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Limb loss experience is a type of body illusion characterized by the sensation of a missing limb or body part. We aimed to investigate the brain areas involved in this unusual somatosensory experience evoked by electric cortical stimulation with stereo-electroencephalography electrodes. We retrospectively reviewed the data of patients with medical intractable epilepsy, from October 2015 to December 2020, who underwent stereo-electroencephalography implantation and electric cortical stimulation in order to locate the epileptogenic zone and obtain a functional map. We included patients who reported experiences of limb loss during the process of electric cortical stimulation for functional mapping. Three patients reported experiences of limb loss in the process of electric cortical stimulation. Limb loss experience (including the right hand, right upper limb and right side of the body) occurred when the cortex of the left posterior insula, posterior dorsal cingulate and parietal operculum were stimulated. Limb loss experience can be evoked by electric cortical stimulation of the posterior insula, parietal operculum, and posterior cingulate cortex, and provides additional evidence that these cortices play a role in the integration of body sensory perception.

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.

Vagus nerve stimulation (VNS) and anterior thalamic deep brain stimulation (ANT-DBS) have both been used for treatments of drug-resistant epilepsy (DRE). However, there is no comparative study on the effectiveness of two methods from one single center. 17 patients with DRE who underwent VNS therapy and 18 patients who underwent DBS were enrolled. A retrospective study was performed starting from baseline before operation extending to 12 months after operation. The seizure types, duration of epilepsy, age at implantation, failed numbers of antiepileptic drugs (AEDs) before operation, history of craniotomy, stimulation parameters and response rate were described. The analysis of liner regression on the age of onset, duration of epilepsy, numbers of AEDs, and the seizure reduction at 12 months after operation was applied. The mean seizure reduction in patients with DBS at 3, 6, 9 and 12 months after the operation was 57.22%, 61.61%, 63.94% and 65.28%, and that in cases with VNS was 36.06%, 39.94%, 45.24% and 48.35%, respectively. At 1 year after the operation, the patients with older operation age, focal seizures and older age of onset responded better to VNS; and those older operation age, focal generalized seizures, history of craniotomy and longer duration of disease responded better to DBS. The efficiency of ANT-DBS was higher than that of VNS at each follow up time point. Patients can choose the appropriate treatment according to the individual clinical characteristics.

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 (p0.05). While, there was no significant difference in hippocampal - thalamic connections in all epilepsy patients or responders with different current intensities (p0.05).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.

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., Dynamic amplitude of low‐frequency fluctuations and regional homogeneity changes existed in drug‐resistant epilepsy patients with vagal nerve stimulators (VNS) under different current intensity and may provide possible therapeutic mechanisms of VNS.

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. 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. 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. 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.

Description, Greater representational transformation during encoding is associated with stronger semantic formats and better long-term memory., Memory is often conceived as a dynamic process that involves substantial transformations of mental representations. However, the neural mechanisms underlying these transformations and their role in memory formation and retrieval have only started to be elucidated. Combining intracranial EEG recordings with deep neural network models, we provide a detailed picture of the representational transformations from encoding to short-term memory maintenance and long-term memory retrieval that underlie successful episodic memory. We observed substantial representational transformations during encoding. Critically, more pronounced semantic representational formats predicted better subsequent long-term memory, and this effect was mediated by more consistent item-specific representations across encoding events. The representations were further transformed right after stimulus offset, and the representations during long-term memory retrieval were more similar to those during short-term maintenance than during encoding. Our results suggest that memory representations pass through multiple stages of transformations to achieve successful long-term memory formation and recall.

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.

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.

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.

Background: Based on data for a large population of patients from a single center in China accumulated over 22 years, we revealed an overall profile of movement disorders (MDs) in terms of their demographic features and surgical treatment. Methods: This study was conducted on 21,005 outpatients (2008–2019) and 5,126 inpatients (1998–2019) with MDs who underwent radiofrequency ablation (RFA) or deep-brain stimulation (DBS). Patients were categorized into those with Parkinson’s disease (PD), essential tremor (ET), dystonia, tics, or involuntary movements (IMs). The clinical data of these patients were analyzed retrospectively. Findings: PD accounted for the largest proportion (75·4%) among surgically treated MD patients, and was associated with the highest surgical rate (18·8%), followed by ET (proportion: 12·1%, surgical rate: 10·4%) and dystonia (proportion: 5·7%, surgical rate: 5·7%). The male:female ratio was higher in surgical patients than in outpatients (1·49 vs 1·27 p< 0·001). The surgery ages in patients with PD, ET, dystonia, tics, or IMs was 62 (54–67), 61 (46–68), 40 (26–53), 21 (19–25), and 21 (17–28) years; and the duration of illness (DOI was 6 (4–10), 14 (9–20), 4 (2–10), 11 (7–17), and 17 (10–22) years, respectively. Between 1998 and 2019, the percentage of patients undergoing DBS among surgically treated MD patients increased from 0% to 85%. Interpretation: PD is the most common MD that necessitates surgical treatment, followed by ET and dystonia. Surgical timing is individualized and varies among different types of MDs. DBS has become the dominant surgical modality for MDs, except ET. Funding: None to declare Declaration of Interest: None to declare. Ethical Approval: The present study was approved by the Ethics Review Board within Xuanwu Hospital of Capital Medical University (Beijing, China). Written informed consent was obtained on the day before surgery.

Visual short-term memory (VSTM) enables humans to form a stable and coherent representation of the external world. However, the nature and temporal dynamics of the neural representations in VSTM that support this stability are barely understood. Here we combined human intracranial electroencephalography (iEEG) recordings with analyses using deep neural networks and semantic models to probe the representational format and temporal dynamics of information in VSTM. We found clear evidence that VSTM maintenance occurred in two distinct representational formats which originated from different encoding periods. The first format derived from an early encoding period (250 to 770 ms) corresponded to higher-order visual representations. The second format originated from a late encoding period (1,000 to 1,980 ms) and contained abstract semantic representations. These representational formats were overall stable during maintenance, with no consistent transformation across time. Nevertheless, maintenance of both representational formats showed substantial arrhythmic fluctuations, i.e., waxing and waning in irregular intervals. The increases of the maintained representational formats were specific to the phases of hippocampal low-frequency activity. Our results demonstrate that human VSTM simultaneously maintains representations at different levels of processing, from higher-order visual information to abstract semantic representations, which are stably maintained via coupling to hippocampal low-frequency activity.

Objectives: Based on data for a large population of patients from a single center accumulated over 22 years, the present study aimed to reveal an overall profile of movement disorders (MDs) in terms of their demographic features and surgical treatment. Methods: This study was conducted on 21,005 outpatients (2008–2019) and 5,126 inpatients (1998–2019) with MDs who underwent radiofrequency ablation (RFA) or deep-brain stimulation (DBS). Patients were categorized into those with Parkinson’s disease (PD), essential tremor (ET), dystonia, tics, or involuntary movements (IMs). The clinical data of these patients were analyzed retrospectively. Results: PD accounted for the largest proportion (75.4%) among surgically treated MD patients, and was associated with the highest surgical rate (18.8%), followed by ET (proportion: 12.1%, surgical rate: 10.4%) and dystonia (proportion: 5.7%, surgical rate: 5.7%). The male:female ratio was higher in surgical patients than in outpatients (1.49 vs. 1.27, p

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.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.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 (P0.05). 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 (P0.05).Epilepsy duration is an independent predictor for responders to VNS. VNS is more likely to be efficacious in those with an epilepsy duration12.5 years, especially those with a duration of 5-12.5 years.

Purpose To explore the effect of vagal nerve stimulation (VNS) on spontaneous brain activity in patients with drug-resistant epilepsy (DRE). Methods 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. Results 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. Conclusions 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.

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.

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.

Objectives The purpose of this study is to explore the surgical outcome of unilateral anterior temporal lobectomy (ATL) for patients with bilateral temporal lobe epilepsy (BTLE). Methods We retrospectively reviewed the data of patients who were diagnosed with BTLE by scalp electroencephalogram (EEG) and underwent ATL from 2001 to 2015. In addition, 80 patients were randomly selected as a control group. Results One hundred seventeen patients were included in this study and were divided into four groups by intracranial recordings as follows: 78 patients with unilateral seizure onset (Group 1), 13 patients with lateralizable dominant seizure onset (Group 2), 14 patients with lateralizable neuroimaging abnormalities (Group 3), and 12 patients without lateralizable dominant seizure onset or neuroimaging abnormalities (Group 4). The 12 patients in Group 4 declined surgical resection, whereas the remaining 105 patients received ATL, and 93 of them were followed up for more than 1 year after surgery. At the 1-, 2-, and 3-year follow-ups the percentage of patients who were seizure free was 52.9%, 56.5%, and 58.9%, respectively. For the mean postoperative efficacy, there was a statistical difference in patients who were seizure free either between Group 1 + Group 2 + Group 3 and the control group (44.1% vs. 67.5%, p = 0.002), or between Group 1 and the control group (48.5% vs. 67.5%, p = 0.019), or between Group 2 + Group 3 and the control group (32.0% vs. 67.5%, p = 0.002). However, the difference was significant only at the first year follow-up, and there was no significant difference afterward. Significance Although the surgical outcome of patients with BTLE is not as good as that of patients with unilateral TLE in short-term follow-up, quite a portion of these patients could benefit from unilateral temporal lobe resection in the long term.

Objective To investigate the properties of afterdischarges (ADs) from intracerebral electrical stimulation (ES) in patients with epilepsy who underwent stereotactic electroencephalography (SEEG) and determine the relationship between epileptogenic zone (EZ) or irritative zone (IZ) and ADs. Methods We retrospectively analyzed 10 patients with intractable epilepsy who underwent SEEG. ESs were delivered following the given parameters: bipolar, biphasic, 50 Hz, 0.2 ms pulse duration, 0.5–10 mA. The properties of ADs were documented, including their incidence, location, threshold, morphology and evolution. Results A total of 213 ADs (5%) were elicited by 4701 trains of ES. Stimulation through contacts implanted in the hippocampus (59%) generally evoked more ADs than contacts elsewhere (19%). AD thresholds for hippocampal stimulation were significantly lower than those for stimulation in grey matter. Polyspikes (58%) were the most common AD morphology. Evolution occurred more commonly with sequential spikes (47%) than with other AD morphologies (14%). There was no significant correlation between the location of ADs and EZ. However, ADs were significantly more frequently localized to IZ than areas outside IZ (P Conclusions There seemed to be a lack of correlation between the location of ADs and EZ. However, ADs were more likely to be elicited in IZ.

Brief-pulse stimulation at 50 Hz has been shown to terminate afterdischarges observed in epilepsy patients. However, the optimal pulse stimulation parameters for terminating cortical electrical stimulation-induced afterdischarges remain unclear. In the present study, we examined the effects of different brief-pulse stimulation frequencies (5, 50 and 100 Hz) on cortical electrical stimulation-induced afterdischarges in 10 patients with refractory epilepsy. Results demonstrated that brief-pulse stimulation could terminate cortical electrical stimulation-induced afterdischarges in refractory epilepsy patients. In conclusion, (1) a brief-pulse stimulation was more effective when the afterdischarge did not extend to the surrounding brain area. (2) A higher brief-pulse stimulation frequency (especially 100 Hz) was more likely to terminate an afterdischarge. (3) A low current intensity of brief-pulse stimulation was more likely to terminate an afterdischarge.

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.

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.

Objective 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. Methods 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. Results 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. Conclusion 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.

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.

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 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. 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.

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.

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.

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.

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.

We present two cases with paroxysmal pain that developed after a somatic injury to the trunk. The main characteristic of the episodes was paroxysmal severe pain, mainly located in the original region of somatic injury, with ipsilateral tonic or dystonic behaviour. The clinical characteristics supported a diagnosis of focal epilepsy. Both scalp EEG and MEG findings suggested epileptic activities on the contralateral central cortex. The focal seizures had a good response to antiepileptic drugs. It is hypothesized that peripheral somatic injuries can modify cortical excitability and lead to plastic changes in the sensory/motor cortex, ultimately resulting in focal seizures. We provide additional evidence for the phenomenon that a peripheral somatic injury could induce focal epilepsy. [Published with video sequence on www.epilepticdisorders.com].

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.

Summary 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.

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.