Objective-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.Methods-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.Results-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.Interpretation-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 HFOgenerating tissue remained, a poor surgical outcome occurred.Thirty percent to 40% of patients with focal epilepsy are medically intractable, 1 and for some, surgical removal of epileptogenic areas is the best option to gain seizure freedom. Intracranial electroencephalographic (iEEG) investigations are indicated for patients in whom noninvasive methods fail to identify a single focal seizure generator. CIHR Author Manuscript CIHR Author Manuscript CIHR Author ManuscriptiEEG is used to define the seizure onset zone (SOZ). 3 Removal of the SOZ alone, however, does not always predict the surgical benefit. 4,5 It is uncertain whether the outcome can be improved by removing areas of interictal spiking, often more widespread than the SOZ. 6,7 Intracranial studies also have limitations, as their results depend on electrode location and type of implantation (intracortical vs subdural). For instance, iEEG electrodes only record neuronal activity in their direct vicinity and are blind for other areas, 8 making it hard to judge whether the activity at seizure onset really represents the seizure generator or is the result of propagation from else-where. Thus the actual focus and its extent may be missed, leading to unsuccessful surgery.Microelectrode-recorded high-frequency oscillations (HFOs), ripples (80 -250Hz), and fast ripples (FRs, 250 -500Hz), were found predominantly in epileptogenic tissue. 9 -11 They can also be recorded with macroelectrodes duri...

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.

Objective: This study aims to identify if oscillations at frequencies higher than the traditional EEG can be recorded on the scalp EEG of patients with focal epilepsy and to analyze the association of these oscillations with interictal discharges and the seizure onset zone (SOZ). Methods:The scalp EEG of 15 patients with focal epilepsy was studied. We analyzed the rates of gamma (40-80 Hz) and ripple (Ͼ80 Hz) oscillations, their co-occurrence with spikes, the number of channels with fast oscillations inside and outside the SOZ, and the specificity, sensitivity, and accuracy of gamma, ripples, and spikes to determine the SOZ.Results: Gamma and ripples frequently co-occurred with spikes (77.5% and 63% of cases). For all events, the proportion of channels with events was consistently higher inside than outside the SOZ: spikes (100% vs 70%), gamma (82% vs 33%), and ripples (48% vs 11%); p Ͻ 0.0001. The mean rates (events/min) were higher inside than outside the SOZ: spikes (2.64 Ϯ 1.70 vs 0.69 Ϯ 0.26, p ϭ 0.02), gamma (0.77 Ϯ 0.71 vs 0.20 Ϯ 0.25, p ϭ 0.02), and ripples (0.08 Ϯ 0.12 vs 0.04 Ϯ 0.09, p ϭ 0.04). The sensitivity to identify the SOZ was spikes 100%, gamma 82%, and ripples 48%; the specificity was spikes 30%, gamma 68%, and ripples 89%; and the accuracy was spikes 43%, gamma 70%, and ripples 81%. Conclusion:The rates and the proportion of channels with gamma and ripple fast oscillations are higher inside the SOZ, indicating that they can be used as interictal scalp EEG markers for the SOZ. These fast oscillations are less sensitive but much more specific and accurate than spikes to delineate the SOZ. Neurology The conventional range of EEG analysis usually involves frequencies below 40 Hz. Studies over the last decade suggest, however, that high-frequency oscillations (HFOs) may have an essential role in normal and pathologic brain function. Reports using microelectrodes combined with depth EEG electrodes showed the presence of HFOs in epileptic patients.

mcgill.ca).

Objective-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.Methods-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.Results-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.Conclusions-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.High-frequency oscillations (HFOs) in intracranial EEG have been associated with epileptogenesis and seizure genesis and have been studied in humans and rats. [1][2][3][4][5][6][7][8][9][10][11][12][13][14] They have been divided into ripples (80 -250 Hz) and fast ripples (FRs; 250 -500 Hz). 13 Ripples have been considered more physiologic in nature because they have also been recorded in healthy animal brains, whereas FRs are more frequent in affected hippocampi. 3,6,[15][16][17][18][19][20] Address correspondence and reprint requests to Dr. Jean Gotman, Montreal Neurological Institute and Hospital, 3801 University St., Montreal, Quebec, Canada H3A 2B4, jean.gotman@mcgill.ca. Disclosure: J.G. was a major shareholder of Stellate. The other authors report no disclosures. AUTHOR CONTRIBUTIONS CIHR Author Manuscript CIHR Author Manuscript CIHR Author ManuscriptHowever, both ripples and FRs have been correlated with the seizure onset zone (SOZ). 7,11,21 HFOs were first recorded with microelectrodes but can also be recorded with clinically used macroelectrodes. 11,13,[21][22][23] HFOs have been associated with seizure genesis because their localization is related to the seizure focus and they occur at seizure onset 1,6,11,24 and with epileptogenesis, as HFOs occurred before spontaneous seizures in kainic acid-injected rats. 7 They may result from a γ-aminobuteric acid-mediated feedback imbalance or pathologic neuronal connecti...

This multicenter atlas is the first to provide region-specific normative values for physiological HFO rates and HFA in common stereotactic space; rates above these can now be considered pathological. Physiological ripples are frequent in eloquent cortex. In contrast, physiological fast ripples are very rare, making fast ripples a good candidate for defining the epileptogenic zone. Ann Neurol 2018;84:374-385.

In recent years, new recording technologies have advanced such that, at high temporal and spatial resolutions, high-frequency oscillations (HFO) can be recorded in human partial epilepsy. However, because of the deluge of multichannel data generated by these experiments, achieving the full potential of parallel neuronal recordings depends on the development of new data mining techniques to extract meaningful information relating to time, frequency and space. Here, we aim to bridge this gap by focusing on up-to-date recording techniques for measurement of HFO and new analysis tools for their quantitative assessment. In particular, we emphasize how these methods can be applied, what property might be inferred from neuronal signals, and potentially productive future directions.

SUMMARYPurpose: 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. Methods: 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 followup 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. Key Findings: 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. Significance: 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.