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Plenty of artifact removal tools and pipelines have been developed to correct the EEG recordings and discover the values below the waveforms. Without visual inspection from the experts, it is susceptible to derive improper preprocessing states, like the insufficient preprocessed EEG (IPE), and the excessive preprocessed EEG (EPE). However, little is known about the impacts of IPE or EPE on the postprocessing in the frequency, spatial and temporal domains, particularly as to the spectra and the functional connectivity (FC) analysis. Here, the clean EEG (CE) was synthesized as the ground truth based on the New-York head model and the multivariate autoregressive model. Later, the IPE and the EPE were simulated by injecting the Gaussian noise and losing the brain activities, respectively. Then, the impacts on postprocessing were quantified by the deviation caused by the IPE or EPE from the CE as to the 4 temporal statistics, the multichannel power, the cross spectra, the dispersion of source imaging, and the properties of scalp EEG network. Lastly, the association analysis was performed between the PaLOSi metric and the varying trends of postprocessing with the evolution of preprocessing states. This study shed light on how the postprocessing outcomes are affected by the preprocessing states and PaLOSi may be a potential effective quality metric.

The brain projects require the collection of massive electrophysiological data, aiming to the longitudinal, sectional, or populational neuroscience studies. Quality metrics automatically label the data after centralized preprocessing. However, although the waveforms-based metrics are partially useful, they may be unreliable by neglecting the spectral profiles. Here, we detected the phenomenon of parallel log spectra (PaLOS) that the scalp EEG power in the log scale were parallel to each other from 10% of 2549 HBN EEG. This phenomenon was reproduced in 8% of 412 PMDT EEG from 4 databases. We designed the PaLOS index (PaLOSi) to indicate this phenomenon by decomposing the cross-spectra at different frequencies into the common principal component spaces. We found that the PaLOS biophysically implied a prominently dominant dipole in the source space which was implausible for the resting EEG. And it may be practically resulted from excessive preprocessing. Compared with the 1966 normative EEG cross-spectra, the HBN and the PMDT EEG with PaLOS presented generally much higher electrode pairwise coherences and higher similarity of coherence-based network patterns, which went against the known frequency dependent characteristic of coherence networks. We suggest the PaLOSi should lay in the range of 0.4-0.7 for large resting EEG quality assurance.

Standardizing terminology to annotate electrophysiological events can improve both computational research and clinical care. Sharing data enriched with standard terms can facilitate data exploration, from case studies to mega-analyses. The machine readability of such electrophysiological event annotations is essential for performing analyses efficiently across software tools and packages. Hierarchical Event Descriptors (HED) provide a framework for describing events in neuroscience experiments. HED library schemas extend the standard HED schema vocabulary to include specialized vocabularies, such as standardized clinical terms for electrophysiological events. The Standardized Computer-based Organized Reporting of EEG (SCORE) defines terms for annotating EEG events, including artifacts. This study developed a HED library schema for SCORE, making the terms machine-readable. We demonstrate that the HED-SCORE library schema can be used to annotate events in EEG data stored in the Brain Imaging Data Structure (BIDS). Clinicians and researchers worldwide can now use the HED-SCORE library schema to annotate and compute on electrophysiological data obtained from the human brain., Comment: 23 pages, 5 figures, 1 table

Kernel smooth is the most fundamental technique for data density and regression estimation. However, time-consuming is the biggest obstacle for the application that the direct evaluation of kernel smooth for $N$ samples needs ${O}\left( {{N}^{2}} \right)$ operations. People have developed fast smooth algorithms using the idea of binning with FFT. Unfortunately, the accuracy is not controllable, and the implementation for multivariable and its bandwidth selection for the fast method is not available. Hence, we introduce a new MATLAB toolbox for fast multivariate kernel regression with the idea of non-uniform FFT (NUFFT), which implemented the algorithm for $M$ gridding points with ${O}\left( N+M\log M \right)$ complexity and accuracy controllability. The bandwidth selection problem utilizes the Fast Monte-Carlo algorithm to estimate the degree of freedom (DF), saving enormous cross-validation time even better when data share the same grid space for multiple regression. Up to now, this is the first toolbox for fast-binning high-dimensional kernel regression. Moreover, the estimation for local polynomial regression, the conditional variance for the heteroscedastic model, and the complex-valued datasets are also implemented in this toolbox. The performance is demonstrated with simulations and an application on the quantitive EEG.

Multiple penalized least squares (MPLS) models are a flexible approach to find adaptive least squares solutions required to be simultaneously sparse and smooth. This is particularly important when addressing real-life inverse problems where there is no ground truth available, such as electrophysiological source imaging. In this work we formalize a modified Newton-Raphson (MNR) algorithm to estimate general MPLS models and propose its extension to perform efficient optimization over the active set of selected features (AMNR). This algorithm can be used to minimize continuously differentiable objective functions with multiple restrictions, including sign constraints. We show that these algorithms provide solutions with acceptable reconstruction in simulated scenarios that do not cope with model assumptions, and for low n/p ratios. We then use both algorithms for estimating different electroencephalography (EEG) inverse models with multiple penalties. We also show how the AMNR allows us to estimate new models in the EEG inverse problem context, such as nonnegative versions of Smooth Garrote and Smooth LASSO. Synthetic data were used for a comparison between solutions obtained using the two algorithms proposed here and the least angle regression (LARS) algorithm, according to well-known quality measures. A visual event-related EEG from healthy young subjects and a resting-state EEG study on the relationship between cognitive ageing and walking speed decline in active elders, were used to illustrate the usefulness of the proposed methods in the analysis of real experimental data.

This paper presents a new toolbox for MEEG source activity and connectivity estimation: Brain Connectivity Variable Resolution Tomographic Analysis version 1.0 (BC-VARETA 1.0). It relies on the third generation of nonlinear methods for the analysis of resting state MEEG Time Series. Into the state of the art of MEEG analysis, the methodology underlying our tool (BC-VARETA) brings out several assets. First: Constitutes a Bayesian Identification approach of Linear Dynamical Systems in the Frequency Domain, grounded in more consistent models (third generation). Second: Achieves Super-Resolution, through the iterative solution of a Sparse Hermitian Source Graphical Model. Third: Tackles efficiently in High Dimensional and Complex set up the estimation of connectivity. Fourth: Incorporates priors at the connectivity level by penalizing the groups of variables, corresponding to the Gray Matter anatomical segmentation, and including a probability mask of the anatomically plausible connections. Along with the implementation of our method, we include in this toolbox a benchmark for the validation of MEEG source analysis methods, that would serve for the evaluation of sophisticated methodologies (third generation). It incorporates two elements. First: A realistic simulation framework, for the generation of MEEG synthetic data, given an underlying source connectivity structure. Second: Sensitive quality measures that allow for a reliable evaluation of the source activity and connectivity reconstruction performance, based on the Spatial Dispersion and Earth Movers Distance, in both source and connectivity space.

Identifying the functional networks underpinning indirectly observed processes poses an inverse problem for neurosciences or other fields. A solution of such inverse problems estimates as a first step the activity emerging within functional networks from EEG or MEG data. These EEG or MEG estimates are a direct reflect functional brain network activity with a temporal resolution that no other in vivo neuroimage may provide. A second step estimating functional connectivity from such activity pseudodata unveil the oscillatory brain networks that strongly correlate with all cognition and behavior. Simulations of such MEG or EEG inverse problem also reveal estimation errors of the functional connectivity determined by any of the state-of-the-art inverse solutions. We disclose a significant cause of estimation errors originating from misspecification of the functional network model incorporated into either inverse solution steps. We introduce the Bayesian identification of a Hidden Gaussian Graphical Spectral (HIGGS) model specifying such oscillatory brain networks model. In human EEG alpha rhythm simulations estimation errors measured as ROC performance do not surpass 2% in our HIGGS inverse solution and reach 20% in state-of-the-art methods. Macaque simultaneous EEG/ECoG recordings provide experimental confirmation for our inverse-solution with 1/3 more congruence according to Riemannian distances than state-of-the-art methods.

Simplistic estimation of neural connectivity in MEEG sensor space is impossible due to volume conduction. The only viable alternative is to carry out connectivity estimation in source space. Among the neuroscience community this is claimed to be impossible or misleading due to Leakage: linear mixing of the reconstructed sources. To address this problematic we propose a novel solution method that caulks the Leakage in MEEG source activity and connectivity estimates: BC-VARETA. It is based on a joint estimation of source activity and connectivity in the frequency domain representation of MEEG time series. To achieve this, we go beyond current methods that assume a fixed gaussian graphical model for source connectivity. In contrast we estimate this graphical model in a Bayesian framework by placing priors on it, which allows for highly optimized computations of the connectivity, via a new procedure based on the local quadratic approximation under quite general prior models. A further contribution of this paper is the rigorous definition of leakage via the Spatial Dispersion Measure and Earth Movers Distance based on the geodesic distances over the cortical manifold. Both measures are extended for the first time to quantify Connectivity Leakage by defining them on the cartesian product of cortical manifolds. Using these measures, we show that BC-VARETA outperforms most state of the art inverse solvers by several orders of magnitude.

Neuroscientists are now able to acquire data at staggering rates across spatiotemporal scales. However, our ability to capitalize on existing datasets, tools, and intellectual capacities is hampered by technical challenges. The key barriers to accelerating scientific discovery correspond to the FAIR data principles: findability, global access to data, software interoperability, and reproducibility/re-usability. We conducted a hackathon dedicated to making strides in those steps. This manuscript is a technical report summarizing these achievements, and we hope serves as an example of the effectiveness of focused, deliberate hackathons towards the advancement of our quickly-evolving field., Comment: 10 pages, 4 figures, hackathon report

Despite the decades of efforts, the choice of EEG reference is still a debated fundamental issue. Non-neutral reference can inevitably inject the uncontrolled temporal biases into all EEG recordings, which may influence the spatiotemporal analysis of brain activity. A method, termed microstates, identifying spatiotemporal EEG features as the quasi-stable topography states in milliseconds, suggests its potential as biomarkers of neurophysiological disease. As reference electrode standardization technique (REST) could reconstruct an infinity reference approximately, it is a question whether REST or the other references will be more reliable than average reference (AR) for the microstates analysis. In this study, we design the microstate-based EEG forward model, and apply different references for microstates analysis. The spatial similarity between the generated and assumed cluster maps is mainly investigated. Furthermore, the real EEG data by the parametric bootstrap method is used to validate the performance of the references. Finally, we find that REST is robust to recover more similar cluster maps to the assumption than AR in the simulation, and the cluster maps between REST and AR on the real EEG data are quite different. This study may indicate that REST contributes to identifying more objective microstates features than AR.

The choice of reference for electroencephalogram (EEG) is a long-lasting unsolved issue resulting in inconsistent usages and endless debates. Currently, both average reference (AR) and reference electrode standardization technique (REST) are two primary, irreconcilable contenders. We propose a theoretical framework to resolve this issue by formulating both a) estimation of potentials at infinity, and, b) determination of the reference, as a unified Bayesian linear inverse problem. We find that AR and REST are very particular cases of this unified framework: AR results from biophysically non-informative prior; while REST utilizes the prior of EEG generative model. We develop the regularized versions of AR and REST, named rAR, and rREST, respectively. Both depend on a regularization parameter that is the noise to signal ratio. Traditional and new estimators are evaluated with this framework, by both simulations and analysis of real EEGs. Generated artificial EEGs, show that relative error in estimating the EEG potentials at infinity is lowest for rREST. It also reveals that realistic volume conductor models improve the performances of REST and rREST. For practical applications, it is shown that average lead field gives the results comparable to the individual lead field. Finally, it is shown that the selection of the regularization parameter with Generalized Cross-Validation (GCV) is close to the 'oracle' choice based on the ground truth. When evaluated with the real 89 resting state EEGs, rREST consistently yields the lowest GCV. This study provides a novel perspective on the EEG reference problem by means of a unified inverse solution framework. It may allow additional principled theoretical formulations and numerical evaluation of performance.

The estimation of EEG generating sources constitutes an Inverse Problem (IP) in Neuroscience. This is an ill-posed problem, due to the non-uniqueness of the solution, and many kinds of prior information have been used to constrain it. A combination of smoothness (L2 norm-based) and sparseness (L1 norm-based) constraints is a flexible approach that have been pursued by important examples such as the Elastic Net (ENET) and mixed-norm (MXN) models. The former is used to find solutions with a small number of smooth non-zero patches, while the latter imposes sparseness and smoothness simultaneously along different dimensions of the spatio-temporal matrix solutions. Both models have been addressed within the penalized regression approach, where the regularization parameters are selected heuristically, leading usually to non-optimal solutions. The existing Bayesian formulation of ENET allows hyperparameter learning, but using computationally intensive Monte Carlo/Expectation Maximization methods. In this work we attempt to solve the EEG IP using a Bayesian framework for models based on mixtures of L1/L2 norms penalization functions (Laplace/Normal priors) such as ENET and MXN. We propose a Sparse Bayesian Learning algorithm based on combining the Empirical Bayes and the iterative coordinate descent procedures to estimate both the parameters and hyperparameters. Using simple but realistic simulations we found that our methods are able to recover complicated source setups more accurately and with a more robust variable selection than the ENET and LASSO solutions using classical algorithms. We also solve the EEG IP using data coming from a visual attention experiment, finding more interpretable neurophysiological patterns with our methods, as compared with other known methods such as LORETA, ENET and LASSO FUSION using the classical regularization approach.

Current high-throughput data acquisition technologies probe dynamical systems with different imaging modalities, generating massive data sets at different spatial and temporal resolutions posing challenging problems in multimodal data fusion. A case in point is the attempt to parse out the brain structures and networks that underpin human cognitive processes by analysis of different neuroimaging modalities (functional MRI, EEG, NIRS etc.). We emphasize that the multimodal, multi-scale nature of neuroimaging data is well reflected by a multi-way (tensor) structure where the underlying processes can be summarized by a relatively small number of components or "atoms". We introduce Markov-Penrose diagrams - an integration of Bayesian DAG and tensor network notation in order to analyze these models. These diagrams not only clarify matrix and tensor EEG and fMRI time/frequency analysis and inverse problems, but also help understand multimodal fusion via Multiway Partial Least Squares and Coupled Matrix-Tensor Factorization. We show here, for the first time, that Granger causal analysis of brain networks is a tensor regression problem, thus allowing the atomic decomposition of brain networks. Analysis of EEG and fMRI recordings shows the potential of the methods and suggests their use in other scientific domains., Comment: 23 pages, 15 figures, submitted to Proceedings of the IEEE

Absence epilepsy is believed to be associated with the abnormal interactions between the cerebral cortex and thalamus. Besides the direct coupling, anatomical evidence indicates that the cerebral cortex and thalamus also communicate indirectly through an important intermediate bridge--basal ganglia. It has been thus postulated that the basal ganglia might play key roles in the modulation of absence seizures, but the relevant biophysical mechanisms are still not completely established. Using a biophysically based model, we demonstrate here that the typical absence seizure activities can be controlled and modulated by the direct GABAergic projections from the substantia nigra pars reticulata (SNr) to either the thalamic reticular nucleus (TRN) or the specific relay nuclei (SRN) of thalamus, through different biophysical mechanisms. Under certain conditions, these two types of seizure control are observed to coexist in the same network. More importantly, due to the competition between the inhibitory SNr-TRN and SNr-SRN pathways, we find that both decreasing and increasing the activation of SNr neurons from the normal level may considerably suppress the generation of SWDs in the coexistence region. Overall, these results highlight the bidirectional functional roles of basal ganglia in controlling and modulating absence seizures, and might provide novel insights into the therapeutic treatments of this brain disorder., Comment: 10 figures and 1 table. This paper has been accepted by PLoS Computational Biology

That physiological oscillations of various frequencies are present in fMRI signals is the rule, not the exception. Herein, we propose a novel theoretical framework, spatio-temporal Granger causality, which allows us to more reliably and precisely estimate the Granger causality from experimental datasets possessing time-varying properties caused by physiological oscillations. Within this framework, Granger causality is redefined as a global index measuring the directed information flow between two time series with time-varying properties. Both theoretical analyses and numerical examples demonstrate that Granger causality is a monotonically increasing function of the temporal resolution used in the estimation. This is consistent with the general principle of coarse graining, which causes information loss by smoothing out very fine-scale details in time and space. Our results confirm that the Granger causality at the finer spatio-temporal scales considerably outperforms the traditional approach in terms of an improved consistency between two resting-state scans of the same subject. To optimally estimate the Granger causality, the proposed theoretical framework is implemented through a combination of several approaches, such as dividing the optimal time window and estimating the parameters at the fine temporal and spatial scales. Taken together, our approach provides a novel and robust framework for estimating the Granger causality from fMRI, EEG, and other related data., Comment: 62 pages, 10 figures

An important field of research in functional neuroimaging is the discovery of integrated, distributed brain systems and networks, whose different regions need to work in unison for normal functioning. The EEG is a non-invasive technique that can provide information for massive connectivity analyses. Cortical signals of time varying electric neuronal activity can be estimated from the EEG. Although such techniques have very high time resolution, two cortical signals even at distant locations will appear to be highly similar due to the low spatial resolution nature of the EEG. In this study a method for eliminating the effect of common sources due to low spatial resolution is presented. It is based on an efficient estimation of the whole-cortex partial coherence matrix. Using as a starting point any linear EEG tomography that satisfies the EEG forward equation, it is shown that the generalized partial coherences for the cortical grey matter current density time series are invariant to the selected tomography. It is empirically shown with simulation experiments that the generalized partial coherences have higher spatial resolution than the classical coherences. The results demonstrate that with as little as 19 electrodes, lag-connected brain regions can often be missed and misplaced even with lagged coherence measures, while the new method detects and localizes correctly the connected regions using the lagged partial coherences.