An altered balance of integrated and segregated brain activity is a marker of cognitive deficits following sleep deprivation.

Sleep deprivation (SD) leads to impairments in cognitive function. Here, we tested the hypothesis that cognitive changes in the sleep-deprived brain can be explained by information processing within and between large-scale cortical networks. We acquired functional magnetic resonance imaging (fMRI) scans of 20 healthy volunteers during attention and executive tasks following a regular night of sleep, a night of SD, and a recovery nap containing nonrapid eye movement (NREM) sleep. Overall, SD was associated with increased cortex-wide functional integration, driven by a rise of integration within cortical networks. The ratio of within versus between network integration in the cortex increased further in the recovery nap, suggesting that prolonged wakefulness drives the cortex towards a state resembling sleep. This balance of integration and segregation in the sleep-deprived state was tightly associated with deficits in cognitive performance. This was a distinct and better marker of cognitive impairment than conventional indicators of homeostatic sleep pressure, as well as the pronounced thalamocortical connectivity changes that occurs towards falling asleep. Importantly, restoration of the balance between segregation and integration of cortical activity was also related to performance recovery after the nap, demonstrating a bidirectional effect. These results demonstrate that intra- and interindividual differences in cortical network integration and segregation during task performance may play a critical role in vulnerability to cognitive impairment in the sleep-deprived state.

Validating MEG source imaging of resting state oscillatory patterns with an intracranial EEG atlas.

BACKGROUND: Magnetoencephalography (MEG) is a widely used non-invasive tool to estimate brain activity with high temporal resolution. However, due to the ill-posed nature of the MEG source imaging (MSI) problem, the ability of MSI to identify accurately underlying brain sources along the cortical surface is still uncertain and requires validation. METHOD: We validated the ability of MSI to estimate the background resting state activity of 45 healthy participants by comparing it to the intracranial EEG (iEEG) atlas (https://mni-open-ieegatlas. RESEARCH: mcgill.ca/). First, we applied wavelet-based Maximum Entropy on the Mean (wMEM) as an MSI technique. Next, we converted MEG source maps into intracranial space by applying a forward model to the MEG-reconstructed source maps, and estimated virtual iEEG (ViEEG) potentials on each iEEG channel location; we finally quantitatively compared those with actual iEEG signals from the atlas for 38 regions of interest in the canonical frequency bands. RESULTS: The MEG spectra were more accurately estimated in the lateral regions compared to the medial regions. The regions with higher amplitude in the ViEEG than in the iEEG were more accurately recovered. In the deep regions, MEG-estimated amplitudes were largely underestimated and the spectra were poorly recovered. Overall, our wMEM results were similar to those obtained with minimum norm or beamformer source localization. Moreover, the MEG largely overestimated oscillatory peaks in the alpha band, especially in the anterior and deep regions. This is possibly due to higher phase synchronization of alpha oscillations over extended regions, exceeding the spatial sensitivity of iEEG but detected by MEG. Importantly, we found that MEG-estimated spectra were more comparable to spectra from the iEEG atlas after the aperiodic components were removed. CONCLUSION: This study identifies brain regions and frequencies for which MEG source analysis is likely to be reliable, a promising step towards resolving the uncertainty in recovering intracerebral activity from non-invasive MEG studies.

Hierarchical Bayesian modeling of the relationship between task-related hemodynamic responses and cortical excitability.

Investigating the relationship between task-related hemodynamic responses and cortical excitability is challenging because it requires simultaneous measurement of hemodynamic responses while applying noninvasive brain stimulation. Moreover, cortical excitability and task-related hemodynamic responses are both associated with inter-/intra-subject variability. To reliably assess such a relationship, we applied hierarchical Bayesian modeling. This study involved 16 healthy subjects who underwent simultaneous Paired Associative Stimulation (PAS10, PAS25, Sham) while monitoring brain activity using functional Near-Infrared Spectroscopy (fNIRS), targeting the primary motor cortex (M1). Cortical excitability was measured by Motor Evoked Potentials (MEPs), and the motor task-related hemodynamic responses were measured using fNIRS 3D reconstructions. We constructed three models to investigate: (1) PAS effects on the M1 excitability, (2) PAS effects on fNIRS hemodynamic responses to a finger tapping task, and (3) the correlation between PAS effects on M1 excitability and PAS effects on task-related hemodynamic responses. Significant increase in cortical excitability was found following PAS25, whereas a small reduction of the cortical excitability was shown after PAS10 and a subtle increase occurred after sham. Both HbO and HbR absolute amplitudes increased after PAS25 and decreased after PAS10. The probability of the positive correlation between modulation of cortical excitability and hemodynamic activity was 0.77 for HbO and 0.79 for HbR. We demonstrated that PAS stimulation modulates task-related cortical hemodynamic responses in addition to M1 excitability. Moreover, the positive correlation between PAS modulations of excitability and hemodynamics brought insight into understanding the fundamental properties of cortical function and cortical excitability.

Cortical gradients of functional connectivity are robust to state-dependent changes following sleep deprivation.

Sleep deprivation leads to significant impairments in cognitive performance and changes to the interactions between large scale cortical networks, yet the hierarchical organization of cortical activity across states is still being explored. We used functional magnetic resonance imaging to assess activations and connectivity during cognitive tasks in 20 healthy young adults, during three states: (i) following a normal night of sleep, (ii) following 24hr of total sleep deprivation, and (iii) after a morning recovery nap. Situating cortical activity during cognitive tasks along hierarchical organizing gradients based upon similarity of functional connectivity patterns, we found that regional variations in task-activations were captured by an axis differentiating areas involved in executive control from default mode regions and paralimbic cortex. After global signal regression, the range of functional differentiation along this axis at baseline was significantly related to decline in working memory performance (2-back task) following sleep deprivation, as well as the extent of recovery in performance following a nap. The relative positions of cortical regions within gradients did not significantly change across states, except for a lesser differentiation of the visual system and increased coupling of the posterior cingulate cortex with executive control areas after sleep deprivation. This was despite a widespread increase in the magnitude of functional connectivity across the cortex following sleep deprivation. Cortical gradients of functional differentiation thus appear relatively insensitive to state-dependent changes following sleep deprivation and recovery, suggesting that there are no large-scale changes in cortical functional organization across vigilance states. Certain features of particular gradient axes may be informative for the extent of decline in performance on more complex tasks following sleep deprivation, and could be beneficial over traditional voxel- or parcel-based approaches in identifying realtionships between state-dependent brain activity and behavior.

How cerebral cortex protects itself from interictal spikes: The alpha/beta inhibition mechanism.

Interactions between interictal epileptiform discharges (IEDs) and distant cortical regions subserve potential effects on cognition of patients with focal epilepsy. We hypothesize that "healthy" brain areas at a distance from the epileptic focus may respond to the interference of IEDs by generating inhibitory alpha and beta oscillations. We predict that more prominent alpha-beta oscillations can be found in patients with less impaired neurocognitive profile. We performed a source imaging magnetoencephalography study, including 41 focal epilepsy patients: 21 with frontal lobe epilepsy (FLE) and 20 with mesial temporal lobe epilepsy. We investigated the effect of anterior (i.e., frontal and temporal) IEDs on the oscillatory pattern over posterior head regions. We compared cortical oscillations (5-80 Hz) temporally linked to 3,749 IEDs (1,945 frontal and 1,803 temporal) versus an equal number of IED-free segments. We correlated results from IED triggered oscillations to global neurocognitive performance. Only frontal IEDs triggered alpha-beta oscillations over posterior head regions. IEDs with higher amplitude triggered alpha-beta oscillations of higher magnitude. The intensity of posterior head region alpha-beta oscillations significantly correlated with a better neuropsychological profile. Our study demonstrated that cerebral cortex protects itself from IEDs with generation of inhibitory alpha-beta oscillations at distant cortical regions. The association of more prominent oscillations with a better cognitive status suggests that this mechanism might play a role in determining the cognitive resilience in patients with FLE.

Evaluation of a personalized functional near infra-red optical tomography workflow using maximum entropy on the mean.

In the present study, we proposed and evaluated a workflow of personalized near infra-red optical tomography (NIROT) using functional near-infrared spectroscopy (fNIRS) for spatiotemporal imaging of cortical hemodynamic fluctuations. The proposed workflow from fNIRS data acquisition to local 3D reconstruction consists of: (a) the personalized optimal montage maximizing fNIRS channel sensitivity to a predefined targeted brain region; (b) the optimized fNIRS data acquisition involving installation of optodes and digitalization of their positions using a neuronavigation system; and (c) the 3D local reconstruction using maximum entropy on the mean (MEM) to accurately estimate the location and spatial extent of fNIRS hemodynamic fluctuations along the cortical surface. The workflow was evaluated on finger-tapping fNIRS data acquired from 10 healthy subjects for whom we estimated the reconstructed NIROT spatiotemporal images and compared with functional magnetic resonance imaging (fMRI) results from the same individuals. Using the fMRI activation maps as our reference, we quantitatively compared the performance of two NIROT approaches, the MEM framework and the conventional minimum norm estimation (MNE) method. Quantitative comparisons were performed at both single subject and group-level. Overall, our results suggested that MEM provided better spatial accuracy than MNE, while both methods offered similar temporal accuracy when reconstructing oxygenated (HbO) and deoxygenated hemoglobin (HbR) concentration changes evoked by finger-tapping. Our proposed complete workflow was made available in the brainstorm fNIRS processing plugin-NIRSTORM, thus providing the opportunity for other researchers to further apply it to other tasks and on larger populations.

Data-driven beamforming technique to attenuate ballistocardiogram artefacts in electroencephalography-functional magnetic resonance imaging without detecting cardiac pulses in electrocardiography recordings.

Simultaneous recording of electroencephalography (EEG) and functional magnetic resonance imaging (fMRI) is a very promising non-invasive neuroimaging technique. However, EEG data obtained from the simultaneous EEG-fMRI are strongly influenced by MRI-related artefacts, namely gradient artefacts (GA) and ballistocardiogram (BCG) artefacts. When compared to the GA correction, the BCG correction is more challenging to remove due to its inherent variabilities and dynamic changes over time. The standard BCG correction (i.e., average artefact subtraction [AAS]), require detecting cardiac pulses from simultaneous electrocardiography (ECG) recording. However, ECG signals are also distorted and will become problematic for detecting reliable cardiac peaks. In this study, we focused on a beamforming spatial filtering technique to attenuate all unwanted source activities outside of the brain. Specifically, we applied the beamforming technique to attenuate the BCG artefact in EEG-fMRI, and also to recover meaningful task-based neural signals during an attentional network task (ANT) which required participants to identify visual cues and respond accurately. We analysed EEG-fMRI data in 20 healthy participants during the ANT, and compared four different BCG corrections (non-BCG corrected, AAS BCG corrected, beamforming + AAS BCG corrected, beamforming BCG corrected). We demonstrated that the beamforming approach did not only significantly reduce the BCG artefacts, but also significantly recovered the expected task-based brain activity when compared to the standard AAS correction. This data-driven beamforming technique appears promising especially for longer data acquisition of sleep and resting EEG-fMRI. Our findings extend previous work regarding the recovery of meaningful EEG signals by an optimized suppression of MRI-related artefacts.

Accuracy and spatial properties of distributed magnetic source imaging techniques in the investigation of focal epilepsy patients.

Source localization of interictal epileptiform discharges (IEDs) is clinically useful in the presurgical workup of epilepsy patients. We aimed to compare the performance of four different distributed magnetic source imaging (dMSI) approaches: Minimum norm estimate (MNE), dynamic statistical parametric mapping (dSPM), standardized low-resolution electromagnetic tomography (sLORETA), and coherent maximum entropy on the mean (cMEM). We also evaluated whether a simple average of maps obtained from multiple inverse solutions (Ave) can improve localization accuracy. We analyzed dMSI of 206 IEDs derived from magnetoencephalography recordings in 28 focal epilepsy patients who had a well-defined focus determined through intracranial EEG (iEEG), epileptogenic MRI lesions or surgical resection. dMSI accuracy and spatial properties were quantitatively estimated as: (a) distance from the epilepsy focus, (b) reproducibility, (c) spatial dispersion (SD), (d) map extension, and (e) effect of thresholding on map properties. Clinical performance was excellent for all methods (median distance from the focus MNE = 2.4 mm; sLORETA = 3.5 mm; cMEM = 3.5 mm; dSPM = 6.8 mm, Ave = 0 mm). Ave showed the lowest distance between the map maximum and epilepsy focus (Dmin lower than cMEM, MNE, and dSPM, p = .021, p = .008, p < .001, respectively). cMEM showed the best spatial features, with lowest SD outside the focus (SD lower than all other methods, p < .001 consistently) and high contrast between the generator and surrounding regions. The average map Ave provided the best localization accuracy, whereas cMEM exhibited the lowest amount of spurious distant activity. dMSI techniques have the potential to significantly improve identification of iEEG targets and to guide surgical planning, especially when multiple methods are combined.

Cortical reactivations during sleep spindles following declarative learning.

Increasing evidence suggests that sleep spindles are involved in memory consolidation, but few studies have investigated the effects of learning on brain responses associated with spindles in humans. Here we used simultaneous electroencephalography (EEG) and functional magnetic resonance imaging (fMRI) during sleep to assess haemodynamic brain responses related to spindles after learning. Twenty young healthy participants were scanned with EEG/fMRI during (i) a declarative memory face sequence learning task, (ii) subsequent sleep, and (iii) recall after sleep (learning night). As a control condition an identical EEG/fMRI scanning protocol was performed after participants over-learned the face sequence task to complete mastery (control night). Results demonstrated increased responses in the fusiform gyrus both during encoding before sleep and during successful recall after sleep, in the learning night compared to the control night. During sleep, a larger response in the fusiform gyrus was observed in the presence of fast spindles during the learning as compared to the control night. Our findings support a cortical reactivation during fast spindles of brain regions previously involved in declarative learning and subsequently activated during memory recall, thereby promoting the cortical consolidation of memory traces.

Clinical yield of magnetoencephalography distributed source imaging in epilepsy: A comparison with equivalent current dipole method.

OBJECTIVE: Source localization of interictal epileptic discharges (IEDs) is clinically useful in the presurgical workup of epilepsy patients. It is usually obtained by equivalent current dipole (ECD) which localizes a point source and is the only inverse solution approved by clinical guidelines. In contrast, magnetic source imaging using distributed methods (dMSI) provides maps of the location and the extent of the generators, but its yield has not been clinically validated. We systematically compared ECD versus dMSI performed using coherent Maximum Entropy on the Mean (cMEM), a method sensitive to the spatial extent of the generators. METHODS: 340 source localizations of IEDs derived from 49 focal epilepsy patients with foci well-defined through intracranial EEG, MRI lesions, and surgery were analyzed. The comparison was based on the assessment of the sublobar concordance with the focus and of the distance between the source and the focus. RESULTS: dMSI sublobar concordance was significantly higher than ECD (81% vs 69%, P < 0.001), especially for extratemporal lobe sources (dMSI = 84%; ECD = 67%, P < 0.001) and for seizure free patients (dMSI = 83%; ECD = 70%, P < 0.001). The median distance from the focus was 4.88 mm for ECD and 3.44 mm for dMSI (P < 0.001). ECD dipoles were often wrongly localized in deep brain regions. CONCLUSIONS: dMSI using cMEM exhibited better accuracy. dMSI also offered the advantage of recovering more realistic maps of the generator, which could be exploited for neuronavigation aimed at targeting invasive EEG and surgical resection. Therefore, dMSI may be preferred to ECD in clinical practice. Hum Brain Mapp 39:218-231, 2018. © 2017 Wiley Periodicals, Inc.

Reproducibility of EEG-MEG fusion source analysis of interictal spikes: Relevance in presurgical evaluation of epilepsy.

Fusion of electroencephalography (EEG) and magnetoencephalography (MEG) data using maximum entropy on the mean method (MEM-fusion) takes advantage of the complementarities between EEG and MEG to improve localization accuracy. Simulation studies demonstrated MEM-fusion to be robust especially in noisy conditions such as single spike source localizations (SSSL). Our objective was to assess the reliability of SSSL using MEM-fusion on clinical data. We proposed to cluster SSSL results to find the most reliable and consistent source map from the reconstructed sources, the so-called consensus map. Thirty-four types of interictal epileptic discharges (IEDs) were analyzed from 26 patients with well-defined epileptogenic focus. SSSLs were performed on EEG, MEG, and fusion data and consensus maps were estimated using hierarchical clustering. Qualitative (spike-to-spike reproducibility rate, SSR) and quantitative (localization error and spatial dispersion) assessments were performed using the epileptogenic focus as clinical reference. Fusion SSSL provided significantly better results than EEG or MEG alone. Fusion found at least one cluster concordant with the clinical reference in all cases. This concordant cluster was always the one involving the highest number of spikes. Fusion yielded highest reproducibility (SSR EEG = 55%, MEG = 71%, fusion = 90%) and lowest localization error. Also, using only few channels from either modality (21EEG + 272MEG or 54EEG + 25MEG) was sufficient to reach accurate fusion. MEM-fusion with consensus map approach provides an objective way of finding the most reliable and concordant generators of IEDs. We, therefore, suggest the pertinence of SSSL using MEM-fusion as a valuable clinical tool for presurgical evaluation of epilepsy.

The movement time analyser task investigated with functional near infrared spectroscopy: an ecologic approach for measuring hemodynamic response in the motor system.

AIMS: Movement time analyzer (MTA) is an objective instrument to evaluate the degree of motor impairment as well as to investigate the dopaminergic drug effect in Parkinson's disease patients. The aim of this study is to validate a new ecologic neuroimaging tool for quantifying MTA-related hemodynamic response of the cortical motor system by means of functional near-infrared spectroscopy (fNIRS). MATERIALS: 11 right-handed healthy volunteers (six male and five female, age range 27-64 years) were studied with fNIRS and functional magnetic resonance imaging (fMRI) while performing MTA task for each hand. RESULTS: MTA performance was better for the dominant hand and younger participants. Both fNIRS and fMRI analyses revealed MTA-related increase of haemoglobin levels in the primary motor and premotor cortices contralateral to the moving hand. This response progressively increased with aging. CONCLUSION: These findings supported the translation of fNIRS-based MTA behavioural tool in clinical practice.

SPARK: Sparsity-based analysis of reliable k-hubness and overlapping network structure in brain functional connectivity.

Functional hubs are defined as the specific brain regions with dense connections to other regions in a functional brain network. Among them, connector hubs are of great interests, as they are assumed to promote global and hierarchical communications between functionally specialized networks. Damage to connector hubs may have a more crucial effect on the system than does damage to other hubs. Hubs in graph theory are often identified from a correlation matrix, and classified as connector hubs when the hubs are more connected to regions in other networks than within the networks to which they belong. However, the identification of hubs from functional data is more complex than that from structural data, notably because of the inherent problem of multicollinearity between temporal dynamics within a functional network. In this context, we developed and validated a method to reliably identify connectors and corresponding overlapping network structure from resting-state fMRI. This new method is actually handling the multicollinearity issue, since it does not rely on counting the number of connections from a thresholded correlation matrix. The novelty of the proposed method is that besides counting the number of networks involved in each voxel, it allows us to identify which networks are actually involved in each voxel, using a data-driven sparse general linear model in order to identify brain regions involved in more than one network. Moreover, we added a bootstrap resampling strategy to assess statistically the reproducibility of our results at the single subject level. The unified framework is called SPARK, i.e. SParsity-based Analysis of Reliable k-hubness, where k-hubness denotes the number of networks overlapping in each voxel. The accuracy and robustness of SPARK were evaluated using two dimensional box simulations and realistic simulations that examined detection of artificial hubs generated on real data. Then, test/retest reliability of the method was assessed using the 1000 Functional Connectome Project database, which includes data obtained from 25 healthy subjects at three different occasions with long and short intervals between sessions. We demonstrated that SPARK provides an accurate and reliable estimation of k-hubness, suggesting a promising tool for understanding hub organization in resting-state fMRI.

Intracranial EEG potentials estimated from MEG sources: A new approach to correlate MEG and iEEG data in epilepsy.

Detection of epileptic spikes in MagnetoEncephaloGraphy (MEG) requires synchronized neuronal activity over a minimum of 4cm2. We previously validated the Maximum Entropy on the Mean (MEM) as a source localization able to recover the spatial extent of the epileptic spike generators. The purpose of this study was to evaluate quantitatively, using intracranial EEG (iEEG), the spatial extent recovered from MEG sources by estimating iEEG potentials generated by these MEG sources. We evaluated five patients with focal epilepsy who had a pre-operative MEG acquisition and iEEG with MRI-compatible electrodes. Individual MEG epileptic spikes were localized along the cortical surface segmented from a pre-operative MRI, which was co-registered with the MRI obtained with iEEG electrodes in place for identification of iEEG contacts. An iEEG forward model estimated the influence of every dipolar source of the cortical surface on each iEEG contact. This iEEG forward model was applied to MEG sources to estimate iEEG potentials that would have been generated by these sources. MEG-estimated iEEG potentials were compared with measured iEEG potentials using four source localization methods: two variants of MEM and two standard methods equivalent to minimum norm and LORETA estimates. Our results demonstrated an excellent MEG/iEEG correspondence in the presumed focus for four out of five patients. In one patient, the deep generator identified in iEEG could not be localized in MEG. MEG-estimated iEEG potentials is a promising method to evaluate which MEG sources could be retrieved and validated with iEEG data, providing accurate results especially when applied to MEM localizations. Hum Brain Mapp 37:1661-1683, 2016. © 2016 Wiley Periodicals, Inc.

Source localization of the seizure onset zone from ictal EEG/MEG data.

INTRODUCTION: Surgical treatment of drug-resistant epilepsy relies on the identification of the seizure onset zone (SOZ) and often requires intracranial EEG (iEEG). We have developed a new approach for non-invasive magnetic and electric source imaging of the SOZ (MSI-SOZ and ESI-SOZ) from ictal magnetoencephalography (MEG) and EEG recordings, using wavelet-based Maximum Entropy on the Mean (wMEM) method. We compared the performance of MSI-SOZ and ESI-SOZ with interictal spike source localization (MSI-spikes and ESI-spikes) and clinical localization of the SOZ (i.e., based on iEEG or lesion topography, denoted as clinical-SOZ). METHODS: A total of 46 MEG or EEG seizures from 13 patients were analyzed. wMEM was applied around seizure onset, centered on the frequency band showing the strongest power change. Principal component analysis applied to spatiotemporal reconstructed wMEM sources (0.4-1 s around seizure onset) identified the main spatial pattern of ictal oscillations. Qualitative sublobar concordance and quantitative measures of distance and spatial overlaps were estimated to compare MSI/ESI-SOZ with MSI/ESI-Spikes and clinical-SOZ. RESULTS: MSI/ESI-SOZ were concordant with clinical-SOZ in 81% of seizures (MSI 90%, ESI 64%). MSI-SOZ was more accurate and identified sources closer to the clinical-SOZ (P = 0.012) and to MSI-Spikes (P = 0.040) as compared with ESI-SOZ. MSI/ESI-SOZ and MSI/ESI-Spikes did not differ in terms of concordance and distance from the clinical-SOZ. CONCLUSIONS: wMEM allows non-invasive localization of the SOZ from ictal MEG and EEG. MSI-SOZ performs better than ESI-SOZ. MSI/ESI-SOZ can provide important additional information to MSI/ESI-Spikes during presurgical evaluation. Hum Brain Mapp 37:2528-2546, 2016. © 2016 Wiley Periodicals, Inc.

Detection and Magnetic Source Imaging of Fast Oscillations (40-160 Hz) Recorded with Magnetoencephalography in Focal Epilepsy Patients.

We present a framework to detect fast oscillations (FOs) in magnetoencephalography (MEG) and to perform magnetic source imaging (MSI) to determine the location and extent of their generators in the cortex. FOs can be of physiologic origin associated to sensory processing and memory consolidation. In epilepsy, FOs are of pathologic origin and biomarkers of the epileptogenic zone. Seventeen patients with focal epilepsy previously confirmed with identified FOs in scalp electroencephalography (EEG) were evaluated. To handle data deriving from large number of sensors (275 axial gradiometers) we used an automatic detector with high sensitivity. False positives were discarded by two human experts. MSI of the FOs was performed with the wavelet based maximum entropy on the mean method. We found FOs in 11/17 patients, in only one patient the channel with highest FO rate was not concordant with the epileptogenic region and might correspond to physiologic oscillations. MEG FOs rates were very low: 0.02-4.55 per minute. Compared to scalp EEG, detection sensitivity was lower, but the specificity higher in MEG. MSI of FOs showed concordance or partial concordance with proven generators of seizures and epileptiform activity in 10/11 patients. We have validated the proposed framework for the non-invasive study of FOs with MEG. The excellent overall concordance with other clinical gold standard evaluation tools indicates that MEG FOs can provide relevant information to guide implantation for intracranial EEG pre-surgical evaluation and for surgical treatment, and demonstrates the important added value of choosing appropriate FOs detection and source localization methods.

Localization Accuracy of Distributed Inverse Solutions for Electric and Magnetic Source Imaging of Interictal Epileptic Discharges in Patients with Focal Epilepsy.

Distributed inverse solutions aim to realistically reconstruct the origin of interictal epileptic discharges (IEDs) from noninvasively recorded electroencephalography (EEG) and magnetoencephalography (MEG) signals. Our aim was to compare the performance of different distributed inverse solutions in localizing IEDs: coherent maximum entropy on the mean (cMEM), hierarchical Bayesian implementations of independent identically distributed sources (IID, minimum norm prior) and spatially coherent sources (COH, spatial smoothness prior). Source maxima (i.e., the vertex with the maximum source amplitude) of IEDs in 14 EEG and 19 MEG studies from 15 patients with focal epilepsy were analyzed. We visually compared their concordance with intracranial EEG (iEEG) based on 17 cortical regions of interest and their spatial dispersion around source maxima. Magnetic source imaging (MSI) maxima from cMEM were most often confirmed by iEEG (cMEM: 14/19, COH: 9/19, IID: 8/19 studies). COH electric source imaging (ESI) maxima co-localized best with iEEG (cMEM: 8/14, COH: 11/14, IID: 10/14 studies). In addition, cMEM was less spatially spread than COH and IID for ESI and MSI (p < 0.001 Bonferroni-corrected post hoc t test). Highest positive predictive values for cortical regions with IEDs in iEEG could be obtained with cMEM for MSI and with COH for ESI. Additional realistic EEG/MEG simulations confirmed our findings. Accurate spatially extended sources, as found in cMEM (ESI and MSI) and COH (ESI) are desirable for source imaging of IEDs because this might influence surgical decision. Our simulations suggest that COH and IID overestimate the spatial extent of the generators compared to cMEM.

MEG-EEG Information Fusion and Electromagnetic Source Imaging: From Theory to Clinical Application in Epilepsy.

The purpose of this study is to develop and quantitatively assess whether fusion of EEG and MEG (MEEG) data within the maximum entropy on the mean (MEM) framework increases the spatial accuracy of source localization, by yielding better recovery of the spatial extent and propagation pathway of the underlying generators of inter-ictal epileptic discharges (IEDs). The key element in this study is the integration of the complementary information from EEG and MEG data within the MEM framework. MEEG was compared with EEG and MEG when localizing single transient IEDs. The fusion approach was evaluated using realistic simulation models involving one or two spatially extended sources mimicking propagation patterns of IEDs. We also assessed the impact of the number of EEG electrodes required for an efficient EEG-MEG fusion. MEM was compared with minimum norm estimate, dynamic statistical parametric mapping, and standardized low-resolution electromagnetic tomography. The fusion approach was finally assessed on real epileptic data recorded from two patients showing IEDs simultaneously in EEG and MEG. Overall the localization of MEEG data using MEM provided better recovery of the source spatial extent, more sensitivity to the source depth and more accurate detection of the onset and propagation of IEDs than EEG or MEG alone. MEM was more accurate than the other methods. MEEG proved more robust than EEG and MEG for single IED localization in low signal-to-noise ratio conditions. We also showed that only few EEG electrodes are required to bring additional relevant information to MEG during MEM fusion.

Spatial correlation of hemodynamic changes related to interictal epileptic discharges with electric and magnetic source imaging.

INTRODUCTION: Blood oxygenation level-dependent (BOLD) signal changes at the time of interictal epileptic discharges (IEDs) identify their associated vascular/hemodynamic responses. BOLD activations and deactivations can be found within the epileptogenic zone but also at a distance. Source imaging identifies electric (ESI) and magnetic (MSI) sources of IEDs, with the advantage of a higher temporal resolution. Therefore, the objective of our study was to evaluate the spatial concordance between ESI/MSI and BOLD responses for similar IEDs. METHODS: Twenty-one patients with similar IEDs in simultaneous electroencephalogram/functional magnetic resonance imaging (EEG/fMRI) and in simultaneous EEG/magnetoencephalogram (MEG) recordings were studied. IEDs in EEG/fMRI acquisition were analyzed in an event-related paradigm within a general linear model (GLM). ESI/MSI of averaged IEDs was performed using the Maximum Entropy on the Mean. We assessed the spatial concordance between ESI/MSI and clusters of BOLD activations/deactivations with surface-based metrics. RESULTS: ESI/MSI were concordant with one BOLD cluster for 20/21 patients (concordance with activation: 14/21 patients, deactivation: 6/21 patients, no concordance: 1/21 patients; concordance with MSI only: 3/21, ESI only: 2/21). These BOLD clusters exhibited in 19/20 cases the most significant voxel. BOLD clusters that were spatially concordant with ESI/MSI were concordant with IEDs from invasive recordings in 8/11 patients (activations: 5/8, deactivations: 3/8). CONCLUSION: As the results of BOLD, ESI and MSI are often concordant, they reinforce our confidence in all of them. ESI and MSI confirm the most significant BOLD cluster within BOLD maps, emphasizing the importance of these clusters for the definition of the epileptic focus.

Systematic review of seizure-onset patterns in stereo-electroencephalography: Current state and future directions.

OBJECTIVE: Increasing evidence suggests that the seizure-onset pattern (SOP) in stereo-electroencephalography (SEEG) is important for localizing the "true" seizure onset. Specifically, SOPs with low-voltage fast activity (LVFA) are associated with seizure-free outcome (Engel I). However, several classifications and various terms corresponding to the same pattern have been reported, challenging its use in clinical practice. METHOD: Following the Preferred Reporting Items of Systematic reviews and Meta-Analyses (PRISMA) guideline, we performed a systematic review of studies describing SOPs along with accompanying figures depicting the reported SOP in SEEG. RESULTS: Of 1799 studies, 22 met the selection criteria. Among the various SOPs, we observed that the terminology for low frequency periodic spikes exhibited the most variability, whereas LVFA is the most frequently used term of this pattern. Some SOP terms were inconsistent with standard EEG terminology. Finally, there was a significant but weak association between presence of LVFA and seizure-free outcome. CONCLUSION: Divergent terms were used to describe the same SOPs and some of these terms showed inconsistencies with the standard EEG terminology. Additionally, our results confirmed the link between patterns with LVFA and seizure-free outcomes. However, this association was not strong. SIGNIFICANCE: These results underline the need for standardization of SEEG terminology.