Identification of Early Hippocampal Dynamics during Recognition Memory with Independent Component Analysis.

The hippocampus is generally considered to have relatively late involvement in recognition memory, its main electrophysiological signature being between 400 and 800 ms after stimulus onset. However, most electrophysiological studies have analyzed the hippocampus as a single responsive area, selecting only a single-site signal exhibiting the strongest effect in terms of amplitude. These classical approaches may not capture all the dynamics of this structure, hindering the contribution of other hippocampal sources that are not located in the vicinity of the selected site. We combined intracerebral electroencephalogram recordings from epileptic patients with independent component analysis during a recognition memory task involving the recognition of old and new images. We identified two sources with different responses emerging from the hippocampus: a fast one (maximal amplitude at ∼250 ms) that could not be directly identified from raw recordings and a latter one, peaking at ∼400 ms. The former component presented different amplitudes between old and new items in 6 out of 10 patients. The latter component had different delays for each condition, with a faster activation (∼290 ms after stimulus onset) for recognized items. We hypothesize that both sources represent two steps of hippocampal recognition memory, the faster reflecting the input from other structures and the latter the hippocampal internal processing. Recognized images evoking early activations would facilitate neural computation in the hippocampus, accelerating memory retrieval of complementary information. Overall, our results suggest that the hippocampal activity is composed of several sources with an early activation related to recognition memory.

Grading system for assessing the confidence in the epileptogenic zone reported in published studies: A Delphi consensus study.

OBJECTIVE: This study was undertaken to develop a standardized grading system based on expert consensus for evaluating the level of confidence in the localization of the epileptogenic zone (EZ) as reported in published studies, to harmonize and facilitate systematic reviews in the field of epilepsy surgery. METHODS: We conducted a Delphi study involving 22 experts from 18 countries, who were asked to rate their level of confidence in the localization of the EZ for various theoretical clinical scenarios, using different scales. Information provided in these scenarios included one or several of the following data: magnetic resonance imaging (MRI) findings, invasive electroencephalography summary, and postoperative seizure outcome. RESULTS: The first explorative phase showed an overall interrater agreement of .347, pointing to large heterogeneity among experts' assessments, with only 17% of the 42 proposed scenarios associated with a substantial level of agreement. A majority showed preferences for the simpler scale and single-item scenarios. The successive Delphi voting phases resulted in a majority consensus across experts, with more than two thirds of respondents agreeing on the rating of each of the tested single-item scenarios. High or very high levels of confidence were ascribed to patients with either an Engel class I or class IA postoperative seizure outcome, a well-delineated EZ according to all available invasive EEG (iEEG) data, or a well-delineated focal epileptogenic lesion on MRI. MRI signs of hippocampal sclerosis or atrophy were associated with a moderate level of confidence, whereas a low level was ascribed to other MRI findings, a poorly delineated EZ according to iEEG data, or an Engel class II-IV postoperative seizure outcome. SIGNIFICANCE: The proposed grading system, based on an expert consensus, provides a simple framework to rate the level of confidence in the EZ reported in published studies in a structured and harmonized way, offering an opportunity to facilitate and increase the quality of systematic reviews and guidelines in the field of epilepsy surgery.

Organization of the epileptogenic zone and signal analysis at seizure onset in patients with drug-resistant epilepsy due to focal cortical dysplasia with mTOR pathway gene mutations-An SEEG study.

Epilepsy surgery in genetic drug-resistant epilepsy is a debated subject as more histological and molecular data are available. We retrospectively collected data from focal drug-resistant epilepsy patients that underwent stereoelectroencephalography (SEEG) invasive recordings. Patients with nonlesional brain imaging or in whom a first epilepsy surgery failed to control seizures were selected. We computed and displayed the intracranial ictal onset activity pattern on structural imaging. Patients underwent epilepsy gene panel testing, next generation sequencing-NGS. Of 113 patients, 13 underwent genetic testing, and in 6 patients, a mechanistic target of rapamycin pathway gene germline mutation (mTOR) was identified. Brain imaging was nonlesional except for one patient in whom two abnormalities suggestive of focal cortical dysplasia (FCD) were found. Patients underwent tailored brain surgery based on SEEG data, tissue analysis revealed FCD and postsurgical outcome was favorable. Our findings are similar to previous case series suggesting that epilepsy surgery can be a treatment option in patients with mTOR pathway mutation. In patients with mTOR pathway mutation, the postsurgical outcome is favorable if complete resection of the epileptogenic zone is performed. Electrophysiological seizure onset patterns in FCDs associated with mTOR pathway mutations display low-voltage fast activity as previously described.

Studying memory processes at different levels with simultaneous depth and surface EEG recordings.

Investigating cognitive brain functions using non-invasive electrophysiology can be challenging due to the particularities of the task-related EEG activity, the depth of the activated brain areas, and the extent of the networks involved. Stereoelectroencephalographic (SEEG) investigations in patients with drug-resistant epilepsy offer an extraordinary opportunity to validate information derived from non-invasive recordings at macro-scales. The SEEG approach can provide brain activity with high spatial specificity during tasks that target specific cognitive processes (e.g., memory). Full validation is possible only when performing simultaneous scalp SEEG recordings, which allows recording signals in the exact same brain state. This is the approach we have taken in 12 subjects performing a visual memory task that requires the recognition of previously viewed objects. The intracranial signals on 965 contact pairs have been compared to 391 simultaneously recorded scalp signals at a regional and whole-brain level, using multivariate pattern analysis. The results show that the task conditions are best captured by intracranial sensors, despite the limited spatial coverage of SEEG electrodes, compared to the whole-brain non-invasive recordings. Applying beamformer source reconstruction or independent component analysis does not result in an improvement of the multivariate task decoding performance using surface sensor data. By analyzing a joint scalp and SEEG dataset, we investigated whether the two types of signals carry complementary information that might improve the machine-learning classifier performance. This joint analysis revealed that the results are driven by the modality exhibiting best individual performance, namely SEEG.

Musicogenic seizures in temporal lobe epilepsy: Case reports based on ictal source localization analysis.

Musicogenic epilepsy is a rare form of reflex epilepsy in which seizures are provoked by music. Different musicogenic stimuli have been identified: pleasant/unpleasant music or specific musical patterns. Several etiologies have been uncovered, such as focal cortical dysplasia, autoimmune encephalitis, tumors, or unspecific gliosis. In this article, we report two patients with musicogenic seizures. The first patient was diagnosed with structural temporal lobe epilepsy. Her seizures were elicited by music that she liked. Interictal and ictal video-electroencephalography (video-EEG) and signal analysis using independent component analysis revealed the right temporal lobe seizure onset extending over the neocortical regions. The patient underwent right temporal lobectomy (including the amygdala, the head, and the body of the hippocampus) and faced an Engel IA outcome 3 years post-surgery. The second patient was diagnosed with autoimmune temporal lobe epilepsy (GAD-65 antibodies). Her seizures were triggered by contemporary hit radio songs without any personal emotional significance. Interictal and ictal video-electroencephalography (video-EEG) and independent component analysis highlighted the left temporal lobe seizure onset extending over the neocortical regions. Intravenous immunoglobulin therapy was initiated, and the patient became seizure-free at 1 year. In conclusion, musicogenic seizures may be elicited by various auditory stimuli, the presence or absence of an emotional component offering an additional clue for the underlying network pathophysiology. Furthermore, in such cases, the use of independent component analysis of the scalp EEG signals proves useful in revealing the location of the seizure generator, and our findings point toward the temporal lobe, both mesial and neocortical regions.

Cingulate Cortex: Anatomy, Structural and Functional Connectivity.

SUMMARY: The cingulate cortex is a paired brain region located on the medial wall of each hemisphere. This review explores the anatomy as well as the structural and functional connectivity of the cingulate cortex underlying essential roles this region plays in emotion, autonomic, cognitive, motor control, visual-spatial processing, and memory.

Routine and sleep EEG: Minimum recording standards of the International Federation of Clinical Neurophysiology and the International League Against Epilepsy.

This article provides recommendations on the minimum standards for recording routine ("standard") and sleep electroencephalography (EEG). The joint working group of the International Federation of Clinical Neurophysiology (IFCN) and the International League Against Epilepsy (ILAE) developed the standards according to the methodology suggested for epilepsy-related clinical practice guidelines by the Epilepsy Guidelines Working Group. We reviewed the published evidence using the Preferred Reporting Items for Systematic Review and Meta-Analysis (PRISMA) statement. The quality of evidence for sleep induction methods was assessed by the Grading of Recommendations, Assessment, Development and Evaluations (GRADE) method. A tool for Quality Assessment of Diagnostic Studies (QUADAS-2) was used to assess the risk of bias in technical and methodological studies. Where high-quality published evidence was lacking, we used modified Delphi technique to reach expert consensus. The GRADE system was used to formulate the recommendations. The quality of evidence was low or moderate. We formulated 16 consensus-based recommendations for minimum standards for recording routine and sleep EEG. The recommendations comprise the following aspects: indications, technical standards, recording duration, sleep induction, and provocative methods.

Routine and sleep EEG: Minimum recording standards of the International Federation of Clinical Neurophysiology and the International League Against Epilepsy.

This article provides recommendations on the minimum standards for recording routine ("standard") and sleep electroencephalography (EEG). The joint working group of the International Federation of Clinical Neurophysiology (IFCN) and the International League Against Epilepsy (ILAE) developed the standards according to the methodology suggested for epilepsy-related clinical practice guidelines by the Epilepsy Guidelines Working Group. We reviewed the published evidence using the Preferred Reporting Items for Systematic Review and Meta-Analysis (PRISMA) statement. The quality of evidence for sleep induction methods was assessed by the Grading of Recommendations, Assessment, Development and Evaluations (GRADE) method. A tool for Quality Assessment of Diagnostic Accuracy Studies (QUADAS-2) was used to assess the risk of bias in technical and methodological studies. Where high-quality published evidence was lacking, we used modified Delphi technique to reach expert consensus. The GRADE system was used to formulate the recommendations. The quality of evidence was low or moderate. We formulated 16 consensus-based recommendations for minimum standards for recording routine and sleep EEG. The recommendations comprise the following aspects: indications, technical standards, recording duration, sleep induction, and provocative methods.

A comparison of uni- and multi-variate methods for identifying brain networks activated by cognitive tasks using intracranial EEG.

Cognitive tasks are commonly used to identify brain networks involved in the underlying cognitive process. However, inferring the brain networks from intracranial EEG data presents several challenges related to the sparse spatial sampling of the brain and the high variability of the EEG trace due to concurrent brain processes. In this manuscript, we use a well-known facial emotion recognition task to compare three different ways of analyzing the contrasts between task conditions: permutation cluster tests, machine learning (ML) classifiers, and a searchlight implementation of multivariate pattern analysis (MVPA) for intracranial sparse data recorded from 13 patients undergoing presurgical evaluation for drug-resistant epilepsy. Using all three methods, we aim at highlighting the brain structures with significant contrast between conditions. In the absence of ground truth, we use the scientific literature to validate our results. The comparison of the three methods' results shows moderate agreement, measured by the Jaccard coefficient, between the permutation cluster tests and the machine learning [0.33 and 0.52 for the left (LH) and right (RH) hemispheres], and 0.44 and 0.37 for the LH and RH between the permutation cluster tests and MVPA. The agreement between ML and MVPA is higher: 0.65 for the LH and 0.62 for the RH. To put these results in context, we performed a brief review of the literature and we discuss how each brain structure's involvement in the facial emotion recognition task.

Motor and emotional facial features in parietal lobe seizures: an ictal functional connectivity study using SEEG

Objectives: Parietal lobe epilepsy is one of the rarest types and patients with this form of epilepsy report multiple subjective symptoms during ictal manifestation. Specific facial coupling of emotion and motor symptoms may take various forms, such as pouting and disgust or smiling. We aimed to highlight brain structures and the network involved during ictal grimacing in parietal lobe seizures. Methods: In this study, we report two patients with drug-resistant epilepsy, with seizure onset located in the inferior parietal lobule and a semiology characterized by ictal grimacing. Patients were explored with intracranial electrodes using the stereo-electroencephalographic method. Time-frequency and functional connectivity (a non-linear regression method based on the h² correlation coefficient) signal analyses were performed time-locked to ictal grimace. For both patients, using spectral analysis, we were able to confirm that the bipolar channels, localized at the level of the inferior parietal lobule, were involved in the seizure onset zone, exhibiting a high frequency discharge. Results: The first patient presented with ictal pouting and disgust and the second with smiling/laughter. Connectivity analysis highlighted two different networks responsible for seizure semiology, consisting of grimacing with different emotional expression. The inferior parietal lobule, connected mainly to the anterior insula, dorsal-lateral prefrontal cortex and frontal operculum were responsible for the typical grimace associated with disgust. Furthermore, the inferior parietal lobule, basal temporal structures, superior temporal gyrus, orbitofrontal cortex and temporal pole were involved in smiling and laughter. Significance: It is of great significance for epileptologists to know that the same seizure onset zone in the inferior parietal lobule can generate contrasting facial expressions, smiling/laughter and pouting/disgust, by engaging different epileptogenic networks; the temporo-basal-orbitofrontal and insulo-opercular networks, respectively.

A brain atlas of axonal and synaptic delays based on modelling of cortico-cortical evoked potentials.

Epilepsy presurgical investigation may include focal intracortical single-pulse electrical stimulations with depth electrodes, which induce cortico-cortical evoked potentials at distant sites because of white matter connectivity. Cortico-cortical evoked potentials provide a unique window on functional brain networks because they contain sufficient information to infer dynamical properties of large-scale brain connectivity, such as preferred directionality and propagation latencies. Here, we developed a biologically informed modelling approach to estimate the neural physiological parameters of brain functional networks from the cortico-cortical evoked potentials recorded in a large multicentric database. Specifically, we considered each cortico-cortical evoked potential as the output of a transient stimulus entering the stimulated region, which directly propagated to the recording region. Both regions were modelled as coupled neural mass models, the parameters of which were estimated from the first cortico-cortical evoked potential component, occurring before 80 ms, using dynamic causal modelling and Bayesian model inversion. This methodology was applied to the data of 780 patients with epilepsy from the F-TRACT database, providing a total of 34 354 bipolar stimulations and 774 445 cortico-cortical evoked potentials. The cortical mapping of the local excitatory and inhibitory synaptic time constants and of the axonal conduction delays between cortical regions was obtained at the population level using anatomy-based averaging procedures, based on the Lausanne2008 and the HCP-MMP1 parcellation schemes, containing 130 and 360 parcels, respectively. To rule out brain maturation effects, a separate analysis was performed for older (>15 years) and younger patients (<15 years). In the group of older subjects, we found that the cortico-cortical axonal conduction delays between parcels were globally short (median = 10.2 ms) and only 16% were larger than 20 ms. This was associated to a median velocity of 3.9 m/s. Although a general lengthening of these delays with the distance between the stimulating and recording contacts was observed across the cortex, some regions were less affected by this rule, such as the insula for which almost all efferent and afferent connections were faster than 10 ms. Synaptic time constants were found to be shorter in the sensorimotor, medial occipital and latero-temporal regions, than in other cortical areas. Finally, we found that axonal conduction delays were significantly larger in the group of subjects younger than 15 years, which corroborates that brain maturation increases the speed of brain dynamics. To our knowledge, this study is the first to provide a local estimation of axonal conduction delays and synaptic time constants across the whole human cortex in vivo, based on intracerebral electrophysiological recordings.

A method to assess the default EEG macrostate and its reactivity to stimulation.

OBJECTIVE: The default mode network (DMN) is deactivated by stimulation. We aimed to assess the DMN reactivity impairment by routine EEG recordings in stroke patients with impaired consciousness. METHODS: Binocular light flashes were delivered at 1 Hz in 1-minute epochs, following a 1-minute baseline (PRE). The EEG was decomposed in a series of binary oscillatory macrostates by topographic spectral clustering. The most deactivated macrostate was labeled the default EEG macrostate (DEM). Its reactivity (DER) was quantified as the decrease in DEM occurrence probability during stimulation. A normalized DER index (DERI) was calculated as DER/PRE. The measures were compared between 14 healthy controls and 32 comatose patients under EEG monitoring following an acute stroke. RESULTS: The DEM was mapped to the posterior DMN hubs. In the patients, these DEM source dipoles were 3-4 times less frequent and were associated with an increased theta activity. Even in a reduced 6-channel montage, a DER below 6.26% corresponding to a DERI below 0.25 could discriminate the patients with sensitivity and specificity well above 80%. CONCLUSION: The method detected the DMN impairment in post-stroke coma patients. SIGNIFICANCE: The DEM and its reactivity to stimulation could be useful to monitor the DMN function at bedside.

Development and Validation of the 5-SENSE Score to Predict Focality of the Seizure-Onset Zone as Assessed by Stereoelectroencephalography.

Importance: Stereoelectroencephalography (SEEG) has become the criterion standard in case of inconclusive noninvasive presurgical epilepsy workup. However, up to 40% of patients are subsequently not offered surgery because the seizure-onset zone is less focal than expected or cannot be identified. Objective: To predict focality of the seizure-onset zone in SEEG, the 5-point 5-SENSE score was developed and validated. Design, Setting, and Participants: This was a monocentric cohort study for score development followed by multicenter validation with patient selection intervals between February 2002 to October 2018 and May 2002 to December 2019. The minimum follow-up period was 1 year. Patients with drug-resistant epilepsy undergoing SEEG at the Montreal Neurological Institute were analyzed to identify a focal seizure-onset zone. Selection criteria were 2 or more seizures in electroencephalography and availability of complete neuropsychological and neuroimaging data sets. For validation, patients from 9 epilepsy centers meeting these criteria were included. Analysis took place between May and July 2021. Main Outcomes and Measures: Based on SEEG, patients were grouped as focal and nonfocal seizure-onset zone. Demographic, clinical, electroencephalography, neuroimaging, and neuropsychology data were analyzed, and a multiple logistic regression model for developing a score to predict SEEG focality was created and validated in an independent sample. Results: A total of 128 patients (57 women [44.5%]; median [range] age, 31 [13-58] years) were analyzed for score development and 207 patients (97 women [46.9%]; median [range] age, 32 [16-70] years) were analyzed for validation. The score comprised the following 5 predictive variables: focal lesion on structural magnetic resonance imaging, absence of bilateral independent spikes in scalp electroencephalography, localizing neuropsychological deficit, strongly localizing semiology, and regional ictal scalp electroencephalography onset. The 5-SENSE score had an optimal mean (SD) probability cutoff for identifying a focal seizure-onset zone of 37.6 (3.5). Area under the curve, specificity, and sensitivity were 0.83, 76.3% (95% CI, 66.7-85.8), and 83.3% (95% CI, 72.30-94.1), respectively. Validation showed 76.0% (95% CI, 67.5-84.0) specificity and 52.3% (95% CI, 43.0-61.5) sensitivity. Conclusions and Relevance: High specificity in score development and validation confirms that the 5-SENSE score predicts patients where SEEG is unlikely to identify a focal seizure-onset zone. It is a simple and useful tool for assisting clinicians to reduce unnecessary invasive diagnostic burden on patients and overutilization of limited health care resources.

Imaging the effective networks associated with cortical function through intracranial high-frequency stimulation.

Direct electrical stimulation (DES) is considered to be the gold standard for mapping cortical function. A careful mapping of the eloquent cortex is key to successful resective or ablative surgeries, with a minimal postoperative deficit, for treatment of drug-resistant epilepsy. There is accumulating evidence suggesting that not only local, but also remote activations play an equally important role in evoking clinical effects. By introducing a new intracranial stimulation paradigm and signal analysis methodology allowing to disambiguate EEG responses from stimulation artifacts we highlight the spatial extent of the networks associated with clinical effects. Our study includes 26 patients that underwent stereoelectroencephalographic investigations for drug-resistant epilepsy, having 337 depth electrodes with 4,351 contacts sampling most brain structures. The routine high-frequency electrical stimulation protocol for eloquent cortex mapping was altered in a subtle way, by alternating the polarity of the biphasic pulses in a train, causing the splitting the spectral lines of the artifactual components, exposing the underlying tissue response. By performing a frequency-domain analysis of the EEG responses during DES we were able to capture remote activations and highlight the effect's network. By using standard intersubject averaging and a fine granularity HCP-MMP parcellation, we were able to create local and distant connectivity maps for 614 stimulations evoking specific clinical effects. The clinical value of such maps is not only for a better understanding of the extent of the effects' networks guiding the invasive exploration, but also for understanding the spatial patterns of seizure propagation given the timeline of the seizure semiology.

Network of autoscopic hallucinations elicited by intracerebral stimulations of periventricular nodular heterotopia: An SEEG study.

Periventricular nodular heterotopias (PVNH) are areas of neurons abnormally located in the white matter that might be involved in physiological cortical functions. Autoscopic hallucinations are changes in self-consciousness determined by a mismatch in integration of multiple sensory inputs. Our goal is to highlight the brain network involved in generation of autoscopic hallucination elicited by electrical stimulation of a PVNH in a drug resistant epilepsy patient. Our patient was explored using stereo-electroencephalography with electrodes covering the right posterior temporal PVNH and the adjacent cortex. Direct electrical high frequency stimulation of the PVNH elicited autoscopic hallucinations mainly involving the face and upper trunk. We then used multiple modalities to determine brain connectivity: single pulse electrical stimulation of the PVNH and stimulation-evoked potentials were used to highlight resting state effective connectivity. High-frequency stimulation using alternating polarity pulses enabled us to identify the network involved, time-locked to the clinical effect and to map symptom-related effective connectivity. Functional connectivity using a non-linear regression method was used to determine dependencies between different cortical regions following the stimulation. Finally, structural connectivity was highlighted using deterministic fiber tracking. Multi-modal connectivity analysis identified a network involving the PVNH, occipital and temporal neocortex, fusiform gyrus and parietal cortex.

Extracting seizure onset from surface EEG with independent component analysis: Insights from simultaneous scalp and intracerebral EEG.

The success of stereoelectroencephalographic (SEEG) investigations depends crucially on the hypotheses on the putative location of the seizure onset zone. This information is derived from non-invasive data either based on visual analysis or advanced source localization algorithms. While source localization applied to interictal spikes recorded on scalp is the classical method, it does not provide unequivocal information regarding the seizure onset zone. Raw ictal activity contains a mixture of signals originating from several regions of the brain as well as EMG artifacts, hampering direct input to the source localization algorithms. We therefore introduce a methodology that disentangles the various sources contributing to the scalp ictal activity using independent component analysis and uses equivalent current dipole localization as putative locus of ictal sources. We validated the results of our analysis pipeline by performing long-term simultaneous scalp - intracerebral (SEEG) recordings in 14 patients and analyzing the wavelet coherence between the independent component encoding the ictal discharge and the SEEG signals in 8 patients passing the inclusion criteria. Our results show that invasively recorded ictal onset patterns, including low-voltage fast activity, can be captured by the independent component analysis of scalp EEG. The visibility of the ictal activity strongly depends on the depth of the sources. The equivalent current dipole localization can point to the seizure onset zone (SOZ) with an accuracy that can be as high as 10 mm for superficially located sources, that gradually decreases for deeper seizure generators, averaging at 47 mm in the 8 analyzed patients. Independent component analysis is therefore shown to have a promising SOZ localizing value, indicating whether the seizure onset zone is neocortical, and its approximate location, or located in mesial structures. That may contribute to a better crafting of the hypotheses used as basis of the stereo-EEG implantations.

SEEG re-exploration in a patient with complex frontal epilepsy with rapid perisylvian propagation and mixed "startle - reflex" seizures.

The SEEG International Course, organised in 2017, focused on the investigation and surgery of insulo-perisylvian epilepsies. We present one representative complex case that was discussed. The patient had seizures displaying startle/reflex components. He was MRI negative, while other non-invasive investigations offered only partially concordant data. Initial SEEG exploration resulted in an incomplete definition of the epileptogenic zone. A second SEEG followed, which led to a thorough assessment of the seizure onset zone and the epileptic network, localised to the lateral inferior premotor cortex, explaining the incongruent data obtained beforehand. This was the basis of a tailored resection with a favourable outcome. The patient has been seizure-free for five years without any motor nor cognitive deficits, but with pharmacodependence to one AED. The electroclinical reasoning is presented, accompanied by relevant commentaries and recommendations from the tutors [Published with video sequences].

Accuracy and Safety of Customized Stereotactic Fixtures for Stereoelectroencephalography in Pediatric Patients.

Stereoelectroencephalography (SEEG) in children with intractable epilepsy presents particular challenges. Their thin and partially ossified cranium, specifically in the temporal area, is prone to fracture while attaching stereotactic systems to the head or stabilizing the head in robot's field of action. Postponing SEEG in this special population of patients can have serious consequences, reducing their chances of becoming seizure-free and impacting their social and cognitive development. This study demonstrates the safety and accuracy offered by a frameless personalized 3D printed stereotactic implantation system for SEEG investigations in children under 4 years of age. SEEG was carried out in a 3-year-old patient with drug-resistant focal epilepsy, based on a right temporal-perisylvian epileptogenic zone hypothesis. Fifteen intracerebral electrodes were placed using a StarFix patient-customized stereotactic fixture. The median lateral entry point localization error of the electrodes was 0.90 mm, median lateral target point localization error was 1.86 mm, median target depth error was 0.83 mm, and median target point localization error was 1.96 mm. There were no perioperative complications. SEEG data led to a tailored right temporal-insular-opercular resection, with resulting seizure freedom (Engel IA). In conclusion, patient-customized stereotactic fixtures are a safe and accurate option for SEEG exploration in young children.

Low-grade epilepsy-associated tumour management with or without presurgical evaluation: a multicentre, retrospective, observational study of postsurgical epilepsy outcome.

Low-grade epilepsy-associated neuroepithelial tumours (LEATs) encompass the broad spectrum of tumours associated with epilepsy. Since the postsurgical seizure outcome in LEATs is favourable, it is speculated that epileptological presurgical evaluation (EPE) might not be required for patients with LEATs. A multicentre study involving referring epilepsy and neurosurgery centres was performed, aimed at evaluating postsurgical epilepsy outcome in patients with LEATs, with and without EPE, including long-term video-EEG monitoring (vEEGM). In total, 149 surgically treated patients were enrolled (age: 31±14 years; age at surgery: 26.4±13.1 years; males; 55.7%) with histopathological confirmation of LEATs and follow-up of more than six months. All patients had undergone standard assessment: clinical, routine EEG and brain MRI. In addition to vEEGM, EPE included other additional investigations. Epileptologists did not assess patients treated in neurosurgical centres. The EPE was performed in 51% of patients. Histopathological diagnosis revealed ganglioglioma in 43.6%, DNET in 32.9%, pilocytic astrocytoma in 17.4%, and others in 6.1% of patients. The majority of patients were seizure-free (ILAE epilepsy surgery outcome Class 1; 71.1%). The median follow-up period was 36 months. Patients who were rendered seizure-free were younger (mean age: 24.2±12.2) than those who were not seizure-free (31.8±14.0) (p=0.001). No difference was identified between evaluated and non-evaluated patients with respect to seizure freedom (p=0.45). EPE patients had a longer epilepsy duration (median: 10 years) and a higher proportion of drug resistance (73.6%) compared to non-evaluated patients (median: two years; 26.4%) (p<0.001). Based on a significant difference in major clinical variables, that may well affect postoperative results, the similar postsurgical seizure outcome in groups with and without EPE observed in our study should be considered with caution, and conclusions as to whether there is value in formal presurgical evaluation in LEAT patients cannot be drawn. Our data strongly encourage the clear need for continued discussion around such patients at epilepsy management conferences.

Cingulate cortex function and multi-modal connectivity mapped using intracranial stimulation.

The cingulate cortex is part of the limbic system. Its function and connectivity are organized in a rostro-caudal and ventral-dorsal manner which was addressed by various other studies using rather coarse cortical parcellations. In this study, we aim at describing its function and connectivity using invasive recordings from patients explored for focal drug-resistant epilepsy. We included patients that underwent stereo-electroencephalographic recordings using intracranial electrodes in the University Emergency Hospital Bucharest between 2012 and 2019. We reviewed all high frequency stimulations (50 â€‹Hz) performed for functional mapping of the cingulate cortex. We used two methods to characterize brain connectivity. Effective connectivity was inferred based on the analysis of cortico-cortical potentials (CCEPs) evoked by single pulse electrical stimulation (SPES) (15 â€‹s inter-pulse interval). Functional connectivity was estimated using the non-linear regression method applied to 60 â€‹s spontaneous electrical brain signal intervals. The effective (stimulation-evoked) and functional (non-evoked) connectivity analyses highlight brain networks in a different way. While non-evoked connectivity evidences areas having related activity, often in close proximity to each other, evoked connectivity highlights spatially extended networks. To highlight in a comprehensive way the cingulate cortex's network, we have performed a bi-modal connectivity analysis that combines the resting-state broadband h2 non-linear correlation with cortico-cortical evoked potentials. We co-registered the patient's anatomy with the fsaverage FreeSurfer template to perform the automatic labeling based on HCP-MMP parcellation. At a group level, connectivity was estimated by averaging responses over stimulated/recorded or recorded sites in each pair of parcels. Finally, for multiple regions that evoked a clinical response during high frequency stimulation, we combined the connectivity of individual pairs using maximum intensity projection. Connectivity was assessed by applying SPES on 2094 contact pairs and recording CCEPs on 3580 contacts out of 8582 contacts of 660 electrodes implanted in 47 patients. Clinical responses elicited by high frequency stimulations in 107 sites (pairs of contacts) located in the cingulate cortex were divided in 10 groups: affective, motor behavior, motor elementary, versive, speech, vestibular, autonomic, somatosensory, visual and changes in body perception. Anterior cingulate cortex was shown to be connected to the mesial temporal, orbitofrontal and prefrontal cortex. In the middle cingulate cortex, we located affective, motor behavior in the anterior region, and elementary motor and somatosensory in the posterior part. This region is connected to the prefrontal, premotor and primary motor network. Finally, the posterior cingulate was shown to be connected with the visual areas, mesial and lateral parietal and temporal cortex.