Magnetoencephalographic yield of interictal spikes in temporal lobe epilepsy. Comparison with scalp EEG recordings

To compare magnetoencephalography (MEG) with scalp electroencephalography (EEG) in the detection of interictal spikes in temporal lobe epilepsy (TLE), we simultaneously recorded MEG and scalp EEG with a whole-scalp neuromagnetometer in 46 TLE patients. We visually searched interictal spikes on MEG and EEG channels and classified them into three types according to their presentation on MEG alone (M-spikes), EEG alone (E-spikes), or concomitantly on both modalities (M/E-spikes). The M-spikes and M/E-spikes were localized with MEG equivalent current dipole modeling. We analyzed the relative contribution of MEG and EEG in the overall yield of spike detection and also compared M-spikes with M/E-spikes in terms of dipole locations and strengths. During the 30- to 40-min MEG recordings, interictal spikes were obtained in 36 (78.3%) of the 46 patients. Among the 36 patients, most spikes were M/E-spikes (68.3%), some were M-spikes (22.1%), and some were E-spikes (9.7%). In comparison with EEG, MEG gave better spike yield in patients with lateral TLE. Sources of M/E- and M-spikes were situated in the same anatomical regions, whereas the average dipole strength was larger for M/E- than M-spikes. In conclusion, some interictal spikes appeared selectively on either MEG or EEG channels in TLE patients although more spikes were simultaneously identified on both modalities. Thus, simultaneous MEG and EEG recordings help to enhance spike detection. Identification of M-spikes would offer important localization of irritative foci, especially in patients with lateral TLE.     

Combined MEG/EEG analysis of the interictal spike complex in mesial temporal lobe epilepsy

We studied the functional organization of the interictal spike complex in 30 patients with mesial temporal lobe epilepsy (MTLE) using combined magnetoencephalography (MEG)/electroencephalography (EEG) recordings. Spikes could be recorded in 14 patients (47%) during the 2- to 3-h MEG/EEG recording session. The MEG and EEG spikes were subjected to separate dipole analyses; the MEG spike dipole localizations were superimposed on MRI scans. All spike dipoles could be localized to the temporal lobe with a clear preponderance in the medial region. Based on dipole orientations in MEG, patients could be classified into two groups: patients with anterior medial vertical (AMV) dipoles, suggesting epileptic activity in the mediobasal temporal lobe and patients with anterior medial horizontal (AMH) dipoles, indicating involvement of the temporal pole and the anterior parts of the lateral temporal lobe. Whereas patients with AMV dipoles had strictly unitemporal interictal and ictal EEG changes during prolonged video-EEG monitoring, 50% of patients with AMH dipoles showed evidence of bitemporal affection on interictal and ictal EEG. Nine patients underwent epilepsy surgery so far. Whereas all five patients with AMV dipoles became completely seizure-free postoperatively (Class Ia), two out of four patients with AMH dipoles experienced persistent auras (Class Ib). This difference, however, was not statistically significant. We therefore conclude that combined MEG/EEG dipole modeling can identify subcompartments of the temporal lobe involved in epileptic activity and may be helpful to differentiate between subtypes of mesial temporal lobe epilepsy noninvasively.     

Localization of abnormal discharges causing insular epilepsy by magnetoencephalography

The insula, one of the five cerebral lobes of the brain, is located deep within the brain and lies mainly beneath the temporal lobe. Insular epilepsy can be easily confused and misdiagnosed as temporal lobe epilepsy (TLE) because of the similar clinical symptoms and scalp electroencephalography (EEG) findings due to the insula location and neuronal connections with the temporal lobe. Magnetoencephalography (MEG) has higher sensitivity and spatial resolution than scalp EEG, and thus can often identify epileptic discharges not revealed by scalp EEG. Simultaneous scalp EEG and MEG were performed to detect and localize epileptic discharges in two patients known to have insular epilepsy associated with cavernous angioma in the insula. Epileptic discharges were detected as abnormal spikes in the EEG and MEG findings. In Patient 1, the sources of all MEG spikes detected simultaneously by EEG and MEG (E/M-spikes) were localized in the anterior temporal lobe, similar to TLE. In contrast, the sources of all MEG spikes detected only by MEG (M-spikes) were adjacent to the insular lesion. In Patient 2, the sources of all MEG spikes detected simultaneously by EEG and MEG (E/M-spikes) were localized in the anterior temporal lobe. These findings indicate that MEG allows us to detect insular activity that is undetectable by scalp EEG. In conclusion, simultaneous EEG and MEG are helpful for detecting spikes and obtaining additional information about the epileptic origin and propagation in patients with insular epilepsy.     

Opercular to interhemispheric source distribution of benign rolandic spikes of childhood

We evaluated the source distribution of benign rolandic spikes of childhood along and across the central sulcus in 15 patients, aged between 7 and 15 years, who suffered from seizure disorders. Previous routine EEG showed centrotemporal spikes, but none of them had major abnormalities on brain magnetic resonance imaging or neurological deficits. The equivalent current dipoles (ECDs) of the spikes measured by whole-head magnetoencephalography (MEG) were compared to the spike distributions detected by simultaneous scalp EEG according to the international 10-20 system. Locations and orientations of the MEG spikes corresponded to the EEG spike distribution as follows: superiorly oriented spike MEG dipoles in the opercular area corresponded to T3/4 negative peaks (8 spike groups in 6 patients); anteriorly oriented spike dipoles in the rolandic area corresponded to C3/4 or P3/4 negative peaks (17 spike groups in 13 patients); laterally oriented spike dipoles in the interhemispheric area corresponded to Cz/Pz negative peaks (4 spike groups in 3 patients); and others (4 spike groups in 4 patients). Rolandic spikes include three main types according to the ECD location from the opercular to the interhemispheric areas. The functional anatomy of benign rolandic spikes was correlated with partial seizure semiology. All three rolandic spike types can be explained by a precentral origin, assuming that the surface negative potential is continuous from the gyral to fissural cortices.     

The saccadic spike artifact in MEG

Electro- and magnetoencephalography (EEG/MEG) are the means to investigate the dynamics of neuronal activity non-invasively in the human brain. However, both EEG and MEG are also sensitive to non-neural sources, which can severely complicate the interpretation. The saccadic spike potential (SP) at saccade onset has been identified as a particularly problematic artifact in EEG because it closely resembles synchronous neuronal gamma band activity. While the SP and its confounding effects on EEG have been thoroughly characterized, the corresponding artifact in MEG, the saccadic spike field (SF), has not been investigated. Here we provide a detailed characterization of the SF. We simultaneously recorded MEG, EEG, gaze position and electrooculogram (EOG). We compared the SF in MEG for different saccade sizes and directions and contrasted it with the well-known SP in EEG. Our results reveal a saccade amplitude and direction dependent, lateralized saccadic spike artifact, which was most prominent in the gamma frequency range. The SF was strongest at frontal and temporal sensors but unlike the SP in EEG did not contaminate parietal sensors. Furthermore, we observed that the source configurations of the SF were comparable for regular and miniature saccades. Using distributed source analysis we identified the sources of the SF in the extraocular muscles. In summary, our results show that the SF in MEG closely resembles neuronal activity in frontal and temporal sensors. Our detailed characterization of the SF constitutes a solid basis for assessing possible saccadic spike related contamination in MEG experiments.     

Spatial intralobar correlation of spike and slow wave activity localisations in focal epilepsies: a MEG analysis

12 patients with focal epilepsy were examined by magnetoencephalography (MEG). Source localisations of interictal epileptiform activity (spikes) yielded clear results. Slow wave dipole density in the frequency range from 2 to 6 Hz, using time selections from an automatic principal component analysis (PCA), was calculated. Results of spike and slow wave dipole density localisations were superimposed on MR-images of each patient. Slow wave dipole densities were increased close to spike localisations. Distances between spike center of mass and slow wave maxima were calculated, average mean distance was 2.0 cm. Independant of the localisation in either TLE or ETLE a concordance of slow wave and spike localisations were found. Slow wave localisations were found in patients with lesions in MRI and patients with no abnormalities on the MRI. In comparison to healthy subjects, slow wave dipole density in patients with epilepsy was clearly increased. The localisation of slow wave dipole density yielded additional important information and may contribute to defining the irritative zone.     

Epilepsy surgery, resection volume and MSI localization in lesional frontal lobe epilepsy

To verify whether interictal noninvasive information detected by magnetoencephalography (MEG) recordings can contribute to localize focal epileptic activity relevant for seizure generation in lesional frontal lobe epilepsy, magnetic source imaging (MSI) localizations of epileptic discharges were compared to the extent of neurosurgical resection and postoperative outcome. Preoperative MEG spike localizations were displayed in postoperative magnetic resonance imaging (MRI) scans to check whether dipole sites were located within the resection cavity. Moreover, MEG localizations were compared with results of prolonged video-EEG monitoring and, in three cases, with invasive EEG recordings. Our results in five cases with lesional frontal lobe epilepsy showed that good surgical outcome could be achieved in those patients where the majority of MEG spike localizations were located within the resected brain volume.     

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.     

Localization of interictal delta and epileptiform EEG activity associated with focal epileptogenic brain lesions

The present study was aimed at investigating the accuracy of electric source reconstruction in the presurgical evaluation of epilepsy patients. Spontaneous EEG activity of 14 patients with focal intracerebral epileptogenic lesions was analyzed by source reconstruction based on high-resolution EEG (64-channel system) and a boundary element method head model accounting for the individual head anatomy. Equivalent dipole modeling was applied to focal delta and interictal epileptiform activity. The localization results were validated quantitatively by comparison with the sites of the structural lesions. In 6 of 9 patients with focal delta activity, the maximum of dipole concentration was closer than 10 mm to the nearest lesion margin and mostly at the border or within pathologically altered cortical tissue. In all 11 patients showing interictal epileptiform activity, the localization results were found in the same lobe as the lesion. In almost half of them, they were closer than 10 mm to the lesion margin. Patients with larger distances (22-36 mm) mostly had hippocampal atrophy or sclerosis. Their dipole locations did not appear in the affected hippocampus, but in the adjacent temporal neocortex. In conclusion, electric source reconstruction applied to both abnormal slow and interictal epileptiform EEG activity seems to be a valuable additional noninvasive component in the multimodal presurgical evaluation of epilepsy patients.     

联合磁源性影像和磁共振波谱技术评估颞叶癫痫的价值

目的：探讨磁源性成像（MSI）和磁共振波谱（^1H—MRS）技术结合在颞叶癫痫诊断定位中的价值。方法：设健康对照者10例，特发颞叶癫痫患者8例，应用MEG定位痫性病灶，选取MEG异常区域、对侧相应区域和双颞叶内侧区域测量NAA／Cho值，并观察是否存在海马硬化。结果：8例患者MEG检查结果均异常，6例MEG异常相应区域MRS检查NAA／Cho值减少，符合率为62．5％；MRI显示海马硬化2例，MRI正常6例，颞叶内侧MRS扫描未见明显改变。结论：联合MSI和MRS技术可进一步提高颞叶癫痫致痫灶的定位准确性。     

Fast oscillations associated with interictal spikes localize the epileptogenic zone in patients with partial epilepsy

Although interictal epileptic spikes are defined as fast transient activity, the spatial distribution of spike-related high-frequency power changes is unknown. In this study, we localized the sources of spike-locked power increases in the beta and gamma band with magnetoencephalography and an adaptive spatial filtering technique and tested the usefulness of these reconstructions for determining the epileptogenic zone in a population of 27 consecutive presurgical patients with medication refractory partial epilepsies. The reliability of this approach was compared to the performance of conventional MEG techniques such as equivalent current dipole (ECD) models. In patients with good surgical outcome after a mean follow-up time of 16 months (Engel class I or II), the surgically resected area was identified with an accuracy of 85% by sources of spike-locked beta/gamma activity, which compared favorably with the accuracy of 69% found for ECD models of single spikes. In patients with a total of more than 50 spikes in their recordings, the accuracies increased to 100% vs. 88%, respectively. Imaging of spike-locked beta/gamma power changes therefore seems to be a reliable and fast alternative to conventional MEG techniques for localizing epileptogenic tissue, in particular, if more than 50 interictal spikes can be recorded.     

Comparison of magnetoencephalographic spikes with and without concurrent electroencephalographic spikes in extratemporal epilepsy

Interictal spikes in patients with epilepsy may be detected by either electroencephalography (EEG) (E-spikes) or magnetoencephalography (MEG) (M-spikes), or both MEG and EEG (E/M-spikes). Localization and amplitude were compared between E/M-spikes and M-spikes in 7 adult patients with extratemporal epilepsy to evaluate the clinical significance of MEG spikes. MEG and EEG were simultaneously measured using a helmet-shaped MEG system with planar-type gradiometers and scalp electrodes of the international 10-20 system. Sources of E/M-spikes and M-spikes were estimated by an equivalent current dipole (ECD) model for MEG at peak latency. Each subject showed 9 to 20 (mean 13.4) E/M-spikes and 9 to 31 (mean 16.3) M-spikes. No subjects showed significant differences in the ECD locations between E/M- and M-spikes. ECD moments of the E/M-spikes were significantly larger in 2 patients and not significantly different in the other 5 patients. The similar localizations of E/M-spikes and M-spikes suggest that combination of MEG and EEG is useful to detect more interictal spikes in patients with extratemporal epilepsy. The smaller tendency of ECD amplitude of the M-spikes than E/M-spikes suggests that scalp EEG may overlook small tangential spikes due to background brain noise. Localization value of M-spikes is clinically equivalent to that of E/M-spikes.     

单侧海马硬化颞叶癫痫患者头皮脑电图发作间期棘波频率与手术疗效的关系

目的:评估单侧海马硬化的颞叶癫痫患者头皮脑电图发作间期棘波(interictal spike,IEDs)频率与手术疗效的关系。方法:回顾性分析33例单侧海马硬化的颞叶癫痫患者头皮脑电图,随机抽取手术前1h清醒期脑电图分析其IEDs频率和分布,并据此将患者分为2类:(1)IEDs高频组和IEDs低频组;(2)IEDs单侧颞叶组和IEDs双侧颞叶组。患者经1年以上随访统计预后。用Fisher确切检验法、广义线性模型分析IEDs频率与手术疗效的关系。结果:IEDs低频组17例,其中16例(94.1%)术后发作消失;IEDs高频组16例,其中10例(62.5%)术后发作消失,两组间疗效差异存在显著性(P=0.039)。患者先兆和全面性发作的存在、病程与患者IEDs频率正相关。结论:单侧海马硬化颞叶癫痫患者清醒期IEDs频率高预示手术疗效不良。     

Source cancellation profiles of electroencephalography and magnetoencephalography

Recorded electric potentials and magnetic fields due to cortical electrical activity have spatial spread even if their underlying brain sources are focal. Consequently, as a result of source cancellation, loss in signal amplitude and reduction in the effective signal-to-noise ratio can be expected when distributed sources are active simultaneously. Here we investigate the cancellation effects of EEG and MEG through the use of an anatomically correct forward model based on structural MRI acquired from 7 healthy adults. A boundary element model (BEM) with four compartments (brain, cerebrospinal fluid, skull and scalp) and highly accurate cortical meshes (~ 300,000 vertices) were generated. Distributed source activations were simulated using contiguous patches of active dipoles. To investigate cancellation effects in both EEG and MEG, quantitative indices were defined (source enhancement, cortical orientation disparity) and computed for varying values of the patch radius as well as for automatically parcellated gyri and sulci. Results were calculated for each cortical location, averaged over all subjects using a probabilistic atlas, and quantitatively compared between MEG and EEG. As expected, MEG sensors were found to be maximally sensitive to signals due to sources tangential to the scalp, and minimally sensitive to radial sources. Compared to EEG, however, MEG was found to be much more sensitive to signals generated antero-medially, notably in the anterior cingulate gyrus. Given that sources of activation cancel each other according to the orientation disparity of the cortex, this study provides useful methods and results for quantifying the effect of source orientation disparity upon source cancellation.     

Usefulness of MEG magnetometer for spike detection in patients with mesial temporal epileptic focus

The present study investigated the sensitivity of magnetoencephalography (MEG) for spikes depending on sensor type in patients with mesial temporal epileptic focus. We recorded MEG in 6 patients with mesial temporal epileptic focus using two sensor types (magnetometer and gradiometer) simultaneously. The number of spikes detected and the corresponding equivalent current dipole (ECD) parameters (distance from the coordinated head center (radius), and dipole moment) were evaluated with respect to sensor type. Among 426 MEG 'consensus spikes' determined by 3 reviewers, 378 spikes satisfied the predetermined criteria for source localization. Comparing ECD parameters, spikes detected by magnetometer alone displayed a smaller radius and larger dipole moment than those detected by gradiometer alone. Spikes estimated in the mesial temporal area were more frequently detected by magnetometer alone (38.5%) than by gradiometer alone (11.5%), whereas spikes in the lateral temporal area were detected less by magnetometer alone (3.7%) than by gradiometer alone (53.9%). The present results suggest that a magnetometer is advantageous for spike detection in patients with mesial temporal epileptic focus. This also implies the higher sensitivity of magnetometer for deep sources.     

BOLD correlates of continuously fluctuating epileptic activity isolated by independent component analysis

Combined EEG/fMRI recordings offer a promising opportunity to detect brain areas with altered BOLD signal during interictal epileptic discharges (IEDs). These areas are likely to represent the irritative zone, which is itself a reflection of the epileptogenic zone. This paper reports on the imaging findings using independent component analysis (ICA) to continuously quantify epileptiform activity in simultaneously acquired EEG and fMRI. Using ICA derived factors coding for the epileptic activity takes into account that epileptic activity is continuously fluctuating with each spike differing in amplitude, duration and maybe topography, including subthreshold epileptic activity besides clear IEDs and may thus increase the sensitivity and statistical power of combined EEG/fMRI in epilepsy. Twenty patients with different types of focal and generalized epilepsy syndromes were investigated. ICA separated epileptiform activity from normal physiological brain activity and artifacts. In 16/20 patients, BOLD correlates of epileptic activity matched the EEG sources, the clinical semiology, and, if present, the structural lesions. In clinically equivocal cases, the BOLD correlates aided to attribute proper diagnosis of the underlying epilepsy syndrome. Furthermore, in one patient with temporal lobe epilepsy, BOLD correlates of rhythmic delta activity could be employed to delineate the affected hippocampus. Compared to BOLD correlates of manually identified IEDs, the sensitivity was improved from 50% (10/20) to 80%. The ICA EEG/fMRI approach is a safe, non-invasive and easily applicable technique, which can be used to identify regions with altered hemodynamic effects related to IEDs as well as intermittent rhythmic discharges in different types of epilepsy.     

Geometrical interpretation of fMRI-guided MEG/EEG inverse estimates

Magneto- and electroencephalography (MEG/EEG) and functional magnetic resonance imaging (fMRI) provide complementary information about the functional organization of the human brain. An important advantage of MEG/EEG is the millisecond time resolution in detecting electrical activity in the cerebral cortex. The interpretation of MEG/EEG signals, however, is limited by the difficulty of determining the spatial distribution of the neural activity. Functional MRI can help in the MEG/EEG source analysis by suggesting likely locations of activity. We present a geometric interpretation of fMRI-guided inverse solutions in which the MEG/EEG source estimate minimizes a distance to a subspace defined by the fMRI data. In this subspace regularization (SSR) approach, the fMRI bias does not assume preferred amplitudes for MEG/EEG sources, only locations. Characteristic dependence of the source estimates on the regularization parameters is illustrated with simulations. When the fMRI locations match the true MEG/EEG source locations, they serve to bias the underdetermined MEG/EEG inverse solution toward the fMRI loci. Importantly, when the fMRI loci do not match the true MEG/EEG loci, the solution is insensitive to those fMRI loci.     

Continuous EEG source imaging enhances analysis of EEG-fMRI in focal epilepsy

IntroductionEEG-correlated fMRI (EEG-fMRI) studies can reveal haemodynamic changes associated with Interictal Epileptic Discharges (IED). Methodological improvements are needed to increase sensitivity and specificity for localising the epileptogenic zone. We investigated whether the estimated EEG source activity improved models of the BOLD changes in EEG-fMRI data, compared to conventional « event-related » designs based solely on the visual identification of IED.MethodsTen patients with pharmaco-resistant focal epilepsy underwent EEG-fMRI. EEG Source Imaging (ESI) was performed on intra-fMRI averaged IED to identify the irritative zone. The continuous activity of this estimated IED source (cESI) over the entire recording was used for fMRI analysis (cESI model). The maps of BOLD signal changes explained by cESI were compared to results of the conventional IED-related model.ResultsESI was concordant with non-invasive data in 13/15 different types of IED. The cESI model explained significant additional BOLD variance in regions concordant with video-EEG, structural MRI or, when available, intracranial EEG in 10/15 IED. The cESI model allowed better detection of the BOLD cluster, concordant with intracranial EEG in 4/7 IED, compared to the IED model. In 4 IED types, cESI-related BOLD signal changes were diffuse with a pattern suggestive of contamination of the source signal by artefacts, notably incompletely corrected motion and pulse artefact. In one IED type, there was no significant BOLD change with either model.ConclusionContinuous EEG source imaging can improve the modelling of BOLD changes related to interictal epileptic activity and this may enhance the localisation of the irritative zone.     

A probabilistic algorithm integrating source localization and noise suppression for MEG and EEG data

We have developed a novel probabilistic model that estimates neural source activity measured by MEG and EEG data while suppressing the effect of interference and noise sources. The model estimates contributions to sensor data from evoked sources, interference sources and sensor noise using Bayesian methods and by exploiting knowledge about their timing and spatial covariance properties. Full posterior distributions are computed rather than just the MAP estimates. In simulation, the algorithm can accurately localize and estimate the time courses of several simultaneously active dipoles, with rotating or fixed orientation, at noise levels typical for averaged MEG data. The algorithm even performs reasonably at noise levels typical of an average of just a few trials. The algorithm is superior to beamforming techniques, which we show to be an approximation to our graphical model, in estimation of temporally correlated sources. Success of this algorithm using MEG data for localizing bilateral auditory cortex, low-SNR somatosensory activations, and for localizing an epileptic spike source are also demonstrated.