Ictal High Frequency Oscillations Research Articles

Frequency-dependent seizure-suppressing effects of optogenetic activation of septal inhibitory cells in mesial temporal lobe epilepsy

Mesial temporal lobe epilepsy (MTLE) is characterized by recurring focal seizures that arise from limbic areas and are often refractory to pharmacological interventions. We have reported that optogenetic stimulation of PV-positive cells in the medial septum at 0.5 Hz exerts seizure-suppressive effects. Therefore, we compared here these results with those obtained by optogenetic stimulation of medial septum PV-positive neurons at 8 Hz in male PV-ChR2 mice (P60-P100) undergoing an initial, pilocarpine-induced status epilepticus (SE). Optogenetic stimulation (5 min ON, 10 min OFF) was performed from day 8 to day 12 after SE at a frequency of 8 Hz (n = 6 animals) or 0.5 Hz (n = 8 animals). Surprisingly, in both groups, no effects were observed on the occurrence of interictal spikes and interictal high frequency oscillations (HFOs). However, 0.5 Hz stimulation induced a significant decrease of seizure occurrence (p < 0.05). Such anti-ictogenic effect was not observed in the 8 Hz protocol that instead triggered seizures (p < 0.05); these seizures were significantly longer under optogenetic stimulation compared to when optogenetic stimulation was not implemented (p < 0.05). Analysis of ictal HFOs revealed that in the 0.5 Hz group, but not in the 8 Hz group, seizures occurring under optogenetic stimulation were associated with significantly lower rates of fast ripples compared to when optogenetic stimulation was not performed (p < 0.05). Our results indicate that activation of GABAergic PV-positive neurons in the medial septum exerts seizure-suppressing effects that are frequency-dependent and associated with low rates of fast ripples. Optogenetic activation of medial septum PV-positive neurons at 0.5 Hz is efficient in blocking seizures in the pilocarpine model of MTLE, an effect that did not occur with 8 Hz stimulation.

Ictal Direct Current Shifts Preceded Much Earlier Than High Frequency Oscillations After Status: Is It the Effect of Status or Antiseizure Medication?

While spikes and sharp waves are considered as markers of epilepsy in conventional electroencephalography, ictal direct current (DC) shifts and high-frequency oscillations (HFOs) appear to be useful biomarkers for epileptogenicity. We analyzed how ictal DC shifts and HFOs were affected by focal status epilepticus and antiseizure medications (ASMs). A 20-year-old female patient who underwent long-term intracranial electrode implantation for epilepsy surgery presented with 72 habitual seizures and a focal status epilepticus episode lasting for 4 h. Ten, 3, and 10 consecutive habitual seizures were analyzed before the status, after the status, and after ASM (valproate) loading, respectively. Before and immediately after the status, ictal DC shifts remained the same in terms of the amplitude, duration, and slope of DC shifts. High-frequency oscillations also remained the same in terms of the duration, frequency, and power except for the power of the lower frequency band. After ASM loading, the duration, amplitude, and slope of the ictal DC shift were significantly attenuated. The duration, frequency, and power of the HFOs were significantly attenuated. Furthermore, the interval between the DC onset and HFO onset was significantly longer and the interval between the HFO onset and ictal DC shift peak was significantly shorter. The attenuation of ictal DC shifts and HFOs after ASM loading implies that astrocyte and neuronal activity may be both attenuated by ASMs. This finding may help with our understanding of the pathophysiology of epilepsy and can aid with the discovery of new approaches for epilepsy management.

Startle-Induced Epileptic Spasms: A Clinical and Video-EEG Study.

ObjectiveThis study aimed to delineate the detailed characteristics of startle-induced epileptic spasms (ES) and explore the brain regions where startle-induced ES originated.MethodsAmong 581 patients with ES registered in our database, 30 were diagnosed with startle-induced ES according to video-electroencephalogram (EEG) and seizure semiology and were included in this study. Patients' clinical characteristics and ictal high-frequency oscillations (HFOs) were analyzed.ResultsMean age at the onset of startle-induced ES was 28.1 months. Half of the patients had structural etiology, two of whom were diagnosed with co-existing structural and genetic etiologies. The focal neuroimaging abnormalities were predominant in the frontal cortex (9/15, 60.0%). Fifteen patients (50%) had prominent interictal epileptiform discharges in the frontal and anterior temporal. Ictal HFOs counts of the startle-induced ES in the anterior region were significantly higher than those in the posterior regions (p < 0.05). Five patients (16.7%) became seizure-free ≥6 months, and ten (33.3%) showed startle-induced ES cessation ≥6 months. All patients except one had mild to severe psychomotor developmental delay after the onset of seizures.ConclusionPatients with startle-induced ES typically had brain lesions and showed drug-resistant. The neuroimaging and EEG findings, including ictal HFOs, support that startle-induced ES often originates from the frontal cortex.

WS1.9. Advances in EEG Analysis – Wide-Band EEG, Dense-Array EEG and Quantitative EEG

1) Wide-band EEG As the faster frequency extreme of wide-band EEG, high frequency oscillation (HFO) was originally described by means of 1) micro-electrode recording in animal model, and ictal HFO occurred before clinical onset. Recently, 2 more types of HFO were well described; 2) invasive electrodes recording in epilepsy surgery (macro-invasive electrodes such as depth-, subdural ones), and 3) scalp electrodes or MEG in epilepsy patients. The multiple mechanisms of HFO generation are considered such as synchronized post-synaptic potentials with sparse pyramidal cell firing, or principal cell action potentials. As the lower frequency of extreme of baseline shifts in the chronic epilepsy focus on epilepsy patients, ictal DC shifts occurred earlier than or as early as ictal HFO significantly (Imamura et al., 2011; Kanazawa et al., 2015). It was newly endorsed by the pathological abnormality, i.e., decreased Kir4.1, selectively seen in the cortices generating ictal DC shifts (Kobayashi et al., 2017). It could suggest more active role of glia before seizure generation, and thus called as active DC shifts. These both findings could represent activity of both epileptic neurons and astrocytes, respectively, mainly as the local field potentials. 2) Quantitative EEG Once digital EEG era has started since 1989, first generation EEG (1989-1996/2000) could provide us with data acquisition of ordinary sampling rate (i.e., 500 Hz) and band pass filter (i.e., 0.5 Hz - 200 Hz). Data display has been much flexible by means of reformat of montage, filter change, sensitivity change, voltage mapping, power spectrum analysis, and 3D source analysis, and so on. It is user friendly, and regarded as the established tool or method. Second generation EEG (1996/2000-present) has been much advanced and complicated tool such as data acquisition such as wide-band EEG, i.e., 0.016 Hz - 600 Hz. It contains DC shifts, infraslow, HFO. Increased sampling rate, i.e., 2000 Hz could widen the extremely faster activitty. Data display such as wide-band display, i.e., 100 ms/page to 5 min/page, time frequency analysis, DSA (Density Modulated Spectral Array), and Ganger causality further led us to the interactive sophisticated circumstances in the clinical and scientific field. 3) Dense-array EEG The more electrodes are placed on the scalp, the better spatial resolution is expected. Once it also could cover the so-called “south hemispheres” of the head, it could delineate the any activity arising from the basal temporal and mesial temporal areas. However, since scalp EEG is attenuated in amplitude and is blurred with wider distribution by means of cortical bone and different soft tissues, the degree of localization map may not be proportionally precise in spite of involvement of many electrodes. In this regard, whole MEG data may overcome of the 2 important factors.

Dual mechanisms of ictal high frequency oscillations in human rhythmic onset seizures

High frequency oscillations (HFOs) are bursts of neural activity in the range of 80 Hz or higher, recorded from intracranial electrodes during epileptiform discharges. HFOs are a proposed biomarker of epileptic brain tissue and may also be useful for seizure forecasting. Despite such clinical utility of HFOs, the spatial context and neuronal activity underlying these local field potential (LFP) events remains unclear. We sought to further understand the neuronal correlates of ictal high frequency LFPs using multielectrode array recordings in the human neocortex and mesial temporal lobe during rhythmic onset seizures. These multiscale recordings capture single cell, multiunit, and LFP activity from the human brain. We compare features of multiunit firing and high frequency LFP from microelectrodes and macroelectrodes during ictal discharges in both the seizure core and penumbra (spatial seizure domains defined by multiunit activity patterns). We report differences in spectral features, unit-local field potential coupling, and information theoretic characteristics of high frequency LFP before and after local seizure invasion. Furthermore, we tie these time-domain differences to spatial domains of seizures, showing that penumbral discharges are more broadly distributed and less useful for seizure localization. These results describe the neuronal and synaptic correlates of two types of pathological HFOs in humans and have important implications for clinical interpretation of rhythmic onset seizures.

Coupling between infraslow activities and high-frequency oscillations precedes seizure onset.

Infraslow activities and high‐frequency oscillations (HFOs) are observed in seizure‐onset zones. However, the relation between them remains unclear. In this study, we investigated phase‐amplitude coupling between infraslow phase (0.016‐1 Hz) and HFOs' amplitude of focal impaired awareness seizures followed by focal to bilateral tonic‐clonic seizures, in a 28‐year‐old right‐handed man with a dysembryoplastic neuroepithelial tumor. We recorded five habitual seizures. After the time of seizure onset, a significant increase in the power of HFOs was observed, and the power was significantly coupled with θ (4‐8 Hz) phase. In contrast, coupling of infraslow activities and HFOs surged a few minutes before the seizure‐onset time, and ictal HFOs discharged after that. Collectively, our results show that coupling of infraslow activities and HFOs precedes the seizure‐onset time. We infer that such coupling may be a potential biomarker for seizure prediction.

Assessing Epileptogenicity Using Phase-Locked High Frequency Oscillations: A Systematic Comparison of Methods.

High frequency oscillations (HFOs) are traditional biomarkers to identify the epileptogenic tissue during presurgical evaluation in pharmacoresistant epileptic patients. Recently, the resection of brain tissue exhibiting coupling between the amplitude of HFOs and the phase of low frequencies demonstrated a more favorable surgical outcome. Here we compare the predictive value of ictal HFOs and four methods for quantifying the ictal phase-amplitude coupling, namely mean vector length, phase-locked high gamma, phase locking value, and modulation index (MI). We analyzed 32 seizures from 16 patients to identify the channels that exhibit HFOs and phase-locked HFOs during seizures. We compared the resection ratio, defined as the percentage of channels exhibiting coupling located in the resected tissue, with the postsurgical outcome. We found that the MI is the only method to show a significant difference between the resection ratios of patients with good and poor outcomes. We further show that the whole seizure, not only the onset, is critical to assess epileptogenicity using the phase-locked HFOs. We postulate that the superiority of MI stems from its capacity to assess coupling of discrete HFO events and its independence from the HFO power. These results confirm that quantitative analysis of HFOs can boost presurgical evaluation and indicate the paramount importance of algorithm selection for clinical applications.

Ictal High-Frequency Oscillation for Lateralizing Patients With Suspected Bitemporal Epilepsy Using Wavelet Transform and Granger Causality Analysis.

Identifying lateralization of bilateral temporal lobe epilepsy (TLE) is a challenging issue; scalp electroencephalography (EEG) and routine band electrocorticography (ECoG) fail to reveal the epileptogenic focus for further temporal lobectomy treatment. High-frequency oscillations (HFOs) can be utilized as a biomarker for lateralizing the onset zone in suspected bitemporal epilepsy. Except subjective vision detect the HFOs, objective verification should be performed to raise the accuracy. In the present research, we prospectively studied 10 patients with refractory temporal seizures and who underwent ECoG with wide-band frequency amplifiers (2,048 Hz); all patients had a class I outcome after temporal resection. Pre- and ictal HFOs will be analyzed by wavelet transform (WT) and Granger causality (GC) to objectively verify lateralization of the seizure onset zone (SOZ). WT analysis showed ictal HFOs in 10 patients mainly covered from 80 to 115 Hz (average, 92.59 ± 10.23 Hz), and there was distinct bandpass boundary between pre-ictal HFOs and ictal HFOs. GC analysis showed five patients (2, 4, 5, 6, and 7), no matter the pre-ictal or ictal state, had the highest GC degree in SOZ itself. The remaining patients (1, 3, 8, 9, and 10) had the highest GC degree in SOZ with its adjacent regions in the pre-ictal and ictal stages. GC analysis further confirmed the result of the WT and suggested HFOs are initiated and propagated in the local brain region mainly, afterward, transmitting to adjacent brain regions. These results indicated that the combination of WT and GC analyses significantly contributes to accurate lateralization in patients with suspected bitemporal epilepsy.

Analysis of the characteristics of ictal high frequency oscillations between infantile spasms and cryptogenic infantile spasms

目的 探讨TBC1D24基因突变引起的一家系致死性癫痫性脑病的临床特点及基因突变。 方法 收集就诊于徐州医科大学附属徐州市儿童医院的1例TBC1D24基因突变的癫痫性脑病患儿及其家系临床资料，在OMIM(在线人类孟德尔遗传数据库)、PubMed(生物医学文献数据库)、CNKI(中国知网期刊数据库)及万方数据知识服务平台建库至2017年1月相关文献进行检索，总结TBC1D24基因变异及相关表型的特征。 结果 患儿，女，8岁1月，因反复无热抽搐8年于2016年04月就诊。患儿1月20天大小时始出现抽搐，表现为局灶性肌阵挛，约半月发作1次，后发作逐渐频繁，逐渐出现阵挛状态、强制-阵挛等多种形式，易出现癫痫持续状态，多种抗癫痫药物治疗效果差，合并发育倒退。体格检测发现抱入体位，竖头不稳，四肢肌力3级，肌张力低，四肢肌肉萎缩明显，双侧膝腱反射弱。早期头颅影像学及脑电图正常，后期出现脑萎缩和脑电图的异常。患儿小弟及妹妹也出现类似表现，且病情发展更快，分别在1岁及1岁10月大小时死亡。在患儿家庭成员的全外显子测序中，一个新的复合杂合突变在TBC1D24基因变异体中被发现，c.76G>T，P.Glu26Ter和c.1612C>T，p.Leu538Val，父母验证后前者遗传自父亲，为无义突变，后者遗传自母亲，为错义突变。 结论 TBC1D24基因突变为该家系致死性癫痫性脑病的致病突变，认识TBC1D24基因突变引起的致死性癫痫性脑病表型具有重要的临床意义。

Analysis of the characteristics of ictal high frequency oscillations between infantile spasms and cryptogenic infantile spasms

目的 对不同病因婴儿痉挛症头皮脑电发作期高频振荡(high frequency oscillation，HFO)进行分析，探讨不同病因的婴儿痉挛症发作期HFO的特点及临床意义。 方法 自2015年9月至2016年9月在广东省妇幼保健院康复科脑电图室进行视频脑电监测的婴儿痉挛症患儿中，选取有发作期HFO的患儿11例，共406次痉挛发作进行回顾性分析，观察不同病因婴儿痉挛症发作期HFO的频率和分布特点，并结合临床表现、影像学资料分析不同类型婴儿痉挛症发作期HFO特点及临床意义。 结果 (1)头皮脑电记录到Ripple频段发作期HFO，且大多分布广泛。(2)406次痉挛发作中，症状性和隐源性发作期HFO的出现率分别为11.35%(21/185)、33.12%(2/224)，隐源性婴儿痉挛发作期HFO的相对出现率分别为75%(21 /28)、25%(7/28)，症状性痉挛发作期HFO出现率明显高于隐源性(P＝0.01)。 结论 头皮脑电能记录到Ripple频段的发作期HFO，为近一步行颅内脑电图检查提供可靠依据；相对于隐源性婴儿痉挛，症状性婴儿痉挛发作期HFO的出现率更高，提示HFO可能与婴儿痉挛症的产生机制相关，病理性损害更易诱发HFO产生。

T115. Magnetoencephalographic imaging of ictal high-frequency oscillations (80–200 Hz) in medically refractory epilepsy

Specificity of ictal high-frequency oscillations (HFOs) in identifying epileptogenic abnormality is significant, compared to the spikes and interictal HFOs. The objectives of the study were to detect and to localize ictal HFOs by magnetoencephalography (MEG) for identifying the seizure onset zone (SOZ), evaluate the cortical excitability from preictal to ictal transition, and establish HFO concordance rates with other modalities and postsurgical resection. Sixty-seven patients with drug-resistant epilepsy had at least 1 spontaneous seizure each during MEG acquisition, and analysis was carried out on 20 seizures from 20 patients. Ictal MEG data were bandpass filtered (80–200 Hz) to visualize, review, and analyze the HFOs co-occurring with ictal spikes. Source montages were generated on both hemispheres, mean fast Fourier transform was computed on virtual time series for determining the preictal to ictal spectral power transition, and source reconstruction was performed with sLORETA and beamformers. The concordance rates of ictal MEG HFOs (SOZ) was estimated with 4 reference epileptogenic regions. In each subject, transient bursts of high-frequency oscillatory cycles, distinct from the background activity, were observed in the periictal continuum. Time–frequency analysis showed significant spectral power surge (85–160 Hz) during ictal state (P < .05) compared to preictal state, but there was no variation in the peak HFO frequencies (P > .05) for each subgroup and at each source montage. HFO source localization was consistent between algorithms (k = 0.8570 ± 0.138), with presumed epileptogenic zone (EZ) comparable to other modalities. In patients who underwent surgery (n = 6), MEG HFO SOZ was concordant with the presumed EZ HFOs could reliably be detected in the MEG periictal state, and its sources were accurately localized in almost 95% of the patients with medically refractory epilepsy. During preictal to ictal transition, HFOs exhibited dynamic augmentation in intrinsic epileptogenicity. Spatial overlap of ictal HFO sources was consistent with EZ determinants including the presumed EZ and the surgical resection area.

Magnetoencephalographic imaging of ictal high-frequency oscillations (80-200Hz) in pharmacologically resistant focal epilepsy.

Specificity of ictal high-frequency oscillations (HFOs) in identifying epileptogenic abnormality is significant, compared to the spikes and interictal HFOs. The objectives of the study were to detect and to localize ictal HFOs by magnetoencephalography (MEG) for identifying the seizure onset zone (SOZ), evaluate the cortical excitability from preictal to ictal transition, and establish HFO concordance rates with other modalities and postsurgical resection. Sixty-seven patients with drug-resistant epilepsy had at least 1 spontaneous seizure each during MEG acquisition, and analysis was carried out on 20 seizures from 20 patients. Ictal MEG data were bandpass filtered (80-200Hz) to visualize, review, and analyze the HFOs co-occurring with ictal spikes. Source montages were generated on both hemispheres, mean fast Fourier transform was computed on virtual time series for determining the preictal to ictal spectral power transition, and source reconstruction was performed with sLORETA and beamformers. The concordance rates of ictal MEG HFOs (SOZ) was estimated with 4 reference epileptogenic regions. In each subject, transient bursts of high-frequency oscillatory cycles, distinct from the background activity, were observed in the periictal continuum. Time-frequency analysis showed significant spectral power surge (85-160Hz) during ictal state (P<.05) compared to preictal state, but there was no variation in the peak HFO frequencies (P>.05) for each subgroup and at each source montage. HFO source localization was consistent between algorithms (k=0.857±0.138), with presumed epileptogenic zone (EZ) comparable to other modalities. In patients who underwent surgery (n=6), MEG HFO SOZ was concordant with the presumed EZ and the surgical resection site (100%), and all were seizure-free during follow-up. HFOs could be detected in the MEG periictal state, and its sources were accurately localized. During preictal to ictal transition, HFOs exhibited dynamic augmentation in intrinsic epileptogenicity. Spatial overlap of ictal HFO sources was consistent with EZ determinants and the surgical resection area.

The role of high-frequency oscillations in epilepsy surgery planning.

Epilepsy is a serious brain disorder characterized by recurrent unprovoked seizures. Approximately two-thirds of seizures can be controlled with antiepileptic medications (Kwan 2000). For some of the others, surgery can completely eliminate or significantly reduce the occurrence of disabling seizures. Localization of epileptogenic areas for resective surgery is far from perfect, and new tools are being investigated to more accurately localize the epileptogenic zone (the zone of the brain where the seizures begin) and improve the likelihood of freedom from postsurgical seizures. Recordings of pathological high-frequency oscillations (HFOs) may be one such tool. To assess the ability of HFOs to improve the outcomes of epilepsy surgery by helping to identify more accurately the epileptogenic areas of the brain. For the latest update, we searched the Cochrane Epilepsy Group Specialized Register (25 July 2016), the Cochrane Central Register of Controlled Trials (CENTRAL) via the Cochrane Register of Studies Online (CRSO, 25 July 2016), MEDLINE (Ovid, 1946 to 25 July 2016), CINAHL Plus (EBSCOhost, 25 July 2016), Web of Science (Thomson Reuters, 25 July 2016), ClinicalTrials.gov (25 July 2016), and the World Health Organization International Clinical Trials Registry Platform ICTRP (25 July 2016). We included studies that provided information on the outcomes of epilepsy surgery for at least six months and which used high-frequency oscillations in making decisions about epilepsy surgery. The primary outcome of the review was the Engel Class Outcome System (class I = no disabling seizures, II = rare disabling seizures, III = worthwhile improvement, IV = no worthwhile improvement). Secondary outcomes were responder rate, International League Against Epilepsy (ILAE) epilepsy surgery outcome, frequency of adverse events from any source and quality of life outcomes. We intended to analyse outcomes via an aggregated data fixed-effect model meta-analysis. Two studies representing 11 participants met the inclusion criteria. Both studies were small non-randomised trials, with no control group and no blinding. The quality of evidence for all outcomes was very low. The combination of these two studies resulted in 11 participants who prospectively used ictal HFOs for epilepsy surgery decision making. Results of the postsurgical seizure freedom Engel class I to IV outcome were determined over a period of 12 to 38 months (average 23.4 months) and indicated that six participants had an Engel class I outcome (seizure freedom), two had class II (rare disabling seizures), three had class III (worthwhile improvement). No adverse effects were reported. Neither study compared surgical results guided by HFOs versus surgical results guided without HFOs. No reliable conclusions can be drawn regarding the efficacy of using HFOs in epilepsy surgery decision making at present.

Does temporal evolution occur in ictal high-frequency oscillations in patients with intractable partial epilepsy?: A concern about local field potentials vs. action potentials

Background: High-frequency oscillations (HFOs), which are usually defined as oscillatory activities above 80 Hz, have been reportedly a possible biomarkers of epileptogenicity. Temporal spectrogram of ictal HFOs represents band like activities, however, they appear as various patterns in temporal change of frequency.

Resection of ictal high frequency oscillations is associated with favorable surgical outcome in pediatric drug resistant epilepsy secondary to tuberous sclerosis complex

Resective epilepsy surgery can improve seizures when the epileptogenic zone (EZ) is limited to a well-defined region. High frequency oscillations (HFO) have been recognized as having a high association with the seizure onset zone. Therefore, we retrospectively identified ictal HFOs and determined their relationship to specific intracranial features of cortical tubers in children with TSC who underwent resective surgery. We identified 14 patients with drug resistant epilepsy secondary to TSC who underwent subdural grid and strip implantation for presurgical evaluation and subsequent resection with adequate post-surgical follow-up. We aimed to determine the relationship between ictal HFOs, post-resection outcome and neuroimaging features in this population.The largest tuber was identified in all 14 patients (100%). Four patients (29%) had unusual tubers. HFOs were observed at ictal onset in all 14 patients. Seven of 10 patients with complete resection of HFOs were seizure free. The better seizure outcome (ILAE=1–3) was achieved with complete HFO resection regardless of the unique TSC structural features (p=0.0140).Our study demonstrates the presence of ripple and fast ripple range HFOs at ictal onset in children with TSC. Our study showed that complete HFO resection led to the better surgical outcome, independent of MR imaging findings.

Interictal high-frequency oscillations (HFOs) as predictors of high frequency and conventional seizure onset zones.

We investigated the relationship between the interictal high-frequency oscillations (HFOs) and the seizure onset zones (SOZs) defined by the ictal HFOs or conventional frequency activity (CFA), and evaluated the usefulness of the interictal HFOs as spatial markers of the SOZs. We analysed seizures showing discrete HFOs at onset on intracranial EEGs acquired at ≥1000-Hz sampling rate in a training cohort of 10 patients with temporal and extratemporal epilepsy. We classified each ictal channel as: HFO+ (HFOs at onset with subsequent evolution), HFO- (HFOs at onset without evolution), CFA (1.6-70-Hz activity at onset with evolution), or non-ictal. We defined the SOZs as: hSOZ (HFO+ channels only), hfo+&-SOZ (HFO+ and HFO- channels), and cSOZ (CFA channels). Using automated methods, we detected the interictal HFOs and extracted five features: density, connectivity, peak frequency, log power, and amplitude. We created logistic regression models using these features, and tested their performance in a separate replication cohort of three patients. The models containing the five interictal HFO features reliably differentiated the channels located inside the SOZ from those outside in the training cohort (p<0.001), reaching the highest accuracy for the classification of hSOZ. Log power and connectivity had the highest odds ratios, both being higher for the channels inside the SOZ compared with those outside the SOZ. In the replication cohort of novel patients, the same models differentiated the HFO+ from HFO- channels, and predicted the extents of the hSOZ and hfo+&-SOZ (F1 measure >0.5) but not the cSOZ. Our study shows that the interictal HFOs are useful in defining the spatial extent of the SOZ, and predicting whether or not a given channel in a novel patient would be involved in the seizure. The findings support the existence of an abnormal network of tightly-linked ictal and interictal HFOs in patients with intractable epilepsy.

Scalp high frequency oscillations (HFOs) in absence epilepsy: An independent component analysis (ICA) based approach

BackgroundHigh frequency oscillations (HFOs) have provided a new insight in understanding ictogenesis and seizure localization. In absence seizures, HFOs were predominantly localized in the medial prefrontal cortex (MPFC) in MEG studies. MethodsWe studied HFOs (80–250Hz) in scalp EEGs in patients with absence epilepsy, and evaluated their frequency bandwidth and spatial-temporal distribution. EEG of 9 patients with absence epilepsy (CAE:JAE–8:1; M:F=7:2; age: 8.1±2.1years; age at onset: 6.6±1.3 years) were evaluated with scalp EEG (sampling rate: 2048Hz). Finite impulse response filters on the unipolar or longitudinal bipolar montages were band-passed between 80 and 250Hz using Cartool® and EEGLAB®. Sensitivity and paper speed were modified accordingly to study the HFOs. Thousand four hundred and thirty eight artifact free ‘spike-wave’ epileptiform discharges were analyzed. Sleep ictal SW discharges, defined as runs of 3Hz GSWDs lasting ≥4s in stages 1 and 2 sleep, were analyzed by independent component analysis and component time-frequency and channel time-frequency maps using cyclical tapering wavelet transform. A total of 926 HFOs were identified of 1438 GSWDS. ResultsThe HFOs were associated with inter-ictal generalized spike-wave discharges (IiGSWDs-241/454), ictal GSWDs (IcGSWD-634/884), sporadic SWDs (sSWDs-51/100). The percentage of HFOs was higher in IcGSWD when compared to both IiGSWDs and sporadic SWDs together (χ2=52.864, d.o.f=1, p<0.0001). The mean frequency of HFOs was 96.4±10.4Hz. A channel wise analysis showed the maximum HFO band width in the right fronto-central region (F4=28Hz, C4=24Hz). ConclusionNarrow bandwidth interictal and ictal HFOs can be identified in scalp EEG of patients with absence epilepsy. Further characterization of the various properties of pHFOs will be helpful in opening up a domain of clinical evaluation and interpretation of the various epileptic disorders. To improve the insights into the onset and spread of absence seizures, and to study the network properties, one could analyze the HFOs in high density EEG arrays with multimodal integration using MEG or fMRI.

1-P-F-7. Analysis of ictal high-frequency oscillation patterns of intracranial EEGs in surgical epilepsy cases due to various etiologies

The patterns of ictal high-frequency oscillation (HFO) of intracranial EEGs in epilepsy patients due to various etiologies were investigated. All patients underwent resective epilepsy surgery, and the pathological diagnoses were confirmed as follows: focal cortical dysplasia (FCD), 5; tumor, 3; tuberous sclerosis (TS), 2; cavernous angioma (CA), 1; and no significant alteration (NSA), 1. EEGs were recorded at a sampling rate of 1 kHz. Ictal HFOs were analyzed by visual inspection and time–frequency analysis (multiple band frequency analysis; MBFA). Ictal HFOs were divided based on the maximum frequency on MBFA: n = 1); 100–150 Hz, FCD type I ( n = 2), FCD type IIA ( n = 1), tumor ( n = 1), CA ( n = 1); 150–200 Hz, FCD type IIB ( n = 1), tumor ( n = 3), TS ( n = 1); 200–250 Hz, FCD type IIB ( n = 1) and TS ( n = 1). FCD type IIB and TS had HFO with a higher frequency, whereas FCD type I and CA had HFO with a lower frequency. The results of this study suggest that the frequency of HFO reflects the epileptogenic substrate and its pathophysiological mechanism. Further investigation of a large series is necessary to determine the relationship between HFO and ictogenesis.

Mapping the coherence of ictal high frequency oscillations in human extratemporal lobe epilepsy.

High frequency oscillations (HFOs) have recently been recorded in epilepsy patients and proposed as possible novel biomarkers of epileptogenicity. Investigation of additional HFO characteristics that correlate with the clinical manifestation of seizures may yield additional insights for delineating epileptogenic regions. To that end, this study examined the spatiotemporal coherence patterns of HFOs (80-400 Hz) so as to characterize the strength of HFO interactions in the epileptic brain. We hypothesized that regions of strong HFO coherence identified epileptogenic networks believed to possess a pathologic locking nature in relation to regular brain activity. We applied wavelet phase coherence analysis to the intracranial EEG (iEEG)s of patients (n = 5) undergoing presurgical evaluation of drug-resistant extratemporal lobe epilepsy (ETLE). We have also computed HFO intensity (related to the square-root of the power), to study the relationship between HFO amplitude and coherence. Strong HFO (80-270 Hz) coherence was observed in a consistent and spatially focused channel cluster during seizures in four of five patients. Furthermore, cortical regions possessing strong ictal HFO coherence coincided with regions exhibiting high ictal HFO intensity, relative to all other channels. Because HFOs have been shown to localize to the epileptogenic zone, and we have demonstrated a correlation between ictal HFO intensity and coherence, we propose that ictal HFO coherence can act as an epilepsy biomarker. Moreover, the seizures studied here showed strong spatial correlation of ictal HFO coherence and intensity in the 80-270 Hz frequency range, suggesting that this band may be targeted when defining seizure-related regions of interest for characterizing ETLE.

Spatial Coherence Profiles of Ictal High-Frequency Oscillations Correspond to Those of Interictal Low-Frequency Oscillations in the ECoG of Epileptic Patients.

We have previously demonstrated that the coherence of high-frequency oscillations (HFOs; 80-300Hz) increased during extratemporal lobe seizures in a consistent and spatially focused electrode cluster. In this study, we have investigated the relationship between cohered HFO intracranial EEG (iEEG) activity with that of slower low-frequency oscillations (LFOs; <80Hz). We applied wavelet phase coherence analysis to the iEEGs of patients with intractable extratemporal lobe epilepsy (ETLE). It was observed that areas on the implanted patient subdural grids, which exhibited strong ictal HFO coherence were similar to tissue regions displaying strong interictal LFO coherence in the 5-12Hz frequency range, relative to all other electrodes. A positive surgical outcome was correlated with having the clinically marked seizure onset zone(s) in close proximity to HFO/LFO coherence highlighted regions of interest (ROIs). Recent studies have suggested that LFOs (in the 8-12Hz frequency range) play an important role in controlling cortical excitability, by exerting an inhibitory effect on cortical processing, and that the presence of strong theta activity (4-8Hz) in awake adults is suggestive of abnormal and/or pathological activity. We speculate that the overlapping spatial regions exhibiting increased coherence in both ictal HFOs and interictal LFOs identified local abnormalities that underlie epileptogenic networks. Whereas it is worthwhile to note that the small patient group ( n = 7) studied here, somewhat limits the clinical significance of our study, the results presented here suggest targeting HFO activity in the 80-300Hz frequency range and/or interictal LFO activity in the 5-12Hz frequency range, when defining seizure-related ROIs in the iEEGs of patients with ETLE.