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Background: Structural income inequality - the uneven income distribution across regions or countries - could affect brain structure and function, beyond individual differences. However, the impact of structural income inequality on the brain dynamics and the roles of demographics and cognition in these associations remains unexplored., Methods: Here, we assessed the impact of structural income inequality, as measured by the Gini coefficient on multiple EEG metrics, while considering the subject-level effects of demographic (age, sex, education) and cognitive factors. Resting-state EEG signals were collected from a diverse sample (countries = 10; healthy individuals = 1394 from Argentina, Brazil, Colombia, Chile, Cuba, Greece, Ireland, Italy, Turkey and United Kingdom). Complexity (fractal dimension, permutation entropy, Wiener entropy, spectral structure variability), power spectral and aperiodic components (1/f slope, knee, offset), as well as graph-theoretic measures were analysed., Findings: Despite variability in samples, data collection methods, and EEG acquisition parameters, structural inequality systematically predicted electrophysiological brain dynamics, proving to be a more crucial determinant of brain dynamics than individual-level factors. Complexity and aperiodic activity metrics captured better the effects of structural inequality on brain function. Following inequality, age and cognition emerged as the most influential predictors. The overall results provided convergent multimodal metrics of biologic embedding of structural income inequality characterised by less complex signals, increased random asynchronous neural activity, and reduced alpha and beta power, particularly over temporoposterior regions., Conclusion: These findings might challenge conventional neuroscience approaches that tend to overemphasise the influence of individual-level factors, while neglecting structural factors. Results pave the way for neuroscience-informed public policies aimed at tackling structural inequalities in diverse populations., (© 2024 The Author(s). Clinical and Translational Medicine published by John Wiley & Sons Australia, Ltd on behalf of Shanghai Institute of Clinical Bioinformatics.)

Diversity in brain health is influenced by individual differences in demographics and cognition. However, most studies on brain health and diseases have typically controlled for these factors rather than explored their potential to predict brain signals. Here, we assessed the role of individual differences in demographics (age, sex, and education; n = 1298) and cognition (n = 725) as predictors of different metrics usually used in case-control studies. These included power spectrum and aperiodic (1/f slope, knee, offset) metrics, as well as complexity (fractal dimension estimation, permutation entropy, Wiener entropy, spectral structure variability) and connectivity (graph-theoretic mutual information, conditional mutual information, organizational information) from the source space resting-state EEG activity in a diverse sample from the global south and north populations. Brain-phenotype models were computed using EEG metrics reflecting local activity (power spectrum and aperiodic components) and brain dynamics and interactions (complexity and graph-theoretic measures). Electrophysiological brain dynamics were modulated by individual differences despite the varied methods of data acquisition and assessments across multiple centers, indicating that results were unlikely to be accounted for by methodological discrepancies. Variations in brain signals were mainly influenced by age and cognition, while education and sex exhibited less importance. Power spectrum activity and graph-theoretic measures were the most sensitive in capturing individual differences. Older age, poorer cognition, and being male were associated with reduced alpha power, whereas older age and less education were associated with reduced network integration and segregation. Findings suggest that basic individual differences impact core metrics of brain function that are used in standard case-control studies. Considering individual variability and diversity in global settings would contribute to a more tailored understanding of brain function., Competing Interests: Declaration of competing interest none., (Copyright © 2024 The Author(s). Published by Elsevier Inc. All rights reserved.)

Mediation analysis assesses whether an exposure directly produces changes in cognitive behavior or is influenced by intermediate "mediators". Electroencephalographic (EEG) spectral measurements have been previously used as effective mediators representing diverse aspects of brain function. However, it has been necessary to collapse EEG measures onto a single scalar using standard mediation methods. In this article, we overcome this limitation and examine EEG frequency-resolved functional connectivity measures as a mediator using the full EEG cross-spectral tensor (CST). Since CST samples do not exist in Euclidean space but in the Riemannian manifold of positive-definite tensors, we transform the problem, allowing for the use of classic multivariate statistics. Toward this end, we map the data from the original manifold space to the Euclidean tangent space, eliminating redundant information to conform to a "compressed CST." The resulting object is a matrix with rows corresponding to frequencies and columns to cross spectra between channels. We have developed a novel matrix mediation approach that leverages a nuclear norm regularization to determine the matrix-valued regression parameters. Furthermore, we introduced a global test for the overall CST mediation and a test to determine specific channels and frequencies driving the mediation. We validated the method through simulations and applied it to our well-studied 50+-year Barbados Nutrition Study dataset by comparing EEGs collected in school-age children (5-11 years) who were malnourished in the first year of life with those of healthy classmate controls. We hypothesized that the CST mediates the effect of malnutrition on cognitive performance. We can now explicitly pinpoint the frequencies (delta, theta, alpha, and beta bands) and regions (frontal, central, and occipital) in which functional connectivity was altered in previously malnourished children, an improvement to prior studies. Understanding the specific networks impacted by a history of postnatal malnutrition could pave the way for developing more targeted and personalized therapeutic interventions. Our methods offer a versatile framework applicable to mediation studies encompassing matrix and Hermitian 3D tensor mediators alongside scalar exposures and outcomes, facilitating comprehensive analyses across diverse research domains., (© 2024 The Authors. Human Brain Mapping published by Wiley Periodicals LLC.)

The power spectra estimated from the brain recordings are the mixed representation of aperiodic transient activity and periodic oscillations, i.e., aperiodic component (AC) and periodic component (PC). Quantitative neurophysiology requires precise decomposition preceding parameterizing each component. However, the shape, statistical distribution, scale, and mixing mechanism of AC and PCs are unclear, challenging the effectiveness of current popular parametric models such as FOOOF, IRASA, BOSC, etc. Here, ξ- π was proposed to decompose the neural spectra by embedding the nonparametric spectra estimation with penalized Whittle likelihood and the shape language modeling into the expectation maximization framework. ξ- π was validated on the synthesized spectra with loss statistics and on the sleep EEG and the large sample iEEG with evaluation metrics and neurophysiological evidence. Compared to FOOOF, both the simulation presenting shape irregularities and the batch simulation with multiple isolated peaks indicated that ξ- π improved the fit of AC and PCs with less loss and higher F1-score in recognizing the centering frequencies and the number of peaks; the sleep EEG revealed that ξ- π produced more distinguishable AC exponents and improved the sleep state classification accuracy; the iEEG showed that ξ- π approached the clinical findings in peak discovery. Overall, ξ- π offered good performance in the spectra decomposition, which allows flexible parameterization using descriptive statistics or kernel functions. ξ- π is a seminal tool for brain signal decoding in fields such as cognitive neuroscience, brain-computer interface, neurofeedback, and brain diseases.

This paper introduces methods and a novel toolbox that efficiently integrates high-dimensional Neural Mass Models (NMMs) specified by two essential components. The first is the set of nonlinear Random Differential Equations (RDEs) of the dynamics of each neural mass. The second is the highly sparse three-dimensional Connectome Tensor (CT) that encodes the strength of the connections and the delays of information transfer along the axons of each connection. To date, simplistic assumptions prevail about delays in the CT, often assumed to be Dirac-delta functions. In reality, delays are distributed due to heterogeneous conduction velocities of the axons connecting neural masses. These distributed-delay CTs are challenging to model. Our approach implements these models by leveraging several innovations. Semi-analytical integration of RDEs is done with the Local Linearization (LL) scheme for each neural mass, ensuring dynamical fidelity to the original continuous-time nonlinear dynamic. This semi-analytic LL integration is highly computationally-efficient. In addition, a tensor representation of the CT facilitates parallel computation. It also seamlessly allows modeling distributed delays CT with any level of complexity or realism. This ease of implementation includes models with distributed-delay CTs. Consequently, our algorithm scales linearly with the number of neural masses and the number of equations they are represented with, contrasting with more traditional methods that scale quadratically at best. To illustrate the toolbox's usefulness, we simulate a single Zetterberg-Jansen and Rit (ZJR) cortical column, a single thalmo-cortical unit, and a toy example comprising 1000 interconnected ZJR columns. These simulations demonstrate the consequences of modifying the CT, especially by introducing distributed delays. The examples illustrate the complexity of explaining EEG oscillations, e.g., split alpha peaks, since they only appear for distinct neural masses. We provide an open-source Script for the toolbox., Competing Interests: Declaration of Competing Interest The authors declare that they have no competing interests., (Copyright © 2023 The Author(s). Published by Elsevier Inc. All rights reserved.)

Objective: Multivariate signal (MS) analysis, especially the assessment of its information transmission (for example, from the perspective of network science), is the key to our understanding of various phenomena in biology, physics and economics. Although there is a large amount of literature demonstrating that MS can be decomposed into space-time-frequency domain information, there seems to be no research confirming that multivariate information transmission (MIT) in these three domains can be quantified. Therefore, in this study, we attempted to combine dynamic mode decomposition (DMD) and parallel communication model (PCM) together to realize it., Methods: We first regarded MS as a large-scale system and then used DMD to decompose it into specific subsystems with their own intrinsic oscillatory frequencies. At the same time, the transition probability matrix (TPM) of information transmission within and between MS at two consecutive moments in each subsystem can also be calculated. Then, communication parameters (CPs) derived from each TPM were calculated in order to quantify the MIT in the space-time-frequency domain. In this study, multidimensional electroencephalogram (EEG) signals were used to illustrate our method., Results: Compared with traditional EEG brain networks, this method shows greater potential in EEG analysis to distinguish between patients and healthy controls., Conclusion: This study demonstrates the feasibility of measuring MIT in the space-time-frequency domain simultaneously., Significance: This study shows that MIT analysis in the space-time-frequency domain is not only completely different from the MS decomposition in these three domains, but also can reveal many new phenomena behind MS that have not yet been discovered.

The current evolution of 'cloud neuroscience' leads to more efforts with the large-scale EEG applications, by using EEG pipelines to handle the rapidly accumulating EEG data. However, there are a few specific cloud platforms that seek to address the cloud computational challenges of EEG big data analysis to benefit the EEG community. In response to the challenges, a WeBrain cloud platform (https://webrain.uestc.edu.cn/) is designed as a web-based brainformatics platform and computational ecosystem to enable large-scale EEG data storage, exploration and analysis using cloud high-performance computing (HPC) facilities. WeBrain connects researchers from different fields to EEG and multimodal tools that have become the norm in the field and the cloud processing power required to handle those large EEG datasets. This platform provides an easy-to-use system for novice users (even no computer programming skills) and provides satisfactory maintainability, sustainability and flexibility for IT administrators and tool developers. A range of resources are also available on https://webrain.uestc.edu.cn/, including documents, manuals, example datasets related to WeBrain, and collected links to open EEG datasets and tools. It is not necessary for users or administrators to install any software or system, and all that is needed is a modern web browser, which reduces the technical expertise required to use or manage WeBrain. The WeBrain platform is sponsored and driven by the China-Canada-Cuba international brain cooperation project (CCC-Axis, http://ccc-axis.org/), and we hope that WeBrain will be a promising cloud brainformatics platform for exploring brain information in large-scale EEG applications in the EEG community., Competing Interests: Declaration of Competing Interest All authors have no conflict of interest to disclose., (Copyright © 2021. Published by Elsevier Inc.)

The Cuban Human Brain Mapping Project (CHBMP) repository is an open multimodal neuroimaging and cognitive dataset from 282 young and middle age healthy participants (31.9 ± 9.3 years, age range 18-68 years). This dataset was acquired from 2004 to 2008 as a subset of a larger stratified random sample of 2,019 participants from La Lisa municipality in La Habana, Cuba. The exclusion criteria included the presence of disease or brain dysfunctions. Participant data that is being shared comprises i) high-density (64-120 channels) resting-state electroencephalograms (EEG), ii) magnetic resonance images (MRI), iii) psychological tests (MMSE, WAIS-III, computerized go-no go reaction time), as well as iv,) demographic information (age, gender, education, ethnicity, handedness, and weight). The EEG data contains recordings with at least 30 minutes in duration including the following conditions: eyes closed, eyes open, hyperventilation, and subsequent recovery. The MRI consists of anatomical T1 as well as diffusion-weighted (DWI) images acquired on a 1.5 Tesla system. The dataset presented here is hosted by Synapse.org and available at https://chbmp-open.loris.ca .

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

In this brief communication, which complements the EEG reference review (Yao et al. in Brain Topogr, 2019), we provide the mathematical derivations that show: (1) any EEG reference admits the general form of a linear transformation of the ideal multichannel EEG potentials with reference to infinity; (2) the average reference (AR), the reference electrode standardization technique (REST), and its regularized version (rREST) are solving the linear inverse problems that can be derived from both the maximum likelihood estimate (MLE) and the Bayesian theory; however, REST is based on more informative prior/constraint of volume conduction than that of AR; (3) we show for the first time that REST is also a unipolar reference (UR), allowing us to define a general family of URs with unified notations; (4) some notable properties of URs are 'no memory', 'rank deficient by 1', and 'orthogonal projector centering'; (5) we also point out here, for the first time, that rREST provides the optimal interpolating function that can be used when the reference channel is missing or the 'bad' channels are rejected. The derivations and properties imply that: (a) any two URs can transform to each other and referencing with URs multiple times will not accumulate artifacts; (b) whatever URs the EEG data was previously transformed with, the minimum norm solution to the reference problem will be REST and AR with and without modeling volume conduction, respectively; (c) the MLE and the Bayesian theory show the theoretical optimality of REST. The advantages and limitations of AR and REST are discussed to guide readers for their proper use.

Many different analysis techniques have been developed and applied to EEG recordings that allow one to investigate how different brain areas interact. One particular class of methods, based on the linear parametric representation of multiple interacting time series, is widely used to study causal connectivity in the brain. However, the results obtained by these methods should be interpreted with great care. The goal of this paper is to show, both theoretically and using simulations, that results obtained by applying causal connectivity measures on the sensor (scalp) time series do not allow interpretation in terms of interacting brain sources. This is because (1) the channel locations cannot be seen as an approximation of a source's anatomical location and (2) spurious connectivity can occur between sensors. Although many measures of causal connectivity derived from EEG sensor time series are affected by the latter, here we will focus on the well-known time domain index of Granger causality (GC) and on the frequency domain directed transfer function (DTF). Using the state-space framework and designing two simulation studies we show that mixing effects caused by volume conduction can lead to spurious connections, detected either by time domain GC or by DTF. Therefore, GC/DTF causal connectivity measures should be computed at the source level, or derived within analysis frameworks that model the effects of volume conduction. Since mixing effects can also occur in the source space, it is advised to combine source space analysis with connectivity measures that are robust to mixing.

Simultaneous electroencephalography (EEG) and functional magnetic resonance imaging (fMRI) have been pursued in an effort to integrate complementary noninvasive information on brain activity. The primary goal involves better information discovery of the event-related neural activations at a spatial region of the BOLD fluctuation with the temporal resolution of the electrical signal. Many techniques and algorithms have been developed to integrate EEGs and fMRIs; however, the relative reliability of the integrated information is unclear. In this work, we propose a hierarchical framework to ensure the relative reliability of the integrated results and attempt to understand brain activation using this hierarchical ideal. First, spatial Independent Component Analysis (ICA) of fMRI and temporal ICA of EEG were performed to extract features at the trial level. Second, the maximal information coefficient (MIC) was adopted to temporally match them across the modalities for both linear and non-linear associations. Third, fMRI-constrained EEG source imaging was utilized to spatially match components across modalities. The simultaneously occurring events in the above two match steps provided EEG-fMRI spatial-temporal reliable integrated information, resulting in the most reliable components with high spatial and temporal resolution information. The other components discovered in the second or third steps provided second-level complementary information for flexible and cautious explanations. This paper contains two simulations and an example of real data, and the results indicate that the framework is a feasible approach to reveal cognitive processing in the human brain., (Copyright © 2014 Elsevier Inc. All rights reserved.)

Discriminating psychogenic nonepileptic seizures (PNES) from epilepsy is challenging, and a reliable and automatic classification remains elusive. In this study, we develop an approach for discriminating between PNES and epilepsy using the common spatial pattern extracted from the brain network topology (SPN). The study reveals that 92% accuracy, 100% sensitivity, and 80% specificity were reached for the classification between PNES and focal epilepsy. The newly developed SPN of resting EEG may be a promising tool to mine implicit information that can be used to differentiate PNES from epilepsy.

Simultaneous electroencephalography (EEG) and functional magnetic resonance imaging (fMRI) provide complementary noninvasive information of brain activity, and EEG/fMRI fusion can achieve higher spatiotemporal resolution than each modality separately. This focuses on independent component analysis (ICA)-based EEG/fMRI fusion. In order to appreciate the issues, we first describe the potential and limitations of the developed fusion approaches: fMRI-constrained EEG imaging, EEG-informed fMRI analysis, and symmetric fusion. We then outline some newly developed hybrid fusion techniques using ICA and the combination of data-/model-driven methods, with special mention of the spatiotemporal EEG/fMRI fusion (STEFF). Finally, we discuss the current trend in methodological development and the existing limitations for extrapolating neural dynamics.

This article reviews the contributions of the Cuban Neuroscience Center to the evolution of the statistical parametric mapping (SPM) of quantitative Multimodal Neuroimages (qMN), from its inception to more recent work. Attention is limited to methods that compare individual qMN to normative databases (n/qMN). This evolution is described in three successive stages: (a) the development of one variant of normative topographical quantitative EEG (n/qEEG-top) which carries out statistical comparison of individual EEG spectral topographies with regard to a normative database--as part of the now popular SPM of brain descriptive parameters; (b) the development of n/qEEG tomography (n/qEEG-TOM), which employs brain electrical tomography (BET) to calculate voxelwise SPM maps of source spectral features with respect to a norm; (c) the development of a more general n/qMN by substituting EEG parameters with other neuroimaging descriptive parameters to obtain SPM maps. The study also describes the creation of Cuban normative databases, starting with the Cuban EEG database obtained in the early 90s, and more recently, the Cuban Human Brain Mapping Project (CHBMP). This project has created a 240 subject database of the normal Cuban population, obtained from a population-based random sample, comprising clinical, neuropsychological, EEG, MRI and SPECT data for the same subjects. Examples of clinical studies using qMN are given and, more importantly, receiver operator characteristics (ROC) analyses of the different developments document a sustained effort to assess the clinical usefulness of the techniques.

This article reviews progress and challenges in model driven EEG/fMRI fusion with a focus on brain oscillations. Fusion is the combination of both imaging modalities based on a cascade of forward models from ensemble of post-synaptic potentials (ePSP) to net primary current densities (nPCD) to EEG; and from ePSP to vasomotor feed forward signal (VFFSS) to BOLD. In absence of a model, data driven fusion creates maps of correlations between EEG and BOLD or between estimates of nPCD and VFFS. A consistent finding has been that of positive correlations between EEG alpha power and BOLD in both frontal cortices and thalamus and of negative ones for the occipital region. For model driven fusion we formulate a neural mass EEG/fMRI model coupled to a metabolic hemodynamic model. For exploratory simulations we show that the Local Linearization (LL) method for integrating stochastic differential equations is appropriate for highly nonlinear dynamics. It has been successfully applied to small and medium sized networks, reproducing the described EEG/BOLD correlations. A new LL-algebraic method allows simulations with hundreds of thousands of neural populations, with connectivities and conduction delays estimated from diffusion weighted MRI. For parameter and state estimation, Kalman filtering combined with the LL method estimates the innovations or prediction errors. From these the likelihood of models given data are obtained. The LL-innovation estimation method has been already applied to small and medium scale models. With improved Bayesian computations the practical estimation of very large scale EEG/fMRI models shall soon be possible., (2008 Wiley-Liss, Inc.)

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. [ABSTRACT FROM AUTHOR]

Objective: This study compares the complementary information from semiquantitative EEG (sqEEG) and spectral quantitative EEG (spectral-qEEG) to detect the life-long effects of early childhood malnutrition on the brain. Methods: Resting-state EEGs (N = 202) from the Barbados Nutrition Study (BNS) were used to examine the effects of protein-energy malnutrition (PEM) on childhood and middle adulthood outcomes. sqEEG analysis was performed on Grand Total EEG (GTE) protocol, and a single latent variable, the semi-quantitative Neurophysiological State (sqNPS) was extracted. A univariate linear mixed-effects (LME) model tested the dependence of sqNPS and nutritional group. sqEEG was compared with scores on the Montreal Cognitive Assessment (MoCA). Stable sparse classifiers (SSC) also measured the predictive power of sqEEG, spectral-qEEG, and a combination of both. Multivariate LME was applied to assess each EEG modality separately and combined under longitudinal settings. Results: The univariate LME showed highly significant differences between previously malnourished and control groups (p < 0.001); age (p = 0.01) was also significant, with no interaction between group and age detected. Childhood sqNPS (p = 0.02) and adulthood sqNPS (p = 0.003) predicted MoCA scores in adulthood. The SSC demonstrated that spectral-qEEG combined with sqEEG had the highest predictive power (mean AUC 0.92 ± 0.005). Finally, multivariate LME showed that the combined spectral-qEEG+sqEEG models had the highest log-likelihood (-479.7). Conclusion: This research has extended our prior work with spectral-qEEG and the long-term impact of early childhood malnutrition on the brain. Our findings showed that sqNPS was significantly linked to accelerated cognitive aging at 45-51 years of age. While sqNPS and spectral-qEEG produced comparable results, our study indicated that combining sqNPS and spectral-qEEG yielded better performance than either method alone, suggesting that a multimodal approach could be advantageous for future investigations. Significance: Based on our findings, a semi-quantitative approach utilizing GTE could be a valuable diagnostic tool for detecting the lasting impacts of childhood malnutrition. Notably, sqEEG has not been previously explored or reported as a biomarker for assessing the longitudinal effects of malnutrition. Furthermore, our observations suggest that sqEEG offers unique features and information not captured by spectral quantitative EEG analysis and could lead to its improvement. [ABSTRACT FROM AUTHOR]

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. [ABSTRACT FROM AUTHOR]

We report on the quantitative electroencephalogram (qEEG) and cognitive effects of Neuroepo in Parkinson’s disease (PD) from a double-blind safety trial (https://clinicaltrials.gov/, number NCT04110678). Neuroepo is a new erythropoietin (EPO) formulation with a low sialic acid content with satisfactory results in animal models and tolerance in healthy participants and PD patients. In this study, 26 PD patients were assigned randomly to Neuroepo (n = 15) or placebo (n = 11) groups to test the tolerance of the drug. Outcome variables were neuropsychological tests and resting-state source qEEG at baseline and 6 months after administering the drug. Probabilistic Canonical Correlation Analysis was used to extract latent variables for the cognitive and for qEEG variables that shared a common source of variance. We obtained canonical variates for Cognition and qEEG with a correlation of 0.97. Linear Mixed Model analysis showed significant positive dependence of the canonical variate cognition on the dose and the confounder educational level (p = 0.003 and p = 0.02, respectively). Additionally, in the mediation equation, we found a positive dependence of Cognition with qEEG for (p = < 0.0001) and with dose (p = 0.006). Despite the small sample, both tests were powered over 89%. A combined mediation model showed that 66% of the total effect of the cognitive improvement was mediated by qEEG (p = 0.0001), with the remaining direct effect between dose and Cognition (p = 0.002), due to other causes. These results suggest that Neuroepo has a positive influence on Cognition in PD patients and that a large portion of this effect is mediated by brain mechanisms reflected in qEEG. [ABSTRACT FROM AUTHOR]

The reconstruction of electrophysiological sources within the brain is sensitive to the constructed head model, which depends on the positioning accuracy of anatomical landmarks known as fiducials. In this work, we propose an algorithm for the automatic detection of fiducial landmarks of EEG electrodes on the 3D human head model. Our proposal combines a dimensional reduction approach with a perspective projection from 3D to 2D object space; the eye and ear automatic detection in a 2D face image by two cascades of classifiers and geometric transformations to obtain 3D spatial coordinates of the landmarks and to generate the head coordinate system, This is accomplished by considering the characteristics of the scanner information. Capturing the 3D model of the head is done with Occipital Inc. ST01 structure sensor and the implementation of our algorithm was carried out on MATLAB R2018b using the Computer Vision Toolbox and the FieldTrip Toolbox. The experimental results were aimed at recursively exploring the efficacy of the facial feature detectors as a function of the projection angle; they show that robust results are obtained in terms of false acceptance rate. Our proposal is an initial step of an approach for the automatic digitization of electrode locations. The experimental results demonstrate that the proposed method detects anatomical facial landmarks automatically, accurately, and rapidly. [ABSTRACT FROM AUTHOR]

Keywords: EEG normative databases; EEG quantitative analysis; EEG maturation; EEG cross-spectra; EEG resting state EN EEG normative databases EEG quantitative analysis EEG maturation EEG cross-spectra EEG resting state N.PAG N.PAG 7 12/05/20 20201201 NES 201201 Introduction Data sharing is one of the principal premises of open science. This data set may be used to study the normal development of second order frequency domain properties of the EEG with new methods like: Evaluation of preprocessing methods such as improved EEG references as in Hu et al. ([14]). EEG normative databases, EEG quantitative analysis, EEG maturation, EEG cross-spectra, EEG resting state. [Extracted from the article]

The Tomographic Quantitative Electroencephalography (qEEGt) toolbox is integrated with the Montreal Neurological Institute (MNI) Neuroinformatics Ecosystem as a docker into the Canadian Brain Imaging Research Platform (CBRAIN). qEEGt produces age-corrected normative Statistical Parametric Maps of EEG log source spectra testing compliance to a normative database. This toolbox was developed at the Cuban Neuroscience Center as part of the first wave of the Cuban Human Brain Mapping Project (CHBMP) and has been validated and used in different health systems for several decades. Incorporation into the MNI ecosystem now provides CBRAIN registered users access to its full functionality and is accompanied by a public release of the source code on GitHub and Zenodo repositories. Among other features are the calculation of EEG scalp spectra, and the estimation of their source spectra using the Variable Resolution Electrical Tomography (VARETA) source imaging. Crucially, this is completed by the evaluation of z spectra by means of the built-in age regression equations obtained from the CHBMP database (ages 5–87) to provide normative Statistical Parametric Mapping of EEG log source spectra. Different scalp and source visualization tools are also provided for evaluation of individual subjects prior to further post-processing. Openly releasing this software in the CBRAIN platform will facilitate the use of standardized qEEGt methods in different research and clinical settings. An updated precis of the methods is provided in Appendix I as a reference for the toolbox. qEEGt/CBRAIN is the first installment of instruments developed by the neuroinformatic platform of the Cuba-Canada-China (CCC) project. [ABSTRACT FROM AUTHOR]

We used EEG source analysis to identify which cortical areas were involved in the automatic and controlled processes of inhibitory control on a flanker task and compared the potential efficacy of recombinant-human erythropoietin (rHuEPO) on the performance of Parkinson's Disease patients. The samples were 18 medicated PD patients (nine of them received rHuEPO in addition to their usual anti-PD medication through random allocation and the other nine patients were on their regular anti-PD medication only) and 9 age and education-matched healthy controls (HCs) who completed the flanker task with simultaneous EEG recordings. N1 and N2 event-related potential (ERP) components were identified and a low resolution tomography (LORETA) inverse solution was employed to localize the neural generators. Reaction times and errors were increased for the incongruent flankers for PD patients compared to controls. EEG source analysis identified an effect of rHuEPO on the lingual gyri for the early N1 component. N2-related sources in middle cingulate and precuneus were associated with the inhibition of automatic responses evoked by incongruent stimuli differentiated PD and HCs. From our results rHuEPO seems to mediate an effect on N1 sources in lingual gyri but not on behavioural performance. N2-related sources in middle cingulate and precuneus were evoked by incongruent stimuli differentiated PD and HCs. [ABSTRACT FROM AUTHOR]

This Research Topic focused the comparison of the effect that various EEG references may have on inference about brain function and disorders - with respect to both physical and computational issues. In sum, this results suggest that recording montage, duration of the analytical window, and EEG activity dynamics should be considered when collecting and analyzing EEG data. He performed simulations, vertices uniformly distributed in eight large-scale brain networks: visual, somatomotor, dorsal attention, ventral attention, limbic, frontoparietal, default networks, and the deep brain structure, were adopted to generate the scalp EEG. ERP cortical source estimates, which are independent of the EEG reference choice, were used as the golden standard to infer the relative utility of different references on the ERP task-related effect. [Extracted from the article]

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. [ABSTRACT FROM AUTHOR]

We review the theory and algorithms of electrophysiological brain connectivity analysis. This tutorial is aimed at providing an introduction to brain functional connectivity from electrophysiological signals, including electroencephalography, magnetoencephalography, electrocorticography, and stereoelectroencephalography. Various connectivity estimators are discussed, and algorithms introduced. Important issues for estimating and mapping brain functional connectivity with electrophysiology are discussed. [ABSTRACT FROM AUTHOR]

The choice of reference for the electroencephalogram (EEG) is a long-lasting unsolved issue resulting in inconsistent usages and endless debates. Currently, both the average reference (AR) and the reference electrode standardization technique (REST) are two primary, apparently irreconcilable contenders. We propose a theoretical framework to resolve this reference issue by formulating both (a) estimation of potentials at infinity, and (b) determination of the reference, as a unified Bayesian linear inverse problem, which can be solved by maximum a posterior estimation. 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 based on the EEG generative model. To allow for simultaneous denoising and reference estimation, 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 variance ratio. Traditional and new estimators are evaluated with this framework, by both simulations and analysis of real resting EEGs. Toward this end, we leverage the MRI and EEG data from 89 subjects which participated in the Cuban Human Brain Mapping Project. Generated artificial EEGs--with a known ground truth, 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. Importantly, for practical applications, it is shown that an 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 to the EEG reference problem by means of a unified inverse solution framework. It may allow additional principled theoretical formulations and numerical evaluation of performance. [ABSTRACT FROM AUTHOR]

In this paper, we present a novel methodology to solve the classification problem, based on sparse (data-driven) regressions, combined with techniques for ensuring stability, especially useful for high-dimensional datasets and small samples number. The sensitivity and specificity of the classifiers are assessed by a stable ROC procedure, which uses a non-parametric algorithm for estimating the area under the ROC curve. This method allows assessing the performance of the classification by the ROC technique, when more than two groups are involved in the classification problem, i.e., when the gold standard is not binary. We apply this methodology to the EEG spectral signatures to find biomarkers that allow discriminating between (and predicting pertinence to) different subgroups of children diagnosed as Not Otherwise Specified Learning Disabilities (LD-NOS) disorder. Children with LD-NOS have notable learning difficulties, which affect education but are not able to be put into some specific category as reading (Dyslexia), Mathematics (Dyscalculia), or Writing (Dysgraphia). By using the EEG spectra, we aim to identify EEG patterns that may be related to specific learning disabilities in an individual case. This could be useful to develop subject-based methods of therapy, based on information provided by the EEG. Here we study 85 LD-NOS children, divided in three subgroups previously selected by a clustering technique over the scores of cognitive tests. The classification equation produced stable marginal areas under the ROC of 0.71 for discrimination between Group 1 vs. Group 2; 0.91 for Group 1 vs. Group 3; and 0.75 for Group 2 vs. Group1. A discussion of the EEG characteristics of each group related to the cognitive scores is also presented. [ABSTRACT FROM AUTHOR]

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, multiscale nature of neuroimaging data is well reflected by a multiway (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. [ABSTRACT FROM PUBLISHER]

Electroencephalography source imaging (ESI) is a useful technique to localize the generators from a given scalp electric measurement and to investigate the temporal dynamics of the large-scale neural circuits. By introducing reasonable priors from other modalities, ESI reveals the most probable sources and communication structures at every moment in time. Here, we review the available priors from such techniques as magnetic resonance imaging (MRI), functional MRI (fMRI), and positron emission tomography (PET). The modality's specific contribution is analyzed from the perspective of source reconstruction. For spatial priors, EEG-correlated fMRI, temporally coherent networks (TCNs) and resting-state fMRI are systematically introduced in the ESI. Moreover, the fiber tracking (diffusion tensor imaging, DTI) and neuro-stimulation techniques (transcranial magnetic stimulation, TMS) are also introduced as the potential priors, which can help to draw inferences about the neuroelectric connectivity in the source space. We conclude that combining EEG source imaging with other complementary modalities is a promising approach toward the study of brain networks in cognitive and clinical neurosciences. [ABSTRACT FROM AUTHOR]

Abstract: This is the final paper in a Comments and Controversies series dedicated to “The identification of interacting networks in the brain using fMRI: Model selection, causality and deconvolution”. We argue that discovering effective connectivity depends critically on state-space models with biophysically informed observation and state equations. These models have to be endowed with priors on unknown parameters and afford checks for model Identifiability. We consider the similarities and differences among Dynamic Causal Modeling, Granger Causal Modeling and other approaches. We establish links between past and current statistical causal modeling, in terms of Bayesian dependency graphs and Wiener–Akaike–Granger–Schweder influence measures. We show that some of the challenges faced in this field have promising solutions and speculate on future developments. [Copyright &y& Elsevier]

Simultaneous electroencephalography (EEG) and functional magnetic resonance imaging (fMRI) have been pursued in an effort to integrate complementary noninvasive information on brain activity. The primary goal involves better information discovery of the event-related neural activations at a spatial region of the BOLD fluctuation with the temporal resolution of the electrical signal. Many techniques and algorithms have been developed to integrate EEGs and fMRIs; however, the relative reliability of the integrated information is unclear. In this work, we propose a hierarchical framework to ensure the relative reliability of the integrated results and attempt to understand brain activation using this hierarchical ideal. First, spatial Independent Component Analysis (ICA) of fMRI and temporal ICA of EEG were performed to extract features at the trial level. Second, the maximal information coefficient (MIC) was adopted to temporally match them across the modalities for both linear and non-linear associations. Third, fMRI-constrained EEG source imaging was utilized to spatially match components across modalities. The simultaneously occurring events in the above two match steps provided EEG-fMRI spatial-temporal reliable integrated information, resulting in the most reliable components with high spatial and temporal resolution information. The other components discovered in the second or third steps provided second-level complementary information for flexible and cautious explanations. This paper contains two simulations and an example of real data, and the results indicate that the framework is a feasible approach to reveal cognitive processing in the human brain. [ABSTRACT FROM AUTHOR]

Abstract: In many situations various methods to analyze EEG/MEG data result in subspaces of the sensor space spanned by potentials of a set of sources. We propose a general model free method to decompose such a subspace into contributions from distinct sources. This unique decomposition can be achieved by first finding the respective subspace in source space using a linear inverse method and then finding the linear transformation such that the source distributions are mutually orthogonal and have a minimum overlap. The corresponding algorithm is a generalization of the recently presented ‘Minimum Overlap Component Analysis’ (MOCA) to more than two sources. The computational cost is negligible and the algorithm is almost never trapped in local minima. The method is illustrated with results for alpha rhythm. [Copyright &y& Elsevier]

Previous studies conducted on subjects with dysphonetic dyslexia (DD) reported inefficient timing integration of information from various brain areas. This dysregulation has been referred as neuronal dyschronia or timing deficiency. The present study examines the effective brain connectivity in Dysphonetic Dyslexic subjects (DD) compared to a group of subjects with non-specific reading delay (NSRD). The hypothesis is that the timing defect should be reflected also in the effective connectivity and the subjects with developmental dyslexia have an altered information flow different from the group of children with non-specific reading delay. The quantitative EEG at the sources of 184 children with DD was compared with that of 43 children with NRSD. The Isolated Effective Coherence (iCoh) was calculated among 17 brain regions data driven selected. To assess statistical differences in the EEG connectivity between the two groups, a Linear Mixed Effect (LME) model was applied. Two very important areas perform as hubs in the information flow: one is the left calcarine sulcus, which is more active in the DD group. The second is the left rolandic operculum, which is more active in the NSRD group. In the DD group, the calcarine sulcus is sending information to the right postcentral gyrus, the left paracentral gyrus, the right angular gyrus and the right supplementary motor area. This flow of information occurs in almost all frequency bands, including delta and theta band. Slow connections may indicate less efficient or even pathological information flow. We consider this as a neurophysiological evidence of Boder's model of dyslexia. • The effective connectivity was measured in dysphonetic dyslexia and non-specific reading delay. • An algorithm for unmixing the signals at the sources was used to reduce leakage • Isolated Effective Coherence, direct and directed information flow was calculated in 17 ROIs. • Linear mixed effect model was applied to assess statistical differences in EEG connectivity. • Left calcarine sulcus was more active in dyslexia and left rolandic operculum in reading delay. [ABSTRACT FROM AUTHOR]

• An IFCN Workgroup supplies recommendations on EEG frequency and topographical analysis for research. • EEG recording, visualization, and extraction/interpretation best features are proposed. • Pros and cons for clinical research of those features are discussed in light of controversies. In 1999, the International Federation of Clinical Neurophysiology (IFCN) published "IFCN Guidelines for topographic and frequency analysis of EEGs and EPs" (Nuwer et al., 1999). Here a Workgroup of IFCN experts presents unanimous recommendations on the following procedures relevant for the topographic and frequency analysis of resting state EEGs (rsEEGs) in clinical research defined as neurophysiological experimental studies carried out in neurological and psychiatric patients: (1) recording of rsEEGs (environmental conditions and instructions to participants; montage of the EEG electrodes; recording settings); (2) digital storage of rsEEG and control data; (3) computerized visualization of rsEEGs and control data (identification of artifacts and neuropathological rsEEG waveforms); (4) extraction of "synchronization" features based on frequency analysis (band-pass filtering and computation of rsEEG amplitude/power density spectrum); (5) extraction of "connectivity" features based on frequency analysis (linear and nonlinear measures); (6) extraction of "topographic" features (topographic mapping; cortical source mapping; estimation of scalp current density and dura surface potential; cortical connectivity mapping), and (7) statistical analysis and neurophysiological interpretation of those rsEEG features. As core outcomes, the IFCN Workgroup endorsed the use of the most promising "synchronization" and "connectivity" features for clinical research, carefully considering the limitations discussed in this paper. The Workgroup also encourages more experimental (i.e. simulation studies) and clinical research within international initiatives (i.e., shared software platforms and databases) facing the open controversies about electrode montages and linear vs. nonlinear and electrode vs. source levels of those analyses. [ABSTRACT FROM AUTHOR]

Oppositional defiant disorder (ODD) is frequently associated with Attention Deficit Hyperactivity Disorder (ADHD) but no clear neurophysiological evidence exists that distinguishes the two groups. Our aim was to identify biomarkers that distinguish children with Attention Deficit Hyperactivity Disorder combined subtype (ADHD_C) from children with ADHD_C + ODD, by combining the results of quantitative EEG (qEEG) and the Junior Temperament Character Inventory (JTCI). 28 ADHD_C and 22 ADHD_C + ODD children who met the DSMV criteria participated in the study. JTCI and EEG were analyzed. Stability based Biomarkers identification methodology was applied to the JTCI and the qEEG separately and combined. The qEEG was tested at the scalp and the sources levels. The classification power of the selected biomarkers was tested with a robust ROC technique. The best discriminant power was obtained when TCI and qEEG were analyzed together. Novelty seeking, self-directedness and cooperativeness were selected as biomarkers together with F4 and Cz in Delta; Fz and F4 in Theta and F7 and F8 in Beta, with a robust AUC of 0.95 for the ROC. At sources level: the regions were the right lateral and medial orbito-frontal cortex, cingular region, angular gyrus, right inferior occipital gyrus, occipital pole and the left insula in Theta, Alpha and Beta. The robust estimate of the total AUC was 0.91. These structures are part of extensive networks of novelty seeking, self-directedness and cooperativeness systems that seem dysregulated in these children. These methods represent an original approach to associate differences of personality and behavior to specific neuronal systems and subsystems. [ABSTRACT FROM AUTHOR]

Abstract: 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. [Copyright &y& Elsevier]

Abstract: There are few studies on the neuroanatomical determinants of EEG spectral properties that would explain its substantial inter-individual variability in spite of decades of biophysical modeling that predicts this type of relationship. An exception is the negative relation between head size and the spectral position of the alpha peak (Pα) reported in Nunez et al. (1978)—proposed as evidence of the influence of global boundary conditions on slightly damped neocortical waves. Here, we attempt to reexamine this finding by computing the correlations of occipital Pα with various measures of head size and cortical surface area, for 222 subjects from the EEG/MRI database of the Cuban Human Brain Mapping Project. No relation is found (p >0.05). On the other hand, biophysical models also predict that white matter architecture, determining time delays and connectivities, could have an important influence on Pα. This led us to explore relations between Pα and DTI fractional anisotropy by means of a multivariate penalized regression. Clusters of voxels with highly significant relations were found. These were positive within the Posterior and Superior Corona Radiata for both hemispheres, supporting biophysical theories predicting that the period of cortico-thalamocortical cycles might be modulating the alpha frequency. Posterior commissural fibers of the Corpus Callosum present the strongest relationships, negative in the inferior part (Splenium), connecting the inferior occipital lobes and positive in the superior part (Isthmus and Tapetum), connecting the superior occipital cortices. We found that white matter architecture rather than neocortical area determines the dynamics of the alpha rhythm. [Copyright &y& Elsevier]