CiftiStorm pipeline: facilitating reproducible EEG/MEG source connectomics.

We present CiftiStorm, an electrophysiological source imaging (ESI) pipeline incorporating recently developed methods to improve forward and inverse solutions. The CiftiStorm pipeline produces Human Connectome Project (HCP) and megconnectome-compliant outputs from dataset inputs with varying degrees of spatial resolution. The input data can range from low-sensor-density electroencephalogram (EEG) or magnetoencephalogram (MEG) recordings without structural magnetic resonance imaging (sMRI) to high-density EEG/MEG recordings with an HCP multimodal sMRI compliant protocol. CiftiStorm introduces a numerical quality control of the lead field and geometrical corrections to the head and source models for forward modeling. For the inverse modeling, we present a Bayesian estimation of the cross-spectrum of sources based on multiple priors. We facilitate ESI in the T1w/FSAverage32k high-resolution space obtained from individual sMRI. We validate this feature by comparing CiftiStorm outputs for EEG and MRI data from the Cuban Human Brain Mapping Project (CHBMP) acquired with technologies a decade before the HCP MEG and MRI standardized dataset.

Identifying oscillatory brain networks with hidden Gaussian graphical spectral models of MEEG.

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 reflection of 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, the 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 results with 1/3 times larger congruence according to Riemannian distances than state-of-the-art methods.

Automatic quality control of the numerical accuracy of EEG lead fields.

Precise individualized EEG source localization is predicated on having accurate subject-specific Lead Fields (LFs) obtained from their Magnetic Resonance Images (MRI). LF calculation is a complex process involving several error-prone steps that start with obtaining a realistic head model from the MRI and finalizing with computationally expensive solvers such as the Boundary Element Method (BEM) or Finite Element Method (FEM). Current Big-Data applications require the calculation of batches of hundreds or thousands of LFs. LF. Quality Control is conventionally checked subjectively by experts, a procedure not feasible in practice for larger batches. To facilitate this step, we introduce the Lead Field Automatic-Quality Control Index (LF-AQI) that flags LF with potential errors. We base our LF-AQI on the assumption that LFs obtained from simpler head models, i.e., the homogeneous head model LF (HHM-LF) or spherical head model LF (SHM-LF), deviate only moderately from a "good" realistic test LF. Since these simpler LFs are easier to compute and check for errors, they may serve as "reference LF" to detect anomalous realistic test LF. We investigated this assumption by comparing correlation-based channel ρmin(ref,test)and source τmin(ref,test) similarity indices (SI) between "gold standards," i.e., very accurate FEM and BEM LFs, and the proposed references (HHM-LF and SHM-LF). Surprisingly we found that the most uncomplicated possible reference, HHM-LF had high SI values with the gold standards-leading us to explore further use of the channel ρmin(HHM-LF,test)and source τmin(HHM-LF,test)SI as a basis for our LF-AQI. Indeed, these SI successfully detected five simulated scenarios of LFs artifacts. This result encouraged us to evaluate the SI on a large dataset and thus define our LF-AQI. We thus computed the SI of 1251 LFs obtained from the Child Mind Institute (CMI) MRI dataset. When ρmin(HHM-LF,test)and source τmin(HHM-LF,test) were plotted for all test subjects on a 2D space, most were tightly clustered around the median of a high similarity centroid (HSC), except for a smaller proportion of outliers. We define the LF-AQI for a given LF as the log Euclidean distance between its SI and the HSC median. To automatically detect outliers, the threshold is at the 90th percentile of the CMI LF-AQIs (-0.9755). LF-AQI greater than this threshold flag individual LF to be checked. The robustness of this LF-AQI screening was checked by repeated out-of-sample validation. Strikingly, minor corrections in re-processing the flagged cases eliminated their status as outliers. Furthermore, the "doubtful" labels assigned by LF-AQI were validated by neuroscience students using a Likert scale questionnaire designed to manually check the LF's quality. Item Response Theory (IRT) analysis was applied to the questionnaire results to compute an optimized model and a latent variable θ for that model. A linear mixed model (LMM) between the θ and LF-AQI resulted in an effect with a Cohen's d value of 1.3 and a p-value <0.001, thus validating the correspondence of LF-AQI with the visual quality control. We provide an open-source pipeline to implement both LF calculation and its quality control to allow further evaluation of our index.

Minimizing the distortions in electrophysiological source imaging of cortical oscillatory activity via Spectral Structured Sparse Bayesian Learning.

Oscillatory processes at all spatial scales and on all frequencies underpin brain function. Electrophysiological Source Imaging (ESI) is the data-driven brain imaging modality that provides the inverse solutions to the source processes of the EEG, MEG, or ECoG data. This study aimed to carry out an ESI of the source cross-spectrum while controlling common distortions of the estimates. As with all ESI-related problems under realistic settings, the main obstacle we faced is a severely ill-conditioned and high-dimensional inverse problem. Therefore, we opted for Bayesian inverse solutions that posited a priori probabilities on the source process. Indeed, rigorously specifying both the likelihoods and a priori probabilities of the problem leads to the proper Bayesian inverse problem of cross-spectral matrices. These inverse solutions are our formal definition for cross-spectral ESI (cESI), which requires a priori of the source cross-spectrum to counter the severe ill-condition and high-dimensionality of matrices. However, inverse solutions for this problem were NP-hard to tackle or approximated within iterations with bad-conditioned matrices in the standard ESI setup. We introduce cESI with a joint a priori probability upon the source cross-spectrum to avoid these problems. cESI inverse solutions are low-dimensional ones for the set of random vector instances and not random matrices. We achieved cESI inverse solutions through the variational approximations via our Spectral Structured Sparse Bayesian Learning (ssSBL) algorithm https://github.com/CCC-members/Spectral-Structured-Sparse-Bayesian-Learning. We compared low-density EEG (10-20 system) ssSBL inverse solutions with reference cESIs for two experiments: (a) high-density MEG that were used to simulate EEG and (b) high-density macaque ECoG that were recorded simultaneously with EEG. The ssSBL resulted in two orders of magnitude with less distortion than the state-of-the-art ESI methods. Our cESI toolbox, including the ssSBL method, is available at https://github.com/CCC-members/BC-VARETA_Toolbox.

Who's driving? The default mode network in healthy elderly individuals at risk of cognitive decline.

Introduction: Age is the main risk factor for the development of neurocognitive disorders, with Alzheimer's disease being the most common. Its physiopathological features may develop decades before the onset of clinical symptoms. Quantitative electroencephalography (qEEG) is a promising and cost-effective tool for the prediction of cognitive decline in healthy older individuals that exhibit an excess of theta activity. The aim of the present study was to evaluate the feasibility of brain connectivity variable resolution electromagnetic tomography (BC-VARETA), a novel source localization algorithm, as a potential tool to assess brain connectivity with 19-channel recordings, which are common in clinical practice. Methods: We explored differences in terms of functional connectivity among the nodes of the default mode network between two groups of healthy older participants, one of which exhibited an EEG marker of risk for cognitive decline. Results: The risk group exhibited increased levels of delta, theta, and beta functional connectivity among nodes of the default mode network, as well as reversed directionality patterns of connectivity among nodes in every frequency band when compared to the control group. Discussion: We propose that an ongoing pathological process may be underway in healthy elderly individuals with excess theta activity in their EEGs, which is further evidenced by changes in their connectivity patterns. BC-VARETA implemented on 19-channels EEG recordings appears to be a promising tool to detect dysfunctions at the connectivity level in clinical settings.

Harmonized-Multinational qEEG norms (HarMNqEEG).

This paper extends frequency domain quantitative electroencephalography (qEEG) methods pursuing higher sensitivity to detect Brain Developmental Disorders. Prior qEEG work lacked integration of cross-spectral information omitting important functional connectivity descriptors. Lack of geographical diversity precluded accounting for site-specific variance, increasing qEEG nuisance variance. We ameliorate these weaknesses. (i) Create lifespan Riemannian multinational qEEG norms for cross-spectral tensors. These norms result from the HarMNqEEG project fostered by the Global Brain Consortium. We calculate the norms with data from 9 countries, 12 devices, and 14 studies, including 1564 subjects. Instead of raw data, only anonymized metadata and EEG cross-spectral tensors were shared. After visual and automatic quality control, developmental equations for the mean and standard deviation of qEEG traditional and Riemannian DPs were calculated using additive mixed-effects models. We demonstrate qEEG "batch effects" and provide methods to calculate harmonized z-scores. (ii) We also show that harmonized Riemannian norms produce z-scores with increased diagnostic accuracy predicting brain dysfunction produced by malnutrition in the first year of life and detecting COVID induced brain dysfunction. (iii) We offer open code and data to calculate different individual z-scores from the HarMNqEEG dataset. These results contribute to developing bias-free, low-cost neuroimaging technologies applicable in various health settings.

An Age-Adjusted EEG Source Classifier Accurately Detects School-Aged Barbadian Children That Had Protein Energy Malnutrition in the First Year of Life.

We have identified an electroencephalographic (EEG) based statistical classifier that correctly distinguishes children with histories of Protein Energy Malnutrition (PEM) in the first year of life from healthy controls with 0.82% accuracy (area under the ROC curve). Our previous study achieved similar accuracy but was based on scalp quantitative EEG features that precluded anatomical interpretation. We have now employed BC-VARETA, a novel high-resolution EEG source imaging method with minimal leakage and maximal sparseness, which allowed us to identify a classifier in the source space. The EEGs were recorded in 1978 in a sample of 108 children who were 5-11 years old and were participants in the 45+ year longitudinal Barbados Nutrition Study. The PEM cohort experienced moderate-severe PEM limited to the first year of life and were age, handedness and gender-matched with healthy classmates who served as controls. In the current study, we utilized a machine learning approach based on the elastic net to create a stable sparse classifier. Interestingly, the classifier was driven predominantly by nutrition group differences in alpha activity in the lingual gyrus. This structure is part of the pathway associated with generating alpha rhythms that increase with normal maturation. Our findings indicate that the PEM group showed a significant decrease in alpha activity, suggestive of a delay in brain development. Childhood malnutrition is still a serious worldwide public health problem and its consequences are particularly severe when present during early life. Deficits during this critical period are permanent and predict impaired cognitive and behavioral functioning later in life. Our EEG source classifier may provide a functionally interpretable diagnostic technology to study the effects of early childhood malnutrition on the brain, and may have far-reaching applicability in low resource settings.

EECoG-Comp: An Open Source Platform for Concurrent EEG/ECoG Comparisons-Applications to Connectivity Studies.

Electrophysiological Source Imaging (ESI) is hampered by lack of "gold standards" for model validation. Concurrent electroencephalography (EEG) and electrocorticography (ECoG) experiments (EECoG) are useful for this purpose, especially primate models due to their flexibility and translational value for human research. Unfortunately, there is only one EECoG experiments in the public domain that we know of: the Multidimensional Recording (MDR) is based on a single monkey ( www.neurotycho.org ). The mining of this type of data is hindered by lack of specialized procedures to deal with: (1) Severe EECoG artifacts due to the experimental produces; (2) Sophisticated forward models that account for surgery induced skull defects and implanted ECoG electrode strips; (3) Reliable statistical procedures to estimate and compare source connectivity (partial correlation). We provide solutions to the processing issues just mentioned with EECoG-Comp: an open source platform ( https://github.com/Vincent-wq/EECoG-Comp ). EECoG lead fields calculated with FEM (Simbio) for MDR data are also provided and were used in other papers of this special issue. As a use case with the MDR, we show: (1) For real MDR data, 4 popular ESI methods (MNE, LCMV, eLORETA and SSBL) showed significant but moderate concordance with a usual standard, the ECoG Laplacian (standard partial [Formula: see text]); (2) In both monkey and human simulations, all ESI methods as well as Laplacian had a significant but poor correspondence with the true source connectivity. These preliminary results may stimulate the development of improved ESI connectivity estimators but require the availability of more EECoG data sets to obtain neurobiologically valid inferences.

Spatio Temporal EEG Source Imaging with the Hierarchical Bayesian Elastic Net and Elitist Lasso Models.

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 regularization or prior information is needed to undertake Electrophysiology Source Imaging. Structured Sparsity priors can be attained through combinations of (L1 norm-based) and (L2 norm-based) constraints such as the Elastic Net (ENET) and Elitist Lasso (ELASSO) models. The former model is used to find solutions with a small number of smooth nonzero patches, while the latter imposes different degrees of sparsity 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 and computationally expensive solutions. The existing Bayesian formulation of ENET allows hyperparameter learning, but using the computationally intensive Monte Carlo/Expectation Maximization methods, which makes impractical its application to the EEG IP. While the ELASSO have not been considered before into the Bayesian context. In this work, we attempt to solve the EEG IP using a Bayesian framework for ENET and ELASSO models. We propose a Structured Sparse Bayesian Learning algorithm based on combining the Empirical Bayes and the iterative coordinate descent procedures to estimate both the parameters and hyperparameters. Using realistic simulations and avoiding the inverse crime we illustrate that our methods are able to recover complicated source setups more accurately and with a more robust estimation of the hyperparameters and behavior under different sparsity scenarios than classical LORETA, ENET and LASSO Fusion solutions. We also solve the EEG IP using data from a visual attention experiment, finding more interpretable neurophysiological patterns with our methods. The Matlab codes used in this work, including Simulations, Methods, Quality Measures and Visualization Routines are freely available in a public website.