Intracortical neural activity distal to seizure-onset-areas predicts human focal seizures

Abstract An improved understanding of the mechanisms underlying neuromodulatory approaches to mitigate seizure onset is needed to identify clinical targets for the treatment of epilepsy. Using a Wilson–Cowan-motivated network of inhibitory and excitatory populations, we examined the role played by intrinsic and extrinsic stimuli on the network’s predisposition to sudden transitions into oscillatory dynamics, similar to the transition to the seizure state. Our joint computational and mathematical analyses revealed that such stimuli, be they noisy or periodic in nature, exert a stabilizing influence on network responses, disrupting the development of such oscillations. Based on a combination of numerical simulations and mean-field analyses, our results suggest that high variance and/or high frequency stimulation waveforms can prevent multi-stability, a mathematical harbinger of sudden changes in network dynamics. By tuning the neurons’ responses to input, stimuli stabilize network dynamics away from these transitions. Furthermore, our research shows that such stabilization of neural activity occurs through a selective recruitment of inhibitory cells, providing a theoretical undergird for the known key role these cells play in both the healthy and diseased brain. Taken together, these findings provide new vistas on neuromodulatory approaches to stabilize neural microcircuit activity.

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Ictal Blinking: Reappraisal of the Lateralization and Localization Value in Focal Seizures

Clinical EEG and Neuroscience ◽

10.1177/15500594211070800 ◽

2022 ◽

pp. 155005942110708

Author(s):

Ayse Nur Ozdag Acarli ◽

Ayse Deniz Elmali ◽

Nermin Gorkem Sirin ◽

Betul Baykan ◽

Nerses Bebek

Keyword(s):

The Other ◽

Eeg Monitoring ◽

Seizure Onset ◽

Future Studies ◽

Focal Seizures ◽

Scalp Eeg ◽

Ictal Activity ◽

Generalized Epilepsy ◽

Video Eeg ◽

Sign Method

Introduction. Although ictal blinking is significantly more frequent in generalized epilepsy, it has been reported as a rare but useful lateralizing sign in focal seizures when it is not associated with facial clonic twitching. This study aimed to raise awareness of eye blinking as a semiological lateralizing sign. Method. Our database over an 11-year period reviewed retrospectively to assess patients who had ictal blinking associated with focal seizures. Results. Among 632 patients, 14 (2.2%), who had 3 to 13 (7 ± 3) seizures during video-EEG monitoring, were included. Twenty-five percent of all 92 seizures displayed ictal blinking and each patient had one to five seizures with ictal blinking. Ictal blinking was unilateral in 17%, asymmetrical in 22% and symmetrical in 61%. The blinking appeared with a mean latency of 6.3 s (range 0-39) after the clinical seizure-onset, localized most often to fronto-temporal, then in frontal or occipital regions. Blinking was ipsilateral to ictal scalp EEG lateralization side in 83% (5/6) of the patients with unilateral/asymmetrical blinking. The exact lateralization and localization of ictal activity could not have been determined via EEG in most of the patients with symmetrical blinking, remarkably. Conclusions. Unilateral/asymmetrical blinking is one of the early components of the seizures and appears as a useful lateralizing sign, often associated with fronto-temporal seizure-onset. Symmetrical blinking, on the other hand, did not seem to be valuable in lateralization and localization of focal seizures. Future studies using invasive recordings and periocular electrodes are needed to evaluate the value of blinking in lateralization and localization.

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Neonatal Onset of Epilepsy of Infancy with Migrating Focal Seizures Associated with a Novel GABRB3 Variant in Monozygotic Twins

Neuropediatrics ◽

10.1055/s-0038-1626708 ◽

2018 ◽

Vol 49 (03) ◽

pp. 204-208 ◽

Cited By ~ 6

Author(s):

Katalin Štěrbová ◽

Markéta Vlčková ◽

Petr Klement ◽

Jana Neupauerová ◽

David Staněk ◽

...

Keyword(s):

Transmembrane Domain ◽

De Novo ◽

Massively Parallel Sequencing ◽

Monozygotic Twins ◽

Neonatal Seizures ◽

Seizure Onset ◽

Focal Seizures ◽

Neonatal Onset ◽

Early Seizure ◽

Insight Into

Background Recently, a study providing insight into GABRB3 mutational spectrum was published (Møller et al 2017). The authors report considerable pleiotropy even for single mutations and were not able to identify any genotype–phenotype correlations. Methods The proband (twin B) was referred for massively parallel sequencing of epilepsy-related gene panel because of hypotonia and neonatal seizures. The revealed variant was confirmed with Sanger sequencing in the proband and the twin A, and both parents were tested for the presence of the variant. Results We report a case of epilepsy of infancy with migrating focal seizures (EIMFS) of neonatal onset in monozygotic twins with a de novo novel GABRB3 variant p.Thr281Ala. The variant has a uniform presentation on an identical genomic background. In addition, early seizure-onset epilepsy associated with GABRB3 mutation has been until now described only for the p.Leu256Gln variant in the GABRB3 (Møller et al 2017, Myers et al 2016) located in the transmembrane domain just as the p.Thr281Ala variant described here. Conclusion De novo GABRB3 mutations may cause neonatal-onset EIMFS with early-onset hypotonia, respiratory distress, and severe developmental delay.

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Frequency of peri-ictal apnea and cardiac arrhythmias in epileptic seizures

The Egyptian Journal of Neurology Psychiatry and Neurosurgery ◽

10.1186/s41983-021-00295-3 ◽

2021 ◽

Vol 57 (1) ◽

Author(s):

Rady Yousif ◽

M. Ossama Abdulghani ◽

A. Gaber ◽

Naglaa El Khayat ◽

Y. A. Abo Elnaga ◽

...

Keyword(s):

Temporal Lobe Epilepsy ◽

Temporal Lobe ◽

Cardiac Arrhythmias ◽

Focal Epilepsy ◽

Epileptic Seizures ◽

Electrode System ◽

Seizure Onset ◽

Unexpected Death ◽

Focal Seizures ◽

Epileptic Patients

Abstract Background Available data from witnessed and monitored sudden unexpected death in epilepsy (SUDEP) cases postulate that ictal central apnea (ICA) and ictal arrhythmias are the main causes of SUDEP. ICA is a frequent semiological feature of focal epilepsy and occasionally the only clinical manifestation of focal seizures. The aim of this study was to assess the frequency of ICA and cardiac arrhythmias in epileptic patients and to study the risk factors and predictors of their occurrence. Methods Fifty patients diagnosed with epilepsy were recruited in this study. All participants underwent prolonged surface video electroencephalography (VEEG) study using the 10-20 international electrode system with concomitant polysomnography including electrocardiography (ECG), heart rate monitoring, and peripheral capillary oxygen saturation (SpO2) using pulse oximetry. Also inductance plethysmography was used to record chest and abdominal excursions. Results Complete datasets were available in 50 patients and 112 seizures were recorded. ICA occurred exclusively in focal epilepsy (P <0.001). Temporal lobe epilepsy was associated with higher occurrence of ICA in comparison to extratemporal epilepsy (P <0.001). In addition, seizures lateralized to the left hemisphere were associated with higher occurrence of ICA (P <0.001). On the other side, tachycardia was found to be more associated with temporal lobe epilepsy and left hemispheric seizure onset (P <0.001). Conclusion ICA occurred exclusively in focal seizures and tachycardia magnitude was more with focal seizures, and both had higher percentage in temporal lobe epilepsy in comparison to other types and in seizures with left hemispheric onset.

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Intracortical neural activity distal to seizure-onset-areas predicts human focal seizures

10.1101/529966 ◽

2019 ◽

Author(s):

Timothée Proix ◽

Mehdi Aghagolzadeh ◽

Joseph R Madsen ◽

Rees Cosgrove ◽

Emad Eskandar ◽

...

Keyword(s):

Large Scale ◽

Neuronal Networks ◽

Microelectrode Arrays ◽

Machine Learning Algorithms ◽

Gradient Boosting ◽

Seizure Onset ◽

Focal Seizures ◽

Multiunit Activity ◽

Extreme Gradient Boosting ◽

Initial Results

AbstractThe apparent unpredictability of epileptic seizures has a major impact in the quality of life of people with pharmacologically resistant seizures. Here, we present initial results and a proof-of-concept of how focal seizures can be predicted early in advance based on intracortical signals recorded from small neocortical patches away from identified seizure onset areas. We show that machine learning algorithms can discriminate between interictal and preictal periods based on multiunit activity (i.e. thresholded action potential counts) and multi-frequency band local field potentials recorded via 4 X 4 mm2 microelectrode arrays. Microelectrode arrays were implanted in 5 patients undergoing neuromonitoring for resective surgery. Post-implant analysis revealed arrays were outside the seizure onset areas. Preictal periods were defined as the 1-hour period leading to a seizure. A 5-minute gap between the preictal period and the putative seizure onset was enforced to account for potential errors in the determination of actual seizure onset times. We used extreme gradient boosting and long short-term memory networks for prediction. Prediction accuracy based on the area under the receiver operating characteristic curves reached 90% for at least one feature type in each patient. Importantly, successful prediction could be achieved based exclusively on multiunit activity. This result indicates that preictal activity in the recorded neocortical patches involved not only subthreshold postsynaptic potentials, perhaps driven by the distal seizure onset areas, but also neuronal spiking in distal recurrent neocortical networks. Beyond the commonly identified seizure onset areas, our findings point to the engagement of large-scale neuronal networks in the neural dynamics building up toward a seizure. Our initial results obtained on currently available human intracortical recordings warrant new studies on larger datasets, and open new perspectives for seizure prediction and control by emphasizing the contribution of multiscale neural signals in large-scale neuronal networks.

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Case Report: Aperiodic Fluctuations of Neural Activity in the Ictal MEG of a Child With Drug-Resistant Fronto-Temporal Epilepsy

Frontiers in Human Neuroscience ◽

10.3389/fnhum.2021.646426 ◽

2021 ◽

Vol 15 ◽

Author(s):

Saskia van Heumen ◽

Jeremy T. Moreau ◽

Elisabeth Simard-Tremblay ◽

Steffen Albrecht ◽

Roy WR. Dudley ◽

...

Keyword(s):

Neural Activity ◽

Brain Activity ◽

Diagnostic Methods ◽

Drug Resistant ◽

Seizure Onset ◽

Source Imaging ◽

Temporal Epilepsy ◽

Aperiodic Component ◽

Temporal Neocortex ◽

Control Regions

Successful surgical treatment of patients with focal drug-resistant epilepsy remains challenging, especially in cases for which it is difficult to define the area of cortex from which seizures originate, the seizure onset zone (SOZ). Various diagnostic methods are needed to select surgical candidates and determine the extent of resection. Interictal magnetoencephalography (MEG) with source imaging has proven to be useful for presurgical evaluation, but the use of ictal MEG data remains limited. The purpose of the present study was to determine whether pre-ictal variations of spectral properties of neural activity from ictal MEG recordings are predictive of SOZ location.We performed a 4 h overnight MEG recording in an 8-year-old child with drug-resistant focal epilepsy of suspected right fronto-temporal origin and captured one ~45-s seizure. The patient underwent a right temporal resection from the anterior temporal neocortex and amygdala to the mid-posterior temporal neocortex, sparing the hippocampus proper. She remains seizure-free 21 months postoperatively. The histopathological assessment confirmed frank focal cortical dysplasia (FCD) type IIa in the MEG-defined SOZ, which was based on source imaging of averaged ictal spikes at seizure onset. We investigated temporal changes (inter-ictal, pre-ictal, and ictal periods) together with spatial differences (SOZ vs. control regions) in spectral parameters of background brain activity, namely the aperiodic broadband offset and slope, and assessed how they confounded the interpretation of apparent variations of signal power in typical electrophysiological bands. Our data show that the SOZ was associated with a higher aperiodic offset and exponent during the seizure compared to control regions. Both parameters increased in all regions from 2 min before the seizure onwards. Regions anatomically closer to the SOZ also expressed higher values compared to contralateral regions, potentially indicating ictal spread. We also show that narrow-band power changes were caused by these fluctuations in the aperiodic component of ongoing brain activity. Our results indicate that the broadband aperiodic component of ongoing brain activity cannot be reduced to background noise of no physiological interest, and rather may be indicative of the neuropathophysiology of the SOZ. We believe these findings will inspire future studies of ictal MEG cases and confirm their significance.

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Less efficacy of valproic acid monotherapy may be caused by neural excitatory rebound in seizures

10.1101/2021.11.02.21265719 ◽

2021 ◽

Author(s):

Xiang Zou ◽

Zilu Zhu ◽

Yu Guo ◽

Hongmiao Zhang ◽

Yuchen Liu ◽

...

Keyword(s):

Valproic Acid ◽

Neural Activity ◽

Field Potential ◽

Multiple Wave ◽

Focal Seizures ◽

Power Shift ◽

Power Spectral ◽

Inhibitory Power ◽

Local Field Potential Lfp ◽

Spike Firing

Valproic acid (VPA) represents one of the most efficient antiepileptic drugs (AEDs) with either general or focal seizures, but a certain percentage of patients are not recovered or even worse, the mechanism under this phenomenon remains unclear. Here, we retrospectively reviewed 16 patients who received awake craniotomy surgery. Intro-operative high density electrocorticogram (ECoG) was used to record the local field potential (LFP) response to VPA treatment. We found the less efficacy of VPA monotherapy was associated with ECoG spectrum power shift from higher to lower frequency after VPA injection, together with increased synchronization of the LFP. Furthermore, we established the computational model to testify the hypothesis that the ineffectivity of VPA may be caused by excitatory dynamic rebound during the inhibitory power increasing. In addition to test the hypothesis, we employed the mice with Kanic Acid (KA)-induced epileptic model to confirm that it would be inhibited by VPA on behavior and neural activity. Also, the neural activity shows significant rebound on spike firing. Then we discovered that the LFP would increase the power spectral density in multiple wave bands after the VPA delivers. These findings suggest that less efficacy of valproic acid monotherapy in focal seizures may be caused by neural excitatory rebound which mediated by elevated inhibitory power.

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Detection of recurrent activation patterns across focal seizures: Application to seizure onset zone identification

Clinical Neurophysiology ◽

10.1016/j.clinph.2017.03.040 ◽

2017 ◽

Vol 128 (6) ◽

pp. 977-985 ◽

Cited By ~ 8

Author(s):

Manel Vila-Vidal ◽

Alessandro Principe ◽

Miguel Ley ◽

Gustavo Deco ◽

Adrià Tauste Campo ◽

...

Keyword(s):

Seizure Onset ◽

Activation Patterns ◽

Focal Seizures ◽

Seizure Onset Zone

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P.103 Midline Spikes and Intractable Seizures in Pediatric Epilepsy

Canadian Journal of Neurological Sciences / Journal Canadien des Sciences Neurologiques ◽

10.1017/cjn.2021.381 ◽

2021 ◽

Vol 48 (s3) ◽

pp. S49-S49

Author(s):

K Luan ◽

J Mailo ◽

N Liu ◽

J Kassiri ◽

DB Sinclair

Keyword(s):

Focal Cortical Dysplasia ◽

Intractable Epilepsy ◽

Pediatric Epilepsy ◽

Seizure Freedom ◽

Epileptogenic Zone ◽

Seizure Onset ◽

Focal Seizures ◽

Intractable Seizures ◽

Epileptic Discharges ◽

Common Etiology

Background: Epileptic discharges localized to the midline vertex are rare. However, they have been associated with intractable seizures and severe long-term consequences in the developing brain. Our study aimed to understand the etiology of pediatric midline seizures and define post-surgical seizure outcomes. Methods: We reviewed charts, electroencephalography (EEG), and neuroimaging studies of ten pediatric patients with epileptic discharges localized to the midline vertex in the Comprehensive Epilepsy Program. The seizures were classified according to the International League Against Epilepsy criteria, patient age, sex, neuroimaging results, seizure etiology and outcomes were obtained. Results: Age of seizure onset was within the first 10 years of life in 90% of patients, with focal seizures being the most prevalent. Focal cortical dysplasia (FCD) was the most common etiology present in 50% of patients. These children had normal neuroimaging studies and intractable epilepsy. However, seizure freedom was achieved following surgical resection of the epileptogenic zone. Conclusions: We demonstrated that patients with midline epileptic discharges are associated with intractable focal seizures and early seizure onset. Despite normal neuroimaging reports, FCD was the most common pathology. Thus our study suggests early localization and resection of the epileptogenic zone may be beneficial for achieving seizure freedom in children with this electroclinical syndrome.

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