Search

The replication crisis in experimental psychology and neuroscience has received much attention recently. This has led to wide acceptance of measures to improve scientific practices, such as preregistration and registered reports. Less effort has been devoted to performing and reporting the results of systematic tests of the functioning of the experimental setup itself. Yet, inaccuracies in the performance of the experimental setup may affect the results of a study, lead to replication failures, and importantly, impede the ability to integrate results across studies. Prompted by challenges we experienced when deploying studies across six laboratories collecting electroencephalography (EEG)/magnetoencephalography (MEG), functional magnetic resonance imaging (fMRI), and intracranial EEG (iEEG), here we describe a framework for both testing and reporting the performance of the experimental setup. In addition, 100 researchers were surveyed to provide a snapshot of current common practices and community standards concerning testing in published experiments' setups. Most researchers reported testing their experimental setups. Almost none, however, published the tests performed or their results. Tests were diverse, targeting different aspects of the setup. Through simulations, we clearly demonstrate how even slight inaccuracies can impact the final results. We end with a standardized, open-source, step-by-step protocol for testing (visual) event-related experiments, shared via protocols.io. The protocol aims to provide researchers with a benchmark for future replications and insights into the research quality to help improve the reproducibility of results, accelerate multicenter studies, increase robustness, and enable integration across studies., (© 2024. The Author(s).)

Background: Multivariate pattern analysis (MVPA) has proven an excellent tool in cognitive neuroscience. It also holds a strong promise when applied to optically-pumped magnetometer-based magnetoencephalography., New Method: To optimize OPM-MEG systems for MVPA experiments this study examines data from a conventional MEG magnetometer array, focusing on appropriate noise reduction techniques for magnetometers. We determined the least required number of sensors needed for robust MVPA for image categorization experiments., Results: We found that the use of signal space separation (SSS) without a proper regularization significantly lowered the classification accuracy considering a sub-array of 102 magnetometers or a sub-array of 204 gradiometers. We also found that classification accuracy did not improve when going beyond 30 sensors irrespective of whether SSS has been applied., Comparison With Existing Methods: The power spectra of data filtered with SSS has a substantially higher noise floor that data cleaned with SSP or HFC. Consequently, MVPA decoding results obtained from the SSS-filtered data are significantly lower compared to all other methods employed., Conclusions: When designing MEG system based on SQUID magnetometers optimized for multivariate analysis for image categorization experiments, about 30 magnetometers are sufficient. We advise against applying SSS filters without a proper regularization to data from MEG and OPM systems prior to performing MVPA as this method, albeit reducing low-frequency external noise contributions, also introduces an increase in broadband noise. We recommend employing noise reduction techniques that either decrease or maintain the noise floor of the data like signal-space projection, homogeneous field correction and gradient noise reduction., Competing Interests: Declaration of Competing Interest The authors report no conflicts of interest, (Copyright © 2024. Published by Elsevier B.V.)

Pre-surgical localization of language function in the brain is critical for patients with medically intractable epilepsy. MEG has emerged as a valuable clinical tool for localizing language areas in clinical populations, however, it is limited for widespread application due to the low availability of the system. Recent advances in optically pumped magnetometer (OPM) systems account for some of the limitations of traditional MEG and have been shown to have a similar signal-to-noise ratio. However, the novelty of these systems means that they have only been tested for limited sensory and motor applications. In this work, we aim to validate a novel on-head OPM MEG procedure for lateralizing language processes. OPM recordings, using a soft cap with flexible sensor placement, were collected from 19 healthy, right-handed controls during an auditory word recognition task. The resulting evoked fields were assessed for hemispheric laterality of the response. Principal component analysis (PCA) of the grand average language response indicated that the first two principal components were lateralized to the left hemisphere. The PCA also revealed that all participants had evoked topographies that closely resembled the average left-lateralized response. Left-lateralized responses were consistent with what is expected for a group of healthy right-handed individuals. These findings demonstrate that language-related evoked fields can be elucidated from on-head OPM MEG recordings in a group of healthy adult participants. In the future, on-head OPM MEG and the associated lateralization methods should be validated in patient populations as they may have utility in the pre-surgical mapping of language functions in patients with epilepsy., (© 2024. The Author(s), under exclusive licence to Springer Science+Business Media, LLC, part of Springer Nature.)

Electroencephalography (EEG) or Magnetoencephalography (MEG) source imaging aims to estimate the underlying activated brain sources to explain the observed EEG/MEG recordings. Solving the inverse problem of EEG/MEG Source Imaging (ESI) is challenging due to its ill-posed nature. To achieve a unique solution, it is essential to apply sophisticated regularization constraints to restrict the solution space. Traditionally, the design of regularization terms is based on assumptions about the spatiotemporal structure of the underlying source dynamics. In this paper, we propose a novel paradigm for ESI via an Explainable Deep Learning framework, termed as XDL-ESI, which connects the iterative optimization algorithm with deep learning architecture by unfolding the iterative updates with neural network modules. The proposed framework has the advantages of (1) establishing a data-driven approach to model the source solution structure instead of using hand-crafted regularization terms; (2) improving the robustness of source solutions by introducing a topological loss that leverages the geometric spatial information applying varying penalties on distinct localization errors; (3) improving the reconstruction efficiency and interpretability as it inherits the advantages from both the iterative optimization algorithms (interpretability) and deep learning approaches (function approximation). The proposed XDL-ESI framework provides an efficient, accurate, and interpretable paradigm to solve the ESI inverse problem with satisfactory performance in both simulated data and real clinical data. Specially, this approach is further validated using simultaneous EEG and intracranial EEG (iEEG)., Competing Interests: Declaration of competing interest The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper., (Copyright © 2024. Published by Elsevier Inc.)

Objective: Somatosensory evoked spikes (SESs) have been reported only in children aged under 14 years and are considered as an age-dependent phenomenon. However, we detected SESs in adult patients with epilepsy using magnetoencephalography (MEG). The present study investigated whether MEG can detect SESs in normal adults., Methods: Spontaneous MEG was recorded during measurement of somatosensory evoked fields (SEFs) for bilateral electrical median nerve stimuli in 30 healthy adults., Results: Bilateral SESs were observed in 10 adults but none in the other 20 subjects. SESs consisted of one or two peaks, and the first peak latency corresponded to that of the second peak (M2) of SEFs. The first SES peak was identical to the M2 in isofield map pattern, as well as location and orientation of the equivalent current dipole (ECD). M2 ECD strength in the 10 subjects with SESs was larger (p <0.0001) than in 20 without SESs., Conclusions: All-or-nothing detection of bilateral SESs by MEG in normal adults must depend on the signal-to-noise issue of symmetrical SEFs and background brain activity., Significance: Our results further confirm the higher sensitivity of MEG compared to scalp EEG for the detection of focal cortical sources tangential to the scalp such as SESs., (Copyright © 2024 International Federation of Clinical Neurophysiology. Published by Elsevier B.V. All rights reserved.)

This study assesses the reliability of resting-state dynamic causal modelling (DCM) of magnetoencephalography (MEG) under conductance-based canonical microcircuit models, in terms of both posterior parameter estimates and model evidence. We use resting-state MEG data from two sessions, acquired 2 weeks apart, from a cohort with high between-subject variance arising from Alzheimer's disease. Our focus is not on the effect of disease, but on the reliability of the methods (as within-subject between-session agreement), which is crucial for future studies of disease progression and drug intervention. To assess the reliability of first-level DCMs, we compare model evidence associated with the covariance among subject-specific free energies (i.e., the 'quality' of the models) with versus without interclass correlations. We then used parametric empirical Bayes (PEB) to investigate the differences between the inferred DCM parameter probability distributions at the between subject level. Specifically, we examined the evidence for or against parameter differences (i) within-subject, within-session, and between-epochs; (ii) within-subject between-session; and (iii) within-site between-subjects, accommodating the conditional dependency among parameter estimates. We show that for data acquired close in time, and under similar circumstances, more than 95% of inferred DCM parameters are unlikely to differ, speaking to mutual predictability over sessions. Using PEB, we show a reciprocal relationship between a conventional definition of 'reliability' and the conditional dependency among inferred model parameters. Our analyses confirm the reliability and reproducibility of the conductance-based DCMs for resting-state neurophysiological data. In this respect, the implicit generative modelling is suitable for interventional and longitudinal studies of neurological and psychiatric disorders., (© 2024 The Author(s). Human Brain Mapping published by Wiley Periodicals LLC.)

Objective: Diseases affecting sensorimotor function impair physical independence. Reliable functional clinical biomarkers allowing early diagnosis or targeting treatment and rehabilitation could reduce this burden. Magnetoencephalography (MEG) non-invasively measures brain rhythms such as the somatomotor 'rolandic' rhythm which shows intermittent high-amplitude beta (14-30 Hz) 'events' that predict behavior across tasks and species and are altered by sensorimotor neurological diseases., Methods: We assessed test-retest stability, a prerequisite for biomarkers, of spontaneous sensorimotor aperiodic (1/f) signal and beta events in 50 healthy human controls across two MEG sessions using the intraclass correlation coefficient (ICC). Beta events were determined using an amplitude-thresholding approach on a narrow-band filtered amplitude envelope obtained using Morlet wavelet decomposition., Results: Resting sensorimotor characteristics showed good to excellent test-retest stability. Aperiodic component (ICC 0.77-0.88) and beta event amplitude (ICC 0.74-0.82) were very stable, whereas beta event duration was more variable (ICC 0.55-0.7). 2-3 minute recordings were sufficient to obtain stable results. Analysis automatization was successful in 86%., Conclusions: Sensorimotor beta phenotype is a stable feature of an individual's resting brain activity even for short recordings easily measured in patients., Significance: Spontaneous sensorimotor beta phenotype has potential as a clinical biomarker of sensorimotor system integrity., (Copyright © 2024 International Federation of Clinical Neurophysiology. Published by Elsevier B.V. All rights reserved.)

Prior studies have used graph analysis of resting-state magnetoencephalography (MEG) to characterize abnormal brain networks in neurological disorders. However, a present challenge for researchers is the lack of guidance on which network construction strategies to employ. The reproducibility of graph measures is important for their use as clinical biomarkers. Furthermore, global graph measures should ideally not depend on whether the analysis was performed in the sensor or source space. Therefore, MEG data of the 89 healthy subjects of the Human Connectome Project were used to investigate test-retest reliability and sensor versus source association of global graph measures. Atlas-based beamforming was used for source reconstruction, and functional connectivity (FC) was estimated for both sensor and source signals in six frequency bands using the debiased weighted phase lag index (dwPLI), amplitude envelope correlation (AEC), and leakage-corrected AEC. Reliability was examined over multiple network density levels achieved with proportional weight and orthogonal minimum spanning tree thresholding. At a 100% density, graph measures for most FC metrics and frequency bands had fair to excellent reliability and significant sensor versus source association. The greatest reliability and sensor versus source association was obtained when using amplitude metrics. Reliability was similar between sensor and source spaces when using amplitude metrics but greater for the source than the sensor space in higher frequency bands when using the dwPLI. These results suggest that graph measures are useful biomarkers, particularly for investigating functional networks based on amplitude synchrony., (© 2021 The Authors. Human Brain Mapping published by Wiley Periodicals LLC.)

The Rolandic beta rhythm, at ∼20 Hz, is generated in the somatosensory and motor cortices and is modulated by motor activity and sensory stimuli, causing a short lasting suppression that is followed by a rebound of the beta rhythm. The rebound reflects inhibitory changes in the primary sensorimotor (SMI) cortex, and thus it has been used as a biomarker to follow the recovery of patients with acute stroke. The longitudinal stability of beta rhythm modulation is a prerequisite for its use in long-term follow-ups. We quantified the reproducibility of beta rhythm modulation in healthy subjects in a 1-year-longitudinal study both for MEG and EEG at T 0 , 1 month ( T 1-month , n = 8) and 1 year ( T 1-year , n = 19). The beta rhythm (13-25 Hz) was modulated by fixed tactile and proprioceptive stimulations of the index fingers. The relative peak strengths of beta suppression and rebound did not differ significantly between the sessions, and intersession reproducibility was good or excellent according to intraclass correlation-coefficient values (0.70-0.96) both in MEG and EEG. Our results indicate that the beta rhythm modulation to tactile and proprioceptive stimulation is well reproducible within 1 year. These results support the use of beta modulation as a biomarker in long-term follow-up studies, e.g., to quantify the functional state of the SMI cortex during rehabilitation and drug interventions in various neurological impairments. NEW & NOTEWORTHY The present study demonstrates that beta rhythm modulation is highly reproducible in a group of healthy subjects within a year. Hence, it can be reliably used as a biomarker in longitudinal follow-up studies in different neurological patient groups to reflect changes in the functional state of the sensorimotor cortex.

In this paper, we analyze spatial sampling of electro- (EEG) and magnetoencephalography (MEG), where the electric or magnetic field is typically sampled on a curved surface such as the scalp. By simulating fields originating from a representative adult-male head, we study the spatial-frequency content in EEG as well as in on- and off-scalp MEG. This analysis suggests that on-scalp MEG, off-scalp MEG and EEG can benefit from up to 280, 90 and 110 spatial samples, respectively. In addition, we suggest a new approach to obtain sensor locations that are optimal with respect to prior assumptions. The approach also allows to control, e.g., the uniformity of the sensor locations. Based on our simulations, we argue that for a low number of spatial samples, model-informed non-uniform sampling can be beneficial. For a large number of samples, uniform sampling grids yield nearly the same total information as the model-informed grids., Competing Interests: Declaration of Competing Interest The authors declare that they have no conflict of interest., (Copyright © 2021. Published by Elsevier Inc.)

Magnetoencephalography (MEG) is a functional neuroimaging tool that records the magnetic fields induced by neuronal activity; however, signal from non-neuronal sources can corrupt the data. Eye-blinks, saccades, and cardiac activity are three of the most common sources of non-neuronal artifacts. They can be measured by affixing eye proximal electrodes, as in electrooculography (EOG), and chest electrodes, as in electrocardiography (ECG), however this complicates imaging setup, decreases patient comfort, and can induce further artifacts from movement. This work proposes an EOG- and ECG-free approach to identify eye-blinks, saccades, and cardiac activity signals for automated artifact suppression. The contribution of this work is three-fold. First, using a data driven, multivariate decomposition approach based on Independent Component Analysis (ICA), a highly accurate artifact classifier is constructed as an amalgam of deep 1-D and 2-D Convolutional Neural Networks (CNNs) to automate the identification and removal of ubiquitous whole brain artifacts including eye-blink, saccade, and cardiac artifacts. The specific architecture of this network is optimized through an unbiased, computer-based hyperparameter random search. Second, visualization methods are applied to the learned abstraction to reveal what features the model uses and to bolster user confidence in the model's training and potential for generalization. Finally, the model is trained and tested on both resting-state and task MEG data from 217 subjects, and achieves a new state-of-the-art in artifact detection accuracy of 98.95% including 96.74% sensitivity and 99.34% specificity on the held out test-set. This work automates MEG processing for both clinical and research use, adapts to the acquired acquisition time, and can obviate the need for EOG or ECG electrodes for artifact detection., Competing Interests: Declaration of Competing Interest The authors declare no conflict of interest., (Copyright © 2021. Published by Elsevier Inc.)

Optically pumped magnetometers (OPMs) are quickly widening the scopes of noninvasive neurophysiological imaging. The possibility of placing these magnetic field sensors on the scalp allows not only to acquire signals from people in movement, but also to reduce the distance between the sensors and the brain, with a consequent gain in the signal-to-noise ratio. These advantages make the technique particularly attractive to characterise sources of brain activity in demanding populations, such as children and patients with epilepsy. However, the technology is currently in an early stage, presenting new design challenges around the optimal sensor arrangement and their complementarity with other techniques as electroencephalography (EEG). In this article, we present an optimal array design strategy focussed on minimising the brain source localisation error. The methodology is based on the Cramér-Rao bound, which provides lower error bounds on the estimation of source parameters regardless of the algorithm used. We utilise this framework to compare whole head OPM arrays with commercially available electro/magnetoencephalography (E/MEG) systems for localising brain signal generators. In addition, we study the complementarity between EEG and OPM-based MEG, and design optimal whole head systems based on OPMs only and a combination of OPMs and EEG electrodes for characterising deep and superficial sources alike. Finally, we show the usefulness of the approach to find the nearly optimal sensor positions minimising the estimation error bound in a given cortical region when a limited number of OPMs are available. This is of special interest for maximising the performance of small scale systems to ad hoc neurophysiological experiments, a common situation arising in most OPM labs., (© 2021 The Authors. Human Brain Mapping published by Wiley Periodicals LLC.)

Individual characterization of subjects based on their functional connectome (FC), termed "FC fingerprinting", has become a highly sought-after goal in contemporary neuroscience research. Recent functional magnetic resonance imaging (fMRI) studies have demonstrated unique characterization and accurate identification of individuals as an accomplished task. However, FC fingerprinting in magnetoencephalography (MEG) data is still widely unexplored. Here, we study resting-state MEG data from the Human Connectome Project to assess the MEG FC fingerprinting and its relationship with several factors including amplitude- and phase-coupling functional connectivity measures, spatial leakage correction, frequency bands, and behavioral significance. To this end, we first employ two identification scoring methods, differential identifiability and success rate, to provide quantitative fingerprint scores for each FC measurement. Secondly, we explore the edgewise and nodal MEG fingerprinting patterns across the different frequency bands (delta, theta, alpha, beta, and gamma). Finally, we investigate the cross-modality fingerprinting patterns obtained from MEG and fMRI recordings from the same subjects. We assess the behavioral significance of FC across connectivity measures and imaging modalities using partial least square correlation analyses. Our results suggest that fingerprinting performance is heavily dependent on the functional connectivity measure, frequency band, identification scoring method, and spatial leakage correction. We report higher MEG fingerprinting performances in phase-coupling methods, central frequency bands (alpha and beta), and in the visual, frontoparietal, dorsal-attention, and default-mode networks. Furthermore, cross-modality comparisons reveal a certain degree of spatial concordance in fingerprinting patterns between the MEG and fMRI data, especially in the visual system. Finally, the multivariate correlation analyses show that MEG connectomes have strong behavioral significance, which however depends on the considered connectivity measure and temporal scale. This comprehensive, albeit preliminary investigation of MEG connectome test-retest identifiability offers a first characterization of MEG fingerprinting in relation to different methodological and electrophysiological factors and contributes to the understanding of fingerprinting cross-modal relationships. We hope that this first investigation will contribute to setting the grounds for MEG connectome identification., Competing Interests: Declaration of Competing Interest The authors declare no competing financial interests., (Copyright © 2021. Published by Elsevier Inc.)

Noninvasive functional neuroimaging of the human brain can give crucial insight into the mechanisms that underpin healthy cognition and neurological disorders. Magnetoencephalography (MEG) measures extracranial magnetic fields originating from neuronal activity with high temporal resolution, but requires source reconstruction to make neuroanatomical inferences from these signals. Many source reconstruction algorithms are available, and have been widely evaluated in the context of localizing task-evoked activities. However, no consensus yet exists on the optimum algorithm for resting-state data. Here, we evaluated the performance of six commonly-used source reconstruction algorithms based on minimum-norm and beamforming estimates. Using human resting-state MEG, we compared the algorithms using quantitative metrics, including resolution properties of inverse solutions and explained variance in sensor-level data. Next, we proposed a data-driven approach to reduce the atlas from the Human Connectome Project's multi-modal parcellation of the human cortex based on metrics such as MEG signal-to-noise-ratio and resting-state functional connectivity gradients. This procedure produced a reduced cortical atlas with 230 regions, optimized to match the spatial resolution and the rank of MEG data from the current generation of MEG scanners. Our results show that there is no "one size fits all" algorithm, and make recommendations on the appropriate algorithms depending on the data and aimed analyses. Our comprehensive comparisons and recommendations can serve as a guide for choosing appropriate methodologies in future studies of resting-state MEG., (© 2021 The Authors. Human Brain Mapping published by Wiley Periodicals LLC.)

Clinical neurophysiology studies can contribute important information about the physiology of human movement and the pathophysiology and diagnosis of different movement disorders. Some techniques can be accomplished in a routine clinical neurophysiology laboratory and others require some special equipment. This review, initiating a series of articles on this topic, focuses on the methods and techniques. The methods reviewed include EMG, EEG, MEG, evoked potentials, coherence, accelerometry, posturography (balance), gait, and sleep studies. Functional MRI (fMRI) is also reviewed as a physiological method that can be used independently or together with other methods. A few applications to patients with movement disorders are discussed as examples, but the detailed applications will be the subject of other articles., Competing Interests: Declaration of Competing Interest The authors declare the following financial interests/personal relationships which may be considered as potential competing interests: [Mark Hallett is an inventor of patents held by NIH for an immunotoxin for the treatment of focal movement disorders and the H-coil for magnetic stimulation; in relation to the latter, he has received license fee payments from the NIH (from Brainsway). He is on the Medical Advisory Boards of CALA Health and Brainsway. He has research grants from Allergan for studies of methods to inject botulinum toxins, Medtronic, Inc. for a study of DBS for dystonia, and CALA Health for studies of a device to suppress tremor. Rodger Elble has served as a consultant for Applied Therapeutics, Cadent, Cavion, Cydan, Five Microns, Jazz, Merz, Neurocrine Biosciences, Osmotica, Praxis Precision Medicines, and Sage in the design and execution of clinical trials for essential tremor. He serves on advisory boards for the International Essential Tremor Foundation and the Neuroscience Research Foundation of Kiwanis International, Illinois-Eastern Iowa District. Fay B. Horak has a significant financial interest in ADPM Wearable Technology, an ERT company that may have a commercial interest in wearable technology. This potential conflict has been reviewed and managed by OHSU. Dr. Horak also consults for Neuropore, Sanofi, and Takeda. Lourdes M. DelRosso, Raffaele Ferri, Stephane Lehericy, Martina Mancini, Masao Matsuhashi, Riki Matsumoto, Muthuraman Muthuraman, Jan Raethjen, Hiroshi Shibasaki: none]., (Published by Elsevier B.V.)

Typically, time-frequency analysis (TFA) of electrophysiological data is aimed at isolating narrowband signals (oscillatory activity) from broadband non-oscillatory (1/f) activity, so that changes in oscillatory activity resulting from experimental manipulations can be assessed. A widely used method to do this is to convert the data to the decibel (dB) scale through baseline division and log transformation. This procedure assumes that, for each frequency, sources of power (i.e., oscillations and 1/f activity) scale by the same factor relative to the baseline (multiplicative model). This assumption may be incorrect when signal and noise are independent contributors to the power spectrum (additive model). Using resting-state EEG data from 80 participants, we found that the level of 1/f activity and alpha power are not positively correlated within participants, in line with the additive but not the multiplicative model. Then, to assess the effects of dB conversion on data that violate the multiplicativity assumption, we simulated a mixed design study with one between-subject (noise level, i.e., level of 1/f activity) and one within-subject (signal amplitude, i.e., amplitude of oscillatory activity added onto the background 1/f activity) factor. The effect size of the noise level × signal amplitude interaction was examined as a function of noise difference between groups, following dB conversion. Findings revealed that dB conversion led to the over- or under-estimation of the true interaction effect when groups differing in 1/f levels were compared, and it also led to the emergence of illusory interactions when none were present. This is because signal amplitude was systematically underestimated in the noisier compared to the less noisy group. Hence, we recommend testing whether the level of 1/f activity differs across groups or conditions and using multiple baseline correction strategies to validate results if it does. Such a situation may be particularly common in aging, developmental, or clinical studies., (Copyright © 2021. Published by Elsevier Inc.)

Aims: To improve the Magnetoencephalography (MEG) spatial localization precision of focal epileptic., Methods: 306-channel simulated or real clinical MEG is estimated as a lower-dimensional tensor by Tucker decomposition based on Higher-order orthogonal iteration (HOOI) before the inverse problem using linearly constraint minimum variance (LCMV). For simulated MEG data, the proposed method is compared with dynamic imaging of coherent sources (DICS), multiple signal classification (MUSIC), and LCMV. For clinical real MEG of 31 epileptic patients, the ripples (80-250 Hz) were detected to compare the source location precision with spikes using the proposed method or the dipole-fitting method., Results: The experimental results showed that the positional accuracy of the proposed method was higher than that of LCMV, DICS, and MUSIC for simulation data. For clinical real MEG data, the positional accuracy of the proposed method was higher than that of dipole-fitting regardless of whether the time window was ripple window or spike window. Also, the positional accuracy of the ripple window was higher than that of the spike window regardless of whether the source location method was the proposed method or the dipole-fitting method. For both shallow and deep sources, the proposed method provided effective performance., Conclusion: Tucker estimation of MEG for source imaging by ripple window is a promising approach toward the presurgical evaluation of epileptics., (© 2021 The Authors. CNS Neuroscience & Therapeutics Published by John Wiley & Sons Ltd.)

Combat-related mild traumatic brain injury (cmTBI) is a leading cause of sustained physical, cognitive, emotional, and behavioral disabilities in Veterans and active-duty military personnel. Accurate diagnosis of cmTBI is challenging since the symptom spectrum is broad and conventional neuroimaging techniques are insensitive to the underlying neuropathology. The present study developed a novel deep-learning neural network method, 3D-MEGNET, and applied it to resting-state magnetoencephalography (rs-MEG) source-magnitude imaging data from 59 symptomatic cmTBI individuals and 42 combat-deployed healthy controls (HCs). Analytic models of individual frequency bands and all bands together were tested. The All-frequency model, which combined delta-theta (1-7 Hz), alpha (8-12 Hz), beta (15-30 Hz), and gamma (30-80 Hz) frequency bands, outperformed models based on individual bands. The optimized 3D-MEGNET method distinguished cmTBI individuals from HCs with excellent sensitivity (99.9 ± 0.38%) and specificity (98.9 ± 1.54%). Receiver-operator-characteristic curve analysis showed that diagnostic accuracy was 0.99. The gamma and delta-theta band models outperformed alpha and beta band models. Among cmTBI individuals, but not controls, hyper delta-theta and gamma-band activity correlated with lower performance on neuropsychological tests, whereas hypo alpha and beta-band activity also correlated with lower neuropsychological test performance. This study provides an integrated framework for condensing large source-imaging variable sets into optimal combinations of regions and frequencies with high diagnostic accuracy and cognitive relevance in cmTBI. The all-frequency model offered more discriminative power than each frequency-band model alone. This approach offers an effective path for optimal characterization of behaviorally relevant neuroimaging features in neurological and psychiatric disorders., (© 2021 The Authors. Human Brain Mapping published by Wiley Periodicals LLC.)

The linearly constrained minimum variance beamformer is frequently used to reconstruct sources underpinning neuromagnetic recordings. When reconstructions must be compared across conditions, it is considered good practice to use a single, "common" beamformer estimated from all the data at once. This is to ensure that differences between conditions are not ascribable to differences in beamformer weights. Here, we investigate the localization accuracy of such a common beamformer. Based on theoretical derivations, we first show that the common beamformer leads to localization errors in source reconstruction. We then turn to simulations in which we attempt to reconstruct a (genuine) source in a first condition, while considering a second condition in which there is an (interfering) source elsewhere in the brain. We estimate maps of mislocalization and assess statistically the difference between "standard" and "common" beamformers. We complement our findings with an application to experimental MEG data. The results show that the common beamformer may yield significant mislocalization. Specifically, the common beamformer may force the genuine source to be reconstructed closer to the interfering source than it really is. As the same applies to the reconstruction of the interfering source, both sources are pulled closer together than they are. This observation was further illustrated in experimental data. Thus, although the common beamformer allows for the comparison of conditions, in some circumstances it introduces localization inaccuracies. We recommend alternative approaches to the general problem of comparing conditions., (Copyright © 2021 The Authors. Published by Elsevier Inc. All rights reserved.)

Signal-to-noise ratio (SNR) maps are a good way to visualize electroencephalography (EEG) and magnetoencephalography (MEG) sensitivity. SNR maps extend the knowledge about the modulation of EEG and MEG signals by source locations and orientations and can therefore help to better understand and interpret measured signals as well as source reconstruction results thereof. Our work has two main objectives. First, we investigated the accuracy and reliability of EEG and MEG finite element method (FEM)-based sensitivity maps for three different head models, namely an isotropic three and four-compartment and an anisotropic six-compartment head model. As a result, we found that ignoring the cerebrospinal fluid leads to an overestimation of EEG SNR values. Second, we examined and compared EEG and MEG SNR mappings for both cortical and subcortical sources and their modulation by source location and orientation. Our results for cortical sources show that EEG sensitivity is higher for radial and deep sources and MEG for tangential ones, which are the majority of sources. As to the subcortical sources, we found that deep sources with sufficient tangential source orientation are recordable by the MEG. Our work, which represents the first comprehensive study where cortical and subcortical sources are considered in highly detailed FEM-based EEG and MEG SNR mappings, sheds a new light on the sensitivity of EEG and MEG and might influence the decision of brain researchers or clinicians in their choice of the best modality for their experiment or diagnostics, respectively., (© 2020 The Authors. Human Brain Mapping published by Wiley Periodicals LLC.)

The Organization for Human Brain Mapping (OHBM) has been active in advocating for the instantiation of best practices in neuroimaging data acquisition, analysis, reporting and sharing of both data and analysis code to deal with issues in science related to reproducibility and replicability. Here we summarize recommendations for such practices in magnetoencephalographic (MEG) and electroencephalographic (EEG) research, recently developed by the OHBM neuroimaging community known by the abbreviated name of COBIDAS MEEG. We discuss the rationale for the guidelines and their general content, which encompass many topics under active discussion in the field. We highlight future opportunities and challenges to maximizing the sharing and exploitation of MEG and EEG data, and we also discuss how this 'living' set of guidelines will evolve to continually address new developments in neurophysiological assessment methods and multimodal integration of neurophysiological data with other data types.

In this article, we present the clinical indications and advances in the use of magnetoencephalography to map the primary sensorimotor (SM1) cortex in neurosurgical patients noninvasively. We emphasize the advantages of magnetoencephalography over sensorimotor mapping using functional magnetic resonance imaging. Recommendations to the referring physicians and the clinical magnetoencephalographers to achieve appropriate sensorimotor cortex mapping using magnetoencephalography are proposed. We finally provide some practical advice for the use of corticomuscular coherence, cortico-kinematic coherence, and mu rhythm suppression in this indication. Magnetoencephalography should now be considered as a method of reference for presurgical functional mapping of the sensorimotor cortex.

Numerous studies have shown that language processing is not limited to a few brain areas. Visual or auditory stimuli activate corresponding cortical areas, then memory identifies the word or image, Wernicke's and Broca's areas support the processing for either reading/listening or speaking and many areas of the brain are recruited. Determining how a normal person processes language helps clinicians and scientist to understand how brain pathologies such as tumor or stroke can affect changes in language processing. Patients with epilepsy may develop atypical language organization. Over time, the chronic nature of epileptic activity, or changes from a tumor or stroke, can result in a shift of language processing area from the left to the right hemisphere, or re-routing of language pathways from traditional to non-traditional areas within the dominant left hemisphere. It is important to determine where these language areas are prior to brain surgery. MEG evoked responses reflecting cerebral activation of receptive and expressive language processing can be localized using several different techniques: Single equivalent current dipole, current distribution techniques or beamformer techniques. Over the past 20 years there have been at least 25 validated MEG studies that indicate MEG can be used to determine the dominant hemisphere for language processing. The use of MEG neuroimaging techniques is needed to reliably predict altered language networks in patients and to provide identification of language eloquent cortices for localization and lateralization necessary for clinical care.

Concise history of fascinating magnetoencephalography (MEG) technology and catalog of very selected milestone preclinical and clinical MEG studies are provided as the background. The focus is the societal context defining a journey of MEG to and through clinical practice and formation of the American Clinical MEG Society (ACMEGS). We aspired to provide an objective historic perspective and document contributions of many professionals while focusing on the role of ACMEGS in the growth and maturation of clinical MEG field. The ACMEGS was born (2006) out of inevitability to address two vital issues-fair reimbursement and proper clinical acceptance. A beacon of accountable MEG practice and utilization is now an expanding professional organization with the highest level of competence in practice of clinical MEG and clinical credibility. The ACMEGS facilitated a favorable disposition of insurances toward MEG in the United States by combining the national replication of the grassroots efforts and teaming up with the strategic partners-particularly the American Academy of Neurology (AAN), published two Position Statements (2009 and 2017), the world's only set of MEG Clinical Practice Guidelines (CPGs; 2011) and surveys of clinical MEG practice (2011 and 2020) and use (2020). In addition to the annual ACMEGS Course (2012), we directly engaged MEG practitioners through an Invitational Summit (2019). The Society remains focused on the improvements and expansion of clinical practice, education, clinical training, and constructive engagement of vendors in these issues and pivotal studies toward additional MEG indications. The ACMEGS not only had the critical role in the progress of Clinical MEG in the United States and beyond since 2006 but positioned itself as the field leader in the future.

The report generated by the magnetoencephalographer's interpretation of the patient's magnetoencephalography examination is the magnetoencephalography laboratory's most important product and is a representation of the quality of the laboratory and the clinical acumen of the personnel. A magnetoencephalography report is not meant to enumerate all the technical details that went into the test nor to fulfill some imagined requirements of the electronic health record. It is meant to clearly and concisely answer the clinical question posed by the referring doctor and to convey the key findings that may inform the next step in the patient's care. The graphical component of a magnetoencephalography report is ordinarily the most welcomed by the referring doctor. Much of the text of the report may be glossed over, so the illustrations must be sufficiently annotated to provide clear and unambiguous findings. The particular images chosen for the report will be a function of the analysis software but should be selected and edited for maximum clarity. There should be a composite pictorial summary slide at the beginning or at the end of the report, which accurately conveys the gist of the report. Along with representative source localizations, reports should contain examples of the simultaneously recorded EEG that enable the referring physician to determine whether epileptic discharges occurred and whether they are consistent with the patient's previously recorded spikes. Information and images (e.g., statistics, magnetic field patterns) that provide convincing evidence of the validity of the source location should also be included.

Unfamiliarity with the indications for and benefits of magnetoencephalography (MEG) persists, even in the epilepsy community, and hinders its acceptance to clinical practice, despite the evidence. The wide treatment gap for patients with drug-resistant epilepsy and immense underutilization of epilepsy surgery had similar effects. Thus, educating referring physicians (epileptologists, neurologists, and neurosurgeons) both about the value of epilepsy surgery and about the potential benefits of MEG can achieve synergy and greatly improve the process of selecting surgical candidates. As a practical step toward a comprehensive educational process to benefit potential MEG users, current MEG referrers, and newcomers to MEG, the authors have elected to provide an illustrated guide to 10 everyday situations where MEG can help in the evaluation of people with drug-resistant epilepsy. They are as follows: (1) lacking or imprecise hypothesis regarding a seizure onset; (2) negative MRI with a mesial temporal onset suspected; (3) multiple lesions on MRI; (4) large lesion on MRI; (5) diagnostic or therapeutic reoperation; (6) ambiguous EEG findings suggestive of "bilateral" or "generalized" pattern; (7) intrasylvian onset suspected; (8) interhemispheric onset suspected; (9) insular onset suspected; and (10) negative (i.e., spikeless) EEG. Only their practical implementation and furtherance of personal and collective education will lead to the potentially impactful synergy of the two-MEG and epilepsy surgery. Thus, while fulfilling our mission as physicians, we must not forget that ignoring the wealth of evidence about the vast underutilization of epilepsy surgery - and about the usefulness and value of MEG in selecting surgical candidates - is far from benign neglect.

A magnetoencephalography (MEG) recording for clinical purposes requires a different level of attention and detail than that for research. As contrasted with a research subject, the MEG technologist must work with a patient who may not fully cooperate with instructions. The patient is on a clinical schedule, with generally no opportunity to return due to an erroneous or poor acquisition. The data will generally be processed by separate MEG analysts, who require a consistent and high-quality recording to complete their analysis and clinical report. To assure a quality recording, (1) MEG technologists must immediately recheck their scalp measurement data during the patient preparation, to catch disturbances and ensure registration accuracy of the patient fiducials, electrodes, and head position indicator coils. During the recording, (2) the technologist must ensure that the patient remains quiet and as far as possible into the helmet. After the recording, (3) the technologist must consistently prepare the data for subsequent clinical analysis. This article aims to comprehensively address these matters for practitioners of clinical MEG in a helpful and practical way. Based on the authors' experiences in recording over three thousand patients between them, presented here are a collection of techniques for implementation into daily routines that ensure good operation and high data quality. The techniques address a gap in the clinical literature addressing the multitude of potential sources of error during patient preparation and data acquisition, and how to prevent, recognize, or correct those.

Noise sources in magnetoencephalography (MEG) include: (1) interference from outside the shielded room, (2) other people and devices inside the shielded room, (3) physiologic or nonphysiologic sources inside the patient, (4) activity from inside the head that is unrelated to the signal of interest, (5) intrinsic sensor and recording electronics noise, and (6) artifacts from other apparatus used during recording such as evoked response stimulators. There are other factors which corrupt MEG recording and interpretation and should also be considered "artifacts": (7) inadequate positioning of the patient, (8) changes in the head position during the recording, (9) incorrect co-registration, (10) spurious signals introduced during postprocessing, and (11) errors in fitting. The major means whereby magnetic interference can be reduced or eliminated are by recording inside a magnetically shielded room, using gradiometers that measure differential magnetic fields, real-time active compensation using reference sensors, and postprocessing with advanced spatio-temporal filters. Many of the artifacts that plague MEG are also seen in EEG, so an experienced electroencephalographer will have the advantage of being able to transfer his knowledge about artifacts to MEG. However, many of the procedures and software used during acquisition and analysis may themselves contribute artifact or distortion that must be recognized or prevented. In summary, MEG artifacts are not worse than EEG artifacts, but many are different, and-as with EEG-must be attended to.

Auditory evoked fields (AEFs) are well suited for studies of auditory processing in patients. Their sources have been localized to Heschl's gyri and to the supratemporal auditory cortices. Auditory evoked fields are known to be modulated by peripheral and central lesions of auditory pathways and to reflect group-level pathophysiology of neurodevelopmental and psychiatric disorders. They are useful in lateralization of language processes for planning neurosurgery and for localization of language-related cortex. The recently developed artifact rejection and movement compensation methods will enhance and extend the use of AEFs in studies of clinical patients and pediatric groups. New pediatric magnetoencephalography systems will facilitate clinical AEF studies of developmental disorders. In addition to their established use in planning neurosurgery, AEF findings in several new clinical patient groups suffering, e.g., from developmental, neurodegenerative, or psychiatric disorders have been reported. Several recent investigations report the correlations with clinical symptoms and sensitivity and specificity profiles of AEFs in studies of these disorders; this development is mandatory in gaining wider clinical approval for the use of AEFs in clinical practice dealing with individual patients. Most promising future research lines of clinical applicability of AEFs focus on developmental and psychiatric disorders.

Purpose: Broader utilization of magnetoencephalography (MEG) and optimization of clinical practice remain strategic goals of the American Clinical Magnetoencephalography Society. Despite the implementation of the first MEG Clinical Practice Guidelines, clinical adoption has been less than expected, prompting a reassessment., Methods: Twenty-five clinical MEG centers were invited to participate anonymously in a survey of clinical practice., Results: Centers (N = 18) mostly operated within an academic medical center (10/18), were owned by the "hospital" (10/18), associated with a level 4 National Association of Epilepsy center (15/18), and directed by neurologists (10/18). A total of 873 (median 59) epilepsy studies, 1,179 evoked fields (of all types), and 1,607 (median 30) research MEG studies were reported. Fourteen of 17 centers serve children (median 35%), but only 5 of 14 sedate children for MEG. All (N = 14) centers record EEG simultaneous with MEG, and 57% used dipole source localization. The median reporting time for epilepsy studies was 12 and 10 days for presurgical mapping studies. Most (12/14) were favorable toward the Clinical Practice Guidelines and "formalized certification" but were against mandating the latter., Conclusions: A plateau in MEG volumes suggests that MEG has not become a part of the standard of care, and correspondingly, the Clinical Practice Guidelines appeared to have had little impact on clinical practice. The American Clinical Magnetoencephalography Society must continue to engage magnetoencephalographers, potential referrers, and vendors.

Magnetoencephalography (MEG) has a unique capacity to resolve the spatio-temporal development of brain activity from non-invasive measurements. Conventional MEG, however, relies on sensors that sample from a distance (20-40 ​mm) to the head due to thermal insulation requirements (the MEG sensors function at 4 ​K in a helmet). A gain in signal strength and spatial resolution may be achieved if sensors are moved closer to the head. Here, we report a study comparing measurements from a seven-channel on-scalp SQUID MEG system to those from a conventional (in-helmet) SQUID MEG system. We compared the spatio-temporal resolution between on-scalp and conventional MEG by comparing the discrimination accuracy for neural activity patterns resulting from stimulating five different phalanges of the right hand. Because of proximity and sensor density differences between on-scalp and conventional MEG, we hypothesized that on-scalp MEG would allow for a more high-resolved assessment of these activity patterns, and therefore also a better classification performance in discriminating between neural activations from the different phalanges. We observed that on-scalp MEG provided better classification performance during an early post-stimulus period (10-20 ​ms). This corresponded to the electroencephalographic (EEG) component P16/N16 and was an unexpected observation as this component is usually not observed in conventional MEG. This finding shows that on-scalp MEG enables a richer registration of the cortical signal, indicating a sensitivity to what are potentially sources in the thalamo-cortical radiation. We had originally expected that on-scalp MEG would provide better classification accuracy based on activity in proximity to the P60m component compared to conventional MEG. This component indeed allowed for the best classification performance for both MEG systems (60-75%, chance 50%). However, we did not find that on-scalp MEG allowed for better classification than conventional MEG at this latency. We suggest that this absence of differences is due to the limited sensor coverage in the recording, in combination with our strategy for positioning the on-scalp MEG sensors. We show how the current sensor coverage may have limited our chances to register the necessary between-phalange source field dissimilarities for fair hypothesis testing, an approach we otherwise believe to be useful for future benchmarking measurements., (Copyright © 2020 The Authors. Published by Elsevier Inc. All rights reserved.)

Using visual evoked fields (VEFs) to differentiate healthy, normal brain function from dysfunctional cortex has been demonstrated to be both valid and reliable. Currently, VEFs are widely implemented to guide intracranial surgeries for epilepsy and brain tumors. There are several areas of possible future clinical use of VEFs, including early identification of disorders, such as multiple sclerosis, Parkinson's disease, stroke, and human immunodeficiency virus-associated neurocognitive disorders. These studies have suggested that VEFs could be used to study disease pathophysiology or as a biomarker for early identification of a disorder. The current clinical practice guidelines of the American Clinical Magnetoencephalography Society for VEFs are sufficient. At this time, VEFs should be used clinically to identify visual cortex and potentially tailor surgical resections.

Normal variants, although not occurring frequently, may appear similar to epileptic activity. Misinterpretation may lead to false diagnoses. In the context of presurgical evaluation, normal variants may lead to mislocalizations with severe impact on the viability and success of surgical therapy. While the different variants are well known in EEG, little has been published in regard to their appearance in magnetoencephalography. Furthermore, there are some magnetoencephalography normal variants that have no counterparts in EEG. This article reviews benign epileptiform variants and provides examples in EEG and magnetoencephalography. In addition, the potential of oscillatory configurations in different frequency bands to appear as epileptic activity is discussed.

Beamformers are applied for estimating spatiotemporal characteristics of neuronal sources underlying measured MEG/EEG signals. Several MEG analysis toolboxes include an implementation of a linearly constrained minimum-variance (LCMV) beamformer. However, differences in implementations and in their results complicate the selection and application of beamformers and may hinder their wider adoption in research and clinical use. Additionally, combinations of different MEG sensor types (such as magnetometers and planar gradiometers) and application of preprocessing methods for interference suppression, such as signal space separation (SSS), can affect the results in different ways for different implementations. So far, a systematic evaluation of the different implementations has not been performed. Here, we compared the localization performance of the LCMV beamformer pipelines in four widely used open-source toolboxes (MNE-Python, FieldTrip, DAiSS (SPM12), and Brainstorm) using datasets both with and without SSS interference suppression. We analyzed MEG data that were i) simulated, ii) recorded from a static and moving phantom, and iii) recorded from a healthy volunteer receiving auditory, visual, and somatosensory stimulation. We also investigated the effects of SSS and the combination of the magnetometer and gradiometer signals. We quantified how localization error and point-spread volume vary with the signal-to-noise ratio (SNR) in all four toolboxes. When applied carefully to MEG data with a typical SNR (3-15 ​dB), all four toolboxes localized the sources reliably; however, they differed in their sensitivity to preprocessing parameters. As expected, localizations were highly unreliable at very low SNR, but we found high localization error also at very high SNRs for the first three toolboxes while Brainstorm showed greater robustness but with lower spatial resolution. We also found that the SNR improvement offered by SSS led to more accurate localization., (Copyright © 2020 The Authors. Published by Elsevier Inc. All rights reserved.)

Determining the anatomical source of brain activity non-invasively measured from EEG or MEG sensors is challenging. In order to simplify the source localization problem, many techniques introduce the assumption that current sources lie on the cortical surface. Another common assumption is that this current flow is orthogonal to the cortical surface, thereby approximating the orientation of cortical columns. However, it is not clear which cortical surface to use to define the current source locations, and normal vectors computed from a single cortical surface may not be the best approximation to the orientation of cortical columns. We compared three different surface location priors and five different approaches for estimating dipole vector orientation, both in simulations and visual and motor evoked MEG responses. We show that models with source locations on the white matter surface and using methods based on establishing correspondences between white matter and pial cortical surfaces dramatically outperform models with source locations on the pial or combined pial/white surfaces and which use methods based on the geometry of a single cortical surface in fitting evoked visual and motor responses. These methods can be easily implemented and adopted in most M/EEG analysis pipelines, with the potential to significantly improve source localization of evoked responses., (Copyright © 2020 The Authors. Published by Elsevier Inc. All rights reserved.)

The cerebellum plays a key role in the regulation of motor learning, coordination and timing, and has been implicated in sensory and cognitive processes as well. However, our current knowledge of its electrophysiological mechanisms comes primarily from direct recordings in animals, as investigations into cerebellar function in humans have instead predominantly relied on lesion, haemodynamic and metabolic imaging studies. While the latter provide fundamental insights into the contribution of the cerebellum to various cerebellar-cortical pathways mediating behaviour, they remain limited in terms of temporal and spectral resolution. In principle, this shortcoming could be overcome by monitoring the cerebellum's electrophysiological signals. Non-invasive assessment of cerebellar electrophysiology in humans, however, is hampered by the limited spatial resolution of electroencephalography (EEG) and magnetoencephalography (MEG) in subcortical structures, i.e., deep sources. Furthermore, it has been argued that the anatomical configuration of the cerebellum leads to signal cancellation in MEG and EEG. Yet, claims that MEG and EEG are unable to detect cerebellar activity have been challenged by an increasing number of studies over the last decade. Here we address this controversy and survey reports in which electrophysiological signals were successfully recorded from the human cerebellum. We argue that the detection of cerebellum activity non-invasively with MEG and EEG is indeed possible and can be enhanced with appropriate methods, in particular using connectivity analysis in source space. We provide illustrative examples of cerebellar activity detected with MEG and EEG. Furthermore, we propose practical guidelines to optimize the detection of cerebellar activity with MEG and EEG. Finally, we discuss MEG and EEG signal contamination that may lead to localizing spurious sources in the cerebellum and suggest ways of handling such artefacts. This review is to be read as a perspective review that highlights that it is indeed possible to measure cerebellum with MEG and EEG and encourages MEG and EEG researchers to do so. Its added value beyond highlighting and encouraging is that it offers useful advice for researchers aspiring to investigate the cerebellum with MEG and EEG., (Copyright © 2020 The Author(s). Published by Elsevier Inc. All rights reserved.)

Electrophysiological signals from the cerebellum have traditionally been viewed as inaccessible to magnetoencephalography (MEG) and electroencephalography (EEG). Here, we challenge this position by investigating the ability of MEG and EEG to detect cerebellar activity using a model that employs a high-resolution tessellation of the cerebellar cortex. The tessellation was constructed from repetitive high-field (9.4T) structural magnetic resonance imaging (MRI) of an ex vivo human cerebellum. A boundary-element forward model was then used to simulate the M/EEG signals resulting from neural activity in the cerebellar cortex. Despite significant signal cancelation due to the highly convoluted cerebellar cortex, we found that the cerebellar signal was on average only 30-60% weaker than the cortical signal. We also made detailed M/EEG sensitivity maps and found that MEG and EEG have highly complementary sensitivity distributions over the cerebellar cortex. Based on previous fMRI studies combined with our M/EEG sensitivity maps, we discuss experimental paradigms that are likely to offer high M/EEG sensitivity to cerebellar activity. Taken together, these results show that cerebellar activity should be clearly detectable by current M/EEG systems with an appropriate experimental setup., (© 2020 The Authors. Human Brain Mapping published by Wiley Periodicals, Inc.)

Functional connectivity is providing new insights into the network nature of epilepsy with growing clinical applications. Our objective was to validate a novel magnetoencephalography-based method to non-invasively measure the epileptic network. We retrospectively identified pediatric and adult patients with refractory focal epilepsy who underwent pre-surgical magnetoencephalography with subsequent intracranial electrographic monitoring. Magnetoencephalography tracings were visually reviewed, and interictal epileptiform discharges ("spikes") were individually marked. We then evaluated differences in whole-brain connectivity during brief epochs preceding the spikes and during the spikes using the Network-Based Statistic to test differences at the network level. In six patients with statistically-significant network differences, we observed substantial overlap between the spike-associated networks and electrographically active areas identified during intracranial monitoring (the spike-associated network was 78% and 83% sensitive for intracranial electroencephalography-defined regions in the irritative and seizure onset zones, respectively). These findings support the neurobiological validity of the spike-associated network method. Assessment of spike-associated networks has the potential to improve surgical planning in epilepsy surgery patients by identifying components of the epileptic network prior to implantation.

The diagnostic process for epilepsy can be lengthy and stressful, which may delay the start of treatment. The objective of this study was to determine the benefit of routine magnetoencephalography (MEG) with regard to diagnostic gain, compared to routine electroencephalography (EEG), EEG following sleep deprivation (EEGsd), and 24-hour EEG. In this prospective study, patients were included from two centres (Academic Centre for Epileptology Kempenhaeghe, Heeze and Elisabeth-Twee Steden Hospital, Tilburg) and MEG recording took place at a single centre (Amsterdam University Medical Centre, Vrije Universiteit Amsterdam) in The Netherlands. Consecutively referred patients from peripheral hospitals were included between August 2013 and March 2016. Patients were offered routine MEG in addition to EEG examination and MRI for the diagnosis of epilepsy. The final clinical diagnosis was based on all available clinical data and test results at the end of the diagnostic process. Sensitivity, specificity, and positive and negative predictive values were calculated for routine EEG, routine EEG plus additional EEG and MEG. In addition, diagnostic gain associated with MEG, relative to the other modalities, was calculated. Secondary outcome was congruence of localization of epileptiform discharges between MEG and MRI or final clinical diagnosis. Based on a cohort of 138 patients, sensitivity and specificity was shown to be 31.6% and 78.4% for routine MEG, 31.6% and 100% for routine EEG, and 52.6% and 97.3% for routine EEG plus additional EEG, respectively. Routine MEG demonstrated a diagnostic gain of 16.8% compared to routine EEG and 9.5% compared to routine EEG plus additional EEG. In 35.7% of patients with a lesion on MRI that was consistent with the final clinical diagnosis, MEG showed epileptiform discharges in the same area. Routine MEG may provide additional value during the initial diagnosis of epilepsy.

Characterizing the neural dynamics underlying sensory processing is one of the central areas of investigation in systems and cognitive neuroscience. Neuroimaging techniques such as magnetoencephalography (MEG) and Electroencephalography (EEG) have provided significant insights into the neural processing of continuous stimuli, such as speech, thanks to their high temporal resolution. Existing work in the context of auditory processing suggests that certain features of speech, such as the acoustic envelope, can be used as reliable linear predictors of the neural response manifested in M/EEG. The corresponding linear filters are referred to as temporal response functions (TRFs). While the functional roles of specific components of the TRF are well-studied and linked to behavioral attributes such as attention, the cortical origins of the underlying neural processes are not as well understood. In this work, we address this issue by estimating a linear filter representation of cortical sources directly from neuroimaging data in the context of continuous speech processing. To this end, we introduce Neuro-Current Response Functions (NCRFs), a set of linear filters, spatially distributed throughout the cortex, that predict the cortical currents giving rise to the observed ongoing MEG (or EEG) data in response to continuous speech. NCRF estimation is cast within a Bayesian framework, which allows unification of the TRF and source estimation problems, and also facilitates the incorporation of prior information on the structural properties of the NCRFs. To generalize this analysis to M/EEG recordings which lack individual structural magnetic resonance (MR) scans, NCRFs are extended to free-orientation dipoles and a novel regularizing scheme is put forward to lessen reliance on fine-tuned coordinate co-registration. We present a fast estimation algorithm, which we refer to as the Champ-Lasso algorithm, by leveraging recent advances in optimization, and demonstrate its utility through application to simulated and experimentally recorded MEG data under auditory experiments. Our simulation studies reveal significant improvements over existing methods that typically operate in a two-stage fashion, in terms of spatial resolution, response function reconstruction, and recovering dipole orientations. The analysis of experimentally-recorded MEG data without MR scans corroborates existing findings, but also delineates the distinct cortical distribution of the underlying neural processes at high spatiotemporal resolution. In summary, we provide a principled modeling and estimation paradigm for MEG source analysis tailored to extracting the cortical origin of electrophysiological responses to continuous stimuli., (Copyright © 2020 The Authors. Published by Elsevier Inc. All rights reserved.)

Cross-frequency coupling (CFC) between neuronal oscillations reflects an integration of spatially and spectrally distributed information in the brain. Here, we propose a novel framework for detecting such interactions in Magneto- and Electroencephalography (MEG/EEG), which we refer to as Nonlinear Interaction Decomposition (NID). In contrast to all previous methods for separation of cross-frequency (CF) sources in the brain, we propose that the extraction of nonlinearly interacting oscillations can be based on the statistical properties of their linear mixtures. The main idea of NID is that nonlinearly coupled brain oscillations can be mixed in such a way that the resulting linear mixture has a non-Gaussian distribution. We evaluate this argument analytically for amplitude-modulated narrow-band oscillations which are either phase-phase or amplitude-amplitude CF coupled. We validated NID extensively with simulated EEG obtained with realistic head modelling. The method extracted nonlinearly interacting components reliably even at SNRs as small as -15 dB. Additionally, we applied NID to the resting-state EEG of 81 subjects to characterize CF phase-phase coupling between alpha and beta oscillations. The extracted sources were located in temporal, parietal and frontal areas, demonstrating the existence of diverse local and distant nonlinear interactions in resting-state EEG data. All codes are available publicly via GitHub., (Copyright © 2020 The Authors. Published by Elsevier Inc. All rights reserved.)

Magnetoencephalography (MEG) is a neuroimaging technique that accurately captures the rapid (sub-millisecond) activity of neuronal populations. Interpretation of functional data from MEG relies upon registration to the participant's anatomical MRI. The key remaining step is to transform the participant's MRI into the MEG head coordinate space. Although both automated and manual approaches to co-registration are available, the relative accuracy of two approaches has not been systematically evaluated. The goal of the present study was to compare the accuracy of manual and automated co-registration. Resting MEG and T1-weighted MRI data were collected from 90 participants. Automated and manual co-registration were performed on the same subjects, and the inter-method reliability of the two methods assessed using the intra-class correlation. Median co-registration error for both methods was within acceptable limits. Inter-method reliability was in the "good" range for co-registration error, and the "good" to "excellent" range for translation and rotation. These results suggest that the output of the automated co-registration procedure is comparable to that achieved using manual co-registration., Competing Interests: The authors have declared that no competing interests exist.

Magnetoencephalography (MEG) has been used in conjunction with resting-state functional connectivity (rsFC) based on band-limited power envelope correlation to study the intrinsic human brain network organization into resting-state networks (RSNs). However, the limited availability of current MEG systems hampers the clinical applications of electrophysiological rsFC. Here, we directly compared well-known RSNs as well as the whole-brain rsFC connectome together with its state dynamics, obtained from simultaneously-recorded MEG and high-density scalp electroencephalography (EEG) resting-state data. We also examined the impact of head model precision on EEG rsFC estimation, by comparing results obtained with boundary and finite element head models. Results showed that most RSN topographies obtained with MEG and EEG are similar, except for the fronto-parietal network. At the connectome level, sensitivity was lower to frontal rsFC and higher to parieto-occipital rsFC with MEG compared to EEG. This was mostly due to inhomogeneity of MEG sensor locations relative to the scalp and significant MEG-EEG differences disappeared when taking relative MEG-EEG sensor locations into account. The default-mode network was the only RSN requiring advanced head modeling in EEG, in which gray and white matter are distinguished. Importantly, comparison of rsFC state dynamics evidenced a poor correspondence between MEG and scalp EEG, suggesting sensitivity to different components of transient neural functional integration. This study therefore shows that the investigation of static rsFC based on the human brain connectome can be performed with scalp EEG in a similar way than with MEG, opening the avenue to widespread clinical applications of rsFC analyses., (Copyright © 2020. Published by Elsevier Inc.)

Mild traumatic brain injury (mTBI) accounts for the vast majority of all pediatric TBI. An important minority of children who have suffered an mTBI have enduring cognitive and emotional symptoms. However, the mechanisms of chronic symptoms in children with pediatric mTBI are not fully understood. This is in part due to the limited sensitivity of conventional neuroimaging technologies. The present study examined resting-state magnetoencephalography (rs-MEG) source images in 12 children who had mTBI and 12 age-matched control children. The rs-MEG exams were performed in children with mTBI 6 months after injury when they reported no clinically significant post-injury psychiatric changes and few if any somatic sensorimotor symptoms but did report cognitive symptoms. MEG source magnitude images were obtained for different frequency bands in alpha (8-12 Hz), beta (15-30 Hz), gamma (30-90 Hz), and low-frequency (1-7 Hz) bands. In contrast to the control participants, rs-MEG source imaging in the children with mTBI showed: 1) hyperactivity from the bilateral insular cortices in alpha, beta, and low-frequency bands, from the left amygdala in alpha band, and from the left precuneus in beta band; 2) hypoactivity from the bilateral dorsolateral prefrontal cortices (dlPFC) in alpha and beta bands, from the ventromedial prefrontal cortex (vmPFC) in beta band, from the ventrolateral prefrontal cortex (vlPFC) in gamma band, from the anterior cingulate cortex (ACC) in alpha band, and from the right precuneus in alpha band. The present study showed that MEG source imaging technique revealed abnormalities in the resting-state electromagnetic signals from the children with mTBI.

Functional brain connectivity is increasingly being seen as critical for cognition, perception and motor control. Magnetoencephalography and electroencephalography are modalities that offer noninvasive mapping of electrophysiological interactions among brain regions, yet suffer from signal leakage and signal cancellation when estimating brain activity. This leads to biased connectivity values which complicate interpretation. In this study, we test the hypothesis that a Multiple Constrained Minimum Variance beamformer (MCMV) outperforms the more traditional Linearly Constrained Minimum Variance beamformer (LCMV) for estimation of electrophysiological connectivity. To this end, MCMV and LCMV performance is compared in task related analyses with both simulated data and human MEG recordings of visual steady state signals, and in resting state analyses with simulated data and human MEG data of 89 subjects. In task related scenarios connectivity was estimated using coherence and phase locking values, whereas envelope correlations were used for the resting state data. We also introduce a novel Augmented Pairwise MCMV (APW-MCMV) approach for signal leakage suppression in resting state analyses and assess its performance against LCMV and more conventional MCMV approaches. We demonstrate that with MCMV effects of signal mixing and coherent source cancellation are greatly reduced in both task related and resting state conditions, while in contrast to other approaches 0- and short time lag interactions are preserved. In addition, we demonstrate that in resting state analyses, APW-MCMV strongly reduces spurious connections while better controlling for false negatives compared to more conservative measures such as symmetrical orthogonalization., (Copyright © 2019. Published by Elsevier Inc.)

Objective: To assess the ability of high-density Electroencephalography (HD-EEG) and magnetoencephalography (MEG) to localize interictal ripples, distinguish between ripples co-occurring with spikes (ripples-on-spike) and independent from spikes (ripples-alone), and evaluate their localizing value as biomarkers of epileptogenicity in children with medically refractory epilepsy., Methods: We retrospectively studied 20 children who underwent epilepsy surgery. We identified ripples on HD-EEG and MEG data, localized their generators, and compared them with intracranial EEG (icEEG) ripples. When ripples and spikes co-occurred, we performed source imaging distinctly on the data above 80 Hz (to localize ripples) and below 70 Hz (to localize spikes). We assessed whether missed resection of ripple sources predicted poor outcome, separately for ripples-on-spikes and ripples-alone. Similarly, predictive value of spikes was calculated., Results: We observed scalp ripples in 16 patients (10 good outcome). Ripple sources were highly concordant to the icEEG ripples (HD-EEG concordance: 79%; MEG: 83%). When ripples and spikes co-occurred, their sources were spatially distinct in 83-84% of the cases. Removing the sources of ripples-on-spikes predicted good outcome with 90% accuracy for HD-EEG (P = 0.008) and 86% for MEG (P = 0.044). Conversely, removing ripples-alone did not predict outcome. Resection of spike sources (generated at the same time as ripples) predicted good outcome for HD-EEG (P = 0.036; accuracy = 87%), while did not reach significance for MEG (P = 0.1; accuracy = 80%)., Interpretation: HD-EEG and MEG localize interictal ripples with high precision in children with refractory epilepsy. Scalp ripples-on-spikes are prognostic, noninvasive biomarkers of epileptogenicity, since removing their cortical generators predicts good outcome. Conversely, scalp ripples-alone are most likely generated by non-epileptogenic areas., (© 2020 The Authors. Annals of Clinical and Translational Neurology published by Wiley Periodicals, Inc on behalf of American Neurological Association.)

Muscular activity recording is of high basic science and clinical relevance and is typically achieved using electromyography (EMG). While providing detailed information about the state of a specific muscle, this technique has limitations such as the need for a priori assumptions about electrode placement and difficulty with recording muscular activity patterns from extended body areas at once. For head and face muscle activity, the present work aimed to overcome these restrictions by exploiting magnetoencephalography (MEG) as a whole head myographic recorder (head magnetomyography, hMMG). This is in contrast to common MEG studies, which treat muscular activity as artifact in electromagnetic brain activity. In a first proof-of-concept step, participants imitated emotional facial expressions performed by a model. Exploiting source projection algorithms, we were able to reconstruct muscular activity, showing spatial activation patterns in accord with the hypothesized muscular contractions. Going one step further, participants passively observed affective pictures with negative, neutral, or positive valence. Applying multivariate pattern analysis to the reconstructed hMMG signal, we were able to decode above chance the valence category of the presented pictures. Underlining the potential of hMMG, a searchlight analysis revealed that generally neglected neck muscles exhibit information on stimulus valence. Results confirm the utility of hMMG as a whole head electromyographic recorder to quantify muscular activation patterns including muscular regions that are typically not recorded with EMG. This key advantage beyond conventional EMG has substantial scientific and clinical potential., (© 2019 The Authors. Psychophysiology published by Wiley Periodicals, Inc. on behalf of Society for Psychophysiological Research.)

Objective: Visual inspection of interictal epileptiform discharges (IEDs) in multi-channel MEG requires a time-consuming evaluation process and often leads to inconsistent results due to variability of IED waveforms. Here, we propose a novel extraction method for IEDs using a T/k type of blind source separation (BSS T/k )., Methods: We applied BSS T/k with seven patients with focal epilepsy to test the accuracy of identification of IEDs. We conducted comparisons of the results of BSS components with those obtained by visual inspection in sensor-space analysis., Results: BSS T/k provided better signal estimation of IEDs compared with sensor-space analysis. Importantly, BSS T/k was able to uncover IEDs that could not be detected by visual inspection. Furthermore, IED components were clearly extracted while preserving spike and wave morphology. Variable IED waveforms were decomposed into one dominant component., Conclusions: BSS T/k was able to visualize the spreading signals over multiple channels into a single component from a single epileptogenic zone. BSS T/k can be applied to focal epilepsy with a simple parameter setting., Significance: Our novel method was able to highlight IEDs with increased accuracy for identification of IEDs from multi-channel MEG data., (Copyright © 2019 International Federation of Clinical Neurophysiology. Published by Elsevier B.V. All rights reserved.)

Objective: By looking at how the accuracy of preoperative brain mapping methods vary according to differences in the distance from the activation clusters used for the analysis, the present study aimed to elucidate how preoperative functional neuroimaging may be used in such a way that maximizes the mapping accuracy., Methods: The eloquent function of 19 patients with a brain tumor or cavernoma was mapped prior to resection with both functional MRI (fMRI) and magnetoencephalography (MEG). The mapping results were then validated using direct cortical stimulation mapping performed immediately after craniotomy and prior to resection. The subset of patients with equivalent MEG and fMRI tasks performed for motor (n = 14) and language (n = 12) were evaluated as both individual and combined predictions. Furthermore, the distance resulting in the maximum accuracy, as evaluated by the J statistic, was determined by plotting the sensitivities and specificities against a linearly increasing distance threshold., Results: fMRI showed a maximum mapping accuracy at 5 mm for both motor and language mapping. MEG showed a maximum mapping accuracy at 40 mm for motor and 15 mm for language mapping. At the standard 10-mm distance used in the literature, MEG showed a greater specificity than fMRI for both motor and language mapping but a lower sensitivity for motor mapping. Combining MEG and fMRI showed a maximum accuracy at 15 mm and 5 mm-MEG and fMRI distances, respectively-for motor mapping and at a 10-mm distance for both MEG and fMRI for language mapping. For motor mapping, combining MEG and fMRI at the optimal distances resulted in a greater accuracy than the maximum accuracy of the individual predictions., Conclusions: This study demonstrates that the accuracy of language and motor mapping for both fMRI and MEG is heavily dependent on the distance threshold used in the analysis. Furthermore, combining MEG and fMRI showed the potential for increased motor mapping accuracy compared to when using the modalities separately.Clinical trial registration no.: NCT01535430 (clinicaltrials.gov).