The “Connectivity Epileptogenicity Index ” (cEI), a method for mapping the different seizure onset patterns in StereoElectroEncephalography recorded seizures

ObjectiveLocalization of epileptogenic brain regions is a crucial aim of pre-surgical evaluation of patients with drug-resistant epilepsy. Several methods have been proposed to identify the seizure onset zone, particularly based on the detection of fast activity. Most of these methods are inefficient to detect slower patterns of onset that account for 20–30% of commonly observed Stereo-Electro-Encephalography (SEEG) patterns. We seek to evaluate the performance of a new quantified measure called the Connectivity Epileptogenicity Index (cEI) in various types of seizure onset patterns.MethodsWe studied SEEG recorded seizures from 51 patients, suffering from focal drug-resistant epilepsy. The cEI combines a directed connectivity measure (“out-degrees”) and the original epileptogenicity index (EI). Quantified results (Out-degrees, cEI and EI) were compared to visually defined seizure onset zone (vSOZ). We computed recall (sensitivity) and precision (proportion of correct detections within all detections) with vSOZ as a reference. The quality of the detector was quantified by the area under the precision-recall curve.ResultsBest results (in terms of match with vSOZ) were obtained for cEI. For seizures with fast onset patterns, cEI and EI gave comparable results. For seizures with slow onset patterns, cEI gave a better estimation of the vSOZ than EI.ConclusionsWe observed that cEI discloses better performance than EI when seizures starts with slower patterns and equal to EI in seizures with fast onset patterns.SignificanceThe cEI is a promising new tool for epileptologists, that helps characterizing the seizure onset zone in sEEG, in a robust way despite variations in seizure onset patterns.     

Cortico-cortical evoked potential by single-pulse electrical stimulation is a generally safe procedure

ObjectiveCortico-cortical evoked potential (CCEP) by single-pulse electrical stimulation (SPES) is useful to investigate effective connectivity and cortical excitability. We aimed to clarify the safety of CCEPs.MethodsWe retrospectively analyzed 29 consecutive patients with intractable partial epilepsy undergoing chronic subdural grid implantation and CCEP recording. Repetitive SPES (1 Hz) was systematically applied to a pair of adjacent electrodes over almost all electrodes. We evaluated the incidences of afterdischarges (ADs) and clinical seizures.ResultsOut of 1283 electrode pairs, ADs and clinical seizures were observed in 12 and 5 pairs (0.94% and 0.39%, per electrode pair) in 7 and 3 patients (23.3% and 10.0%, per patient), respectively. Of the 18–82 pairs per patient, ADs and clinical seizures were induced in 0–4 and 0–3 pairs, respectively. Stimulating 4 SOZ (seizure onset zone) (2.5%) and 8 non-SOZ pairs (0.75%) resulted in ADs. We observed clinical seizures in stimulating 4 SOZ (2.5%) and 1 non-SOZ pair (0.09%). The incidence of clinical seizures varied significantly between SOZ and non-SOZ stimulations (p = 0.001), while the difference in AD incidence tended towards significance (p = 0.058).ConclusionAlthough caution should be taken in stimulating SOZ, CCEP is a safe procedure for presurgical evaluation.SignificanceCCEP is safe under the established protocol.     

Individual localization value of resting-state fMRI in epilepsy presurgical evaluation: A combined study with stereo-EEG

ObjectiveTo examine the individual-patient-level localization value of resting-state functional MRI (rsfMRI) metrics for the seizure onset zone (SOZ) defined by stereo-electroencephalography (SEEG) in patients with medically intractable focal epilepsies.MethodsWe retrospectively included 19 patients who underwent SEEG implantation for epilepsy presurgical evaluation. Voxel-wise whole-brain analysis was performed on 3.0 T rsfMRI to generate clusters for amplitude of low-frequency fluctuations (ALFF), regional homogeneity (ReHo) and degree centrality (DC), which were co-registered with the SEEG-defined SOZ to evaluate their spatial overlap. Subgroup and correlation analyses were conducted for various clinical characteristics.ResultsALFF demonstrated concordant clusters with SEEG-defined SOZ in 73.7% of patients, with 93.3% sensitivity and 77.8% PPV. The concordance rate showed no significant difference when subgrouped by lesional/non-lesional MRI, SOZ location, interictal epileptiform discharges on scalp EEG, pathology or seizure outcomes. No significant correlation was seen between ALFF concordance rate and epilepsy duration, seizure-onset age, seizure frequency or number of antiseizure medications. ReHo and DC did not achieve favorable concordance results (10.5% and 15.8%, respectively). All concordant clusters showed regional activation, representing increased neural activities.ConclusionALFF had high concordance rate with SEEG-defined SOZ at individual-patient level.SignificanceALFF activation on rsfMRI can add localizing information for the noninvasive presurgical workup of intractable focal epilepsies.     

Phase-amplitude coupling of ripple activities during seizure evolution with theta phase

ObjectiveHigh-frequency activities (HFAs) and phase-amplitude coupling (PAC) are key neurophysiological biomarkers for studying human epilepsy. We aimed to clarify and visualize how HFAs are modulated by the phase of low-frequency bands during seizures.MethodsWe used intracranial electrodes to record seizures of focal epilepsy (12 focal-to-bilateral tonic-clonic seizures and three focal-aware seizures in seven patients). The synchronization index, representing PAC, was used to analyze the coupling between the amplitude of ripples (80–250 Hz) and the phase of lower frequencies. We created a video in which the intracranial electrode contacts were scaled linearly to the power changes of ripple.ResultsThe main low frequency band modulating ictal-ripple activities was the θ band (4–8 Hz), and after completion of ictal-ripple burst, δ (1–4 Hz)-ripple PAC occurred. The ripple power increased simultaneously with rhythmic fluctuations from the seizure onset zone, and spread to other regions.ConclusionsRipple activities during seizure evolution were modulated by the θ phase. The PAC phenomenon was visualized as rhythmic fluctuations.SignificanceRipple power associated with seizure evolution increased and spread with fluctuations. The θ oscillations related to the fluctuations might represent the common neurophysiological processing involved in seizure generation.     

Intracranial correlates of small sharp spikes

ObjectiveTo identify cortical correlates of scalp small sharp spikes (SSS) using simultaneous scalp and intracranial EEG recordings.MethodsPatients were retrospectively evaluated based on a database of intracranial long-term recordings at the Epilepsy Center Freiburg. Inclusion criteria were: simultaneous recordings with intracranial and scalp EEGs and the presence of at least five unequivocal SSS in the scalp EEG.Intracranial recordings were analyzed regarding the co-occurring intracranial potentials during scalp SSS.Results33 patients, aged 9-60y, 17 females, fulfilled the above-mentioned criteria. Almost all patients had intracranial SSS correlates in the form of spike/polyspike-waves in the temporal lobe, predominantly in the hippocampus (24/28), less frequently involving the amygdala (5/29), temporal basal (3/18), lateral neocortical (4/32), entorhinal cortices (1/12), and the parietal lobe (2/13). Amplitudes of intrahippocampal spikes or polyspikes co-occurring with SSS were significantly higher than intracranial discharges without scalp correlates. In 45% of patients, intracranial spikes accompanying SSS were located within the seizure onset zone (SOZ).ConclusionsOur results strongly support an epileptic origin of SSS and provide evidence about their heterogenous generators.SignificanceThis study suggests that SSS cannot with certainty be classified as “benign” but rather considered as one of the EEG manifestations of focal epilepsy.     

Seizure onset location shapes dynamics of initiation

ObjectiveIctal electrographic patterns are widely thought to reflect underlying neural mechanisms of seizures. Here we studied the degree to which seizure patterns are consistent in a given patient, relate to particular brain regions and if two candidate biomarkers (high-frequency oscillations, HFOs; infraslow activity, ISA) and network activity, as assessed with cross-frequency interactions, can discriminate between seizure types.MethodsWe analyzed temporal changes in low and high frequency oscillations recorded during seizures, as well as phase-amplitude coupling (PAC) to monitor the interactions between delta/theta and ripple/fast ripple frequency bands at seizure onset.ResultsSeizures of multiple electrographic patterns were observed in a given patient and brain region. While there was an increase in HFO rate across different electrographic patterns, there are specific relationships between types of HFO activity and onset region. Similarly, changes in PAC dynamics were more closely related to seizure onset region than they were to electrographic patterns while ISA was a poor indicator for seizure onset.ConclusionsOur findings suggest that the onset region sculpts neurodynamics at seizure initiation and that unique features of the cytoarchitecture and/or connectivity of that region play a significant role in determining seizure mechanism.SignificanceTo learn how seizures are initiated, researchers would do well to consider other aspects of their manifestation, in addition to their electrographic patterns. Examination of onset pattern in conjunction with the interactions between different oscillatory frequencies in the context of different brain regions might be more informative and lead to more reliable clinical inference as well as novel therapeutic approaches.     

Differentiating ictal/subclinical spikes and waves in childhood absence epilepsy by spectral and network analyses: A pilot study

ObjectiveChildhood absence epilepsy (CAE) is a disease with distinct seizure semiology and electroencephalographic (EEG) features. Differentiating ictal and subclinical generalized spikes and waves discharges (GSWDs) in the EEG is challenging, since they appear to be identical upon visual inspection. Here, spectral and functional connectivity (FC) analyses were applied to routine EEG data of CAE patients, to differentiate ictal and subclinical GSWDs.MethodsTwelve CAE patients with both ictal and subclinical GSWDs were retrospectively selected for this study. The selected EEG epochs were subjected to frequency analysis in the range of 1–30 Hz. Further, FC analysis based on the imaginary part of coherency was used to determine sensor level networks.ResultsDelta, alpha and beta band frequencies during ictal GSWDs showed significantly higher power compared to subclinical GSWDs. FC showed significant network differences for all frequency bands, demonstrating weaker connectivity between channels during ictal GSWDs.ConclusionUsing spectral and FC analyses significant differences between ictal and subclinical GSWDs in CAE patients were detected, suggesting that these features could be used for machine learning classification purposes to improve EEG monitoring.SignificanceIdentifying differences between ictal and subclinical GSWDs using routine EEG, may improve understanding of this syndrome and the management of patients with CAE.     

A network approach to investigate the bi-hemispheric synchrony in absence epilepsy

ObjectiveOur objective was to unravel the dynamics underlying spike-and-wave discharges (SWDs) characteristic for childhood absence epilepsy.MethodsSWDs were recorded for a cohort of 28 children using magnetoencephalography. Non-linear association analyses and a graph theoretical metric of local connectedness (LoC) were utilized in a sliding window starting one s before till four s after ictal onset.ResultsA focal pattern of bilateral frontal and parietal areas with high LoC during the spikes alternated by generalized patterns during the waves was found for all children studied during generalization of the SWDs. In the interval preceding the generalization a focal parietal region was most often (16/28) encountered and less often an occipital (4/28), temporal (5/28) or frontal (3/28) region. 55% of the children with a parietal/occipital focal onset became seizure free after the administration of two anti-epileptic drugs, and only 12.5% with a temporal/frontal focal onset.ConclusionsThe transition from the interictal to the ictal state is for some of the children characterized by dominant LoC at either the parietal/occipital and for others at the frontal/temporal region.SignificanceThe focal onset of the SWDs varies in location among the children with a clinical similar profile, who, however, seemingly are differing with regard to seizure control.     

Simultaneously recorded intracranial and scalp high frequency oscillations help identify patients with poor postsurgical seizure outcome

ObjectiveHigh frequency oscillations (HFO) between 80–500 Hz are markers of epileptic areas in intracranial and maybe also scalp EEG. We investigate simultaneous recordings of scalp and intracranial EEG and hypothesize that scalp HFOs provide important additional clinical information in the presurgical setting.MethodsSpikes and HFOs were visually identified in all intracranial scalp EEG channels. Analysis of correlation of event location between intracranial and scalp EEG as well as relationship between events and the SOZ and zone of surgical removal was performed.Results24 patients could be included, 23 showed spikes and 19 HFOs on scalp recordings. In 15/19 patients highest scalp HFO rate was located over the implantation side, with 13 patients having the highest scalp and intracranial HFO rate over the same region. 17 patients underwent surgery, 7 became seizure free. Patients with poor post-operative outcome showed significantly more regions with HFO than those with seizure free outcome.ConclusionsScalp HFOs are mostly located over the SOZ. Widespread scalp HFOs are indicative of a larger epileptic network and associated with poor postsurgical outcome.SignificanceAnalysis of scalp HFO add clinically important information about the extent of epileptic areas during presurgical simultaneous scalp and intracranial EEG recordings.     

Source imaging of seizure onset predicts surgical outcome in pediatric epilepsy

ObjectiveTo assess whether ictal electric source imaging (ESI) on low-density scalp EEG can approximate the seizure onset zone (SOZ) location and predict surgical outcome in children with refractory epilepsy undergoing surgery.MethodsWe examined 35 children with refractory epilepsy. We dichotomized surgical outcome into seizure- and non-seizure-free. We identified ictal onsets recorded with scalp and intracranial EEG and localized them using equivalent current dipoles and standardized low-resolution magnetic tomography (sLORETA). We estimated the localization accuracy of scalp EEG as distance of scalp dipoles from intracranial dipoles. We also calculated the distances of scalp dipoles from resection, as well as their resection percentage and compared between seizure-free and non-seizure-free patients. We built receiver operating characteristic curves to test whether resection percentage predicted outcome.ResultsResection distance was lower in seizure-free patients for both dipoles (p = 0.006) and sLORETA (p = 0.04). Resection percentage predicted outcome with a sensitivity of 57.1% (95% CI, 34–78.2%), a specificity of 85.7% (95% CI, 57.2–98.2%) and an accuracy of 68.6% (95% CI, 50.7–83.5%) (p = 0.01).ConclusionIctal ESI performed on low-density scalp EEG can delineate the SOZ and predict outcome.SignificanceSuch an application may increase the number of children who are referred for epilepsy surgery and improve their outcome.     

A standardized nomenclature for spectrogram EEG patterns: Inter-rater agreement and correspondence with common intensive care unit EEG patterns

ObjectiveTo determine the inter-rater agreement (IRA) of a standardized nomenclature for EEG spectrogram patterns, and to estimate the probability distribution of ictal-interictal continuum (IIC) patterns vs. other EEG patterns within each category in this nomenclature.MethodsWe defined seven spectrogram categories: “Solid Flames”, “Irregular Flames”, “Broadband-monotonous”, “Narrowband-monotonous”, “Stripes”, “Low power”, and “Artifact”. Ten electroencephalographers scored 115 spectrograms and the corresponding raw EEG samples. Gwet's agreement coefficient was used to calculate IRA.ResultsSolid Flames represented seizures or IIC patterns 69.4% of the time. Irregular Flames represented seizures or IIC patterns 38.7% of the time. Broadband-monotonous primarily corresponded with seizures or IIC (54.3%) and Narrowband-monotonous with focal or generalized slowing (43.8%). Stripes were associated with burst-suppression (37.2%) and generalized suppression (34.4%). Low Power category was associated with generalized suppression (94%). There was “near perfect” agreement for Solid Flames (κ = 94.36), Low power (κ = 92.61), and Artifact (κ = 93.72). There was “substantial agreement” for all other categories (κ = 74.65–79.49).ConclusionsThis EEG spectrogram nomenclature has high IRA among electroencephalographers.SignificanceThe nomenclature can be a useful tool for EEG screening. Future studies are needed to determine if using this nomenclature shortens time to IIC identification, and how best to use it in practice to reduce time to intervention.     

Spatio-temporal dynamics of interictal activity in musicogenic epilepsy: Two case reports and a systematic review of the literature

ObjectiveTo explore neurophysiological features of musicogenic epilepsy (ME), discussing experimental findings in the framework of a systematic review on ME.MethodsTwo patients with ME underwent high-density-electroencephalography (hd-EEG) while listening to ictogenic songs. In one case, musicogenic seizures were elicited. Independent component analysis (ICA) was applied to hd-EEG, and components hosting interictal and ictal elements were identified and localized. Finally, the temporal dynamics of spike-density was studied relative to seizures. All findings were compared against the results of a systematic review on ME, collecting 131 cases.ResultsInterictal spikes appeared isolated in specific fronto-temporal independent components, whose cortical generators were located in the anterior temporal and inferior frontal lobe. In the patient undergoing seizure, ictal discharge relied in the same component, with the interictal spike-density decreasing before the seizure onset.ConclusionOur study shows how ICA can isolate neurophysiological features of ictal and interictal discharges in ME, highlighting a fronto-temporal localization and a suppression of spike-density preceding the seizure onset.SignificanceWhile the localization of ME activity could indicate which aspect within the musical stimulus might trigger musicogenic seizures for each patient, the study of ME dynamics could contribute to the development of models for seizure-prediction and their validation.     

Ictal gamma-band interactions localize ictogenic nodes of the epileptic network in focal cortical dysplasia

ObjectiveEpilepsy surgery fails in > 30% of patients with focal cortical dysplasia (FCD). The seizure persistence after surgery can be attributed to the inability to precisely localize the tissue with an endogenous potential to generate seizures. In this study, we aimed to identify the critical components of the epileptic network that were actively involved in seizure genesis.MethodsThe directed transfer function was applied to intracranial EEG recordings and the effective connectivity was determined with a high temporal and frequency resolution. Pre-ictal network properties were compared with ictal epochs to identify regions actively generating ictal activity and discriminate them from the areas of propagation.ResultsAnalysis of 276 seizures from 30 patients revealed the existence of a seizure-related network reconfiguration in the gamma-band (25–170 Hz; p < 0.005) – ictogenic nodes. Unlike seizure onset zone, resecting the majority of ictogenic nodes correlated with favorable outcomes (p < 0.012).ConclusionThe prerequisite to successful epilepsy surgery is the accurate identification of brain areas from which seizures arise. We show that in FCD-related epilepsy, gamma-band network markers can reliably identify and distinguish ictogenic areas in macroelectrode recordings, improve intracranial EEG interpretation and better delineate the epileptogenic zone.SignificanceIctogenic nodes localize the critical parts of the epileptogenic tissue and increase the diagnostic yield of intracranial evaluation.     

Predictive value of electrically induced seizures for postsurgical seizure outcome

ObjectiveTo determine whether semiological similarity of electrically induced seizures (EIS) and spontaneously occurring habitual seizures (SHS) is associated with postsurgical seizure outcome in patients undergoing invasive video-EEG monitoring (VEM) before resective epilepsy surgery.MethodsData of patients undergoing invasive VEM were retrospectively reviewed and included if at least one EIS and SHS during VEM occurred and the brain region in which EIS were elicited was resected. Seizure outcome was evaluated at three follow-up (FU) visits after surgery (1, 2 years and last available FU) according to the classification by Engel and the International League Against Epilepsy (ILAE). The level of semiological similarity of EIS and SHS was rated blinded to the surgical outcome. Statistics were done using Fisher’s exact test and a mixed linear-logistic regression model.Results65 patients were included. Postsurgical seizure freedom was achieved in 51% (ILAE class 1) and 58% (Engel class I) at last FU (median 36 months). Patients with identical EIS and SHS displayed significantly better postsurgical seizure outcomes (ILAE class 1 at last FU: 76% vs. 31%, p < 0.001; Engel class I: 83% vs. 39%, p < 0.001).ConclusionEIS are useful to confirm the location of the epileptogenic zone. A high level of similarity between EIS and SHS is associated with a favorable postsurgical seizure outcome.SignificanceEIS may be used as an additional predictor of postsurgical outcome when counselling patients to proceed to resective epilepsy surgery.     

A pediatric case of autoimmune encephalitis with chronologically moving seizure foci and cortical lesions: A case report

IntroductionAutoimmune encephalitis (AIE) is a relatively newly described category of immune-mediated diseases involving the central nervous system with a wide spectrum of clinical presentations, ranging from relatively mild or insidious onset of cognitive impairment to more complex forms of encephalopathy with medically refractory seizures. Single or multifocal seizures accompanied by neuropsychiatric symptoms and cognitive or memory impairments are suggestive of clinical features at AIE onset.Case reportA six-year-old boy presented with repetitive focal seizures, slowly progressive emotional liability, and attention-deficit/hyperactivity disorder-like symptoms. Seizure types varied during the clinical course, sometimes emerging as clusters or statuses. MRI performed during seizure clustering/status revealed moving signal abnormalities. We successfully treated the patient with high-dose intravenous methylprednisolone. Cerebrospinal fluid analysis revealed pleocytosis and marked elevation of antibodies against N-terminals of N-methyl-d-aspartate type glutamate receptor subunits and granzyme B.ConclusionWe report a case of moving seizure foci with abnormal MRI findings. Although the onset of psychiatric symptoms slowly progressed to those atypical for AIE, responsiveness to immunotherapy, cerebrospinal fluid pleocytosis, and autoantibodies all indicated AIE. We thus suggest that moving seizure foci and abnormal MRI signals may be findings of AIE.     

Safe and sound: Meta-analyzing the Mozart effect on epilepsy

ObjectiveThe use of music-based neuro-stimulation for treating seizures and interictal epileptiform discharges (IED) (the so-called “Mozart effect”) remains a controversial issue. We have conducted an updated meta-analysis in order to systematically review literature evidence and provide further insights about the role of the Mozart effect in epilepsy.MethodsFollowing the “Preferred Reporting Items for Systematic Reviews and Meta-Analyses” (PRISMA) guidelines, we searched three bibliographic databases from their date of inception to January 2020. Nine meta-analyses were performed according to both music stimulation protocols and outcome measures. We applied the Cochrane Q-test and the I²-index for heterogeneity evaluation, and either fixed-effect or random-effect models to compute mean differences and pool data.ResultsOf 147 abstracts, 12 studies were included and grouped according to stimulation protocols and outcome measures. The nine meta-analyses showed significant reductions in seizures and IED frequencies after long-term music treatment, and in IED frequency during and after a single music stimulus.ConclusionsMusic-based neurostimulation may improve the clinical outcome of individuals with epilepsy, by reducing the frequency of seizures and IED. Further and stronger evidence will allow defining its potential in the different forms of epilepsy, and the most effective stimulation protocols.SignificanceMusic therapy should be considered as a complementary, non-invasive approach for treating epilepsy and epileptiform discharges.     

Source-level EEG and graph theory reveal widespread functional network alterations in focal epilepsy

ObjectiveThe hypersynchronous neuronal activity associated with epilepsy causes widespread functional network disruptions extending beyond the epileptogenic zone. This altered network topology is considered a mediator for non-seizure symptoms, such as cognitive impairment. The aim of this study was to investigate functional network alterations in focal epilepsy patients with good seizure control and high quality of life.MethodsWe compared twenty-two focal epilepsy patients and sixteen healthy controls on graph metrics derived from functional connectivity of source-level resting-state EEG. Graph metrics were calculated over a range of network densities in five frequency bands.ResultsWe observed a significantly increased small world index in patients relative to controls. On the local level, two left-hemisphere regions displayed a shift towards greater alpha band “hubness”. The findings were not mediated by age, sex or education, nor by age of epilepsy onset, duration or focus lateralisation.ConclusionsWidespread functional network alterations are evident in focal epilepsy, even in a cohort characterised by successful anti-seizure medication therapy and high quality of life. These findings might support the position that functional network analysis could hold clinical relevance for epilepsy.SignificanceFocal epilepsy is accompanied by global and local functional network aberrancies which might be implied in the sustenance of non-seizure symptoms.     

Myoclonic super-refractory status epilepticus with favourable evolution in a teenager with FIRES: Is the association of vagus nerve stimulation and cannabidiol effective?

BackgroundFebrile infection-related epilepsy syndrome (FIRES) is a rare and catastrophic clinical syndrome occurring in previously healthy patients. Aetiology is still unknown and outcome usually poor. We describe a case of myoclonic prolonged super refractory status epilepticus (P-SRSE) in FIRES in a patient admitted to the paediatric intensive care unit of Padova, Italy.Case reportA previously healthy 14-year-old girl with onset of myoclonic status epilepticus after a mild febrile illness was admitted to our hospital with a diagnosis of FIRES. Extensive diagnostic work-up was inconclusive. Status epilepticus and electroclinical seizures recurred every time weaning from anaesthetic agents was attempted. Eventually, a vagal nerve stimulator (VNS) was implanted and cannabidiol (CBD) administered, 43 days and 70 days after P-SRSE onset, respectively. Two days after CBD introduction, status epilepticus weaned and the girl rapidly regained complete consciousness showing a brilliant and unexpected recovery. At last follow-up, 12 months later, she is 8-months seizure free on multiple antiseizure medications, has only mild neuropsychological impairment with no neurological and intellective deficit.ConclusionsTo our knowledge, this represents a unique case with an extremely favourable evolution with a possible effect of the association of VNS and CBD to traditional antiseizure medications.     

Inter-ictal network of focal epilepsy and effects of clinical factors on network activity

ObjectiveAim of the study was to explore the inter-ictal, resting-state EEG network in patients with focal epilepsy (FE) and to specify clinical factors that influence network activity.MethodsFunctional EEG connectivity (EEGfC) differences were computed between 232 FE patients (FE group) and 77 healthy controls. EEGfC was computed among 23 cortical regions within each hemisphere, for 25 very narrow bands from 1 to 25 Hz. We computed independent effects for six clinical factors on EEGfC in the FE group, by ANOVA and post-hoc t-statistics, corrected for multiple comparisons by false discovery rate method.ResultsRobust, statistically significant EEGfC differences emerged between the FE and the healthy control groups. Etiology, seizure type, duration of the illness and antiepileptic treatment were independent factors that influenced EEGfC. Statistically significant results occurred selectively in one or a few very narrow bands and outlined networks. Most abnormal EEGfC findings occurred at frequencies that mediate integrative and motor activities.ConclusionsFE patients have abnormal resting-state EEGfC network activity. Clinical factors significantly modify EEGfC.SignificanceDelineation of the FE network and modifying factors can open the way for targeted investigations and introduction of EEGfC into epilepsy research and practice.     

Electrical cortical stimulations modulate spike and post-spike slow-related high-frequency activities in human epileptic foci

ObjectiveUsing interictal epileptiform discharges (IEDs), consisting of spikes and post-spike slow waves (PSSs), and IED-related high-frequency activities (HFAs), we elucidated inhibitory effects of electrical cortical stimulation (ECS) on human epileptic foci.MethodsWe recruited 8 patients with intractable focal epilepsy, and 50-Hz ECS was applied to the seizure-onset zone (SOZ) and non-SOZ. Before (5-min) and after (20-min) ECS, we evaluated the number of IED, the amplitudes of spikes and PSSs, spike-related HFA power, and PSS-related low gamma (30–50 Hz) activities.ResultsSOZ stimulation significantly decreased the number of IEDs and amplitude of spikes. Spike-related HFA power values in fast ripple (200–300 Hz) and ripple (80–150 Hz) bands were significantly suppressed only by SOZ stimulation in 4 and 3 patients, respectively. Among 4 patients with discrete PSSs, the amplitude ratio of spike/PSS decreased and the PSS-related low gamma activity power increased significantly in 2 patients and marginally in 1 patient.ConclusionsECS potentially modulates cortical excitability by reducing excitation and increasing inhibition, and monitoring IED-related HFAs may help achieve the optimal effects of ECS.SignificanceIED and IED-related HFAs are dynamic, potential surrogate markers for epileptic excitability during the interictal period.