Neuronal oscillations span a wide range of spatial and temporal scales that extend beyond traditional clinical EEG. Recent research suggests that high-frequency oscillations (HFO), in the ripple (80–250Hz) and fast ripple (250–1000Hz) frequency range, may be signatures of epileptogenic brain and involved in the generation of seizures. However, most research investigating HFO in humans comes from microwire recordings, whose relationship to standard clinical intracranial EEG (iEEG) has not been explored. In this study iEEG recordings (DC − 9000Hz) were obtained from human medial temporal lobe using custom depth electrodes containing both microwires and clinical macroelectrodes. Ripple and fast-ripple HFO recorded from both microwires and clinical macroelectrodes were increased in seizure generating brain regions compared to control regions. The distribution of HFO frequencies recorded from the macroelectrodes was concentrated in the ripple frequency range, compared to a broad distribution of HFO frequencies recorded from microwires. The average frequency of ripple HFO recorded from macroelectrodes was lower than that recorded from microwires (143.3 ± 49.3 Hz versus 116.3 ± 38.4, Wilcoxon rank sum P<0.0001). Fast-ripple HFO were most often recorded on a single microwire, supporting the hypothesis that fast-ripple HFO are primarily generated by highly localized, sub-millimeter scale neuronal assemblies that are most effectively sampled by microwire electrodes. Future research will address the clinical utility of these recordings for localizing epileptogenic networks and understanding seizure generation.
high-frequency oscillations; ripple; fast ripple; intracranial EEG; epilepsy
High frequency oscillations (HFOs) are a biomarker of epileptogenicity. Visual marking of HFOs is highly time-consuming and inevitably subjective, making automatic detection necessary. We compare four existing detectors on the same dataset.
HFOs and baselines were identified by experienced reviewers in intracerebral EEGs from 20 patients. A new feature of our detector to deal with channels where baseline cannot be found is presented. The original and an optimal configuration are implemented. Receiver operator curves, false discovery rate, and channel ranking are used to evaluate performance.
All detectors improve performance with the optimal configuration. Our detector had higher sensitivity, lower false positives than the others, and similar false detections. The main difference in performance was in very active channels.
Each detector was developed for different recordings and with different aims. Our detector performed better in this dataset, but was developed on data similar to the test data. Moreover, optimizing on a particular data type improves performance in any detector.
Automatic HFO detection is crucial to propel their clinical use as biomarkers of epileptogenic tissue. Comparing detectors on a single dataset is important to analyze their performance and to emphasize the issues involved in validation.
PMID: 21763191 CAMSID: cams3336
High frequency oscillations; HFO; Automatic detector; Intracerebral EEG
The discovery that electroencephalography (EEG) contains useful information at frequencies above the traditional 80Hz limit has had a profound impact on our understanding of brain function. In epilepsy, high-frequency oscillations (HFOs, >80Hz) have proven particularly important and useful. This literature review describes the morphology, clinical meaning, and pathophysiology of epileptic HFOs. To record HFOs, the intracranial EEG needs to be sampled at least at 2,000Hz. The oscillatory events can be visualized by applying a high-pass filter and increasing the time and amplitude scales, or EEG time-frequency maps can show the amount of high-frequency activity. HFOs appear excellent markers for the epileptogenic zone. In patients with focal epilepsy who can benefit from surgery, invasive EEG is often required to identify the epileptic cortex, but current information is sometimes inadequate. Removal of brain tissue generating HFOs has been related to better postsurgical outcome than removing the seizure onset zone, indicating that HFOs may mark cortex that needs to be removed to achieve seizure control. The pathophysiology of epileptic HFOs is challenging, probably involving populations of neurons firing asynchronously. They differ from physiological HFOs in not being paced by rhythmic inhibitory activity and in their possible origin from population spikes. Their link to the epileptogenic zone argues that their study will teach us much about the pathophysiology of epileptogenesis and ictogenesis. HFOs show promise for improving surgical outcome and accelerating intracranial EEG investigations. Their potential needs to be assessed by future research.
PMID: 22367988 CAMSID: cams3339
Epilepsy is one of the most frequent neurological diseases. In focal medically refractory epilepsies, successful surgical treatment largely depends on the identification of epileptogenic zone. High-frequency oscillations (HFOs) between 80 and 500 Hz, which can be recorded with EEG, may be novel markers of the epileptogenic zone. This review discusses the clinical importance of HFOs as markers of epileptogenicity and their application in different types of epilepsies. HFOs are clearly linked to the seizure onset zone, and the surgical removal of regions generating them correlates with a seizure free post-surgical outcome. Moreover, HFOs reflect the seizure-generating capability of the underlying tissue, since they are more frequent after the reduction of antiepileptic drugs. They can be successfully used in pediatric epilepsies such as epileptic spasms and help to understand the generation of this specific type of seizures. While mostly recorded on intracranial EEGs, new studies suggest that identification of HFOs on scalp EEG or magnetoencephalography (MEG) is possible as well. Thus not only patients with refractory epilepsies and invasive recordings but all patients might profit from the analysis of HFOs. Despite these promising results, the analysis of HFOs is not a routine clinical procedure; most results are derived from relatively small cohorts of patients and many aspects are not yet fully understood. Thus the review concludes that even if HFOs are promising biomarkers of epileptic tissue, there are still uncertainties about mechanisms of generation, methods of analysis, and clinical applicability. Large multicenter prospective studies are needed prior to widespread clinical application.
Epilepsy; Ripple; Fast ripple; EEG; Seizure; Infantile spasms
Background and Purpose
There is growing interest in high-frequency oscillations (HFO) as electrophysiological biomarkers of the epileptic brain. We evaluated the clinical utility of interictal HFO events, especially their occurrence rates, by comparing the spatial distribution with a clinically determined epileptogenic zone by using subdural macroelectrodes.
We obtained intracranial electroencephalogram data with a high temporal resolution (2000 Hz sampling rate, 0.05-500 Hz band-pass filter) from seven patients with medically refractory epilepsy. Three epochs of 5-minute, artifact-free data were selected randomly from the interictal period. HFO candidates were first detected by an automated algorithm and subsequently screened to discard false detections. Validated events were further categorized as fast ripple (FR) and ripple (R) according to their spectral profiles. The occurrence rate of HFOs was calculated for each electrode contact. An HFO events distribution map (EDM) was constructed for each patient to allow visualization of the spatial distribution of their HFO events.
The subdural macroelectrodes were capable of detecting both R and FR events from the epileptic neocortex. The occurrence rate of HFO events, both FR and R, was significantly higher in the seizure onset zone (SOZ) than in other brain regions. Patient-specific HFO EDMs can facilitate the identification of the location of HFO-generating tissue, and comparison with findings from ictal recordings can provide additional useful information regarding the epileptogenic zone.
The distribution of interictal HFOs was reasonably consistent with the SOZ. The detection of HFO events and construction of spatial distribution maps appears to be useful for the presurgical mapping of the epileptogenic zone.
partial epilepsy; high-frequency oscillations; fast ripple; ripple; intracranial EEG; seizure onset zone
High frequency oscillations (HFOs) called ripples (80–250 Hz) and fast ripples (FR, 250–500 Hz) can be recorded from intracerebral EEG macroelectrodes in patients with intractable epilepsy. HFOs occur predominantly in the seizure onset zone (SOZ) but their relationship to the underlying pathology is unknown. It was the aim of this study to investigate whether HFOs are specific to the SOZ or result from pathologically changed tissue, whether or not it is epileptogenic. Patients with different lesion types, namely mesial temporal atrophy (MTA), focal cortical dysplasia (FCD) and nodular heterotopias (NH) were investigated. Intracranial EEG was recorded from depth macroelectrodes with a sampling rate of 2000 Hz. Ripples (80–250 Hz) and Fast Ripples (250–500 Hz) were visually marked in 12 patients: five with MTA, four with FCD and three with NH. Rates of events were statistically compared in channels in four areas: lesional SOZ, non-lesional SOZ, lesional non-SOZ and non-lesional non-SOZ. HFO rates were clearly more linked to the SOZ than to the lesion. They were highest in areas in which lesion and SOZ overlap, but in patients with a SOZ outside the lesion, such as in NHs, HFO rates were clearly higher in the non-lesional SOZ than in the inactive lesions. No specific HFO pattern could be identified for the different lesion types. The findings suggest that HFOs represent a marker for SOZ areas independent of the underlying pathology and that pathologic tissue changes alone do not lead to high rates of HFOs.
PMID: 19297507 CAMSID: cams3471
high frequency oscillations; focal cortical dysplasia; nodular heterotopia; temporal atrophy; seizure onset zone; intracranial EEG
High-frequency oscillations (HFOs) known as ripples (80–250 Hz) and fast ripples (250–500 Hz) can be recorded from macroelectrodes inserted in patients with intractable focal epilepsy. They are most likely linked to epileptogenesis and have been found in the seizure onset zone (SOZ) of human ictal and interictal recordings. HFOs occur frequently at the time of interictal spikes, but were also found independently. This study analyses the relationship between spikes and HFOs and the occurrence of HFOs in nonspiking channels.
Intracerebral EEGs of 10 patients with intractable focal epilepsy were studied using macroelectrodes. Rates of HFOs within and outside spikes, the overlap between events, event durations, and the percentage of spikes carrying HFOs were calculated and compared according to anatomical localization, spiking activity, and relationship to the SOZ.
HFOs were found in all patients, significantly more within mesial temporal lobe structures than in neocortex. HFOs could be seen in spiking as well as nonspiking channels in all structures. Rates and durations of HFOs were significantly higher in the SOZ than outside. It was possible to establish a rate of HFOs to identify the SOZ with better sensitivity and specificity than with the rate of spikes.
HFOs occurred to a large extent independently of spikes. They are most frequent in mesial temporal structures. They are prominent in the SOZ and provide additional information on epileptogenicity independently of spikes. It was possible to identify the SOZ with a high specificity by looking at only 10 min of HFO activity.
PMID: 18479382 CAMSID: cams3466
Epilepsy; High-frequency oscillations; Spikes; Seizure onset zone; Intracranial electrodes
Intracranial electroencephalography (EEG) is performed as part of an epilepsy surgery evaluation when noninvasive tests are incongruent or the putative seizure-onset zone is near eloquent cortex. Determining the seizure-onset zone using intracranial EEG has been conventionally based on identification of specific ictal patterns with visual inspection. High-frequency oscillations (HFOs, >80 Hz) have been recognized recently as highly correlated with the epileptogenic zone. However, HFOs can be difficult to detect because of their low amplitude. Therefore, the prevalence of ictal HFOs and their role in localization of epileptogenic zone on intracranial EEG are unknown.
We identified 48 patients who underwent surgical treatment after the surgical evaluation with intracranial EEG, and 44 patients met criteria for this retrospective study. Results were not used in surgical decision making. Intracranial EEG recordings were collected with a sampling rate of 2,000 Hz. Recordings were first inspected visually to determine ictal onset and then analyzed further with time-frequency analysis. Forty-one (93%) of 44 patients had ictal HFOs determined with time-frequency analysis of intracranial EEG.
Twenty-two (54%) of the 41 patients with ictal HFOs had complete resection of HFO regions, regardless of frequency bands. Complete resection of HFOs (n = 22) resulted in a seizure-free outcome in 18 (82%) of 22 patients, significantly higher than the seizure-free outcome with incomplete HFO resection (4/19, 21%).
Our study shows that ictal HFOs are commonly found with intracranial EEG in our population largely of children with cortical dysplasia, and have localizing value. The use of ictal HFOs may add more promising information compared to interictal HFOs because of the evidence of ictal propagation and followed by clinical aspect of seizures. Complete resection of HFOs is a favorable prognostic indicator for surgical outcome.
High-frequency oscillations; Intracranial EEG; Time-frequency analysis; Surgical outcome; Nonlesional epilepsy
High-frequency oscillations (HFOs) at ≧80 Hz of nonepileptic nature spontaneously emerge from human cerebral cortex. In 10 patients with extra-occipital lobe epilepsy, we compared the spectral-spatial characteristics of HFOs spontaneously arising from the nonepileptic occipital cortex with those of HFOs driven by a visual task as well as epileptogenic HFOs arising from the extra-occipital seizure focus. We identified spontaneous HFOs at ≧80 Hz with a mean duration of 330 msec intermittently emerging from the occipital cortex during interictal slow-wave sleep. The spectral frequency band of spontaneous occipital HFOs was similar to that of visually-driven HFOs. Spontaneous occipital HFOs were spatially sparse and confined to smaller areas, whereas visually-driven HFOs involved the larger areas including the more rostral sites. Neither spectral frequency band nor amplitude of spontaneous occipital HFOs significantly differed from those of epileptogenic HFOs. Spontaneous occipital HFOs were strongly locked to the phase of delta activity, but the strength of delta-phase coupling decayed from 1 to 3 Hz. Conversely, epileptogenic extra-occipital HFOs were locked to the phase of delta activity about equally in the range from 1 to 3 Hz. The occipital cortex spontaneously generates physiological HFOs which may stand out on electrocorticography traces as prominently as pathological HFOs arising from elsewhere; this observation should be taken into consideration during presurgical evaluation. Coupling of spontaneous delta and HFOs may increase the understanding of significance of delta-oscillations during slow-wave sleep. Further studies are warranted to determine whether delta-phase coupling distinguishes physiological from pathological HFOs or simply differs across anatomical locations.
epilepsy surgery; fast ripples; in-vivo animation of event-related gamma-oscillations; electroencephalography (EEG); memory consolidation; perceptual visual learning; slow-wave sleep
High Frequency Oscillations (HFOs) in the EEG are a promising biomarker of epileptogenic tissue. Given that the visual marking of HFOs is highly time-consuming and subjective, automatic detectors are necessary. In this study, we present a novel automatic detector that detects HFOs by incorporating information of previously detected baselines. The detector was trained on 72 channels and tested on 278, achieving a mean sensitivity of 96.8% with a mean false positive rate of 4.86%. This low rate is reasonable since only visually marked baseline segments were considered as the true negatives. This detector could be useful for the systematic study of HFOs and for their eventual clinical application.
PMID: 21096802 CAMSID: cams3401
High-frequency oscillations (HFOs) can be recorded in epileptic patients with clinical intracranial EEG. HFOs have been associated with seizure genesis because they occur in the seizure focus and during seizure onset. HFOs are also found interictally, partly co-occurring with epileptic spikes. We studied how HFOs are influenced by antiepileptic medication and seizure occurrence, to improve understanding of the pathophysiology and clinical meaning of HFOs.
Intracerebral depth EEG was partly sampled at 2,000 Hz in 42 patients with intractable focal epilepsy. Patients with five or more usable nights of recording were selected. A sample of slow-wave sleep from each night was analyzed, and HFOs (ripples: 80–250 Hz, fast ripples: 250–500 Hz) and spikes were identified on all artifact-free channels. The HFOs and spikes were compared before and after seizures with stable medication dose and during medication reduction with no intervening seizures.
Twelve patients with five to eight nights were included. After seizures, there was an increase in spikes, whereas HFO rates remained the same. Medication reduction was followed by an increase in HFO rates and mean duration.
Contrary to spikes, high-frequency oscillations (HFOs) do not increase after seizures, but do so after medication reduction, similarly to seizures. This implies that spikes and HFOs have different pathophysiologic mechanisms and that HFOs are more tightly linked to seizures than spikes. HFOs seem to play an important role in seizure genesis and can be a useful clinical marker for disease activity.
PMID: 19289737 CAMSID: cams3470
High frequency oscillations (HFOs) have been implicated in ictogenesis and epileptogenesis. The effect of contact size (in the clinical range: 1–10 mm2) on HFO detection has not been determined. This study assesses the feasibility of HFO detection in a rat epilepsy model using macrocontacts and clinical amplifiers, and the effect of contact size on HFO detection within the macrocontact range.
Eight epileptic rats were implanted with intracerebral electrodes containing three adjacent contacts of different sizes (0.02, 0.05 and 0.09 mm2). HFOs were manually marked on 5 min interictal EEG segments. HFO rates and durations were compared between the different contacts.
10,966 ripples and 1475 fast ripples were identified in the recordings from 30 contacts. There were no significant differences in spike or HFO rates between the different contact sizes, nor was there a significant difference in HFO duration.
HFOs can be detected in a rat epilepsy model using macrocontacts. Within the studied range, size did not significantly influence HFO detection.
Using comparative anatomy of rat and human limbic structures, these findings suggest that reducing the size of macrocontacts (compared to those commercially available) would not improve HFO detection rates.
PMID: 21429792 CAMSID: cams3346
High frequency oscillation; HFO; Ripple; Fast ripple; Intracerebral recording; Depth electrode; SEEG
Intracranial depth macroelectrode recordings from patients with focal seizures demonstrate interictal and ictal high frequency oscillations (HFOs, 80–500 Hz). These HFOs are more frequent in the seizure-onset zone (SOZ) and reported to be linked to seizure genesis. We evaluated whether HFO activity changes in a systematic way during the preictal period.
Fifteen minutes of preictal intracranial electroencephalography (EEG) recordings were evaluated in seven consecutive patients with well-defined SOZ. EEG was filtered at 500 Hz and sampled at 2,000 Hz. Ripples (80–250 Hz) and fast ripples (250–500 Hz) were visually marked, and spectral analysis was performed in seizure-onset as well as nonseizure-onset channels. Linear regressions fitted to the power trends corresponding to intervals of 1, 5, and 15 min before the seizure onset was calculated.
Total rates of HFOs were significantly higher in the SOZ than outside. Preictal increases and decreases in HFO rates and band power could be detected in all patients, and they were not limited to the SOZs. These measures were very variable, and nosystematic trends were observed when comparing patients or seizures in the same patient.
High frequencies in the range of 80–500 Hz are present during the preictal period and are more prominent in the SOZ. They do not change in a systematic way before seizure onset for the horizons we tested. The 80–500 Hz band may be used for the localization of seizure-onset areas but may be more difficult to use for seizure prediction purposes.
PMID: 19400871 CAMSID: cams3402
Intracranial EEG; Epilepsy; Ripples; Fast ripples; Seizure prediction
Electrical stimulation (ES) is used during intracranial electroencephalography (EEG) investigations to delineate epileptogenic areas and seizure-onset zones (SOZs) by provoking afterdischarges (ADs) or patients’ typical seizure. High frequency oscillations (HFOs—ripples, 80–250 Hz; fast ripples, 250–500 Hz) are linked to seizure onset. This study investigates whether interictal HFOs are more frequent in areas with a low threshold to provoke ADs or seizures.
Intracranial EEG studies were filtered at 500 Hz and sampled at 2,000 Hz. HFOs were visually identified. Twenty patients underwent ES, with gradually increasing currents. Results were interpreted as agreeing or disagreeing with the intracranial study (clinical-EEG seizure onset defined the SOZ). Current thresholds provoking an AD or seizure were correlated with the rate of HFOs of each channel.
ES provoked a seizure in 12 and ADs in 19 patients. Sixteen patients showed an ES response inside the SOZ, and 10 had additional areas with ADs. The response was more specific for mesiotemporal than for neocortical channels. HFO rates were negatively correlated with thresholds for ES responses; especially in neo-cortical regions; areas with low threshold and high HFO rate were colocalized even outside the SOZ.
Areas showing epileptic HFOs colocalize with those reacting to ES. HFOs may represent a pathologic correlate of regions showing an ES response; both phenomena suggest a more widespread epileptogenicity.
PMID: 19845730 CAMSID: cams3394
Ripple; Fast ripple; Electrical stimulation; Seizure-onset zone
Removal of areas generating high-frequency oscillations (HFOs) recorded from the intracerebral electroencephalography (iEEG) of patients with medically intractable epilepsy has been found to be correlated with improved surgical outcome. However, whether differences exist according to the type of epilepsy is largely unknown. We performed a comparative assessment of the impact of removing HFO-generating tissue on surgical outcome between temporal lobe epilepsy (TLE) and extratemporal lobe epilepsy (ETLE). We also assessed the relationship between the extent of surgical resection and surgical outcome.
We studied 30 patients with drug-resistant focal epilepsy, 21 with TLE and 9 with ETLE. Two thirds of the patients were included in a previous report and for these, clinical and imaging data were updated and follow-up was extended. All patients underwent iEEG investigations (500 Hz high-pass filter and 2,000 Hz sampling rate), surgical resection, and postoperative magnetic resonance imaging (MRI). HFOs (ripples, 80–250 Hz; fast ripples, >250 Hz) were identified visually on a 5–10 min interictal iEEG sample. HFO rates inside versus outside the seizure-onset zone (SOZ), in resected versus nonresected tissue, and their association with surgical outcome (ILAE classification) were assessed in the entire cohort, and in the TLE and ETLE subgroups. We also tested the correlation of resected brain hippocampal and amygdala volumes (as measured on postoperative MRIs) with surgical outcome.
HFO rates were significantly higher inside the SOZ than outside in the entire cohort and TLE subgroup, but not in the ETLE subgroup. In all groups, HFO rates did not differ significantly between resected and nonresected tissue. Surgical outcome was better when higher HFO rates were included in the surgical resection in the entire cohort and TLE subgroup, but not in the ETLE subgroup. Resected brain hippocampal and amygdala volumes were not correlated with surgical outcome.
In TLE, removal of HFO-generating areas may lead to improved surgical outcome. Less consistent findings emerge from ETLE, but these may be related to sample size limitations of this study. Size of resection, a factor that was ignored and that could have affected results of earlier studies did not influence results.
PMID: 23294353 CAMSID: cams2976
High-frequency oscillations; Intracerebral EEG; Epilepsy surgery; Temporal lobe epilepsy; Extra-temporal lobe epilepsy
We present a multistage fuzzy rule-based algorithm for epileptic seizure onset detection. Amplitude, frequency, and entropy-based features were extracted from intracranial electroencephalogram (iEEG) recordings and considered as the inputs for a fuzzy system. These features extracted from multichannel iEEG signals were combined using fuzzy algorithms both in feature domain and in spatial domain. Fuzzy rules were derived based on experts' knowledge and reasoning. An adaptive fuzzy subsystem was used for combining characteristics features extracted from iEEG. For the spatial combination, three channels from epileptogenic zone and one from remote zone were considered into another fuzzy subsystem. Finally, a threshold procedure was applied to the fuzzy output derived from the final fuzzy subsystem. The method was evaluated on iEEG datasets selected from Freiburg Seizure Prediction EEG (FSPEEG) database. A total of 112.45 hours of intracranial EEG recordings was selected from 20 patients having 56 seizures was used for the system performance evaluation. The overall sensitivity of 95.8% with false detection rate of 0.26 per hour and average detection latency of 15.8 seconds was achieved.
High-frequency oscillations (HFOs) of up to 500 Hz in EEG are considered to have close relation with ictogenesis. We had the unique opportunity to record a seizure in EEG with intracerebral macroelectrodes and a sampling frequency of 10 kHz. Considering the notion that faster HFOs are likely more ictogenic, we investigated this ictal EEG data to find if even faster HFOs were present.
HFOs were investigated in interictal spikes and seizure activity using time–frequency spectra: t values corresponding to frequencies from 100 to 1000 Hz were obtained by comparison to the background and controlled by the false discovery rate (FDR).
The seizure had a right hippocampal onset. HFOs up to 800 Hz as well as HFOs below 500 Hz built up in the hippocampal discharges more at the beginning of the seizure and during the preictal period than in the interictal period. These HFOs were visually confirmed in temporally expanded EEG traces.
We demonstrated for the first time the existence of HFOs above 500 Hz and up to 800 Hz with intracerebral macroelectrodes in an epileptic patient; they occurred primarily in association with the seizure discharge. HFOs above 500 Hz possibly reflect facilitation of ictogenic neuronal hypersynchronization.
PMID: 19914804 CAMSID: cams3395
High-frequency oscillation; Mesial temporal lobe epilepsy; Ictal EEG; Time–frequency analysis; False discovery rate
Many recent studies have reported the importance of high-frequency oscillations (HFOs) in the intracerebral electroencephalography (EEG) of patients with epilepsy. These HFOs have been defined as events that stand out from the background. We have noticed that this background often consists itself of high-frequency rhythmic activity. The purpose of this study is to perform a first evaluation of the characteristics of high-frequency continuous or semicontinuous background activity.
Because the continuous high-frequency pattern was noted mainly in mesial temporal structures, we reviewed the EEG studies from these structures in 24 unselected patients with electrodes implanted in these regions. Sections of background away from interictal spikes were marked visually during periods of slow-wave sleep and wakefulness. They were then high-passed filtered at 80 Hz and categorized as having high-frequency rhythmic activity in one of three patterns: continuous/semicontinuous, irregular, sporadic. Wavelet entropy, which measures the degree of rhythmicity of a signal, was calculated for the marked background sections.
Ninety-six bipolar channels were analyzed. The continuous/semicontinuous pattern was found frequently (29/96 channels during wake and 34/96 during sleep). The different patterns were consistent between sleep and wakefulness. The continuous/semicontinuous pattern was found significantly more often in the hippocampus than in the parahippocampal gyrus and was rarely found in the amygdala. The types of pattern were not influenced by whether a channel was within the seizure-onset zone, or whether it was a lesional channel. The continuous/semicontinuous pattern was associated with a higher frequency of spikes and with high rates of ripples and fast ripples.
It appears that high-frequency activity (above 80 Hz) does not appear only in the form of brief paroxysmal events but also in the form of continuous rhythmic activity or very long bursts. In this study limited to mesial temporal structures, we found a clear anatomic preference for the hippocampus. Although associated with spikes and with distinct HFOs, this pattern was not clearly associated with the seizure-onset zone. Future studies will need to evaluate systematically the presence of this pattern, as it may have a pathophysiologic significance and it will also have an important influence on the very definition of HFOs.
PMID: 22416973 CAMSID: cams3340
High-frequency EEG; Mesial temporal structures; High-frequency oscillations; Intracerebral electrodes
High-frequency oscillations (HFOs) in the intracerebral electroencephalogram (EEG) have been linked to the seizure onset zone (SOZ). We investigated whether HFOs can delineate epileptogenic areas even outside the SOZ by correlating the resection of HFO-generating areas with surgical outcome.
Twenty patients who underwent a surgical resection for medically intractable epilepsy were studied. All had presurgical intracerebral EEG (500Hz filter and 2,000Hz sampling rate), at least 12-month postsurgical follow-up, and a postsurgical magnetic resonance imaging (MRI). HFOs (ripples, 80 –250Hz; fast ripples, >250Hz) were identified visually during 5 to 10 minutes of slow-wave sleep. Rates and extent of HFOs and interictal spikes in resected versus nonresected areas, assessed on postsurgical MRIs, were compared with surgical outcome (Engel’s classification). We also evaluated the predictive value of removing the SOZ in terms of surgical outcome.
The mean duration of follow-up was 22.7 months. Eight patients had good (Engel classes 1 and 2) and 12 poor (classes 3 and 4) surgical outcomes. Patients with a good outcome had a significantly larger proportion of HFO-generating areas removed than patients with a poor outcome. No such difference was seen for spike-generating regions or the SOZ.
The correlation between removal of HFO-generating areas and good surgical outcome indicates that HFOs could be used as a marker of epileptogenicity and may be more accurate than spike-generating areas or the SOZ. In patients in whom the majority of HFO-generating tissue remained, a poor surgical outcome occurred.
PMID: 20225281 CAMSID: cams3398
High-frequency oscillations (HFOs) are EEG field potentials with frequencies higher than 30 Hz; commonly the frequency band between 30 – 70 Hz is denominated the gamma band, but with the discovery of activities at frequencies higher than 70 Hz a variety of terms have been proposed to describe the latter (Gotman and Crone 2011). In general we may consider that the term HFO encompasses activities from 30 – 600 Hz. The best practice is to indicate always explicitly the frequency range of the HFOs in any specific study. There are numerous types of HFOs: those in normal brain appear to facilitate synchronization and information transfer necessary for cognitive processes and memory, while a particular class of HFOs in the brain of animals and people with epilepsy appear to reflect fundamental mechanisms of epileptic phenomena and could serve as biomarkers of epileptogenesis and epileptogenicity in abnormal conditions such as epilepsy. A better understanding of the significance of HFOs depends on a deeper analysis of the mechanisms of generation of different kinds of HFOs, that typically are at the crossroads between intrinsic membrane properties and neuronal interactions, both chemical and electrical. There is still a lack of understanding of how specific information is carried by HFOs and can be operational in normal cognitive processes such as in working and long-term memory and abnormal conditions such as epilepsy. The complexity of these processes makes the development of relevant computational models of dynamical neuronal networks most compelling.
Epilepsy; Cognitive function; High-frequency oscillations; EEG
High frequency oscillations (HFOs) have been associated with epileptogenicity. In rats, the extent of HFOs (>200 Hz) is correlated with seizure frequency. We studied whether the same applies to patients with focal epilepsy. Thirty-nine patients with intracerebral EEG sampled at 2000 Hz were studied for interictal ripples (80–250 Hz), fast ripples (FR, 250–500 Hz) and spikes. Seizure frequency before implantation was compared to numbers of channels with HFOs (>1/min). Analyses were repeated for HFO rates of >5, >10 and >20. Separate analyses were done for 25 patients with temporal lobe epilepsy only and for a selection of similar unilateral temporal channels in 12 patients. No linear correlation or trend was found relating the number of channels with HFOs and seizure frequency. There was a linear positive correlation between the number of channels with more than 20 FRs/min and seizure frequency. The hypothesis that the more tissue generating HFOs, the higher the seizure frequency, was not confirmed, though there might be a correlation for high FR rates.
PMID: 19403269 CAMSID: cams3403
Intracranial electrodes; Epilepsy surgery; Ripple; Fast ripple; Seizure prediction
To investigate the characteristics of intracranial ictal high frequency oscillations (HFOs).
Among neocortical epilepsy patients who underwent intracranial monitoring and surgery, we studied patients with well-defined, unifocal seizure onsets characterized by discrete HFOs (≥70 Hz). Patients with multifocal or bilateral independent seizure onsets, EEG acquired at <1,000 Hz sampling rate and non-resective surgery were excluded. Based on a prospectively-defined protocol, we defined the seizure onset zone (SOZ) presurgically to include only those channels with HFOs that showed subsequent sustained evolution (HFOs+ev channels) but not the channels that lacked evolution (HFOs-ev channels). We then resected the SOZ as defined above, 1 cm of the surrounding cortex and immediate spread area, modified by the presence of eloquent cortex in the vicinity. For purposes of this study, we also defined the SOZ based on the conventional frequency activity (CFA: <70 Hz) at seizure onset although that information was not considered for preoperative determination of the surgical boundary. We investigated the temporal and spatial characteristics of the ictal HFOs post-hoc by visual and spectral methods, and also compared them to the seizure onset defined by the CFA.
Out of 14 consecutive neocortical epilepsy patients, six patients met the inclusion criteria. MRI was normal or showed heterotopia. All had subdural electrodes, with additional intracerebral depth electrodes in some. Electrode coverage was extensive (median 94 channels), including limited contralateral coverage. Seizure onsets were lobar or multilobar. Resections were performed per protocol except in two patients where complete resection of the SOZ could not be done due to overlap with speech area. Histology was abnormal in all patients. Postoperative outcome was class I/II (n=5, 83%) or class III over a mean follow-up of 27 months. Post-hoc analysis of 15 representative seizures showed that the ictal HFOs were widespread at seizure onset but evolved subsequently with different characteristics. In contrast to HFOs-ev, the HFOs+ev were significantly higher in peak frequency (97.1 versus 89.1 Hz, p=0.001), more robust (nearly 2-fold higher peak power, p<0.0001), and spatially restricted [mean 12.2 versus 22.4 channels; odds ratio (OR) 0.51, 95% confidence interval (CI) 0.42–0.62; p<0.0001]. The seizure onset defined by HFOs+ev was earlier (by an average of 0.41 sec), and occurred in a significantly different and smaller distribution (OR 0.27, 95% CI 0.21–0.34, p<0.0001), than the seizure onset defined by the CFA. As intended, the HFOs+ev channels were 10 times more likely to have been resected than the HFOs-ev channels (OR 9.7, 95% CI 5–17, p<0.0001).
Our study demonstrates the widespread occurrence of ictal HFOs at seizure onset, outlines a practical method to localize the SOZ based on their restricted pattern of evolution, and highlights the differences between the SOZs defined by HFOs and CFA. We show that smaller resections, restricted mainly to the HFOs channels with evolution, can lead to favorable seizure outcome. Our findings support the notion of widespread epileptic networks underlying neocortical epilepsy.
Epilepsy surgery; High frequency oscillations; Intracranial EEG; HFOs; Seizure
Much of the information on the physiologic effects, mechanisms of gas exchange, and potential utility of high-frequency oscillation (HFO) has been acquired in animal studies. Specifically, large animal data have been useful in assessing adult application because large animals present many of the same concerns and challenges as adults.
To review the literature on HFO testing in large animal models, identifying contributions to the understanding of mechanisms of action and the physiology of HFO.
Large animal studies have clarified the mechanisms of gas exchange during HFO, identified approaches to setting mean airway pressure based on lung mechanics, and identified a potentially better approach to applying partial liquid ventilation.
The study of HFO in large animal models has been essential to our understanding of the optimal approach to applying HFO in human studies.
high-frequency oscillatory ventilation; partial liquid ventilation; regional gas transport; conventional ventilation; large-animal models
While infantile spasms is the most common catastrophic epilepsy of infancy and early-childhood, very little is known about the basic mechanisms responsible for this devastating disorder. In experiments reported here, spasms were induced in rats by the chronic infusion of TTX into the neocortex beginning on postnatal day 10–12. Studies of focal epilepsy suggest that high frequency EEG oscillations (HFOs) occur interictally at sites that are most likely responsible for seizure generation. Thus, our goal was to determine if HFOs occurred and where they occurred in cortex in the TTX model. We also undertook multiunit recordings to begin to analyze the basic mechanisms responsible for HFOs. Our results show that HFOs occur most frequently during hypsarrhythmia and NREM sleep and are most prominent contralateral to the TTX infusion site in the homotopic cortex and anterior to this region in frontal cortex. While HFOs were largest and most frequent in these contralateral regions, they were also commonly recorded synchronously across multiple and widely-spaced recordings sites. The amplitude and spatial distribution of interictal HFOs were found to be very similar to the high frequency bursts seen at seizure onset. However, the latter differed from the interictal events in that the high frequency activity was more intense at seizure onset. Microwire recordings showed that neuronal unit firing increased abruptly with the generation of HFOs. A similar increase in neuronal firing occurred at the onset of the ictal events. Taken together, results suggest that neocortical networks are abnormally excitable, particularly contralateral to TTX infusion, and that these abnormalities are not restricted to small areas of cortex. Multiunit firing coincident with HFOs are fully consistent with a neocortical hyperexcitability hypothesis particularly since they both occur at seizure onset.
Epilepsy; Seizures; Infantile Spasms; TTX; High Frequency Oscillations; EEG
High Frequency Oscillations (HFOs), including Ripples (80–250 Hz) and Fast Ripples (250– 500 Hz), can be recorded from intracranial macroelectrodes in patients with intractable epilepsy. We implemented a procedure to establish the duration for which a stable measurement of rate of HFOs is achieved.
To determine concordance, Kappa coefficient was computed. The information gained when increasing the duration was analyzed in terms of HFO rates and ranking of channels with respect to HFO and spike rates.
In a group of 30 patients, Kappa was 0.7 for ripples, 0.7 for fast ripples and 0.67 for spikes. Five minutes provided the same information as 10 min in terms of rates in 9/10 patients and with respect to ranking of channels in 8/10 patients; 5/30 patients did not achieve stable measurements of HFOs or spikes and needed marking for 10 min.
We propose that 5 min provides in most cases the same information as a longer interval when identifying HFOs and spikes in slow wave sleep, and present methods to identify when this is not the case.
This procedure is useful to control for consistency between readers and to evaluate if the selected interval provides stable information, for automatic and visual identification of events.
PMID: 19576848 CAMSID: cams3407
High Frequency Oscillations, Ripple; Fast ripple; Kappa; Jensen-Shannon Divergence; Ranking Distance