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

2020 ◽  
Author(s):  
Elliot H. Smith ◽  
Edward M. Merricks ◽  
Jyun-You Liou ◽  
Camilla Casadei ◽  
Lucia Melloni ◽  
...  

ABSTRACTHigh frequency oscillations (HFOs) recorded from intracranial electrodes during epileptiform discharges are a proposed biomarker of epileptic brain tissue and may also be useful for seizure forecasting, with mixed results. Despite such potential for HFOs, there is limited investigation into the spatial context of HFOs and their relationship to simultaneously recorded neuronal activity. We sought to further understand the biophysical underpinnings of ictal HFOs using unit recordings in the human neocortex and mesial temporal lobe during rhythmic onset seizures. We compare features of 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 HFOs before and after local seizure invasion. Furthermore, we tie these timing-related differences to spatial domains of seizures, showing that penumbral discharges are widely distributed and less useful for seizure localization.

Author(s):  
Elliot H. Smith ◽  
Edward M. Merricks ◽  
Jyun-You Liou ◽  
Camilla Casadei ◽  
Lucia Melloni ◽  
...  

ABSTRACTObjectiveHigh frequency oscillations (HFOs) recorded from intracranial electrodes during epileptiform discharges have been proposed as a biomarker of epileptic brain sites and may also be a useful feature for seizure forecasting, with mixed results. Currently, pathological subclasses of HFOs have been defined primarily by frequency characteristics. Despite this, there has been limited investigation into the spatial context of HFOs with recruitment of local cortex into seizure discharging. We sought to further understand the biophysical underpinnings of ictal HFOs.MethodsHere we examine ictal HFOs from multi-scale electrophysiological recordings during spontaneous human rhythmic onset seizures. We compare features of ictal discharges in both the seizure core and penumbra, as defined by multiunit activity patterns.ResultsWe show marked differences in spectral features, unit coupling, and information theoretic characteristics of HFOs during ictal discharges before and after local seizure invasion. Furthermore, we tie these timing-related differences to different spatial domains of seizures, showing that eccentric, penumbral discharges are widely distributed and less useful for seizure localization, which may explain the variable utility of HFOs in seizure localization and forecasting.InterpretationWe thus identify two distinct classes of ictal HFOs, implying two different mechanisms underlying pathological HFOs with contrasting significance for seizure localization.


2020 ◽  
Vol 10 (1) ◽  
Author(s):  
Elliot H. Smith ◽  
Edward M. Merricks ◽  
Jyun-You Liou ◽  
Camilla Casadei ◽  
Lucia Melloni ◽  
...  

Abstract 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.


2016 ◽  
Vol 27 (01) ◽  
pp. 1650049 ◽  
Author(s):  
Stephen V. Gliske ◽  
William C. Stacey ◽  
Eugene Lim ◽  
Katherine A. Holman ◽  
Christian G. Fink

Previous experimental studies have demonstrated the emergence of narrowband local field potential oscillations during epileptic seizures in which the underlying neural activity appears to be completely asynchronous. We derive a mathematical model explaining how this counterintuitive phenomenon may occur, showing that a population of independent, completely asynchronous neurons may produce narrowband oscillations if each neuron fires quasi-periodically, without requiring any intrinsic oscillatory cells or feedback inhibition. This quasi-periodicity can occur through cells with similar frequency–current ([Formula: see text]–[Formula: see text]) curves receiving a similar, high amount of uncorrelated synaptic noise. Thus, this source of oscillatory behavior is distinct from the usual cases (pacemaker cells entraining a network, or oscillations being an inherent property of the network structure), as it requires no oscillatory drive nor any specific network or cellular properties other than cells that repetitively fire with continual stimulus. We also deduce bounds on the degree of variability in neural spike-timing which will permit the emergence of such oscillations, both for action potential- and postsynaptic potential-dominated LFPs. These results suggest that even an uncoupled network may generate collective rhythms, implying that the breakdown of inhibition and high synaptic input often observed during epileptic seizures may generate narrowband oscillations. We propose that this mechanism may explain why so many disparate epileptic and normal brain mechanisms can produce similar high frequency oscillations.


2019 ◽  
Author(s):  
Neela K. Codadu ◽  
Robert Graham ◽  
Richard J. Burman ◽  
R. Thomas Jackson-Taylor ◽  
Joseph V. Raimondo ◽  
...  

AbstractAimMuch debate exists about how the brain transitions into an epileptic seizure. One source of confusion is that there are likely to be critical differences between experimental seizure models. To address this, we compared the evolving activity patterns in two, widely used, in vitro models of epileptic discharges.MethodsWe compared brain slices, prepared in the same way from young adult mice, that were bathed either in 0 Mg2+, or 100µM 4AP, artificial cerebrospinal fluid.ResultsWe find that while local field potential recordings of epileptiform discharges in the two models appear broadly similar, patch-clamp analysis reveals an important difference in the relative degree of glutamatergic involvement. 4AP affects parvalbumin-expressing interneurons more than other cortical populations, destabilizing their resting state and inducing spontaneous bursting behavior. Consequently, the most prominent pattern of transient discharge (“interictal event”) in this model is almost purely GABAergic, although the transition to seizure-like events (SLEs) involves pyramidal recruitment. In contrast, interictal discharges in 0 Mg2+ are only maintained by a very large glutamatergic component that also involves transient discharges of the interneurons. Seizure-like events in 0 Mg2+ have significantly higher power in the high gamma frequency band (60-120Hz) than these events do in 4AP, and are greatly delayed in onset by diazepam, unlike 4AP events.ConclusionsThe 0 Mg2+ and 4AP models display fundamentally different levels of glutamatergic drive, demonstrating how ostensibly similar pathological discharges can arise from different sources. We contend that similar interpretative issues will also be relevant to clinical practice.


2021 ◽  
Vol 14 ◽  
Author(s):  
Olivia N. Arski ◽  
Julia M. Young ◽  
Mary-Lou Smith ◽  
George M. Ibrahim

Working memory (WM) deficits are pervasive co-morbidities of epilepsy. Although the pathophysiological mechanisms underpinning these impairments remain elusive, it is thought that WM depends on oscillatory interactions within and between nodes of large-scale functional networks. These include the hippocampus and default mode network as well as the prefrontal cortex and frontoparietal central executive network. Here, we review the functional roles of neural oscillations in subserving WM and the putative mechanisms by which epilepsy disrupts normative activity, leading to aberrant oscillatory signatures. We highlight the particular role of interictal epileptic activity, including interictal epileptiform discharges and high frequency oscillations (HFOs) in WM deficits. We also discuss the translational opportunities presented by greater understanding of the oscillatory basis of WM function and dysfunction in epilepsy, including potential targets for neuromodulation.


2018 ◽  
Vol 28 (07) ◽  
pp. 1850001 ◽  
Author(s):  
Lucia Rita Quitadamo ◽  
Roberto Mai ◽  
Francesca Gozzo ◽  
Veronica Pelliccia ◽  
Francesco Cardinale ◽  
...  

Pathological High-Frequency Oscillations (HFOs) have been recently proposed as potential biomarker of the seizure onset zone (SOZ) and have shown superior accuracy to interictal epileptiform discharges in delineating its anatomical boundaries. Characterization of HFOs is still in its infancy and this is reflected in the heterogeneity of analysis and reporting methods across studies and in clinical practice. The clinical approach to HFOs identification and quantification usually still relies on visual inspection of EEG data. In this study, we developed a pipeline for the detection and analysis of HFOs. This includes preliminary selection of the most informative channels exploiting statistical properties of the pre-ictal and ictal intracranial EEG (iEEG) time series based on spectral kurtosis, followed by wavelet-based characterization of the time–frequency properties of the signal. We performed a preliminary validation analyzing EEG data in the ripple frequency band (80–250 Hz) from six patients with drug-resistant epilepsy who underwent pre-surgical evaluation with stereo-EEG (SEEG) followed by surgical resection of pathologic brain areas, who had at least two-year positive post-surgical outcome. In this series, kurtosis-driven selection and wavelet-based detection of HFOs had average sensitivity of 81.94% and average specificity of 96.03% in identifying the HFO area which overlapped with the SOZ as defined by clinical presurgical workup. Furthermore, the kurtosis-based channel selection resulted in an average reduction in computational time of 66.60%.


PLoS ONE ◽  
2021 ◽  
Vol 16 (12) ◽  
pp. e0259933
Author(s):  
Zsófia Nyerges-Bohák ◽  
Krisztina Nagy ◽  
László Rózsa ◽  
Péter Póti ◽  
Levente Kovács

Changes in heart rate and heart rate variabilty (HRV) were investigated in untrained (UT; starting their first racing season) and detrained (DT; with 1–3 years of race experience) racehorses before and after 14-week conventional training. HRV was measured at rest over 1 h between 9:00 and 10:00 AM on the usual rest day of the horses. The smallest worthwhile change (SWC) rate was calculated for all HRV parameters. UT horses had significantly higher heart rate compared to DT (P<0.001). There were no gender- or training-related differences in heart rate. The root-mean-square of successive differences (rMSSD) in the consecutive inter-beat-intervals obtained after the 14-week training period was lower compared to pre-training rMSSD (P<0.001). The rMSSD was not influenced by breed, age or gender. In DT horses, there was a significant decrease in the high frequency (HF) component of HRV (P≤0.05) as the result of the 14-week training. These results may reflect saturation of high-frequency oscillations of inter-beat intervals rather than the reduction in parasympathetic influence on the heart. The HF did not differ significantly between the two measurements in UT horses; however, 16.6% of the animals showed a decrease in HF below SWC (P≤0.05). This supports the likelihood of parasympathetic saturation. Although no significant decrease in heart rate was found for the post-training, 30.0% of DT and 58.3% of UT horses still showed a decrease in heart rate below the SWC. Also by individual examination, it was also visible that despite significant post-training decrease in rMSSD, 1 (4.6%) DT and 2 (6.7%) UT horses reached SWC increase in rMMSD. In the case of these horses, the possibility of maladaptation should be considered. The present results indicate that similar to as found in human athletes, cardiac ANS status of racehorses also changes during the physiological adaptation to training. To explore more precise links between HRV and training effectiveness in horses, a more frequent recording would be necessary. Detailed analysis of HRV parameters based on SWC will be able to highlight the importance of fitness evaluation at individual level.


2021 ◽  
Vol 15 ◽  
Author(s):  
Hanan El Shakankiry ◽  
Susan T. Arnold

IntroductionDespite all the efforts for optimizing epilepsy management in children over the past decades, there is no clear consensus regarding whether to treat or not to treat epileptiform discharges (EDs) after a first unprovoked seizure or the optimal duration of therapy with anti-seizure medication (ASM). It is therefore highly needed to find markers on scalp electroencephalogram (EEG) that can help identify pathological EEG discharges that require treatment.Aim of the studyThis retrospective study aimed to identify whether the coexistence of ripples/high-frequency oscillations (HFOs) with interictal EDs (IEDs) in routinely acquired scalp EEG is associated with a higher risk of seizure recurrence and could be used as a prognostic marker.Methods100 children presenting with new onset seizure to Children’s Medical Center- Dallas during 2015–2016, who were not on ASM and had focal EDs on an awake and sleep EEG recorded with sample frequency of 500 HZ, were randomly identified by database review. EEGs were analyzed blinded to the data of the patients. HFOs were visually identified using review parameters including expanded time base and adjusted filter settings.ResultsThe average age of patients was 6.3 years (±4.35 SD). HFOs were visually identified in 19% of the studied patients with an inter-rater reliability of 99% for HFO negative discharges and 78% agreement for identification of HFOs. HFOs were identified more often in the younger age group; however, they were identified in 11% of patients &gt;5 years old. They were more frequently associated with spikes than with sharp waves and more often with higher amplitude EDs. Patients with HFOs were more likely to have a recurrence of seizures in the year after the first seizure (P &lt; 0.05) and to continue to have seizures after 2 years (P &lt; 0.0001). There was no statistically significant difference between the two groups with regards to continuing ASM after 2 years.ConclusionIncluding analysis for HFOs in routine EEG interpretation may increase the yield of the study and help guide the decision to either start or discontinue ASM. In the future, this may also help to identify pathological discharges with deleterious effects on the growing brain and set a new target for the management of epilepsy.


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