Christophe Grova

Negative BOLD responses to epileptic spikes

Simultaneous electroencephalogram/functional magnetic resonance imaging (EEG‐fMRI) during interictal epileptiform discharges can result in positive (activation) and negative (deactivation) changes in the blood oxygenation level‐dependent (BOLD) signal. Activation probably reflects increased neuronal activity and energy demand, but deactivation is more difficult to explain. Our objective was to evaluate the occurrence and significance of deactivations related to epileptiform discharges in epilepsy. We reviewed all EEG‐fMRI studies from our database, identified those with robust responses (P = 0.01, with ≥5 contiguous voxels with a |t| > 3.1, including ≥1 voxel at |t| > 5.0), and divided them into three groups: activation (A = 8), deactivation (D = 9), and both responses (AD = 43). We correlated responses with discharge type and location and evaluated their spatial relationship with regions involved in the “default” brain state (Raichle et al. [ 2001 ]: Proc Natl Acad Sci 98:676–682]. Deactivations were seen in 52/60 studies (AD+D): 26 related to focal discharges, 12 bilateral, and 14 generalized. Deactivations were usually distant from anatomical areas related to the discharges and more frequently related to polyspike‐ and spike‐and‐slow waves than to spikes. The “default” pattern occurred in 10/43 AD studies, often associated with bursts of generalized discharges. In conclusion, deactivations are frequent, mostly with concomitant activation, for focal and generalized discharges. Discharges followed by a slow wave are more likely to result in deactivation, suggesting neuronal inhibition as the underlying phenomenon. Involvement of the “default” areas, related to bursts of generalized discharges, provides evidence of a subclinical effect of the discharges, temporarily suspending normal brain function in the resting state. Hum Brain Mapp, 2005.

Evaluation of EEG localization methods using realistic simulations of interictal spikes.

Performing an accurate localization of sources of interictal spikes from EEG scalp measurements is of particular interest during the presurgical investigation of epilepsy. The purpose of this paper is to study the ability of six distributed source localization methods to recover extended sources of activated cortex. Due to the frequent lack of a gold standard to evaluate source localization methods, our evaluation was performed in a controlled environment using realistic simulations of EEG interictal spikes, involving several anatomical locations with several spatial extents. Simulated data were corrupted by physiological EEG noise. Simulations involving pairs of sources with the same amplitude were also studied. In addition to standard validation criteria (e.g., geodesic distance or mean square error), we proposed an original criterion dedicated to assess detection accuracy, based on receiver operating characteristic (ROC) analysis. Six source localization methods were evaluated: the minimum norm, the minimum norm weighted by multivariate source prelocalization (MSP), cortical LORETA with or without additional minimum norm regularization, and two derivations of the maximum entropy on the mean (MEM) approach. Results showed that LORETA-based and MEM-based methods were able to accurately recover sources of different spatial extents, with the exception of sources in temporo-mesial and fronto-mesial regions. Several spurious sources were generated by those methods, however, whereas methods using the MSP always located very accurately the maximum of activity but not its spatial extent. These findings suggest that one should always take into account the results from different localization methods when analyzing real interictal spikes.

Patterns of altered functional connectivity in mesial temporal lobe epilepsy

Purpose:  In mesial temporal lobe epilepsy (MTLE) the epileptogenic area is confined to the mesial temporal lobe, but other cortical and subcortical areas are also affected and cognitive and psychiatric impairments are usually documented. Functional connectivity methods are based on the correlation of the blood oxygen level dependent (BOLD) signal between brain regions, which exhibit consistent and reproducible functional networks from resting state data. The aim of this study is to compare functional connectivity of patients with MTLE during the interictal period with healthy subjects. We hypothesize that patients show reduced functional connectivity compared to controls, the interest being to determine which regions show this reduction.

Symmetrical event-related EEG/fMRI information fusion in a variational Bayesian framework.

In this work, we propose a symmetrical multimodal EEG/fMRI information fusion approach dedicated to the identification of event-related bioelectric and hemodynamic responses. Unlike existing, asymmetrical EEG/fMRI data fusion algorithms, we build a joint EEG/fMRI generative model that explicitly accounts for local coupling/uncoupling of bioelectric and hemodynamic activities, which are supposed to share a common substrate. Under a dedicated assumption of spatio-temporal separability, the spatial profile of the common EEG/fMRI sources is introduced as an unknown hierarchical prior on both markers of cerebral activity. Thereby, a devoted Variational Bayesian (VB) learning scheme is derived to infer common EEG/fMRI sources from a joint EEG/fMRI dataset. This yields an estimate of the common spatial profile, which is built as a trade-off between information extracted from EEG and fMRI datasets. Furthermore, the spatial structure of the EEG/fMRI coupling/uncoupling is learned exclusively from the data. The proposed data generative model and devoted VBEM learning scheme thus provide an un-supervised well-balanced approach for the fusion of EEG/fMRI information. We first demonstrate our approach on synthetic data. Results show that, in contrast to classical EEG/fMRI fusion approach, the method proved efficient and robust regardless of the EEG/fMRI discordance level. We apply the method on EEG/fMRI recordings from a patient with epilepsy, in order to identify brain areas involved during the generation of epileptic spikes. The results are validated using intracranial EEG measurements.

Using voxel-specific hemodynamic response function in EEG-fMRI data analysis.

Most existing analytical techniques for EEG-fMRI data need specific assumptions about the hemodynamic response function (HRF). These assumptions may not be appropriate when the HRF varies from subject to subject or from region to region. In this article, we introduce a deconvolution method for EEG-fMRI activation detection, which can be implemented with voxel-specific HRFs. A comparison of performance is made between three fixed HRFs and the deconvolution method under the framework of the general linear model. The main results are as follows: (1) the volume of detected regions from the deconvolved HRFs is larger. (2) In some subjects, the deconvolution technique can find areas of activation that have not been detected with the three fixed HRFs at our threshold of significance. (3) Deconvolution obtained higher adjusted coefficients of multiple determination compared to those obtained with the three fixed HRFs. The results suggest that the fixed HRF methods may not be the most appropriate for the analysis of epileptic activity with EEG-fMRI, and the deconvolution method may be a better choice.

PET-SORTEO: validation and development of database of Simulated PET volumes

We present here the features and validation results of a Monte Carlo-based PET simulation platform designed to address the increasing need of simulated studies. The simulation tool, named PET-SORTEO, includes i) the generation of the raw data in accordance with both the numerical phantom description as well as with the scanner geometry and physical characteristics, and ii) the correction and reconstruction of the raw data. Validation results show that the platform reliably reproduces the image formation processes and includes correctly the sources of noise and biases. This platform allows for parallel processing and complete dynamic PET studies, including emission and transmission data, can be generated within few hours using a cluster of machines. Using PET-SORTEO, we generated a database of realistic simulated PET data accounting for inter-subject anatomical variability. This database has the merit to provide the community with realistic simulated 3D and 4D PET studies for commonly used radiotracers. This database as well as information about PET-SORTEO can be found at the address: http://sorteo.cermep.fr.

Widespread and intense BOLD changes during brief focal electrographic seizures

Background: Combined recording of EEG and fMRI has shown changes in blood oxygenation level dependent (BOLD) signal during focal interictal epileptic spikes. Due to difficult assessment of seizures inside the scanner little is known about BOLD changes during seizures. Objectives: To describe BOLD changes related to brief focal electrographic seizures in a patient with right temporo-parietal gray matter nodular heterotopia. Methods: The patient underwent two EEG-fMRI sessions during which several focal seizures were recorded. EEG was acquired continuously during scanning and seizure timing was used for statistical analysis. Functional maps were thresholded to disclose positive (activation) and negative (deactivation) BOLD changes. Results: Twenty-five focal electrographic seizures were analyzed, consisting of runs of polyspikes lasting 2 to 6 s in the right temporal region. Activation included a large volume, involving the heterotopia and the abnormal temporo-parietal cortex overlying the nodule, with a clear maximum over the angular gyrus. Deactivation was bilateral and maximum in the occipital regions. The hemodynamic response function showed a return to baseline of the BOLD signal 30 s after seizure end. Conclusions: The brief focal seizures resulted in high amplitude and widespread blood oxygenation level dependent (BOLD) responses taking 30 s to return to baseline. This suggests that such brief events could have important behavioral consequences despite absent overt manifestations. A clear focal BOLD peak was found at some distance from the main EEG discharge, raising the possibility that the seizure could have started in a region that did not generate a visible EEG change despite its superficial location.

Concordance between distributed EEG source localization and simultaneous EEG-fMRI studies of epileptic spikes.

In order to analyze where epileptic spikes are generated, we assessed the level of concordance between EEG source localization using distributed source models and simultaneous EEG-fMRI which measures the hemodynamic correlates of EEG activity. Data to be compared were first estimated on the same cortical surface and two comparison strategies were used: (1) MEM-concordance: a comparison between EEG sources localized with the Maximum Entropy on the Mean (MEM) method and fMRI clusters showing a significant hemodynamic response. Minimal geodesic distances between local extrema and overlap measurements between spatial extents of EEG sources and fMRI clusters were used to quantify MEM-concordance. (2) fMRI-relevance: estimation of the fMRI-relevance index alpha quantifying if sources located in an fMRI cluster could explain some scalp EEG data, when this fMRI cluster was used to constrain the EEG inverse problem. Combining MEM-concordance and fMRI-relevance (alpha) indexes, each fMRI cluster showing a significant hemodynamic response (p<0.05 corrected) was classified according to its concordance with EEG data. Nine patients with focal epilepsy who underwent EEG-fMRI examination followed by EEG recording outside the scanner were selected for this study. Among the 62 fMRI clusters analyzed (7 patients), 15 (24%) found in 6 patients were highly concordant with EEG according to both MEM-concordance and fMRI-relevance. EEG concordance was found for 5 clusters (8%) according to alpha only, suggesting sources missed by the MEM. No concordance with EEG was found for 30 clusters (48%) and for 10 clusters (16%) alpha was significantly negative, suggesting EEG-fMRI discordance. We proposed two complementary strategies to assess and classify EEG-fMRI concordance. We showed that for most patients, part of the hemodynamic response to spikes was highly concordant with EEG sources, whereas other fMRI clusters in response to the same spikes were found distant or discordant with EEG sources.

Functional connectivity in patients with idiopathic generalized epilepsy

Purpose:  Idiopathic generalized epilepsy (IGE) is characterized by electroencephalography (EEG) recordings with generalized spike wave discharges (GSWDs) arising from normal background activity. Although GSWDs are the result of highly synchronized activity in the thalamocortical network, EEG without GSWDs is believed to represent normal brain activity. The aim of this study was to investigate whether thalamocortical interactions are altered even during GSWD‐free EEG periods in patients with IGE.

Oscillatory Activity in Parietal and Dorsolateral Prefrontal Cortex During Retention in Visual Short-Term Memory: Additive Effects of Spatial Attention and Memory Load

We used whole‐head magnetoencephalography to study the representation of objects in visual short‐term memory (VSTM) in the human brain. Subjects remembered the location and color of either two or four colored disks that were encoded from the left or right visual field (equal number of distractors in the other visual hemifield). The data were analyzed using time‐frequency methods, which enabled us to discover a strong oscillatory activity in the 8–15 Hz band during the retention interval. The study of the alpha power variation revealed two types of responses, in different brain regions. The first was a decrease in alpha power in parietal cortex, contralateral to the stimuli, with no load effect. The second was an increase of alpha power in parietal and lateral prefrontal cortex, as memory load increased, but without interaction with the hemifield of the encoded stimuli. The absence of interaction between side of encoded stimuli and memory load suggests that these effects reflect distinct underlying mechanisms. A novel method to localize the neural generators of load‐related oscillatory activity was devised, using cortically‐constrained distributed source‐localization methods. Some activations were found in the inferior intraparietal sulcus (IPS) and intraoccipital sulcus (IOS). Importantly, strong oscillatory activity was also found in dorsolateral prefrontal cortex (DLPFC). Alpha oscillatory activity in DLPFC was synchronized with the activity in parietal regions, suggesting that VSTM functions in the human brain may be implemented via a network that includes bilateral DLPFC and bilateral IOS/IPS as key nodes. Hum Brain Mapp, 2009.