Abstracts

Rationale: Focal cortical dysplasia (FCD) is the most common cause of intractable epilepsy. Previous studies on animal epilepsy models induced by FCD have demonstrated that a reduction in the number of cortical interneurons, a relative lack of excitatory drive in fast-spiking (FS) interneurons, and the inhibitory function of cerebral cortical tissue is decreased in the epileptogenic region. There are limited studies utilizing human FCD tissue so the electrophysiological mechanism of epileptogenesis in FCD in humans is still unclear. In this study, we collected epileptic neocortex and non-epileptic temporal cortex resected from patients with FCD and applied patch clamp techniques to observe and compare the membrane characteristics, spontaneous synaptic activity, and induced action potential generation in the seizure onset zone (SOZ), non-seizure onset zone (non-SOZ), and non-epileptic temporal cortex. We aim to explore the neurophysiological mechanism of epileptogenesis in humans caused by FCD. Methods: We collected resected epileptic cortex from 17 FCD patients and non-epileptic lateral temporal lobe cortex from 8 medial temporal lobe epilepsy (MTLE) patients from January 2017 to March 2018 in Xuanwu Hospital of Capital Medical University. The protocols were approved by the Medical Ethics Committee of Xuanwu Hospital. All patients signed informed. After reviewing the intraoperative electrocorticography, we confirmed the SOZ and non-SOZ (both in the epileptogenic zone) and non-epileptic cortex in the TLE. All cortical tissue was cut into 400µm slices. Whole cell recording was performed. We recorded the membrane characteristics, spontaneous excitatory postsynaptic currents (sEPSCs) and inhibitory postsynaptic currents (sIPSCs), evoked action potential activity of interneurons and pyramidal cells . Results: Our results show that there is no statistical difference the resting membrane potential, the average amplitude and frequency of action potential between the excitatory and inhibitory neurons in the three groups (P<0.05). The frequency of sEPSC and sIPSC of interneurons in the SOZ group (3.64±0.40 Hz and 2.41±0.41 Hz) were significantly lower than those of the non-SOZ group (6.20±0.77 Hz and 6.29±1.60 Hz, P<0.01)and the MTLE cortex group (9.03±1.15Hz and 3.16±0.83 Hz p<0.01). For pyramidal cells, the frequency of sEPSC was significantly higher in the SOZ group (1.65±0.27 Hz) than in the non-SOZ and MTLE cortex groups (0.83±0.15 Hz and 0.73±0.10, P<0.05). sIPSC frequency was significantly lower in the SOZ group (1.34±0.21 Hz) compared to the non-SOZ and MTLE cortex groups (2.82±0.32 Hz and 3.01±0.52 Hz, P<0.001). All of the above data are mean value± standard error. Conclusions: In human focal cortical dysplasia, the EPSC and IPSC of interneurons in the SOZ were significantly lower than those in the non-SOZ and MTLE cortex. This suggests that the synaptic connections between the SOZ neurons and the surrounding glutamatergic neurons are decreased and the excitatory driving force of interneurons is relatively low. Furthermore, synaptic contacts between interneurons and GABA receptor sensitivity are decreased in the SOZ. This may result in the inability of interneurons in the SOZ to perform their normal inhibitory function in local neural networks. The above results may be one of the mechanisms by which FCD induces epileptogenesis. Funding: This work was supported by the Natural Science Foundation of China (81471328, 81471391, 81671367); Natural Science Foundation of Beijing (KZ201610025027); and Beijing Municipal Commission of Health and Family Plan (PXM2014-026283-000001).