Influence of a silastic ECoG grid on EEG/ECoG based source analysis.

The simultaneous evaluation of the local electrocorticogram (ECoG) and the more broadly distributed electroencephalogram (EEG) from humans undergoing evaluation for epilepsy surgery has been shown to further the understanding of how pathologies give rise to spontaneous seizures. However, a well-known problem is that the disruption of the conducting properties of the brain coverings can render simultaneous scalp and intracranial recordings unrepresentative of the habitual EEG. The ECoG electrodes for measuring the potential on the surface of the cortex are commonly embedded into one or more sheets of a silastic material. These highly resistive silastic sheets influence the volume conduction and might therefore also influence the scalp EEG and ECoG measurements. We carried out a computer simulation study to examine how the scalp EEG and the ECoG, as well as the source reconstruction therefrom, employing equivalent current dipole estimation methods, are affected by the insulating ECoG grids. The finite element method with high quality tetrahedral meshes, generated using a constrained Delaunay tetrahedralization meshing approach, was used to model the volume conductor that incorporates the very thin ECoG sheets. It is shown that the insulating silastic substrate of the ECoG grids can have a large impact on the scalp potential and on source reconstruction from scalp EEG data measured in the presence of the grids. The reconstruction errors are characterized with regard to the location of the source in the brain and the mislocalization tendency. In addition, we found a non-negligible influence of the insulating grids on ECoG based source analysis. We conclude, that the thin insulating ECoG sheets should be taken into account, when performing source analysis of simultaneously measured ECoG and scalp EEG data.

Fast evaluation of interictal spikes in long-term EEG by hyper-clustering.

PURPOSE: The burden of reviewing long-term scalp electroencephalography (EEG) is not much alleviated by automated spike detection if thousands of events need to be inspected and mentally classified by the reviewer. This study investigated a novel technique of clustering and 24-h hyper-clustering on top of automated detection to assess whether fast review of focal interictal spike types was feasible and comparable to the spikes types observed during routine EEG review in epilepsy monitoring. METHODS: Spike detection used a transformation of scalp EEG into 29 regional source activities and adaptive thresholds to increase sensitivity. Our rule-based algorithm estimated 18 parameters around each detected peak and combined multichannel detections into one event. Similarity measures were derived from equivalent location, scalp topography, and source waveform of each event to form clusters over 2-h epochs using a density-based algorithm. Similar measures were applied to all 2-h clusters to form 24-h hyper-clusters. Independent raters evaluated electroencephalography data of 50 patients with epilepsy (25 children) using traditional visual spike review and optimized hyper-cluster inspection. Congruence between visual spike types and epileptiform hyper-clusters was assessed on a sublobar level using three-dimensional (3D) peak topographies. KEY FINDINGS: Visual rating found 126 different epileptiform spike types (2.5 per patient). Independently, 129 hyper-clusters were classified as epileptiform and originating in separate sublobar regions (2.6 per patient). Ninety-one percent of visual spike types matched with hyper-clusters (temporal lobe spikes 94%, extratemporal 89%). Conversely, 11% of hyper-clusters rated epileptiform had no corresponding visual spike type. Numbers were comparable in adults and children. On average, 15 hyper-clusters had to be inspected and rated per patient with an evaluation time of around 5 min. SIGNIFICANCE: Hyper-clustering over 24 h provides an independent tool for rapid daily evaluation of interictal spikes in long-term video-EEG monitoring. If used in addition to routine review of 2-5 min EEG per hour, sensitivity and reliability in noninvasive diagnosis of focal epilepsy increases.

Learn to interpret voltage maps: an atlas of topographies.

Describing the location of EEG abnormalities, such as interictal epileptiform discharges, is an important step in the interpretation of EEG recordings and has clinical relevance, as it is expected to point out the region of the brain generating these abnormal signals. Traditionally, the location is reported by specifying the area on the scalp where maximum negativity is located. However, this only reflects the correct localization in the brain when the cortical generator is located on the convexity (radial orientation). When the cortical generator is in the wall of a sulcus (tangential orientation), due to current flow (volume conduction), the maximum negativity is not over the generator, but at a distance from it. Voltage maps are widely available in most EEG reader software programs. Simple rules for reading voltage maps help to estimate the orientation and location of the source in the brain, avoiding false lateralization and false localization. In this seminar in epileptology, using a didactic approach, we explain how to read voltage maps and provide an atlas of voltage maps.

EEG-fMRI: Ballistocardiogram Artifact Reduction by Surrogate Method for Improved Source Localization.

For the analysis of simultaneous EEG-fMRI recordings, it is vital to use effective artifact removal tools. This applies in particular to the ballistocardiogram (BCG) artifact which is difficult to remove without distorting signals of interest related to brain activity. Here, we documented the use of surrogate source models to separate the artifact-related signals from brain signals with minimal distortion of the brain activity of interest. The artifact topographies used for surrogate separation were created automatically using principal components analysis (PCA-S) or by manual selection of artifact components utilizing independent components analysis (ICA-S). Using real resting-state data from 55 subjects superimposed with simulated auditory evoked potentials (AEP), both approaches were compared with three established BCG artifact removal methods: Blind Source Separation (BSS), Optimal Basis Set (OBS), and a mixture of both (OBS-ICA). Each method was evaluated for its applicability for ERP and source analysis using the following criteria: the number of events surviving artifact threshold scans, signal-to-noise ratio (SNR), error of source localization, and signal variance explained by the dipolar model. Using these criteria, PCA-S and ICA-S fared best overall, with highly significant differences to the established methods, especially in source localization. The PCA-S approach was also applied to a single subject Berger experiment performed in the MRI scanner. Overall, the removal of BCG artifacts by the surrogate methods provides a substantial improvement for the analysis of simultaneous EEG-fMRI data compared to the established methods.

Relative Source Power: A novel method for localizing epileptiform EEG discharges.

OBJECTIVE: To validate relative source power (RSP) imaging of extratemporal interictal epileptiform discharges (IEDs). METHODS: The accuracy of RSP was validated in a cohort of patients with extratemporal focal epilepsy and a confined epileptogenic lesion (<19 cm3) using distance to the lesion, concordance with resected area and postoperative outcome. Performance was compared with three conventional methods: voltage maps, equivalent current dipole and a distributed source model. RESULTS: Thirty-three of 41 consecutive patients (80%) had IED averages suitable for analysis. While the peak negativity in voltage maps localized above the epileptogenic lesion only in 18 cases, RSP-maps matched in 29 cases (88%, p < 0.0026). Source localization showed a median distance of 9.8 mm from the lesion. Source-regions with 20 mm radius included 98% of all source-to-lesion distances. In the 21 surgical cases, outcome showed a sensitivity of 82.35% and specificity of 50% without significant differences between the three source imaging methods. CONCLUSIONS: RSP-maps provide a rapid, intuitive and more accurate source estimation than voltage maps. At sublobar level, RSP localizes with an accuracy similar to conventional methods and results of previous studies. SIGNIFICANCE: The definition of a source region with 20 mm radius helps in guiding further exploration in extratemporal focal epilepsy.

Criteria for defining interictal epileptiform discharges in EEG: A clinical validation study.

OBJECTIVE: To define and validate criteria for accurate identification of EEG interictal epileptiform discharges (IEDs) using (1) the 6 sensor space criteria proposed by the International Federation of Clinical Neurophysiology (IFCN) and (2) a novel source space method. Criteria yielding high specificity are needed because EEG over-reading is a common cause of epilepsy misdiagnosis. METHODS: Seven raters reviewed EEG sharp transients from 100 patients with and without epilepsy (diagnosed definitively by video-EEG recording of habitual events). Raters reviewed the transients, randomized, and classified them as epileptiform or nonepileptiform in 3 separate rounds: in 2, EEG was reviewed in sensor space (scoring the presence/absence of each IFCN criterion for each transient or classifying unrestricted by criteria [expert scoring]); in the other, review and classification were performed in source space. RESULTS: Cutoff values of 4 and 5 criteria in sensor space and analysis in source space provided high accuracy (91%, 88%, and 90%, respectively), similar to expert scoring (92%). Two methods had specificity exceeding the desired threshold of 95%: using 5 IFCN criteria as cutoff and analysis in source space (both 95.65%); the sensitivity of these methods was 81.48% and 85.19%, respectively. CONCLUSIONS: The presence of 5 IFCN criteria in sensor space and analysis in source space are optimal for clinical implementation. By extracting these objective features, diagnostic accuracy similar to expert scorings is achieved. CLASSIFICATION OF EVIDENCE: This study provides Class III evidence that IFCN criteria in sensor space and analysis in source space have high specificity (>95%) and sensitivity (81%-85%) for identification of IEDs.

Structural and functional asymmetry of lateral Heschl's gyrus reflects pitch perception preference.

The relative pitch of harmonic complex sounds, such as instrumental sounds, may be perceived by decoding either the fundamental pitch (f0) or the spectral pitch (fSP) of the stimuli. We classified a large cohort of 420 subjects including symphony orchestra musicians to be either f0 or fSP listeners, depending on the dominant perceptual mode. In a subgroup of 87 subjects, MRI (magnetic resonance imaging) and magnetoencephalography studies demonstrated a strong neural basis for both types of pitch perception irrespective of musical aptitude. Compared with f0 listeners, fSP listeners possessed a pronounced rightward, rather than leftward, asymmetry of gray matter volume and P50m activity within the pitch-sensitive lateral Heschl's gyrus. Our data link relative hemispheric lateralization with perceptual stimulus properties, whereas the absolute size of the Heschl's gyrus depends on musical aptitude.

Taking the EEG Back Into the Brain: The Power of Multiple Discrete Sources.

Background: In contrast to many neuroimaging modalities, clinical interpretation of EEG does not take advantage of post-processing and digital signal analysis. In most centers, EEG is still interpreted at sensor level, exactly as half a century ago. A major task in clinical EEG interpretation is the identification of interictal epileptiform discharges (IEDs). However, due to the overlap of background activity, IEDs can be hard to detect in the scalp EEG. Since traditional montages, like bipolar and average reference, are linear transformations of the recorded channels, the question is whether we can provide linear transformations of the digital EEG to take it back into the brain, at least on a macroscopic level. The goal is to improve visibility of epileptiform activities and to separate out most of the overlap. Methods: Multiple discrete sources provide a stable linear inverse to transform the EEG into source space with little cross-talk between source regions. The model can be based on a few dipoles or regional sources, adapted to the individual EEG and MRI data, or on selected standard sources evenly distributed throughout the brain, e.g. below the 25 EEG standard electrodes. Results: Auditory and somatosensory evoked potentials serve as teaching examples to show how various source spaces can reveal the underlying source components including their loss or alteration due to lesions. Source spaces were able to reveal the propagation of source activities in frontal IEDs and the sequential activation of the major nodes of the underlying epileptic network in myoclonic epilepsy. The power of multiple discrete sources in separating the activities of different brain regions was also evident in the ongoing EEG of cases with frontal cortical dysplasia and bitemporal lobe epilepsy. The new source space 25 made IEDs more clearly visible over the EEG background signals. The more focal nature of source vs. scalp space was quantitatively confirmed using a new measurement of focality. Conclusion: Multiple discrete sources have the power to transform the EEG back into the brain by defining new EEG traces in source space. Using standard source space 25, these can provide for improved clinical interpretation of EEG.

Morphology of Heschl's gyrus reflects enhanced activation in the auditory cortex of musicians.

Using magnetoencephalography (MEG), we compared the processing of sinusoidal tones in the auditory cortex of 12 non-musicians, 12 professional musicians and 13 amateur musicians. We found neurophysiological and anatomical differences between groups. In professional musicians as compared to non-musicians, the activity evoked in primary auditory cortex 19-30 ms after stimulus onset was 102% larger, and the gray matter volume of the anteromedial portion of Heschl's gyrus was 130% larger. Both quantities were highly correlated with musical aptitude, as measured by psychometric evaluation. These results indicate that both the morphology and neurophysiology of Heschl's gyrus have an essential impact on musical aptitude.

LORETA With Cortical Constraint: Choosing an Adequate Surface Laplacian Operator.

Low resolution electromagnetic tomography (LORETA) is a well-known method for the solution of the l2-based minimization problem for EEG/MEG source reconstruction. LORETA with a volume-based source space is widely used and much effort has been invested in the theory and the application of the method in an experimental context. However, it is especially interesting to use anatomical prior knowledge and constrain the LORETA's solution to the cortical surface. This strongly reduces the number of unknowns in the inverse approach. Unlike the Laplace operator in the volume case with a rectangular and regular grid, the mesh is triangulated and highly irregular in the surface case. Thus, it is not trivial to choose or construct a Laplace operator (termed Laplace-Beltrami operator when applied to surfaces) that has the desired properties and takes into account the geometry of the mesh. In this paper, the basic methodology behind cortical LORETA is discussed and the method is applied for source reconstruction of simulated data using different Laplace-Beltrami operators in the smoothing term. The results achieved with the different operators are compared with respect to their accuracy using various measures. Conclusions about the choice of an appropriate operator are deduced from the results.

Mental chronometry of working memory retrieval: a combined functional magnetic resonance imaging and event-related potentials approach.

We used the combination of functional magnetic resonance imaging and event-related potentials to decompose the processing stages (mental chronometry) of working memory retrieval. Our results reveal an early transient activation of inferotemporal cortex, which was accompanied by the onset of a sustained activation of posterior parietal cortex. We furthermore observed late transient responses in ventrolateral prefrontal cortex and late sustained activity in medial frontal and premotor areas. We propose that these neural signatures reflect the cognitive stages of task processing, perceptual evaluation (inferotemporal cortex), storage buffer operations (posterior parietal cortex), active retrieval (ventrolateral prefrontal cortex), and action selection (medial frontal and premotor cortex). This is also supported by their differential temporal contribution to specific subcomponents of the P300 cognitive potential.

Neuromagnetic correlates of streaming in human auditory cortex.

The brain is constantly faced with the challenge of organizing acoustic input from multiple sound sources into meaningful auditory objects or perceptual streams. The present study examines the neural bases of auditory stream formation using neuromagnetic and behavioral measures. The stimuli were sequences of alternating pure tones, which can be perceived as either one or two streams. In the first experiment, physical stimulus parameters were varied between values that promoted the perceptual grouping of the tone sequence into one coherent stream and values that promoted its segregation into two streams. In the second experiment, an ambiguous tone sequence produced a bistable percept that switched spontaneously between one- and two-stream percepts. The first experiment demonstrated a strong correlation between listeners' perception and long-latency (>60 ms) activity that likely arises in nonprimary auditory cortex. The second demonstrated a covariation between this activity and listeners' perception in the absence of physical stimulus changes. Overall, the results indicate a tight coupling between auditory cortical activity and streaming perception, suggesting that an explicit representation of auditory streams may be maintained within nonprimary auditory areas.

Noninvasive source localization of interictal EEG spikes: effects of signal-to-noise ratio and averaging.

Source localization using single current dipoles estimates equivalent centers of the spiking gray matter. The extent of the active cortex, however, is difficult to assess from scalp EEG because of the unknown individual volume conduction. The spatial scatter of dipole localizations of single spikes has been proposed as a measure of extent. Single spike localization, however, is strongly dependent on the signal-to-noise ratio (SNR), that is, the ratio of spike and background EEG amplitudes. On the other hand, averaging of all spikes yields only the localization of equivalent centers of activity. We investigated the influence of SNR and multiple subaverages on the estimation of spatial extent by comparing the localization scatter of 100 single spikes in 27 spike types of 25 epilepsy patients with 1000 different subaverages computed by random sampling and bootstrapping. Averaging increased SNR and therefore allowed for localization not only at the spike peak but also during spike onset when less cortex is active. In several subjects with known cortical lesions, the single spike scatter considerably exceeded the lesion. Single dipole scatter was highly correlated with SNR (r = -0.83, P < 0.0001) and was greatly reduced when analyzing multiple subaverages of 10, 25, 50, and 100 spikes. Thus, we found a dominant role of the SNR on the estimated extent and improvement by scatterplots based on the dipole localization of randomly sampled subaverages.

MEG versus EEG: influence of background activity on interictal spike detection.

The comparative sensitivity of EEG and magnetoencephalography (MEG) in the visual detection of focal epileptiform activity in simultaneous interictal sleep recordings were investigated. The authors examined 14 patients aged 3.5 to 17 years with localization-related epilepsy. Simultaneous 122-channel whole-head MEG and 33-channel EEG were recorded for 20 to 40 minutes during spontaneous sleep. The EEG and MEG data were separated and four blinded independent reviewers marked the presence and timing of epileptic discharges (ED) in the 28 data segments. EEG and MEG data were matched and spikes identified by at least three reviewers were classified in three categories according to the following criteria: type 1 MEG > EEG, type 2 EEG > MEG (type 1/2: difference of three or more raters), and type 3 EEG = MEG (three or more raters each). The presence of simultaneous sleep changes was visually determined for every single EEG-segment. Spikes with high spatiotemporal correlation were averaged and subjected to single dipole analysis of peak activity in EEG. Out of 4704 marked patterns, 1387 spikes fulfilled the above criteria. In fact, more spikes were unique to MEG (689) than to EEG (136) and to the combination of both modalities (562). ED were detected predominantly by MEG in eight patients and by EEG in two patients. The presence of vertex waves and spindles lead to a significantly higher number of spikes identified only in MEG. Averaging of type 1 spikes produced clear spike activity in EEG in 9 of 12 cases. On the contrary, only 2 of 10 type 2 spikes were visible in MEG after averaging. Dipoles of spikes visible in MEG showed a more tangential orientation compared with more radial dipoles of type 2 spikes. Spike characteristics, e.g., dipole orientation, are a key factor for a sole EEG representation. Exclusive MEG detection is more likely influenced by overlapping background activity in EEG. Because MEG is indifferent to radial activity, i.e., sleep changes, a higher ratio of spikes unique to MEG compared with EEG is detected in the case of overlapping sleep changes.

Ictal EEG source imaging in presurgical evaluation: High agreement between analysis methods.

PURPOSE: To determine the agreement between five different methods of ictal EEG source imaging, and to assess their accuracy in presurgical evaluation of patients with focal epilepsy. It was hypothesized that high agreement between methods was associated with higher localization-accuracy. METHODS: EEGs were recorded with a 64-electrode array. Thirty-eight seizures from 22 patients were analyzed using five different methods phase mapping, dipole fitting, CLARA, cortical-CLARA and minimum norm. Localization accuracy was determined at sub-lobar level. Reference standard was the final decision of the multidisciplinary epilepsy surgery team, and, for the operated patients, outcome one year after surgery. RESULTS: Agreement between all methods was obtained in 13 patients (59%) and between all but one methods in additional six patients (27%). There was a trend for minimum norm being less accurate than phase mapping, but none of the comparisons reached significance. Source imaging in cases with agreement between all methods was not more accurate than in the other cases. Ictal source imaging achieved an accuracy of 73% (for operated patients: 86%). CONCLUSION: There was good agreement between different methods of ictal source imaging. However, good inter-method agreement did not necessarily imply accurate source localization, since all methods faced the limitations of the inverse solution.

Epileptiform discharge propagation: Analyzing spikes from the onset to the peak.

OBJECTIVE: To investigate how often discharge propagation occurs within the spikes recorded in patients evaluated for epilepsy surgery, and to assess its impact on the accuracy of source imaging. METHODS: Data were analyzed from 50 consecutive patients who had presurgical workup. Discharge propagation was analyzed using sequential voltage-maps of the averaged spikes, and principal components analysis. When propagation was detected, sources were modeled both at onset and peak. RESULTS: Propagation occurred in half of the patients. The median time of propagation between onset and peak was 17 ms. In 60% of the cases with propagation (15/25 patients) this remained in the same sub-lobar area where onset occurred. The accuracy of source imaging in cases of propagating spikes was 67% when only analyzing onset or peak. This was lower as compared to cases without propagation (79%). Combining source imaging at onset and at peak increased the accuracy to 83% for the propagating spikes. CONCLUSIONS: Propagation occurs often in patients with focal epilepsy, evaluated for surgery. In 40% of the propagating cases, the source of onset and peak were in different sub-lobar regions. SIGNIFICANCE: For optimal clinical utility, sources should be modeled both at onset and at peak epochs of the spikes.

Visualizing spikes in source-space: Rapid and efficient evaluation of magnetoencephalography.

OBJECTIVE: Reviewing magnetoencephalography (MEG) recordings is time-consuming: signals from the 306 MEG-sensors are typically reviewed divided into six arrays of 51 sensors each, thus browsing each recording six times in order to evaluate all signals. A novel method of reconstructing the MEG signals in source-space was developed using a source-montage of 29 brain-regions and two spatial components to remove magnetocardiographic (MKG) artefacts. Our objective was to evaluate the accuracy of reviewing MEG in source-space. METHODS: In 60 consecutive patients with epilepsy, we prospectively evaluated the accuracy of reviewing the MEG signals in source-space as compared to the classical method of reviewing them in sensor-space. RESULTS: All 46 spike-clusters identified in sensor-space were also identified in source-space. Two additional spike-clusters were identified in source-space. As 29 source-channels can be easily displayed simultaneously, MEG recordings had to be browsed only once. Yet, this yielded a global coverage of the recorded signals and enhanced detectability of epileptiform discharges because MKG-artefacts were suppressed and did not impede evaluation in source-space. CONCLUSIONS: Our results show that reviewing MEG recordings in source-space is accurate and much more rapid than the classical method of reviewing in sensor-space. SIGNIFICANCE: This novel method facilitates the clinical use of MEG.

Localizing P300 generators in visual target and distractor processing: a combined event-related potential and functional magnetic resonance imaging study.

Constraints from functional magnetic resonance imaging (fMRI) were used to identify the sources of the visual P300 event-related potential (ERP). Healthy subjects performed a visual three-stimulus oddball paradigm with a difficult discrimination task while fMRI and high-density ERP data were acquired in separate sessions. This paradigm allowed us to differentiate the P3b component of the P300, which has been implicated in the detection of rare events in general (target and distractor), from the P3a component, which is mainly evoked by distractor events. The fMRI-constrained source model explained >99% of the variance of the scalp ERP for both components. The P3b was mainly produced by parietal and inferior temporal areas, whereas frontal areas and the insula contributed mainly to the P3a. This source model reveals that both higher visual and supramodal association areas contribute to the visual P3b and that the P3a has a strong frontal contribution, which is compatible with its more anterior distribution on the scalp. The results point to the involvement of distinct attentional subsystems in target and distractor processing.

Frontal and posterior sources of event-related potentials in semantic comprehension.

An important question in brain and language research is how activity in multiple brain networks is coordinated over time during semantic comprehension. To address this question, we applied spatiotemporal source analysis to event-related potentials (ERPs) recorded as subjects read words that were meaningful or incongruous in the context of a sentence (N400 paradigm). The incongruous word was placed either early in the sentence or at the end. Source analysis showed activity in language areas of the left hemisphere, right temporal cortex and medial limbic cortex. The initial detection of semantic incongruity (approximately 250 ms) engaged the left prefrontal cortex and left anterior cingulate. In the critical (300-500 ms) interval, regional sources in left and right lateral prefrontal cortex, right temporal cortex, and both anterior and posterior cingulate were responsive to the semantic manipulation. Left hemisphere activity preceded right hemisphere activity, and semantic effects in frontal regions began earlier and were more sustained than the transient effects within posterior cortical regions. Findings are discussed with respect to recent theories of corticothalamic and corticolimbic networks in attention and semantic processing.

Temporal resolution of the human primary auditory cortex in gap detection.

The temporal resolution of the primary auditory cortex was studied by recording the magnetic middle latency fields (MAEF) evoked by gaps of 3, 6 and 9 ms inserted in the middle of 600 ms broadband noise bursts. Spatio-temporal source modelling showed that a significant neural representation as reflected by MAEF responses is present at gap durations as low as 3 sms. The comparison of the MAEF waveforms elicited by the onset, gap and offset of the noise bursts indicates that the gap related response near threshold is largely determined by the onset to the burst following the gap. The electro-physiologically derived minimum detectable gap closely resembled the psychoacoustic threshold of 2.0 ms obtained in the same subjects.