning the mechanisms that drive neurons to hypersynchronize remain unsolved, but synaptic as well as non-synaptic events are likely to be involved. Here Optical Imaging (OI) of the epileptic brain by concomitant electroencephalography (FOS-ECoG/HD-EEG), allow investigating the changes in the cellular environment associated with Interictal Epileptic Spikes (IES). The FOS changes (milliseconds) are related to non-synaptic events neuronal activation while ECoG-HDEEG investigates the synaptic events related to the IES. In 3 patients with frontal epileptic spikes, High-Density EEG (HD-EEG) was acquired with 64 electrodes. In 15 epileptic penicillin rats’ experiments, ECoG signals were acquired with two monopolar electrodes disposed over the somatosensory cortex. FOS were recorded with a frequency-domain spectrophotometer at a sampling rate of 62.5 Hz with 16/2 detectors and 4/2 sources in patients and rats respectively. In order to provide an independent control condition to evaluate the method and the specificity of FOS in IES, the FOS signal in response to electrical stimulation of the median nerve was evaluated in both species. In both species median nerve stimulation (mERP) induces similar changes in FOS signal consisted in an increase followed by a decrease in the FOS concomitant to the mERP. In both species, alternating increase–decrease-increase in FOS occurred 200 ms before to 180 ms after the IES peak. This started before any changes in EEG signal. Time–frequency domain ECoG-HD EEG analysis revealed alternating decrease-increase–decrease in the EEG spectral power concomitantly with changes in FOS during IES. The FOS response was weaker with a lower signal-to-noise ratio when recorded on the scalp than when recorded from the cortex.This suggests a tight relationship between (de) synchronization and neuronal volume changes during IES. FOS-ECoG/HDEEG analysis revel complex changes surrounding the IES and illustrating the complexity of the underlying mechanisms of IES generation. These changes in the neuronal environment around IES in frontal lobe epilepsy in children and in rats raise new questions about the synaptic and non-synaptic mechanisms that propel the neurons to IES hypersynchronization. Because it unable to evaluate non-invasively the synaptic and non-synaptic compartments, this multiscale multimodal high temporal resolution approach offer the opportunity to thoroughly investigate the pathophysiology of the IES. FOS response was specific to exogenous stimuli or endogenous neuronal activation (IES). The observed responses in epileptic patients were similar to those on epileptic rats using similar acquisition protocol and data analysis processes. This suggests that the mechanisms involved are fairly specific to the epileptic spikes, independently of the species and of the type of epilepsy.