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Objective: We evaluated changes in cognitive domains after neurosurgical lesioning of cortical sites with significant high‐gamma power modulations (HGM) during a visual naming task, although these sites were found language‐negative on standard‐of‐care electrical stimulation mapping (ESM). Methods: In drug‐resistant epilepsy patients who underwent resection/ablation after stereo‐electroencephalography (SEEG), we computed reliable change indices (RCIs) from a battery of presurgical and 1‐year postsurgical neuropsychological assessments. We modeled RCIs as a function of lesioning even one HGM language site, number of HGM language sites lesioned, and the magnitude of naming‐related HGM. The analyses were adjusted for 1‐year seizure freedom, operated hemispheres, and the volumes of surgical lesions. Results: In 37 patients with 4455 SEEG electrode contacts (1839 and 2616 contacts in right and left hemispheres, respectively), no ESM language sites were lesioned. Patients with lesioning of even one HGM language site showed significantly lower RCIs for Peabody Picture Vocabulary Test (PPVT), working memory, and verbal learning immediate (VLI) scores. RCI declines with higher number of HGM language sites lesioned were seen in PPVT (slope [β] = −.10), working memory (β = −.10), VLI (β = −.14), and letter–word identification (LWI; β = −.14). No neuropsychological domains improved after lesioning of HGM language sites. Significant effects of the HGM magnitude at lesioned sites were seen on working memory (β = −.31), story memory immediate (β = −.27), verbal learning recognition (β = −.18), LWI (β = −.16), spelling (β = −.49), and passage comprehension (β = −.33). Because working memory was significantly affected in all three analyses, patients with maximal working memory decline were examined post hoc, revealing that all such patients had HGM naming sites lesioned in the posterior quadrants of either hemisphere. Significance: HGM language mapping should be used as an adjunct to ESM in clinical practice and may help counsel patients/families about postsurgical cognitive deficits. [ABSTRACT FROM AUTHOR]

Epileptic seizures recorded with stereo-EEG can take a fraction of a second or several seconds to propagate from one region to another. What explains such propagation patterns? We combine tractography and stereo-EEG to determine the relationship between seizure propagation and the white matter architecture and to describe seizure propagation mechanisms. Patient-specific spatiotemporal seizure propagation maps were combined with tractography from diffusion imaging of matched subjects from the Human Connectome Project. The onset of seizure activity was marked on a channel-by-channel basis by two board-certified neurologists for all channels involved in the seizure. We measured the tract connectivity (number of tracts) between regions-of-interest pairs among the seizure onset zone, regions of seizure spread and non-involved regions. We also investigated how tract-connected the seizure onset zone is to regions of early seizure spread compared with regions of late spread. Comparisons were made after correcting for differences in distance. Sixty-nine seizures were marked across 26 patients with drug-resistant epilepsy; 11 were seizure free after surgery (Engel IA) and 15 were not (Engel IB–Engel IV). The seizure onset zone was more tract-connected to regions of seizure spread than to non-involved regions (P < 0.0001); however, regions of seizure spread were not differentially tract-connected to other regions of seizure spread compared with non-involved regions. In seizure-free patients only, regions of seizure spread were more tract-connected to the seizure onset zone than to other regions of spread (P < 0.0001). Over the temporal evolution of a seizure, the seizure onset zone was significantly more tract-connected to regions of early spread compared with regions of late spread in seizure-free patients only (P < 0.0001). By integrating information on structure, we demonstrate that seizure propagation is likely to be mediated by white matter tracts. The pattern of connectivity between seizure onset zone, regions of spread and non-involved regions demonstrates that the onset zone might be largely responsible for seizures propagating throughout the brain, rather than seizures propagating to intermediate points, from which further propagation takes place. Our findings also suggest that seizure propagation over seconds might be the result of a continuous bombardment of action potentials from the seizure onset zone to regions of spread. In non-seizure-free patients, the paucity of tracts from the presumed seizure onset zone to regions of spread suggests that the onset zone was missed. Fully understanding the structure–propagation relationship might eventually provide insight into selecting the correct targets for epilepsy surgery. [ABSTRACT FROM AUTHOR]

• Our multimodal quantitative method unveils directional dynamics of epileptic network during interictal to ictal transition. • Epileptogenic zone exhibits maximum outflow during preictal, and at seizure onset. • Regions that are hypoperfused during seizures exhibit maximum outflow during ictal evolution and can serve as a control network. Ictal Single Photon Emission Computed Tomography (SPECT) and stereo-electroencephalography (SEEG) are diagnostic techniques used for the management of patients with drug-resistant focal epilepsies. While hyperperfusion patterns in ictal SPECT studies reveal seizure onset and propagation pathways, the role of ictal hypoperfusion remains poorly understood. The goal of this study was to systematically characterize the spatio-temporal information flow dynamics between differently perfused brain regions using stereo-EEG recordings. We identified seizure-free patients after resective epilepsy surgery who had prior ictal SPECT and SEEG investigations. We estimated directional connectivity between the epileptogenic-zone (EZ), non-resected areas of hyperperfusion, hypoperfusion, and baseline perfusion during the interictal, preictal, ictal, and postictal periods. Compared to the background, we noted significant information flow (1) during the preictal period from the EZ to the baseline and hyperperfused regions, (2) during the ictal onset from the EZ to all three regions, and (3) during the period of seizure evolution from the area of hypoperfusion to all three regions. Hypoperfused brain regions were found to indirectly interact with the EZ during the ictal period. Our unique study, combining intracranial electrophysiology and perfusion imaging, presents compelling evidence of dynamic changes in directional connectivity between brain regions during the transition from interictal to ictal states. [ABSTRACT FROM AUTHOR]

The success of deep brain stimulation (DBS) for treating Parkinsons disease has led to its application to several other disorders, including treatment-resistant depression. Results with DBS for treatment-resistant depression have been heterogeneous, with inconsistencies largely driven by incomplete understanding of the brain networks regulating mood, especially on an individual basis. We report results from the first subject treated with DBS for treatment-resistant depression using an approach that incorporates intracranial recordings to personalize understanding of network behavior and its response to stimulation. These recordings enabled calculation of individually optimized DBS stimulation parameters using a novel inverse solution approach. In the ensuing double-blind, randomized phase incorporating these bespoke parameter sets, DBS led to remission of symptoms and dramatic improvement in quality of life. Results from this initial case demonstrate the feasibility of this personalized platform, which may be used to improve surgical neuromodulation for a vast array of neurologic and psychiatric disorders.

Abstract Objective Cortical stimulation is an important component of stereoelectroencephalography (SEEG). Despite this, there is currently no standardized approach and significant heterogeneity in the literature regarding cortical stimulation practices. Via an international survey of SEEG clinicians, we sought to examine the spectrum of cortical stimulation practices to reveal areas of consensus and variability. Methods A 68‐item questionnaire was developed to understand cortical stimulation practices including neurostimulation parameters, interpretation of epileptogenicity, functional and cognitive assessment and subsequent surgical decisions. Multiple recruitment pathways were pursued, with the questionnaire distributed directly to 183 clinicians. Results Responses were received from 56 clinicians across 17 countries with experience ranging from 2 to 60 years (M = 10.73, SD = 9.44). Neurostimulation parameters varied considerably, with maximum current ranging from 3 to 10 mA (M = 5.33, SD = 2.29) for 1 Hz and from 2 to 15 mA (M = 6.54, SD = 3.68) for 50 Hz stimulation. Charge density ranged from 8 to 200 μC/cm2, with up to 43% of responders utilizing charge densities higher than recommended upper safety limits, i.e. 55 μC/cm2. North American responders reported statistically significant higher maximum current (P

Language lateralization in patients with focal epilepsy frequently diverges from the left-lateralized pattern that prevails in healthy right-handed people, but the mechanistic explanations are still a matter of debate. Here, we debate the complex interaction between focal epilepsy, language lateralization, and functional neuroimaging techniques by introducing the case of a right-handed patient with unaware focal seizures preceded by aphasia, in whom video-EEG and PET examination suggested the presence of focal cortical dysplasia in the right superior temporal gyrus, despite a normal structural MRI. The functional MRI for language was inconclusive, and the neuropsychological evaluation showed mild deficits in language functions. A bilateral stereo-EEG was proposed confirming the right superior temporal gyrus origin of seizures, revealing how ictal aphasia emerged only once seizures propagated to the left superior temporal gyrus and confirming, by cortical mapping, the left lateralization of the posterior language region. Stereo-EEG-guided radiofrequency thermocoagulations of the (right) focal cortical dysplasia not only reduced seizure frequency but led to the normalization of the neuropsychological assessment and the "restoring" of a classical left-lateralized functional MRI pattern of language. This representative case demonstrates that epileptiform activity in the superior temporal gyrus can interfere with the functioning of the contralateral homologous cortex and its associated network. In the case of presurgical evaluation in patients with epilepsy, this interference effect must be carefully taken into consideration. The multimodal language lateralization assessment reported for this patient further suggests the sensitivity of different explorations to this interference effect. Finally, the neuropsychological and functional MRI changes after thermocoagulations provide unique cues on the network pathophysiology of focal cortical dysplasia and the role of diverse techniques in indexing language lateralization in complex scenarios. [ABSTRACT FROM AUTHOR]

• A new measure called connectivity high-frequency epileptogenicity index (cHFEI) is developed in order to localize the epileptogenic zone (EZ). • cHFEI employs directed connectivity and high-frequency oscillations (HFOs) to improve the ability of EZ localization. • cHFEI outperforms some existing methods in the estimation of EZ. Precise localization of the epileptogenic zone (EZ) is essential for epilepsy surgery. Existing methods often fail to detect slow onset patterns or similar neural activities presented in the recorded signals. To address this issue, we propose a new measure to quantify epileptogenicity, i.e., the connectivity high-frequency epileptogenicity index (cHFEI). The cHFEI method combines directed connectivity and high-frequency oscillations (HFOs) to measure the epileptogenicity of regions involved in a brain network. By applying this method to stereoelectroencephalography (SEEG) recordings of 49 seizures in 20 patients, we calculated the accuracy, sensitivity, and precision with a visually identified epileptogenic zone as a reference. The performance was evaluated by the confusion matrix and the area under the receiver operating characteristic (ROC) curve. Epileptic network estimation based on cHFEI successfully distinguished brain regions involved in seizure onset from the propagation network. Moreover, cHFEI outperformed other existing detection methods in the estimation of EZs in all patients, with an average area under the ROC curve of 0.88 and an accuracy of 0.85. cHFEI can characterize EZ in a robust manner despite various seizure onset patterns and has potential application in epilepsy therapy. [ABSTRACT FROM AUTHOR]

Objective: Cortical stimulation is an important component of stereoelectroencephalography (SEEG). Despite this, there is currently no standardized approach and significant heterogeneity in the literature regarding cortical stimulation practices. Via an international survey of SEEG clinicians, we sought to examine the spectrum of cortical stimulation practices to reveal areas of consensus and variability. Methods: A 68‐item questionnaire was developed to understand cortical stimulation practices including neurostimulation parameters, interpretation of epileptogenicity, functional and cognitive assessment and subsequent surgical decisions. Multiple recruitment pathways were pursued, with the questionnaire distributed directly to 183 clinicians. Results: Responses were received from 56 clinicians across 17 countries with experience ranging from 2 to 60 years (M = 10.73, SD = 9.44). Neurostimulation parameters varied considerably, with maximum current ranging from 3 to 10 mA (M = 5.33, SD = 2.29) for 1 Hz and from 2 to 15 mA (M = 6.54, SD = 3.68) for 50 Hz stimulation. Charge density ranged from 8 to 200 μC/cm2, with up to 43% of responders utilizing charge densities higher than recommended upper safety limits, i.e. 55 μC/cm2. North American responders reported statistically significant higher maximum current (P < 0.001) for 1 Hz stimulation and lower pulse width for 1 and 50 Hz stimulation (P = 0.008, P < 0.001, respectively) compared to European responders. All clinicians evaluated language, speech, and motor function during cortical stimulation; in contrast, 42% assessed visuospatial or visual function, 29% memory, and 13% executive function. Striking differences were reported in approaches to assessment, classification of positive sites, and surgical decisions guided by cortical stimulation. Patterns of consistency were observed for interpretation of the localizing capacity of stimulated electroclinical seizures and auras, with habitual electroclinical seizures induced by 1 Hz stimulation considered the most localizing. Significance: SEEG cortical stimulation practices differed vastly across clinicians internationally, highlighting the need for consensus‐based clinical guidelines. In particular, an internationally standardized approach to assessment, classification, and functional prognostication will provide a common clinical and research framework for optimizing outcomes for people with drug‐resistant epilepsy. [ABSTRACT FROM AUTHOR]

ObjectiveIntracranial electroencephalography (ICEEG) recordings are performed for seizure localization in medically refractory epilepsy. Signal quantifications such as frequency power can be projected as heatmaps on personalized three-dimensional (3D) reconstructed cortical surfaces to distill these complex recordings into intuitive cinematic visualizations. However, simultaneously reconciling deep recording locations and reliably tracking evolving ictal patterns remain significant challenges.MethodsWe fused oblique magnetic resonance imaging (MRI) slices along depth probe trajectories with cortical surface reconstructions and projected dynamic heatmaps using a simple mathematical metric of epileptiform activity (line-length). This omni-planar and surface casting of epileptiform activity approach (OPSCEA) thus illustrated seizure onset and spread among both deep and superficial locations simultaneously with minimal need for signal processing supervision. We utilized the approach on 41 patients at our center implanted with grid, strip, and/or depth electrodes for localizing medically refractory seizures. Peri-ictal data were converted into OPSCEA videos with multiple 3D brain views illustrating all electrode locations. Five people of varying expertise in epilepsy (medical student through epilepsy attending level) attempted to localize the seizure-onset zones.ResultsWe retrospectively compared this approach with the original ICEEG study reports for validation. Accuracy ranged from 73.2% to 97.6% for complete or overlapping onset lobe(s), respectively, and ~56.1% to 95.1% for the specific focus (or foci). Higher answer certainty for a given case predicted better accuracy, and scorers had similar accuracy across different training levels.SignificanceIn an era of increasing stereo-EEG use, cinematic visualizations fusing omni-planar and surface functional projections appear to provide a useful adjunct for interpreting complex intracranial recordings and subsequent surgery planning.

Language lateralization in patients with focal epilepsy frequently diverges from the left-lateralized pattern that prevails in healthy right-handed people, but the mechanistic explanations are still a matter of debate. Here, we debate the complex interaction between focal epilepsy, language lateralization, and functional neuroimaging techniques by introducing the case of a right-handed patient with unaware focal seizures preceded by aphasia, in whom video-EEG and PET examination suggested the presence of focal cortical dysplasia in the right superior temporal gyrus, despite a normal structural MRI. The functional MRI for language was inconclusive, and the neuropsychological evaluation showed mild deficits in language functions. A bilateral stereo-EEG was proposed confirming the right superior temporal gyrus origin of seizures, revealing how ictal aphasia emerged only once seizures propagated to the left superior temporal gyrus and confirming, by cortical mapping, the left lateralization of the posterior language region. Stereo-EEG-guided radiofrequency thermocoagulations of the (right) focal cortical dysplasia not only reduced seizure frequency but led to the normalization of the neuropsychological assessment and the “restoring” of a classical left-lateralized functional MRI pattern of language. This representative case demonstrates that epileptiform activity in the superior temporal gyrus can interfere with the functioning of the contralateral homologous cortex and its associated network. In the case of presurgical evaluation in patients with epilepsy, this interference effect must be carefully taken into consideration. The multimodal language lateralization assessment reported for this patient further suggests the sensitivity of different explorations to this interference effect. Finally, the neuropsychological and functional MRI changes after thermocoagulations provide unique cues on the network pathophysiology of focal cortical dysplasia and the role of diverse techniques in indexing language lateralization in complex scenarios.

• Ictal phase-amplitude coupling (PAC) between high-frequency and low-frequency activity can be used as a preoperative biomarker of focal cortical dysplasia (FCD) subtypes. • Ictal PAC was significantly higher in patients with FCD type II compared to type I, only on the electrodes of the seizure-onset zone (SOZ). • Ictal PAC applied to SOZ-electrodes during stereo-EEG offers a high predictive value of FCD histopathology. To evaluate whether ictal phase-amplitude coupling (PAC) between high-frequency activity and low-frequency activity could be used as a preoperative biomarker of Focal Cortical Dysplasia (FCD) subtypes. We hypothesize that FCD seizures present unique PAC characteristics that may be linked to their specific histopathological features. We retrospectively examined 12 children with FCD and refractory epilepsy who underwent successful epilepsy surgery. We identified ictal onsets recorded with stereo-EEG. We estimated the strength of PAC between low-frequencies and high-frequencies for each seizure by means of modulation index. Generalized mixed effect models and receiver operating characteristic (ROC) curve analysis were used to test the association between ictal PAC and FCD subtypes. Ictal PAC was significantly higher in patients with FCD type II compared to type I, only on SOZ-electrodes (p < 0.005). No differences in ictal PAC were found on non-SOZ electrodes. Pre-ictal PAC registered on SOZ electrodes predicted FCD histopathology with a classification accuracy > 0.9 (p < 0.05). The correlations between histopathology and neurophysiology provide evidence for the contribution of ictal PAC as a preoperative biomarker of FCD subtypes. Developed into a proper clinical application, such a technique may help improve clinical management and facilitate the prediction of surgical outcome in patients with FCD undergoing stereo-EEG monitoring. [ABSTRACT FROM AUTHOR]

IInvestigating 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 visualmemory 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. [ABSTRACT FROM AUTHOR]

Background. Surgical treatment has shown its effectiveness for patients with drug-resistant focal epilepsy: resection or disconnection of the epileptogenic zone leads to relief from epileptic seizures. However, in some cases non-invasive examination may not be sufficient for localization of epileptogenic zone boundaries. Hence, such patients undergo invasive encephalography (EEG) to clarify zone location accounting for seizure development.Objective: to evaluate effectiveness of invasive stereo-EEG in the diagnostics of drug-resistant focal epilepsy.Material and methods. The data collected from 65 patients who underwent stereo-EEG during pre-surgical examination for pharmacoresistant focal epilepsy were retrospectively analyzed within the period of 2016–2019. According to the results of magnetic resonance imaging (MRI), 34 patients had MRI-negative forms of epilepsy, and 31 patients had MRI-positive forms with multiple structural changes in the brain or discrepancies between electro-clinical data and MRI findings.Results. Based on the information obtained by stereo-EEG, 49 patients (75.4%) underwent resection operations. In 16 (24.6%) cases surgical treatment was not carried out due to detected bilateral epileptogenic zone, the lack of convincing data on its location or detecting an epileptogenic zone in a functionally significant region. In 44 operated patients, the follow-up comprised more than 12 months; it was not possible to contact 5 patients. Engel outcomes: I class – 27 (61.3%) patients, II class – 7 (15.9%), III class – 4 (9.1%), IV class – 6 (13.6%). As a result of stereo-EEG, hemorrhagic complications developed in 2 (3.1%) patients: epidural hematoma in 1 case (1.5%), and intracerebral hematoma in 1 case (1.5%). No persistent neurological deficit was noted during continued monitoring.Conclusion. The method of stereo-EEG is effective for determining the epileptogenic zone boundaries in patients with drug- resistant focal epilepsy.

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.

Background: Cortico-cortical evoked potentials (CCEPs) recorded by stereo-electroencephalography (SEEG) are a valuable tool to investigate brain reactivity and effective connectivity. However, invasive recordings are spatially sparse since they depend on clinical needs. This sparsity hampers systematic comparisons across-subjects, the detection of the whole-brain effects of intracortical stimulation, as well as their relationships to the EEG responses evoked by non-invasive stimuli. Objective: To demonstrate that CCEPs recorded by high-density electroencephalography (hd-EEG) provide additional information with respect SEEG alone and to provide an open, curated dataset to allow for further exploration of their potential. Methods: The dataset encompasses SEEG and hd-EEG recordings simultaneously acquired during Single Pulse Electrical Stimulation (SPES) in drug-resistant epileptic patients (N = 36) in whom stimulations were delivered with different physical, geometrical, and topological parameters. Differences in CCEPs were assessed by amplitude, latency, and spectral measures. Results: While invasively and non-invasively recorded CCEPs were generally correlated, differences in pulse duration, angle and stimulated cortical area were better captured by hd-EEG. Further, intracranial stimulation evoked site-specific hd-EEG responses that reproduced the spectral features of EEG responses to transcranial magnetic stimulation (TMS). Notably, SPES, albeit unperceived by subjects, elicited scalp responses that were up to one order of magnitude larger than the responses typically evoked by sensory stimulation in awake humans. Conclusions: CCEPs can be simultaneously recorded with SEEG and hd-EEG and the latter provides a reliable descriptor of the effects of SPES as well as a common reference to compare the whole-brain effects of intracortical stimulation to those of non-invasive transcranial or sensory stimulations in humans.

• Estimates of meaningful ASM reduction or discontinuation are uncertain following epilepsy surgery. • Half of patients undergoing resection can expect ASM reduction, though only a tenth can expect to discontinue ASMs completely. • Less than a third of patients undergoing neuromodulation can expect ASM reduction. • ASM reduction decreases over long-term follow-up, which is especially notable in patients undergoing neuromodulation. • If reduction is not seen early, it likely does not occur later during long-term follow-up. Many patients pursue epilepsy surgery with the hope of reducing or stopping anti-seizure medications (ASMs), in addition to reducing their seizure frequency and severity. While ASM decrease is primarily driven by surgical outcomes and patient preferences, preoperative estimates of meaningful ASM reduction or discontinuation are uncertain, especially when accounting for the various forking paths possible following intracranial EEG (iEEG), including resection, neuromodulation, or even the absence of further surgery. Here, we characterize in detail the ASM reduction in a large cohort of patients who underwent iEEG, facilitating proactive, early counseling for a complicated cohort considering surgical treatment. We identified a multi-institutional cohort of patients who underwent iEEG between 2001 and 2022, with a minimum of two years follow-up. The total number of ASMs prescribed immediately prior to surgery, choice of investigation modality, and subsequent surgical treatment were extracted for each patient. Primary endpoints included decreases in ASM counts from preoperative baseline to various follow-up intervals. A total of 284 patients were followed for a median of 6.0 (range 2,22) years after iEEG surgery. Patients undergoing resection saw an average reduction of ∼ 0.5 ASMs. Patients undergoing neuromodulation saw no decrease and trended towards requiring increased ASM usage during long-term follow-up. Only patients undergoing resection were likely to completely discontinue all ASMs, with an increasing probability over time approaching ∼ 10 %. Up to half of resection patients saw ASM decreases, which was largely stable during long-term follow-up, whereas only a quarter of neuromodulation patients saw a reduction, though their ASM reduction decreased over time. With the increasing use of stereotactic EEG and non-curative neuromodulation procedures, realistic estimates of ASM reduction and discontinuation should be considered preoperatively. Almost half of patients undergoing resective surgery can expect to reduce their ASMs, though only a tenth can expect to discontinue ASMs completely. If reduction is not seen early, it likely does not occur later during long-term follow-up. Less than a third of patients undergoing neuromodulation can expect ASM reduction, and instead most may require increased usage during long-term follow-up. [ABSTRACT FROM AUTHOR]

Scalp EEG is one of the main tools in the clinical evaluation of epilepsy. In some cases intracranial Interictal Epileptiform Discharges (IEDs) are not visible from the scalp. Recent studies have shown the feasibility of revealing them in the EEG if their timings are extracted from simultaneous intracranial recordings, but their potential for the localization of the epileptogenic zone is not yet well defined. We recorded simultaneous high-density EEG (HD-EEG) and stereo-electroencephalography (SEEG) during interictal periods in 8 patients affected by drug-resistant focal epilepsy. We identified IEDs in the SEEG and systematically analyzed the time-locked signals on the EEG by means of evoked potentials, topographical analysis and Electrical Source Imaging (ESI). The dataset has been standardized and is being publicly shared. Our results showed that IEDs that were not clearly visible at single-trials could be uncovered by averaging, in line with previous reports. They also showed that their topographical voltage distributions matched the position of the SEEG electrode where IEDs had been identified, and that ESI techniques can reconstruct it with an accuracy of ∼2 cm. Finally, the present dataset provides a reference to test the accuracy of different methods and parameters. Our study is the first to systematically compare ESI methods on simultaneously recorded IEDs, and to share a public resource with in-vivo data for their evaluation. Simultaneous HD-EEG and SEEG recordings can unveil hidden IEDs whose origins can be reconstructed using topographical and ESI analyses, but results depend on the selected methods and parameters. • Simultaneous HD-EEG and SEEG recordings allow revealing hidden scalp IEDs. • The scalp topographical voltage distributions are indicative of their putative origin. • ESI can reconstruct their putative origin with an accuracy of ∼ 2 cm. • A comparative analysis of the ESI methods and their parameters has been performed. • The dataset is being shared, providing a common ground to develop and compare methods. [ABSTRACT FROM AUTHOR]

Radiofrequency thermocoagulation (RF-TC) is a wide-used procedure for drug-resistant epilepsy. The technique is considered safe with an overall risk of 1.1% of permanent complications, mainly focal neurological deficits. We report the case of a patient with drug-resistant epilepsy who complained of immediate seizure worsening and an unexpected event seven months following RF-TC.A 35-year-old male with drug-resistant epilepsy from the age of 18 years underwent stereoelectroencephalography (SEEG) implantation for a right peri-silvian polymicrogyria. He was excluded from surgery due to extent of the epileptogenic zone and the risk of visual field deficits. RF-TC was attempted to ablate the most epileptogenic zone identified by SEEG. After RF-TC, the patient reported an increase in seizure severity/frequency and experienced episodes of postictal psychosis. Off-label cannabidiol treatment led to improved seizure control and resolution of postictal psychosis.Patients with polymicrogyria (PwP) may present with a disruption of normal anatomy and the co-existence between epileptogenic zone and eloquent cortex within the malformation.RF-TC should be considered in PwP when they are excluded from surgery for prognostic and palliative purposes. However, given the complex interplay between pathological and electrophysiological networks in these patients, the remote possibility of clinical exacerbation after RF-TC should also be taken into account.

Objective: Seizures are known to occur with diurnal and other rhythms. To gain insight into the neurophysiology of periodicity of seizures, we tested the hypothesis that intracranial high-frequency oscillations (HFOs) show diurnal rhythms and sleep-wake cycle variation. We further hypothesized that HFOs have different rhythms within and outside the seizure-onset zone (SOZ).Methods: In drug-resistant epilepsy patients undergoing stereotactic-EEG (SEEG) monitoring to localize SOZ, we analyzed the number of 50-200 Hz HFOs/channel/minute (HFO density) through a 24-hour period. The distribution of HFO density during the 24-hour period as a function of the clock time was analyzed with cosinor model, and for non-uniformity with the sleep-wake cycle.Results: HFO density showed a significant diurnal rhythm overall and both within and outside SOZ. This diurnal rhythm of HFO density showed significantly lower amplitude and longer acrophase within SOZ compared to outside SOZ. The peaks of difference in HFO density within and outside SOZ preceded the seizures by approximately 4 hours. The difference in HFO density within and outside SOZ also showed a non-uniform distribution as a function of sleep-wake cycle, with peaks at first hour after arousal and ±2 hours around sleep onset.Conclusions: Our study shows that the diurnal rhythm of intracranial HFOs is more robust outside the SOZ. This suggests cortical tissue within SOZ generates HFOs relatively more uniformly throughout the day with attenuation of expected diurnal rhythm. The difference in HFO density within and outside SOZ also showed non-uniform distribution according to clock times and the sleep-wake cycle, which can be a potential biomarker for preferential times of pathological cortical excitability. A temporal correlation with seizure occurrence further substantiates this hypothesis. [ABSTRACT FROM AUTHOR]

Objective: Epileptic spasms (ES) are common in tuberous sclerosis complex (TSC). However, the underlying network alterations and relationship with epileptogenic tubers are poorly understood. We examined interictal functional connectivity (FC) using stereo‐electroencephalography (SEEG) in patients with TSC to investigate the relationship between tubers, epileptogenicity, and ES. Methods: We analyzed 18 patients with TSC who underwent SEEG (mean age = 11.5 years). The dominant tuber (DT) was defined as the most epileptogenic tuber using the epileptogenicity index. Epileptogenic zone (EZ) organization was quantitatively separated into focal (isolated DT) and complex (all other patterns). Using a 20‐min interictal recording, FC was estimated with nonlinear regression, h2. We calculated (1) intrazone FC within all sampled tubers and normal‐appearing cortical zones, respectively; and (2) interzone FC involving connections between DT, other tubers, and normal cortex. The relationship between FC and (1) presence of ES as a current seizure type at the time of SEEG, (2) EZ organization, and (3) epileptogenicity was analyzed using a mixed generalized linear model. Spike rate and distance between zones were considered in the model as covariates. Results: Six patients had ES as a current seizure type at time of SEEG. ES patients had a greater number of tubers with a fluid‐attenuated inversion recovery hypointense center (p <.001), and none had TSC1 mutations. The presence of ES was independently associated with increased FC within both intrazone (p =.033) and interzone (p =.011) networks. Post hoc analyses identified that increased FC was associated with ES across tuber and nontuber networks. EZ organization and epileptogenicity biomarkers were not associated with FC. Significance: Increased cortical synchrony among both tuber and nontuber networks is characteristic of patients with ES and independent of both EZ organization and tuber epileptogenicity. This further supports the prospect of FC biomarkers aiding treatment paradigms in TSC. [ABSTRACT FROM AUTHOR]

Surgical resection for epilepsy often fails due to incomplete Epileptogenic Zone Network (EZN) localization from scalp electroencephalography (EEG), stereo-EEG (SEEG), and Magnetic Resonance Imaging (MRI). Subjective interpretation based on interictal, or ictal recordings limits conventional EZN localization. This study employs multimodal analysis using high-density-EEG (HDEEG), Magnetoencephalography (MEG), functional-MRI (fMRI), and SEEG to overcome these limitations in a patient with drug-resistant MRI-negative focal epilepsy. A 17-year-old with drug-resistant epilepsy underwent evaluation. HDEEG, MEG, fMRI, and SEEG were used, with a novel HDEEG-cap facilitating simultaneous EEG-MEG and EEG-fMRI recordings. Electrical and magnetic source imaging were performed, and fMRI data were analysed for homogenous regions. SEEG analysis involved spike detection, spike timing analysis, ictal fast activity quantification, and Granger-based connectivity analysis. Non-invasive sessions revealed consistent interictal source imaging results identifying the EZN in the right anterior cingulate cortex. EEG-fMRI highlighted broader activation in the right cingulate cortex. SEEG analysis localized spikes and fast activity in the right anterior and posterior cingulate gyri. Multi-modal analysis suggested the EZN in the right frontal lobe, primarily involving the anterior and mid-cingulate cortices. Multi-modal non-invasive analyses can optimise SEEG implantation and surgical decision-making. Invasive analyses corroborated non-invasive findings, emphasising the importance of individual-case quantitative analysis across modalities in complex epilepsy cases., (Copyright © 2024 The Author(s). Published by Elsevier Masson SAS.. All rights reserved.)

Single pulse electrical stimulation experiments produce pulse-evoked potentials used to infer brain connectivity. The choice of recording reference for intracranial electrodes remains non-standardized and can significantly impact data interpretation. When the reference electrode is affected by stimulation or evoked brain activity, it can contaminate the pulse-evoked potentials recorded at all other electrodes and influence interpretation of findings. We highlight this specific issue in intracranial EEG datasets from two subjects recorded at separate institutions. We present several intuitive metrics to detect the presence of reference contamination and offer practical guidance on different mitigation strategies. Either switching the reference electrode or re-referencing to an adjusted common average effectively mitigated the reference contamination issue, as evidenced by increased variability in pulse-evoked potentials across the brain. Overall, we demonstrate the importance of clear quality checks and preprocessing steps that should be performed before analysis of single pulse electrical stimulation data., Competing Interests: Declaration of competing interest S. A. S. is a consultant for Boston Scientific, Neuropace, Koh Young, Zimmer Biomet, Varian Medical, and Sensoria Therapeutics and co-founder of Motif Neurotech. K. R. B. has one issued patent and one patent pending, both unrelated to the current work (US 63/592,453, and US 11,241,575). N. M. G. has consulted for NeuroOne, Inc. (funds to Mayo Clinic). The authors declare no other competing interests.

Epilepsy surgery and intracranial monitoring have a long history in the Kingdom of Saudi Arabia, spanning over 30 years. Stereo-EEG however, is a more recent offering. In this short communication, we discuss how Stereo-EEG has grown in the context of the Kingdom's healthcare model and the Vision 2030 model. We discuss the various positives of this technique and methodology as well as the various challenges that the hospitals offering Stereo-EEG have faced., Competing Interests: Declaration of competing interest All authors declare no conflict of interest., (Copyright © 2024 Elsevier Masson SAS. All rights reserved.)

The success of deep brain stimulation (DBS) for treating Parkinson's disease has led to its application to several other disorders, including treatment-resistant depression. Results with DBS for treatment-resistant depression have been heterogeneous, with inconsistencies largely driven by incomplete understanding of the brain networks regulating mood, especially on an individual basis. We report results from the first subject treated with DBS for treatment-resistant depression using an approach that incorporates intracranial recordings to personalize understanding of network behavior and its response to stimulation. These recordings enabled calculation of individually optimized DBS stimulation parameters using a novel inverse solution approach. In the ensuing double-blind, randomized phase incorporating these bespoke parameter sets, DBS led to remission of symptoms and dramatic improvement in quality of life. Results from this initial case demonstrate the feasibility of this personalized platform, which may be used to improve surgical neuromodulation for a vast array of neurologic and psychiatric disorders. [ABSTRACT FROM AUTHOR]

Drug-resistant focal epilepsy presents a significant morbidity burden globally, and epilepsy surgery has been shown to be an effective treatment modality. Therefore, accurate identification of the epileptogenic zone for surgery is crucial, and in those with unclear noninvasive data, stereoencephalography is required. This review covers the history and current practices in the field of intracranial EEG, particularly analyzing how stereotactic image-guidance, robot-assisted navigation, and improved imaging techniques have increased the accuracy, scope, and use of SEEG globally. We provide a perspective on the future directions in the field, reviewing improvements in predicting electrode bending, image acquisition, machine learning and artificial intelligence, advances in surgical planning and visualization software and hardware. We also see the development of EEG analysis tools based on machine learning algorithms that are likely to work synergistically with neurophysiology experts and improve the efficiency of EEG and SEEG analysis and 3D visualization. Improving computer-assisted planning to minimize manual input from the surgeon, and seamless integration into an ergonomic and adaptive operating theater, incorporating hybrid microscopes, virtual and augmented reality is likely to be a significant area of improvement in the near future. [ABSTRACT FROM AUTHOR]

Thanks to its unrivalled spatial and temporal resolutions and signal-to-noise ratio, intracranial EEG (iEEG) is becoming a valuable tool in neuroscience research. To attribute functional properties to cortical tissue, it is paramount to be able to determine precisely the localization of each electrode with respect to a patient's brain anatomy. Several software packages or pipelines offer the possibility to localize manually or semi-automatically iEEG electrodes. However, their reliability and ease of use may leave to be desired. Voxeloc (voxel electrode locator) is a Matlab-based graphical user interface to localize and visualize stereo-EEG electrodes. Voxeloc adopts a semi-automated approach to determine the coordinates of each electrode contact, the user only needing to indicate the deep-most contact of each electrode shaft and another point more proximally. With a deliberately streamlined functionality and intuitive graphical user interface, the main advantages of Voxeloc are ease of use and inter-user reliability. Additionally, oblique slices along the shaft of each electrode can be generated to facilitate the precise localization of each contact. Voxeloc is open-source software and is compatible with the open iEEG-BIDS (Brain Imaging Data Structure) format. Localizing full patients' iEEG implants was faster using Voxeloc than two comparable software packages, and the inter-user agreement was better. Voxeloc offers an easy-to-use and reliable tool to localize and visualize stereo-EEG electrodes. This will contribute to democratizing neuroscience research using iEEG. • Designed to be fast and easy to use and to yield reproducible results. • Outputs oblique slices along stereo-EEG electrodes to assist visualization. • Open-source, compatible with iEEG-BIDS specification to facilitate data exchange. [ABSTRACT FROM AUTHOR]

Cortico-cortical evoked potentials (CCEPs) recorded by stereo-electroencephalography (SEEG) are a valuable tool to investigate brain reactivity and effective connectivity. However, invasive recordings are spatially sparse since they depend on clinical needs. This sparsity hampers systematic comparisons across-subjects, the detection of the whole-brain effects of intracortical stimulation, as well as their relationships to the EEG responses evoked by non-invasive stimuli. To demonstrate that CCEPs recorded by high-density electroencephalography (hd-EEG) provide additional information with respect SEEG alone and to provide an open, curated dataset to allow for further exploration of their potential. The dataset encompasses SEEG and hd-EEG recordings simultaneously acquired during Single Pulse Electrical Stimulation (SPES) in drug-resistant epileptic patients (N = 36) in whom stimulations were delivered with different physical, geometrical, and topological parameters. Differences in CCEPs were assessed by amplitude, latency, and spectral measures. While invasively and non-invasively recorded CCEPs were generally correlated, differences in pulse duration, angle and stimulated cortical area were better captured by hd-EEG. Further, intracranial stimulation evoked site-specific hd-EEG responses that reproduced the spectral features of EEG responses to transcranial magnetic stimulation (TMS). Notably, SPES, albeit unperceived by subjects, elicited scalp responses that were up to one order of magnitude larger than the responses typically evoked by sensory stimulation in awake humans. CCEPs can be simultaneously recorded with SEEG and hd-EEG and the latter provides a reliable descriptor of the effects of SPES as well as a common reference to compare the whole-brain effects of intracortical stimulation to those of non-invasive transcranial or sensory stimulations in humans. • CCEPs recorded with hd-EEG and SEEG are correlated. • hd-EEG recording is highly sensitive to changes in stimulation parameters. • Hd-EEG responses to SPES are characterized by site-specific mean frequencies. • hd-EEG responses to SPES are larger than typical sensory evoked potentials. • An open dataset of simultaneous hd-EEG and SEEG during SPES is provided. [ABSTRACT FROM AUTHOR]

There are different diagnostic methods that used for localization of the seizure onset zone in focal refractory epilepsy cases. Invasive video-EEG recording is the «gold standard» in determining the epileptogenic zone among other diagnostic methods. Invasive EEG already has a long history of using. This article provides historical review and analysis of the techniques, their advantages and disadvantages, current issues.

Magnetoencephalography (MEG) is a noninvasive diagnostic modality that directly measures neuronal signaling by recording the magnetic field created from dendritic, intracellular, electrical currents of the neuron at the surface of the head. In clinical practice, MEG is used in the epilepsy presurgical evaluation and most commonly is an “interictal” study that can provide source localization of spike-wave discharges.However, seizures may be recorded during MEG (“ictal MEG”) and mapping of these discharges may provide more accurate localization of the seizure onset zone. In addition, spike-negative EEG with unique MEG spike-waves may be present in up to 1/3 of MEG studies and unique MEG seizures (EEG-negative seizures) have been reported. This case report describes a patient with unique MEG seizures that exhibited MEG pre-ictal spiking in a tight cluster consistent with the independent interictal epileptiform activity. Stereotactic EEG demonstrated pre-ictal spiking concordant with the MEG pre-ictal spiking.

The functional anatomy of the anteromesial portion of the temporal lobe and its involvement in epilepsy can be explored by means of intracerebral electrical stimulations. Here, we aimed to expand the knowledge of its physiological and pathophysiological symptoms by conducting the first large‐sample systematic analysis of 1529 electrical stimulations of this anatomical region. We retrospectively analysed all clinical manifestations induced by intracerebral electrical stimulations in 173 patients with drug‐resistant focal epilepsy with at least one electrode implanted in this area. We found that high‐frequency stimulations were more likely to evoke electroclinical manifestations (p <.0001) and also provoked 'false positive' seizures. Multimodal symptoms were associated with EEG electrical modification (after discharge) (p <.0001). Visual symptoms were not associated with after discharge (p =.0002) and were mainly evoked by stimulation of the hippocampus (p =.009) and of the parahippocampal gyrus (p =.0212). 'False positive seizures' can be evoked by stimulation of the hippocampus, parahippocampal gyrus and amygdala, likely due to their intrinsic low epileptogenic threshold. Visual symptoms evoked in the hippocampus and parahippocampal gyrus, without EEG changes, are physiological symptoms and suggest involvement of these areas in the visual ventral stream. Our findings provide meaningful guidance in the interpretation of intracranial EEG studies of the temporal lobe. [ABSTRACT FROM AUTHOR]

Sleep spindles and slow waves are the hallmarks of non‐rapid eye movement (NREM) sleep and are produced by the dynamic interplay between thalamic and cortical regions. Several studies in both human and animal models have focused their attention on the relationship between electroencephalographic (EEG) spindles and slow waves during NREM, using the power in the sigma and delta bands as a surrogate for the production of spindles and slow waves. A typical report is an overall inverse relationship between the time course of sigma and delta power as measured by a single correlation coefficient both within and across NREM episodes. Here we analysed stereotactically implanted intracerebral electrode (Stereo‐EEG [SEEG]) recordings during NREM simultaneously acquired from thalamic and from several neocortical sites in six neurosurgical patients. We investigated the relationship between the time course of delta and sigma power and found that, although at the cortical level it shows the expected inverse relationship, these two frequency bands follow a parallel time course at the thalamic level. Both these observations were consistent across patients and across different cortical as well as thalamic regions. These different temporal dynamics at the neocortical and thalamic level are discussed, considering classical as well as more recent interpretations of the neurophysiological determinants of sleep spindles and slow waves. These findings may also help understanding the regulatory mechanisms of these fundamental sleep EEG graphoelements across different brain compartments. [ABSTRACT FROM AUTHOR]

BackgroundHigh-frequency oscillation (HFO) represents a promising biomarker of epileptogenicity. However, the significant interindividual differences among patients limit its application in clinical practice. Here, we applied and evaluated an individualized, frequency-based approach of HFO analysis in stereoelectroencephalography (SEEG) data for localizing the epileptogenic zones (EZs).MethodsClinical and SEEG data of 19 patients with drug-resistant focal epilepsy were retrospectively analyzed. The individualized spectral power of all signals recorded by electrode array, i.e., the relative strength of HFO, was computed with a wavelet method for each patient. Subsequently, the clinical value of the relative strength of HFO for identifying the EZ was evaluated.ResultsFocal increase in the relative strength of HFO in SEEG recordings were identified in all 19 patients. HFOs identified inside the clinically identified seizure onset zone had more spectral power than those identified outside (p < 0.001), and HFOs in 250–500 Hz band (fast ripples) seemed to be more specific identifying the EZ than in those in 80–250 Hz band (ripples) (p < 0.01). The resection of brain regions generating HFOs resulted in a favorable seizure outcome in 17 patients (17/19; 89.5%), while in the cases of other patients with poor outcomes, the brain regions generating HFOs were not removed completely.ConclusionThe relative strength of HFO, especially fast ripples, is a promising effective biomarker for identifying the EZ and can lead to a favorable seizure outcome if used to guide epilepsy surgery.

Up to 11% of patients with mesial temporal lobe epilepsy experience somatosensory auras, although these structures do not have any somatosensory physiological representation. We present the case of a patient with left mesial temporal lobe epilepsy who had somatosensory auras on the right side of the body. Stereo-EEG recording demonstrated seizure onset in the left mesial temporal structures, with propagation to the sensory cortices, when the patient experienced the somatosensory aura. Direct electrical stimulation of both the left amygdala and the hippocampus elicited the patient's habitual, somatosensory aura, with afterdischarges propagating to sensory cortices. These unusual responses to cortical stimulation suggest that in patients with epilepsy, aberrant neural networks are established, which have an essential role in ictogenesis.

Sawtooth waves (STW) are bursts of frontocentral slow oscillations recorded in the scalp electroencephalogram (EEG) during rapid eye movement (REM) sleep. Little is known about their cortical generators and functional significance. Stereo-EEG performed for presurgical epilepsy evaluation offers the unique possibility to study neurophysiology in situ in the human brain. We investigated intracranial correlates of scalp-detected STW in 26 patients (14 women) undergoing combined stereo-EEG/polysomnography. We visually marked STW segments in scalp EEG and selected stereo-EEG channels exhibiting normal activity for intracranial analyses. Channels were grouped in 30 brain regions. The spectral power in each channel and frequency band was computed during STW and non-STW control segments. Ripples (80-250 Hz) were automatically detected during STW and control segments. The spectral power in the different frequency bands and the ripple rates were then compared between STW and control segments in each brain region. An increase in 2-4 Hz power during STW segments was found in all brain regions, except the occipital lobe, with large effect sizes in the parietotemporal junction, the lateral and orbital frontal cortex, the anterior insula, and mesiotemporal structures. A widespread increase in high-frequency activity, including ripples, was observed concomitantly, involving the sensorimotor cortex, associative areas, and limbic structures. This distribution showed a high spatiotemporal heterogeneity. Our results suggest that STW are associated with widely distributed, but locally regulated REM sleep slow oscillations. By driving fast activities, STW may orchestrate synchronized reactivations of multifocal activities, allowing tagging of complex representations necessary for REM sleep-dependent memory consolidation. [ABSTRACT FROM AUTHOR]

Background: High-frequency oscillation (HFO) represents a promising biomarker of epileptogenicity. However, the significant interindividual differences among patients limit its application in clinical practice. Here, we applied and evaluated an individualized, frequency-based approach of HFO analysis in stereoelectroencephalography (SEEG) data for localizing the epileptogenic zones (EZs). Methods: Clinical and SEEG data of 19 patients with drug-resistant focal epilepsy were retrospectively analyzed. The individualized spectral power of all signals recorded by electrode array, i.e., the relative strength of HFO, was computed with a wavelet method for each patient. Subsequently, the clinical value of the relative strength of HFO for identifying the EZ was evaluated. Results: Focal increase in the relative strength of HFO in SEEG recordings were identified in all 19 patients. HFOs identified inside the clinically identified seizure onset zone had more spectral power than those identified outside (p < 0.001), and HFOs in 250–500 Hz band (fast ripples) seemed to be more specific identifying the EZ than in those in 80–250 Hz band (ripples) (p < 0.01). The resection of brain regions generating HFOs resulted in a favorable seizure outcome in 17 patients (17/19; 89.5%), while in the cases of other patients with poor outcomes, the brain regions generating HFOs were not removed completely. Conclusion: The relative strength of HFO, especially fast ripples, is a promising effective biomarker for identifying the EZ and can lead to a favorable seizure outcome if used to guide epilepsy surgery. [ABSTRACT FROM AUTHOR]

• Local and distant connections are differently modulated by sleep. • Clear interhemispheric difference in epileptogenic areas' connectivity during sleep. • Different patterns of information flow during sleep in physiologic versus pathologic structures. Sleep is an active process with an important role in memory. Epilepsy patients often display a disturbed sleep architecture, with consequences on cognition. We aimed to investigate the effect of sleep on cortical networks' organization. We analyzed cortico-cortical evoked responses elicited by single pulse electrical stimulation (SPES) using intracranial depth electrodes in 25 patients with drug-resistant focal epilepsy explored using stereo-EEG. We applied the SPES protocol during wakefulness and NREM – N2 sleep. We analyzed 31,710 significant responses elicited by 799 stimulations covering most brain structures, epileptogenic or non-epileptogenic. We analyzed effective connectivity between structures using a graph-theory approach. Sleep increases excitability in the brain, regardless of epileptogenicity. Local and distant connections are differently modulated by sleep, depending on the tissue epileptogenicity. In non-epileptogenic areas, frontal lobe connectivity is enhanced during sleep. There is increased connectivity between the hippocampus and temporal neocortex, while perisylvian structures are disconnected from the temporal lobe. In epileptogenic areas, we found a clear interhemispheric difference, with decreased connectivity in the right hemisphere during sleep. Sleep modulates brain excitability and reconfigures functional brain networks, depending on tissue epileptogenicity. We found specific patterns of information flow during sleep in physiologic and pathologic structures, with possible implications for cognition. [ABSTRACT FROM AUTHOR]

The role of fast activity as a potential biomarker in localization of the epileptogenic zone (EZ) remains controversial due to recently reported unsatisfactory performance. We recently identified a "fingerprint" of the EZ as a time‐frequency pattern that is defined by a combination of preictal spike(s), fast oscillatory activity, and concurrent suppression of lower frequencies. Here we examine the generalizability of the fingerprint in application to an independent series of patients (11 seizure‐free and 13 non‐seizure‐free after surgery) and show that the fingerprint can also be identified in seizures with lower frequency (such as beta) oscillatory activity. In the seizure‐free group, only 5 of 47 identified EZ contacts were outside the resection. In contrast, in the non‐seizure‐free group, 104 of 142 identified EZ contacts were outside the resection. We integrated the fingerprint prediction with the subject's MR images, thus providing individualized anatomical estimates of the EZ. We show that these fingerprint‐based estimates in seizure‐free patients are almost always inside the resection. On the other hand, for a large fraction of the nonseizure‐free patients the estimated EZ was not well localized and was partially or completely outside the resection, which may explain surgical failure in such cases. We also show that when mapping fast activity alone onto MR images, the EZ was often over‐estimated, indicating a reduced discriminative ability for fast activity relative to the full fingerprint for localization of the EZ. [ABSTRACT FROM AUTHOR]

Objective: In tuberous sclerosis complex (TSC)‐associated drug‐resistant epilepsy, the optimal invasive electroencephalographic (EEG) and operative approach remains unclear. We examined the role of stereo‐EEG in TSC and used stereo‐EEG data to investigate tuber and surrounding cortex epileptogenicity. Methods: We analyzed 18 patients with TSC who underwent stereo‐EEG (seven adults). One hundred ten seizures were analyzed with the epileptogenicity index (EI). In 13 patients with adequate tuber sampling, five anatomical regions of interest (ROIs) were defined: dominant tuber (tuber with highest median EI), perituber cortex, secondary tuber (tuber with second highest median EI), nearby cortex (normal‐appearing cortex in the same lobe as dominant tuber), and distant cortex (in other lobes). At the seizure level, epileptogenicity of ROIs was examined by comparing the highest EI recorded within each anatomical region. At the patient level, epileptogenic zone (EZ) organization was separated into focal tuber (EZ confined to dominant tuber) and complex (all other patterns). Results: The most epileptogenic ROI was the dominant tuber, with higher EI than perituber cortex, secondary tuber, nearby cortex, and distant cortex (P <.001). A focal tuber EZ organization was identified in seven patients. This group had 80% Engel IA postsurgical outcome and distinct dominant tuber characteristics: continuous interictal discharges (IEDs; 100%), fluid‐attenuated inversion recovery (FLAIR) hypointense center (86%), center‐to‐rim EI gradient, and stimulation‐induced seizures (71%). In contrast, six patients had a complex EZ organization, characterized by nearby cortex as the most epileptogenic region and 40% Engel IA outcome. At the intratuber level, the combination of FLAIR hypointense center, continuous IEDs, and stimulation‐induced seizures offered 98% specificity for a focal tuber EZ organization. Significance: Tubers with focal EZ organization have a striking similarity to type II focal cortical dysplasia. The presence of distinct EZ organizations has significant implications for EZ hypothesis generation, invasive EEG approach, and resection strategy. [ABSTRACT FROM AUTHOR]

To analyze the involvement of the posterior cingulate gyrus (PCG) during mesial temporal lobe seizures (MTLS). We retrospectively reviewed the stereo-EEG (SEEG) recordings of patients with MTLS performed in our institution from February 2013 to December 2020. Only patients who had electrode implantation in the PCG were included. Patients with lesions that could potentially alter the seizure spread pathways were excluded. We assessed the propagation patterns of MTLS with respect to the different structures sampled. Nine of 97 patients who had at least one seizure originating in the mesial temporal region met the inclusion criteria. A total of 174 seizures were analyzed. The PCG was the first site of propagation in most of the cases (8/9 patients and 77.5% of seizures, and 7/8 patients and 65.6% of seizures after excluding an outlier patient). The fastest propagation times were towards the contralateral mesial temporal region and ipsilateral PCG. Seven patients underwent standard anterior temporal lobectomy and, of these, all but one were Engel 1 at last follow up. We found the PCG to be the first propagation site of MTLS in this group of patients. These results outline the relevance of the PCG in SEEG planning strategies. Further investigations are needed to corroborate whether fast propagation to the PCG predicts a good surgical outcome. • We retrospectively explored the propagation areas of mesial temporal lobe seizures. • Propagation brain areas and time to propagation were analyzed by stereo-EEG. • Only patients who had electrodes in the posterior cingulate gyrus were included. • The posterior cingulate gyrus was the first propagation area in most cases. • Further studies are required to assess potential surgical implications. [ABSTRACT FROM AUTHOR]

Electrical stimulation mapping using depth stereo-EEG electrodes is an important method in the structure of presurgical diagnostics in patients with drug-resistant forms of epilepsy. Electrical stimulation mapping was first used in the 1960s and has been actively developed since then, but despite such a long history, a unified protocol for the use of this technique has not been developed and different approaches to stimulation mapping are used in different countries. Based on publications on the topic in PubMed and other available resources, we tried to briefly outline the current opinion on the significance of this technique, paying special attention to the methodological approaches of different schools to stimulation parameters when mapping epileptogenic zones, highlighting in a separate section approaches to stimulation of functionally significant zones Finally, we summarize data on the effectiveness of this method in the presurgical diagnostics of epilepsy.

Robot-assisted implantation of deep electrodes for stereo-EEG monitoring has become popular in recent years in patients with drug-resistant epilepsy. However, there are still few data on safety of this technique., Objective: To assess the incidence of complications in patients with drug-resistant epilepsy undergoing robot-assisted implantation of stereo-EEG electrodes., Material and Methods: We retrospectively studied the results of implantation of stereo-EEG electrodes in 187 patients with drug-resistant epilepsy. All patients underwent non-invasive preoperative examination (video-EEG, MRI, PET, SPECT, MEG). In case of insufficient data, stereo-EEG monitoring was prescribed. We determined electrode insertion trajectory using a robotic station and MR images. Implantation of electrodes was carried out using a Rosa robot (Medtech, France). All patients underwent invasive EEG monitoring after implantation., Results: There were 11.25±3 electrodes per a patient. Implantation of one electrode took 7.5±4.9 min. Postoperative MRI revealed electrode malposition in 2.3% of cases. None was associated with complications. The complication rate per electrode was 0.6%. Complications affected stereo-EEG monitoring only in 3 cases (1.6%). The mortality rate was 0.5%. Bilateral implantation ( p =0.005), insular ( p =0.040) and occipital ( p =0.045) deep electrode implantation were associated with lower incidence of complications. Longer duration of the procedure influenced the incidence of electrode placement in the lateral ventricle ( p =0.028), and implantation in the frontal lobe was more often associated with epidural placement of electrodes ( p =0.039)., Conclusion: Robot-assisted implantation of stereo-EEG electrodes is a safe procedure with minimal risk of complications. Rare electrode malposition does not usually affect invasive monitoring.

Purpose: To define Stereo-EEG (SEEG) ictal and interictal patterns associated with different pathologies in a cohort of patients with drug-resistant focal epilepsy.Methods: We retrospectively analyzed findings from 102 patient with epilepsy due to Polymicrogyria (PMG), Periventricular Nodular Heterotopia (PNH), Focal Cortical Dysplasia (FCD) type I, IIa, IIb and Hippocampal Sclerosis (HS). Ictal and interictal SEEG recordings were reviewed to describe Seizure Onset Zone (SEEG-SOZ) patterns and to define the Lesional and Irritative Zones.Results: Five SEEG-SOZ patterns were identified: significant associations were found between low-voltage fast activity and PMG and between repetitive fast spikes bursts and FCD type IIa. A trend was found between fast activity and PNH, rhythmic sharp activity and FCD type I, repetitive fast spikes bursts and FCD type IIb, slow burst and HS. In 62 of the 102 patients, a complete surgical resection of the SEEG-SOZ was performed, and in 12 patients a partial resection was carried out to preserve eloquent areas. In 18 patients (15 with PNH) the SEEG-SOZ was thermo-coagulated. Seizure freedom was achieved in 58% of surgically treated patients and in 72% of those treated with thermocoagulation (mean ± SD follow-up 5.9 ± 2.3 years). Seizure freedom after surgery was achieved in 84% of the patients with PMG, FCD I, IIa and IIb presenting with characteristic SEEG-SOZ patterns. With the exception of FCD type II, interictal activity was not sufficient to identify SEEG-SOZ boundaries.Conclusion: The study demonstrates that specific histopathologies correlate with particular neurophysiological patterns, reflecting lesion-specific seizure patterns in focal epilepsies. [ABSTRACT FROM AUTHOR]

Objective: To assess factors associated with favorable outcome in refractory insular epilepsy treated by volume‐based stereotactic radiofrequency thermocoagulation (RFTC). Methods: We performed volume‐based RFTC in 19 patients (11 males, 7‐44 years old). The volume for thermocoagulation was identified by multimodal data including electroencephalography (EEG)‐video, magnetic resonance imaging (MRI), and fluorodeoxyglucose–positron emission tomography (PET) in all patients, and epileptogenic zone (EZ) was assessed by stereo‐electroencephalography (SEEG) in 16. MRI showed insular lesions in four patients (benign tumors, n = 2; focal cortical dysplasia [FCD], n = 1; polymicrogyria, n = 1). MRI was negative in 15 cases; however, PET was positive in 18, and FCD pattern was detected by SEEG in nine cases. The dominant hemisphere was involved in 12 cases. RFTC was performed as a separate procedure after SEEG, or as a single MRI‐guided procedure. The insular volume to be coagulated was determined by a tridimensional identification of the epileptogenic cortex using MRI, PET, and SEEG, and was destroyed with coalescent thermal lesions. Results: Seizure‐free outcome was achieved in 10 patients (53%), including Engel class IA in three (follow‐up = 1‐12 years, mean = 5.4). The responder rate (including Engel classes I‐III) was 89%. Transient postoperative deficits (mild hemiparesia, dysarthria, hypoesthesia, dysgeusia) were observed in eight patients (42%), with rapid and total recovery in all but one with persistent mild dysarthria. Neurological deficits were related to higher number of RFTC procedures (P = .036) and greater volume of RFTC (P = .028). Neuropsychological status was unchanged or improved in all; however, psychiatric status transitorily worsened in three patients. Factors contributing to seizure‐free outcome were the detection of FCD pattern (P = .009), localized EZ (P = .038), low RFTC volume (P = .002), low number of RFTC procedures (P = .001), and low RFTC volume/number ratio (P = .012). Optimal volume of RFTC around 2 cm3 offered the best compromise between efficacy and safety. Significance: RFTC may be curative in insular epilepsy after accurate localization of EZ with SEEG. Best outcome was associated with low volume of thermolesions. [ABSTRACT FROM AUTHOR]

Summary: Objectives: We aimed to describe intracerebral aspects of postictal generalized electroencephalography suppression (PGES) following focal to bilateral tonic–clonic ("secondarily generalized tonic–clonic") seizures (GTCS) recorded using stereoelectroencephalographic (SEEG), and to correlate these with electroclinical features. Methods: Three independent observers scored semiologic and SEEG features. Patient and epilepsy characteristics were collected. Descriptive statistics and multivariate analysis were performed. The operational definition of PGES on SEEG used strict criteria (absence of visible signal at 20 μV/mm amplitude, in all readable channels). Postictal regional suppression (RS) was identified if only a subset of implanted electrodes showed absence of signal. Results: We evaluated 100 seizures in 52 patients. Interobserver agreement was good (κ 0.72 for clinical features and 0.73 for EEG features). PGES was present in 27 of 100 and RS without PGES present in 42 of 100 seizures. Region of RS included epileptogenic zone in 43 of 51 (86%). No effect of sampling (multilobar or bilateral exploration) was seen. Oral tonicity (mouth opening and/or tonic vocalization during the tonic phase of GTCS) was associated with the presence of PGES (P = 0.029; negative predictive value [NPV] 0.91). Bilateral upper limb extension during the tonic phase correlated with PGES (P = 0.041; NPV 0.85). Association of both oral tonicity and bilateral upper limb extension had a high NPV of 0.96. Significance: SEEG recordings confirm true absence of signal during postictal EEG suppression. PGES is unlikely when both upper limb extension and oral tonicity are absent. We hypothesize that bilateral tonic seizure discharge at bulbar level brainstem regions is associated with the production of oral signs and may relate to mechanisms of PGES. [ABSTRACT FROM AUTHOR]