Brief segments of neurophysiological activity enable individual differentiation.

Large, openly available datasets and current analytic tools promise the emergence of population neuroscience. The considerable diversity in personality traits and behaviour between individuals is reflected in the statistical variability of neural data collected in such repositories. Recent studies with functional magnetic resonance imaging (fMRI) have concluded that patterns of resting-state functional connectivity can both successfully distinguish individual participants within a cohort and predict some individual traits, yielding the notion of an individual's neural fingerprint. Here, we aim to clarify the neurophysiological foundations of individual differentiation from features of the rich and complex dynamics of resting-state brain activity using magnetoencephalography (MEG) in 158 participants. We show that akin to fMRI approaches, neurophysiological functional connectomes enable the differentiation of individuals, with rates similar to those seen with fMRI. We also show that individual differentiation is equally successful from simpler measures of the spatial distribution of neurophysiological spectral signal power. Our data further indicate that differentiation can be achieved from brain recordings as short as 30 seconds, and that it is robust over time: the neural fingerprint is present in recordings performed weeks after their baseline reference data was collected. This work, thus, extends the notion of a neural or brain fingerprint to fast and large-scale resting-state electrophysiological dynamics.

Adapting non-invasive human recordings along multiple task-axes shows unfolding of spontaneous and over-trained choice.

Choices rely on a transformation of sensory inputs into motor responses. Using invasive single neuron recordings, the evolution of a choice process has been tracked by projecting population neural responses into state spaces. Here, we develop an approach that allows us to recover similar trajectories on a millisecond timescale in non-invasive human recordings. We selectively suppress activity related to three task-axes, relevant and irrelevant sensory inputs and response direction, in magnetoencephalography data acquired during context-dependent choices. Recordings from premotor cortex show a progression from processing sensory input to processing the response. In contrast to previous macaque recordings, information related to choice-irrelevant features is represented more weakly than choice-relevant sensory information. To test whether this mechanistic difference between species is caused by extensive over-training common in non-human primate studies, we trained humans on >20,000 trials of the task. Choice-irrelevant features were still weaker than relevant features in premotor cortex after over-training.

Statistical power: Implications for planning MEG studies.

Statistical power is key for robust, replicable science. Here, we systematically explored how numbers of trials and subjects affect statistical power in MEG sensor-level data. More specifically, we simulated "experiments" using the MEG resting-state dataset of the Human Connectome Project (HCP). We divided the data in two conditions, injected a dipolar source at a known anatomical location in the "signal condition", but not in the "noise condition", and detected significant differences at sensor level with classical paired t-tests across subjects, using amplitude, squared amplitude, and global field power (GFP) measures. Group-level detectability of these simulated effects varied drastically with anatomical origin. We thus examined in detail which spatial properties of the sources affected detectability, looking specifically at the distance from closest sensor and orientation of the source, and at the variability of these parameters across subjects. In line with previous single-subject studies, we found that the most detectable effects originate from source locations that are closest to the sensors and oriented tangentially with respect to the head surface. In addition, cross-subject variability in orientation also affected group-level detectability, boosting detection in regions where this variability was small and hindering detection in regions where it was large. Incidentally, we observed a considerable covariation of source position, orientation, and their cross-subject variability in individual brain anatomical space, making it difficult to assess the impact of each of these variables independently of one another. We thus also performed simulations where we controlled spatial properties independently of individual anatomy. These additional simulations confirmed the strong impact of distance and orientation and further showed that orientation variability across subjects affects detectability, whereas position variability does not. Importantly, our study indicates that strict unequivocal recommendations as to the ideal number of trials and subjects for any experiment cannot be realistically provided for neurophysiological studies and should be adapted according to the brain regions under study.

Assessment of Effective Network Connectivity among MEG None Contaminated Epileptic Transitory Events.

Characterizing epileptogenic zones EZ (sources responsible of excessive discharges) would assist a neurologist during epilepsy diagnosis. Locating efficiently these abnormal sources among magnetoencephalography (MEG) biomarker is obtained by several inverse problem techniques. These techniques present different assumptions and particular epileptic network connectivity. Here, we proposed to evaluate performances of distributed inverse problem in defining EZ. First, we applied an advanced technique based on Singular Value Decomposition (SVD) to recover only pure transitory activities (interictal epileptiform discharges). We evaluated our technique's robustness in separation between transitory and ripples versus frequency range, transitory shapes, and signal to noise ratio on simulated data (depicting both epileptic biomarkers and respecting time series and spectral properties of realistic data). We validated our technique on MEG signal using detector precision on 5 patients. Then, we applied four methods of inverse problem to define cortical areas and neural generators of excessive discharges. We computed network connectivity of each technique. Then, we confronted obtained noninvasive networks to intracerebral EEG transitory network connectivity using nodes in common, connection strength, distance metrics between concordant nodes of MEG and IEEG, and average propagation delay. Coherent Maximum Entropy on the Mean (cMEM) proved a high matching between MEG network connectivity and IEEG based on distance between active sources, followed by Exact low-resolution brain electromagnetic tomography (eLORETA), Dynamical Statistical Parametric Mapping (dSPM), and Minimum norm estimation (MNE). Clinical performance was interesting for entire methods providing in an average of 73.5% of active sources detected in depth and seen in MEG, and vice versa, about 77.15% of active sources were detected from MEG and seen in IEEG. Investigated problem techniques succeed at least in finding one part of seizure onset zone. dSPM and eLORETA depict the highest connection strength among all techniques. Propagation delay varies in this range [18, 25]ms, knowing that eLORETA ensures the lowest propagation delay (18 ms) and the closet one to IEEG propagation delay.

Lag-invariant detection of interactions in spatially-extended systems using linear inverse modeling.

Measurements on physical systems result from the systems' activity being converted into sensor measurements by a forward model. In a number of cases, inversion of the forward model is extremely sensitive to perturbations such as sensor noise or numerical errors in the forward model. Regularization is then required, which introduces bias in the reconstruction of the systems' activity. One domain in which this is particularly problematic is the reconstruction of interactions in spatially-extended complex systems such as the human brain. Brain interactions can be reconstructed from non-invasive measurements such as electroencephalography (EEG) or magnetoencephalography (MEG), whose forward models are linear and instantaneous, but have large null-spaces and high condition numbers. This leads to incomplete unmixing of the forward models and hence to spurious interactions. This motivated the development of interaction measures that are exclusively sensitive to lagged, i.e. delayed interactions. The drawback of such measures is that they only detect interactions that have sufficiently large lags and this introduces bias in reconstructed brain networks. We introduce three estimators for linear interactions in spatially-extended systems that are uniformly sensitive to all lags. We derive some basic properties of and relationships between the estimators and evaluate their performance using numerical simulations from a simple benchmark model.

Variability and bias between magnetoencephalography systems in localization of the primary visual cortex.

OBJECTIVES: When using MEG for pre-surgical mapping it is critically important that reliable estimates of functional locations, such as the primary visual cortex (V1) can be provided. Several different models of MEG systems exist, each with varying software and hardware configurations, and it is not currently known how the system type contributes to variability in V1 localization. PATIENTS AND METHODS: In this study, participants underwent MEG sessions using two different systems (Vector View and CTF) during which they were presented with a repeating grating stimulus to the lower-left visual quadrant to generate a visual evoked field (VEF). The location, amplitude and latency of the VEF source was compared between systems for each participant. RESULTS: No significant differences were found in latency and amplitude between systems, however, a significant bias in the latero-medial position of the localization was present. The median inter-system Euclidian distance between V1 localization across participants was 10.5 mm. CONCLUSIONS: Overall, our results indicate that mapping of V1 can be reliably reproduced within approximately one centimetre by different MEG systems. SIGNIFICANCE: This result provides knowledge of the useful limits on the reliability of localization which can be taken into consideration in clinical practice.

Non-Invasive Functional-Brain-Imaging with an OPM-based Magnetoencephalography System.

A non-invasive functional-brain-imaging system based on optically-pumped-magnetometers (OPM) is presented. The OPM-based magnetoencephalography (MEG) system features 20 OPM channels conforming to the subject's scalp. We have conducted two MEG experiments on three subjects: assessment of somatosensory evoked magnetic field (SEF) and auditory evoked magnetic field (AEF) using our OPM-based MEG system and a commercial MEG system based on superconducting quantum interference devices (SQUIDs). We cross validated the robustness of our system by calculating the distance between the location of the equivalent current dipole (ECD) yielded by our OPM-based MEG system and the ECD location calculated by the commercial SQUID-based MEG system. We achieved sub-centimeter accuracy for both SEF and AEF responses in all three subjects. Due to the proximity (12 mm) of the OPM channels to the scalp, it is anticipated that future OPM-based MEG systems will offer enhanced spatial resolution as they will capture finer spatial features compared to traditional MEG systems employing SQUIDs.

The Relationship between Trial-by-Trial Variability and Oscillations of Cortical Population Activity.

Neural activity fluctuates over time, creating considerable variability across trials. This trial-by-trial neural variability is dramatically reduced ("quenched") after the presentation of sensory stimuli. Likewise, the power of neural oscillations, primarily in the alpha-beta band, is also reduced after stimulus onset. Despite their similarity, these phenomena have so far been studied and discussed independently. We hypothesized that the two phenomena are tightly coupled in electrophysiological recordings of large cortical neural populations. To test this, we examined magnetoencephalography (MEG) recordings of healthy subjects viewing repeated presentations of a visual stimulus. The timing, amplitude, and spatial topography of variability-quenching and power-suppression were remarkably similar. Neural variability quenching was eliminated by excluding the alpha-beta band from the recordings, but not by excluding other frequency-bands. Moreover, individual magnitudes of alpha-beta band-power explained 86% of between-subject differences in variability quenching. An alternative mechanism that may generate variability quenching is increased phase alignment across trials. However, changes in inter-trial-phase-coherence (ITPC) exhibited distinct timing and no correlations with the magnitude of variability quenching in individual participants. These results reveal that neural variability quenching is tightly coupled with stimulus-induced changes in the power of alpha-beta band oscillations, associating two phenomena that have so far been studied in isolation.

Permutation Statistics for Connectivity Analysis between Regions of Interest in EEG and MEG Data.

Connectivity estimates based on electroencephalography (EEG) and magnetoencephalography (MEG) are unique in their ability to provide neurophysiologically meaningful spectral and temporal information non-invasively. This multi-dimensional aspect of the MEG/EEG based connectivity increases the challenges of the analysis and interpretation of the data. Many MEG/EEG studies address this complexity by using a hypothesis-driven approach, which focuses on particular regions of interest (ROI). However, if an effect is distributed unevenly over a large ROI and variable across subjects, it may not be detectable using conventional methods. Here, we propose a novel approach, which enhances the statistical power for weak and spatially discontinuous effects. This results in the ability to identify statistically significant connectivity patterns with spectral, temporal, and spatial specificity while correcting for multiple comparisons using nonparametric permutation methods. We call this new approach the Permutation Statistics for Connectivity Analysis between ROI (PeSCAR). We demonstrate the processing steps with simulated and real human data. The open-source Matlab code implementing PeSCAR are provided online.

Spatial neuronal synchronization and the waveform of oscillations: Implications for EEG and MEG.

Neuronal oscillations are ubiquitous in the human brain and are implicated in virtually all brain functions. Although they can be described by a prominent peak in the power spectrum, their waveform is not necessarily sinusoidal and shows rather complex morphology. Both frequency and temporal descriptions of such non-sinusoidal neuronal oscillations can be utilized. However, in non-invasive EEG/MEG recordings the waveform of oscillations often takes a sinusoidal shape which in turn leads to a rather oversimplified view on oscillatory processes. In this study, we show in simulations how spatial synchronization can mask non-sinusoidal features of the underlying rhythmic neuronal processes. Consequently, the degree of non-sinusoidality can serve as a measure of spatial synchronization. To confirm this empirically, we show that a mixture of EEG components is indeed associated with more sinusoidal oscillations compared to the waveform of oscillations in each constituent component. Using simulations, we also show that the spatial mixing of the non-sinusoidal neuronal signals strongly affects the amplitude ratio of the spectral harmonics constituting the waveform. Finally, our simulations show how spatial mixing can affect the strength and even the direction of the amplitude coupling between constituent neuronal harmonics at different frequencies. Validating these simulations, we also demonstrate these effects in real EEG recordings. Our findings have far reaching implications for the neurophysiological interpretation of spectral profiles, cross-frequency interactions, as well as for the unequivocal determination of oscillatory phase.

Identification of major depressive disorder and prediction of treatment response using functional connectivity between the prefrontal cortices and subgenual anterior cingulate: A real-world study.

BACKGROUND: Major depressive disorder (MDD) is associated with a heavy disease burden due to the difficulty in diagnosing the disorder and the uncertainty of treatment outcomes. Previous studies have demonstrated the value of functional connectivity (FC) between the dorsolateral prefrontal cortex (DLPFC) and the subgenual anterior cingulate cortex (sgACC) in the identification of MDD and the prediction of antidepressant efficacy. In the present study, we aimed to investigate whether FC is helpful in discriminating patients from healthy controls and in predicting treatment outcome. METHODS: Seventy-six medication-free patients with MDD and 28 healthy controls were enrolled in the study. Magnetoencephalography (MEG) and the Hamilton Rating Score for Depression (HRSD-17) were administered at baseline. Then, the HRSD-17 was assessed weekly until each patient met the remission criteria, defined as a total HRSD-17 score ≤ 7. Time-dependent Cox regression analysis was used to evaluate the association between FC and the incidence of remission. RESULTS: Healthy controls and MDD patients had opposite FC patterns; this may be helpful for identifying MDD (AUC = 0.8, p < 0.001, sensitivity 85.7%, specificity 67.9%). Alpha connectivity between the DLPFC and sgACC (HR 1.858, 95%CI 1.013-3.408, p = 0.045) was found to be an independent factor associated with better final antidepressant outcome. LIMITATIONS: This study was conducted in a small sample of subjects. Further, the direction of regulation between the DLPFC and sgACC was not considered. CONCLUSIONS: FC may help identify depression and may be related to the severity of depressive symptoms and predict the efficacy of antidepressant treatment.

Modeling neuronal avalanches and long-range temporal correlations at the emergence of collective oscillations: Continuously varying exponents mimic M/EEG results.

We revisit the CROS ("CRitical OScillations") model which was recently proposed as an attempt to reproduce both scale-invariant neuronal avalanches and long-range temporal correlations. With excitatory and inhibitory stochastic neurons locally connected in a two-dimensional disordered network, the model exhibits a transition where alpha-band oscillations emerge. Precisely at the transition, the fluctuations of the network activity have nontrivial detrended fluctuation analysis (DFA) exponents, and avalanches (defined as supra-threshold activity) have power law distributions of size and duration. We show that, differently from previous results, the exponents governing the distributions of avalanche size and duration are not necessarily those of the mean-field directed percolation universality class (3/2 and 2, respectively). Instead, in a narrow region of parameter space, avalanche exponents obtained via a maximum-likelihood estimator vary continuously and follow a linear relation, in good agreement with results obtained from M/EEG data. In that region, moreover, the values of avalanche and DFA exponents display a spread with positive correlations, reproducing human MEG results.

Enhanced Data Covariance Estimation Using Weighted Combination of Multiple Gaussian Kernels for Improved M/EEG Source Localization.

In the recent past, estimating brain activity with magneto/electroencephalography (M/EEG) has been increasingly employed as a noninvasive technique for understanding the brain functions and neural dynamics. However, one of the main open problems when dealing with M/EEG data is its non-Gaussian and nonstationary structure. In this paper, we introduce a methodology for enhancing the data covariance estimation using a weighted combination of multiple Gaussian kernels, termed WM-MK, that relies on the Kullback-Leibler divergence for associating each kernel weight to its relevance. From the obtained results of validation on nonstationary and non-Gaussian brain activity (simulated and real-world EEG data), WM-MK proves that the accuracy of the source estimation raises by more effectively exploiting the measured nonlinear structures with high time and space complexity.

Deep brain activities can be detected with magnetoencephalography.

The hippocampus and amygdala are key brain structures of the medial temporal lobe, involved in cognitive and emotional processes as well as pathological states such as epilepsy. Despite their importance, it is still unclear whether their  neural activity can be recorded non-invasively. Here, using simultaneous intracerebral and magnetoencephalography (MEG) recordings in patients with focal drug-resistant epilepsy, we demonstrate a direct contribution of amygdala and hippocampal activity to surface MEG recordings. In particular, a method of blind source separation, independent component analysis, enabled activity arising from large neocortical networks to be disentangled from that of deeper structures, whose amplitude at the surface was small but significant. This finding is highly relevant for our understanding of hippocampal and amygdala brain activity as it implies that their activity could potentially be measured non-invasively.

Discovering heritable modes of MEG spectral power.

Brain structure and many brain functions are known to be genetically controlled, but direct links between neuroimaging measures and their underlying cellular-level determinants remain largely undiscovered. Here, we adopt a novel computational method for examining potential similarities in high-dimensional brain imaging data between siblings. We examine oscillatory brain activity measured with magnetoencephalography (MEG) in 201 healthy siblings and apply Bayesian reduced-rank regression to extract a low-dimensional representation of familial features in the participants' spectral power structure. Our results show that the structure of the overall spectral power at 1-90 Hz is a highly conspicuous feature that not only relates siblings to each other but also has very high consistency within participants' own data, irrespective of the exact experimental state of the participant. The analysis is extended by seeking genetic associations for low-dimensional descriptions of the oscillatory brain activity. The observed variability in the MEG spectral power structure was associated with SDK1 (sidekick cell adhesion molecule 1) and suggestively with several other genes that function, for example, in brain development. The current results highlight the potential of sophisticated computational methods in combining molecular and neuroimaging levels for exploring brain functions, even for high-dimensional data limited to a few hundred participants.

Cluster-based permutation tests of MEG/EEG data do not establish significance of effect latency or location.

Cluster-based permutation tests are gaining an almost universal acceptance as inferential procedures in cognitive neuroscience. They elegantly handle the multiple comparisons problem in high-dimensional magnetoencephalographic and EEG data. Unfortunately, the power of this procedure comes hand in hand with the allure for unwarranted interpretations of the inferential output, the most prominent of which is the overestimation of the temporal, spatial, and frequency precision of statistical claims. This leads researchers to statements about the onset or offset of a certain effect that is not supported by the permutation test. In this article, we outline problems and common pitfalls of using and interpreting cluster-based permutation tests. We illustrate these with simulated data in order to promote a more intuitive understanding of the method. We hope that raising awareness about these issues will be beneficial to common scientific practices, while at the same time increasing the popularity of cluster-based permutation procedures.

Real-Time Clustered Multiple Signal Classification (RTC-MUSIC).

Magnetoencephalography (MEG) and electroencephalography provide a high temporal resolution, which allows estimation of the detailed time courses of neuronal activity. However, in real-time analysis of these data two major challenges must be handled: the low signal-to-noise ratio (SNR) and the limited time available for computations. In this work, we present real-time clustered multiple signal classification (RTC-MUSIC) a real-time source localization algorithm, which can handle low SNRs and can reduce the computational effort. It provides correlation information together with sparse source estimation results, which can, e.g., be used to identify evoked responses with high sensitivity. RTC-MUSIC clusters the forward solution based on an anatomical brain atlas and optimizes the scanning process inherent to MUSIC approaches. We evaluated RTC-MUSIC by analyzing MEG auditory and somatosensory data. The results demonstrate that the proposed method localizes sources reliably. For the auditory experiment the most dominant correlated source pair was located bilaterally in the superior temporal gyri. The highest activation in the somatosensory experiment was found in the contra-lateral primary somatosensory cortex.

Similarities and differences between on-scalp and conventional in-helmet magnetoencephalography recordings.

The development of new magnetic sensor technologies that promise sensitivities approaching that of conventional MEG technology while operating at far lower operating temperatures has catalysed the growing field of on-scalp MEG. The feasibility of on-scalp MEG has been demonstrated via benchmarking of new sensor technologies performing neuromagnetic recordings in close proximity to the head surface against state-of-the-art in-helmet MEG sensor technology. However, earlier work has provided little information about how these two approaches compare, or about the reliability of observed differences. Herein, we present such a comparison, based on recordings of the N20m component of the somatosensory evoked field as elicited by electric median nerve stimulation. As expected from the proximity differences between the on-scalp and in-helmet sensors, the magnitude of the N20m activation as recorded with the on-scalp sensor was higher than that of the in-helmet sensors. The dipole pattern of the on-scalp recordings was also more spatially confined than that of the conventional recordings. Our results furthermore revealed unexpected temporal differences in the peak of the N20m component. An analysis protocol was therefore developed for assessing the reliability of this observed difference. We used this protocol to examine our findings in terms of differences in sensor sensitivity between the two types of MEG recordings. The measurements and subsequent analysis raised attention to the fact that great care has to be taken in measuring the field close to the zero-line crossing of the dipolar field, since it is heavily dependent on the orientation of sensors. Taken together, our findings provide reliable evidence that on-scalp and in-helmet sensors measure neural sources in mostly similar ways.

Current clinical magnetoencephalography practice across Europe: Are we closer to use MEG as an established clinical tool?

PURPOSE: This comprehensive survey aims at characterizing the current clinical use of magnetoencephalography (MEG) across European MEG centres. METHODS: Forty-four MEG centres across Europe were contacted in May 2015 via personalized e-mail to contribute to survey. The web-based survey was available on-line for 1 month and the MEG centres that did not respond were further contacted to maximize participation. RESULTS: Among the 57% of responders, 12 centres from 10 different countries reported to use MEG for clinical applications. A total of 524 MEG investigations were performed in 2014 for the pre-surgical evaluation of epilepsy, while in the same period 244 MEG investigations were performed for pre-surgical functional brain mapping. Seven MEG centres located in different European countries performed ≥50 MEG investigations for epilepsy mapping in 2014, both in children and adults. In those centres, time from patient preparation to MEG data reporting tends to be lower than those investigating a lower annual number of patients. CONCLUSION: This survey demonstrates that there is in Europe an increasing and widespread expertise in the field of clinical MEG. These findings should serve as a basis to harmonize clinical MEG procedures and promote the clinical added value of MEG across Europe. MEG should now be considered in Europe as a mature clinical neurophysiological technique that should be used routinely in two specific clinical indications, i.e, the pre-surgical evaluation of refractory focal epilepsy and functional brain mapping.

The Cambridge Centre for Ageing and Neuroscience (Cam-CAN) data repository: Structural and functional MRI, MEG, and cognitive data from a cross-sectional adult lifespan sample.

This paper describes the data repository for the Cambridge Centre for Ageing and Neuroscience (Cam-CAN) initial study cohort. The Cam-CAN Stage 2 repository contains multi-modal (MRI, MEG, and cognitive-behavioural) data from a large (approximately N=700), cross-sectional adult lifespan (18-87years old) population-based sample. The study is designed to characterise age-related changes in cognition and brain structure and function, and to uncover the neurocognitive mechanisms that support healthy cognitive ageing. The database contains raw and preprocessed structural MRI, functional MRI (active tasks and resting state), and MEG data (active tasks and resting state), as well as derived scores from cognitive behavioural experiments spanning five broad domains (attention, emotion, action, language, and memory), and demographic and neuropsychological data. The dataset thus provides a depth of neurocognitive phenotyping that is currently unparalleled, enabling integrative analyses of age-related changes in brain structure, brain function, and cognition, and providing a testbed for novel analyses of multi-modal neuroimaging data.