Detection of seizure onset in childhood absence epilepsy.

OBJECTIVE: This study aims to detect the seizure onset, in childhood absence epilepsy, as early as possible. Indeed, interfering with absence seizures with sensory simulation has been shown to be possible on the condition that the stimulation occurs soon enough after the seizure onset. METHODS: We present four variations (two supervised, two unsupervised) of an algorithm designed to detect the onset of absence seizures from 4 scalp electrodes, and compare their performance with that of a state-of-the-art algorithm. We exploit the characteristic shape of spike-wave discharges to detect the seizure onset. Their performance is assessed on clinical electroencephalograms from 63 patients with confirmed childhood absence epilepsy. RESULTS: The proposed approaches succeed in early detection of the seizure onset, contrary to the classical detection algorithm. Indeed, the results clearly show the superiority of the proposed methods for small delays of detection, under 750 ms from the onset. CONCLUSION: The performance of the proposed unsupervised methods is equivalent to that of the supervised ones. The use of only four electrodes makes the pipeline suitable to be embedded in a wearable device. SIGNIFICANCE: The proposed pipelines perform early detection of absence seizures, which constitutes a prerequisite for a closed-loop system.

Long-term Effect of Multichannel tDCS Protocol in Patients with Central Cortex Epilepsies Associated with Epilepsia Partialis Continua.

Epilepsia partialis continua (EPC) is a rare type of focal motor status epilepticus that causes continuous muscle jerking in a specific part of the body. Experiencing this type of seizure, along with other seizure types, such as focal motor seizures and focal to bilateral tonic-clonic seizures, can result in a disabling situation. Non-invasive brain stimulation methods like transcranial direct current stimulation (tDCS) show promise in reducing seizure frequency (SF) when medications are ineffective. However, research on tDCS for EPC and related seizures is limited. We evaluated personalized multichannel tDCS in drug-resistant EPC of diverse etiologies for long-term clinical efficacy We report three EPC patients undergoing a long-term protocol of multichannel tDCS. The patients received several cycles (11, 9, and 3) of five consecutive days of stimulation at 2 mA for 2 × 20 min, targeting the epileptogenic zone (EZ), including the central motor cortex with cathodal electrodes. The primary measurement was SF changes. In three cases, EPC was due to Rasmussen's Encephalitis (case 1), focal cortical dysplasia (case 2), or remained unknown (case 3). tDCS cycles were administered over 6 to 22 months. The outcomes comprised a reduction of at least 75% in seizure frequency for two patients, and in one case, a complete cessation of severe motor seizures. However, tDCS had no substantial impact on the continuous myoclonus characterizing EPC. No serious side effects were reported. Long-term application of tDCS cycles is well tolerated and can lead to a considerable reduction in disabling seizures in patients with various forms of epilepsy with EPC.

Improving Fast Ripples Recording With Model-Guided Design of Microelectrodes.

OBJECTIVE: Microelectrodes allow the recording of neural activities with a high spatial resolution. However, their small sizes result in high impedance causing high thermal noise and poor signal-to-noise ratio. In drug-resistant epilepsy, the accurate detection of Fast Ripples (FRs) can help in the identification of epileptogenic networks. Consequently, good-quality recordings are instrumental in improving surgical outcomes. In this work, we propose a novel model-based approach for the design of microelectrodes optimized for FRs recording. METHODS: A 3D microscale computational model was developed to simulate FRs generated in the hippocampus. It was coupled with a model of the Electrode-Tissue Interface that accounts for the biophysical properties of intracortical microelectrode. This hybrid model was used to analyze the microelectrode geometrical and physical characteristics and their impact on recorded FRs. For model validation, experimental signals (local field potentials, LFPs) were recorded from CA1 using different electrode materials: stainless steel, gold, and gold coated with poly(3,4-ethylene dioxythiophene)/Poly(styrene sulfonate) (Au:PEDOT/PSS). RESULTS: results indicated that a radius between 65 and 120 µm for a wire microelectrode is the most optimal for recording FRs. In addition, in silico and in vivo quantified results showed a possible improvement in FRs observability using PEDOT/PSS coated microelectrodes. CONCLUSION: the optimization of the design of microelectrodes for FRs recording can improve the observability and detectability of FRs which are a recognized marker of epileptogenicity. SIGNIFICANCE: This model-based approach can assist in the design of hybrid electrodes that can be used in the presurgical evaluation of epileptic patients with drug-resistant epilepsy.

HD-EEG for tracking sub-second brain dynamics during cognitive tasks.

This work provides the community with high-density Electroencephalography (HD-EEG, 256 channels) datasets collected during task-free and task-related paradigms. It includes forty-three healthy participants performing visual naming and spelling tasks, visual and auditory naming tasks and a visual working memory task in addition to resting state. The HD-EEG data are furnished in the Brain Imaging Data Structure (BIDS) format. These datasets can be used to (i) track brain networks dynamics and their rapid reconfigurations at sub-second time scale in different conditions, (naming/spelling/rest) and modalities, (auditory/visual) and compare them to each other, (ii) validate several parameters involved in the methods used to estimate cortical brain networks through scalp EEG, such as the open question of optimal number of channels and number of regions of interest and (iii) allow the reproducibility of results obtained so far using HD-EEG. We hope that delivering these datasets will lead to the development of new methods that can be used to estimate brain cortical networks and to better understand the general functioning of the brain during rest and task. Data are freely available from https://openneuro.org .

Effect of connectivity measures on the identification of brain functional core network at rest.

Magneto/Electro-encephalography (M/EEG) source connectivity is an emergent tool to identify brain networks with high time/space resolution. Here, we aim to identify the brain core network (s-core decomposition) using dense-EEG. We also evaluate the effect of the functional connectivity methods used and more precisely the effect of the correction for the so-called source leakage problem. Two connectivity measures were evaluated: the phase locking value (PLV) and phase lag index (PLI) that supposed to deal with the leakage problem by removing the zero-lag connections. Both methods were evaluated on resting state dense-EEG signals recorded from 19 healthy participants. Core networks obtained by each method was compared to those computed using fMRI from 487 healthy participants at rest (from the Human Connectome Project - HCP). The correlation between networks obtained by EEG and fMRI was used as performance criterion. Results show that PLV networks are closer to fMRI networks with significantly higher correlation values with fMRI networks, than PLI networks. Results suggest caution when selecting the functional connectivity methods and mainly methods that remove the zero-lag connections as it can severely affect the network characteristics. The choice of functional connectivity measure is indeed crucial not only in cognitive neuroscience but also in clinical neuroscience.

Dynamic reshaping of functional brain networks during visual object recognition.

OBJECTIVE: Emerging evidence shows that the modular organization of the human brain allows for better and efficient cognitive performance. Many of these cognitive functions are very fast and occur in a sub-second time scale such as the visual object recognition. APPROACH: Here, we investigate brain network modularity while controlling stimuli meaningfulness and measuring a participant's reaction time. We particularly raised two questions: i) does the dynamic brain network modularity change during the recognition of meaningful and meaningless visual images? And (ii) is there a correlation between network modularity and the reaction time of the participants? To tackle these issues, we collected dense-electroencephalography (EEG, 256 channels) data from 20 healthy human subjects performing a cognitive task consisting of naming meaningful (tools, animals…) and meaningless (scrambled) images. Functional brain networks in both categories were estimated at the sub-second time scale using the EEG source connectivity method. By using multislice modularity algorithms, we tracked the reconfiguration of functional networks during the recognition of both meaningful and meaningless images. MAIN RESULTS: Results showed a difference in the module's characteristics of both conditions in term of integration (interactions between modules) and occurrence (probability on average of any two brain regions to fall in the same module during the task). Integration and occurrence were greater for meaningless than for meaningful images. Our findings revealed also that the occurrence within the right frontal regions and the left occipito-temporal can help to predict the ability of the brain to rapidly recognize and name visual stimuli. SIGNIFICANCE: We speculate that these observations are applicable not only to other fast cognitive functions but also to detect fast disconnections that can occur in some brain disorders.

Reduced integration and improved segregation of functional brain networks in Alzheimer's disease.

OBJECTIVE: Emerging evidence shows that cognitive deficits in Alzheimer's disease (AD) are associated with disruptions in brain functional connectivity. Thus, the identification of alterations in AD functional networks has become a topic of increasing interest. However, to what extent AD induces disruption of the balance of local and global information processing in the human brain remains elusive. The main objective of this study is to explore the dynamic topological changes of AD networks in terms of brain network segregation and integration. APPROACH: We used electroencephalography (EEG) data recorded from 20 participants (10 AD patients and 10 healthy controls) during resting state. Functional brain networks were reconstructed using EEG source connectivity computed in different frequency bands. Graph theoretical analyses were performed assess differences between both groups. MAIN RESULTS: Results revealed that AD networks, compared to networks of age-matched healthy controls, are characterized by lower global information processing (integration) and higher local information processing (segregation). Results showed also significant correlation between the alterations in the AD patients' functional brain networks and their cognitive scores. SIGNIFICANCE: These findings may contribute to the development of EEG network-based test that could strengthen results obtained from currently-used neurophysiological tests in neurodegenerative diseases.

The dynamic functional core network of the human brain at rest.

The human brain is an inherently complex and dynamic system. Even at rest, functional brain networks dynamically reconfigure in a well-organized way to warrant an efficient communication between brain regions. However, a precise characterization of this reconfiguration at very fast time-scale (hundreds of millisecond) during rest remains elusive. In this study, we used dense electroencephalography data recorded during task-free paradigm to track the fast temporal dynamics of spontaneous brain networks. Results obtained from network-based analysis methods revealed the existence of a functional dynamic core network formed of a set of key brain regions that ensure segregation and integration functions. Brain regions within this functional core share high betweenness centrality, strength and vulnerability (high impact on the network global efficiency) and low clustering coefficient. These regions are mainly located in the cingulate and the medial frontal cortex. In particular, most of the identified hubs were found to belong to the Default Mode Network. Results also revealed that the same central regions may dynamically alternate and play the role of either provincial (local) or connector (global) hubs.

Functional connectivity disruptions correlate with cognitive phenotypes in Parkinson's disease.

Cognitive deficits in Parkinson's disease are thought to be related to altered functional brain connectivity. To date, cognitive-related changes in Parkinson's disease have never been explored with dense-EEG with the aim of establishing a relationship between the degree of cognitive impairment, on the one hand, and alterations in the functional connectivity of brain networks, on the other hand. This study was aimed at identifying altered brain networks associated with cognitive phenotypes in Parkinson's disease using dense-EEG data recorded during rest with eyes closed. Three groups of Parkinson's disease patients (N = 124) with different cognitive phenotypes coming from a data-driven cluster analysis, were studied: G1) cognitively intact patients (63), G2) patients with mild cognitive deficits (46) and G3) patients with severe cognitive deficits (15). Functional brain networks were identified using a dense-EEG source connectivity method. Pairwise functional connectivity was computed for 68 brain regions in different EEG frequency bands. Network statistics were assessed at both global (network topology) and local (inter-regional connections) level. Results revealed progressive disruptions in functional connectivity between the three patient groups, typically in the alpha band. Differences between G1 and G2 (p < 0.001, corrected using permutation test) were mainly frontotemporal alterations. A statistically significant correlation (ρ = 0.49, p < 0.001) was also obtained between a proposed network-based index and the patients' cognitive score. Global properties of network topology in patients were relatively intact. These findings indicate that functional connectivity decreases with the worsening of cognitive performance and loss of frontotemporal connectivity may be a promising neuromarker of cognitive impairment in Parkinson's disease.

Brain (Hyper)Excitability Revealed by Optimal Electrical Stimulation of GABAergic Interneurons.

BACKGROUND: Neurological disorders are often characterized by an excessive and prolonged imbalance between neural excitatory and inhibitory processes. An ubiquitous finding among these disorders is the disrupted function of inhibitory GABAergic interneurons. OBJECTIVE: The objective is to propose a novel stimulation procedure able to evaluate the efficacy of inhibition imposed by GABAergic interneurons onto pyramidal cells from evoked responses observed in local field potentials (LFPs). METHODS: Using a computational modeling approach combined with in vivo and in vitro electrophysiological recordings, we analyzed the impact of electrical extracellular, local, bipolar stimulation (ELBS) on brain tissue. We implemented the ELBS effects in a neuronal population model in which we can tune the excitation-inhibition ratio and we investigated stimulation-related parameters. Computer simulations led to sharp predictions regarding: i) the shape of evoked responses as observed in local field potentials, ii) the type of cells (pyramidal neurons and interneurons) contributing to these field responses and iii) the optimal tuning of stimulation parameters (intensity and frequency) to evoke meaningful responses. These predictions were tested in vivo (mouse). Neurobiological mechanisms were assessed in vitro (hippocampal slices). RESULTS: Appropriately-tuned ELBS allows for preferential activation of GABAergic interneurons. A quantitative neural network excitability index (NNEI) is proposed. It is computed from stimulation-induced responses as reflected in local field potentials. NNEI was used in four patients with focal epilepsy. Results show that it can readily reveal hyperexcitable brain regions. CONCLUSION: Well-tuned ELBS and NNEI can be used to locally probe brain regions and quantify the (hyper)excitability of the underlying brain tissue.

Complex patterns of spatially extended generators of epileptic activity: Comparison of source localization methods cMEM and 4-ExSo-MUSIC on high resolution EEG and MEG data.

Electric Source Imaging (ESI) and Magnetic Source Imaging (MSI) of EEG and MEG signals are widely used to determine the origin of interictal epileptic discharges during the pre-surgical evaluation of patients with epilepsy. Epileptic discharges are detectable on EEG/MEG scalp recordings only when associated with a spatially extended cortical generator of several square centimeters, therefore it is essential to assess the ability of source localization methods to recover such spatial extent. In this study we evaluated two source localization methods that have been developed for localizing spatially extended sources using EEG/MEG data: coherent Maximum Entropy on the Mean (cMEM) and 4th order Extended Source Multiple Signal Classification (4-ExSo-MUSIC). In order to propose a fair comparison of the performances of the two methods in MEG versus EEG, this study considered realistic simulations of simultaneous EEG/MEG acquisitions taking into account an equivalent number of channels in EEG (257 electrodes) and MEG (275 sensors), involving a biophysical computational neural mass model of neuronal discharges and realistically shaped head models. cMEM and 4-ExSo-MUSIC were evaluated for their sensitivity to localize complex patterns of epileptic discharges which includes (a) different locations and spatial extents of multiple synchronous sources, and (b) propagation patterns exhibited by epileptic discharges. Performance of the source localization methods was assessed using a detection accuracy index (Area Under receiver operating characteristic Curve, AUC) and a Spatial Dispersion (SD) metric. Finally, we also presented two examples illustrating the performance of cMEM and 4-ExSo-MUSIC on clinical data recorded using high resolution EEG and MEG. When simulating single sources at different locations, both 4-ExSo-MUSIC and cMEM exhibited excellent performance (median AUC significantly larger than 0.8 for EEG and MEG), whereas, only for EEG, 4-ExSo-MUSIC showed significantly larger AUC values than cMEM. On the other hand, cMEM showed significantly lower SD values than 4-ExSo-MUSIC for both EEG and MEG. When assessing the impact of the source spatial extent, both methods provided consistent and reliable detection accuracy for a wide range of source spatial extents (source sizes ranging from 3 to 20cm2 for MEG and 3 to 30cm2 for EEG). For both EEG and MEG, 4-ExSo-MUSIC localized single source of large signal-to-noise ratio better than cMEM. In the presence of two synchronous sources, cMEM was able to distinguish well the two sources (their location and spatial extent), while 4-ExSo-MUSIC only retrieved one of them. cMEM was able to detect the spatio-temporal propagation patterns of two synchronous activities while 4-ExSo-MUSIC favored the strongest source activity. Overall, in the context of localizing sources of epileptic discharges from EEG and MEG data, 4-ExSo-MUSIC and cMEM were found accurately sensitive to the location and spatial extent of the sources, with some complementarities. Therefore, they are both eligible for application on clinical data.

Dynamic changes of depolarizing GABA in a computational model of epileptogenic brain: Insight for Dravet syndrome.

Abnormal reemergence of depolarizing GABAA current during postnatal brain maturation may play a major role in paediatric epilepsies, Dravet syndrome (DS) being among the most severe. To study the impact of depolarizing GABA onto distinct patterns of EEG activity, we extended a neural mass model as follows: one sub-population of pyramidal cells was added as well as two sub-populations of interacting interneurons, perisomatic-projecting interneurons (basket-like) with fast synaptic kinetics GABAA (fast, I1) and dendritic-projecting interneurons with slow synaptic kinetics GABAA (slow, I2). Basket-like cells were interconnected to reproduce mutual inhibition mechanisms (I1➔I1). The firing rate of interneurons was adapted to mimic the genetic alteration of voltage gated sodium channels found in DS patients, SCN1A(+/-). We implemented the "dynamic depolarizing GABAA" mediated post-synaptic potential in the model, as some studies reported that the chloride reversal potential can switch from negative to more positive value depending on interneuron activity. The "shunting inhibition" promoted by GABAA receptor activation was also implemented. We found that increasing the proportion of depolarizing GABAA mediated IPSP (I1➔I1 and I1➔P) only (i.e., other parameters left unchanged) was sufficient to sequentially switch the EEG activity from background to (1) interictal isolated polymorphic epileptic spikes, (2) fast onset activity, (3) seizure like activity and (4) seizure termination. The interictal and ictal EEG patterns observed in 4 DS patients were reproduced by the model via tuning the amount of depolarizing GABAA postsynaptic potential. Finally, we implemented the modes of action of benzodiazepines and stiripentol, two drugs recommended in DS. Both drugs blocked seizure-like activity, partially and dose-dependently when applied separately, completely and with a synergic effect when combined, as has been observed in DS patients. This computational modeling study constitutes an innovative approach to better define the role of depolarizing GABA in infantile onset epilepsy and opens the way for new therapeutic hypotheses, especially in Dravet syndrome.

Computational modeling of high frequency oscillations recorded with clinical intracranial macroelectrodes.

High Frequency Oscillations (HFOs) are a potential biomarker of epileptogenic regions. They have been extensively investigated in terms of automatic detection, classification and feature extraction. However, the mechanisms governing the generation of HFOs as well as the observability conditions on clinical intracranial macroelectrodes remain elusive. In this paper, we propose a novel physiologically-relevant macroscopic model for accurate simulation of HFOs as invasively recorded in epileptic patients. This model accounts for both the temporal and spatial properties of the cortical patch at the origin of epileptiform activity. Indeed, neuronal populations are combined with a 3D geometrical representation to simulate an extended epileptic source. Then, by solving the forward problem, the contributions of neuronal population signals are projected onto intracerebral electrode contacts. The obtained signals are qualitatively and quantitatively compared to real HFOs, and a relationship is drawn between macroscopic model parameters such as synchronization and spatial extent on the one hand, and HFO features such as the wave and fast ripple (200-600 Hz) components, on the other hand.

A new algorithm for spatiotemporal analysis of brain functional connectivity.

Specific networks of interacting neuronal assemblies distributed within and across distinct brain regions underlie brain functions. In most cognitive tasks, these interactions are dynamic and take place at the millisecond time scale. Among neuroimaging techniques, magneto/electroencephalography - M/EEG - allows for detection of very short-duration events and offers the single opportunity to follow, in time, the dynamic properties of cognitive processes (sub-millisecond temporal resolution). In this paper, we propose a new algorithm to track the functional brain connectivity dynamics. During a picture naming task, this algorithm aims at segmenting high-resolution EEG signals (hr-EEG) into functional connectivity microstates. The proposed algorithm is based on the K-means clustering of the connectivity graphs obtained from the phase locking value (PLV) method applied on hr-EEG. Results show that the analyzed evoked responses can be divided into six clusters representing distinct networks sequentially involved during the cognitive task, from the picture presentation and recognition to the motor response.

Identification of epileptogenic networks from dense EEG: A model-based study.

Epilepsy is a network disease. Identifying the epileptogenic networks from noninvasive recordings is a challenging issue. In this context, M/EEG source connectivity is a promising tool to identify brain networks with high temporal and spatial resolution. In this paper, we analyze the impact of the two main factors that intervene in EEG source connectivity processing: i) the algorithm used to solve the EEG inverse problem and ii) the method used to measure the functional connectivity. We evaluate three inverse solutions algorithms (dSPM, wMNE and cMEM) and three connectivity measures (r(2), h(2) and MI) on data simulated from a combined biophysical/physiological model able to generate realistic interictal epileptic spikes reflected in scalp EEG. The performance criterion used here is the similarity between the network identified by each of the inverse/connectivity combination and the original network used in the source model. Results show that the choice of the combination has a high impact on the identified network. Results suggest also that nonlinear methods (nonlinear correlation coefficient and mutual information) for measuring the connectivity are more efficient than the linear one (the cross correlation coefficient). The dSPM as inverse solution shows the lowest performance compared to cMEM and wMNE.

EEG extended source localization: tensor-based vs. conventional methods.

The localization of brain sources based on EEG measurements is a topic that has attracted a lot of attention in the last decades and many different source localization algorithms have been proposed. However, their performance is limited in the case of several simultaneously active brain regions and low signal-to-noise ratios. To overcome these problems, tensor-based preprocessing can be applied, which consists in constructing a space-time-frequency (STF) or space-time-wave-vector (STWV) tensor and decomposing it using the Canonical Polyadic (CP) decomposition. In this paper, we present a new algorithm for the accurate localization of extended sources based on the results of the tensor decomposition. Furthermore, we conduct a detailed study of the tensor-based preprocessing methods, including an analysis of their theoretical foundation, their computational complexity, and their performance for realistic simulated data in comparison to conventional source localization algorithms such as sLORETA, cortical LORETA (cLORETA), and 4-ExSo-MUSIC. Our objective consists, on the one hand, in demonstrating the gain in performance that can be achieved by tensor-based preprocessing, and, on the other hand, in pointing out the limits and drawbacks of this method. Finally, we validate the STF and STWV techniques on real measurements to demonstrate their usefulness for practical applications.

Recording of fast activity at the onset of partial seizures: depth EEG vs. scalp EEG.

Rapid discharges (25-80 Hz), a characteristic EEG pattern often recorded at seizure onset in partial epilepsies, are often considered as electrophysiological signatures of the epileptogenic zone. While the recording of rapid discharges from intracranial electrodes has long been established, their observation from the scalp is challenging. The prevailing view is that rapid discharges cannot be seen clearly (or at all) in scalp EEG because they have low signal-to-noise ratio. To date, however, no studies have investigated the 'observability' of rapid discharges, i.e. under what conditions and to what extent they can be visible in recorded EEG signals. Here, we used a model-based approach to examine the impact of several factors (distance to sources, skull conductivity, source area, source synchrony, and background activity) on the observability of rapid discharges in simultaneously simulated depth EEG and scalp EEG signals. In our simulations, the rapid discharge was clearly present in depth EEG signals but mostly almost not visible in scalp EEG signals. We identified some of the factors that may limit the observability of the rapid discharge on the scalp. Notably, surrounding background activity was found to be the most critical factor. The findings are discussed in relation to the presurgical evaluation of epilepsy.

Detecting causal interdependence in simulated neural signals based on pairwise and multivariate analysis.

Our objective is to analyze EEG signals recorded with depth electrodes during seizures in patients with drug-resistant epilepsy. Usually, different phases are observed during the seizure process, including a fast onset activity (FOA). We aim to determine how cerebral structures get involved during this FOA, in particular whether some structure can "drive" some other structures. This paper focuses on a linear Granger causality based measure to detect causal relation of interdependence in multivariate signals generated by a physiology-based model of coupled neuronal populations. When coupling between signals exists, statistical analysis supports the relevance of this index for characterizing the information flow and its direction among neuronal populations.

Energy deprivation transiently enhances rhythmic inhibitory events in the CA3 hippocampal network in vitro.

Oxygen glucose deprivation (OGD) leads to rapid suppression of synaptic transmission. Here we describe an emergence of rhythmic activity at 8 to 20 Hz in the CA3 subfield of hippocampal slice cultures occurring for a few minutes prior to the OGD-induced cessation of evoked responses. These oscillations, dominated by inhibitory events, represent network activity, as they were abolished by tetrodotoxin. They were also completely blocked by the GABAergic antagonist picrotoxin, and strongly reduced by the glutamatergic antagonist NBQX. Applying CPP to block NMDA receptors had no effect and neither did UBP302, an antagonist of GluK1-containing kainate receptors. The gap junction blocker mefloquine disrupted rhythmicity. Simultaneous whole-cell voltage-clamp recordings from neighboring or distant CA3 pyramidal cells revealed strong cross-correlation of the incoming rhythmic activity. Interneurons in the CA3 area received similar correlated activity. Interestingly, oscillations were much less frequently observed in the CA1 area. These data, together with the observation that the recorded activity consists primarily of inhibitory events, suggest that CA3 interneurons are important for generating these oscillations. This transient increase in inhibitory network activity during OGD may represent a mechanism contributing to the lower vulnerability to ischemic insults of the CA3 area as compared to the CA1 area.

Pitfalls of high-pass filtering for detecting epileptic oscillations: a technical note on "false" ripples.

OBJECTIVES: To analyze interictal High frequency oscillations (HFOs) as observed in the medial temporal lobe of epileptic patients and animals (ripples, 80-200Hz and fast ripples, 250-600Hz). To show that the identification of interictal HFOs raises some methodological issues, as the filtering of sharp transients (e.g., epileptic spikes or artefacts) or signals with harmonics can result in "false" ripples. To illustrate and quantify the occurrence of false ripples on filtered EEG traces. METHODS: We have performed high-pass filtering on both simulated and real data. We have also used two alternate methods: time-frequency analysis and matching pursuit. RESULTS: Two types of events were shown to produce oscillations after filtering that could be confounded with actual oscillatory activity: sharp transients and harmonics of non-sinusoidal signals. CONCLUSIONS: High-pass filtering of EEG traces for detection of oscillatory activity should be performed with great care. Filtered traces should be compared to original traces for verification of presence of transients. Additional techniques such as time-frequency transforms or sparse decompositions are highly beneficial. SIGNIFICANCE: Our study draws the attention on an issue of great importance in the marking of HFOs on EEG traces. We illustrate complementary methods that can help both researchers and clinicians.