脑磁图在癫痫灶定位中的应用

目的：应用脑磁图（MEG）对癫痫灶进行定位，探讨脑磁图对癫痫灶定位的价值。方法：应用美国4D Vectorview306通道全头型生物磁仪，对21例癫痫患（其中男13例，女8例，年龄3－52岁，平均23．7岁）进行发作间期脑磁图检查。结果：17例测得发作间期棘波，4例未检测到棘波，结论：脑磁图对癫痫灶定位有很高的应用价值。     

Magnetoencephalographic studies on spike foci using a 37-channel biomagnetometer system]

We report the results of a clinical trial of Magnetoencephalography (MEG) on spike foci in patients with epilepsy, which was performed from December 1990 to June 1991 at The University of Tokyo Hospital. Fifty patients with focal epilepsy; 26 primary epilepsy, 24 secondary epilepsy (7 brain tumor, 4 arteriovenous malformation, 4 encephalitis, 3 porencephaly, 2 arachnoid cyst, 1 brain abscess, 1 hemimegaloencephaly, 1 Lance-Adams syndrome, 1 hygroma), and ten normal subjects were enrolled in this study. MEG data were recorded using a 37-channel biomagnetometer system SMI-1001 (BTi Magnes, Biomagnetic Technologies, Inc., San Diego). A simultaneous 19-channel EEG recording with linked-ear reference was also obtained. The overall study was completed safely and none of the normal subjects showed abnormal paroxysmal MEG activity. Two patients showed interictal EEG spikes which would not have been noticed without first noting the presence of corresponding prominent MEG spikes. On the whole, the MEG signal seemed to have a wider frequency bandwidth than EEG. In most cases, the source localization predicted by MEG corresponded well with the EEG findings. The relative accuracy of MEG spike source localization was estimated to be within a cubic centimeter from the cases which showed tightly clustered localization of individual spikes. High-pass filtering reduced interference by superimposed slow wave activity, thereby improving the localization of spike sources. These results demonstrate that 37-channel biomagnetometer system could be a useful tool for analyzing epileptic spike sources.     

Comparison of Brain Networks During Interictal Oscillations and Spikes on Magnetoencephalography and Intracerebral EEG

Electromagnetic source localization in electroencephalography (EEG) and magnetoencephalography (MEG) allows finding the generators of transient interictal epileptiform discharges (‘interictal spikes’). In intracerebral EEG (iEEG), oscillatory activity (above 30 Hz) has also been shown to be a marker of neuronal dysfunction. Still, the difference between networks involved in transient and oscillatory activities remains largely unknown. Our goal was thus to extract and compare the networks involved in interictal oscillations and spikes, and to compare the non-invasive results to those obtained directly within the brain. In five patients with both MEG and iEEG recordings, we computed correlation graphs across regions, for (1) interictal spikes and (2) epileptic oscillations around 30 Hz. We show that the corresponding networks can involve a widespread set of regions (average of 10 per patient), with only partial overlap (38 % of the total number of regions in MEG, 50 % in iEEG). The non-invasive results were concordant with intracerebral recordings (79 % for the spikes and 50 % for the oscillations). We compared our interictal results to iEEG ictal data. The regions labeled as seizure onset zone (SOZ) belonged to interictal networks in a large proportion of cases: 75 % (resp. 58 %) for spikes and 58 % (resp. 33 %) for oscillations in iEEG (resp. MEG). A subset of SOZ regions were detected by one type of discharges but not the other (25 % for spikes and 8 % for oscillations). Our study suggests that spike and oscillatory activities involve overlapping but distinct networks, and are complementary for presurgical mapping.     

MEG and EEG Sensitivity in a Case of Medial Occipital Epilepsy

Interictal or ictal events in partial epilepsies may project on scalp EEG contralaterally to the side of the epileptogenic lesion. Such paradoxical lateralization can be observed in case of para-sagittal generators, and is likely due to the spatial orientation of the generator, presenting an oblique projection towards the midline. We present here a case of medial occipital epilepsy investigated using EEG, MEG and stereoelectroencephalography (SEEG). MRI displayed a focal cortical dysplasia in the superior margin of the right calcarine fissure. SEEG demonstrated bilateral medial occipital interictal spikes, with an inversion of polarity at the level of the lesion and a contralateral propagation occurring in 10 ms. Interictal iterative EEG cartographies showed a large posterior field, with a maximum contralateral to the initial generator (EEG paradoxical lateralization). With the same number of channels, interictal iterative MEG cartographies were more precise and more complex than EEG ones, indicating an onset accurately lateralized. A few milliseconds later, MEG cartographies were quadripolar, thus indicating two homotopic active generators. These MEG and EEG cartographies have been reproduced using BESA dipole simulator. Relative merits of MEG and EEG are still debated. With 151 channels, MEG source localizations indicated the right medial occipital area, as demonstrated by SEEG. An investigation with a corresponding number of EEG channels was not performed. After a down sampling to 64 sensors, this precision was lost. MEG and EEG source localization results, both with 64 channels, were quite comparable, indicating both medial occipital areas. However, a careful analysis of MEG/EEG iterative cartographies, performed with the same number of channels in both modalities, demonstrated that, in this configuration, MEG sensitivity was superior to the EEG one, allowing separating two medial occipital sources, characterized in SEEG by a time delay of 10 ms.     

Regional Differences in the Sensitivity of MEG for Interictal Spikes in Epilepsy

MEG interictal spikes as recorded in epilepsy patients are a reflection of intracranial interictal activity. This study investigates the relationship between the estimated sources of MEG spikes and the location, distribution and size of interictal spikes in the invasive ECoG of a group of 38 epilepsy patients that are monitored for pre-surgical evaluation. An amplitude/surface area measure is defined to quantify and rank ECoG spikes. It is found that all MEG spikes are associated with an ECoG spike that is among the three highest ranked in a patient. Among the different brain regions considered, the fronto-orbital, inter-hemispheric, tempero-lateral and central regions stand out. In an accompanying simulation study it is shown that for hypothesized extended sources of larger sizes, as suggested by the data, source location, orientation and curvature can partly explain the observed sensitivity of MEG for interictal spikes.     

Different patterns of dipole source localization in gelastic seizure with or without a sense of mirth

Dipole source localization corresponding to interictal spikes were estimated using EEG dipole tracing with a realistic three-shell head model in three patients with cryptogenic gelastic epilepsy. The dipole sources in two patients, whose gelastic seizures were accompanied by a subjective feeling of mirth, were estimated in the right or left medio-basal temporal regions. In the other patient, with gelastic seizures without a sense of mirth, the dipole sources were localized in the right frontal region corresponding to the anterior cingulate. The results suggest that the neural activities in hippocampal regions are involved with the generation of gelastic seizures with a sense of mirth and those in the cingulate might be associated with the motor act of laughter.     

Dipole Localization of Human Induced Focal Afterdischarge Seizure in Simultaneous Magnetoencephalography and Electrocorticography

Localizations were compared for the same human seizure between simultaneously measured MEG and iEEG, which were both co-registered to MRI. The whole-cortex neuromagnetometer localized a dipole in a sphere phantom, co-registered to the MEG sensor array, with an error of 1.4 mm. A focal afterdischarge seizure was induced in a patient with partial epilepsy, by stimulation at a subdural electrocorticography (ECoG) electrode with a known location, which was co-registered to the MRI and to the MEG sensor array. The simultaneous MEG and ECoG during the 30-second seizure was measured and analyzed using the single, moving dipole model, which is the localization model used clinically. The dipole localizations from simultaneous whole cortex 68-channel MEG and 64-channel ECoG were then compared for the repetitive spiking at six different times during the seizure. There were two main regions of MEG and ECoG activity. The locations of these regions were confirmed by determining the location clusters of 8,000 dipoles on ECoG at consecutive time points during the seizure. The mean distances between the stimulated electrode location versus the dipole location of the MEG and versus the dipole location of the ECoG were each about one (1) centimeter. The mean distance between the dipole locations of the MEG versus the dipole locations of the ECoG was about 2 cm. These errors were compared to errors of MEG and ECoG reported previously for phantoms and for somatosensory evoked responses (SER) in patients. Comparing the findings from the present study to those from prior studies, there appeared to be the expected stepwise increase in mean localization error progressing from the phantom, to the SER, to the seizure.     

Source Connectivity Analysis from MEG and its Application to Epilepsy Source Localization

We report an approach to perform source connectivity analysis from MEG, and initially evaluate this approach to interictal MEG to localize epileptogenic foci and analyze interictal discharge propagations in patients with medically intractable epilepsy. Cortical activities were reconstructed from MEG using individual realistic geometry boundary element method head models. Directional connectivity among cortical regions of interest was then estimated using directed transfer function. The MEG source connectivity analysis method was implemented in the eConnectome software, which is open-source and freely available at . As an initial evaluation, the method was applied to study MEG interictal spikes from five epilepsy patients. Estimated primary epileptiform sources were consistent with surgically resected regions, suggesting the feasibility of using cortical source connectivity analysis from interictal MEG for potential localization of epileptiform activities.     

A technique to consider mismatches between fMRI and EEG/MEG sources for fMRI-constrained EEG/MEG source imaging: a preliminary simulation study

fMRI-constrained EEG/MEG source imaging can be a powerful tool in studying human brain functions with enhanced spatial and temporal resolutions. Recent studies on the combination of fMRI and EEG/MEG have suggested that fMRI prior information could be readily implemented by simply imposing different weighting factors to cortical sources overlapping with the fMRI activations. It has been also reported, however, that such a hard constraint may cause severe distortions or elimination of meaningful EEG/MEG sources when there are distinct mismatches between the fMRI activations and the EEG/MEG sources. If one wants to obtain the actual EEG/MEG source locations and uses the fMRI prior information as just an auxiliary tool to enhance focality of the distributed EEG/MEG sources, it is reasonable to weaken the strength of fMRI constraint when severe mismatches between fMRI and EEG/MEG sources are observed. The present study suggests an efficient technique to automatically adjust the strength of fMRI constraint according to the mismatch level. The use of the proposed technique rarely affects the results of conventional fMRI-constrained EEG/MEG source imaging if no major mismatch between the two modalities is detected; while the new results become similar to those of typical EEG/MEG source imaging without fMRI constraint if the mismatch level is significant. A preliminary simulation study using realistic EEG signals demonstrated that the proposed technique can be a promising tool to selectively apply fMRI prior information to EEG/MEG source imaging.     

Magnetoencephalography-guided epilepsy surgery for children with intractable focal epilepsy: SickKids experience.

We introduced magnetoencephalography (MEG)-guided epilepsy surgery for children with intractable focal epilepsy at The Hospital for Sick Children (SickKids) in Toronto, Canada. Surgical candidacy and decisions on surgical procedure for children with intractable focal epilepsy are based on long-term scalp video EEG (VEEG) results, magnetic resonance imaging (MRI) findings, and the distribution of MEG spike sources. After multidisciplinary discussion at the seizure conference, for the patients requiring intracranial VEEG, custom-made subdural electrode grids are designed using three-dimensional MRI superimposed with MEG spike sources to cover the area of clustered MEG spike sources. At the first surgery, neurosurgeons use the intraoperative neuronavigation system to visualize the area of clustered spike dipoles and somatosensory evoked fields on MEG to place the subdural grid and depth electrodes. At the second surgery, the area of seizure onset and active interictal spike discharges on the intracranial VEEG recording, which usually correlates with the zone of clustered MEG spike sources, is resected. This combination leads to successful surgical outcome to control seizures in these challenging paediatric patients. MEG is a useful tool in children with intractable focal epilepsy to determine the surgical candidacy and focal cortical resection to stop seizures.     

Magnetoencephalography in pediatric lesional epilepsy surgery

This study was performed to assess the usefulness of magnetoencephalography (MEG) as a presurgical evaluation modality in Korean pediatric patients with lesional localization-related epilepsy. The medical records and MEG findings of 13 pediatric patients (6 boys and 7 girls) with localization-related epilepsy, who underwent epilepsy surgery at Seoul National University Children's Hospital, were retrospectively reviewed. The hemispheric concordance rate was 100% (13/13 patients). The lobar or regional concordance rate was 77% (10/13 patients). In most cases, the MEG spike sources were clustered in the proximity of the lesion, either at one side of the margin (nine patients) or around the lesion (one patient); clustered spike sources were distant from the lesion in one patient. Among the patients with clustered spike sources near the lesion, further extensions (three patients) and distal scatters (three patients) were also observed. MEG spike sources were well lateralized and localized even in two patients without focal epileptiform discharges in the interictal scalp electroencephalography. Ten patients (77%) achieved Engel class I postsurgical seizure outcome. It is suggested that MEG is a safe and useful presurgical evaluation modality in pediatric patients with lesion localization-related epilepsy.     

Precision of dipole localization in a spherical volume conductor: A comparison of referential EEG,magnetoencephalography and scalp current density methods

Summary In this study, we determined the influence of dipole orientation, dipole location, and number of recording sites on the precision of dipole localization in a spherical volume conductor. We compared localization from referential EEG (R-EEG), scalp current density EEG (SCD-EEG) and magnetoencephalography (MEG). Dipole orientation had a small influence on the precision of dipole localization for R-EEG and SCD-EEG. Dipole location relative to the recording sites, dipole depth, and number of recording channels strongly influenced the precision of dipole localization. Assuming equal signal to noise conditions for each recording method, MEG and SCD-EEG had a similar precision for dipole localization of a single tangential dipole source and both methods were more precise than R-EEG. However, SCD-EEG was inferior to MEG for distinguishing a single tangential current source from a pair of deeper radial current sources. In summary, these results suggest that the MEG will be most useful for localization of multiple simultaneous dipole sources.     

Dipole Source Analysis May Differentiate Benign Focal Epilepsy of Childhood with Occipital Paroxysms from Symptomatic Occipital Lobe Epilepsy

The aim of the study was to distinguish Benign Focal Epilepsy of Childhood with Occipital Paroxysms (BEOP) from its symptomatic counterpart on the basis of the location of the sources of the interictal EEG spikes. Patients were classified into two groups: idiopathic BEOP and symptomatic occipital lobe epilepsy. Source analysis of the averaged occipital spikes was performed using a homogeneously conducting sphere as the volume conductor model. Results showed a statistically significant difference in the eccentricity, i.e., the distance of the occipital spike focus from the centre of the head. The dipole sources of the occipital spikes in the BEOP group were found to be located more superficially than in the symptomatic group, corresponding in six of the nine cases with a source position estimated to be within the cortical layer just below the skull. The eccentricity of the symptomatic occipital spikes suggests a location deeper than the cortical layer. The results were validated in two patients from the symptomatic group. In one patient the estimated deeper dipole source location corresponded with a deeper location of spike activity observed during ECoG; in the other patient's ECoG, spike activity was observed superficially but over an extended area. The discrepancy between estimated and real location may be explained by the method of dipole source analysis used. It is concluded that the finding of a superficial dipole source location of the occipital spikes provides an indication for the diagnosis BEOP (sensitivity: 67%; specificity: 74%).     

Two-Dimensional Temporal Clustering Analysis for Patients with Epilepsy: Detecting Epilepsy-Related Information in EEG-fMRI Concordant,Discordant and Spike-Less Patients

EEG acquired simultaneously with fMRI (EEG-fMRI) is a multimodal method that has shown promise in mapping the seizure onset zone in patients with focal epilepsy. However, there are many instances when this method is unsuccessful or not applicable, and other data driven fMRI methods may be utilized. One such method is the two-dimensional temporal clustering analysis (2dTCA). In this study we compared the classic EEG-fMRI and 2dTCA performance in mapping regions related to the seizure onset region in 18 focal epilepsy patients (12 presenting interictal epileptiform discharges (IEDs), during EEG-fMRI acquisition) with Engel I or II surgical outcome. Activation maps of both 2dTCA timing outputs (positive and negative histograms) and EEG detected IEDs were computed and compared to the region of epilepsy surgical resection. Patients were evaluated in three categories based on frequency of EEG detected spiking during the MRI. EEG-fMRI maps were concordant to the epilepsy region in 5/12 subjects, four with frequent IEDs on EEG. The 2dTCA was successful in mapping 13/18 patients including 3/6 with no IEDs detected (10/12 with IEDs detected). The epilepsy-related activities were successfully mapped by both methods in only 4/12 patients. This work suggests that the epilepsy-related information detected by each method may be different: while EEG-fMRI is more accurate in patients with high rather than lower numbers of EEG detected IEDs; 2dTCA can be useful in evaluating patients even when no concurrent EEG spikes are detected or EEG-fMRI is not effective. Therefore, our results support that 2dTCA might be an alternative for mapping epilepsy-related BOLD activity in negative EEG-fMRI (6/7 patients) and spike-less patients.     

Localization of the Epileptic Focus by Low-Resolution Electromagnetic Tomography in Patients with a Lesion Demonstrated by MRI

Patients with medically intractable partial epilepsy and well-defined symptomatic MRI lesions were studied using phase-encoded frequency spectral analysis (PEFSA) combined with low-resolution electromagnetic tomography (LORETA). Ten patients admitted to the epilepsy monitoring unit with MRI-identified lesions and intractable partial epilepsy were studied using 31-electrode scalp EEG. The scalp electrodes were located in three-dimensional space using a magnetic digitizer and coregistered with the patient's MRI. PEFSA was used to obtain a phase-encoded scalp map for the ictal frequencies. The ictal generators were obtained from the scalp map using LORETA. In addition, the generators of interictal epileptogenic spikes were identified using time-domain LORETA. The LORETA generators were rostral to the MRI lesion in 87% (7/8) of patients with temporal lobe lesions, but all were located in the mesial temporal lobe in concordance with the patients' MRI lesions. In patients with frontal lobe epilepsy, the ictal generators at the time that the spectral power was maximal localized to the MRI lesions. Eight of 10 patients had interictal spikes, of which 4 were bilateral independent temporal lobe spikes. Only generators of the interictal spikes that were ipsilateral to seizure onset correlated with the ictal generators. LORETA combined with PEFSA of the ictal discharge can localize ictal EEG discharges accurately and improve correlation with brain anatomy by allowing coregistration of the ictal generator with the MRI. Analysis of interictal spikes was less useful than analysis of the ictal discharge.     

Multiple Equivalent Current Dipole Source Localization of Visual Event-Related Potentials During Oddball Paradigm With Motor Response

Event-related potentials (ERPs) during a visual oddball paradigm with button-pressing responses were recorded in 12 right-handed subjects from 32 scalp electrodes. The single equivalent current dipole (ECD) of the target C1 (weak occipito-parietal negativity from 30-80ms) was consistently located at the primary visual cortex. From the 4-ECD localization of the target P1/N1 (temporally coincident frontal positivity and occipito-temporal negativity), it was suggested that this complex reflected activities from distributed sources along both dorsal occipito-parietal and ventral occipito-temporal areas. The stable multiple ECD solutions for the target P3b were chosen as those including the left primary motor and/or sensorimotor dipole and satisfying goodness-of-fit (GOF) of more than 98% and confidence limit (CL) of less than 1mm. The obtained frontal dipoles were discussed in terms of visual working memory and sustained attention in reference to the previous PET, fMRI and MEG studies. The distributed multiple ECDs may suggest that P3 should be interpreted as being the embodiment of the cortico-limbic-thalamic network which involves Halgren and Marinkovic's emotional and behavioral model and Mesulam's attentional circuit.     

Spike voltage topography and equivalent dipole localization in complex partial epilepsy

Summary The EEG of 45 patients with complex partial epilepsy was recorded from standard and supplementary inferior temporal electrode sites for 2 or more days via cable telemetry onto video (VHS) tape (22–25 channels, common reference). Epochs with "temporal spikes" were read into a topographic EEG device where individual spikes were visually identified and averaged in sums of 8–32. Analysis of spike voltage topography revealed two distinct patterns - dipolar, Type 1 and non-dipolar, Type 2. One or the other spike type predominated in all but two patients. Application of source modeling techniques (3 shells, single dipole, 6 parameters) to the spike topography data revealed that both spike types had similar equivalent dipoles in terms of location and orientation, except for vector elevation. However, calculated dipoles for Type 1 spikes were more stable over the course of the spike peak. Correlations with clinical data and intracranial EEG suggest that Type 1 spikes originate in mesial temporal structures, while Type 2 spikes arise from temporal or frontal neocortex. Spike voltage topography and equivalent dipole localization appear to be useful in the presurgical evaluation of patients with focal epilepsy.Acknowledgements: We appreciate the co-operation of our colleagues, Peter Williamson, Susan Spencer, and Richard Mattson and the assistance of their fellows, Vijay Thidani, Amiram Katz, David Marks, and Richard Scheyer.     

发作期及发作间期痫性放电对癫痫的诊断价值

目的探讨发作期及发作间期脑电图对癫痫诊断的意义。方法对５６例癫痫患者常规脑电图（ＲＥＥＧ）与２４ｈ脑电图（ＡＥＥＧ）进行比较研究。结果①ＲＥＥＧ的阳性率为３０％，而ＡＥＥＧ的阳性率为８６％；②不同类型癫痫在发作期和发作间期大脑活动的规律和特点，ＲＥＥＧ无１例记录到癫痫发作，而ＡＥＥＧ有２７例（４８％）记录到癫痫发作全过程的大脑电活动变化。结论发作期的ＥＥＧ对确定癫痫类型有重要意义，全身性癫痫在发作的同时发作波在两侧半球同时出现，而部分性发作患者在临床发作的同时ＥＥＧ常局限在某一脑叶有单个棘波发放，此棘波处是癫痫的病灶的部位，这种局限棘波可扩散至全脑而临床出现全身阵挛发作，此类患者为部分性癫痫并非全身性癫痫。     

Properties of Advanced Headmodelling and Source Reconstruction for the Localization of Epileptiform Activity

During the last decade multiple work has been done to determine the sources of epileptiform activity by means of dipole source localization based on recordings of the magnetoencephalogram (MEG) or the electroencephalogram (EEG). The actual available advanced volume conductor models and the multiple source reconstruction by regularization may give new impulse to EEG based source analyses in epilepsy patients. This study demonstrates the principal properties of these techniques. We applied two different EEG source reconstruction techniques within different volume conductor models to localize induced spike activity in a selected patient suffering from medically intractable temporal lobe epilepsy: 1) single moving dipole solution in a 3-shell spherical model versus individual head models (boundary-element-model, BEM, and finite-element-model, FEM); 2) a regularization technique for current density reconstructions using both BEM and FEM. When compared to findings of invasive recordings no adequate source locations were derived from the moving dipole solution in both the 3-shell head model and BEM. In contrast, a high congruence of source reconstruction and invasive determination of the focus was obtained using the regularization techniques in both BEM and FEM, indicating the high spatial accuracy of this technique in individual head models.     

EEG-fMRI validation studies in comparison with icEEG: a review

Simultaneous EEG-fMRI is a non-invasive investigation technique developed to localize the generators of interictal epileptiform discharges (IED) in patients with epilepsy. Although the value of EEG-fMRI in epilepsy presurgical evaluation is being assessed clinically, its utility is still controversial. In this review, we considered EEG-fMRI applications in epilepsy presurgical evaluation with a focus on validation studies that compared the results of EEG-fMRI with those of the current "gold standard" intracranial EEG (icEEG) in order to assess its utility of seizure focus localization and the possibility for EEG-fMRI to reduce the need for invasive techniques such as icEEG. Since the advances of EEG-fMRI partially rely on the maturation of its data analysis, we also reviewed the methodological developments in EEG-fMRI analysis. It is possible that combining with other neuroimaging modalities such as MEG/MSI and ESI, EEG-fMRI may play a greater role in epilepsy presurgical evaluation.