Deep brain activities can be detected with magnetoencephalography.

The hippocampus and amygdala are key brain structures of the medial temporal lobe, involved in cognitive and emotional processes as well as pathological states such as epilepsy. Despite their importance, it is still unclear whether their  neural activity can be recorded non-invasively. Here, using simultaneous intracerebral and magnetoencephalography (MEG) recordings in patients with focal drug-resistant epilepsy, we demonstrate a direct contribution of amygdala and hippocampal activity to surface MEG recordings. In particular, a method of blind source separation, independent component analysis, enabled activity arising from large neocortical networks to be disentangled from that of deeper structures, whose amplitude at the surface was small but significant. This finding is highly relevant for our understanding of hippocampal and amygdala brain activity as it implies that their activity could potentially be measured non-invasively.

The neuronal sources of EEG: modeling of simultaneous scalp and intracerebral recordings in epilepsy.

In many applications which make use of EEG to investigate brain functions, a central question is often to relate the recorded signals to the spatio-temporal organization of the underlying neuronal sources of activity. A modeling attempt to quantitatively investigate this imperfectly known relationship is reported. The proposed plausible model of EEG generation relies on an accurate representation of the neuronal sources of activity. It combines both an anatomically realistic description of the spatial features of the sources (convoluted dipole layer) and a physiologically relevant description of their temporal activities (coupled neuronal populations). The model was used in the particular context of epileptiform activity (interictal spikes) to interpret simultaneously generated scalp and intracerebral EEG. Its integrative properties allowed for the bridging between source-related parameters (spatial extent, location, synchronization) and the properties of resulting EEG signals (amplitude of spikes, amplitude gradient along intracerebral electrodes, topography over scalp electrodes). The sensitivity of both recording modalities to source-related parameters was also studied. The model confirmed that the cortical area involved in interictal spikes is rather large. Its relative location with respect to recording electrodes was found to strongly influence the properties of EEG signals as the source geometry is a critical parameter. The influence, on simulated signals, of the synchronization degree between neuronal populations within the epileptic source was also investigated. The model revealed that intracerebral EEG can reflect epileptic activities corresponding to weak synchronization between neuronal populations of the epileptic patch. These results, as well as the limitations of the model, are discussed.

[High-resolution EEG (HR-EEG) and magnetoencephalography (MEG)]. / EEG haute résolution (EEG-HR) et magnétoencéphalographie (MEG).

HR-EEG (high resolution EEG) and MEG (magnetoencephalography) allow the recording of cerebral electromagnetic activities with excellent temporal resolution. These tools have also considerably progressed in spatial resolution and now constitute real methods of Electric and Magnetic Source Imaging. Their limits and the precision of the results obtained are discussed in distinct types of partial epilepsy. HR-EEG and MEG allow localization of scalp-EEG interictal spikes and more rarely ictal activities. They now contribute to the presurgical evaluation of pharmacoresistant partial epilepsies. These investigations appear to be of particular importance in presurgical assessment of MRI-negative epilepsy.

Preoperative and intraoperative neurophysiological investigations for surgical resections in functional areas.

Brain regions are removed to treat lesions, but great care must be taken not to disturb or remove functional areas in the lesion and in surrounding tissue where healthy and diseased cells may be intermingled, especially for infiltrating tumors. Cortical functional areas and fiber tracts can be localized preoperatively by probabilistic anatomical tools, but mapping of functional integrity by neurophysiology is essential. Identification of the primary motor cortex seems to be more effectively performed with transcranial magnetic stimulation (TMS) than functional magnetic resonance imaging (fMRI). Language area localization requires auditory evoked potentials or TMS, as well as fMRI and diffusion tensor imaging for fiber tracts. Somatosensory cortex is most effectively mapped by somatosensory evoked potentials. Crucial eloquent areas, such as the central sulcus, primary somatomotor areas, corticospinal tract must be defined and for some areas that must be removed, potential compensations may be identified. Oncological/functional ratio must be optimized, resecting the tumor maximally but also sparingly, as far as possible, the areas that mediate indispensable functions. In some cases, a transient postoperative deficit may be inevitable. In this article, we review intraoperative exploration of motricity, language, somatosensory, visual and vestibular function, calculation, memory and components of consciousness.

Technical solutions for simultaneous MEG and SEEG recordings: towards routine clinical use.

OBJECTIVE: The simultaneous recording of intracerebral EEG (stereotaxic EEG, SEEG) and magnetoencephalography (MEG) is a promising strategy that provides both local and global views on brain pathological activity. Yet, acquiring simultaneous signals poses difficult technical issues that hamper their use in clinical routine. Our objective was thus to develop a set of solutions for recording a high number of SEEG channels while preserving signal quality. APPROACH: We recorded data in a patient with drug resistant epilepsy during presurgical evaluation. We used dedicated insertion screws and optically insulated amplifiers. We recorded 137 SEEG contacts on 10 depth electrodes (5-15 contacts each) and 248 MEG channels (magnetometers). Signal quality was assessed by comparing the distribution of RMS values in different frequency bands to a reference set of MEG acquisitions. MAIN RESULTS: The quality of signals was excellent for both MEG and SEEG; for MEG, it was comparable to that of MEG signals without concurrent SEEG. Discharges involving several structures on SEEG were visible on MEG, whereas discharges limited in space were not seen at the surface. SIGNIFICANCE: SEEG can now be recorded simultaneously with whole-head MEG in routine. This opens new avenues, both methodologically for understanding signals and improving signal processing methods, and clinically for future combined analyses.

AnyWave: a cross-platform and modular software for visualizing and processing electrophysiological signals.

BACKGROUND: The importance of digital signal processing in clinical neurophysiology is growing steadily, involving clinical researchers and methodologists. There is a need for crossing the gap between these communities by providing efficient delivery of newly designed algorithms to end users. We have developed such a tool which both visualizes and processes data and, additionally, acts as a software development platform. NEW METHOD: AnyWave was designed to run on all common operating systems. It provides access to a variety of data formats and it employs high fidelity visualization techniques. It also allows using external tools as plug-ins, which can be developed in languages including C++, MATLAB and Python. RESULTS: In the current version, plug-ins allow computation of connectivity graphs (non-linear correlation h2) and time-frequency representation (Morlet wavelets). The software is freely available under the LGPL3 license. COMPARISON WITH EXISTING METHODS: AnyWave is designed as an open, highly extensible solution, with an architecture that permits rapid delivery of new techniques to end users. CONCLUSIONS: We have developed AnyWave software as an efficient neurophysiological data visualizer able to integrate state of the art techniques. AnyWave offers an interface well suited to the needs of clinical research and an architecture designed for integrating new tools. We expect this software to strengthen the collaboration between clinical neurophysiologists and researchers in biomedical engineering and signal processing.

Intracerebral evoked potentials in pitch perception reveal a functional asymmetry of the human auditory cortex.

One acoustic feature that plays an important role in pitch perception is frequency. Studies on the processing of frequency in the human and animal brain have shown that the auditory cortex is tonotopically organized: low frequencies are represented laterally whereas high frequencies are represented medially. To date, the study of the functional organization of the human auditory cortex in the processing of frequency has been limited to the use of either scalp-recorded auditory evoked potentials (AEPs), which have relatively poor spatial resolving power, or functional imagery techniques, which have poor temporal resolving power. The present study uses intracerebrally recorded AEPs to explore this topic in the primary and secondary auditory cortices of both hemispheres of the human brain. Recordings were carried out in 45 adult patients with drug-resistant partial seizures. In the right hemisphere, clear spectrally organized tonotopic maps were observed with distinct separations between different frequency-processing regions. AEPs for high frequencies were recorded medially, whereas AEPs for low frequencies were recorded laterally. In the left hemisphere, however, this tonotopic organization was less evident, with different regions involved in the processing of a range of frequencies. The hemisphere-related difference in the processing of tonal frequency is discussed in relation to pitch perception.

Spatio-temporal characteristics of paroxysmal interictal events in human temporal lobe epilepsy.

A spatio-temporal mapping technique was applied to stereotactically-implanted depth electrode recordings (SEEG). This technique was used to study the interictal activity in 13 epileptic patients with temporal lobe epilepsies during the pre-surgical evaluation of their epileptogenic zone prior to surgery. The method further provided the precise localization of distinct interictal activities in each explored structure. The high sensitivity of the technique is showed and has demonstrated the evidence of multiple sources during one single sequence of interictal activity. The stability of such an activity was also demonstrated in each patient. A temporal relationship existed between the activity recorded in different structures. Paroxysmal interictal activity thus appeared as an ordered and successive activation of different interictal loci overlapping each other. In this way it was possible to distinguish two different types of activities: primary foci that are activated independently of each other, and secondary foci activated by the primary foci. Finally, in addition to the source localization of interictal activity, the problem of detection and discrimination of the different components must be considered.

Localized brain metabolic response correlated with potentials evoked by words.

Evoked potentials (EPs) measure synaptic current flows that propagate from brain to scalp, Alternatively, positron emission tomography (PET) using fluoro-deoxyglucose (FDG) can measure the increased glucose metabolism supporting this synaptic activation. It is difficult to localize the brain activity-generating EPs from their scalp distribution, because activity originating in different regions tends to produce overlapping scalp topographies. In contrast, FDG-PET provides better spatial resolution for activity throughout the brain, but shows only the total metabolism integrated over a 30-min uptake period. We combined the temporal and psychological resolution of EPs with the spatial resolution of PET to help define when and where in the brain words are encoded for meaning.

Non-supervised spatio-temporal analysis of interictal magnetic spikes: comparison with intracerebral recordings.

OBJECTIVE: Our main goal was to evaluate the accuracy of an original non-supervised spatio-temporal magnetoencephalography (MEG) localization method used to characterize interictal spikes generators. METHODS: MEG and stereotactic intracerebral recordings (stereo-electro-encephalographic exploration, SEEG) data were analyzed independently in 4 patients. MEG localizations were performed with and without anatomical constraints. RESULTS: We analyzed 1326 interictal spikes recorded using MEG. For each patient, 2-3 typical source patterns were described. These source configurations were compared with SEEG. SEEG findings and MEG spatio-temporal localization results were remarkably coherent in our 4 patients. Most of the MEG patterns were similar to interictal SEEG patterns from a spatio-temporal point of view. CONCLUSIONS: We were able to evaluate the usefulness of our non-invasive localization method. This approach described correctly the part of the epileptogenic network involved in the generation of interictal events. Our results demonstrate the potential of MEG in the non-invasive spatio-temporal characterization of generators of interictal spikes.

Seizures of temporal lobe epilepsy: identification of subtypes by coherence analysis using stereo-electro-encephalography.

OBJECTIVES: Two subtypes of temporal lobe epilepsy (TLE) according to the structures initially involved during seizures are currently recognized: medial TLE (MTLE) and lateral (or neocortical) TLE (LTLE). A few reports have suggested that the classification of TLE subtypes might be larger according to variations in the interactions between medial structures and the neocortex. In this study, we analyzed these interactions using coherence analysis of stereo-encephalographic (SEEG) signals during spontaneous seizures. METHODS: Twenty-seven patients with drug-resistant TLE, diagnosed from ictal SEEG recordings obtained during pre-surgical evaluation, were studied. Orthogonally implanted depth electrodes with multiple leads according to Talairach's method were used to sample medial and neocortical structures. Coherence analysis of ictal discharges was performed between two SEEG bipolar signals from adjacent leads located either in medial structures (amygdala and hippocampus) or in neocortical regions of the temporal lobe. A new algorithm, which was designed to reduce the bias inherent in coherence estimation, was used to compute the coherence. RESULTS: We were able to classify TLE seizures (TLES) into 4 distinct categories: (1) 'medial' TLES, characterized by medial onset with later involvement of the neocortex in the form of a 'phasic' discharge. High ictal coherence values were observed between medial structures; (2) 'medial-lateral' TLES which started in medial structures with a fast low-voltage discharge (FLVD) which rapidly affects the neocortex (< or = 3 s). High coherence values were observed between medial and lateral structures; (3) 'lateral-medial' TLES, which are different from medial-lateral TLES in that the FLVD starts in the lateral neocortex and involves the amygdala and/or hippocampus almost immediately after; (4) 'lateral' TLES: characterized by a neocortical onset, a delayed involvement of medial structures (when present), and high coherence values between neocortical structures. CONCLUSIONS: These results demonstrate the existence of numerous interactions between medial limbic structures and the neocortex during TLE seizures. Such findings could have implications for surgical strategies and the prognosis of epilepsy surgery, particularly when limited resection is indicated.

Extraction of spatio-temporal signatures from depth EEG seizure signals based on objective matching in warped vectorial observations.

In the field of epilepsy, the analysis of stereoelectroencephalographic (SEEG) signals recorded with depth electrodes provides major information on interactions between brain structures during seizures. A comprehensive methodology of comparing SEEG seizure recordings is presented. It proceeds in three steps: 1) segmentation of SEEG signals; 2) characterization and labeling of segments; and 3) comparison of observations coded as sequences of symbol vectors. The third step reports a vectorial extension of the Wagner and Fischer's algorithm to first, quantify similarities between observations and second, extract invariant sequences of events, referred to as spatiotemporal signatures. The study shows that two observations of nonequal duration can be matched by deforming the first one to optimally fit the second, under cost constraints. Results show that the methodology allows to exhibit signatures occurring during epileptic seizures and to point out different types of seizure patterns. The study brings objective results on reproducible interactions between brain structures during ictal periods and may help in the understanding of epileptogenic networks.

Time-frequency matching of warped depth-EEG seizure observations.

A methodology of comparing depth-EEG seizure recordings is presented. The approach is based on an extension of Wagner and Fischer's algorithm to N x 2-dimensional sets, allowing a confrontation of nonequal duration observations characterized by their time-frequency distributions. It proceeds by time and frequency warping on the first observation to match the second, under cost constraints. Preliminary results show that relevant signatures can be extracted from recordings.

[EEG and video-EEG explorations in refractory partial epilepsy]. / Explorations EEG et vidéo-EEG des epilepsies partielles pharmaco-résistantes.

The assessment of drug -resistant partial epilepsy by electrophysiological explorations (based on non-invasive EEG) involves two types of analysis: the study of the seizures, primarily by video-EEG exploration, and the study of interictal activities based on visual analysis, and in some centers on techniques of source localization (high resolution EEG and magnetoencephalography, MEG). Seizure recording can be used to confirm the focal nature and the epileptic origin of the seizure as well as other features such as severity (secondary generalization, frequency, falls etc.). In the pre-surgical approach, the video-EEG recordings enable study of the electro-clinical correlations and allow assumptions on the anatomical localization of the epileptogenic zone. Precise analysis of the localization of the interictal activities (especially within the framework of extra-temporal epilepsies) based on source localization methods, makes it possible to put forth assumptions on the localization of the irritative zone.

[The "epileptogenic zone" in humans: representation of intercritical events by spatio-temporal maps]. / La "zone épileptogène" chez l'homme: représentation des événements intercritiques par cartes spatio-temporelles.

In the preoperative investigation of partial epilepsies, electrical characteristics of the so-called epileptogenic area are of critical interest to localize this area. We have always emphasized that the analysis of ictal events themselves, is more valuable than that of inter-ictal anomalis. One reason for this emphasis has been the absence of a reliable method to evaluate the relationship between the topography of ictal and interictal events. An technique for imaging an intracerebral potential field is reported. It allows to analyse the spatio-temporal distribution of interictal events recorded during the SEEG exploration. This technique applied to an illustrative patient shows that the temporo-spatial distribution of interictal spikes is related to that of the ictal discharge itself. A new hypothesis concerning the build up of an epileptogenic area in man is presented.

[Cortical mechanisms of auditive perception in man: contribution of cerebral potentials and evoked magnetic fields by auditive stimulations]. / Etude des mécanismes corticaux de la perception auditive chez l'homme: apport des potentiels intracérébraux et des champs magnétiques évoqués par les stimulations auditives.

The goal of this study is to determine and localize the generators of different components of middle latency auditory evoked potentials (MLAEPs) through intracerebral recordings in auditory cortex in Human (Heschl's gyrus and Planum Temporale). The intracerebral data show that the generators of components at 30, 50, 60 and 75 msec latency are distributed medio-laterally along the Heschl's gyrus. The 30 msec component is generated in the dorso-postero-medial part of the Heschl's gyrus (primary area) and the 50 msec component is generated laterally in the primary area. The generators of the later components (60-75 msec) are localized in the lateral part of the Heschl's gyrus that are the secondary areas. The comparison with the generators of the components of the magnetic auditory evoked field and the tonotopic organization of the auditory cortex are discussed.

Modeling and interpretation of scalp-EEG and depth-EEG signals during interictal activity.

In epileptic patients candidate to surgery, the interpretation of electrophysiological signals recorded invasively (depth-EEG) and non-invasively (scalp-EEG) is a crucial issue to determine epileptogenic network and to define subsequent therapeutic strategy. This issue is addressed in this work through realistic modeling of both scalp-EEG and depth-EEG signals. The model allows for studying the influence, on signals, of source-related parameters leading to the generation of epileptic transient activity (interictal spikes). This parametric study is based on a variety of scenarios in which either spatial or temporal features of the sources of activity are modified. Statistical quantities measured on simulated signals allow for better understanding of the influence of source-related parameters on the information conveyed by these signals, collected from scalp or depth electrodes.

A realistic spatiotemporal source model for EEG activity: application to the reconstruction of epileptic depth-EEG signals.

The context of this work is the interpretation of depth-EEG signals recorded in epileptic patients. This study focuses on the relationship between spatial and temporal properties of neuronal sources and depth-EEG signals observed along intracerebral electrodes (source/sensor relationship). We developed an extended source model which connects two levels of representation: a model of coupled neuronal populations and a distributed current dipole model. This model was used to simulate epileptic spiking depth-EEG signals from the forward solution at each intracerebral sensor location. Results showed that realistic spikes were obtained in the model under two specific conditions: a sufficiently large spatial extension of the neocortical source and a high degree of coupling between activated neuronal populations composing this extended source.

Segmentation of depth-EEG seizure signals: method based on a physiological parameter and comparative study.

The analysis of stereoelectroencephalographic (intracerebral recording) signals provides information on the electrical activity of brain structures implied in epileptic seizures. A simple nonparametric adaptive segmentation method, based on a physiologically relevant parameter, is presented and compared with three methods reported in the literature. The comparative frame allows us to objectively test methods for their performances on the same basis. Results show that the proposed method is robust with respect to the types of change studied and easier to conduct, even if it is less accurate about the estimation of instants of change than another method presented in this study. Signals are segmented throughout the duration of seizures without parameter readjustment and generate instants of change in accordance with those interactively delimited by the clinician.