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Fabrice Bartolomei

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10 papers

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YNIMG Journal 2023 Journal Article

Comparison of beamformer and ICA for dynamic connectivity analysis: A simultaneous MEG-SEEG study

Stefania Coelli
Samuel Medina Villalon
Francesca Bonini
Jayabal Velmurugan
Víctor J. López-Madrona
Romain Carron
Fabrice Bartolomei
Jean-Michel Badier

Magnetoencephalography (MEG) is a powerful tool for estimating brain connectivity with both good spatial and temporal resolution. It is particularly helpful in epilepsy to characterize non-invasively the epileptic networks. However, using MEG to map brain networks requires solving a difficult inverse problem that introduces uncertainty in the activity localization and connectivity measures. Our goal here was to compare independent component analysis (ICA) followed by dipole source localization and the linearly constrained minimum-variance beamformer (LCMV-BF) for characterizing regions with interictal epileptic activity and their dynamic connectivity. After a simulation study, we compared ICA and LCMV-BF results with intracerebral EEG (stereotaxic EEG, SEEG) recorded simultaneously in 8 epileptic patients, which provide a unique 'ground truth' to which non-invasive results can be confronted. We compared the signal time courses extracted applying ICA and LCMV-BF on MEG data to that of SEEG, both for the actual signals and the dynamic connectivity computed using cross-correlation (evolution of links in time). With our simulations, we illustrated the different effect of the temporal and spatial correlation among sources on the two methods. While ICA was more affected by the temporal correlation but robust against spatial configurations, LCMV-BF showed opposite behavior. Moreover, ICA seems more suited to retrieve the simulated networks. In case of real patient data, good MEG/SEEG correlation and good localization were obtained in 6 out of 8 patients. In 4 of them ICA had the best performance (higher correlation, lower localization distance). In terms of dynamic connectivity, the evolution in time of the cross-correlation links could be retrieved in 5 patients out of 6, however, with more variable results in terms of correlation and distance. In two patients LCMV-BF had better results than ICA. In one patient the two methods showed equally good outcomes, and in the remaining two patients ICA performed best. In conclusion, our results obtained by exploiting simultaneous MEG/SEEG recordings suggest that ICA and LCMV-BF have complementary qualities for retrieving the dynamics of interictal sources and their network interactions.

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YNIMG Journal 2022 Journal Article

Virtual MEG sensors based on beamformer and independent component analysis can reconstruct epileptic activity as measured on simultaneous intracerebral recordings

Jayabal Velmurugan
Jean-Michel Badier
Francesca Pizzo
Samuel Medina Villalon
Christos Papageorgakis
Victor López-Madrona
Aude Jegou
Romain Carron

The prevailing gold standard for presurgical determination of epileptogenic brain networks is intracerebral EEG, a potent yet invasive approach. Magnetoencephalography (MEG) is a state-of-the art non-invasive method for investigating epileptiform discharges. However, it is not clear at what level the precision offered by MEG can reach that of SEEG. Here, we present a strategy for non-invasively retrieving the constituents of the interictal network, with high spatial and temporal precision. Our method is based on MEG and a combination of spatial filtering and independent component analysis (ICA). We validated this approach in twelve patients with drug-resistant focal epilepsy, thanks to the unprecedented ground truth provided by simultaneous recordings of MEG and SEEG. A minimum variance adaptive beamformer estimated the source time series and ICA was used to further decompose these time series into network constituents (MEG-ICs), each having a time series (virtual electrode) and a topography (spatial distribution of amplitudes in the brain). We show that MEG has a considerable sensitivity of 0.80 and 0.84 and a specificity of 0.93 and 0.91 for reconstructing deep and superficial sources, respectively, when compared to the ground truth (SEEG). For each epileptic MEG-IC (n = 131), we found at least one significantly correlating SEEG contact close to zero lag after correcting for multiple comparisons. All the patients except one had at least one epileptic component that was highly correlated (Spearman rho>0.3) with that of SEEG traces. MEG-ICs correlated well with SEEG traces. The strength of correlation coefficients did not depend on the depth of the SEEG contacts or the clinical outcome of the patient. A significant proportion of the MEG-ICs (n = 83/131) were localized in proximity with their maximally correlating SEEG, within a mean distance of 20±12.18mm. Our research is the first to validate the MEG-retrieved beamformer IC sources against SEEG-derived ground truth in a simultaneous MEG-SEEG framework. Observations from the present study suggest that non-invasive MEG source components may potentially provide additional information, comparable to SEEG in a number of instances.

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YNICL Journal 2019 Journal Article

Connectivity strength, time lag structure and the epilepsy network in resting-state fMRI

S. Kathleen Bandt
Pierre Besson
Ben Ridley
Francesca Pizzo
Romain Carron
Jean Regis
Fabrice Bartolomei
Jean Philippe Ranjeva

The relationship between the epilepsy network, intrinsic brain networks and hypersynchrony in epilepsy remains incompletely understood. To converge upon a synthesized understanding of these features, we studied two elements of functional connectivity in epilepsy: correlation and time lag structure using resting state fMRI data from both SEEG-defined epileptic brain regions and whole-brain fMRI analysis. Functional connectivity (FC) was analyzed in 15 patients with epilepsy and 36 controls. Correlation strength and time lag were selected to investigate the magnitude of and temporal interdependency across brain regions. Zone-based analysis was carried out investigating directed correlation strength and time lag between both SEEG-defined nodes of the epilepsy network and between the epileptogenic zone and all other brain regions. Findings were compared between patients and controls and against a functional atlas. FC analysis on the nodal and whole brain levels identifies consistent patterns of altered correlation strength and altered time lag architecture in epilepsy patients compared to controls. These patterns include 1) broadly distributed increased strength of correlation between the seizure onset node and the remainder of the brain, 2) decreased time lag within the seizure onset node, and 3) globally increased time lag throughout all regions of the brain not involved in seizure onset or propagation. Comparing the topographic distribution of findings against a functional atlas, all resting state networks were involved to a variable degree. These local and whole brain findings presented here lead us to propose the network steal hypothesis as a possible mechanistic explanation for the non-seizure clinical manifestations of epilepsy.

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YNIMG Journal 2017 Journal Article

Brain sodium MRI in human epilepsy: Disturbances of ionic homeostasis reflect the organization of pathological regions

Ben Ridley
Angela Marchi
Jonathan Wirsich
Elisabeth Soulier
Sylviane Confort-Gouny
Lothar Schad
Fabrice Bartolomei
Jean-Philippe Ranjeva

In light of technical advancements supporting exploration of MR signals other than 1H, sodium (23Na) has received attention as a marker of ionic homeostasis and cell viability. Here, we evaluate for the first time the possibility that 23Na-MRI is sensitive to pathological processes occurring in human epilepsy. A normative sample of 27 controls was used to normalize regions of interest (ROIs) from 1424 unique brain locales on quantitative 23Na-MRI and high-resolution 1H-MPRAGE images. ROIs were based on intracerebral electrodes in ten patients undergoing epileptic network mapping. The stereo-EEG gold standard was used to define regions as belonging to primarily epileptogenic, secondarily irritative and to non-involved regions. Estimates of total sodium concentration (TSC) on 23Na-MRI and cerebrospinal fluid (CSF) on 1H imaging were extracted for each patient ROI, and normalized against the same region in controls. ROIs with disproportionate CSF contributions (ZCSF≥1. 96) were excluded. TSC levels were found to be elevated in patients relative to controls except in one patient, who suffered non-convulsive seizures during the scan, in whom we found reduced TSC levels. In the remaining patients, an ANOVA (F1100= 12. 37, p<0. 0001) revealed a highly significant effect of clinically-defined zones (F1100= 11. 13, p<0. 0001), with higher normalized TSC in the epileptogenic zone relative to both secondarily irritative (F1100= 11, p=0. 0009) and non-involved regions (F1100= 17. 8, p<0. 0001). We provide the first non-invasive, in vivo evidence of a chronic TSC elevation alongside ZCSF levels within the normative range, associated with the epileptogenic region even during the interictal period in human epilepsy, and the possibility of reduced TSC levels due to seizure. In line with modified homeostatic mechanisms in epilepsy – including altered mechanisms underlying ionic gating, clearance and exchange – we provide the first indication of 23Na-MRI as an assay of altered sodium concentrations occurring in epilepsy associated with the organization of clinically relevant divisions of pathological cortex.

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YNICL Journal 2017 Journal Article

Localizing value of electrical source imaging: Frontal lobe, malformations of cortical development and negative MRI related epilepsies are the best candidates

Chifaou Abdallah
Louis G. Maillard
Estelle Rikir
Jacques Jonas
Anne Thiriaux
Martine Gavaret
Fabrice Bartolomei
Sophie Colnat-Coulbois

OBJECTIVE: We aimed to prospectively assess the anatomical concordance of electric source localizations of interictal discharges with the epileptogenic zone (EZ) estimated by stereo-electroencephalography (SEEG) according to different subgroups: the type of epilepsy, the presence of a structural MRI lesion, the aetiology and the depth of the EZ. METHODS: In a prospective multicentric observational study, we enrolled 85 consecutive patients undergoing pre-surgical SEEG investigation for focal drug-resistant epilepsy. Electric source imaging (ESI) was performed before SEEG. Source localizations were obtained from dipolar and distributed source methods. Anatomical concordance between ESI and EZ was defined according to 36 predefined sublobar regions. ESI was interpreted blinded to- and subsequently compared with SEEG estimated EZ. RESULTS: = 0.03). The rate of ESI full concordance with EZ was not statistically different according to the depth of the EZ. SIGNIFICANCE: We prospectively demonstrated that ESI more accurately estimated the EZ in subgroups of patients who are often the most difficult cases in epilepsy surgery: frontal lobe epilepsy, negative MRI and the presence of MCD.

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YNICL Journal 2016 Journal Article

Whole-brain analytic measures of network communication reveal increased structure-function correlation in right temporal lobe epilepsy

Jonathan Wirsich
Alistair Perry
Ben Ridley
Timothée Proix
Mathieu Golos
Christian Bénar
Jean-Philippe Ranjeva
Fabrice Bartolomei

The in vivo structure-function relationship is key to understanding brain network reorganization due to pathologies. This relationship is likely to be particularly complex in brain network diseases such as temporal lobe epilepsy, in which disturbed large-scale systems are involved in both transient electrical events and long-lasting functional and structural impairments. Herein, we estimated this relationship by analyzing the correlation between structural connectivity and functional connectivity in terms of analytical network communication parameters. As such, we targeted the gradual topological structure-function reorganization caused by the pathology not only at the whole brain scale but also both in core and peripheral regions of the brain. We acquired diffusion (dMRI) and resting-state fMRI (rsfMRI) data in seven right-lateralized TLE (rTLE) patients and fourteen healthy controls and analyzed the structure-function relationship by using analytical network communication metrics derived from the structural connectome. In rTLE patients, we found a widespread hypercorrelated functional network. Network communication analysis revealed greater unspecific branching of the shortest path (search information) in the structural connectome and a higher global correlation between the structural and functional connectivity for the patient group. We also found evidence for a preserved structural rich-club in the patient group. In sum, global augmentation of structure-function correlation might be linked to a smaller functional repertoire in rTLE patients, while sparing the central core of the brain which may represent a pathway that facilitates the spread of seizures.

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YNIMG Journal 2015 Journal Article

Nodal approach reveals differential impact of lateralized focal epilepsies on hub reorganization

Ben Gendon Yeshe Ridley
Celia Rousseau
Jonathan Wirsich
Arnaud Le Troter
Elisabeth Soulier
Sylvianne Confort-Gouny
Fabrice Bartolomei
Jean-Philippe Ranjeva

The impact of the hemisphere affected by impairment in models of network disease is not fully understood. Among such models, focal epilepsies are characterised by recurrent seizures generated in epileptogenic areas also responsible for wider network dysfunction between seizures. Previous work focusing on functional connectivity within circumscribed networks suggests a divergence of network integrity and compensatory capacity between epilepsies as a function of the laterality of seizure onset. We evaluated the ability of complex network theory to reveal changes in focal epilepsy in global and nodal parameters using graph theoretical analysis of functional connectivity data obtained with resting-state fMRI. Graphs of functional connectivity networks were derived from 19 right and 13 left focal epilepsy patients and 15 controls. Topological metrics (degree, local efficiency, global efficiency and modularity) were computed for a whole-brain, atlas-defined network. We also calculated a hub disruption index for each graph metric, measuring the capacity of the brain network to demonstrate increased connectivity in some nodes for decreased connectivity in others. Our data demonstrate that the patient group as a whole is characterised by network-wide pattern of reorganization, even while global parameters fail to distinguish between groups. Furthermore, multiple metrics indicate that epilepsies with differently lateralized epileptic networks are asymmetric in their burden on functional brain networks; with left epilepsy patients being characterised by reduced efficiency and modularity, while in right epilepsy patients we provide the first evidence that functional brain networks are characterised by enhanced connectivity and efficiency at some nodes whereas reduced in others.

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YNIMG Journal 2014 Journal Article

Simultaneous recording of MEG, EEG and intracerebral EEG during visual stimulation: From feasibility to single-trial analysis

Anne-Sophie Dubarry
Jean-Michel Badier
Agnès Trébuchon-Da Fonseca
Martine Gavaret
Romain Carron
Fabrice Bartolomei
Catherine Liégeois-Chauvel
Jean Régis

Electroencephalography (EEG), magnetoencephalography (MEG), and intracerebral stereotaxic EEG (SEEG) are the three neurophysiological recording techniques, which are thought to capture the same type of brain activity. Still, the relationships between non-invasive (EEG, MEG) and invasive (SEEG) signals remain to be further investigated. In early attempts at comparing SEEG with either EEG or MEG, the recordings were performed separately for each modality. However such an approach presents substantial limitations in terms of signal analysis. The goal of this technical note is to investigate the feasibility of simultaneously recording these three signal modalities (EEG, MEG and SEEG), and to provide strategies for analyzing this new kind of data. Intracerebral electrodes were implanted in a patient with intractable epilepsy for presurgical evaluation purposes. This patient was presented with a visual stimulation paradigm while the three types of signals were simultaneously recorded. The analysis started with a characterization of the MEG artifact caused by the SEEG equipment. Next, the average evoked activities were computed at the sensor level, and cortical source activations were estimated for both the EEG and MEG recordings; these were shown to be compatible with the spatiotemporal dynamics of the SEEG signals. In the average time–frequency domain, concordant patterns between the MEG/EEG and SEEG recordings were found below the 40Hz level. Finally, a fine-grained coupling between the amplitudes of the three recording modalities was detected in the time domain, at the level of single evoked responses. Importantly, these correlations have shown a high level of spatial and temporal specificity. These findings provide a case for the ability of trimodal recordings (EEG, MEG, and SEEG) to reach a greater level of specificity in the investigation of brain signals and functions.

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YNIMG Journal 2010 Journal Article

Computational modeling of high-frequency oscillations at the onset of neocortical partial seizures: From ‘altered structure’ to ‘dysfunction’

Behnam Molaee-Ardekani
Pascal Benquet
Fabrice Bartolomei
Fabrice Wendling

In this paper, a neural mass model is proposed to analyze some mechanisms underlying the generation of fast oscillations (80 Hz and beyond) at the onset of seizures. This model includes one sub-population of pyramidal cells and one sub-population of interneurons targeting the perisomatic region of pyramidal cells where fast GABAergic currents are mediated. We identified some conditions for which the model can reproduce the features of high-frequency, chirp-like (from ∼100 to ∼70 Hz) signatures observed in real depth-EEG signals recorded in epileptic patients at seizure onset (“fast onset activity”). These conditions included appropriate alterations in (i) the strengths of GABAergic and glutamatergic connections, and (ii) the amplitude of average EPSPs/IPSPs. Results revealed that a subtle balance between excitatory and inhibitory feedbacks is required in the model for reproducing a ‘realistic’ fast activity, i. e. , showing a reduction of frequency with a simultaneous increase in amplitude, as actually observed in epileptogenic cerebral cortex. Results also demonstrated that the number of scenarios (variation, in time, of model parameters) leading to chirp-like signatures was rather limited. First, to produce high-frequency output signals, the model should operate in a “resonance” region, at the frontier between a stable and an unstable region. Second both EPSP and IPSP amplitudes should decrease with time in order to obey the frequency/amplitude constraint. These scenarios obtained through a mathematical analysis of the model show how some alteration in the structure of neural networks can lead to dysfunction. They also provide insights into potentially important mechanisms for high-frequency epileptic activity generation.

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YNIMG Journal 2010 Journal Article

Source localization of ictal epileptic activity investigated by high resolution EEG and validated by SEEG

Laurent Koessler
Christian Benar
Louis Maillard
Jean-Michel Badier
Jean Pierre Vignal
Fabrice Bartolomei
Patrick Chauvel
Martine Gavaret

High resolution electroencephalography (HR-EEG) combined with source localization methods has mainly been used to study interictal spikes and there have been few studies comparing source localization of scalp ictal patterns with depth EEG. To address this issue, 10 patients with four different scalp ictal patterns (ictal spikes, rhythmic activity, paroxysmal fast activity, obscured) were investigated by both HR-EEG and stereoelectroencephalography (SEEG). Sixty-four scalp-EEG sensors and a sampling rate of 1kHz were used to record scalp ictal patterns. Five different source models (moving dipole, rotating dipole, MUSIC, LORETA, and sLORETA) were used in order to perform source localization. Seven to 10 intracerebral electrodes were implanted during SEEG investigations. For each source model, the concordance between ictal source localization and epileptogenic zone defined by SEEG was assessed. Results were considered to agree if they localized in the same sublobar area as defined by a trained epileptologist. Across the study population, the best concordance between source localization methods and SEEG (9/10) was obtained with equivalent current dipole modeling. MUSIC and LORETA had a concordance of 7/10 whereas sLORETA had a concordance of only 5/10. Four of our patients classified into different groups (ictal spikes, paroxysmal fast activity, obscured) had complete concordance between source localization methods and SEEG. A high signal to noise ratio, a short time window of analysis (<1s) and bandpass filtering around the frequency of rhythmic activity allowed improvement of the source localization results. A high level of agreement between source localization methods and SEEG can be obtained for ictal spike patterns and for scalp-EEG paroxysmal fact activities whereas scalp rhythmic discharges can be accurately localized but originated from seizure propagation network.

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