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Objective: We aimed to explore the value of magnetoencephalography in the presurgical evaluation of patients with posterior cortex epilepsy., Methods: A total of 39 patients with posterior cortex epilepsy (PCE) and intact magnetoencephalography (MEG) images were reviewed from August 2019 to July 2022. MEG dipole clusters were classified into single clusters, multiple clusters, and scatter dipoles based on tightness criteria. The association of the surgical outcome with MEG dipole classifications was evaluated using Fisher's exact tests., Results: Among the 39 cases, there were 24 cases of single clusters (61.5%), nine cases of multiple clusters (23.1%), and six cases of scattered dipoles (15.4%). Patients with single dipole clusters were more likely to become seizure-free. Among single dipole cluster cases (n = 24), complete MEG dipole resection yielded a more favorable surgical outcome than incomplete resection (83.3% vs. 16.7%, p = 0.007). Patients with concordant MRI and MEG findings achieved a significantly more favorable surgical outcome than discordant patients (66.7% vs. 33.3%, p = 0.044), especially in single dipole cluster patients (87.5% vs. 25.0%, p = 0.005)., Significance: MEG can provide additional valuable information regarding surgical candidate selection, epileptogenic zone localization, electrode implantation schedule, and final surgical planning in patients with posterior cortex epilepsy., (© 2024 The Authors. CNS Neuroscience & Therapeutics published by John Wiley & Sons Ltd.)

Our understanding of cingulate cortex function is limited. As a method for locating the epileptogenic zone, direct electrical cortical stimulation (ECS) provides an opportunity to understand the functional localization of the cingulate cortex. This study aimed to learn more about the function of the cingulate cortex by analyzing a large body of data from our center and by reviewing existing literature on cortical mapping. We retrospectively analyzed the ECS data of 124 patients with drug-resistant epilepsy who had undergone electrode implantation in the cingulate cortex. The standard stimulation parameters included a biphasic pulse and bipolar stimulation at 50 Hz. Furthermore, we reviewed existing studies on cingulate responses elicited by the ECS and compared them with our results. A total of 329 responses were evoked in 276 contacts using ECS. Of these, 196 were physiological functional responses, which included sensory, affective, autonomic, language, visual, vestibular, and motor responses, along with a few other sensations. Sensory, motor, vestibular, and visual responses were concentrated in the cingulate sulcus visual area (CSv). Furthermore, 133 epilepsy-related responses were evoked, most of which were concentrated in the ventral cingulate cortex. No responses were evoked by 498 contacts. Furthermore, the comparison of our ECS results with those reported in 11 comprehensive reviews revealed that the cingulate cortex is involved in complicated functions. The cingulate cortex is involved in sensory, affective, autonomic, language, visual, vestibular, and motor functions. The CSv is an integrating node of sensory, motor, vestibular, and visual systems., (© 2023 The Authors. Human Brain Mapping published by Wiley Periodicals LLC.)

Objectives: We investigated both the metabolic differences and interictal/ictal discharges of the anterior nucleus of the thalamus (ANT) in patients with epilepsy to clarify the relationship between the ANT and the epileptic network., Methods: Nineteen patients with drug-resistant epilepsy who underwent stereoelectroencephalography were studied. Metabolic differences in ANT were analyzed using [18F] fluorodeoxyglucose-positron emission tomography with three-dimensional (3D) visual and quantitative analyses. Interictal and ictal discharges in the ANT were analyzed using visual and time-frequency analyses. The relationship between interictal discharge and metabolic differences was analyzed., Results: We found that patients with temporal lobe epilepsy (TLE) showed significant metabolic differences in bilateral ANT compared with extratemporal lobe epilepsy in 3D visual and quantitative analyses. Four types of interictal activities were recorded from the ANT: spike, high-frequency oscillation (HFO), slow-wave, and α-rhythmic activity. Spike and HFO waveforms were recorded mainly in patients with TLE. Two spike patterns were recorded: synchronous and independent. In 83.3% of patients, ANT was involved during seizures. Three seizure onset types of ANT were recorded: low-voltage fast activity, rhythmic spikes, and theta band discharge. The time interval of seizure onset between the seizure onset zone and ANT showed two patterns: immediate and delayed., Interpretation: ANT can receive either interictal discharges or ictal discharges which propagate from the epileptogenic zones. Independent epileptic discharges can also be recorded from the ANT in some patients. Metabolic anomalies and epileptic discharges in the ANT indicate that the ANT plays a role in the epileptic network in most patients with epilepsy, especially TLE., (© 2022 The Authors. Annals of Clinical and Translational Neurology published by Wiley Periodicals LLC on behalf of American Neurological Association.)

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.)

Objective: The objective of the study was to develop and clinically test a trial-free online-based language mapping method for localizing the eloquent cortex easily in epilepsy operation., Methods: Nine patients with refractory epilepsy were included in this study according to the results of preoperative evaluation for their epileptogenic zones (EZs) located adjacent to the eloquent cortex. When patients were awakened up from general anesthesia during operation, the trial-free online-based language-mapping paradigm was performed. All positive points marked on the cortex in each test were labeled and superimposed together as the result of functional mapping for each patient. The eloquent cortex was mapped according to the results obtained both from the intraoperative trial-free task localization method and the traditional electrical cortical stimulation (ECS)., Results: All patients completed this paradigms twice within 10 min. Based on the results of mapping, the EZs were tried to fully resected on the premise of preserving the mapped eloquent cortex as much as possible. The postoperative follow-up showed the outcome of Engel I in six patients and Engel II in three patients, whereas only two patients had aphemia after surgery and recovered within one week and three months, respectively., Significance: The intraoperative trial-free online-based language mapping method was primarily identified to be safe and effective. This novel method seems to be promising and worthy of improvement., Competing Interests: Declaration of competing interest None., (Copyright © 2020 Elsevier Inc. All rights reserved.)

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.)

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: Magnetoencephalography (MEG) is considered to be a useful clinical tool to provide additional information for localising the epileptogenic zone or planning intracranial electrode implantation. This study aimed to evaluate the value of MEG in the presurgical localisation of the operculo-insular epileptogenic zone in patients with negative magnetic resonance imaging (MRI)., Methods: Thirteen patients with operculo-insular epilepsy and negative MRI who were identified by presurgical evaluation and underwent resective surgery from January 2011 to June 2015 were included and analysed in the study., Results: In presurgical evaluation, the ictal symptoms looked reliable enough to characterise operculo-insular seizures in four patients. MEG spike sources were shown in the operculo-insular region in 11 of 13 (84.6%) patients, including cluster spike sources in 7 patients and scatter spike sources in 4 patients. After MEG examination, the original plan of intracranial electrode implantation was changed in five patients. In these patients, electrodes exploring the operculo-insular cortex were not part of the original plan. The pathological examination showed focal cortical dysplasia (FCD) in 12 patients and FCD with heterotopia in 1 patient. Nine (69.2%)patients were seizure-free in 2-6 years' follow-up., Conclusions: MEG played an additional and valuable role in the localisation of operculo-insular epilepsy for patients with a negative MRI finding., (Copyright © 2018 British Epilepsy Association. Published by Elsevier Ltd. All rights reserved.)

Epilepsy has been classically seen as a brain disorder resulting from abnormally enhanced neuronal excitability and synchronization. Although it has been described since antiquity, there are still significant challenges achieving the therapeutic goal of seizure freedom. Deep brain stimulation of the anterior nucleus of the thalamus has emerged as a promising therapy for focal drug-resistant epilepsy; the basic mechanism of action, however, remains unclear. Here, we show that desynchronization is a potential mechanism of deep brain stimulation of the anterior nucleus of the thalamus by studying local field potentials recordings from the cortex during high-frequency stimulation (130 Hz) of the anterior nucleus of the thalamus in nine patients with drug-resistant focal epilepsy. We demonstrate that high-frequency stimulation applied to the anterior nucleus of the thalamus desynchronizes ipsilateral hippocampal background electrical activity over a broad frequency range, and reduces pathological epileptic discharges including interictal spikes and high-frequency oscillations. Furthermore, high-frequency stimulation of the anterior nucleus of the thalamus is capable of decoupling large-scale neural activity involving the hippocampus and distributed cortical areas. We found that stimulation frequencies ranging from 15 to 45 Hz were associated with synchronization of hippocampal local field potentials, whereas higher frequencies (>45 Hz) promoted desynchronization of ipsilateral hippocampal activity. Moreover, reciprocal effective connectivity between the anterior nucleus of the thalamus and the hippocampus was demonstrated by hippocampal-thalamic evoked potentials and thalamic-hippocampal evoked potentials. In summary, high-frequency stimulation of the anterior nucleus of the thalamus is shown to desynchronize focal and large-scale epileptic networks, and here is proposed as the mechanism for reducing seizure generation and propagation. Our data also demonstrate position-specific correlation between deep brain stimulation applied to the anterior nucleus of the thalamus and patients with temporal lobe epilepsy and seizure onset zone within the Papaz circuit or limbic system. Our observation may prove useful for guiding electrode implantation to increase clinical efficacy.

Localizing the semiology of ictal fear and seizure onset in epilepsy patients is commonly challenging due to limited value of routine electroencephalography (EEG) and very few surgical attempts. Here we reported a case of refractory epilepsy characterized by aura of extreme fear and hypermotor seizures, in which the left (dominant hemisphere) anterior cingulate gyrus (ACG) was determined to be the epileptogenic zone (EZ) through multiple modalities of presurgical evaluation including analysis of high frequency oscillation on intracranial EEG. Tailored resection of EZ was thus performed and pathological examination revealed focal cortical dysplasia (FCD) type IIb. The patient has been seizure free during an 18-month follow-up. The report has provided novel anatomical, electrophysiological and surgical evidences suggesting the critical role of ACG in ictal fear and possibility of surgical management of fear-manifesting refractory epilepsy., (Copyright © 2017 Elsevier B.V. All rights reserved.)

Object: To study the role of epilepsy surgery for patients with focal lesions who exhibited the semiology of clinically generalised seizures., Methods: From our epilepsy surgery series, we identified 29 patients who underwent surgery for seizures, including certain types of generalised seizures, according to their ictal semiology. We systematically reviewed the brain imaging, video-EEG, surgical operation, and pathological findings data of these patients., Results: All patients had at least one type of generalised seizure according to the semiology; these seizures included epileptic spasms, myoclonic seizures, tonic seizures, atonic seizures and atypical absence seizures. Eight patients had a single type of seizure, 11 patients had two types of seizures, and 10 patients had more than two types of seizures. In addition to symptomatic generalised seizures, complex partial seizures were also recorded in eight patients. In 24 patients, the ictal semiology showed slight asymmetric movements in certain types of seizures. Generalised interictal epileptic discharges were recorded in 24 patients; and generalised ictal epileptic discharges as the only EEG pattern were recorded in 13 patients. Intracranial recording was performed in 20 patients; 10 of whom showed a rhythm of fast activities at the initiation of the seizures. Functional hemispherectomy was performed for three patients with hemispheric lesions. Focal resection of the epileptogenic zone was performed in 26 patients. The resected epileptogenic zones involved a single lobe in 10 patients, two lobes in 11 patients, and three lobes in 5 patients; the parietal lobe was the most commonly involved lobe (in 19 cases). Scar lesions (in 17 patients) were most commonly observed on pathological examination. At the last follow-up (mean 18±8.3 months, range 12-48), 17 (58.6%) patients were seizure-free., Conclusions: Certain patients with local brain lesions can have seizures with specific types of generalised semiology. An appropriate operation may be helpful for a portion of these patients., (Copyright © 2015 Elsevier B.V. All rights reserved.)

Objective: The purpose of this study was to improve the surgical treatment of epilepsy by maximising seizure control while protecting language function., Methods: A combined process of extra-operative electrical cortical stimulation (ECS) mapping, direct ECS and intra-operative continuous language assessment was performed during complicated operative cases. Of the 24 epilepsy patients, nine had a complex relationship between the seizure onset zone and the language cortices. The combined process was used in these nine patients. In the other 15 patients, surgical resection was completed based on extra-operative ECS results alone. Evaluations were performed before and after surgery to assess language function and seizure control., Results: The intra-operative continuous language assessment provided important information at the time of the resection. Seven extra-operative ECS positive language sites were resected without obvious language deficits in two patients. Resection was interrupted by language disturbances in an area where no extra-operative ECS positive site was identified in one patient. In three other patients, functional boundary was undefined in extra-operative ECS result, epileptogenic cortices were maximally resected during the continuous language assessment. In terms of seizure control, 18 of 24 (75%) patients reached Engel's class I, including all nine patients who underwent intra-operative continuous language assessment. One patient had minor surgery-related language deficits three months after resection., Conclusions: Intra-operative continuous language assessment proved to be complementary to extra-operative ECS mappings. The combination of ECS mappings and intra-operative continuous language assessment can maximise the resection of epileptogenic cortices and preserve language function in difficult cases involving the language cortex., (Copyright © 2013 British Epilepsy Association. Published by Elsevier Ltd. All rights reserved.)

Objective: The goal of this study was to summarize the results of language cortex mapping using electrical cortical stimulation with modified language tasks for Mandarin-speaking patients with epilepsy., Methods: Electrical currents were delivered through implanted subdural electrodes to six Mandarin-speaking patients before epilepsy surgery. The current intensities inducing any language disturbance during comprehension, repetition, and speech tasks were recorded, and individual cortical mapping was completed to guide subsequent resection, with the distance between mapped language sites and resected zones kept at a minimum of 0.5 cm. Language function was reassessed and followed up after surgery., Results: Language cortices were successfully identified in three patients, but demonstrated great variability in distribution. There seemed to be no difference in the intensity threshold that induced language interference. None of the six patients exhibited language deficits postsurgery., Conclusions: Electrical cortical stimulation with modified language tasks is valid for identification of cortices underlying Mandarin processing. The great variability in language cortex distribution enhances the necessity of individual language cortical mapping in epilepsy surgery., (Copyright © 2010 Elsevier Inc. All rights reserved.)

Objective: The cortical representation of emotions is complex, and cortical mapping of emotional experience is incomplete. We aimed to contribute to cortical mapping of emotional experience. Methods: Clinical data from 400 patients with medically refractory epilepsy who underwent stereo‐electroencephalography implantation for localization of the epileptogenic zone at the Beijing Institute of Functional Neurosurgery between October 2015 and June 2021 were collected retrospectively. Furthermore, we reviewed studies that described cortical mapping of emotional experience through electrical cortical stimulation (ECS). Affective responses similar to ictal aura and electrode contacts located in the SOZ were excluded to investigate emotional experiences in normal brain regions. Results: Emotional experiences were evoked by stimulation at 10 electrode contacts in the seven patients, including five contacts that evoked mirth and excitement, one contact that evoked calmness, three contacts that evoked fear, and one contact that evoked sadness. In addition, 21 studies that evaluated emotional experiences in response to cortical electrical stimulation were reviewed. Emotions were distributed in the amygdala, hippocampus, temporal lobe, frontal lobe, insula, frontal operculum, parietal operculum, and cingulate cortex. Significance: We provided additional evidence that brain regions including the amygdala, hippocampus, temporal lobe, frontal lobe, insula, frontal operculum, parietal operculum, and cingulate cortex were associated with emotional experience. [ABSTRACT FROM AUTHOR]

Background: Vagus nerve stimulation (VNS) is an effective treatment for patients with refractory epilepsy, yet with varied predictive factors and heterogeneous long-term outcomes. Adjustment of VNS parameters is critical for obtaining favorable efficacy. In this study, we aimed to investigate the long-term outcomes and the possible predictive factors of VNS in patients with refractory epilepsy. Methods: Eighty-six patients (59 males and 27 females) who underwent VNS implantation for treatment of refractory epilepsy between May 2016 and May 2017 at five Epilepsy Centers were enrolled. The clinical data, including sex, age at epilepsy onset, VNS implantation, epilepsy duration, seizure type, MRI findings, history of neurosurgical operations, and responder rate (responders were those with ≥50% seizure reduction), were analyzed. Results: Four-year follow-up data were available for 76 patients (53 males and 23 females). The mean current intensity at the last follow-up was 1.8 ± 0.3 mA (range: 0.75–2.5 mA). The mean seizure reduction was 36.2% at 6 months, 38.5% at 1 year, 69.4% at 3 years, and 56.7% at 4 years. A favorable outcome of ≥50% reduction in seizure frequency occurred in 40.0% of the patients at 6 months, 55.9% at 1 year with 4 patients being seizure-free, 63.2% at 3 years with 5 patients being seizure-free, and 68.4% at 4 years with 5 patients being seizure-free. Earlier onset age (P < 0.001) and shorter duration (P = 0.042) were associated with favorable prognosis. Compared with generalized tonic-clonic seizures, tonic seizures had a favorable outcome (P = 0.026). Twenty-three patients underwent neurosurgical operations before VNS implantation, and the responder rate was 60.9% at the last follow-up. Conclusions: VNS is an adjunctive and effective treatment for patients with refractory epilepsy who are not good candidates for surgical resection or have failed to respond to surgical treatment. The stimulation efficacy increases over time after implantation, and earlier exposure to VNS improves the prognosis. [ABSTRACT FROM AUTHOR]

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]

Purpose: Delineation of subtle lesions in magnetic resonance imaging (MRI)-negative patients is of great importance in preoperative epilepsy evaluation. The aim of our study was to explore the diagnostic value of the novel fluid and white matter suppression (FLAWS) sequence in comparison with a voxel-based MRI postprocessing morphometric analysis program (MAP) in a consecutive cohort of non-lesional patients. Methods: Surgical candidates with a negative finding on an official neuroradiology report were enrolled. High-resolution FLAWS image and MAP maps generated based on high-resolution three-dimensional (3D) T1 image were visually inspected for each patient. The findings of FLAWS or MAP-positive (FLAWS/MAP+) regions were compared with the surgical resection cavity in correlation with surgical outcome and pathology. Results: Forty-five patients were enrolled; the pathological examination revealed focal cortical dysplasia (FCD) in 32 patients and other findings in 13 patients. The positive rate, sensitivity, and specificity were 48.9%, 0.43, and 0.87, respectively, for FLAWS and 64.4%, 0.57, and 0.8, respectively, for MAP. Concordance between surgical resection and FLAWS+ or MAP+ regions was significantly associated with a seizure-free outcome (FLAWS: p = 0.002; MAP: p = 0.0003). A positive finding in FLAWS and MAP together with abnormalities in the same gyrus (FLAWS–MAP gyral+) was detected in 31.1% of patients. FLAWS+ only and MAP+ only were found in 7 (15.5%) and 14 (31.1%) patients, respectively. Conclusions: FLAWS showed a promising value for identifying subtle epileptogenic lesions and can be used as a complement to current MAP in patients with MRI-negative epilepsy. [ABSTRACT FROM AUTHOR]

Objective: Pharmaco-refractory focal motor epileptic seizures pose a significant challenge. Deep brain stimulation (DBS) is a recently recognized therapeutic option for the treatment of refractory epilepsy. To identify the specific target for focal motor seizures, we evaluate the modulatory effects of the subthalamic nucleus (STN) stimulation because of the critical role of STN in cortico-subcortical motor processing.Methods: Seven patients with epilepsy with refractory seizures who underwent chronic stereoelectroencephalography (SEEG) monitoring were studied in presurgical evaluation. Seizure onset zone was hypothesized to be partially involved in the motor areas in 6 patients. For each patient, one electrode was temporally implanted into the STN that was ipsilateral to the seizure onset zone. The cortical-subcortical seizure propagation was systemically evaluated. The simultaneously electrophysiological responses over distributed cortical areas to STN stimulation at varied frequencies were quantitatively assessed.Results: We observed the consistent downstream propagation of seizures from the motor cortex toward the ipsilateral STN and remarkable cortical responses on motor cortex to single-pulse STN stimulation. Furthermore, we showed frequency-dependent upstream modulatory effect of STN stimulation on motor cortex specifically. In contrast to the enhanced effects of low frequency stimulation, high-frequency stimulation of the STN can significantly reduce interictal spikes, high-frequency oscillations over motor cortex disclosing effective connections to the STN.Interpretation: This result showed that the STN is not only engaged in as a propagation network of focal motor seizures but STN stimulation can profoundly modulate the epileptic activity of motor cortex in humans, suggesting a mechanism-based alternative for patients suffering from refractory focal motor seizures. ANN NEUROL 2020;88:283-296. [ABSTRACT FROM AUTHOR]

Epilepsy has been classically seen as a brain disorder resulting from abnormally enhanced neuronal excitability and synchronization. Although it has been described since antiquity, there are still significant challenges achieving the therapeutic goal of seizure freedom. Deep brain stimulation of the anterior nucleus of the thalamus has emerged as a promising therapy for focal drug-resistant epilepsy; the basic mechanism of action, however, remains unclear. Here, we show that desynchronization is a potential mechanism of deep brain stimulation of the anterior nucleus of the thalamus by studying local field potentials recordings from the cortex during high-frequency stimulation (130 Hz) of the anterior nucleus of the thalamus in nine patients with drug-resistant focal epilepsy. We demonstrate that high-frequency stimulation applied to the anterior nucleus of the thalamus desynchronizes ipsilateral hippocampal background electrical activity over a broad frequency range, and reduces pathological epileptic discharges including interictal spikes and high-frequency oscillations. Furthermore, high-frequency stimulation of the anterior nucleus of the thalamus is capable of decoupling large-scale neural activity involving the hippocampus and distributed cortical areas. We found that stimulation frequencies ranging from 15 to 45 Hz were associated with synchronization of hippocampal local field potentials, whereas higher frequencies (>45 Hz) promoted desynchronization of ipsilateral hippocampal activity. Moreover, reciprocal effective connectivity between the anterior nucleus of the thalamus and the hippocampus was demonstrated by hippocampal-thalamic evoked potentials and thalamic-hippocampal evoked potentials. In summary, high-frequency stimulation of the anterior nucleus of the thalamus is shown to desynchronize focal and large-scale epileptic networks, and here is proposed as the mechanism for reducing seizure generation and propagation. Our data also demonstrate position-specific correlation between deep brain stimulation applied to the anterior nucleus of the thalamus and patients with temporal lobe epilepsy and seizure onset zone within the Papaz circuit or limbic system. Our observation may prove useful for guiding electrode implantation to increase clinical efficacy. [ABSTRACT FROM AUTHOR]

The authors present a case of an out-of- body experience (OBE) that occurred in a child with intractable epilepsy when stimulating the anterior insular cortex (AIC) by intracranial electrodes. After destroying several sites precisely located at the left AIC by radiofrequency thermocoagulation, the patient’s seizures disappeared, and the OBE could not be reproduced when repeatedly stimulating these sites. To our knowledge, it has never been reported that an OBE occurred in the AIC. We analyze the mechanism of an OBE mostly appearing in temporo-parietal junction (TPJ) and propose two perspectives for a possible mechanism involving the AIC causing the OBE. [ABSTRACT FROM AUTHOR]

Highlights • Laughter occurred when stimulating posterior insula. • Laughter related to a variety of brain regions. • Progression of mirth in the insula contribute to laughter. • Posterior insula in involuntary pathway related to laughter. Abstract Laughter induced in the insula is uncommon. In this case-report we present a description of a patient with drug-resistant focal epilepsy for whom laughter with mirth was elicited when the posterior insula (PI) was stimulated by intracranial electrodes. We attempted to analyze the progression of laughter in the insula and suggest a possible pathway for the expression of laughter. [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]

• 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]

Highlights • Insula and opercula perform various and complicated functions. • Insula have functions in cardiovascular systems. • Posterior insula and parietal operculum related to body-ownership symptoms. • Complicated visual phenomena related to temporal operculum. Abstract Purpose Using direct intracerebral electrical stimulation (ES) in epileptic patients to evoke symptoms to help identify the functional neuroanatomy of the insular lobe and opercula. Methods We selected 43 patients who had at least 1 electrode inserted into the insula or opercula via an oblique approach among 135 patients with intractable epilepsy. Bipolar stimulation was chosen, and the stimulation parameters of the biphasic waves included a pulse width of 0.2 ms, a frequency of 50 Hz, a duration of 3 s, and an intensity gradually increasing from 0.5 to 4 mA. Results In total, 93 electrodes were implanted into the insula or insular opercula, and 169 of 281 contacts (60.1%) evoked 212 responses by ES of the insula. 142 responses were induced by stimulating the insular opercula in 126 of 343 sites (36.7%). Usual responses, such as somatosensory, visceral sensory, speech, auditory, and motor responses, were evoked. In addition, rarely reported responses, including cardiovascular symptoms (tachycardia), visual symptoms evoked by ES of the parietal and temporal opercula, and vestibular symptoms (like the loss of ownership of the body) evoked following stimulation of the posterior insula and parietal operculum, were also induced in our study. Conclusions The insula and opercula perform various and complicated functions. The posterior insula and parietal operculum could play important roles in body-ownership symptoms. The complicated visual phenomena were partially related to the temporal operculum. [ABSTRACT FROM AUTHOR]

Purpose: Surgical resection is the most effective treatment for focal cortical dysplasia (FCD). However, many patients with FCD have unremarkable or even negative findings on conventional magnetic resonance imaging (MRI). In this study, we explored the brain volume abnormalities of FCD patients at the individual level using an experimental volume-based morphometry algorithm and further estimated whether the volume abnormalities can help in the detection of FCD lesions.Materials and Methods: Sixteen patients with histologically-proven FCD lesions were retrospectively studied. Among them, eight patients had no visible abnormalities on routine MRI, three had abnormalities which partly matched the location of the surgical resection regions, and two did not match. For each patient, cerebral high-resolution T1-weighted magnetization-prepared rapid acquisition with gradient echo (MPRAGE) images were segmented into 45 structures, according to a brain anatomy template, and the volume of each structure was compared with an age- and gender-matched normal population at the individual level, based on a MorphoBox prototype. A Receiver Operating Characteristics (ROC) curve was used to evaluate the performance of the prototype in patients. To find the most appropriate threshold value for localizing the epileptogenic zones, deviations from the normative ranges of each resulting volume estimate were assessed by z-scores.Results: Volume abnormalities including atrophic and hypertrophic volumes could be found in all the patients. Epileptogenic zones were found in brain structures with an abnormal volume in 87.5% (14/16) of patients. In 71.4% of patients (10/14), these zones were fully located in regions with an atrophic volume. This suggests that FCD lesions are more likely to be in regions with an atrophic volume than in those with a hypertrophic volume. When the best cut-off z-score value was -3.0, the sensitivity, specificity, and ROC area under the curve of the volume estimates were 93.9%, 79.6%, and 0.89, respectively.Conclusion: Volume abnormalities can assist in the diagnosis of epileptogenic zones at the individual level in FCD patients with negative or positive findings on conventional MR images. Atrophic regions are more likely than hypertrophic ones to represent epileptogenic zones. Volume-based morphometry based on a MorphoBox prototype has potential to assist a careful scrutiny by radiologists with target in atrophic regions in patients who are initially deemed to be MR-negative, further trying to increase the detection rate of FCD. [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]

• Presurgical evaluation of patients with MRI-negative cingulate epilepsy (MRI-negative CE) is challenging. • Ten patients with MRI-negative CE were assessed using MAP and PET/MRI co-registration. • MRI post-processing and PET/MRI co-registration complements with each other. • MAP and PET/MRI co-registration are useful in MRI-negative CE. Diagnostic challenges exist in the presurgical evaluation of patients with magnetic resonance imaging (MRI) negative cingulate epilepsy (CE) because of the heterogeneity in clinical semiology and lack of localizing findings on scalp electroencephalographic (EEG) recordings. We aimed to examine the neuroimaging characteristics in a consecutive cohort of patients with MRI-negative CE with a focus on two image post-processing methods, including the MRI post-processing morphometric analysis program (MAP) and 18F-fluorodeoxyglucose-positron emission tomography-MRI (PET/MRI) co-registration. Included in this retrospective study were patients with MRI-negative CE who met the following criteria: negative on preoperative MRI, invasive EEG (iEEG) confirmed cingulate gyrus-onset seizures, surgical resection of the cingulate gyrus with/without adjacent cortex, and seizure-free for more than 12 months. MAP and PET/MRI co-registration were performed and investigated by comparison to ictal intracranial EEG findings. Other characteristics obtained from scalp EEG, magnetoencephalography (MEG), iEEG, and pathological study were also reported. Ten patients were included, of which eight were diagnosed with anterior CE, one with middle CE, and one with posterior CE. The semiology included fear, embarrassment, vocalization, ictal pouting, asymmetric tonic posture, hypermotor, and automatism. Scalp EEG revealed unilateral or bilateral frontal-temporal onset. MEG localized the dipoles correctly in one patient (1/10). MAP detected subtle abnormalities in regions concordant with iEEG onset in seven patients (7/10) while PET/MRI co-registration revealed focal concordant hypometabolism in five patients (5/10). Combining MAP with PET/MRI co-registration improved the detection rate to 90 % in this cohort. The pathology was focal cortical dysplasia (FCD), including FCD type IIA in three, type IIB in three, and type I in four. MAP and PET/MRI co-registration show promising results in identifying subtle FCD abnormalities in CE with negative results on conventional MRI, which can be otherwise challenging. More importantly, a combination of MRI post-processing and PET/MRI co-registration can greatly improve the identification of epileptic abnormalities, which can be used as surgical target. MAP and PET/MRI co-registration should be incorporated into the routine presurgical evaluation. [ABSTRACT FROM AUTHOR]