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Summary: Subclinical rhythmic EEG discharge of adults is an uncommon variant that represents a diagnostic challenge in the clinical practice because it can be mistaken for an electrographic seizure. We present a case series of four patients who underwent EEG because of suspicious events or an unclear medical history of epilepsy. In all cases, the EEG revealed atypical features including focal and asymmetric distribution, presentation during NREM and REM sleep, rhythmic activity in the delta range with a notched appearance and blocked by eyes opening., Competing Interests: The authors have no funding or conflicts of interest to disclose, (Copyright © 2023 by the American Clinical Neurophysiology Society.)

Objective: To determine if properties of epileptic networks could be delineated using interictal spike propagation seen on stereo-electroencephalography (SEEG) and if these properties could predict surgical outcome in patients with drug-resistant epilepsy., Methods: We studied the SEEG of 45 consecutive drug-resistant epilepsy patients who underwent subsequent epilepsy surgery: 18 patients with good post-surgical outcome (Engel I) and 27 with poor outcome (Engel II-IV). Epileptic networks were derived from interictal spike propagation; these networks described the generation and propagation of interictal epileptic activity. We compared the regions in which spikes were frequent and the regions responsible for generating spikes to the area of resection and post-surgical outcome. We developed a measure termed source spike concordance, which integrates information about both spike rate and region of spike generation., Results: Inclusion in the resection of regions with high spike rate is associated with good post-surgical outcome (sensitivity = 0.82, specificity = 0.73). Inclusion in the resection of the regions responsible for generating interictal epileptic activity independently of rate is also associated with good post-surgical outcome (sensitivity = 0.88, specificity = 0.82). Finally, when integrating the spike rate and the generators, we find that the source spike concordance measure has strong predictability (sensitivity = 0.91, specificity = 0.94)., Interpretations: Epileptic networks derived from interictal spikes can determine the generators of epileptic activity. Inclusion of the most active generators in the resection is strongly associated with good post-surgical outcome. These epileptic networks may aid clinicians in determining the area of resection during pre-surgical evaluation., (© 2021 The Authors. Annals of Clinical and Translational Neurology published by Wiley Periodicals LLC on behalf of American Neurological Association.)

Stereo-electroencephalography (SEEG) has gained global popularity in recent years. In Japan, a country in which invasive studies using subdural electrodes (SDEs) have been the mainstream, SEEG has been approved for insurance coverage in 2020 and is expected to gain in popularity. Some concepts supporting SEEG methodology are fundamentally different from that of SDE studies. Clinicians interested in utilizing SEEG in their practice should be aware of those aspects in which they differ. Success in utilizing the SEEG methodology relies heavily on the construction of an a priori hypothesis regarding the putative seizure onset zone (SOZ) and propagation. This article covers the technical and theoretical aspects of SEEG, including the surgical techniques and precautions, hypothesis construction, and the interpretation of the recording, all with the aim of providing an introductory guide to SEEG.

Purpose: In comatose patients, distinguishing between nonconvulsive status epilepticus and diffuse structural or metabolic encephalopathies is often challenging. Both conditions can generate periodic discharges on EEG with similar morphology and periodicity. We investigated the occurrence of high-frequency oscillations-potential biomarkers of epileptogenesis-on scalp EEG of comatose patients with periodic discharges in the EEG., Methods: Fifteen patients were included. Patients were divided into three groups, according to underlying etiology: Group 1, seizure related; group 2, structural; group 3, nonstructural. EEG recordings were compared with respect to the presence and rates of gamma (30-80 Hz) and ripples (80-250 Hz)., Results: Patients were 23 to 106 years old (median, 68 years); 60% were female. 206 channels were eligible for analysis (median, 15 channels/patient). Overall, 43% of channels showed gamma, and 24% had ripples. Group 2 showed the highest proportion of channels with gamma (47%), followed by group 1 (38%) and group 3 (36%). Mean gamma rates were higher in group 2 (4.65 gamma/min/channel) than in group 1 (1.52) and group 3 (1.44) (P < 0.001). Group 2 showed the highest proportion of channels with ripples (29.2%), followed by group 1 (15%) and group 3 (24.2%). Mean ripple rates were higher in group 2 (5.09 ripple/min/channel) than in group 1 (0.96) and group 3 (0.83) (P < 0.001)., Conclusions: Fast oscillations, including high-frequency oscillations, can be detected in scalp EEG of patients with altered consciousness. High rates of fast activity may suggest an underlying structural brain lesion. Future studies are needed to determine whether fast oscillations in the setting of acute/subacute brain lesions are a biomarker of subsequent development of human epilepsy.

Many patients with medically refractory epilepsy now undergo successful surgery based on noninvasive diagnostic information, but intracranial electroencephalography (IEEG) continues to be used as increasingly complex cases are considered surgical candidates. The indications for IEEG and the modalities employed vary across epilepsy surgical centers; each modality has its advantages and limitations. IEEG can be performed in the same intraoperative setting, that is, intraoperative electrocorticography, or through an independent implantation procedure with chronic extraoperative recordings; the latter are not only resource intensive but also carry risk. A lack of understanding of IEEG limitations predisposes to data misinterpretation that can lead to denying surgery when indicated or, worse yet, incorrect resection with adverse outcomes. Given the lack of class 1 or 2 evidence on IEEG, a consensus-based expert recommendation on the diagnostic utility of IEEG is presented, with emphasis on the application of various modalities in specific substrates or locations, taking into account their relative efficacy, safety, ease, and incremental cost-benefit. These recommendations aim to curtail outlying indications that risk the over- or underutilization of IEEG, while retaining substantial flexibility in keeping with most standard practices at epilepsy centers and addressing some of the needs of resource-poor regions around the world., (Wiley Periodicals, Inc. © 2016 International League Against Epilepsy.)

To evaluate the possibility of detecting fast ripples (FRs) on the surface EEG of patients with focal pharmacoresistant epilepsy, and to investigate the relationship between scalp FRs and localization of the seizure onset zone (SOZ). We included 10 patients undergoing combined surface-intracranial EEG with ≥10 spikes in the surface EEG during the first 30 consecutive minutes of N3 sleep. FRs (≥4 consecutive oscillations above 250 Hz with an amplitude clearly exceeding that of the background) on the surface EEG (F3-C3, C3-P3, Fz-Cz, Cz-Pz, F4-C4, C4-P4) were visually marked, and verified by two EEG experts. FRs were categorized as related to the SOZ, if localized in the brain lobe of the SOZ. Low-amplitude FRs with a rate of 0.09/min were found in 6/10 patients: two exhibited events related to the SOZ, three showed no relationship with the SOZ, and in one patient the SOZ was not identified. It may be possible to detect FRs with surface EEG using subdermal electrodes in patients with focal epilepsy. The relationship between surface FRs and the SOZ remains unclear. Future studies aiming at a higher spatial EEG coverage are needed to elucidate their significance.

Objective: To evaluate scalp ripples distribution in secondary bilateral synchrony as a tool to lateralize the epileptic focus and to differentiate focal from generalized epilepsy., Methods: Seventeen EEG recordings with bilateral synchronous discharges of focal (focal group-FG: 10) and generalized (generalized group-GG: 7) epilepsy patients were selected for spikes and ripples marking; the spike-normalized ripple rate was calculated in each hemisphere (right/left - anterior/posterior) and a ripple-dominant hemisphere (the one with the highest rate) was identified. Concordance in FG between the ripple dominant hemisphere and the hemisphere of clinical lateralization was evaluated. The ripple-dominant/ripple-nondominant spike-normalized ripple rate ratio was studied to compare groups., Results: In FG the hemisphere of clinical lateralization and the ripple-dominant hemisphere were 100% concordant. In GG only 3/7 patients showed ripples (vs 10/10 FG), all with anterior dominance. No difference in hemisphere ripple dominance between groups was found., Conclusions: Ripples in secondary bilateral synchrony help to lateralize the epileptic focus but do not help to differentiate between focal and generalized epilepsy. This is the first report of visually identified ripples in idiopathic generalized epilepsy., Significance: Ripples confirm the clinical lateralization of the epileptic focus in secondary bilateral synchrony but cannot distinguish between focal and generalized epilepsy., (Copyright © 2015 International Federation of Clinical Neurophysiology. Published by Elsevier Ireland Ltd. All rights reserved.)

Objective: Although a clear correlation has been observed between high-frequency oscillations (HFOs) and the seizure-onset zone in distinct lesions, the role of the underlying pathologic substrates in the generation of HFOs is not well established. We aimed to investigate HFO correlates of different pathologic substrates in patients with drug-resistant epilepsy, and to examine the relation of HFOs with the anatomic location of the dysplastic lesion and surrounding tissue in patients with focal cortical dysplasia (FCD)., Methods: We studied consecutive patients with drug-resistant epilepsy who underwent intracranial electroencephalography (iEEG) investigations with depth electrodes at the Montreal Neurological Institute and Hospital, between November 2004 and May 2013. Inclusion criteria were the following: a focal lesion documented by magnetic resonance imaging (MRI); EEG recording at a 2,000 Hz sampling rate; and seizures starting from depth electrode contacts placed in lesion and perilesional tissue., Results: Thirty-seven patients (13 FCD, 12 mesial temporal sclerosis, five cortical atrophy, three polymicrogyria, three nodular heterotopia, and one tuberous sclerosis) were included; 18 were women (median age 34). Ripples and fast ripples were found in all lesion types, except tuberous sclerosis, which showed no fast ripples. There was a significant difference in rates of ripples and fast ripples across different lesions (p < 0.001), with higher rates in FCD, mesial temporal sclerosis, and nodular heterotopia than in atrophy, polymicrogyria, and tuberous sclerosis. Regarding patients with FCD, HFOs rates differed significantly across the three types of tissue (lesional, perilesional, and nonlesional; p < 0.001), being higher within the borders of the MRI-visible dysplastic lesion, followed by the surrounding area, and rare in the remote cortex., Significance: Our findings suggest that in patients who are all intractable, the HFO rates vary with different pathologies, and reflect different types of neuronal derangements. Our results also emphasize the potential usefulness of HFOs as an additional method to better define the extent of the epileptogenic dysplastic tissue in FCD., (Wiley Periodicals, Inc. © 2015 International League Against Epilepsy.)

Background: Using clinical parameters to identify and monitor treatment response in patients with delayed cerebral ischemia (DCI) following subarachnoid hemorrhage is challenging. We sought to determine whether continuous electroencephalography (CEEG) aids the prediction of the clinical course and response to treatment of DCI., Methods: Patients deemed high-risk for DCI based on the modified Fisher scale were prospectively monitored. A novel CEEG parameter measuring relative alpha power and variability in the anterior brain quadrants termed composite alpha index (CAI) was graphically displayed. Predictions of the status of patients for the ensuing day were made by an independent reviewer, first using clinical data then repeated following the addition of CAI trends. These were compared to the actual clinical state. The reviewer was blinded to the presence and treatment of DCI. Patients with DCI were further studied by trending the daily mean alpha power against the modulation of treatment and clinical evolution., Results: Fifty-nine predictions were made in 12 patients (mean age 54.3 years, range 35-70; nine females) with Hunt-Hess grades ranging I-V. Sensitivity of predicting clinical deterioration with CEEG improved from 40 to 67% and clinical improvement from 8 to 50%. In three patients, CEEG was predictive greater than 24 h prior to clinical change. Tracking the daily mean alpha power accurately identified DCI recurrence and poor responders to first-line therapy at pre-clinical stages., Conclusion: CEEG is a useful non-invasive tool to supplement routine clinical parameters in the prediction of DCI. It can dynamically monitor the response to treatment and might aid pre-clinical management decisions.

Purpose: Idiopathic generalized epilepsy (IGE) is characterized by electroencephalography (EEG) recordings with generalized spike wave discharges (GSWDs) arising from normal background activity. Although GSWDs are the result of highly synchronized activity in the thalamocortical network, EEG without GSWDs is believed to represent normal brain activity. The aim of this study was to investigate whether thalamocortical interactions are altered even during GSWD-free EEG periods in patients with IGE., Methods: A GSWD-related group analysis was performed in 12 IGE patients to define seeds in areas involved during GSWDs. EEG-functional magnetic resonance imaging (fMRI) datasets from 22 IGE patients without GSWDs during the investigation and 30 age-matched healthy controls were then selected to investigate functional connectivity in GSWD-related areas. Blood oxygen level dependent (BOLD) signal changes were extracted from seeds defined by the GSWD-related group analysis. The averaged time course within each seed was used to detect brain regions with BOLD signal correlated with the seed. Group differences between patients and controls were estimated., Key Findings: The GSWD-related group analysis showed BOLD activation in the thalamus, the frontomesial cortex, and the cerebellum and BOLD deactivation in default mode areas. For the connectivity analysis, eight seeds were placed bilaterally in the thalamus, mesial frontal cortex, precuneus, and cerebellum. The functional connectivity analysis of these seeds did not show clearly altered functional connectivity for patients versus controls., Significance: The results underscore the paroxysmal nature of GSWDs: Although GSWDs are characterized by highly synchronized activity in the thalamocortical network, the functional connectivity in areas involved during GSWDs does not demonstrate abnormality in GSWD-free periods., (Wiley Periodicals, Inc. © 2011 International League Against Epilepsy.)

Purpose: Absences are characterized by an abrupt onset and end of generalized 3-4 Hz spike and wave discharges (GSWs), accompanied by unresponsiveness. Although previous electroencephalography-functional magnetic resonance imaging (EEG-fMRI) studies showed that thalamus, default mode areas, and caudate nuclei are involved in absence seizures, the contribution of these regions throughout the ictal evolution of absences remains unclear. Furthermore, animal models provide evidence that absences are initiated by a cortical focus with a secondary involvement of the thalamus. The aim of this study was to investigate dynamic changes during absences., Methods: Seventeen absences from nine patients with absence epilepsy and classical pattern of 3-4 Hz GSWs during EEG-fMRI recording were included in the study. The absences were studied in a sliding window analysis, providing a temporal sequence of blood oxygen-level dependent (BOLD) response maps., Results: Thalamic activation was found in 16 absences (94%), deactivation in default mode areas in 15 (88%), deactivation of the caudate nuclei in 10 (59%), and cortical activation in patient-specific areas in 10 (59%) of the absences. Cortical activations and deactivations in default mode areas and caudate nucleus occurred significantly earlier than thalamic responses., Discussion: Like a fingerprint, patient-specific BOLD signal changes were remarkably consistent in space and time across different absences of one patient but were quite different from patient to patient, despite having similar EEG pattern and clinical semiology. Early frontal activations could support the cortical focus theory, but with an addition: This early activation is patient specific., (Wiley Periodicals, Inc. © 2010 International League Against Epilepsy.)

Purpose: In simultaneous electroencephalography (EEG) and functional magnetic resonance imaging (fMRI), increased neuronal activity from epileptiform spikes commonly elicits positive blood oxygenation level-dependent (BOLD) responses. Negative responses are also occasionally seen and have not been explained. Recent studies describe BOLD signal changes before focal EEG spikes. We aimed to systematically study if the undershoot of a preceding positive response might explain the negative BOLD seen in the focus., Methods: Eighty-two patients with focal epilepsy who underwent EEG-fMRI at 3T were retrospectively studied. Studies with a focal negative BOLD response in the region of the spike field were reanalyzed using models with hemodynamic response functions (HRFs) peaking from -9 to +9 s around the spike., Results: Eight patients met the inclusion criteria, showing negative BOLD responses in the spike field on standard analysis. None had positive BOLD responses immediately adjacent to the areas of deactivation. Regions of deactivation were found to have congruent preceding positive responses in two cases. These early activations were seen at the combined maps of -5 to -9 s., Discussion: This study indicates that in a small proportion of patients with focal epilepsy in whom the standard analysis reveals focal negative responses, an earlier positive BOLD response is probably the cause. The origin of negative BOLD signal changes in the focus as a result of an epileptic event remains, however, unexplained in most of the patients in whom it occurs., (Wiley Periodicals, Inc. © 2010 International League Against Epilepsy.)

Epileptic seizures are due to abnormal synchronized neuronal discharges. Techniques measuring electrical changes are commonly used to analyze seizures. Neuronal activity can be also defined by concomitant hemodynamic and metabolic changes. Simultaneous electroencephalogram (EEG)-functional MRI (fMRI) measures noninvasively with a high-spatial resolution BOLD changes during seizures in the whole brain. Until now, only a static image representing the whole seizure was provided. We report in 10 focal epilepsy patients a new approach to dynamic imaging of seizures including the BOLD time course of seizures and the identification of brain structures involved in seizure onset and discharge propagation. The first activation was observed in agreement with the expected location of the focus based on clinical and EEG data (three intracranial recordings), thus providing validity to this approach. The BOLD signal preceded ictal EEG changes in two cases. EEG-fMRI may detect changes in smaller and deeper structures than scalp EEG, which can only record activity form superficial cortical areas. This method allowed us to demonstrate that seizure onset zone was limited to one structure, thus supporting the concept of epileptic focus, but that a complex neuronal network was involved during propagation. Deactivations were also found during seizures, usually appearing after the first activation in areas close or distant to the activated regions. Deactivations may correspond to actively inhibited regions or to functional disconnection from normally active regions. This new noninvasive approach should open the study of seizure generation and propagation mechanisms in the whole brain to groups of patients with focal epilepsies., (2009 Wiley-Liss, Inc.)

Purpose: Simultaneous electroencephalogram (EEG) and functional magnetic resonance imaging (fMRI) (EEG-fMRI) recording is a noninvasive tool for investigating epileptogenic networks. Most EEG-fMRI studies in epilepsy have been performed in adults. Childhood epilepsies, however, differ from those in adults due to interactions between epileptogenic and developmental processes. The purpose of this study was to investigate EEG-fMRI in children with lesional epilepsies., Methods: Thirteen children with symptomatic epilepsy underwent a 20-min EEG-fMRI acquisition at 3 T under sedation-induced sleep. Statistical analysis was performed using the timing of spikes as events, modelled with hemodynamic response functions (HRFs) that peaked at 3, 5, 7, and 9 s after the spike., Results: Each spike type was analyzed separately, resulting in 25 studies. In 84% of the studies, blood oxygenation level-dependent (BOLD) responses were localized in the lesion or brain area presumably generating spikes. Activation (positive BOLD) corresponding with the lesion was seen in 20% and deactivation (negative BOLD) in 52% of the studies. In the area of spike generation, activation was found in 48% of studies and deactivation in 36%., Conclusions: Despite the necessarily short recording times (20 min), good results could be obtained from the EEG-fMRI recordings, performed in sedated children using a high field scanner and individual HRFs. In contrast to studies in adults, deactivations in the lesion and the irritative zone were more common than activations. The impact of age, sleep, and sedation on the BOLD response might explain these findings, but future studies in children should not disregard the importance of deactivations in relation to the epileptogenic network.

Purpose: High-frequency activity has been recorded with intracerebral microelectrodes in epileptic patients and related to seizure genesis. Our goal was to analyze high-frequency activity recorded with electroencephalograph (EEG) macroelectrodes during the slow wave immediately following interictal spikes, given the potential importance of this presumed hyperpolarization in transforming spikes into seizures., Methods: Depth electrode EEG recordings from 10 patients with intractable focal epilepsy were low-pass filtered at 500 Hz and sampled at 2,000 Hz. Spikes were categorized according to localization and morphology. Segments of 256 ms were selected immediately following (postspike), and 2 s before each spike (baseline). Power was estimated in subgamma (0-40 Hz), gamma (40-100 Hz), high frequency (100-200 Hz), and very high frequency (250-500 Hz) bands., Results: Changes in power above 100 Hz were seen in 22 of 29 spike categories, consisting primarily of a widespread decrease in frequencies above 100 Hz. This decrease became spatially more restricted as frequencies increased, and coincided with the localization of largest spikes for the highest frequencies. High-frequency power decreases were prominent in the hippocampus but less common in amygdala and neocortex. High-frequency power increases were observed in the amygdala., Conclusions: Thus high-frequency EEG activity can be recorded with macroelectrodes in humans and may provide insights on neuronal mechanisms related to human epilepsy. This activity undergoes consistent modifications after EEG spikes. We propose that the reduction in high frequencies reflects a postspike depression in neuronal activity that is more pronounced in the region of spike generation. This depression is almost always seen in hippocampus but less in amygdala.

Purpose: To investigate the clinical characteristics and surgical outcomes in patients with unilateral hippocampal sclerosis whose scalp ictal EEG recordings localize to the opposite temporal lobe., Methods: We retrospectively reviewed the data of all adult patients who had undergone depth electrode implantation for suspected temporal lobe epilepsy (TLE) at UCLA (1993-2000) or the Montreal Neurological Institute (1991-1998) to identify patients who had (a) unilateral hippocampal atrophy, and (b) surface ictal recordings in which the majority of seizures appeared to initiate in the opposite temporal lobe, with few or none that were concordant with the hippocampal atrophy., Results: Of 109 patients with suspected TLE who underwent depth electrode study at the two centers, five patients met the aforementioned criteria. Four of these five had very severe hippocampal atrophy, whereas the fifth had mild atrophy but extensive signal change on magnetic resonance imaging (MRI). Depth electrode recordings in four of the five patients yielded clear ictal onset in the mesial temporal lobe ipsilateral to the imaging abnormality (contralateral to apparent scalp ictal onset). One patient had an unusual bitemporal onset pattern, which was nonetheless suggestive of onset in the sclerotic hippocampus. No patient had intracranial ictal onset contralateral to the imaging abnormality. All patients underwent resection of the structurally abnormal temporal lobe. After follow-up of > or = 2 years, four (80%) of five patients were seizure free, while the fifth showed lesser improvement (class III)., Conclusions: Some patients with severe hippocampal sclerosis (sometimes called a "burned-out hippocampus") have atypical spread of ictal discharges, resulting in apparent gross discordance between imaging and scalp ictal recordings. These patients nonetheless have excellent surgical outcomes on the whole. Whether such patients may forego intracranial recordings requires further study., (Copyright 2004 International League Against Epilepsy)

ObjectiveTo evaluate the use of interictal high-frequency oscillations (HFOs) in epilepsy surgery for prediction of postsurgical seizure outcome in a prospective multicenter trial.MethodsWe hypothesized that a seizure-free outcome could be expected in patients in whom the surgical planning included the majority of HFO-generating brain tissue while a poor seizure outcome could be expected in patients in whom only a few such areas were planned to be resected. Fifty-two patients were included from 3 tertiary epilepsy centers during a 1-year period. Ripples (80-250 Hz) and fast ripples (250-500 Hz) were automatically detected during slow-wave sleep with chronic intracranial EEG in 2 centers and acute intraoperative electrocorticography in 1 patient.ResultsThere was a correlation between the removal of HFO-generating regions and seizure-free outcome at the group level for all patients. No correlation was found, however, for the center-specific analysis, and an individual prognostication of seizure outcome was true in only 36 patients (67%). Moreover, some patients became seizure-free without removal of the majority of HFO-generating tissue. The investigation of influencing factors, including comparisons of visual and automatic analysis, using a threshold analysis for areas with high HFO activity, and excluding contacts bordering the resection, did not result in improved prognostication.ConclusionsOn an individual patient level, a prediction of outcome was not possible in all patients. This may be due to the analysis techniques used. Alternatively, HFOs may be less specific for epileptic tissue than earlier studies have indicated.

Purpose: The role of posterior structural lesions leading to inadequate results after inferomesial temporal resection is well recognized. Here we present poor surgical outcome in six patients with nonlesional intractable epilepsy, well-defined focal anterior and inferomesial temporal epileptic discharges, and posterior temporoparietal symptoms. Methods: We reviewed patient data including scalp video-EEG telemetry, intracranial EEG recording, magnetic resonance imaging (MRI) sequences (1.5 Tesla), and single-photon emission computed tomography (SPECT) findings. Results: Ictal onset was uni- or bilateral diffuse with late preponderance over one temporal, or centrotemporoparietal regions. Four patients had preresection intracranial EEG monitoring, which suggested an epileptogenic zone in the posterior temporal and inferior parietal area in two, in the temporal lobe in one, and was inconclusive in the remaining one, who showed late epileptiform activity in the temporal neocortex. A second intracranial implantation was performed in three of them after a first anterior temporal resection. This led to posterior temporal neocortical localization in two and posterior temporal–inferior parietal localization in one. Including subpial transection, these six patients had one to four operations each, but only limited improvement occurred as a result of surgery in this group of individuals. Conclusions: We conclude that anterior and inferomesial interictal epileptiform temporal discharges and at times even intracranial EEG monitoring may be misleading. Anteromesial temporal resection is ineffective in patients with posterior temporoparietal clinical ictal features. [ABSTRACT FROM AUTHOR]

Objective High-frequency oscillations (80–500 Hz; HFOs) have been shown to be a specific biomarker of the seizure-onset zone. The relationship of HFOs with seizures having different intracranial electroencephalography (iEEG) morphological onsets, however, has shown significant relationships in experimental animals but has not been studied in humans. We investigated how interictal and ictal HFOs relate to different seizure-onset morphological patterns. Methods We analyzed the most representative seizure type of 37 patients with drug-resistant focal epilepsy who underwent iEEG for diagnostic evaluation. According to the morphology, 211 seizure-onset zone channels were classified in six patterns (low-voltage fast activity; sharp activity at ≤13 Hz; low-frequency high-amplitude periodic spikes; burst of high-amplitude polyspikes; spike-and-wave activity; and delta brush). Interictal and ictal HFOs were compared between the six seizure-onset patterns. Results Interictal ripple and fast ripple rates differed significantly across seizure-onset patterns (p < 0.001). Significant differences were also found for ictal HFOs density across the different seizure-onset patterns (p < 0.001). Sharp activity at ≤13 Hz was associated with the lowest interictal HFO rate suggesting either that the mechanism that generates this type of EEG morphology do not generate HFOs or possibly that this pattern is more likely to be generated in a region of seizure spread. Regarding the difference in HFO density between pre-ictal baseline and seizure-onset section across the six patterns, burst of high-amplitude polyspikes and delta brushes had the highest densities of both ripples and fast ripples (p < 0.001). Significance We demonstrated that distinct seizure-onset patterns correlate specific interictal and ictal HFO profiles confirming that seizures with different morphological patterns likely have different mechanisms of generation. This study emphazises that, in clinical practice, seizure-onset patterns should be distinguished and specified when analyzing HFOs, particularly if they are used in presurgical evaluation to better localize the seizure-onset zone. [ABSTRACT FROM AUTHOR]