Neocortical Epilepsy Research Articles

State-dependent effects of responsive neurostimulation depend on seizure localization.

Brain-responsive neurostimulation is firmly ensconced among treatment options for drug-resistant focal epilepsy, but over a quarter of patients treated with the RNS System do not experience meaningful seizure reduction. Initial titration of RNS therapy is typically similar for all patients, raising the possibility that treatment response might be enhanced by consideration of patient-specific variables. Indeed, small, single-center studies have yielded preliminary evidence that RNS System effectiveness depends on the brain state during which stimulation is applied. The generalizability of these findings remains unclear, however, and it is unknown whether state-dependent effects of responsive neurostimulation are also stratified by location of the seizure onset zone where stimulation is delivered. We aimed to determine whether state-dependent effects of the RNS System are evident in the large, diverse, multi-center cohort of RNS System clinical trial participants and to test whether these effects differ between mesiotemporal and neocortical epilepsies. Eighty-one of 256 patients who were treated with the RNS System across 31 centers during clinical trials met criteria for inclusion in this retrospective study. Risk states were defined in relation to phases of daily and multi-day cycles of interictal epileptiform activity that are thought to determine seizure likelihood. We found that the probabilities of risk state transitions depended on the stimulation parameter being changed, the starting seizure risk state, and the stimulated brain region. Changes in two commonly adjusted stimulation parameters, charge density and stimulation frequency, produced opposite effects on risk state transitions depending on seizure localization. Greater variance in acute risk state transitions was explained by state-dependent responsive neurostimulation for bipolar stimulation for neocortical epilepsies and for monopolar stimulation for mesiotemporal epilepsies. Variability in effectiveness of RNS System therapy across individuals may relate, at least partly, to the fact that current treatment paradigms do not account fully for fluctuations in brain states or locations of simulation sites. State-dependence of electrical brain stimulation may inform development of next-generation closed-loop devices that can detect changes in brain state and deliver adaptive, localization-specific patterns of stimulation to maximize therapeutic effects.

High-Frequency Stimulation of the Centromedian Thalamic Nucleus Aborts Seizures and Ictal Apnea.

A 32-year-old right-handed woman presented with medically and surgically refractory left temporal neocortical epilepsy secondary to focal cortical dysplasia who underwent stereoelectroencephalography involving the centromedian nucleus of the thalamus. With the use of real-time stereoelectroencephalography monitoring, four electroclinical seizures were aborted by administering high-frequency stimulation at the centromedian nucleus at seizure onset. Seizures before stimulation were all associated with ictal apnea, while those with stimulation had no ictal apnea. This case demonstrates how providing high-frequency stimulation to the centromedian nucleus of the thalamus can abort electroclinical seizures and ictal apnea.

Circumscribing Laser Cuts Attenuate Seizure Propagation in a Mouse Model of Focal Epilepsy.

In partial onset epilepsy, seizures arise focally in the brain and often propagate. Patients frequently become refractory to medical management, leaving neurosurgery, which can cause neurologic deficits, as a primary treatment. In the cortex, focal seizures spread through horizontal connections in layers II/III, suggesting that severing these connections can block seizures while preserving function. Focal neocortical epilepsy is induced in mice, sub-surface cuts are created surrounding the seizure focus using tightly-focused femtosecond laser pulses, and electrophysiological recordings are acquired at multiple locations for 3-12 months. Cuts reduced seizure frequency in most animals by 87%, and only 5% of remaining seizures propagated to the distant electrodes, compared to 80% in control animals. These cuts produced a modest decrease in cortical blood flow that recovered and left a ≈20-µm wide scar with minimal collateral damage. When placed over the motor cortex, cuts do not cause notable deficits in a skilled reaching task, suggesting they hold promise as a novel neurosurgical approach for intractable focal cortical epilepsy.

Who are the Better Candidates for Epilepsy Surgery?

The resective epilepsy surgery can be the effective procedure to get seizure-free outcome in these drug resistant epilepsy (DRE) patients. Class I evidence firmly establishes the superiority of epilepsy surgery over medical treatments in both seizure control and quality of life for DRE patients. For the effective identification of optimal surgical candidates, it's essential to understand the prognostic factors of epilepsy surgery based on the surgical methods employed. Established positive prognostic indicators for temporal resection include the presence of hippocampal sclerosis on magnetic resonance imaging (MRI), focal lesions on MRI, unilateral temporal spikes, concordant ictal electroencephalography (EEG), and a history of prolonged febrile convulsion. Potential negative predictors encompass preoperative secondary generalized tonic-clonic seizures, a normal MRI, postoperative EEG spikes, and age at the time of surgery. For neocortical epilepsy, the prognostic factors identified through multivariate analysis were the presence of a discrete lesion, localized hypometabolism on Fluorodeoxyglucose positron emission tomography (FDG-PET), and localized ictal EEG. A significant correlation was found between achieving a seizure-free outcome in no visible lesion on MRI (MR-negative) epilepsy patients and having concordance in two or more presurgical evaluations, specifically in interictal EEG, ictal EEG, FDG-PET, and ictal single-photon emission computed tomography. There was a marked improvement in the seizure-free outcome in MR-negative temporal lobe epilepsy (TLE) by the application of this strategy. The better surgical candidates for epilepsy surgery are the followings: patients displaying a discrete lesion on MRI with concordant video-EEG monitoring (VEM) results, patients diagnosed with unilateral hippocampal sclerosis who have concordant VEM results, patients with unilateral hippocampal sclerosis but discordant VEM results, patients with focal cortical dysplasia and concordant VEM results, and patients diagnosed with MR-negative TLE who exhibit two or more consistent results from presurgical evaluations.

Mouse model of focal cortical dysplasia type II generates a wide spectrum of high-frequency activities

High-frequency oscillations (HFOs) represent an electrographic biomarker of endogenous epileptogenicity and seizure-generating tissue that proved clinically useful in presurgical planning and delineating the resection area. In the neocortex, the clinical observations on HFOs are not sufficiently supported by experimental studies stemming from a lack of realistic neocortical epilepsy models that could provide an explanation of the pathophysiological substrates of neocortical HFOs. In this study, we explored pathological epileptiform network phenomena, particularly HFOs, in a highly realistic murine model of neocortical epilepsy due to focal cortical dysplasia (FCD) type II. FCD was induced in mice by the expression of the human pathogenic mTOR gene mutation during embryonic stages of brain development. Electrographic recordings from multiple cortical regions in freely moving animals with FCD and epilepsy demonstrated that the FCD lesion generates HFOs from all frequency ranges, i.e., gamma, ripples, and fast ripples up to 800 Hz. Gamma-ripples were recorded almost exclusively in FCD animals, while fast ripples occurred in controls as well, although at a lower rate. Gamma-ripple activity is particularly valuable for localizing the FCD lesion, surpassing the utility of fast ripples that were also observed in control animals, although at significantly lower rates. Propagating HFOs occurred outside the FCD, and the contralateral cortex also generated HFOs independently of the FCD, pointing to a wider FCD network dysfunction. Optogenetic activation of neurons carrying mTOR mutation and expressing Channelrhodopsin-2 evoked fast ripple oscillations that displayed spectral and morphological profiles analogous to spontaneous oscillations. This study brings experimental evidence that FCD type II generates pathological HFOs across all frequency bands and provides information about the spatiotemporal properties of each HFO subtype in FCD. The study shows that mutated neurons represent a functionally interconnected and active component of the FCD network, as they can induce interictal epileptiform phenomena and HFOs.

Interictal magnetoencephalography abnormalities to guide intracranial electrode implantation and predict surgical outcome.

Intracranial EEG is the gold standard technique for epileptogenic zone localization but requires a preconceived hypothesis of the location of the epileptogenic tissue. This placement is guided by qualitative interpretations of seizure semiology, MRI, EEG and other imaging modalities, such as magnetoencephalography. Quantitative abnormality mapping using magnetoencephalography has recently been shown to have potential clinical value. We hypothesized that if quantifiable magnetoencephalography abnormalities were sampled by intracranial EEG, then patients' post-resection seizure outcome may be better. Thirty-two individuals with refractory neocortical epilepsy underwent magnetoencephalography and subsequent intracranial EEG recordings as part of presurgical evaluation. Eyes-closed resting-state interictal magnetoencephalography band power abnormality maps were derived from 70 healthy controls as a normative baseline. Magnetoencephalography abnormality maps were compared to intracranial EEG electrode implantation, with the spatial overlap of intracranial EEG electrode placement and cerebral magnetoencephalography abnormalities recorded. Finally, we assessed if the implantation of electrodes in abnormal tissue and subsequent resection of the strongest abnormalities determined by magnetoencephalography and intracranial EEG corresponded to surgical success. We used the area under the receiver operating characteristic curve as a measure of effect size. Intracranial electrodes were implanted in brain tissue with the most abnormal magnetoencephalography findings-in individuals that were seizure-free postoperatively (T = 3.9, P = 0.001) but not in those who did not become seizure-free. The overlap between magnetoencephalography abnormalities and electrode placement distinguished surgical outcome groups moderately well (area under the receiver operating characteristic curve = 0.68). In isolation, the resection of the strongest abnormalities as defined by magnetoencephalography and intracranial EEG separated surgical outcome groups well, area under the receiver operating characteristic curve = 0.71 and area under the receiver operating characteristic curve = 0.74, respectively. A model incorporating all three features separated surgical outcome groups best (area under the receiver operating characteristic curve = 0.80). Intracranial EEG is a key tool to delineate the epileptogenic zone and help render individuals seizure-free postoperatively. We showed that data-driven abnormality maps derived from resting-state magnetoencephalography recordings demonstrate clinical value and may help guide electrode placement in individuals with neocortical epilepsy. Additionally, our predictive model of postoperative seizure freedom, which leverages both magnetoencephalography and intracranial EEG recordings, could aid patient counselling of expected outcome.

Stereo-electroencephalography Guided Laser Ablation in Neocortical Epilepsy: Electrophysiological correlations and Outcome.

We aim to study the correlation between seizure outcomes in patients with drug-resistant epilepsy (DRE) who underwent laser interstitial thermal therapy (LITT) and stereo-electroencephalographic (SEEG) electrophysiologic patterns with respect to the extent of laser ablation. We retrospectively analyzed 16 consecutive DRE patients who underwent LITT. A seizure onset zone (SOZ) was obtained from multidisciplinary patient management conferences and again was confirmed independently by two epileptologists based on conventional analysis. SOZ were retrospectively divided into localized, lobar and multilobar, and nonlocalized onset types. A posteriori predicted epileptogenic zone (PEZ) was identified using the previously developed "EZ fingerprint" pipeline. The completeness of the SOZ and PEZ ablation was compared and correlated with the duration of seizure freedom (SF). Out of 16 patients, 11 had a posteriori-identified PEZ. Three patients underwent complete ablation of SOZ with curative intent, and the other 13 with palliative intent. Out of three patients with complete ablation of the SOZ, two had concordant PEZ and SOZ and achieved 40- and 46-month SF without seizure recurrence. The remaining patient, without any PEZ identified, had seizure recurrence within one month. Six out of 13 patients with partial ablation of the SOZ and PEZ achieved a mean SF of 19.8 months (range: 1 to 44) with subsequent seizure recurrence. The remaining seven patients had partial ablation of the SOZ without the PEZ identified or ablation outside the PEZ with seizure recurrence within one to two months, except one patient who had 40 months SF after ablation of periventricular heterotopia. Only complete ablation of the well-restricted SOZ concordant with the PEZ was associated with long-term SF, whereas partial ablation of the PEZ might lead to SF with eventual seizure recurrence. Failure to identify PEZ and ablation limited to the SOZ often led to one to two months of SF.

Novel Approaches for Treatment of Epilepsy

Epilepsy is a serious neurological disorder on the juncture of psychiatry and neurology. It is characterized by recurrent and episodic seizures which are due to excessive discharge by the brain neurons. The therapeutic response failure of more than one or two antiepileptic drugs (AEDs) is the benchmark of refractory or intractable epilepsy. The aim of the study was to determine new approaches which lead towards the treatment of epilepsy. In order to treat focal mesial temporal lobe epilepsy or neocortical epilepsy in adults and any malformation of cortical development such as focal dysplasia surgical resection remains the gold standard treatment. Disconnection procedures such as corpus callosotomy and multiple subpial transections are the best alternative treatment for that patient whose seizure origin is in eloquent cortex or having generalized epilepsy syndromes. Palliative neuromodulation procedures such as Vagus nerve stimulation (VNS), Responsive neurostimulation (RNS) and Deep brain stimulation (DBS) are best approach to treat intractable epileptic patients who are not suitable candidates of surgery. As the search of better management of epilepsy continues gene therapy and optogenetics gain a momentum in neuroscience.

Improving the accuracy of epileptogenic zone localization in stereo EEG with machine learning algorithms

The precise identification of the epileptogenic zone (EZ) is paramount in the presurgical evaluation of epilepsy patients to ensure successful surgical outcomes. The analysis of Stereo EEG, an instrumental tool for EZ localization, poses considerable challenges even for experienced epileptologists. Consequently, the development of machine learning (ML)-based computational tools for enhanced EZ localization is imperative. In this investigation, we developed ML models utilizing Stereo EEG from 15 patients, who remained seizure-free (Engel 1 a-d) following EZ resection, over an average follow-up period of 44.4 months. Utilizing Delphos and MNI detectors, spikes and High Frequency Oscillations (HFOs) were identified from Stereo EEG in Resected Zone (RZ) and non-Resected Zone (non-RZ). Linear and non-linear features were estimated from each modality using MATLAB. A total of 27,744 spikes, 7,790 ripples, and 7,632 fast ripples, along with their combinations, were employed to train the ML models. The Gradient Boosting classifier demonstrated the highest prediction accuracy of 98.5% for EZ localization in Mesial Temporal Lobe Epilepsy (MTLE) when trained with features derived from the spike-ripple combination. In the case of Neocortical Epilepsy (NE), the Extra Trees classifier achieved an accuracy of 87.6% when utilizing features from fast ripples. The Random Forest, Extra Trees, and Gradient Boosting algorithms were the most effective for predicting the RZ. Linear features outperformed non-linear features in predicting epileptogenic zones within the epileptic brain. Our study establishes the capability of ML methodologies in localizing epileptogenic zones with high accuracy. Future studies that focus on increasing the training sample size and incorporating more advanced machine learning (ML) algorithms have the potential to significantly improve the accuracy of these models in pinpointing epileptogenic networks. Additionally, implementing this ML approach across multiple research centers would contribute to the broader validation and generalizability of this technique.

Radiofrequency ablation during stereoelectroencephalography: from diagnostic tool to therapeutic intervention. Illustrative case.

Radiofrequency thermocoagulation (RFTC) during intracranial stereoelectroencephalography (sEEG) was first described as a safe technique for creating lesions of epileptic foci in 2004. Since that time, the method has been applied as a diagnostic and/or palliative intervention. Although widely practiced in European epilepsy surgical programs, the technique has not been popularized in the United States given the lack of Food and Drug Administration (FDA)-approved technologies permitting safe usage of in situ sEEG electrodes for this purpose. The authors present a case report of a young female patient with refractory left neocortical temporal lobe epilepsy undergoing sEEG electrode implantation, who underwent sEEG-guided RFTC via a stereotactic temperature-sensing pallidotomy probe. Although used as a diagnostic step in her workup, the patient has remained seizure-free for nearly 18 months. The use of in situ sEEG electrodes for RFTC remains limited in the United States. In this context, this case highlights a safe alternative and temporizing approach to performing diagnostic sEEG-guided RFTC, using a temperature-sensing pallidotomy probe to create small, precise stereotactic lesions. The authors caution careful consideration of this technique as a temporary work-around solution while also highlighting the rising need for new FDA-approved technologies for safe RFTC through in situ temperature-sensing sEEG electrodes.

Characteristics of ictal thalamic EEG in pediatric-onset neocortical focal epilepsy

ObjectiveTo characterize ictal EEG change in the centromedian (CM) and anterior nucleus (AN) of the thalamus, using stereoelectroencephalography (SEEG) recordings. MethodsForty habitual seizures were analyzed in nine patients with pediatric-onset neocortical drug-resistant epilepsy who underwent SEEG (age 2–25 y) with thalamic coverage. Both visual and quantitative analysis was used to evaluate ictal EEG signal in the cortex and thalamus. The amplitude and cortico-thalamic latencies of broadband frequencies at ictal onset were measured. ResultsVisual analysis demonstrated consistent detection of ictal EEG changes in both the CM nucleus and AN nucleus with latency to thalamic ictal EEG changes of less than 400 ms in 95% of seizures, with low-voltage fast activity being the most common ictal pattern. Quantitative broadband amplitude analysis showed consistent power changes across the frequency bands, corresponding to ictal EEG onset, while while ictal EEG latency was variable from −18.0 seconds to 13.2 seconds. There was no significant difference between detection of CM and AN ictal activity on visual or amplitude analysis. Four patients with subsequent thalamic responsive neurostimulation (RNS) demonstrated ictal EEG changes consistent with SEEG findings. ConclusionsIctal EEG changes were consistently seen at the CM and AN of the thalamus during neocortical seizures. SignificanceIt may be feasible to use a closed-loop system in the thalamus to detect and modulate seizure activity for neocortical epilepsy.

ID: 218087 RNS for Medically Uncontrolled Bilateral Neocortical Temporal Lobe Epilepsy Confers Favorable Long-Term Seizure Control

Patients with refractory neocortical temporal lobe epilepsy are challenging surgical candidates. Preoperative evaluation often fails to accurately localize SOZs, which necessitates the use of intracranial electroencephalography (iEEG). Furthermore, once SOZ can be defined, patients are typically not candidates for resective surgery. We present a retrospective case series of our experience with diagnosis and management of “bilateral neocortical temporal lobe epilepsy” (bnTLE) treated with responsive neurostimulation (RNS).?

High Frequency Stimulation of the Centromedian Thalamic Nucleus to Abort Seizures and Interictal Discharges During Stereoelectroencephalography Evaluation (P5-1.007)

<h3>Objective:</h3> To assess whether high frequency stimulation of the centromedian nucleus of the thalamus can disrupt seizures and/or interictal discharges. <h3>Background:</h3> There is growing evidence that subcortical structures, including the thalamus, are involved in seizure networks in patients with neocortical epilepsy. Responsive neurostimulation of the centromedian nucleus of the thalamus (CMT) has been shown to terminate seizures in case reports of patients with generalized and focal neocortical epilepsy [Burdette, et al. <i>Epilepsy and Behavior</i>, 2020]. However, to our knowledge, no prior reports have demonstrated the utility of stimulating the thalamus during a sEEG evaluation. We present two patients with refractory neocortical epilepsy who underwent sEEG evaluation including an electrode in the CMT. <h3>Design/Methods:</h3> Both patients underwent real-time high frequency stimulation (HFS) at CMT during runs of interictal discharges. Patient 1 was also stimulated during seizures. Stimulation settings for both patients were 50Hz, 0.3msec pulse duration, for 3 seconds. Patient 1 underwent stimulation at 2mA while Patient 2 was 1mA. For patient 1, seizure characteristics before and after stimulation were compared using a student’s t-test (duration) and Fisher exact test (apnea). <h3>Results:</h3> For Patient 1, HFS of the CMT successfully aborted 4 seizures. Compared to 11 seizures prior to stimulation, those with HFS were significantly shorter (9.5 vs. 20.5 seconds, p=0.018). The patient did not develop clinical apnea in any of the 4 seizures aborted with HFS, but did with all of the 11 seizures without stimulation (p=0.001). Stimulation during runs of interictal discharges was inconclusive. In Patient 2, HFS aborted runs of inter-ictal discharges in all 10 attempts. <h3>Conclusions:</h3> These cases demonstrate that stimulation of the CMT during sEEG evaluation can abort electroclinical seizures and potentially interictal discharges. This supports the idea that the CMT is involved in focal neocortical epilepsy networks. Stimulation during sEEG may be useful in predicting efficacy of thalamic neurostimulation. <b>Disclosure:</b> Dr. Nathan has nothing to disclose. Dr. Adney has received research support from NINDS. Joshua M Rosenow, MD, FAANS, FACS has received personal compensation in the range of $10,000-$49,999 for serving as a Consultant for Boston Scientific Neuromodulation. Dr. Schuele has received personal compensation in the range of $500-$4,999 for serving as a Consultant for Monteris. Dr. Schuele has received personal compensation in the range of $500-$4,999 for serving on a Speakers Bureau for Neurelis. Dr. Schuele has received personal compensation in the range of $10,000-$49,999 for serving on a Speakers Bureau for SK Life Science. Dr. Schuele has received personal compensation in the range of $500-$4,999 for serving on a Speakers Bureau for Jazz. Dr. Schuele has received personal compensation in the range of $50,000-$99,999 for serving as an Editor, Associate Editor, or Editorial Advisory Board Member for Journal of Clinical Neurophysiology. Dr. Schuele has received personal compensation in the range of $500-$4,999 for serving as an Expert Witness for Thomas Needham. Dr. Schuele has received research support from National Institute of Health. Dr. Gerard has received personal compensation in the range of $500-$4,999 for serving as a Consultant for Greenwich Pharmaceuticals. The institution of Dr. Gerard has received research support from NIH/NINDS. The institution of Dr. Gerard has received research support from Xenon Pharmaceuticals. The institution of an immediate family member of Dr. Gerard has received research support from NIH. The institution of an immediate family member of Dr. Gerard has received research support from Novo Nordisk. The institution of Dr. Gerard has received research support from Eisai, Inc. (via Stanford University).

Metabolic profiles and correlation with surgical outcomes in mesial versus neocortical temporal lobe epilepsy.

Differentiating mesial temporal lobe epilepsy (MTLE) and neocortical temporal lobe epilepsy (NTLE) remains challenging. Our study characterized the metabolic profiles between MTLE and NTLE and their correlation with surgical prognosis using 18 F-FDG-PET. A total of 137 patients with intractable temporal lobe epilepsy (TLE) and 40 age-matched healthy controls were recruited. Patients were divided into the MTLE group (N = 91) and the NTLE group (N = 46). 18 F-FDG-PET was used to measure the metabolism of regional cerebra, which was analyzed using statistical parametric mapping. The volume of abnormal metabolism in cerebral regions and their relationship with surgical prognosis were calculated for each surgical patient. The cerebral hypometabolism of MTLE was limited to the ipsilateral temporal and insular lobes (p < 0.001, uncorrected). The NTLE patients showed hypometabolism in the ipsilateral temporal, frontal, and parietal lobes (p < 0.001, uncorrected). The MTLE patients showed extensive hypermetabolism in cerebral regions (p < 0.001, uncorrected). Hypermetabolism in NTLE was limited to the contralateral temporal lobe and cerebellum, ipsilateral frontal lobe, occipital lobe, and bilateral thalamus (p < 0.001, uncorrected). Among patients who underwent resection of epileptic lesions, 51 (67.1%) patients in the MTLE group and 10 (43.5%) in the NTLE group achieved Engel class IA outcome (p = 0.041). The volumes of metabolic increase for the frontal lobe or thalamus in the MTLE group were larger in non-Engel class IA patients than Engel class IA patients (p < 0.05). The spatial metabolic profile discriminated NTLE from MTLE. Hypermetabolism of the thalamus and frontal lobe in MTLE may facilitate preoperative counseling and surgical planning.

Now We Can Tame the Wild West of Controlling Astrocytes for Treating Neocortical Epilepsy.

Now We Can Tame the Wild West of Controlling Astrocytes for Treating Neocortical Epilepsy.

MEG abnormalities and mechanisms of surgical failure in neocortical epilepsy.

Epilepsy surgery fails to achieve seizure freedom in 30%-40% of cases. It is not fully understood why some surgeries are unsuccessful. By comparing interictal magnetoencephalography (MEG) band power from patient data to normative maps, which describe healthy spatial and population variability, we identify patient-specific abnormalities relating to surgical failure. We propose three mechanisms contributing to poor surgical outcome: (1) not resecting the epileptogenic abnormalities (mislocalization), (2) failing to remove all epileptogenic abnormalities (partial resection), and (3) insufficiently impacting the overall cortical abnormality. Herein we develop markers of these mechanisms, validating them against patient outcomes. Resting-state MEG recordings were acquired for 70 healthy controls and 32 patients with refractory neocortical epilepsy. Relative band-power spatial maps were computed using source-localized recordings. Patient and region-specific band-power abnormalities were estimated as the maximum absolute z-score across five frequency bands using healthy data as a baseline. Resected regions were identified using postoperative magnetic resonance imaging (MRI). We hypothesized that our mechanistically interpretable markers would discriminate patients with and without postoperative seizure freedom. Our markers discriminated surgical outcome groups (abnormalities not targeted: area under the curve [AUC]=0.80, p=.003; partial resection of epileptogenic zone: AUC=0.68, p=.053; and insufficient cortical abnormality impact: AUC=0.64, p=.096). Furthermore, 95% of those patients who were not seizure-free had markers of surgical failure for at least one of the three proposed mechanisms. In contrast, of those patients without markers for any mechanism, 80% were ultimately seizure-free. The mapping of abnormalities across the brain is important for a wide range of neurological conditions. Here we have demonstrated that interictal MEG band-power mapping has merit for the localization of pathology and improving our mechanistic understanding of epilepsy. Our markers for mechanisms of surgical failure could be used in the future to construct predictive models of surgical outcome, aiding clinical teams during patient pre-surgical evaluations.

Characterizing physiological high-frequency oscillations using deep learning

Objective. Intracranially-recorded interictal high-frequency oscillations (HFOs) have been proposed as a promising spatial biomarker of the epileptogenic zone. However, HFOs can also be recorded in the healthy brain regions, which complicates the interpretation of HFOs. The present study aimed to characterize salient features of physiological HFOs using deep learning (DL). Approach. We studied children with neocortical epilepsy who underwent intracranial strip/grid evaluation. Time-series EEG data were transformed into DL training inputs. The eloquent cortex (EC) was defined by functional cortical mapping and used as a DL label. Morphological characteristics of HFOs obtained from EC (ecHFOs) were distilled and interpreted through a novel weakly supervised DL model. Main results. A total of 63 379 interictal intracranially-recorded HFOs from 18 children were analyzed. The ecHFOs had lower amplitude throughout the 80–500 Hz frequency band around the HFO onset and also had a lower signal amplitude in the low frequency band throughout a one-second time window than non-ecHFOs, resembling a bell-shaped template in the time–frequency map. A minority of ecHFOs were HFOs with spikes (22.9%). Such morphological characteristics were confirmed to influence DL model prediction via perturbation analyses. Using the resection ratio (removed HFOs/detected HFOs) of non-ecHFOs, the prediction of postoperative seizure outcomes improved compared to using uncorrected HFOs (area under the ROC curve of 0.82, increased from 0.76). Significance. We characterized salient features of physiological HFOs using a DL algorithm. Our results suggested that this DL-based HFO classification, once trained, might help separate physiological from pathological HFOs, and efficiently guide surgical resection using HFOs.

Localizing epileptogenic network from SEEG using non-linear correlation, mutual information and graph theory analysis.

The key challenge in epilepsy surgery is precise localization and removal of the epileptogenic zone (EZ) from the brain. Localization of the epileptogenic network by visual analysis of intracranial EEG is extremely difficult. In this retrospective study, we used interictal connectivity and graph theory analysis on intracranial EEG to better delineate the epileptogenic zone. Patients who underwent surgery for drug-refractory mesial temporal and neocortical epilepsy were included. Computational measures, such as h2 nonlinear correlation and mutual information, were used to estimate the interdependency of intracranial EEGs. We observed that the Out-Degree, Out-Strength, and Betweenness centrality (graph properties) were the best predictors of EZ. From the results, we also found that graph properties with a normalized value above 0.75 were found to be a useful measure to localize the EZ with a sensitivity of 87.88 and a specificity of 87.13. Our results also validate that frequently occurring types of interictal fast discharges (IFD) with connectivity measures and graph properties can better localize the EZ. We foresee graph theory analysis of interictal intracranial EEG data can help precise localization of EZ for cortical resection as well as in minimally invasive radiofrequency ablation of epileptogenic hubs. Further, prospective validation is required for clinical use.

Synchronization clusters located on epileptic onset zones in neocortical epilepsy

BackgroundBrain function is thought to rely on complex interactions of dynamic neural systems, which depend on the integrity of structural and functional networks. Focal epilepsy is considered to result from excessive focal synchronization in the network. Synchronization analysis of multichannel electrocorticography (ECoG) contributes to the understanding of and orientation of epilepsy. The aim of this study was to explore the synchronization in multichannel ECoG recordings from patients with neocortical epilepsy and characterize neural activity inside and outside the onset zone.MethodsFour patients with neocortical epilepsy, who became seizure-free for more than 1 year after surgery guided by ECoG monitoring, were included in this study. ECoG data recorded during pre-surgical evaluation were analyzed. Synchronizations in phase and amplitude of different frequency bands between ECoG channels was analyzed using MATLAB. We generated 100 surrogate data from the original ECoG data using Amplitude Adjusted Fourier Transform to calculate the enhanced synchronization. The relationship between synchronization characteristics and seizure onset zone was analyzed.ResultsWe found synchronization clusters in the 14–30 Hz and 30–80 Hz bands around the onset areas during both interictal and the beginning of ictal periods in all four patients.ConclusionsThe enhanced-synchronization clusters play a central role in epilepsy, and may activate the onset areas and contribute to the spreading of epileptiform activity.

The spatial relationship between the MRI lesion and intraoperative electrocorticography in focal epilepsy surgery.

MRI and intraoperative electrocorticography are often used in tandem to delineate epileptogenic tissue in resective surgery for focal epilepsy. Both the resection of the MRI lesion and tissue with high rates of electrographic discharges on electrocorticography, e.g. spikes and high-frequency oscillations (80-500 Hz), lead to a better surgical outcome. How MRI and electrographic markers are related, however, is currently unknown. The aim of this study was to find the spatial relationship between MRI lesions and spikes/high-frequency oscillations. We retrospectively included 33 paediatric and adult patients with lesional neocortical epilepsy who underwent electrocorticography-tailored surgery (14 females, median age = 13.4 years, range = 0.6-47.0 years). Mesiotemporal lesions were excluded. We used univariable linear regression to find correlations between pre-resection spike/high-frequency oscillation rates on an electrode and its distance to the MRI lesion. We tested straight lines to the centre and the edge of the MRI lesion, and the distance along the cortical surface to determine which of these distances best reflects the occurrence of spikes/high-frequency oscillations. We conducted a moderator analysis to investigate the influence of the underlying pathology type and lesion volume on our results. We found spike and high-frequency oscillation rates to be spatially linked to the edge of the MRI lesion. The underlying pathology type influenced the spatial relationship between spike/high-frequency oscillation rates and the MRI lesion (P spikes < 0.0001, P ripples < 0.0001), while the lesion volume did not (P spikes = 0.64, P ripples = 0.89). A higher spike rate was associated with a shorter distance to the edge of the lesion for cavernomas [F(1,64) = -1.37, P < 0.0001, η 2 = 0.22], focal cortical dysplasias [F(1,570) = -0.25, P < 0.0001, η 2 = 0.05] and pleomorphic xanthoastrocytomas [F(1,66) = -0.18, P = 0.01, η 2 = 0.09]. In focal cortical dysplasias, a higher ripple rate was associated with a shorter distance [F(1,570) = -0.35, P < 0.0001, η 2 = 0.05]. Conversely, low-grade gliomas showed a positive correlation; the further an electrode was away from the lesion, the higher the rate of spikes [F(1,75) = 0.65, P < 0.0001, η 2 = 0.37] and ripples [F(1,75) = 2.67, P < 0.0001, η 2 = 0.22]. Pathophysiological processes specific to certain pathology types determine the spatial relationship between the MRI lesion and electrocorticography results. In our analyses, non-tumourous lesions (focal cortical dysplasias and cavernomas) seemed to intrinsically generate spikes and high-frequency oscillations, particularly at the border of the lesion. This advocates for a resection of this tissue. Low-grade gliomas caused epileptogenicity in the peritumoural tissue. Whether a resection of this tissue leads to a better outcome is unclear. Our results suggest that the underlying pathology type should be considered when intraoperative electrocorticography is interpreted.