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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., (© The Author(s) 2021. Published by Oxford University Press. All rights reserved. For permissions, please e-mail: journals.permissions@oup.com.)

Background: The combination of high-frequency oscillations (HFOs) with single-mode imaging methods has been proved useful in identifying epileptogenic zones, whereas few studies have examined HFOs combined with multimodal imaging methods. The aim of this study was to evaluate the prognostic value of ripples, an HFO subtype with a frequency of 80 to 200 Hz is combined with multimodal imaging methods in predicting epilepsy surgery outcome., Methods: HFOs were analyzed in 21 consecutive medically refractory epilepsy patients who underwent epilepsy surgery. All patients underwent positron emission tomography (PET) and deep electrode implantation for stereo-electroencephalography (SEEG); 11 patients underwent magnetoencephalography (MEG). Sensitivity, specificity, positive predictive value, negative predictive value, and accuracy in predicting surgical outcome were calculated for ripples combined with PET, MEG, both PET and MEG, and PET combined with MEG. Kaplan-Meier survival analyses were conducted in each group to estimate prognostic value., Results: The study included 13 men and 8 women. Accuracy for ripples, PET, and MEG alone in predicting surgical outcome was 42.9%, 42.9%, and 81.8%, respectively. Accuracy for ripples combined with PET and MEG was the highest. Resection of regions identified by ripples, MEG dipoles, and combined PET findings was significantly associated with better surgical outcome (P  < 0.05)., Conclusions: Intracranial electrodes are essential to detect regions which generate ripples and to remove these areas which indicate good surgical outcome for medically intractable epilepsy. With the assistance of presurgical noninvasive imaging examinations, PET and MEG, for example, the SEEG electrodes would identify epileptogenic regions more effectively., (Copyright © 2022 The Chinese Medical Association, produced by Wolters Kluwer, Inc. under the CC-BY-NC-ND license.)

Objectives: Vagus nerve stimulation (VNS) has been widely used as an effective treatment for patients with drug-resistant epilepsy (DRE). However, little is known about grey matter (GM) and white matter (WM) microstructure changes caused by VNS. This study aimed to detect consistent GM and WM alterations in epilepsy patients with vagus nerve stimulators., Methods: The diffusion tensor imaging data was acquired from 15 patients who underwent VNS implantation. The voxel-based morphometry (VBM) and tract-based spatial statistics (TBSS) were used to detect group differences in GM and WM microstructure and explore their correlation with postoperative seizure reduction., Results: After 3 months of stimulation, GM density reduced in right cerebellum, left superior temporal gyrus, right inferior temporal gyrus and left thalamus, and increased in left cerebellum, left inferior parietal lobule, left middle occipital gyrus and left gyrus rectus. No significant volume changes had been found in 14 subcortical nuclei. The fractional anisotropy (FA) values reduced in left superior longitudinal fasciculus and left corticospinal tract, and increased in bilateral cingulum and body of corpus callosum. The mean diffusivity (MD) values reduced in right retrolenticular part of internal capsule, right posterior corona radiata and right superior longitudinal fasciculus. The seizure reduction had positive correlation trends with the volume reduction in left nucleus accumbens and right amygdala, and MD reduction in right medial lemniscus and right posterior corona radiata., Conclusions: The results showed that VNS could cause changes of GM density, WM FA and MD values in epilepsy patients. The volume and MD reduction in some subcortical structures might participate in the seizure frequency reduction of VNS., (Copyright © 2021 Elsevier B.V. All rights reserved.)

Purpose: To evaluate the clinical and stereoelectroencephalography (SEEG) features and postsurgical outcome in a uniform series of patients who underwent epilepsy surgery and had pathologically confirmation of focal cortical dysplasia (FCD)., Methods: We studied consecutive patients with drug-refractory epilepsy who underwent SEEG recording. The high-frequency oscillations (HFOs) features of SEEG, clinical characteristics, and surgical outcome were evaluated., Results: Sixty patients (31 FCD type I, 13 II, and 16 III) were analyzed retrospectively. Patients with type II tended to have their seizures at an earlier age than those with I and III (p < .01). Six different ictal onset patterns (IOPs) were identified. In patients with temporal lobe epilepsy (TLE), the most common patterns were rhythmic spikes or spike waves and LFRS, and in patients with extratemporal epilepsy, the most common patterns were low-voltage fast activity (LVFA) and rhythmic spikes or spike waves. In addition, ripple density was found to increase significantly from the interictal to ictal onset sections and from the ictal onset to ictal evolution sections in patients with FCD I (p < .001). Regarding the distinct IOPs, ripple density continued to increase significantly between the interictal and ictal onset sections in LVFA, rhythmic spikes or spike waves, and burst of high-amplitude polyspikes (p < .05). Ripple density decreased between ictal onset and ictal evolution sections in patterns of LVFA and rhythmic spikes or spike waves (p < .05). The mean follow-up duration was 2.7 years (range 1-4.2), and 66.7% (n = 40) were class I. Patients with subtypes III and II had favorable surgical outcome than those with I., Conclusion: The clinical expression of seizure may depend on the pathological types with FCD II patients exhibiting their seizures at an earlier age. Distinct IOPs may demonstrate different ripple features and distinguishing the IOPs is very necessary to have an insight into the electrophysiological characteristics., (© 2021 The Authors. Brain and Behavior published by Wiley Periodicals LLC.)

Purpose: This study aimed to analyze the topological characteristics of brain structural network in pediatric epilepsy patients with vagus nerve stimulation (VNS) by applying graph theoretical approaches., Methods: Nine patients with generalized seizures and eight normal controls (NC) were enrolled. Based on diffusion tensor imaging, graph theory analysis was used to characterize the topological properties in preoperative patients (EP-pre), postoperative patients (EP-post) and NC. The global properties included clustering coefficient (Cp), shortest path length (Lp), small-worldness (γ, λ, δ), global network efficiency (Eg) and local network efficiency (Eloc). The regional properties included degree centrality (DC), nodal efficiency (NE), nodal local efficiency (NLE) and nodal shortest path length (Np). Two sample t-test and paired sample t-test were utilized to compare properties difference., Results: All three groups followed small-world characteristics. There was no significant difference in small-worldness, Cp, Lp, Eg or Eloc between EP-pre and EP-post. Compared with EP-pre: DC in EP-post decreased in the right cuneus and right temporal gyri, while increased in the right paracentral lobule; NE in EP-post decreased in the left dorsolateral superior frontal gyrus, right cuneus, right supramarginal gyrus, and right rolandic operculum, while increased in the right paracentral lobule; NLE in EP-post decreased in the left posterior cingulate gyrus and right supramarginal gyrus, while increased in the left parahippocampal gyrus; NP in EP-post decreased in the right paracentral lobule, while increased in the right cuneus., Conclusion: VNS causes topological characteristics changes in pediatric patients with generalized seizures through regulating regional properties in some brain structures., (Copyright © 2020 The Japanese Society of Child Neurology. Published by Elsevier B.V. All rights reserved.)

Background: Vagus nerve stimulation (VNS) is a form of neuromodulation that has been used to treat individuals with drug-resistant epilepsy (DRE). Although many retrospective studies have explored the predictors of VNS treatment efficacy, the data have been inconsistent, and no VNS studies to date have used the 2017 ILAE epilepsy classification system., Methods: In this single-center retrospective study, we reviewed data from 77 patients who underwent VNS implantation between 2011 and 2019. Data regarding patient gender, epilepsy duration, age at implantation, numbers of antiepileptic drugs, MRI findings, history of craniotomy, epilepsy classification, stimulation current intensity, stimulation duration, and responder status (responders were those with ≥ 50 % seizure frequency reduction) were analyzed via univariate analysis or receiver operating characteristic (ROC) curves to select possible related factors and classification cutoffs. Then, binary logistic regression analysis was used to identify the variables that significantly predicted responder status., Results: In the inclusion group, the mean stimulation duration, mean seizure reduction, and responder rate was 47.2 months, 42.6 %, and 50.6 %, respectively. The univariate analysis indicated that seizure types and MRI findings might be related categorical variables (P < 0.05). After performing binary logistic regression and creating ROC curves for the continuous variables, epilepsy duration was chosen as a related variable, with 12.5 years as the classification cutoff (P = 0.002). A binary logistic regression of risk factors showed that epilepsy duration was significantly related to responder status (P < 0.05)., Conclusion: Epilepsy duration is an independent predictor for responders to VNS. VNS is more likely to be efficacious in those with an epilepsy duration < 12.5 years, especially those with a duration of 5-12.5 years., (Copyright © 2020 Elsevier B.V. All rights reserved.)

Navigated transcranial magnetic stimulation (nTMS) is increasingly applied in language mapping. However, the application mode and task selection of nTMS are not standardized. The aim of this study was to assessed the necessity and validity of multitask nTMS language mapping by comparing results with extraoperative electrical cortical stimulation (eoECS). In this study, sixteen epilepsy surgery patients were examined by nTMS and eoECS language mapping, and the two results were compared. The mapping results were validated with pre- to postoperative language assessments. Compared with eoECS, nTMS showed the overall sensitivity of 82.4%, specificity of 95.1%, positive predictive value of 66.7%, and negative predictive value of 97.8%. Spontaneous speech was the most sensitive task in the frontal area, naming was the sensitive task in both frontal and temporal areas. The false responses were mainly located in the perisylvian region. Multitask nTMS helps to reduce missing language relevant cortex preoperatively. Selecting spontaneous speech and naming tasks in frontal area, comprehension and naming tasks in temporal and posterior language area would strike the balance between the validity and efficiency of the mapping procedure. These results manifested the necessity of applying multitask in nTMS language mapping. Our study highlighted the importance of the nTMS evaluation mode and task selection for epilepsy patients., Competing Interests: Declaration of Competing Interest The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper., (Copyright © 2020 Elsevier Ltd. All rights reserved.)

Objective: Magnetoencephalography (MEG) is valuable for guiding resective surgery in patients with epilepsy. However, its value for minimally invasive treatment is still unknown. This study aims to evaluate the value of MEG for stereo-electroencephalogram (EEG)-guided radiofrequency thermocoagulation (SEEG-guided RF-TC) in magnetic resonance imaging (MRI)-negative epilepsies., Methods: An observational cohort study was performed and 19 MRI-negative patients who underwent SEEG-guided RF-TC in our epilepsy center were included. In addition, 16 MRI-positive patients were included as a reference group. Semiology, electrophysiology, and imaging information were collected. To evaluate the value of locating the MEG cluster, the proportion of the RF-TC contacts located in the MEG cluster out of all contacts used to perform RF-TC in each patient was calculated. All patients underwent the standard SEEG-guided RF-TC procedure and were followed up after the treatment., Results: Nineteen MRI-negative patients were divided into two groups based on the existence of MEG clusters; 10 patients with MEG clusters were in group I and nine patients without any MEG cluster were in group II. No significant difference was observed in terms of age, sex, type of seizures, or number of SEEG electrodes implanted. The median of the proportion of contacts in the MEG cluster was 77.0 % (IQR 57.7-100.0 %). The follow-up results showed that the probability of being seizure-free at one year after RFTC in MRI-negative patients with an MEG cluster was 30.0 % (95 % CI 11.6-77.3 %), significantly (p = 0.014) higher than that in patients without an MEG cluster; there was no significant difference when compared with MRI-positive patients., Conclusion: This is the first study to evaluate the value of MEG in SEEG-guided RF-TC in MRI-negative epilepsies. MEG is a useful supplement for patients with MRI-negative epilepsy. MEG can be applied in minimally invasive treatment. MEG clusters can help identify better candidates and provide a valuable target for SEEG-guided RF-TC, which leads to better outcomes., (Copyright © 2020 The Authors. Published by Elsevier B.V. All rights reserved.)

Purpose: To explore abnormalities of topological properties in drug-resistant epilepsy (DRE) patients after vagus nerve stimulation (VNS) by analyzing brain functional networks using graph theory.Methods: Fifteen patients and eight healthy controls (HC) were scanned separately with resting-state functional magnetic resonance imaging (rs-fMRI). Graph theoretical analyses were chosen to compare the global (small-world parameters [γ, λ, σ, Cp, and Lp], and network efficiency [Eg and Eloc]), and nodal (BC, DC, and NE) properties in preoperative patients (EPpre), postoperative patients (EPpost) and HC.Results: HC, EPpre and EPpost all satisfied the criteria for small-world properties (σ > 1) within the sparsity range of 0.05-0.5. Compared with EPpre, EPpost performed higher in λ and Eloc but lower in γ, σ, and Cp. Compared with HC, EPpre exhibited decreased BC, DC or NE in the right inferior frontal gyrus, right superior temporal gyrus, bilateral cingulate gyri, right supplementary motor area, right superior occipital gyrus, right Heschl gyrus, and left calcarine fissure; increased BC in the left postcentral/precentral gyrus, right paracentral lobule, left rolandic operculum, and left supramarginal gyrus, and increased NE in the right caudate nucleus. Compared with EPpre, EPpost showed increased BC, DC or NE in the bilateral inferior frontal gyrus, right middle frontal gyrus, bilateral cingulate gyri, right superior temporal gyrus, and right Heschl gyrus and decreased BC in the left fusiform gyrus.Conclusion: VNS downregulated small-world properties in DRE, and caused changes in some key nodes to reorganize the transmission ability of the large-scale network. [ABSTRACT FROM AUTHOR]

Purpose: Seizure originates from different pathological substrate; however, the same pathologies may have distinct mechanisms underlying seizure generation. We aimed to improve the understanding of such mechanisms in patients with temporal lobe epilepsy (TLE) by investigating the stereoelectroencephalography (SEEG) ictal onset patterns (IOPs). Methods: We analyzed data from a cohort of 19 consecutive patients explored by SEEG and had 1–3-year seizure-freedom following temporal lobe resection. Results: Six IOPs were identified. They were low voltage fast activity (LVFA) (36.5%), rhythmic spikes or spike-waves at low frequency and with high amplitude (34.1%), runs of spikes (10.6%), rhythmic sharp waves (8.2%), low frequency high amplitude repetitive spiking (LFRS) (7.1%), and delta activity (3.5%). All six patterns were found in patients with mesial temporal onset and only two patterns were found in patients with temporal neocortical onset. The most prevalent patterns for patients with mesial temporal onset were rhythmic spikes or spike-waves, followed by LVFA with a mean discharge rate 74 Hz. For patients with temporal neocortical onset, the most prevalent IOP pattern was LVFA with a mean discharge rate 35 Hz, followed by runs of spikes. Compared with Lateral TLE (LTLE), the duration between the onset of the IOPs to the onset of the symptom was longer for patients with MTLE (Mesial TLE) (MTLE:55.7 ± 50.6 s vs LTLE:19.5 ± 16.4 s). Conclusion: Multiple IOPs underlie seizure generation in patients with TLE. However, the mesial and lateral temporal lobes share distinct IOPs. [ABSTRACT FROM AUTHOR]

• Less than 1.5 mA may not affect hippocampal-thalamic functional connectivity. • Shorter than 3 months may not affect hippocampal-thalamic functional connectivity. • VNS may be suitable for patients with low left hippocampal-left thalamic connections. • VNS may be suitable for patients with low left hippocampal-right thalamic connections. • Current intensity should increase > 1.5 mA to cause functional connectivity changes. Vagal nerve stimulation (VNS) is widely used as an auxiliary treatment for patients with intractable epilepsy. Up to now, the therapeutic mechanisms remain elusive, and no surgical prediction criteria has been proposed. In this study, the resting-state functional magnetic resonance imaging (rs-fMRI) was chosen to explore aberrant intrinsic brain activity and functional connections in 14 epilepsy patients with VNS stimulators between March 2019 and April 2019. Seven patients who ≥ 50 % seizure reduction was defined as responders, and seven non-responders. All patients had got rs-fMRI scan before and after operation. The hippocampal - thalamic connections (hippocampal and thalamus as regions of interest) were detected to evaluate the diversity in all 14 patients and seven responders with stimulation at 0, 0.5, 1.0, and 1.5 mA. The hippocampal-thalamic connections before operation were also examined between responders and non-responders. The preoperative left hippocampal - left thalamic connections and left hippocampal - right thalamic connections in responders were lower than those in non-responders (p < 0.05). While, there was no significant difference in hippocampal - thalamic connections in all epilepsy patients or responders with different current intensities (p > 0.05). VNS may be more suitable for patients with lower left hippocampal - left thalamic connections and/or left hippocampal - right thalamic connections. The current intensity ≤ 1.5 mA and stimulation time ≤ 3 months may not cause significant changes in hippocampal-thalamic functional connectivity. [ABSTRACT FROM AUTHOR]

• VNS may cause thalamus-precentral gyrus FC changes in DRE patients. • Enhanced FC was observed between bilateral thalamus and bilateral precentral gyrus in responders. • Decreased FC was observed between bilateral thalamus and bilateral precentral gyrus in nonresponders. Vagal nerve stimulation (VNS) is an effective treatment for patients with drug-resistant epilepsy who are unsuitable for surgical epilepsy treatment. However, the mechanism of action of VNS remains unclear, and the efficacy of VNS treatment regarding seizure frequency reduction cannot be assessed before surgery. This study measured changes in functional connectivity between thalamus and precentral gyrus which are activated as vital targets of deep brain stimulation (DBS) and transcranial magnetic stimulation (TMS) using resting-state functional MRI to evaluate the effects of VNS. 16 epilepsy patients who underwent VNS were collected and scanned by resting-state functional MRI before and after operation. The functional connections (regions of interest: thalamus, precentral gyrus) were examined. After three months of stimulation, there were eight responders (≥50 % seizure reduction) and eight non-responders to VNS. No significant difference in thalamus-precentral gyrus functional connectivity was found between responders and nonresponders before operation. Enhanced functional connections were observed between bilateral thalamus and bilateral precentral gyrus in responders, which decreased in nonresponders, while functional connections between bilateral thalamus decreased in both responders and nonresponders. Short-term stimulation may cause thalamus-precentral gyrus functional connectivity changes in DRE patients, and control seizures by enhancing functional connections between bilateral thalamus and bilateral precentral gyrus. [ABSTRACT FROM AUTHOR]

• A summary of aura symptoms in a large number of frontal lobe epilepsy (FLE) patients. • A detailed classification of aura symptoms. • Report two unusual auras: sensation of weightlessness and heart contraction. Auras are essential in preoperative evaluation and can provide valuable information for delineating seizure onset zones. Frontal lobe epilepsy (FLE) is the second most common focal epilepsy, while a few studies have focused on auras in FLE. To better understand FLE, we analyzed the clinical characteristics, values, and limitations of auras in FLE. The incidence rate of aura in FLE was 37.9% in our study. We included 54 patients and 76 auras in 11 categories were reported. The rate of auras in the decreasing order are as follows: autonomic aura; emotional aura; somatosensory aura; psychic aura; cephalic aura; abdominal aura; whole-body sensory aura, visual aura; auditory aura; and vestibular and unclassified aura. A significant number of aura types can be reported by FLE patients; autonomic aura was the most frequent category and somatosensory auras are most likely associated with the contralateral motor areas. [ABSTRACT FROM AUTHOR]