Mechanistic Analysis of Micro-Neurocircuits Underlying the Epileptogenic Zone in Focal Cortical Dysplasia Patients

Abstract

We aim to explore the microscopic neurophysiology of focal cortical dysplasia (FCD) induced epileptogenesis in specific macroscopic brain regions, therefore mapping a micro–macro neuronal network that potentially indicates the epileptogenic mechanism. Epileptic and relatively non-epileptic temporal neocortex specimens were resected from FCD and mesial temporal lobe epilepsy (mTLE) patients, respectively. Whole-cell patch-clamping was performed on cells from the seizure onset zone (SOZ) and non-SOZ inside the epileptogenic zone (EZ) of FCD patients, as well as the non-epileptic neocortex of mTLE patients. Microscopic data were recorded, including membrane characteristics, spontaneous synaptic activities, and evoked action potentials. Immunohistochemistry was also performed on parvalbumin-positive (PV+) interneurons. We found that SOZ interneurons exhibited abnormal neuronal expression and distribution as well as reduced overall function compared with non-SOZ and mTLE interneurons. The SOZ pyramidal cells experienced higher excitation but lower inhibition than the mTLE controls, whereas the non-SOZ pyramidal cells exhibited intermediate excitability. Action potential properties of both types of neurons also suggested more synchronized neuronal activity inside the EZ, particularly inside the SOZ. Together, our research provides evidence for a potential neurocircuit underlying SOZ epileptogenesis and non-SOZ seizure susceptibility. Further investigation of this microscopic network may promote understanding of the mechanism of FCD-induced epileptogenesis.

Inhibiting acid‐sensing ion channel exerts neuroprotective effects in experimental epilepsy via suppressing ferroptosis

“…To further confirm the changes of ASIC1a in epileptogenic foci from patients with chronic epilepsy, we selected inpatients diagnosed with DRE for surgical evaluation as subjects. According to a previous study, we chose the temporal neocortex tissue, which is distant from the epileptogenic zone, from patients with mesial temporal epilepsy as the control group 34 . Then, we performed immunostaining with anti‐ASIC1a and anti‐NeuN antibodies and observed a high intensity of ASIC1a on the NeuN‐positive cells.…”

“…All patients were diagnosed with DRE based on the ILAE updated definition and were hospitalized for preoperative evaluation at the Epilepsy Center in the Beijing Tiantan Hospital of Capital Medical University 3 . We selected the neocortical regions in the epileptogenic zone and corresponding distant non‐epileptic temporal neocortex based on preoperative evaluation, including clinical history, neurological examination, scalp video‐electroencephalogram (EEG) monitoring, magnetic resonance imaging (MRI), and 18‐fluoro‐deoxyglucose positron emission tomography, as epilepsy and control groups, respectively 33,34 . All resected tissues were presented by using photographs taken after surgery and classified into two groups, namely, epilepsy and control groups (Figure 1C).…”

“… 3 We selected the neocortical regions in the epileptogenic zone and corresponding distant non‐epileptic temporal neocortex based on preoperative evaluation, including clinical history, neurological examination, scalp video‐electroencephalogram (EEG) monitoring, magnetic resonance imaging (MRI), and 18‐fluoro‐deoxyglucose positron emission tomography, as epilepsy and control groups, respectively. 33 , 34 All resected tissues were presented by using photographs taken after surgery and classified into two groups, namely, epilepsy and control groups (Figure 1C ). Compared with the preoperative MRI, the postoperative CT clearly showed the location and extent of the resected zone (Figure 1A,B ).…”

Enhanced KNa1.1 Channel Underlies Cortical Hyperexcitability and Seizure Susceptibility after Traumatic Brain Injury

“…As previously described ( Cheng, et al,2022; Shore, et al,2020 ), electrophysiological parameters recorded in our experiments included intrinsic membrane properties, and synaptic activities. We first divided neurons into excitatory pyramidal neurons (PNs) and non-fast spiking interneurons (INs) according to different morphological characteristics.…”

Imbalance between the function of Na+-K+-2Cl and K+-Cl impairs Cl– homeostasis in human focal cortical dysplasia

“…However, there is currently no clear definition of “non-SOZ.” In this study, SOZ is confirmed as the area of cortex that initiates clinical seizures by combining presurgical intracranial investigations and symptomatology ( Figure 1A , electrode B). For the other area expect SOZ in the surgical resection, as our previous study, we choose “non-SOZ” as one of brain tissue which is also located in the area to be excised but showing the least abnormal electrophysiological recordings under subdural recording ( Figure 1B ; Cheng et al, 2022 ).…”