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Background and ObjectivesAccurate delineation of the seizure-onset zone (SOZ) in focal drug-resistant epilepsy often requires stereo-EEG (SEEG) recordings. Our aims were to propose a truly objective and quantitative comparison between EEG/magnetoencephalography (MEG) source imaging (EMSI), EEG/fMRI responses for similar spikes with primary irritative zone (PIZ) and SOZ defined by SEEG and to evaluate the value of EMSI and EEG/fMRI to predict postsurgical outcome.MethodsWe identified patients with drug-resistant epilepsy who underwent EEG/MEG, EEG/fMRI, and subsequent SEEG at the Epilepsy Service from the Montreal Neurological Institute and Hospital. We quantified multimodal concordance within the SEEG channel space as spatial overlap with PIZ/SOZ and distances to the spike-onset, spike maximum amplitude and seizure core intracerebral channels by applying a new methodology consisting of converting EMSI results into SEEG electrical potentials (EMSIe–SEEG) and projecting the most significant fMRI response on the SEEG channels (fMRIp–SEEG). Spatial overlaps with PIZ/SOZ (AUCPIZ, AUCSOZ) were assessed by using the area under the receiver operating characteristic curve (AUC). Here, AUC represents the probability that a randomly picked active contact exhibited higher amplitude when located inside the spatial reference than outside.ResultsSeventeen patients were included. Mean spatial overlaps with the PIZ and SOZ were 0.71 and 0.65 for EMSIe–SEEG and 0.57 and 0.62 for fMRIp–SEEG. Good EMSIe–SEEG spatial overlap with the PIZ was associated with smaller distance from the maximum EMSIe–SEEG contact to the spike maximum amplitude channel (median distance 14 mm). Conversely, good fMRIp–SEEG spatial overlap with the SOZ was associated with smaller distances from the maximum fMRIp–SEEG contact to the spike-onset and seizure core channels (median distances 10 and 5 mm, respectively). Surgical outcomes were correctly predicted by EEG/MEG in 12 of 15 (80%) patients and EEG/fMRI in 6 of 11(54%) patients.DiscussionWith the use of a unique quantitative approach estimating EMSI and fMRI results in the reference SEEG channel space, EEG/MEG and EEG/fMRI accurately localized the SOZ and the PIZ. Precisely, EEG/MEG more accurately localized the PIZ, whereas EEG/fMRI was more sensitive to the SOZ. Both neuroimaging techniques provide complementary localization that can help guide SEEG implantation and select good candidates for surgery.

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., In FLE patients “healthy” brain areas at a distance from the epileptic focus respond to the interference of IEDs by generating inhibitory alpha and beta oscillations. More prominent alpha‐beta oscillations can be found in patients with less impaired neurocognitive profile. Cerebral cortex protects itself from IEDs with generation of inhibitory alpha‐beta oscillations at distant cortical regions.

Introduction Source localization of interictal epileptic discharges (IEDs) is clinically useful in the presurgical workup of epilepsy patients. Recently, we have demonstrated that distributed magnetic source imaging (dMSI) has better accuracy than clinically approved equivalent current dipole method (ECD). Here, we aimed to compare the performance of four different dMSI techniques: Minimum Norm Estimate (MNE), dynamic Statistical Parametric Mapping (dSPM), standardized Low-Resolution Electromagnetic Tomography (sLORETA) and coherent Maximum Entropy on the Mean (cMEM, an entropy-based technique). Methods We analyzed dMSI results of 206 IEDs derived from MEG recordings in 28 focal epilepsy patients who had a well-defined focus determined through intracranial EEG, epileptogenic MRI lesions or surgical resection. dMSI accuracy and spatial properties were quantitatively estimated as: (a) minimum distance between the source peak and the focus; (b) within-subject reproducibility; (c) spatial dispersion of the source map outside the focus; (d) extension of cortical map; (e) effect of thresholding on map size and properties. Results Distance between the map peak and epilepsy focus as well as within subject reproducibility were clinically comparable across methods (median distance from the focus around 1 cm). Spatial dispersion was significantly lower for cMEM. cMEM maps display typically higher contrast between the source maximum and surrounding regions, being therefore less sensitive to map thresholding. Conclusions All dMSI techniques under investigation provided excellent performance in localizing the epileptic focus. cMEM provides the lowest amount of spurious activity, while obtaining similar localization accuracy compared to other techniques. dMSI techniques currently available for clinical use have the potential to significantly improve identification of intracranial EEG targets and to guide surgical planning.

Funder: Helmholts International BigBrain Analytics & Learning Laboratory, Neurotransmitter receptors support the propagation of signals in the human brain. How receptor systems are situated within macro-scale neuroanatomy and how they shape emergent function remain poorly understood, and there exists no comprehensive atlas of receptors. Here we collate positron emission tomography data from more than 1,200 healthy individuals to construct a whole-brain three-dimensional normative atlas of 19 receptors and transporters across nine different neurotransmitter systems. We found that receptor profiles align with structural connectivity and mediate function, including neurophysiological oscillatory dynamics and resting-state hemodynamic functional connectivity. Using the Neurosynth cognitive atlas, we uncovered a topographic gradient of overlapping receptor distributions that separates extrinsic and intrinsic psychological processes. Finally, we found both expected and novel associations between receptor distributions and cortical abnormality patterns across 13 disorders. We replicated all findings in an independently collected autoradiography dataset. This work demonstrates how chemoarchitecture shapes brain structure and function, providing a new direction for studying multi-scale brain organization., For the Cambridge authors (Coles, Fryer & Aigbirhio): This work was funded by an MRC PET Neuroscience programme grant (Training and Novel Probes Programme in PET Neurochemistry - MR/K02308X/1) and by an MRC Developmental Pathway Funding Scheme grant (MR/L013215/1). This research in Cambridge was supported by the NIHR Cambridge Biomedical Research Centre (BRC-1215-20014). The views expressed are those of the authors and not necessarily those of the NIHR or the Department of Health and Social Care. JPC was supported by a British Journal of Anaesthesia/Royal College of Anaesthetists grant from the National Institute of Academic Anaesthesia.

Objective Drug-resistant temporal lobe epilepsy (TLE) is the most common type of epilepsy for which patients undergo surgery. Despite the best clinical judgment and currently available prediction algorithms, surgical outcomes remain variable. We aimed to build and to evaluate the performance of multidimensional Bayesian network classifiers (MBCs), a type of probabilistic graphical model, at predicting probability of seizure freedom after TLE surgery. Methods Clinical, neurophysiological, and imaging variables were collected from 231 TLE patients who underwent surgery at the University of California, San Francisco (UCSF) or the Montreal Neurological Institute (MNI) over a 15-year period. Postsurgical Engel outcomes at year 1 (Y1), Y2, and Y5 were analyzed as primary end points. We trained an MBC model on combined data sets from both institutions. Bootstrap bias corrected cross-validation (BBC-CV) was used to evaluate the performance of the models. Results The MBC was compared with logistic regression and Cox proportional hazards according to the area under the receiver-operating characteristic curve (AUC). The MBC achieved an AUC of 0.67 at Y1, 0.72 at Y2, and 0.67 at Y5, which indicates modest performance yet superior to what has been reported in the state-of-the-art studies to date. Significance The MBC can more precisely encode probabilistic relationships between predictors and class variables (Engel outcomes), achieving promising experimental results compared to other well-known statistical methods. Multisite application of the MBC could further optimize its classification accuracy with prospective data sets. Online access to the MBC is provided, paving the way for its use as an adjunct clinical tool in aiding pre-operative TLE surgical counseling.

Objective Surgical specimens from patients with mesial temporal lobe epilepsy (MTLE) show abnormalities in tissue concentrations of metabotropic glutamate receptor type 5 (mGluR5). To clarify whether these abnormalities are specific to the epileptogenic zone (EZ), we characterized in vivo whole-brain mGluR5 availability in MTLE patients using positron emission tomography (PET) and [11 C]ABP688, a radioligand that binds specifically to the mGluR5 allosteric site. Methods Thirty-one unilateral MTLE patients and 30 healthy controls underwent [11 C]ABP688 PET. We compared partial volume corrected [11 C]ABP688 nondisplaceable binding potentials (BPND ) between groups using region-of-interest and whole-brain voxelwise analyses. [18 F]Fluorodeoxyglucose (FDG) PET was acquired in 15 patients, for whom we calculated asymmetry indices of [11 C]ABP688 BPND and [18 F]FDG uptake to compare lateralization and localization differences. Results [11 C]ABP688 BPND was focally reduced in the epileptogenic hippocampal head and amygdala (p 1 year of follow-up, 13 were seizure-free (Engel Ia) and showed significantly lower [11 C]ABP688 BPND in the ipsilateral entorhinal cortex. Interpretation [11 C]ABP688 PET provides a focal biomarker for the EZ in MTLE with higher spatial accuracy compared to [18 F]FDG PET. Focally reduced mGluR5 availability in the EZ might reflect receptor internalization or conformational changes in response to excessive extracellular glutamate, supporting a potential role for mGluR5 as therapeutic target in human MTLE. Ann Neurol 2019; 1-11 ANN NEUROL 2019;85:218-228.

OBJECTIVE Previous positron emission tomography (PET) studies using [11 C]ABP688 show reduced metabotropic glutamate receptor type 5 (mGluR5) allosteric binding site availability in the epileptogenic hippocampus of mesial temporal lobe epilepsy (MTLE) patients. However, the link between mGluR5 abnormalities and postsurgical outcomes remains unclear. Here, we test whether reduced PET [11 C]ABP688 binding in cornu ammonis (CA) sectors more vulnerable to glutamatergic excitotoxicity relates to surgical outcomes. METHODS We obtained magnetic resonance imaging (MRI) and [11 C]ABP688-PET from 31 unilateral MTLE patients and 30 healthy controls. MRI hippocampal subfields were segmented using FreeSurfer. To respect the lower PET special resolution, MRI-derived anatomical subfields were combined into CA1-3, CA4/dentate gyrus, and Subiculum. Partial volume corrected [11 C]ABP688 nondisplaceable binding potential (BPND ) values were averaged across each subfield, and Z-scores were calculated. Subfield [11 C]ABP688-BPND was compared between seizure-free and non-seizure-free patients. In addition, we also assessed subfield volumes and [18 F]fluorodeoxyglucose (FDG) uptake in each clinical group. RESULTS MTLE [11 C]ABP688-BPND was reduced in ipsilateral (epileptogenic) CA1-3 and CA4/dentate-gyrus (p

Introduction: During the past decades there has been an increasing interest in tracking brain network fluctuations in health and disease by means of resting state functional magnetic resonance imaging (rs-fMRI). Rs-fMRI however does not provide the ideal environmental setting, as participants are continuously exposed to noise generated by MRI coils during acquisition of Echo Planar Imaging (EPI). We investigated the effect of EPI noise on resting state activity and connectivity using magnetoencephalography (MEG), by reproducing the acoustic characteristics of rs-fMRI environment during the recordings. As compared to fMRI, MEG has little sensitivity to brain activity generated in deep brain structures, but has the advantage to capture both the dynamic of cortical magnetic oscillations with high temporal resolution and the slow magnetic fluctuations highly correlated with BOLD signal. Methods: Thirty healthy subjects were enrolled in a counterbalanced design study including three conditions: a) silent resting state (Silence), b) resting state upon EPI noise (fMRI), and c) resting state upon white noise (White). White noise was employed to test the specificity of fMRI noise effect. The amplitude envelope correlation (AEC) in alpha band measured the connectivity of seven Resting State Networks (RSN) of interest (default mode network, dorsal attention network, language, left and right auditory and left and right sensory-motor). Vigilance dynamic was estimated from power spectral activity. Results: fMRI and White acoustic noise consistently reduced connectivity of cortical networks. The effects were widespread, but noise and network specificities were also present. For fMRI noise, decreased connectivity was found in the right auditory and sensory-motor networks. Progressive increase of slow theta-delta activity related to drowsiness was found in all conditions, but was significantly higher for fMRI . Theta-delta significantly and positively correlated with variations of cortical connectivity. Discussion: rs-fMRI connectivity is biased by unavoidable environmental factors during scanning, which warrant more careful control and improved experimental designs. MEG is free from acoustic noise and allows a sensitive estimation of resting state connectivity in cortical areas. Although underutilized, MEG could overcome issues related to noise during fMRI, in particular when investigation of motor and auditory networks is needed.

In functional near infrared spectroscopy (fNIRS), deconvolution analysis of oxy and deoxy-hemoglobin concentration changes allows estimating specific hemodynamic response functions (HRF) elicited by neuronal activity, taking advantage of the fNIRS excellent temporal resolution. Diffuse optical tomography (DOT) is also becoming the new standard reconstruction procedure as it is more accurate than the modified Beer Lambert law approach at the sensor level. The objective of this study was to assess the relevance of HRF deconvolution after DOT constrained along the cortical surface. We used local personalized fNIRS montages which consists in optimizing the position of fNIRS optodes to ensure maximal sensitivity to subject specific target brain regions. We carefully evaluated the accuracy of deconvolution when applied after DOT, using realistic simulations involving several HRF models at different signal to noise ratio (SNR) levels and on real data related to motor and visual tasks in healthy subjects and from spontaneous pathological activity in one patient with epilepsy. We demonstrated that DOT followed by deconvolution was able to accurately recover a large variability of HRFs over a large range of SNRs. We found good performances of deconvolution analysis for SNR levels usually encountered in our applications and we were able to reconstruct accurately the temporal dynamics of HRFs in real conditions.

Highlights • Utilized graph theory to study mGluR5 networks in FCD patients. • Global reductions were observed in mGluR5 network efficiency and resilience. • Epilepsy duration was associated with network efficiency in hub regions. • Focal epileptogenic lesions may progressively reduce whole brain network integration., To determine the extent of metabotropic glutamate receptor type 5 (mGluR5) network abnormalities associated with focal cortical dysplasia (FCD), we performed graph theoretical analysis of [11C]ABP688 PET binding potentials (BPND), which allows for quantification of mGluR5 availability. Undirected graphs were constructed for the entire cortex in 17 FCD patients and 33 healthy controls using inter-regional similarity of [11C]ABP688 BPND. We assessed group differences in network integration between healthy controls and the ipsilateral and contralateral hemispheres of FCD patients. Compared to healthy controls, FCD patients showed reduced network efficiency and reduced small-world connectivity. The mGluR5 network of FCD patients was also less resilient to targeted removal of high centrality nodes, suggesting a less integrated network organization. In highly efficient hub nodes of FCD patients, we observed a significant negative correlation between local efficiency and duration of epilepsy only in the contralateral hemisphere, suggesting that some nodes may be more vulnerable to persistent epileptic activity. Our study provides the first in vivo evidence for a widespread reduction in cortical mGluR5 network integration in FCD patients. In addition, we find that ongoing epileptic activity may alter chemoarchitectural brain organization resulting in reduced efficiency in distant regions that are essential for network integration.

Background Application of functional Near InfraRed Spectroscopy (fNIRS) in neurology is still limited as a good optical coupling and optimized optode coverage of specific brain regions remains challenging, notably for prolonged monitoring. Methods We propose to evaluate a new procedure allowing accurate investigation of specific brain regions. The procedure consists in: (i) A priori maximization of spatial sensitivity of fNIRS measurements targeting specific brain regions, while reducing the number of applied optodes in order to decrease installation time and improve subject comfort. (ii) Utilization of a 3D neuronavigation device and usage of collodion to glue optodes on the scalp, ensuring good optical contact for prolonged investigations. (iii) Local reconstruction of the hemodynamic activity along the cortical surface using inverse modelling. Results Using realistic simulations, we demonstrated that maps derived from optimal montage acquisitions showed, after reconstruction, spatial resolution only slightly lower to that of ultra high density montages while significantly reducing the number of optodes. The optimal montages provided overall good quantitative accuracy especially at the peak of the spatially reconstructed map. We also evaluated real motor responses in two healthy subjects and obtained reproducible motor responses over different sessions. Comparison with existing methods We are among the first to propose a mathematical optimization strategy, allowing high sensitivity measurements. Conclusions Our results support that using personalized optimal montages should allow to conduct accurate fNIRS studies in clinical settings and realistic lifestyle conditions.

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.

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

Background The present study aims at evaluating and comparing electrical and magnetic distributed source imaging methods applied to high-density Electroencephalography (hdEEG) and Magnetoencephalography (MEG) data. We used resolution matrices to characterize spatial resolution properties of Minimum Norm Estimate (MNE), dynamic Statistical Parametric Mapping (dSPM), standardized Low-Resolution Electromagnetic Tomography (sLORETA) and coherent Maximum Entropy on the Mean (cMEM, an entropy-based technique). The resolution matrix provides information of the Point Spread Functions (PSF) and of the Crosstalk functions (CT), this latter being also called source leakage, as it reflects the influence of a source on its neighbors. Methods The spatial resolution of the inverse operators was first evaluated theoretically and then with real data acquired using electrical median nerve stimulation on five healthy participants. We evaluated the Dipole Localization Error (DLE) and the Spatial Dispersion (SD) of each PSF and CT map. Results cMEM showed the smallest spatial spread (SD) for both PSF and CT maps, whereas localization errors (DLE) were similar for all methods. Whereas cMEM SD values were lower in MEG compared to hdEEG, the other methods slightly favored hdEEG over MEG. In real data, cMEM provided similar localization error and significantly less spatial spread than other methods for both MEG and hdEEG. Whereas both MEG and hdEEG provided very accurate localizations, all the source imaging methods actually performed better in MEG compared to hdEEG according to all evaluation metrics, probably due to the higher signal-to-noise ratio of the data in MEG. Conclusion Our overall results show that all investigated methods provide similar localization errors, suggesting very accurate localization for both MEG and hdEEG when similar number of sensors are considered for both modalities. Intrinsic properties of source imaging methods as well as their behavior for well-controlled tasks, suggest an overall better performance of cMEM in regards to spatial resolution and spatial leakage for both hdEEG and MEG. This indicates that cMEM would be a good candidate for studying source localization of focal and extended generators as well as functional connectivity studies.

Metabotropic glutamate receptor type 5 (mGluR5) abnormalities have been described in tissue resected from epilepsy patients with focal cortical dysplasia (FCD). To determine if these abnormalities could be identified in vivo, we investigated mGluR5 availability in 10 patients with focal epilepsy and an MRI diagnosis of FCD using positron-emission tomography (PET) and the radioligand [11C]ABP688. Partial volume corrected [11C]ABP688 binding potentials (BPND) were computed using the cerebellum as a reference region. Each patient was compared to homotopic cortical regions in 33 healthy controls using region-of-interest (ROI) and vertex-wise analyses. Reduced [11C]ABP688 BPND in the FCD was seen in 7/10 patients with combined ROI and vertex-wise analyses. Reduced FCD BPND was found in 4/5 operated patients (mean follow-up: 63 months; Engel I), of whom surgical specimens revealed FCD type IIb or IIa, with most balloon cells showing negative or weak mGluR5 immunoreactivity as compared to their respective neuropil and normal neurons at the border of resections. [11C]ABP688 PET shows for the first time in vivo evidence of reduced mGluR5 availability in FCD, indicating focal glutamatergic alterations in malformations of cortical development, which cannot be otherwise clearly demonstrated through resected tissue analyses.

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, 2016. © 2016 Wiley Periodicals, Inc.

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.

Objective Focal epilepsy is a disorder affecting several brain networks; however, epilepsy surgery usually targets a restricted region, the so-called epileptic focus. There is a growing interest in embedding resting state (RS) connectivity analysis into pre-surgical workup. Approach In this retrospective study, we analyzed Magnetoencephalography (MEG) long-range RS functional connectivity patterns in patients with drug-resistant focal epilepsy. MEG recorded prior to surgery from seven seizure-free (Engel Ia) and five non seizure-free (Engel III or IV) patients were analyzed (minimum 2-years post-surgical follow-up). MEG segments without any detectable epileptic activity were source localized using wavelet-based Maximum Entropy on the Mean method. Amplitude envelope correlation in the theta (4-8 Hz), alpha (8-13 Hz), and beta (13-26 Hz) bands were used for assessing connectivity. Main results For seizure-free patients, we found an isolated epileptic network characterized by weaker connections between the brain region where interictal epileptic discharges (IED) are generated and the rest of the cortex, when compared to connectivity between the corresponding contralateral homologous region and the rest of the cortex. Contrarily, non seizure-free patients exhibited a widespread RS epileptic network characterized by stronger connectivity between the IED generator and the rest of the cortex, in comparison to the contralateral region and the cortex. Differences between the two seizure outcome groups concerned mainly distant long-range connections and were found in the alpha-band. Significance Importantly, these connectivity patterns suggest specific mechanisms describing the underlying organization of the epileptic network and were detectable at the individual patient level, supporting the prospect use of MEG connectivity patterns in epilepsy to predict post-surgical seizure outcome.

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Surgical specimens from patients with mesial temporal lobe epilepsy (MTLE) show abnormalities in tissue concentrations of metabotropic glutamate receptor type 5 (mGluR5). To clarify whether these abnormalities are specific to the epileptogenic zone (EZ), we characterized in vivo whole-brain mGluR5 availability in MTLE patients using positron emission tomography (PET) and [Thirty-one unilateral MTLE patients and 30 healthy controls underwent [[[

Metabotropic glutamate receptor type 5 (mGluR5) is a G protein-coupled receptor that has been implicated in several psychiatric and neurological diseases. The radiopharmaceutical [(11)C]ABP688 allows for in vivo quantification of mGluR5 availability using positron emission tomography (PET). In this study, we aimed to detail the regional distribution of [(11)C]ABP688 binding potential (BPND) and the existence of age/sex effects in healthy individuals.Thirty-one healthy individuals aged 20 to 77 years (men, n = 18, 45.3 ± 18.2 years; females, n = 13, 41.5 ± 19.6 years) underwent imaging with [(11)C]ABP688 using the high-resolution research tomograph (HRRT). We developed an advanced partial volume correction (PVC) method using surface-based analysis in order to accurately estimate the regional variation of radioactivity. BPND was calculated using the simplified reference tissue model, with the cerebellum as the reference region. Surface-based and volume-based analyses were performed for 39 cortical and subcortical regions of interest per hemisphere.We found the highest [(11)C]ABP688 BPND in the lateral prefrontal and anterior cingulate cortices. The lowest [(11)C]ABP688 BPND was observed in the pre- and post-central gyri as well as the occipital lobes and the thalami. No sex effect was observed. Associations between age and [(11)C]ABP688 BPND without PVC were observed in the right amygdala and left putamen, but were not significant after multiple comparisons correction.The present results highlight complexities underlying brain adaptations during the aging process, and support the notion that certain aspects of neurotransmission remain stable during the adult life span.

Whether occurring before or after an epilepsy surgery, psychogenic nonepileptic seizures (PNES) impact treatment options and quality of life of patients with epilepsy. We investigated the frequency of pre- and postsurgical PNES, and the postsurgical Engel and psychiatric outcomes in patients with drug-resistant temporal lobe epilepsy (TLE). We reviewed 278 patients with mean age at surgery of 37.1±12.4years. Postsurgical follow-up information was available in 220 patients, with average follow-up of 4years. Nine patients (9/278 or 3.2%) had presurgical documented PNES. Eight patients (8/220 or 3.6%) developed de novo PNES after surgery. Pre- and postsurgery psychiatric comorbidities were similar to the patients without PNES. After surgery, in the group with presurgical PNES, five patients were seizure-free, and three presented persistent PNES. In the group with de novo postsurgery PNES, 62.5% had Engel II-IV, and 37.5% had Engel I. All presented PNES at last follow-up. Presurgical video-EEG monitoring is crucial in the diagnosis of coexisting PNES. Patients presenting presurgical PNES and drug-resistant TLE should not be denied surgery based on this comorbidity, as they can have good postsurgical epilepsy and psychiatric outcomes. Psychogenic nonepileptic seizures may appear after TLE surgery in a low but noteworthy proportion of patients regardless of the Engel outcome.

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