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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. [ABSTRACT FROM AUTHOR]

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. [ABSTRACT FROM AUTHOR]

Background: The mechanisms of vagal nerve stimulation (VNS) for the treatment of drug‐resistant epilepsy (DRE) remain unclear. This study aimed to measure spontaneous brain activity changes caused by VNS in DRE patients using resting‐state functional MRI (rs‐fMRI). Methods: The rs‐fMRI scans were performed in 16 DRE patients who underwent VNS surgery. Amplitude of low‐frequency fluctuations (ALFF) and regional homogeneity (ReHo) was generated and examined using paired sample t‐test to compare activity changes at different current intensity stage. The preoperative and postoperative ALFF/ReHo were also compared in eight responders (≥50% reduction of seizure frequency three months after surgery) and eight nonresponders using paired sample t‐test. Results: The significant ALFF and ReHo changes were shown in various cortical/subcortical structures in patients under different current intensity. After three months of stimulation, responders exhibited increased ALFF in the right middle cingulate gyrus, left parahippocampal gyrus, and left cerebellum, and increased ReHo in the right postcentral gyrus, left precuneus, left postcentral gyrus, right superior parietal gyrus, right precentral gyrus, and right superior frontal gyrus. Nonresponders exhibited decreased ALFF in the left temporal lobe and right cerebellum, increased ALFF in bilateral brainstem, decreased ReHo in bilateral lingual gyri, and increased ReHo in the right middle frontal gyrus and right anterior cingulate gyrus. Conclusions: The spontaneous neural activity changes in DRE patients caused by VNS were in an ongoing process. Increased ALFF/ReHo in frontal cortex, cingulate gyri, precentral/postcentral gyri, parahippocampal gyri, precuneus, parietal cortex, and cerebellum may implicate in VNS‐induced improvement in seizure frequency. [ABSTRACT FROM AUTHOR]

Background: Fear, as one of the basic emotions, is crucial in helping humans to perceive hazards and adapt to social activities. Clinically, fear memory is also involved in a wide spectrum of psychiatric disorders. A better understanding of the neural mechanisms of fear thereby has both neuroscientific and clinical significance. In recent years, data from animal models have demonstrated the key role of the amygdala-hippocampal circuit in the development of fear. However, the neural processing of fear memory remains unclear in humans, which is mainly due to the limitation of indirect measure of neural activity. Methods: Herein, we investigated fear memory by direct intracranial recordings from 8 intractable epilepsy patients with depth electrodes in both the hippocampus and ipsilateral amygdala. All the patients were subjected to a well-established Pavlovian fear memory paradigm consisted of the familiarization task, conditioning task, and retrieval task, respectively. Simultaneous local field potentials from the hippocampus and amygdala were recorded during different stages. The oscillatory activities from the amygdala and hippocampus were analyzed during fear memory retrieval compared with neutral stages. Results: Consistent with previous rodent studies, our results showed that the amygdala was involved in fear memory retrieval rather than neutral memory retrieval, while the hippocampus was involved both in fear memory retrieval and neutral memory retrieval. In particular, we found that there was an enhanced synchronized activity between the amygdala and hippocampus at beta frequencies (14–30 Hz), which suggested that enhanced synchronized activity at beta frequencies between the amygdala and hippocampus play a pivotal role during retrieval of fear memory in human. Conclusions: Thus, our observation that the amygdala-hippocampal system contributing to fear memory retrieval in human with frequency-depended specificity has provided new insights into the mechanism of fear and have potential clinical relevance. [ABSTRACT FROM AUTHOR]

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. 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. 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. VNS causes topological characteristics changes in pediatric patients with generalized seizures through regulating regional properties in some brain structures. [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]

Abstract: 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 0.5cm. 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. [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]

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. 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). 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. 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. • A trial-free online-based language mapping paradigms is newly developed. • Language mapping by HGP is low-risk, timesaving, and multiprocessing. • The novel language mapping paradigms were underwent easily and quickly in operation. • This language mapping method is primarily verified safe and effective. [ABSTRACT FROM AUTHOR]

To explore the effect of vagal nerve stimulation (VNS) on spontaneous brain activity in patients with drug-resistant epilepsy (DRE). 15 patients and eight healthy controls (HC) were enrolled and scanned by resting-state functional MRI to investigate changes in the fractional amplitude of low-frequency fluctuation (fALFF) and regional homogeneity (ReHo). A two-sample t -test or paired sample t -test was used to compare activity between the HCs, preoperative patients (EP-pre), and postoperative patients (EP-post). We also performed correlation analyses to examine the seizure improvement ratio. The voxel-level analyses indicated that, compared with the HC, the EP-pre group exhibited decreased or increased fALFF and ReHo in the frontal cortex, temporal cortex, precentral/postcentral gyrus, amygdala, insula, cerebellum, and lingual gyrus. Furthermore, compared with the EP-pre group, the EP-post group exhibited decreased or increased fALFF and ReHo in the frontal cortex, temporal cortex, precentral gyrus, insula, anterior/median cingulate gyri, and cerebellum. The regions of interest-level analyses indicated that, compared with HC, the EP-pre group exhibited decreased fALFF or ReHo in the caudate nucleus, supramarginal gyrus, precuneus and middle temporal gyrus. Furthermore, compared with the EP-pre group, the EP-post group exhibited increased fALFF or ReHo in the olfactory cortex, gyrus rectus, and superior temporal gyrus. Increased ReHo in the right superior or middle temporal gyrus was positively correlated with the improvement ratio. Altered regional activity in DRE patients was reorganized after 3 months of stimulation. Increased ReHo in the right superior or middle temporal gyrus was implicated in VNS-induced improvement in seizure frequency. [ABSTRACT FROM AUTHOR]

• This is the first study to evaluate the value of MEG in SEEG-guided RF-TC in MRI-negative epilepsies. • 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. 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. 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 RF TC 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. 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. [ABSTRACT FROM AUTHOR]