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.     

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.     

BOLD changes occur prior to epileptic spikes seen on scalp EEG

This study examined BOLD changes prior to interictal discharges in the EEG of patients with epilepsy. From a database of 143 EEG-fMRI studies, we selected the 16 data sets that showed both strong fMRI activation in the original analysis and only a single spike type in the EEG. Scans were then analyzed using seven model HRFs, peaking 3 or 1 s before the event, or 1, 3, 5, 7, or 9 s after it. An HRF was calculated using a deconvolution method for all activations seen in each analysis. The results showed that seven data sets had HRFs that peaked 1 s after the event or earlier, indicating a BOLD change starting prior to the spike seen on the scalp EEG. This is surprising since the BOLD change is expected to result from the spike. For most of the data sets with early peaking HRFs, the maximum activation in all of the statistical maps was when the model HRF peaked 1 s after the event, suggesting that the early activation was at least as important as any later activation. We suggest that this early activity is the result of neuronal changes occurring several seconds prior to a surface EEG event, but that these changes are not visible on the scalp. This is the first report of a BOLD response occurring several seconds prior to an interictal event seen on the scalp and could have important implications for our understanding of the generation of epileptic discharges.     

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.     

Resting functional MRI with temporal clustering analysis for localization of epileptic activity without EEG

We report on the methods and initial findings of a novel noninvasive technique, resting functional magnetic resonance imaging (fMRI) with temporal clustering analysis (TCA), for localizing interictal epileptic activity. Nine subjects were studied including six temporal lobe epilepsy (TLE) patients with confirmed localization indicated by successful seizure control after resection. The remaining three subjects had standard presurgical evaluations with inconsistent results or suspected extratemporal lobe foci. Peaks of activity, presumably epileptic, were detected in all nine subjects, using the resting functional MRI with temporal clustering analysis. In all six patients who underwent resective surgery, the fMRI with temporal clustering analysis accurately determined the epileptogenic hippocampal hemisphere (P = 0.005). In the three subjects without confirmed localization, the technique determined regions of activity consistent with those determined by the presurgical assessments. Though more studies are required to validate this technique, the results demonstrate the potential of the resting fMRI with temporal clustering technique to detect and localize epileptic activity without the need for simultaneous electroencephalography (EEG). The greatest potential benefit of this technique will be in the evaluation of patients with suspected extratemporal lobe epilepsy and patients whose standard assessments are discordant.     

Simultaneous intracranial EEG-fMRI in humans: Protocol considerations and data quality

We have recently performed simultaneous intracranial EEG and fMRI recordings (icEEG-fMRI) in patients with epilepsy. In this technical note, we examine limited thermometric data for potential electrode heating during our protocol and found that heating was ≤0.1°C in-vitro at least 10 fold less than in-vivo limits. We quantify EEG quality, which can be degraded by MRI scanner-induced artefacts, and fMRI image (gradient echo echo-planar imaging: GE-EPI) signal quality around the electrodes, which can be degraded by electrode interactions with B1 (radiofrequency) and B0 (static) magnetic fields. We recorded EEG outside and within the MRI scanner with and without scanning. EEG quality was largely preserved during scanning and in particular heartbeat-related artefacts were small compared to epileptic events. To assess the GE-EPI signal reduction around the electrodes, we compared image signal intensity along paths into the brain normal to its surface originating from the individual platinum-iridium electrode contacts. GE-EPI images were obtained at 1.5T with an echo time (TE) of 40ms and repetition time (TR) of 3000ms and a slice thickness of 2.5mm. We found that GE-EPI signal intensity reduction was confined to a 10mm radius and that it was reduced on average by less than 50% at 5mm from the electrode contacts. The GE-EPI image signal reduction also varied with electrode orientation relative to the MRI scanner axes; in particular, cortical grid contacts with a normal along the scanner's main magnetic field (B(0)) axis have higher artefact levels relative to those with a normal perpendicular to the z-axis. This suggests that the artefacts were predominantly susceptibility-related rather than due to B1 interactions. This information can be used to guide interpretation of results of icEEG-fMRI experiments proximal to the electrodes, and to optimise artefact reduction strategies.     

磁源性影像对癫痫灶定位的临床应用 ——与VEEG、ECoG比较

目的:探讨磁源性影像在癫痫灶定位中的应用价值。方法:20例难治性癫痫患者,男15例,女5例,手术前均行视频脑电图(Video-Electroencephalography,VEEG)、MRI及脑磁图(Magnetoencephalography,MEG)检查。将MEG所得的电生理资料与MRI所获得的解剖结构资料叠加,形成磁源性影像(magnetic source imaging,MSI)。所有患者手术均在MSI指导下进行术中皮层脑电图(Electrocorticography,ECoG)监测。结果:20例患者MSI与VEEG符合率为50%,与ECoG符合率为70%,术后(3~20月)随访16例患者疗效满意。结论:MSI是难治性癫痫患者手术前无创伤性癫痫灶精确定位方法。     

Anisotropic partial volume CSF modeling for EEG source localization

Electromagnetic source localization (ESL) provides non-invasive evaluation of brain electrical activity for neurology research and clinical evaluation of neurological disorders such as epilepsy. Accurate ESL results are dependent upon the use of patient specific models of bioelectric conductivity. While the effects of anisotropic conductivities in the skull and white matter have been previously studied, little attention has been paid to the accurate modeling of the highly conductive cerebrospinal fluid (CSF) region. This study examines the effect that partial volume errors in CSF segmentations have upon the ESL bioelectric model. These errors arise when segmenting sulcal channels whose widths are similar to the resolution of the magnetic resonance (MR) images used for segmentation, as some voxels containing both CSF and gray matter cannot be definitively assigned a single label. These problems, particularly prevalent in pediatric populations, make voxelwise segmentation of CSF compartments a difficult problem. Given the high conductivity of CSF, errors in modeling this region may result in large errors in the bioelectric model. We introduce here a new approach for using estimates of partial volume fractions in the construction of patient specific bioelectric models. In regions where partial volume errors are expected, we use a layered gray matter-CSF model to construct equivalent anisotropic conductivity tensors. This allows us to account for the inhomogeneity of the tissue within each voxel. Using this approach, we are able to reduce the error in the resulting bioelectric models, as evaluated against a known high resolution model. Additionally, this model permits us to evaluate the effects of sulci modeling errors and quantify the mean error as a function of the change in sulci width. Our results suggest that both under and over-estimation of the CSF region leads to significant errors in the bioelectric model. While a model with fixed partial volume fraction is able to reduce this error, we see the largest improvement when using voxel specific partial volume estimates. Our cross-model analyses suggest that an approximately linear relationship exists between sulci error and the error in the resulting bioelectric model. Given the difficulty of accurately segmenting narrow sulcal channels, this suggests that our approach may be capable of improving the accuracy of patient specific bioelectric models by several percent, while introducing only minimal additional computational requirements.     

Feasibility of simultaneous intracranial EEG-fMRI in humans: A safety study

In epilepsy patients who have electrodes implanted in their brains as part of their pre-surgical assessment, simultaneous intracranial EEG and fMRI (icEEG-fMRI) may provide important localising information and improve understanding of the underlying neuropathology. However, patient safety during icEEG-fMRI has not been addressed.Here the potential health hazards associated with icEEG-fMRI were evaluated theoretically and the main risks identified as: mechanical forces on electrodes from transient magnetic effects, tissue heating due to interaction with the pulsed RF fields and tissue stimulation due to interactions with the switched magnetic gradient fields. These potential hazards were examined experimentally in vitro on a Siemens 3 T Trio, 1.5 T Avanto and a GE 3 T Signa Excite scanner using a Brain Products MR compatible EEG system.No electrode flexion was observed. Temperature measurements demonstrated that heating well above guideline limits can occur. However heating could be kept within safe limits (< 1.0 °C) by using a head transmit RF coil, ensuring EEG cable placement to exit the RF coil along its central z-axis, using specific EEG cable lengths and limiting MRI sequence specific absorption rates (SARs). We found that the risk of tissue damage due to RF-induced heating is low provided implant and scanner specific SAR limits are observed with a safety margin used to account for uncertainties (e.g. in scanner-reported SAR). The observed scanner gradient switching induced current (0.08 mA) and charge density (0.2 μC/cm²) were well within safety limits (0.5 mA and 30 μC/cm², respectively). Site-specific testing and a conservative approach to safety are required to avoid the risk of adverse events.     

Dynamic Causal Modelling of epileptic seizure propagation pathways: a combined EEG-fMRI study

Simultaneous EEG-fMRI offers the possibility of non-invasively studying the spatiotemporal dynamics of epileptic activity propagation from the focus towards an extended brain network, through the identification of the haemodynamic correlates of ictal electrical discharges. In epilepsy associated with hypothalamic hamartomas (HH), seizures are known to originate in the HH but different propagation pathways have been proposed. Here, Dynamic Causal Modelling (DCM) was employed to estimate the seizure propagation pathway from fMRI data recorded in a HH patient, by testing a set of clinically plausible network connectivity models of discharge propagation. The model consistent with early propagation from the HH to the temporal-occipital lobe followed by the frontal lobe was selected as the most likely model to explain the data. Our results demonstrate the applicability of DCM to investigate patient-specific effective connectivity in epileptic networks identified with EEG-fMRI. In this way, it is possible to study the propagation pathway of seizure activity, which has potentially great impact in the decision of the surgical approach for epilepsy treatment.     

伴中央-颞区棘波的儿童良性癫痫临床与脑电图分析

目的 探讨伴中央颞区棘波儿童良性癫痫（benign ctfildhood epilepsy with centro-temporal spikes，BECT）的临床特点、脑电图（EEG）改变及预后情况。方法 采用数字视频脑电图仪和动态脑电监测，对31例BECT患儿进行清醒和睡眠脑电图描记，结合临床表现及影像学资料进行随访分析。结果 本组发病年龄为2．5岁-14岁，其中5—10岁发病24例（占77．42％），发作均与睡眠有关，2例发病后有语言障碍。发作间期EEG背景波正常，在一侧或双侧中央区和中颞区出现负性、双向或多向的棘波或尖波，或棘慢综合波，入睡后放电频率明显增加。影像学检查有1例侧脑室扩大，其余正常。结论 BECT多见于5—10岁儿童，临床发作与睡眠密切相关，EEG有特征性改变，表现为一侧或双侧中央和／或中颞区有尖波、棘波或棘慢综合波发放。抗癫痫药物治疗有效，大部分预后良好，2例有认知功能障碍。     

Evaluation of different cortical source localization methods using simulated and experimental EEG data

Different cortical source localization methods have been developed to directly link the scalp potentials with the cortical activities. Up to now, these methods are the only possible solution to noninvasively investigate cortical activities with both high spatial and time resolutions. However, the application of these methods is hindered by the fact that they have not been rigorously evaluated nor compared. In this paper, the performances of several source localization methods (moving dipoles, minimum Lp norm, and low resolution tomography (LRT) with Lp norm, p equal to 1, 1.5, and 2) were evaluated by using simulated scalp EEG data, scalp somatosensory evoked potentials (SEPs), and upper limb motor-related potentials (MRPs) obtained on human subjects (all with 163 scalp electrodes). By using simulated EEG data, we first evaluated the source localization ability of the above methods quantitatively. Subsequently, the performance of the various methods was evaluated qualitatively by using experimental SEPs and MRPs. Our results show that the overall LRT Lp norm method with p equal to 1 has a better source localization ability than any of the other investigated methods and provides physiologically meaningful reconstruction results. Our evaluation results provide useful information for choosing cortical source localization approaches for future EEG/MEG studies.     

伴中央颞区棘波儿童良性癫痫的脑电图分析

目的探讨伴中央颞区棘波儿童良性癫痫(BECT)患儿的脑电图特征和临床意义。方法选择2013年6月至2014年7月BECT患儿22例,分析其脑电图表现及发作时间。结果 22例全部在睡眠中出现癫痫样波,在清醒描记时出现15例;癫痫样波仅出现在中央和(或)颞区者17例,除见于中央、颞区外亦散在性出现于其他脑区者5例;左侧中央颞区明显者9例,右侧中央颞区明显者8例;晚上睡眠发作者10例,中午睡眠发作2例,晨起觉醒前发作者2例,晚上和觉醒前均有发作者8例。结论 BECT是一种特殊癫痫综合征,预后良好,认识其临床和EEG演变的特点及规律可提高对BECT的检出率。     

Systematic regularization of linear inverse solutions of the EEG source localization problem

Distributed linear solutions of the EEG source localization problem are used routinely. Here we describe an approach based on the weighted minimum norm method that imposes constraints using anatomical and physiological information derived from other imaging modalities to regularize the solution. In this approach the hyperparameters controlling the degree of regularization are estimated using restricted maximum likelihood (ReML). EEG data are always contaminated by noise, e.g., exogenous noise and background brain activity. The conditional expectation of the source distribution, given the data, is attained by carefully balancing the minimization of the residuals induced by noise and the improbability of the estimates as determined by their priors. This balance is specified by hyperparameters that control the relative importance of fitting and conforming to prior constraints. Here we introduce a systematic approach to this regularization problem, in the context of a linear observation model we have described previously. In this model, basis functions are extracted to reduce the solution space a priori in the spatial and temporal domains. The basis sets are motivated by knowledge of the evoked EEG response and information theory. In this paper we focus on an iterative "expectation-maximization" procedure to jointly estimate the conditional expectation of the source distribution and the ReML hyperparameters on which this solution rests. We used simulated data mixed with real EEG noise to explore the behavior of the approach with various source locations, priors, and noise levels. The results enabled us to conclude: (i) Solutions in the space of informed basis functions have a high face and construct validity, in relation to conventional analyses. (ii) The hyperparameters controlling the degree of regularization vary largely with source geometry and noise. The second conclusion speaks to the usefulness of using adaptative ReML hyperparameter estimates.     

癫痫患者与健康人脑电信息熵的对比研究

目的:为了获得癫痫脑电的某些非线性特征,研究了癫痫患者脑电的信息熵,并和健康人脑电的信息熵作比较。方法:采用基于相空间重构脑电信号的新方法来计算脑电信息熵。分别计算了100例癫痫患者和50例健康者的脑电样本。结果:癫痫脑电的平均信息熵为1.696。而健康者脑电的平均信息熵为1.920。值得注意的是,随着嵌入维数的增加,癫痫脑电的信息熵呈现出逐渐减小的趋势,而健康脑电却正好相反,呈现出逐渐增大的趋势。结论:癫痫脑电在低维空间的信息熵比高维空间的大,而健康脑电的情况正好相反。     

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.     

Correspondence between EEG-fMRI and EEG dipole localisation of interictal discharges in focal epilepsy

EEG-fMRI and EEG dipole source localisation are two non-invasive imaging methods that can be applied to the study of the haemodynamic and electrical consequences of epileptic discharges. Using them in combination has the potential to allow imaging with the spatial resolution of fMRI and the temporal resolution of EEG. However, although considerable data are available concerning their concordance in studies involving event-related potentials (ERPs), less is known about how well they agree in epilepsy. To this end, 17 patients were selected from a database of 57 who had undergone an EEG-fMRI scanning session followed by a separate EEG session outside of the scanner. Spatiotemporal dipole modelling was compared with the peak and closest EEG-fMRI activations and deactivations. On average, the dipoles were 58.5 mm from the voxel with the highest positive t value and 32.5 mm from the nearest activated voxel. For deactivations, the corresponding values were 60.8 and 34.0 mm. These values are considerably higher than is generally observed with ERPs, probably as a result of the relatively widespread field, which can lead to artificially deep dipoles, and the occurrence of EEG-fMRI responses remote from the presumed focus of the epileptic activity. The results suggest that EEG and MEG inverse solutions for equivalent current dipole approaches should not be strongly constrained by EEG-fMRI results in epilepsy, and that the use of distributed source modelling will be a more appropriate way of combining EEG-fMRI results with source localisation techniques.     

Ictal localization by source analysis of infraslow activity in DC-coupled scalp EEG recordings

New bedside long-term DC-coupled EEG techniques have demonstrated that infraslow (<0.5 Hz) activity lateralizes temporal lobe seizures (Vanhatalo, S., Holmes, M.D., Tallgren, P., Voipio, J., Kaila, K., Miller, J.W., 2003a. Very slow EEG responses indicate the laterality of temporal lobe seizures: a DC-EEG study. Neurology 60, 1098-1104). However, even high amplitude infraslow activity is difficult to localize by simple visual inspection if there is overlying faster EEG activity or slow artifact. In this study, we address this with improved DC-coupled EEG recording and analysis techniques and also extend observation to both temporal and extratemporal seizures. Recordings were performed during presurgical evaluation of medically intractable epilepsy, with 20 seizures in 11 patients analyzed. A commercial DC-coupled recording device was used, with sintered Ag/AgCl electrodes in a standard 10-10 system array, with additional anterior temporal and subtemporal electrodes. Seizures were localized with a software package by means of source montage analysis. Infraslow signals occurred with all seizures, often with amplitude orders of magnitude higher than conventional frequencies (0.5 to 70 Hz). The most reliable method to localize these signals and distinguish them from artifacts used a source montage after low-pass filtering below 0.5 Hz. Five of the eight patients who received epilepsy surgery had follow-up documenting significant seizure reduction, and infraslow signal analysis correctly localized the region of seizure onset in all five, while conventional noninvasive EEG recording and analysis localized only three of the five. Several seizures were also analyzed using principle component analysis source localization methods, with the results less consistently localizing than source montage analysis. DC-coupled EEG recordings give clinically useful information to noninvasively localize the seizure focus. The value of this method is increased by source analysis tools that reveal localized changes more clearly than direct visual inspection.     

Hemodynamic changes preceding the interictal EEG spike in patients with focal epilepsy investigated using simultaneous EEG-fMRI

EEG-fMRI is a non-invasive technique that allows the investigation of epileptogenic networks in patients with epilepsy. Lately, BOLD changes occurring before the spike were found in patients with generalized epilepsy. The study of metabolic changes preceding spikes might improve our knowledge of spike generation. We tested this hypothesis in patients with idiopathic and symptomatic focal epilepsy.Eleven consecutive patients were recorded at 3 T: five with idiopathic focal and 6 with symptomatic focal epilepsy. Thirteen spike types were analyzed separately. Statistical analysis was performed using the timing of spikes as events, modeled with HRFs peaking between − 9 s and + 9 s around the spike. HRFs were calculated the most focal BOLD response. Eleven of the thirteen studies showed prespike BOLD responses. Prespike responses were more focal than postspike responses. Three studies showed early positive followed by later negative BOLD responses in the spike field. Three had early positive BOLD responses in the spike field, which remained visible in the later maps. Three others had positive BOLD responses in the spike field, later propagating to surrounding areas. HRFs peaked between − 5 and + 6 s around the spike timing. No significant EEG changes could be identified prior to the spike.BOLD changes prior to the spike frequently occur in focal epilepsies. They are more focal than later BOLD changes and strongly related to the spike field. Early changes may result from increased neuronal activity in the spike field prior to the EEG spike and reflect an event more localized than the spike itself.