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.     

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.     

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.     

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.     

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.     

EEG-fMRI of epileptic spikes: concordance with EEG source localization and intracranial EEG

Simultaneous EEG and fMRI recordings permit the non-invasive investigation of the generators of spontaneous brain activity such as epileptic spikes. Despite a growing interest in this technique, the precise relationship between its results and the actual regions of activated cortex is not clear. In this study, we have quantified for the first time the concordance between EEG-fMRI results and stereotaxic EEG (SEEG) recordings in 5 patients with partial epilepsy. We also compared fMRI and SEEG with other non-invasive maps based on scalp EEG alone. We found that SEEG measures largely validated the results of EEG and fMRI. Indeed, when there is an intracranial electrode in the vicinity of an EEG or fMRI peak (in the range 20-40 mm), then it usually includes one active contact. This was the case for both increases ('activations') and decreases ('deactivations') of the fMRI signal: in our patients, fMRI signal decrease could be as important in understanding the complete picture of activity as increase of fMRI signal. The concordance between EEG and fMRI was not as good as the concordance between either of these non-invasive techniques and SEEG. This shows that the two techniques can show different regions of activity: they are complementary for the localization of the areas involved in the generation of epileptic spikes. Moreover, we found that the sign of the fMRI response correlated with the low frequency content of the SEEG epileptic transients, this latter being a reflection of the slow waves. Thus, we observed a higher proportion of energy in the low frequencies for the SEEG recorded in regions with fMRI signal increase compared to the regions with fMRI signal decrease. This could reflect an increase of metabolism linked to the presence of slow waves, which suggests that fMRI is a new source of information on the mechanisms of spike generation.     

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.     

Three-dimensional neuroimaging in diagnosis and surgical treatment for epilepsy

Development of functional neuroimaging is contributed to diagnosis and treatment in epilepsy patients. The dipole analysis of interictal spikes on EEG or MEG provides 3D-localization of the irritable zone. Interictal and ictal CBF-SPECT reveals the local change in CBF associated to epileptic focus. Three-dimensional stereotactic surface projection (3D-SSP) of SPECT is useful to recognize the seizure generation area. Furthermore, Subtraction ictal SPECT coregistration of MRI (SISCOM), that is fusion image of anatomical and functional brain images, is beneficial to understand the localization of seizure-induced hyperperfusion area. During epilepsy surgery, image-guided system makes less-invasive and accurate surgery possible. Functional image-guided surgery for epilepsy will be available in near future.     

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.     

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.     

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。     

Source analysis of interictal spikes in polymicrogyria: loss of relevant cortical fissures requires simultaneous EEG to avoid MEG misinterpretation

PURPOSE: Multiple source analysis of interictal EEG and MEG spikes was used to identify irritative zones in polymicrogyria (PMG). Spike onset times and source localization were compared between both modalities. PMG is characterized by a marked loss of deep cortical fissures. Hence, differences between EEG and MEG were expected since MEG signals are predominantly generated from tangentially orientated neurons in fissures. PATIENTS: We studied 7 children and young adults (age 7.5 to 19 years) with localization-related epilepsy and unilateral polymicrogyria (PMG) as defined from anatomical MRI. METHODS: 122-channel whole-head MEG and 32-channel EEG were recorded simultaneously for 25 to 40 min. Using the BESA program, interictal spikes were identified visually and used as templates to search for similar spatio-temporal spike patterns throughout the recording. Detected similar spikes (r > 0.85) were averaged, high-pass filtered (5 Hz) to enhance spike onset, and subjected to multiple spatio-temporal source analysis. Source localization was visualized by superposition on T1-weighted MRI and compared to the lesion. RESULTS: Nine spike types were identified in seven patients (2 types in 2 patients). Eight out of nine EEG sources and seven MEG sources modeling spike onset were localized within the visible lesion. EEG spike onset preceded MEG significantly in two spike types by 19 and 25 ms. This was related to radial onset activity in EEG while MEG localized propagated activity. In one case, the earliest MEG spike activity was localized to the normal hemisphere while the preceding radial EEG onset activity was localized within the lesion. Distances between EEG and MEG onset sources varied markedly between 9 and 51 mm in the eight spike types with concordant lateralization. CONCLUSION: Interictal irritative zones were localized within the lesion in PMG comparable to other malformations, e.g., FCD. Discrepancies in MEG and EEG were related to the lack of deep fissures in PMG. In two cases, MEG was blind to the onset of radial interictal spike activity and localized propagated spike activity. In two other cases, MEG localized to the more peripheral parts of the irritative zone. Simultaneous EEG recordings with MEG and multiple source analysis are required to avoid problems of MEG interpretation.     

Quantification of the benefit from integrating MEG and EEG data in minimum l2-norm estimation

Source current estimation from electromagnetic (MEG and EEG) signals is an ill-posed problem that often produces blurry or inaccurately positioned estimates. The two modalities have distinct factors limiting the resolution, e.g., MEG cannot detect radially oriented sources, while EEG is sensitive to accuracy of the head model. This makes combined EEG + MEG estimation techniques desirable, but different acquisition noise statistics, complexity of the head models, and lack of pertinent metrics all complicate the assessment of the resulting improvements. We investigated analytically the effect of including EEG recordings in MEG studies versus the addition of new MEG channels when computing noise-normalized minimum ℓ₂-norm estimates. Three-compartment boundary-element forward models were constructed using structural MRI scans for four subjects. Singular value analysis of the resulting forward models predicted better performance of the EEG + MEG case in the form of higher matrix rank. MNE inverse operators for EEG, MEG and EEG + MEG were constructed using the sensor noise covariance estimated from data. Metrics derived from the resolution matrices predicted higher spatial resolution in EEG + MEG as compared to MEG due to decreased spread (lower spatial dispersion, higher resolution index) with no reduction in dipole localization error. The effect was apparent in all source locations, with increased magnitude for deep areas such as the cingulate cortex. We were also able to corroborate the results for the somatosensory cortex using median nerve responses.     

Simultaneous MEG and intracranial EEG recordings during attentive reading

The relationship between neural oscillations recorded at various spatial scales remains poorly understood partly due to an overall dearth of studies utilizing simultaneous measurements. In an effort to study quantitative markers of attention during reading, we performed simultaneous magnetoencephalography (MEG) and intracranial electroencephalography (iEEG) recordings in four epileptic patients. Patients were asked to attend to a specific color when presented with an intermixed series of red words and green words, with words of a given color forming a cohesive story. We analyzed alpha, beta, and gamma band oscillatory responses to the word presentation and compared the strength and spatial organization of those responses in both electrophysiological recordings. Time-frequency analysis of iEEG revealed a network of clear attention-modulated high gamma band (50–150 Hz) power increases and alpha/beta (9–25 Hz) suppressions in response to the words. In addition to analyses at the sensor level, MEG time-frequency analysis was performed at the source level using a sliding window beamformer technique. Strong alpha/beta suppressions were observed in MEG reconstructions, in tandem with iEEG effects. While the MEG counterpart of high gamma band enhancement was difficult to interpret at the sensor level in two patients, MEG time-frequency source reconstruction revealed additional activation patterns in accordance with iEEG results. Importantly, iEEG allowed us to confirm that several sources of gamma band modulation observed with MEG were indeed of cortical origin rather than EMG muscular or ocular artifact.     

脑磁图与视频脑电图定位癫痫灶的结果比较

背景: 多数癫痫患者的癫痫发作经药物治疗可得到控制,但对于难治性癫痫患者来说,手术可能是一种治疗选择,正确定位癫痫患者的致痫灶是癫痫手术成功的基础.癫痫患者的术前评估包括视频脑电图、MRI、正电子发射计算机体层摄影/单光子发射计算机体层摄影和神经心理测试等.脑磁图作为一种新的无创性术前检测技术,已被许多国家用于癫痫外科手术计划和大脑功能的研究.目的:术前采用磁源成像技术进行对手术治疗的难治性癫痫患者进行致痫灶定位,并与无创性视频脑电图对比,参考手术效果,评估其定位价值.设计、时间及地点:回顾性病例分析,于2001-11/2005-12在广东三九脑科医院脑磁图室完成.对象:选择进行脑磁图检查618例的癫痫患者,采集其自发磁场信号进行单偶极子定位分析诊断.对其中149例MRI检查有结构改变、病史在2年以上者进行了手术治疗,病程2～35年,平均9.5年.方法:用148通道全头型脑磁系统(Magnes WH2500, 4-D Neuroimaging, San Diego, CA, USA)在磁屏蔽室采集脑自发磁场,采样频率为508.63 Hz,带通为1.0～100 Hz,采集30 min发作间歇期的自发脑磁,采用单个等效电流偶极子进行数据分析.分析结果最后重叠在MRI-T1加权像上,形成磁源成像.主要观察指标:术前视频脑电图、MRI和脑磁图结果及术后随访结果.结果:30 min发作间期的脑磁图检测到明显的癫痫样活动的敏感度为91%,并且大部分患者,其等效偶极子主要分布于结构性异常的边缘和邻近区域.与无创性视频脑电图(38.9%,58/149)相比,利用脑磁图可以对大部分MRI上有病变的患者(62.4%,93/149)进行精确定位并且能够确定切除区域.对资料完整的89 例患者进行了3～35个月的随访,平均随访9个月.89例患者中有72例(80.9%)术后未出现癫痫发作(EngelⅠ);7例(7.9%)癫痫发作极少或癫痫发作频率减少90%以上(Engel Ⅱ和 Engel Ⅲ);10例(11.2%)癫痫发作频率无明显减少(Engel Ⅳ和Engel Ⅴ),总有效率达88.8%(EngelⅠ～Ⅲ).结论:与无创性视频脑电图相比,利用脑磁图可以对大部分MRI上出现结构性病变的癫痫患者致痫灶进行精确定位,并且能够确定切除区域.     

Three-dimensional brain current source reconstruction from intra-cranial ECoG recordings

We have investigated 3-dimensional brain current density reconstruction (CDR) from intracranial electrocorticogram (ECoG) recordings by means of finite element method (FEM). The brain electrical sources are modeled by a current density distribution and estimated from the ECoG signals with the aid of a weighted minimum norm estimation algorithm. A series of computer simulations were conducted to evaluate the performance of ECoG-CDR by comparing with the scalp EEG based CDR results. The present computer simulation results indicate that the ECoG-CDR provides enhanced performance in localizing single dipole sources which are located in regions underneath the implanted subdural ECoG grids, and in distinguishing and imaging multiple separate dipole sources, in comparison to the CDR results as obtained from the scalp EEG under the same conditions. We have also demonstrated the applicability of the present ECoG-CDR method to estimate 3-dimensional current density distribution from the subdural ECoG recordings in a human epilepsy patient. Eleven interictal epileptiform spikes (seven from the frontal region and four from parietal region) in an epilepsy patient undergoing surgical evaluation were analyzed. The present promising results indicate the feasibility and applicability of the developed ECoG-CDR method of estimating brain sources from intracranial electrical recordings, with detailed forward modeling using FEM.     

Using patient-specific hemodynamic response functions in combined EEG-fMRI studies in epilepsy

Combining electroencephalogram (EEG) and functional MRI (fMRI) allows localization of brain regions activated as a result of epileptic spikes. The statistical analysis of fMRI data usually includes a standard model of the hemodynamic response function (HRF) but it is not known how well this fits the actual HRF of epileptic spikes. The objective of this exploratory study was to compare the activated areas and t-statistical scores obtained with a standard HRF to those obtained with a patient-specific HRF. Eight patients with focal epilepsy were studied. We obtained an estimate of the patient-specific HRFs for each patient at the local maximum of activation in the standard HRF analysis. The activated areas obtained with the patient-specific HRFs were larger or similar to the originally activated areas. Additional activated areas were seen in five patients, and most were compatible with the EEG and anatomical MRI localization of epileptogenic and lesional regions. Using patient-specific HRFs brings increased sensitivity to the analysis of epileptic spikes by EEG-fMRI.     

Magnetoencephalographic studies of two cases of diffuse subcortical laminar heterotopia or so-called double cortex

Two cases (a young male and a girl, suffering intractable epilepsy) of diffuse subcortical laminar heterotopia, or so-called double cortex (DC) have been investigated using magnetoencephalography (MEG). MEG confirmed involvement of both cortices (hetero- and normocortex) in the genesis of interictal spikes, and, according to the heterogeneity of DC syndrome, some differences were observed: spike initiation in the normocortex and latter involvement of the heterotopic cortex in the man, and rather a cancellation in both cortices in the girl. In addition, participation of heterotopic cortex in physiological activities could be demonstrated in the man.     

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.     

Investigations of dipole localization accuracy in MEG using the bootstrap

We describe the use of the nonparametric bootstrap to investigate the accuracy of current dipole localization from magnetoencephalography (MEG) studies of event-related neural activity. The bootstrap is well suited to the analysis of event-related MEG data since the experiments are repeated tens or even hundreds of times and averaged to achieve acceptable signal-to-noise ratios (SNRs). The set of repetitions or epochs can be viewed as a set of independent realizations of the brain's response to the experiment. Bootstrap resamples can be generated by sampling with replacement from these epochs and averaging. In this study, we applied the bootstrap resampling technique to MEG data from somatotopic experimental and simulated data. Four fingers of the right and left hand of a healthy subject were electrically stimulated, and about 400 trials per stimulation were recorded and averaged in order to measure the somatotopic mapping of the fingers in the S1 area of the brain. Based on single-trial recordings for each finger we performed 5000 bootstrap resamples. We reconstructed dipoles from these resampled averages using the Recursively Applied and Projected (RAP)-MUSIC source localization algorithm. We also performed a simulation for two dipolar sources with overlapping time courses embedded in realistic background brain activity generated using the prestimulus segments of the somatotopic data. To find correspondences between multiple sources in each bootstrap, sample dipoles with similar time series and forward fields were assumed to represent the same source. These dipoles were then clustered by a Gaussian Mixture Model (GMM) clustering algorithm using their combined normalized time series and topographies as feature vectors. The mean and standard deviation of the dipole position and the dipole time series in each cluster were computed to provide estimates of the accuracy of the reconstructed source locations and time series.