Search

State-space models are widely employed across various research disciplines to study unobserved dynamics. Conventional estimation techniques, such as Kalman filtering and expectation maximisation, offer valuable insights but incur high computational costs in large-scale analyses. Sparse inverse covariance estimators can mitigate these costs, but at the expense of a trade-off between enforced sparsity and increased estimation bias, necessitating careful assessment in low signal-to-noise ratio (SNR) situations. To address these challenges, we propose a three-fold solution: (1) Introducing multiple penalised state-space (MPSS) models that leverage data-driven regularisation; (2) Developing novel algorithms derived from backpropagation, gradient descent, and alternating least squares to solve MPSS models; (3) Presenting a K-fold cross-validation extension for evaluating regularisation parameters. We validate this MPSS regularisation framework through lower and more complex simulations under varying SNR conditions, including a large-scale synthetic magneto- and electro-encephalography (MEG/EEG) data analysis. In addition, we apply MPSS models to concurrently solve brain source localisation and functional connectivity problems for real event-related MEG/EEG data, encompassing thousands of sources on the cortical surface. The proposed methodology overcomes the limitations of existing approaches, such as constraints to small-scale and region-of-interest analyses. Thus, it may enable a more accurate and detailed exploration of cognitive brain functions.

Electromagnetic source imaging (ESI) offers unique capability of imaging brain dynamics for studying brain functions and aiding the clinical management of brain disorders. Challenges exist in ESI due to the ill-posedness of the inverse problem and thus the need of modeling the underlying brain dynamics for regularizations. Advances in generative models provide opportunities for more accurate and realistic source modeling that could offer an alternative approach to ESI for modeling the underlying brain dynamics beyond equivalent physical source models. However, it is not straightforward to explicitly formulate the knowledge arising from these generative models within the conventional ESI framework. Here we investigate a novel source imaging framework based on mesoscale neuronal modeling and deep learning (DL) that can learn the sensor-source mapping relationship directly from MEG data for ESI. Two DL-based ESI models were trained based on data generated by neural mass models and either generic or personalized head models. The robustness of the two DL models was evaluated by systematic computer simulations and clinical validation in a cohort of 29 drug-resistant focal epilepsy patients who underwent intracranial EEG (iEEG) evaluation or surgical resection. Results estimated from pre-operative MEG interictal spikes were quantified using the overlap with resection regions and the distance to the seizure-onset zone (SOZ) defined by iEEG recordings. The DL-based ESI provided robust results when no personalized head geometry is considered, reaching a spatial dispersion of 21.90 ± 19.03 mm, sublobar concordance of 83 %, and sublobar sensitivity and specificity of 66 and 97 % respectively. When using personalized head geometry derived from individual patients’ MRI in the training data, personalized DL-based ESI model can further improve the performance and reached a spatial dispersion of 8.19 ± 8.14 mm, sublobar concordance of 93 %, and sublobar sensitivity and specificity of 77 and 99 % respectively. When compared to the SOZ, the localization error of the personalized approach is 15.78 ± 5.54 mm, outperforming the conventional benchmarks. This work demonstrates that combining generative models and deep learning enables an accurate and robust imaging of epileptogenic zone from MEG recordings with strong sublobar precision, suggesting its added value to enhancing MEG source localization and imaging, and to epilepsy source localization and other clinical applications.

The accurate characterization of cortical functional connectivity from Magnetoencephalography (MEG) data remains a challenging problem due to the subjective nature of the analysis, which requires several decisions at each step of the analysis pipeline, such as the choice of a source estimation algorithm, a connectivity metric and a cortical parcellation, to name but a few. Recent studies have emphasized the importance of selecting the regularization parameter in minimum norm estimates with caution, as variations in its value can result in significant differences in connectivity estimates. In particular, the amount of regularization that is optimal for MEG source estimation can actually be suboptimal for coherence-based MEG connectivity analysis. In this study, we expand upon previous work by examining a broader range of commonly used connectivity metrics, including the imaginary part of coherence, corrected imaginary part of Phase Locking Value, and weighted Phase Lag Index, within a larger and more realistic simulation scenario. Our results show that the best estimate of connectivity is achieved using a regularization parameter that is 1 or 2 orders of magnitude smaller than the one that yields the best source estimation. This remarkable difference may imply that previous work assessing source-space connectivity using minimum-norm may have benefited from using less regularization, as this may have helped reduce false positives. Importantly, we provide the code for MEG data simulation and analysis, offering the research community a valuable open source tool for informed selections of the regularization parameter when using minimum-norm for source space connectivity analyses.

Multivariate pattern analysis (MVPA) of Magnetoencephalography (MEG) and Electroencephalography (EEG) data is a valuable tool for understanding how the brain represents and discriminates between different stimuli. Identifying the spatial and temporal signatures of stimuli is typically a crucial output of these analyses. Such analyses are mainly performed using linear, pairwise, sliding window decoding models. These allow for relative ease of interpretation, e.g. by estimating a time-course of decoding accuracy, but have limited decoding performance. On the other hand, full epoch multiclass decoding models, commonly used for brain–computer interface (BCI) applications, can provide better decoding performance. However interpretation methods for such models have been designed with a low number of classes in mind. In this paper, we propose an approach that combines a multiclass, full epoch decoding model with supervised dimensionality reduction, while still being able to reveal the contributions of spatiotemporal and spectral features using permutation feature importance. Crucially, we introduce a way of doing supervised dimensionality reduction of input features within a neural network optimised for the classification task, improving performance substantially. We demonstrate the approach on 3 different many-class task-MEG datasets using image presentations. Our results demonstrate that this approach consistently achieves higher accuracy than the peak accuracy of a sliding window decoder while estimating the relevant spatiotemporal features in the MEG signal.

Functional connectivity is crucial for cognitive processes in the healthy brain and serves as a marker for a range of neuropathological conditions. Non-invasive exploration of functional coupling using temporally resolved techniques such as MEG allows for a unique opportunity of exploring this fundamental brain mechanism.The indirect nature of MEG measurements complicates the estimation of functional coupling due to the volume conduction and spatial leakage effects. In the previous work (Ossadtchi et al., 2018), we introduced PSIICOS, a method that for the first time allowed us to suppress the volume conduction effect and yet retain information about functional networks whose nodes are coupled with close to zero or zero mutual phase lag.In this paper, we demonstrate analytically that the PSIICOS projection is optimal in achieving a controllable trade-off between suppressing mutual spatial leakage and retaining information about zero- or close to zero-phase coupled networks. We also derive an alternative solution using the regularization-based inverse of the mutual spatial leakage matrix and show its equivalence to the original PSIICOS.We then discuss how PSIICOS solution to the functional connectivity estimation problem can be incorporated into the conventional source estimation framework. Instead of sources, the unknowns are the elementary dyadic networks and their activation time series are formalized by the corresponding source-space cross-spectral coefficients. This view on connectivity estimation as a regression problem opens up new opportunities for formulating a set of principled estimators based on the rich intuition accumulated in the neuroimaging community.

The relationship between structural and functional connectivity in the brain is a key question in connectomics. Here we quantify patterns of structure-function coupling across the neocortex, by comparing structural connectivity estimated using diffusion MRI with functional connectivity estimated using both neurophysiological (MEG-based) and haemodynamic (fMRI-based) recordings. We find that structure-function coupling is heterogeneous across brain regions and frequency bands. The link between structural and functional connectivity is generally stronger in multiple MEG frequency bands compared to resting state fMRI. Structure-function coupling is greater in slower and intermediate frequency bands compared to faster frequency bands. We also find that structure-function coupling systematically follows the archetypal sensorimotor-association hierarchy, as well as patterns of laminar differentiation, peaking in granular layer IV. Finally, structure-function coupling is better explained using structure-informed inter-regional communication metrics than using structural connectivity alone. Collectively, these results place neurophysiological and haemodynamic structure-function relationships in a common frame of reference and provide a starting point for a multi-modal understanding of structure-function coupling in the brain.

Most neuroimaging techniques require the participant to remain still for reliable recordings to be made. Optically pumped magnetometer (OPM) based magnetoencephalography (OP-MEG) however, is a neuroimaging technique which can be used to measure neural signals during large participant movement (approximately 1 m) within a magnetically shielded room (MSR) (Boto et al., 2018; Seymour et al., 2021). Nevertheless, environmental magnetic fields vary both spatially and temporally and OPMs can only operate within a limited magnetic field range, which constrains participant movement. Here we implement real-time updates to electromagnetic coils mounted on-board of the OPMs, to cancel out the changing background magnetic fields. The coil currents were chosen based on a continually updating harmonic model of the background magnetic field, effectively implementing homogeneous field correction (HFC) in real-time (Tierney et al., 2021). During a stationary, empty room recording, we show an improvement in very low frequency noise of 24 dB. In an auditory paradigm, during participant movement of up to 2 m within a magnetically shielded room, introduction of the real-time correction more than doubled the proportion of trials in which no sensor saturated recorded outside of a 50 cm radius from the optimally-shielded centre of the room. The main advantage of such model-based (rather than direct) feedback is that it could allow one to correct field components along unmeasured OPM axes, potentially mitigating sensor gain and calibration issues (Borna et al., 2022).

To what extent does language production activate cross-modal conceptual representations? In picture naming, we view specific exemplars of concepts and then name them with a label, like “dog”. In overt reading, the written word does not express a specific exemplar. Here we used a decoding approach with magnetoencephalography (MEG) to address whether picture naming and overt word reading involve shared representations of superordinate categories (e.g., animal). This addresses a fundamental question about the modality-generality of conceptual representations and their temporal evolution. Crucially, we do this using a language production task that does not require explicit categorization judgment and that controls for word form properties across semantic categories. We trained our models to classify the animal/tool distinction using MEG data of one modality at each time point and then tested the generalization of those models on the other modality. We obtained evidence for the automatic activation of cross-modal semantic category representations for both pictures and words later than their respective modality-specific representations. Cross-modal representations were activated at 150 ms and lasted until around 450 ms. The time course of lexical activation was also assessed revealing that semantic category is represented before lexical access for pictures but after lexical access for words. Notably, this earlier activation of semantic category in pictures occurred simultaneously with visual representations. We thus show evidence for the spontaneous activation of cross-modal semantic categories in picture naming and word reading. These results serve to anchor a more comprehensive spatio-temporal delineation of the semantic feature space during production planning.

The infant auditory system rapidly matures across the first years of life, with a primary goal of obtaining ever-more-accurate real-time representations of the external world. Our understanding of how left and right auditory cortex neural processes develop during infancy, however, is meager, with few studies having the statistical power to detect potential hemisphere and sex differences in primary/secondary auditory cortex maturation. Using infant magnetoencephalography (MEG) and a cross-sectional study design, left and right auditory cortex P2m responses to pure tones were examined in 114 typically developing infants and toddlers (66 males, 2 to 24 months). Non-linear maturation of P2m latency was observed, with P2m latencies decreasing rapidly as a function of age during the first year of life, followed by slower changes between 12 and 24 months. Whereas in younger infants auditory tones were encoded more slowly in the left than right hemisphere, similar left and right P2m latencies were observed by ∼21 months of age due to faster maturation rate in the left than right hemisphere. No sex differences in the maturation of the P2m responses were observed. Finally, an earlier left than right hemisphere P2m latency predicted better language performance in older infants (12 to 24 months). Findings indicate the need to consider hemisphere when examining the maturation of auditory cortex neural activity in infants and toddlers and show that the pattern of left–right hemisphere P2m maturation is associated with language performance.

When does the mind begin? Infant psychology is mysterious in part because we cannot remember our first months of life, nor can we directly communicate with infants. Even more speculative is the possibility of mental life prior to birth. The question of when consciousness, or subjective experience, begins in human development thus remains incompletely answered, though boundaries can be set using current knowledge from developmental neurobiology and recent investigations of the perinatal brain. Here, we offer our perspective on how the development of a sensory perturbational complexity index (sPCI) based on auditory (“beep-and-zip”), visual (“flash-and-zip”), or even olfactory (“sniff-and-zip”) cortical perturbations in place of electromagnetic perturbations (“zap-and-zip”) might be used to address this question. First, we discuss recent studies of perinatal cognition and consciousness using techniques such as functional magnetic resonance imaging (fMRI), electroencephalography (EEG), and, in particular, magnetoencephalography (MEG). While newborn infants are the archetypal subjects for studying early human development, researchers may also benefit from fetal studies, as the womb is, in many respects, a more controlled environment than the cradle. The earliest possible timepoint when subjective experience might begin is likely the establishment of thalamocortical connectivity at 26 weeks gestation, as the thalamocortical system is necessary for consciousness according to most theoretical frameworks. To infer at what age and in which behavioral states consciousness might emerge following the initiation of thalamocortical pathways, we advocate for the development of the sPCI and similar techniques, based on EEG, MEG, and fMRI, to estimate the perinatal brain's state of consciousness.

The discovery that human brain connectivity data can be used as a “fingerprint” to identify a given individual from a population, has become a burgeoning research area in the neuroscience field. Recent studies have identified the possibility to extract these brain signatures from the temporal rich dynamics of resting-state magneto encephalography (MEG) recordings. Nevertheless, it is still uncertain to what extent MEG signatures can serve as an indicator of human identifiability during task-related conduct. Here, using MEG data from naturalistic and neurophysiological tasks, we show that identification improves in tasks relative to resting-state, providing compelling evidence for a task dependent axis of MEG signatures. Notably, improvements in identifiability were more prominent in strictly controlled tasks. Lastly, the brain regions contributing most towards individual identification were also modified when engaged in task activities. We hope that this investigation advances our understanding of the driving factors behind brain identification from MEG signals.

During listening, brain activity tracks the rhythmic structures of speech signals. Here, we directly dissociated the contribution of neural envelope tracking in the processing of speech acoustic cues from that related to linguistic processing. We examined the neural changes associated with the comprehension of Noise-Vocoded (NV) speech using magnetoencephalography (MEG). Participants listened to NV sentences in a 3-phase training paradigm: (1) pre-training, where NV stimuli were barely comprehended, (2) training with exposure of the original clear version of speech stimulus, and (3) post-training, where the same stimuli gained intelligibility from the training phase. Using this paradigm, we tested if the neural responses of a speech signal was modulated by its intelligibility without any change in its acoustic structure. To test the influence of spectral degradation on neural envelope tracking independently of training, participants listened to two types of NV sentences (4-band and 2-band NV speech), but were only trained to understand 4-band NV speech. Significant changes in neural tracking were observed in the delta range in relation to the acoustic degradation of speech. However, we failed to find a direct effect of intelligibility on the neural tracking of speech envelope in both theta and delta ranges, in both auditory regions-of-interest and whole-brain sensor-space analyses. This suggests that acoustics greatly influence the neural tracking response to speech envelope, and that caution needs to be taken when choosing the control signals for speech-brain tracking analyses, considering that a slight change in acoustic parameters can have strong effects on the neural tracking response.

Listening to speech with poor signal quality is challenging. Neural speech tracking of degraded speech has been used to advance the understanding of how brain processes and speech intelligibility are interrelated. However, the temporal dynamics of neural speech tracking and their relation to speech intelligibility are not clear. In the present MEG study, we exploited temporal response functions (TRFs), which has been used to describe the time course of speech tracking on a gradient from intelligible to unintelligible degraded speech. In addition, we used inter-related facets of neural speech tracking (e.g., speech envelope reconstruction, speech-brain coherence, and components of broadband coherence spectra) to endorse our findings in TRFs. Our TRF analysis yielded marked temporally differential effects of vocoding: ∼50–110 ms (M50TRF), ∼175–230 ms (M200TRF), and ∼315–380 ms (M350TRF). Reduction of intelligibility went along with large increases of early peak responses M50TRF, but strongly reduced responses in M200TRF. In the late responses M350TRF, the maximum response occurred for degraded speech that was still comprehensible then declined with reduced intelligibility. Furthermore, we related the TRF components to our other neural “tracking“ measures and found that M50TRF and M200TRF play a differential role in the shifting center frequency of the broadband coherence spectra. Overall, our study highlights the importance of time-resolved computation of neural speech tracking and decomposition of coherence spectra and provides a better understanding of degraded speech processing.

Heartbeat-evoked responses (HERs) can interact with external stimuli and play a crucial role in shaping perception, self-related processes, and emotional processes. On the one hand, the external stimulus could modulate HERs. On the other hand, the HERs could affect cognitive processing of the external stimulus. Whether the same neural mechanism underlies these two processes, however, remains unclear. Here, we investigated this interactive mechanism by measuring HERs using magnetoencephalography (MEG) and two name perception tasks. Specifically, we tested (1) how hearing a subject's own name (SON) modulates HERs and (2) how the judgment of an SON is biased by prestimulus HERs. The results showed a dual interaction between HERs and SON. In particular, SON can modulate HERs for heartbeats occurring from 200 to 1200 ms after SON presentation. In addition, prestimulus HERs can bias the SON judgment when a stimulus is presented. Importantly, MEG activities from these two types of interactions differed in spatial and temporal patterns, suggesting that they may be associated with distinct neural pathways. These findings extend our understanding of brain-heart interactions.

Human neuromagnetic activity is characterised by a complex combination of transient bursts with varying spatial and temporal characteristics. The characteristics of these transient bursts change during task performance and normal ageing in ways that can inform about underlying cortical sources. Many methods have been proposed to detect transient bursts, with the most successful ones being those that employ multi-channel, data-driven approaches to minimize bias in the detection procedure. There has been little research, however, into the application of these data-driven methods to large datasets for group-level analyses. In the current work, we apply a data-driven convolutional dictionary learning (CDL) approach to detect neuromagnetic transient bursts in a large group of healthy participants from the Cam-CAN dataset. CDL was used to extract repeating spatiotemporal motifs in 538 participants between the ages of 18–88 during a sensorimotor task. Motifs were then clustered across participants based on similarity, and relevant task-related clusters were analysed for age-related trends in their spatiotemporal characteristics. Seven task-related motifs resembling known transient burst types were identified through this analysis, including beta, mu, and alpha type bursts. All burst types showed positive trends in their activation levels with age that could be explained by increasing burst rate with age. This work validated the data-driven CDL approach for transient burst detection on a large dataset and identified robust information about the complex characteristics of human brain signals and how they change with age.

Magnetoencephalography (MEG) is a powerful tool for estimating brain connectivity with both good spatial and temporal resolution. It is particularly helpful in epilepsy to characterize non-invasively the epileptic networks. However, using MEG to map brain networks requires solving a difficult inverse problem that introduces uncertainty in the activity localization and connectivity measures. Our goal here was to compare independent component analysis (ICA) followed by dipole source localization and the linearly constrained minimum-variance beamformer (LCMV-BF) for characterizing regions with interictal epileptic activity and their dynamic connectivity. After a simulation study, we compared ICA and LCMV-BF results with intracerebral EEG (stereotaxic EEG, SEEG) recorded simultaneously in 8 epileptic patients, which provide a unique ‘ground truth’ to which non-invasive results can be confronted. We compared the signal time courses extracted applying ICA and LCMV-BF on MEG data to that of SEEG, both for the actual signals and the dynamic connectivity computed using cross-correlation (evolution of links in time).With our simulations, we illustrated the different effect of the temporal and spatial correlation among sources on the two methods. While ICA was more affected by the temporal correlation but robust against spatial configurations, LCMV-BF showed opposite behavior. Moreover, ICA seems more suited to retrieve the simulated networks.In case of real patient data, good MEG/SEEG correlation and good localization were obtained in 6 out of 8 patients. In 4 of them ICA had the best performance (higher correlation, lower localization distance). In terms of dynamic connectivity, the evolution in time of the cross-correlation links could be retrieved in 5 patients out of 6, however, with more variable results in terms of correlation and distance. In two patients LCMV-BF had better results than ICA. In one patient the two methods showed equally good outcomes, and in the remaining two patients ICA performed best.In conclusion, our results obtained by exploiting simultaneous MEG/SEEG recordings suggest that ICA and LCMV-BF have complementary qualities for retrieving the dynamics of interictal sources and their network interactions.

Distinguishing groups of subjects or experimental conditions in a high-dimensional feature space is a common goal in modern neuroimaging studies. Successful classification depends on the selection of relevant features as not every neuronal signal component or parameter is informative about the research question at hand. Here, we developed a novel unsupervised multistage analysis approach that combines dimensionality reduction, bootstrap aggregating and multivariate classification to select relevant neuronal features. We tested the approach by identifying changes of brain-wide electrophysiological coupling in Multiple Sclerosis. Multiple Sclerosis is a demyelinating disease of the central nervous system that can result in cognitive decline and physical disability. However, related changes in large-scale brain interactions remain poorly understood and corresponding non-invasive biomarkers are sparse. We thus compared brain-wide phase- and amplitude-coupling of frequency specific neuronal activity in relapsing-remitting Multiple Sclerosis patients (n = 17) and healthy controls (n = 17) using magnetoencephalography. Changes in this dataset included both, increased and decreased phase- and amplitude-coupling in wide-spread, bilateral neuronal networks across a broad range of frequencies. These changes allowed to successfully classify patients and controls with an accuracy of 84%. Furthermore, classification confidence predicted behavioral scores of disease severity. In sum, our results unravel systematic changes of large-scale phase- and amplitude coupling in Multiple Sclerosis. Furthermore, our results establish a new analysis approach to efficiently contrast high-dimensional neuroimaging data between experimental groups or conditions.

Empirical observations of how labs conduct research indicate that the adoption rate of open practices for transparent, reproducible, and collaborative science remains in its infancy. This is at odds with the overwhelming evidence for the necessity of these practices and their benefits for individual researchers, scientific progress, and society in general. To date, information required for implementing open science practices throughout the different steps of a research project is scattered among many different sources. Even experienced researchers in the topic find it hard to navigate the ecosystem of tools and to make sustainable choices. Here, we provide an integrated overview of community-developed resources that can support collaborative, open, reproducible, replicable, robust and generalizable neuroimaging throughout the entire research cycle from inception to publication and across different neuroimaging modalities. We review tools and practices supporting study inception and planning, data acquisition, research data management, data processing and analysis, and research dissemination. An online version of this resource can be found at https://oreoni.github.io. We believe it will prove helpful for researchers and institutions to make a successful and sustainable move towards open and reproducible science and to eventually take an active role in its future development.

Recent evidence suggests that beta bursts in subthalamic nucleus (STN) play an important role in Parkinsonian pathophysiology.We studied the spatio-temporal relationship between STN beta bursts and cortical activity in 26 Parkinson's disease (PD) patients undergoing deep brain stimulation (DBS) surgery. Postoperatively, we simultaneously recorded STN local field potentials (LFP) from externalized DBS leads and cortical activity using whole-brain magnetoencephalography. Event-related magnetic fields (ERF) were averaged time-locked to STN beta bursts and subjected to source localization.Our results demonstrate that ERF exhibiting activity significantly different from baseline activity were localized within areas functionally related to associative, limbic, and motor systems as well as regions pertinent for visual and language processing.Our data suggest that STN beta bursts are involved in network formation between STN and cortex. This interaction is in line with the idea of parallel processing within the basal ganglia-cortex loop, specifically within the functional subsystems of the STN (i.e., associative, limbic, motor, and the related cortical areas). ERFs within visual and language-related cortical areas indicate involvement of beta bursts in STN-cortex networks beyond the associative, limbic, and motor loops.In sum, our results highlight the involvement of STN beta bursts in the formation of multiple STN - cortex loops in patients with PD.

Visual focal attention is both fast and spatially localized, making it challenging to investigate using human neuroimaging paradigms. Here, we used a new multivariate multifocal mapping method with magnetoencephalography (MEG) to study how focal attention in visual space changes stimulus-evoked responses across the visual field. The observer's task was to detect a color change in the target location, or at the central fixation. Simultaneously, 24 regions in visual space were stimulated in parallel using an orthogonal, multifocal mapping stimulus sequence. First, we used univariate analysis to estimate stimulus-evoked responses in each channel. Then we applied multivariate pattern analysis to look for attentional effects on the responses. We found that attention to a target location causes two spatially and temporally separate effects. Initially, attentional modulation is brief, observed at around 60–130 ms post stimulus, and modulates responses not only at the target location but also in adjacent regions. A later modulation was observed from around 200 ms, which was specific to the location of the attentional target. The results support the idea that focal attention employs several processing stages and suggest that early attentional modulation is less spatially specific than late.

Identifying the directed connectivity that underlie networked activity between different cortical areas is critical for understanding the neural mechanisms behind sensory processing. Granger causality (GC) is widely used for this purpose in functional magnetic resonance imaging analysis, but there the temporal resolution is low, making it difficult to capture the millisecond-scale interactions underlying sensory processing. Magnetoencephalography (MEG) has millisecond resolution, but only provides low-dimensional sensor-level linear mixtures of neural sources, which makes GC inference challenging. Conventional methods proceed in two stages: First, cortical sources are estimated from MEG using a source localization technique, followed by GC inference among the estimated sources. However, the spatiotemporal biases in estimating sources propagate into the subsequent GC analysis stage, may result in both false alarms and missing true GC links. Here, we introduce the Network Localized Granger Causality (NLGC) inference paradigm, which models the source dynamics as latent sparse multivariate autoregressive processes and estimates their parameters directly from the MEG measurements, integrated with source localization, and employs the resulting parameter estimates to produce a precise statistical characterization of the detected GC links. We offer several theoretical and algorithmic innovations within NLGC and further examine its utility via comprehensive simulations and application to MEG data from an auditory task involving tone processing from both younger and older participants. Our simulation studies reveal that NLGC is markedly robust with respect to model mismatch, network size, and low signal-to-noise ratio, whereas the conventional two-stage methods result in high false alarms and mis-detections. We also demonstrate the advantages of NLGC in revealing the cortical network-level characterization of neural activity during tone processing and resting state by delineating task- and age-related connectivity changes.

Spatial hearing in humans is a high-level auditory process that is crucial to rapid sound localization in the environment. Both neurophysiological models with animals and neuroimaging evidence from human subjects in the wakefulness stage suggest that the localization of auditory objects is mainly located in the posterior auditory cortex. However, whether this cognitive process is preserved during sleep remains unclear. To fill this research gap, we investigated the sleeping brain's capacity to identify sound locations by recording simultaneous electroencephalographic (EEG) and magnetoencephalographic (MEG) signals during wakefulness and non-rapid eye movement (NREM) sleep in human subjects. Using the frequency-tagging paradigm, the subjects were presented with a basic syllable sequence at 5 Hz and a location change that occurred every three syllables, resulting in a sound localization shift at 1.67 Hz. The EEG and MEG signals were used for sleep scoring and neural tracking analyses, respectively. Neural tracking responses at 5 Hz reflecting basic auditory processing were observed during both wakefulness and NREM sleep, although the responses during sleep were weaker than those during wakefulness. Cortical responses at 1.67 Hz, which correspond to the sound location change, were observed during wakefulness regardless of attention to the stimuli but vanished during NREM sleep. These results for the first time indicate that sleep preserves basic auditory processing but disrupts the higher-order brain function of sound localization.

Source reconstruction of magnetoencephalography (MEG) has been used to assess brain reorganization after brain damage, such as stroke. Lesions result in parts of the brain having an electrical conductivity that differs from the normal values. The effect this has on the forward solutions (i.e., the propagation of electric currents and magnetic fields generated by cortical activity) is well predictable. However, their influence on source localization results is not well characterized and understood. This is specifically a concern for patient studies with asymmetric (i.e., within one hemisphere) lesions focusing on asymmetric and lateralized brain activity, such as language. In particular, it is good practice to consider the level of geometrical detail that is necessary to compute and interpret reliable source reconstruction results.To understand the effect of lesions on source estimates and propose recommendations to researchers working with clinical data, in this study we consider the trade off between improved accuracy and the additional effort to compute more realistic head models, with the aim to answer the question whether the additional effort is worth it. We simulated and analyzed the effects of a stroke lesion (i.e., an asymmetrically distributed CSF-filled cavity) in the head model with three different sizes and locations when performing MEG source reconstruction using a finite element method (FEM). We compared the effect of the lesion with a homogeneous head model that neglects the lesion. We computed displacement and attenuation/amplification maps to quantify the localization errors and signal magnitude modulation.We conclude that brain lesions leading to asymmetrically distributed CSF-filled cavities should be modeled when performing MEG source reconstruction, especially when investigating deep sources or post-stroke hemispheric lateralization of functions. The strongest effects are not only visible in perilesional areas, but can extend up to 20 mm from the lesion. Bigger lesions lead to stronger effects impacting larger areas, independently from the lesion location. Lastly, we conclude that more priority should be given to usability and accessibility of the required computational tools, to allow researchers with less technical expertise to use the improved methods that are available but currently not widely adopted yet.

Theoretical work and empirical observations suggest a contribution of regions along the intraparietal sulcus to the process of evidence accumulation during episodic memory retrieval. In the present study, we recorded magnetoencephalographic signals in a group of healthy human participants to test whether the pattern of oscillatory modulations in the lateral parietal lobe is consistent with the mnemonic accumulator hypothesis. To this aim, the dynamic properties and the spatial distribution of MEG oscillatory power modulations were investigated during an item recognition task in which the amount of evidence for old vs. new memory decisions was manipulated across three levels. A data-driven approach was employed to identify brain nodes where oscillatory activity was sensitive to both retrieval success and the amount of evidence for old decisions. The analysis identified three nodes in the left lateral parietal lobe where the event-related desynchronization (ERD) in the alpha frequency band showed both effects. Further analyses revealed that the alpha ERD in the intraparietal sulcus, but not in other parietal nodes: i. showed modulation of duration in response to the amount of evidence for both old and new decisions, ii. was behaviorally significant, and iii. more accurately tracked the subjective memory judgment rather than the objective memory status. The present findings provide support for a recent anatomical-functional model of the parietal involvement in episodic memory retrieval and suggest that the alpha ERD in the intraparietal sulcus might represent a neural signature of the evidence accumulation process during simple memory-based decisions.

Background: Assessing brain activity during rest has become a widely used approach in developmental neuroscience. Extant literature has measured resting brain activity both during eyes-open and eyes-closed conditions, but the difference between these conditions has not yet been well characterized. Studies, limited to fMRI and EEG, have suggested that eyes-open versus -closed conditions may differentially impact neural activity, especially in visual cortices. Methods: Spontaneous cortical activity was recorded using MEG from 108 typically developing youth (9-15 years-old; 55 female) during separate sessions of eyes-open and eyes-closed rest. MEG source images were computed, and the strength of spontaneous neural activity was estimated in the canonical delta, theta, alpha, beta, and gamma bands, respectively. Power spectral density maps for eyes-open were subtracted from eyes-closed rest, and then submitted to vertex-wise regression models to identify spatially specific differences between conditions and as a function of age and sex. Results: Relative alpha power was weaker in the eyes-open compared to -closed condition, but otherwise eyes-open was stronger in all frequency bands, with differences concentrated in the occipital cortex. Relative theta power became stronger in the eyes-open compared to the eyes-closed condition with increasing age in frontal cortex. No differences were observed between males and females. Conclusions: The differences in relative power from eyes-closed to -open conditions are consistent with changes observed in task-based visual sensory responses. Age differences occurred in relatively late developing frontal regions, consistent with canonical attention regions, suggesting that these differences could be reflective of developmental changes in attention processes during puberty. Taken together, resting-state paradigms using eyes-open versus -closed produce distinct results and, in fact, can help pinpoint sensory related brain activity.

Sensory processing during development is important for the emerging cognitive skills underlying goal-directed behavior. Yet, it is not known how auditory processing in children is related to their cognitive functions. Here, we utilized combined magneto- and electroencephalographic (M/EEG) measurements in school-aged children (6-14y) to show that child auditory cortical activity at ∼250 ms after auditory stimulation predicts the performance in inhibition tasks. While unaffected by task demands, the amplitude of the left-hemisphere activation pattern was significantly correlated with the variability of behavioral response time. Since this activation pattern is typically not present in adults, our results suggest divergent brain mechanisms in adults and children for consistent performance in auditory-based cognitive tasks. This difference can be explained as a shift in cortical resources for cognitive control from sensorimotor associations in the auditory cortex of children to top–down regulated control processes involving (pre)frontal and cingulate areas in adults.

Representational Similarity Analysis (RSA) has emerged as a popular method for relating representational spaces from human brain activity, behavioral data, and computational models. RSA is based on the comparison of representational (dis-)similarity matrices (RDMs or RSMs), which characterize the pairwise (dis-)similarities of all conditions across all features (e.g. fMRI voxels or units of a model). However, classical RSA treats each feature as equally important. This ‘equal weights’ assumption contrasts with the flexibility of multivariate decoding, which reweights individual features for predicting a target variable. As a consequence, classical RSA may lead researchers to underestimate the correspondence between a model and a brain region and, in case of model comparison, may lead them to select an inferior model. The aim of this work is twofold: First, we sought to broadly test feature-reweighted RSA (FR-RSA) applied to computational models and reveal the extent to which reweighting model features improves RSM correspondence and affects model selection. Previous work suggested that reweighting can improve model selection in RSA but it has remained unclear to what extent these results generalize across datasets and data modalities. To draw more general conclusions, we utilized a range of publicly available datasets and three popular deep neural networks (DNNs). Second, we propose voxel-reweighted RSA, a novel use case of FR-RSA that reweights fMRI voxels, mirroring the rationale of multivariate decoding of optimally combining voxel activity patterns. We found that reweighting individual model units markedly improved the fit between model RSMs and target RSMs derived from several fMRI and behavioral datasets and affected model selection, highlighting the importance of considering FR-RSA. For voxel-reweighted RSA, improvements in RSM correspondence were even more pronounced, demonstrating the utility of this novel approach. We additionally show that classical noise ceilings can be exceeded when FR-RSA is applied and propose an updated approach for their computation. Taken together, our results broadly validate the use of FR-RSA for improving the fit between computational models, brain, and behavioral data, allowing us to better adjudicate between competing computational models. Further, our results suggest that FR-RSA applied to brain measurement channels could become an important new method to assess the correspondence between representational spaces.

Cortical oscillations and scale-free neural activity are thought to influence a variety of cognitive functions, but their differential relationships to neural stability and flexibility has never been investigated. Based on the existing literature, we hypothesize that scale-free and oscillatory processes in the brain exhibit different trade-offs between stability and flexibility; specifically, cortical oscillations may reflect variable, task-responsive aspects of brain activity, while scale-free activity is proposed to reflect a more stable and task-unresponsive aspect. We test this hypothesis using data from two large-scale MEG studies (HCP: n = 89; CamCAN: n = 195), operationalizing stability and flexibility by task-responsiveness and spontaneous intra-subject variability in resting state. We demonstrate that the power-law exponent of scale-free activity is a highly stable parameter, which responds little to external cognitive demands and shows minimal spontaneous fluctuations over time. In contrast, oscillatory power, particularly in the alpha range (8–13 Hz), responds strongly to tasks and exhibits comparatively large spontaneous fluctuations over time. In sum, our data support differential roles for oscillatory and scale-free activity in the brain with respect to neural stability and flexibility. This result carries implications for criticality-based theories of scale-free activity, state-trait models of variability, and homeostatic views of the brain with regulated variables vs. effectors.

Chunking language has been proposed to be vital for comprehension enabling the extraction of meaning from a continuous stream of speech. However, neurocognitive mechanisms of chunking are poorly understood. The present study investigated neural correlates of chunk boundaries intuitively identified by listeners in natural speech drawn from linguistic corpora using magneto- and electroencephalography (MEEG). In a behavioral experiment, subjects marked chunk boundaries in the excerpts intuitively, which revealed highly consistent chunk boundary markings across the subjects. We next recorded brain activity to investigate whether chunk boundaries with high and medium agreement rates elicit distinct evoked responses compared to non-boundaries. Pauses placed at chunk boundaries elicited a closure positive shift with the sources over bilateral auditory cortices. In contrast, pauses placed within a chunk were perceived as interruptions and elicited a biphasic emitted potential with sources located in the bilateral primary and non-primary auditory areas with right-hemispheric dominance, and in the right inferior frontal cortex. Furthermore, pauses placed at stronger boundaries elicited earlier and more prominent activation over the left hemisphere suggesting that brain responses to chunk boundaries of natural speech can be modulated by the relative strength of different linguistic cues, such as syntactic structure and prosody.

The increasing requirements for adoption of FAIR data management and sharing original research data from neuroimaging studies can be at odds with protecting the anonymity of the research participants due to the person-identifiable anatomical features in the data. We propose a solution to this dilemma for anatomical MRIs used in MEG source analysis. In MEG analysis, the channel-level data is reconstructed to the source-level using models derived from anatomical MRIs. Sharing data, therefore, requires sharing the anatomical MRI to replicate the analysis. The suggested solution is to replace the individual anatomical MRIs with individualised warped templates that can be used to carry out the MEG source analysis and that provide sufficient geometrical similarity to the original participants’ MRIs.First, we demonstrate how the individualised template warping can be implemented with one of the leading open-source neuroimaging analysis toolboxes. Second, we compare results from four different MEG source reconstruction methods performed with an individualised warped template to those using the participant's original MRI. While the source reconstruction results are not numerically identical, there is a high similarity between the results for single dipole fits, dynamic imaging of coherent sources beamforming, and atlas-based virtual channel beamforming. There is a moderate similarity between minimum-norm estimates, as anticipated due to this method being anatomically constrained and dependent on the exact morphological features of the cortical sheet.We also compared the morphological features of the warped template to those of the original MRI. These showed a high similarity in grey matter volume and surface area, but a low similarity in the average cortical thickness and the mean folding index within cortical parcels.Taken together, this demonstrates that the results obtained by MEG source reconstruction can be preserved with the warped templates, whereas the anatomical and morphological fingerprint is sufficiently altered to protect the anonymity of research participants. In cases where participants consent to sharing anatomical MRI data, it remains preferable to share the original defaced data with an appropriate data use agreement. In cases where participants did not consent to share their MRIs, the individualised warped MRI template offers a good compromise in sharing data for reuse while retaining anonymity for research participants.

Dyslexia is a frequent developmental disorder in which reading acquisition is delayed and that is usually associated with difficulties understanding speech in noise. At the neuronal level, children with dyslexia were reported to display abnormal cortical tracking of speech (CTS) at phrasal rate. Here, we aimed to determine if abnormal tracking relates to reduced reading experience, and if it is modulated by the severity of dyslexia or the presence of acoustic noise.We included 26 school-age children with dyslexia, 26 age-matched controls and 26 reading-level matched controls. All were native French speakers. Children's brain activity was recorded with magnetoencephalography while they listened to continuous speech in noiseless and multiple noise conditions. CTS values were compared between groups, conditions and hemispheres, and also within groups, between children with mild and severe dyslexia.Syllabic CTS was significantly reduced in the right superior temporal gyrus in children with dyslexia compared with controls matched for age but not for reading level. Severe dyslexia was characterized by lower rapid automatized naming (RAN) abilities compared with mild dyslexia, and phrasal CTS lateralized to the right hemisphere in children with mild dyslexia and all control groups but not in children with severe dyslexia. Finally, an alteration in phrasal CTS was uncovered in children with dyslexia compared with age-matched controls in babble noise conditions but not in other less challenging listening conditions (non-speech noise or noiseless conditions); no such effect was seen in comparison with reading-level matched controls.Overall, our results confirmed the finding of altered neuronal basis of speech perception in noiseless and babble noise conditions in dyslexia compared with age-matched peers. However, the absence of alteration in comparison with reading-level matched controls demonstrates that such alterations are associated with reduced reading level, suggesting they are merely driven by reduced reading experience rather than a cause of dyslexia. Finally, our result of altered hemispheric lateralization of phrasal CTS in relation with altered RAN abilities in severe dyslexia is in line with a temporal sampling deficit of speech at phrasal rate in dyslexia.

Analyzing non-invasive recordings of electroencephalography (EEG) and magnetoencephalography (MEG) directly in sensor space, using the signal from individual sensors, is a convenient and standard way of working with this type of data. However, volume conduction introduces considerable challenges for sensor space analysis. While the general idea of signal mixing due to volume conduction in EEG/MEG is recognized, the implications have not yet been clearly exemplified. Here, we illustrate how different types of activity overlap on the level of individual sensors. We show spatial mixing in the context of alpha rhythms, which are known to have generators in different areas of the brain. Using simulations with a realistic 3D head model and lead field and data analysis of a large resting-state EEG dataset, we show that electrode signals can be differentially affected by spatial mixing by computing a sensor complexity measure. While prominent occipital alpha rhythms result in less heterogeneous spatial mixing on posterior electrodes, central electrodes show a diversity of rhythms present. This makes the individual contributions, such as the sensorimotor mu-rhythm and temporal alpha rhythms, hard to disentangle from the dominant occipital alpha. Additionally, we show how strong occipital rhythms can contribute the majority of activity to frontal channels, potentially compromising analyses that are solely conducted in sensor space. We also outline specific consequences of signal mixing for frequently used assessment of power, power ratios and connectivity profiles in basic research and for neurofeedback application. With this work, we hope to illustrate the effects of volume conduction in a concrete way, such that the provided practical illustrations may be of use to EEG researchers to in order to evaluate whether sensor space is an appropriate choice for their topic of investigation.

Early detection of Alzheimer's disease (AD) is essential for developing effective treatments. Neuroimaging techniques like Magnetic Resonance Imaging (MRI) have the potential to detect brain changes before symptoms emerge. Structural MRI can detect atrophy related to AD, but it is possible that functional changes are observed even earlier. We therefore examined the potential of Magnetoencephalography (MEG) to detect differences in functional brain activity in people with Mild Cognitive Impairment (MCI) – a state at risk of early AD. We introduce a framework for multimodal combination to ask whether MEG data from a resting-state provides complementary information beyond structural MRI data in the classification of MCI versus controls. More specifically, we used multi-kernel learning of support vector machines to classify 163 MCI cases versus 144 healthy elderly controls from the BioFIND dataset. When using the covariance of planar gradiometer data in the low Gamma range (30–48 Hz), we found that adding a MEG kernel improved classification accuracy above kernels that captured several potential confounds (e.g., age, education, time-of-day, head motion). However, accuracy using MEG alone (68%) was worse than MRI alone (71%). When simply concatenating (normalized) features from MEG and MRI into one kernel (Early combination), there was no advantage of combining MEG with MRI versus MRI alone. When combining kernels of modality-specific features (Intermediate combination), there was an improvement in multimodal classification to 74%. The biggest multimodal improvement however occurred when we combined kernels from the predictions of modality-specific classifiers (Late combination), which achieved 77% accuracy (a reliable improvement in terms of permutation testing). We also explored other MEG features, such as the variance versus covariance of magnetometer versus planar gradiometer data within each of 6 frequency bands (delta, theta, alpha, beta, low gamma, or high gamma), and found that they generally provided complementary information for classification above MRI. We conclude that MEG can improve on the MRI-based classification of MCI.

Our mental representation of egocentric space is influenced by the disproportionate sensory perception of the body. Previous studies have focused on the neural architecture for egocentric representations within the visual field. However, the space representation underlying the body is still unclear. To address this problem, we applied both functional Magnitude Resonance Imaging (fMRI) and Magnetoencephalography (MEG) to a spatial-memory paradigm by using a virtual environment in which human participants remembered a target location left, right, or back relative to their own body. Both experiments showed larger involvement of the frontoparietal network in representing a retrieved target on the left/right side than on the back. Conversely, the medial temporal lobe (MTL)-parietal network was more involved in retrieving a target behind the participants. The MEG data showed an earlier activation of the MTL-parietal network than that of the frontoparietal network during retrieval of a target location. These findings suggest that the parietal cortex may represent the entire space around the self-body by coordinating two distinct brain networks.

Two techniques for analyzing human extracranial neurophysiological signals, namely the periodic/aperiodic parameterization of neural power spectra and the transient events framework of oscillatory activity, have recently emerged in the scientific literature. In this work, we integrate these two analysis perspectives to analyze extracranial neurophysiological signals as a series of transient rhythmic events disambiguated from the background aperiodic activity. We call this novel technique the periodic/aperiodic parametrization of transient oscillations (PAPTO). We demonstrate PAPTO by investigating resting-state sensorimotor magnetoencephalography recordings from the Cambridge Center for Ageing and Neuroscience cross-sectional study on healthy ageing (n = 600, ages 18–88). We show that PAPTO is more sensitive to neocortical transient beta rhythms compared to more conventional transient event detection algorithms and captures more variance in the resting-state occurrence rate of beta events across participants. The improved sensitivity of PAPTO reveals that the beta occurrence rate almost doubles over the adult lifespan which we discuss in terms of thalamocortical beta generation in the somatosensory cortex and the age-related decline of sensory perception.

Falling asleep is a dynamical process that is poorly defined. The period preceding sleep, characterized by the progressive alteration of behavioral responses to the environment, which may last several minutes, has no electrophysiological definition, and is embedded in the first stage of sleep (N1). We aimed at better characterizing this drowsiness period looking for neurophysiological predictors of responsiveness using electro and magneto-encephalography. Healthy participants were recorded when falling asleep, while they were presented with continuous auditory stimulations and asked to respond to deviant sounds. We analysed brain responses to sounds and markers of ongoing activity, such as information and connectivity measures, in relation to rapid fluctuations of brain rhythms observed at sleep onset and participants’ capabilities to respond. Results reveal a drowsiness period distinct from wakefulness and sleep, from alpha rhythms to the first sleep spindles, characterized by diverse and transient brain states that come on and off at the scale of a few seconds and closely reflects, mainly through neural processes in alpha and theta bands, decreasing probabilities to be responsive to external stimuli. Results also show that the global P300 was only present in responsive trials, regardless of vigilance states. A better consideration of the drowsiness period through a formalized classification and its specific brain markers such as described here should lead to significant advances in vigilance assessment in the future, in medicine and ecological environments.

We recorded neural responses in human participants to three types of pitch-evoking regular stimuli at rates below and above the lower limit of pitch using magnetoencephalography (MEG). These bandpass filtered (1–4 kHz) stimuli were harmonic complex tones (HC), click trains (CT), and regular interval noise (RIN). Trials consisted of noise-regular-noise (NRN) or regular-noise-regular (RNR) segments in which the repetition rate (or fundamental frequency F0) was either above (250 Hz) or below (20 Hz) the lower limit of pitch. Neural activation was estimated and compared at the senor and source levels.The pitch-relevant regular stimuli (F0 = 250 Hz) were all associated with marked evoked responses at around 140 ms after noise-to-regular transitions at both sensor and source levels. In particular, greater evoked responses to pitch-relevant stimuli than pitch-irrelevant stimuli (F0 = 20 Hz) were localized along the Heschl's sulcus around 140 ms. The regularity-onset responses for RIN were much weaker than for the other types of regular stimuli (HC, CT). This effect was localized over planum temporale, planum polare, and lateral Heschl's gyrus. Importantly, the effect of pitch did not interact with the stimulus type. That is, we did not find evidence to support different responses for different types of regular stimuli from the spatiotemporal cluster of the pitch effect (∼140 ms).The current data demonstrate cortical sensitivity to temporal regularity relevant to pitch that is consistently present across different pitch-relevant stimuli in the Heschl's sulcus between Heschl's gyrus and planum temporale, both of which have been identified as a “pitch center” based on different modalities.

How does brain activity in distributed semantic brain networks evolve over time, and how do these regions interact to retrieve the meaning of words? We compared spatiotemporal brain dynamics between visual lexical and semantic decision tasks (LD and SD), analysing whole-cortex evoked responses and spectral functional connectivity (coherence) in source-estimated electroencephalography and magnetoencephalography (EEG and MEG) recordings. Our evoked analysis revealed generally larger activation for SD compared to LD, starting in primary visual area (PVA) and angular gyrus (AG), followed by left posterior temporal cortex (PTC) and left anterior temporal lobe (ATL). The earliest activation effects in ATL were significantly left-lateralised. Our functional connectivity results showed significant connectivity between left and right ATL, PTC and right ATL in an early time window, as well as between left ATL and IFG in a later time window. The connectivity of AG was comparatively sparse. We quantified the limited spatial resolution of our source estimates via a leakage index for careful interpretation of our results. Our findings suggest that the different demands on semantic information retrieval in lexical and semantic decision tasks first modulate visual and attentional processes, then multimodal semantic information retrieval in the ATLs and finally control regions (PTC and IFG) in order to extract task-relevant semantic features for response selection. Whilst our evoked analysis suggests a dominance of left ATL for semantic processing, our functional connectivity analysis also revealed significant involvement of right ATL in the more demanding semantic task. Our findings demonstrate the complementarity of evoked and functional connectivity analysis, as well as the importance of dynamic information for both types of analyses.

Beamforming is a popular method for functional source reconstruction using magnetoencephalography (MEG) and electroencephalography (EEG) data. Beamformers, which were first proposed for MEG more than two decades ago, have since been applied in hundreds of studies, demonstrating that they are a versatile and robust tool for neuroscience. However, certain characteristics of beamformers remain somewhat elusive and there currently does not exist a unified documentation of the mathematical underpinnings and computational subtleties of beamformers as implemented in the most widely used academic open source software packages for MEG analysis (Brainstorm, FieldTrip, MNE, and SPM). Here, we provide such documentation that aims at providing the mathematical background of beamforming and unifying the terminology. Beamformer implementations are compared across toolboxes and pitfalls of beamforming analyses are discussed. Specifically, we provide details on handling rank deficient covariance matrices, prewhitening, the rank reduction of forward fields, and on the combination of heterogeneous sensor types, such as magnetometers and gradiometers. The overall aim of this paper is to contribute to contemporary efforts towards higher levels of computational transparency in functional neuroimaging.

The goal of this paper is to present a theoretical and practical introduction to generalized eigendecomposition (GED), which is a robust and flexible framework used for dimension reduction and source separation in multichannel signal processing. In cognitive electrophysiology, GED is used to create spatial filters that maximize a researcher-specified contrast. For example, one may wish to exploit an assumption that different sources have different frequency content, or that sources vary in magnitude across experimental conditions. GED is fast and easy to compute, performs well in simulated and real data, and is easily adaptable to a variety of specific research goals. This paper introduces GED in a way that ties together myriad individual publications and applications of GED in electrophysiology, and provides sample MATLAB and Python code that can be tested and adapted. Practical considerations and issues that often arise in applications are discussed.

One of the primary technical challenges facing magnetoencephalography (MEG) is that the magnitude of neuromagnetic fields is several orders of magnitude lower than interfering signals. Recently, a new type of sensor has been developed – the optically pumped magnetometer (OPM). These sensors can be placed directly on the scalp and move with the head during participant movement, making them wearable. This opens up a range of exciting experimental and clinical opportunities for OPM-based MEG experiments, including paediatric studies, and the incorporation of naturalistic movements into neuroimaging paradigms. However, OPMs face some unique challenges in terms of interference suppression, especially in situations involving mobile participants, and when OPMs are integrated with electrical equipment required for naturalistic paradigms, such as motion capture systems. Here we briefly review various hardware solutions for OPM interference suppression. We then outline several signal processing strategies aimed at increasing the signal from neuromagnetic sources. These include regression-based strategies, temporal filtering and spatial filtering approaches. The focus is on the practical application of these signal processing algorithms to OPM data. In a similar vein, we include two worked-through experiments using OPM data collected from a whole-head sensor array. These tutorial-style examples illustrate how the steps for suppressing external interference can be implemented, including the associated data and code so that researchers can try the pipelines for themselves. With the popularity of OPM-based MEG rising, there will be an increasing need to deal with interference suppression. We hope this practical paper provides a resource for OPM-based MEG researchers to build upon.

Optically pumped magnetometers (OPMs) developed for magnetoencephalography (MEG) typically operate in the spin-exchange-relaxation-free (SERF) regime and measure a magnetic field component perpendicular to the propagation axis of the optical-pumping photons. The most common type of OPM for MEG employs alkali atoms, e.g. 87Rb, as the sensing element and one or more lasers for preparation and interrogation of the magnetically sensitive states of the alkali atoms ensemble. The sensitivity of the OPM can be greatly enhanced by operating it in the SERF regime, where the alkali atoms’ spin exchange rate is much faster than the Larmor precession frequency. The SERF regime accommodates remnant static magnetic fields up to ±5 nT. However, in the presented work, through simulation and experiment, we demonstrate that multi-axis magnetic signals in the presence of small remnant static magnetic fields, not violating the SERF criteria, can introduce significant error terms in OPM's output signal. We call these deterministic errors cross-axis projection errors (CAPE), where magnetic field components of the MEG signal perpendicular to the nominal sensing axis contribute to the OPM signal giving rise to substantial amplitude and phase errors. Furthermore, through simulation, we have discovered that CAPE can degrade localization and calibration accuracy of OPM-based magnetoencephalography (OPM-MEG) systems.

Electrophysiological population signals contain oscillatory and non-oscillatory aperiodic (1/frequency-like) components. So far research has largely focused on oscillatory activity, and only recently, interest in aperiodic population activity has gained momentum. Accordingly, while the cortical correlation structure of oscillatory population activity has been characterized, little is known about the correlation of aperiodic neuronal activity. To address this, we investigated aperiodic neuronal population activity in the human brain using resting-state magnetoencephalography (MEG). We combined source-analysis, signal orthogonalization and irregular-resampling auto-spectral analysis (IRASA) to systematically characterize the cortical distribution and correlation of aperiodic neuronal activity. We found that aperiodic population activity is robustly correlated across the cortex and that this correlation is spatially well structured. Furthermore, we found that the cortical correlation structure of aperiodic activity is similar but distinct from the correlation structure of oscillatory neuronal activity. Anterior cortical regions showed the strongest differences between oscillatory and aperiodic correlation patterns. Our results suggest that correlations of aperiodic population activity serve as robust markers of cortical network interactions. Furthermore, our results show that aperiodic and oscillatory signal components provide non-redundant information about large-scale neuronal correlations. This may reflect at least partly distinct neuronal mechanisms underlying and reflected by oscillatory and aperiodic neuronal population activity.

Synchronization of neuronal responses over large distances is hypothesized to be important for many cortical functions. However, no straightforward methods exist to estimate synchrony non-invasively in the living human brain. MEG and EEG measure the whole brain, but the sensors pool over large, overlapping cortical regions, obscuring the underlying neural synchrony. Here, we developed a model from stimulus to cortex to MEG sensors to disentangle neural synchrony from spatial pooling of the instrument. We find that synchrony across cortex has a surprisingly large and systematic effect on predicted MEG spatial topography. We then conducted visual MEG experiments and separated responses into stimulus-locked and broadband components. The stimulus-locked topography was similar to model predictions assuming synchronous neural sources, whereas the broadband topography was similar to model predictions assuming asynchronous sources. We infer that visual stimulation elicits two distinct types of neural responses, one highly synchronous and one largely asynchronous across cortex.

Visualization of complex data is commonplace in neurophysiology research. Here, we highlight specific perceptual issues related to the ongoing misuse of variations of the rainbow colour scheme, with a particular emphasis on time-frequency decompositions in electrophysiology as an illustrative example. We review the risks of biased interpretation of neurophysiological data in this context, and provide guidelines to improve the use of colour maps to visualise complex, multidimensional data in neurophysiology research.