PubMed Health⌕ Search

Biomedical subjects

Fabrice Wendling

Publications and source records attributed to Fabrice Wendling.

14 recordsLinked to original sources

Cell domain-dependent changes in the glutamatergic and GABAergic drives during epileptogenesis in the rat CA1 region.

An increased ratio of the glutamatergic drive to the overall glutamatergic/GABAergic drive characterizes the chronic stage of temporal lobe epilepsy (TLE), but it is unclear whether this modification is present during the latent period that often precedes the epileptic stage. Using the pilocarpine model of TLE in rats, we report that this ratio is decreased in hippocampal CA1 pyramidal cells during the early phase of the latent period (3-5 days post pilocarpine). It is, however, increased during the late phase of the latent period (7-10 days post pilocarpine), via cell domain-dependent alterations in synaptic current properties, concomitant with the occurrence of interictal-like activity in vivo. During the late latent period, the glutamatergic drive was increased in somata via an enhancement in EPSC decay time constant and in dendrites via an increase in EPSC frequency and amplitude. The GABAergic drive remained unchanged in the soma but was decreased in dendrites, since the drop off in IPSC frequency was more marked than the increase in IPSC kinetics. Theoretical considerations suggest that these modifications are sufficient to produce interictal-like activity. In epileptic animals, the ratio of the glutamatergic drive to the overall synaptic drive was not further modified, despite additional changes in synaptic current frequency and kinetics. These results show that the global changes to more glutamatergic and less GABAergic activities in the CA1 region precede the chronic stage of epilepsy, possibly facilitating the occurrence and/or the propagation of interictal activity.

Algorithms↗

Quantitative evaluation of linear and nonlinear methods characterizing interdependencies between brain signals.

Brain functional connectivity can be characterized by the temporal evolution of correlation between signals recorded from spatially-distributed regions. It is aimed at explaining how different brain areas interact within networks involved during normal (as in cognitive tasks) or pathological (as in epilepsy) situations. Numerous techniques were introduced for assessing this connectivity. Recently, some efforts were made to compare methods performances but mainly qualitatively and for a special application. In this paper, we go further and propose a comprehensive comparison of different classes of methods (linear and nonlinear regressions, phase synchronization, and generalized synchronization) based on various simulation models. For this purpose, quantitative criteria are used: in addition to mean square error under null hypothesis (independence between two signals) and mean variance computed over all values of coupling degree in each model, we provide a criterion for comparing performances. Results show that the performances of the compared methods are highly dependent on the hypothesis regarding the underlying model for the generation of the signals. Moreover, none of them outperforms the others in all cases and the performance hierarchy is model dependent.

Brain↗

The role of corticothalamic coupling in human temporal lobe epilepsy.

The EEG activity of the thalamus and temporal lobe structures (hippocampus, entorhinal cortex and neocortex) was obtained using intracerebral recordings (stereoelectroencephalography, SEEG) performed in patients with TLE seizures undergoing pre-surgical evaluation. Synchrony was studied using a statistical measure of SEEG signal interdependencies (non-linear correlation). The results demonstrated an overall increase of synchrony between the thalamus and temporal lobe structures during seizures. Moreover, although there was great inter-individual variability, we found that values from seizure onset period were significantly higher than values from the background period (P = 0.001). Values at the end of seizure were significantly higher than values from the seizure onset (P < 0.0001). Several indices were also defined in order to correlate some clinical features to the degree of coupling between cortical structures and the thalamus. In patients with mesial TLE seizures, a correlation was found between the degree of thalamocortical synchrony and the presence of an early loss of consciousness but not with other clinical parameters. In addition, surgical prognosis seemed better in patients with low values of thalamocortical couplings at the seizure onset. This report demonstrates that the thalamus and remote cortical structures synchronize their activity during TLE seizures and suggest that the extension of the epileptogenic network to the thalamus is a potential important factor determining surgical prognosis.

Adolescent↗

Recollection of vivid memories after perirhinal region stimulations: synchronization in the theta range of spatially distributed brain areas.

Electrical stimulation of the temporal cortex in patients with epilepsy sometimes elicits experiential phenomena such as recollection of vivid memories. The neurophysiological substrate of such phenomena is poorly understood. Furthermore, the relation between the site of stimulation and the type of memory elicited has only recently started to be investigated. We investigated these issues in patient FGA who had intracerebral electrodes stereotaxically implanted in the right temporal lobe for investigation of drug-resistant epilepsy. We report the results of electrical stimulations of the perirhinal region. Two stimulations elicited experiential phenomena consisting of visual memories that belonged to FGA's past, but which were not related to any particular episode. These visual memories consisted of objects or of details of objects. These two stimulations were contrasted with other stimulations in the same subhippocampal region. Cross-correlation analysis of the depth-EEG signals filtered in frequency sub-bands revealed that experiential phenomena occurred only when the various brain structures involved in the after-discharge were synchronized in the theta range. These structures included the perirhinal region, the hippocampus, other limbic structures as well as a primary visual area. Our results suggest that recollection of vivid memory after electric stimulation of the cortex may rely on wide networks of brain areas that transiently synchronize. These results also highlight the role of the perirhinal region in human memory. Experiential phenomena are rarely obtained after brain stimulation. Replication of these results is thus required due to the small number of observations reported.

Adult↗

Acute alteration of emotional behaviour in epileptic seizures is related to transient desynchrony in emotion-regulation networks.

OBJECTIVE: During focal epileptic seizures, patients may express intense agitation, screaming and facial expressions of rage, fear or anger. The precise anatomical origin of such intense ictal emotional behaviour is not fully understood and the mechanisms by which the epileptic discharges provoke these phenomena are unknown. In the present study, we analysed the neurophysiological mechanisms underlying ictal emotional behaviour in 3 patients with frontal lobe epilepsies undergoing intracerebral recordings for presurgical evaluation. METHODS: We analyzed the interactions between regions forming 'emotional networks', before and during behavioural alterations. Intracerebral recordings (SEEG method) of seizures from 3 patients presenting with frontal lobe seizures were analyzed. A nonlinear measure of SEEG signal interdependencies was used to evaluate the functional couplings occurring between brain structures. RESULTS: We found that these intense emotional alterations were associated with a decrease of synchrony between signals recorded from the neural networks known to be involved in emotional processing, and in particular a loss of synchrony between the orbito-frontal cortex and the amygdala. This disruption of functional connections could then result in the disruption of emotional regulation leading to the release of altered behaviour, as observed in epileptic patients during seizures. CONCLUSIONS: We propose that the occurrence of intense ictal emotional behaviour disturbance in frontal lobe seizures is related to a disruption of the normal mechanisms of emotional regulation SIGNIFICANCE: These results provide some insight into our understanding of the pathophysiological processes involved in human partial epilepsies as well as in the interpretation of clinical semiology.

Adult↗

Time-frequency characterization of interdependencies in nonstationary signals: application to epileptic EEG.

For the past decades, numerous works have been dedicated to the development of signal processing methods aimed at measuring the degree of association between electroencephalographic (EEG) signals. This interdependency parameter, which may be defined in various ways, is often used to characterize a functional coupling between different brain structures or regions during either normal or pathological processes. In this paper, we focus on the time-frequency characterization of the interdependency between signals. Particularly, we propose a novel estimator of the linear relationship between nonstationary signals based on the cross correlation of narrow band filtered signals. This estimator is compared to a more classical estimator based on the coherence function. In a simulation framework, results show that it may exhibit better statistical performances (bias and variance or mean square error) when a priori knowledge about time delay between signals is available. On real data (intracerebral EEG signals), results show that this estimator may also enhance the readability of the time-frequency representation of relationship and, thus, can improve the interpretation of nonstationary interdependencies in EEG signals. Finally, we illustrate the importance of characterizing the relationship in both time and frequency domains by comparing with frequency-independent methods (linear and nonlinear).

Algorithms↗

Propagation dynamics of epileptiform activity acutely induced by bicuculline in the hippocampal-parahippocampal region of the isolated Guinea pig brain.

PURPOSE: Aim of the study is to investigate the involvement of parahippocampal subregions in the generation and in the propagation of focal epileptiform discharges in an acute model of seizure generation in the temporal lobe induced by arterial application of bicuculline in the in vitro isolated guinea pig brain preparation. METHODS: Electrophysiological recordings were simultaneously performed with single electrodes and multichannel silicon probes in the entorhinal, perirhinal, and piriform cortices and in the area CA1 of the hippocampus of the in vitro isolated guinea pig brain. Interictal and ictal epileptiform discharges restricted to the temporal region were induced by a brief (3-5 min) arterial perfusion of the GABA(A) receptor antagonist, bicuculline methiodide (50 microM). Current source density analysis of laminar field profiles performed with the silicon probes was carried out at different sites to establish network interactions responsible for the generation of epileptiform potentials. Nonlinear regression analysis was conducted on extracellular recordings during ictal onset in order to quantify the degree of interaction between fast activities generated at different sites, as well as time delays. RESULTS: Experiments were performed in 31 isolated guinea pig brains. Bicuculline-induced interictal and ictal epileptiform activities that showed variability of spatial propagation and time course in the olfactory-temporal region. The most commonly observed pattern (n = 23) was characterized by the initial appearance of interictal spikes (ISs) in the piriform cortex (PC), which propagated to the lateral entorhinal region. Independent and asynchronous preictal spikes originated in the entorhinal cortex (EC)/hippocampus and progressed into ictal fast discharges (around 25 Hz) restricted to the entorhinal/hippocampal region. The local generation of fast activity was verified and confirmed both by CSD and phase shift analysis performed on laminar profiles. Fast activity was followed by synchronous afterdischarges that propagated to the perirhinal cortex (PRC) (but not to the PC). Within 1-9 min, the ictal discharge ceased and a postictal period of depression occurred, after which periodic ISs in the PC resumed. Unlike preictal ISs, postictal ISs propagated to the PRC. CONCLUSIONS: Several studies proposed that reciprocal connections between the entorhinal and the PRC are under a very efficient inhibitory control (1). We report that ISs determined by acute bicuculline treatment in the isolated guinea pig brain progress from the PC to the hippocampus/EC just before ictal onset. Ictal discharges are characterized by a peculiar pattern of fast activity that originates from the entorhinal/hippocampal region and only secondarily propagates to the PRC. Postictal propagation of ISs to the PRC occurred exclusively when an ictal discharge was generated in the hippocampal/entorhinal region. The results suggest that reiteration of ictal events may promote changes in propagation pattern of epileptiform discharges that could act as trigger elements in the development of temporal lobe epilepsy.

Action Potentials↗

Entorhinal cortex involvement in human mesial temporal lobe epilepsy: an electrophysiologic and volumetric study.

PURPOSE: Several studies have demonstrated diminution in the volume of entorhinal cortex (EC) ipsilateral to the pathologic side in patients with temporal lobe epilepsy (TLE). The relation between the degree of EC atrophy and the epileptogenicity of this structure has never been directly studied. The purpose of the study was to determine whether atrophy of the EC evaluated by the quantitative magnetic resonance imaging (MRI) method is correlated with the epileptogenicity of this structure in TLE. METHODS: Intracerebral recordings (SEEG method) of seizures from 11 patients with mesial TLE were analyzed. Seizures were classified according to patterns of onset: pattern 1 was the emergence of a low-frequency, high-amplitude rhythmic spiking followed by a tonic discharge, and pattern 2 was the emergence of a tonic discharge in the mesial structures. A nonlinear measure of SEEG signal interdependencies was used to evaluate the functional couplings occurring between hippocampus (Hip) and EC at seizure onset. MRI volumetric analysis was performed by using a T(1)-weighted three-dimensional gradient-echo sequence in TLE patients and 12 healthy subjects. RESULTS: Significant interactions between Hip and Ec were quantified at seizure onset. The EC was found to be the leader structure in most of the pattern 2 seizures. Volumetric measurements of EC demonstrated an atrophy in 63% of patients ipsilateral to the epileptic side. A significant correlation between the strength of EC-Hip coupling and the degree of atrophy was found. In addition, in those patients that had a normal EC volume, the EC was never the leader structure in Ec-Hip coupling. CONCLUSIONS: These results validate the potential role of volumetry to predict the epileptogenesis of the EC in patients with hippocampal sclerosis and MTLE.

Adolescent↗

Interictal to ictal transition in human temporal lobe epilepsy: insights from a computational model of intracerebral EEG.

In human partial epilepsies and in experimental models of chronic and/or acute epilepsy, the role of inhibition and the relationship between the inhibition and excitation and epileptogenesis has long been questioned. Besides experimental methods carried out either in vitro (human or animal tissue) or in vivo (animals), pathophysiologic mechanisms can be approached by direct recording of brain electrical activity in human epilepsy. Indeed, in some clinical presurgical investigation methods like stereoelectroencephalography, intracerebral electrodes are used in patients suffering from drug resistant epilepsy to directly record paroxysmal activities with excellent temporal resolution (in the order of 1 millisecond). The study of neurophysiologic mechanisms underlying such depth-EEG activities is crucial to progress in the understanding of the interictal to ictal transition. In this study, the authors relate electrophysiologic patterns typically observed during the transition from interictal to ictal activity in human mesial temporal lobe epilepsy (MTLE) to mechanisms (at a neuronal population level) involved in seizure generation through a computational model of EEG activity. Intracerebral EEG signals recorded from hippocampus in five patients with MTLE during four periods (during interictal activity, just before seizure onset, during seizure onset, and during ictal activity) were used to identify the three main parameters of a model of hippocampus EEG activity (related to excitation, slow dendritic inhibition and fast somatic inhibition). The identification procedure used optimization algorithms to minimize a spectral distance between real and simulated signals. Results demonstrated that the model generates very realistic signals for automatically identified parameters. They also showed that the transition from interictal to ictal activity cannot be simply explained by an increase in excitation and a decrease in inhibition but rather by time-varying ensemble interactions between pyramidal cells and local interneurons projecting to either their dendritic or perisomatic region (with slow and fast GABAA kinetics). Particularly, during preonset activity, an increasing dendritic GABAergic inhibition compensates a gradually increasing excitation up to a brutal drop at seizure onset when faster oscillations (beta and low gamma band, 15 to 40 Hz) are observed. These faster oscillations are then explained by the model feedback loop between pyramidal cells and interneurons targeting their perisomatic region. These findings obtained from model identification in human temporal lobe epilepsy are in agreement with some results obtained experimentally, either on animal models of epilepsy or on the human epileptic tissue.

Algorithms↗

Mining reproducible activation patterns in epileptic intracerebral EEG signals: application to interictal activity.

The study of interictal transient events may substantially complement the analysis of seizures in the presurgical evaluation of intractable epilepsy. A comprehensive methodology of quantifying reproducibility of activation patterns in intracerebral electroencephalography signals is presented. It may be applied to various forms of transient epileptic events under the assumption that a time of occurrence may be assigned to them. In this paper, the method is used on two different forms of interictal events (interictal spikes or sharpwaves and transient bursts of fast activity). The methodology is based on signal processing and data mining algorithms and proceeds in three steps: 1) detection of transient paroxysmal events (monochannel event); 2) identification of quasisynchronous transient paroxysmal events (multichannel events); and 3) automatic extraction of similar activation patterns. Results show that the methodology allows reproducible sequential activation sets to be identified from signals recorded in four patients. Potential advantages of the method are discussed with respect to other approaches.

Algorithms↗

Epileptic transient detection: wavelets and time-frequency approaches.

This paper is aimed at presenting the two main classes of nonstationary signal transforms that are currently used to analyze and to characterize EEG observations. Time-scale methods, or wavelet transforms, allow a time versus duration analysis to be performed whereas time-frequency methods allow spectral contents to be analyzed as a function of time. These two types of transform are well suited to the study of changes either localized or progressive that may be observed in EEG signal dynamics and that sign the evolution of underlying physiological mechanisms. The potential interest of these methods in nonstationary signal representation is illustrated through several academic examples. Then, methods are applied on real EEG signals to solve problems such that the detection of interictal transient signals (like spikes or spike-waves) and the recognition of signatures during ictal periods.

Algorithms↗

Neural networks underlying epileptic humming.

PURPOSE: Humming is a rare automatism occurring in partial seizures that has received little attention. Its study could shed light on the neural networks underlying melodic expression. In this study, we examined the anatomoelectroclinical correlates of humming during epileptic seizures METHODS: Three patients undergoing presurgical stereoelectroencephalography (SEEG) for medically intractable temporal lobe epilepsy were studied. Coherence analysis of SEEG activity was carried out to study the functional coupling of different regions of the brain, whereas time-frequency (TF) analysis was conducted to assess epileptic discharge patterns. Changes in coherence were studied to identify the neural structures/systems implicated in humming. RESULTS: Humming began after the onset of seizures generated in medial limbic regions of the temporal lobe. At seizure onset, coherence analysis showed an increase in amygdala-hippocampus coupling. Humming began after the onset of a rhythmic discharge over lateral regions of the superior temporal gyrus (STG). A highly significant increase in coherence was observed between prefrontal regions and the STG. TF analysis of the STG discharge showed a reproducible pattern with a single fundamental frequency and associated harmonics. This frequency was approximately 6 Hz for two patients and 15 Hz for one patient. CONCLUSIONS: These findings suggest that the occurrence of humming during epileptic seizures of the temporal lobe is associated with activity in a neural network involving the STG and the inferior frontal gyrus.

Adult↗

Fear, anger and compulsive behavior during seizure: involvement of large scale fronto-temporal neural networks.

UNLABELLED: Seizure-related, abnormal affective and gestural behavior may involve some of the same processes as those underlying non-pathological behavior, but their mechanisms remain largely unknown. In this report, we studied a patient in whom seizures initially involved the medial temporal region before involving the frontal cortex. Seizure semiology of the second part of the seizure included marked emotional disturbances (dominated by intense fear and anger) and compulsive behavior to bite into something. This patient underwent presurgical evaluation including intracerebral electroencephalographic recordings (SEEG, stereoelectroencephalography). METHODS: In addition to SEEG examination, we used coherence analysis of signals as a means of studying functional coupling between different regions of the brain. Two seizures were studied. Coherence values from different periods of interest were compared to identify the neural structures involved at the onset of seizure activity as well as during the emotional behavioral changes. RESULTS: A first network of neural structures was identified within the right anterior temporal regions (amygdala, temporal pole, hippocampus, temporal neocortex). At the time of intense affective and compulsive changes, and by comparison with the first ictal period, a second network was identified characterized by significant functional coupling between the amygdala, the orbito-frontal structures and the frontal opercular region, while a decrease in functional coupling between these regions and the dorsolateral region and the cingulate gyrus was apparent. CONCLUSION: This study show that the emergence of an intense affective and behavioral state during a temporal lobe seizure could be related to the involvement of a network of structures including the anterior temporal lobe and the orbito-frontal cortex. The decrease of coupling between these regions and the lateral prefrontal and cingulate regions could also participate in these phenomena.

Adult↗