Multivariate sharp-wave ripples in schizophrenia during awake state.

AIMS: Schizophrenia (SZ) is a brain disorder characterized by psychotic symptoms and cognitive dysfunction. Recently, irregularities in sharp-wave ripples (SPW-Rs) have been reported in SZ. As SPW-Rs play a critical role in memory, their irregularities can cause psychotic symptoms and cognitive dysfunction in patients with SZ. In this study, we investigated the SPW-Rs in human SZ. METHODS: We measured whole-brain activity using magnetoencephalography (MEG) in patients with SZ (n = 20) and sex- and age-matched healthy participants (n = 20) during open-eye rest. We identified SPW-Rs and analyzed their occurrence and time-frequency traits. Furthermore, we developed a novel multivariate analysis method, termed "ripple-gedMEG" to extract the global features of SPW-Rs. We also examined the association between SPW-Rs and brain state transitions. The outcomes of these analyses were modeled to predict the positive and negative syndrome scale (PANSS) scores of SZ. RESULTS: We found that SPW-Rs in the SZ (1) occurred more frequently, (2) the delay of the coupling phase (3) appeared in different brain areas, (4) consisted of a less organized spatiotemporal pattern, and (5) were less involved in brain state transitions. Finally, some of the neural features associated with the SPW-Rs were found to be PANSS-positive, a pathological indicator of SZ. These results suggest that widespread but disorganized SPW-Rs underlies the symptoms of SZ. CONCLUSION: We identified irregularities in SPW-Rs in SZ and confirmed that their alternations were strongly associated with SZ neuropathology. These results suggest a new direction for human SZ research.

Estimation and model selection in general spatial dynamic panel data models.

Commonly used methods for estimating parameters of a spatial dynamic panel data model include the two-stage least squares, quasi-maximum likelihood, and generalized moments. In this paper, we present an approach that uses the eigenvalues and eigenvectors of a spatial weight matrix to directly construct consistent least-squares estimators of parameters of a general spatial dynamic panel data model. The proposed methodology is conceptually simple and efficient and can be easily implemented. We show that the proposed parameter estimators are consistent and asymptotically normally distributed under mild conditions. We demonstrate the superior performance of our approach via extensive simulation studies. We also provide a real data example.

A tutorial on generalized eigendecomposition for denoising, contrast enhancement, and dimension reduction in multichannel electrophysiology.

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

A Method for Unsupervised Semi-Quantification of Inmunohistochemical Staining with Beta Divergences.

In many research laboratories, it is essential to determine the relative expression levels of some proteins of interest in tissue samples. The semi-quantitative scoring of a set of images consists of establishing a scale of scores ranging from zero or one to a maximum number set by the researcher and assigning a score to each image that should represent some predefined characteristic of the IHC staining, such as its intensity. However, manual scoring depends on the judgment of an observer and therefore exposes the assessment to a certain level of bias. In this work, we present a fully automatic and unsupervised method for comparative biomarker quantification in histopathological brightfield images. The method relies on a color separation method that discriminates between two chromogens expressed as brown and blue colors robustly, independent of color variation or biomarker expression level. For this purpose, we have adopted a two-stage stain separation approach in the optical density space. First, a preliminary separation is performed using a deconvolution method in which the color vectors of the stains are determined after an eigendecomposition of the data. Then, we adjust the separation using the non-negative matrix factorization method with beta divergences, initializing the algorithm with the matrices resulting from the previous step. After that, a feature vector of each image based on the intensity of the two chromogens is determined. Finally, the images are annotated using a systematically initialized k-means clustering algorithm with beta divergences. The method clearly defines the initial boundaries of the categories, although some flexibility is added. Experiments for the semi-quantitative scoring of images in five categories have been carried out by comparing the results with the scores of four expert researchers yielding accuracies that range between 76.60% and 94.58%. These results show that the proposed automatic scoring system, which is definable and reproducible, produces consistent results.

Classification of Motor Functions from Electroencephalogram (EEG) Signals Based on an Integrated Method Comprised of Common Spatial Pattern and Wavelet Transform Framework.

In this work, an algorithm for the classification of six motor functions from an electroencephalogram (EEG) signal that combines a common spatial pattern (CSP) filter and a continuous wavelet transform (CWT), is investigated. The EEG data comprise six grasp-and-lift events, which are used to investigate the potential of using EEG as input signals with brain computer interface devices for controlling prosthetic devices for upper limb movement. Selected EEG channels are the ones located over the motor cortex, C3, Cz and C4, as well as at the parietal region, P3, Pz and P4. In general, the proposed algorithm includes three main stages, band pass filtering, CSP filtering, and wavelet transform and training on GoogLeNet for feature extraction, feature learning and classification. The band pass filtering is performed to select the EEG signal in the band of 7 Hz to 30 Hz while eliminating artifacts related to eye blink, heartbeat and muscle movement. The CSP filtering is applied on two-class EEG signals that will result in maximizing the power difference between the two-class dataset. Since CSP is mathematically developed for two-class events, the extension to the multiclass paradigm is achieved by using the approach of one class versus all other classes. Subsequently, continuous wavelet transform is used to convert the band pass and CSP filtered signals from selected electrodes to scalograms which are then converted to images in grayscale format. The three scalograms from the motor cortex regions and the parietal region are then combined to form two sets of RGB images. Next, these RGB images become the input to GoogLeNet for classification of the motor EEG signals. The performance of the proposed classification algorithm is evaluated in terms of precision, sensitivity, specificity, accuracy with average values of 94.8%, 93.5%, 94.7%, 94.1%, respectively, and average area under the receiver operating characteristic (ROC) curve equal to 0.985. These results indicate a good performance of the proposed algorithm in classifying grasp-and-lift events from EEG signals.

Rhythmic entrainment source separation: Optimizing analyses of neural responses to rhythmic sensory stimulation.

Steady-state evoked potentials (SSEPs) are rhythmic brain responses to rhythmic sensory stimulation, and are often used to study perceptual and attentional processes. We present a data analysis method for maximizing the signal-to-noise ratio of the narrow-band steady-state response in the frequency and time-frequency domains. The method, termed rhythmic entrainment source separation (RESS), is based on denoising source separation approaches that take advantage of the simultaneous but differential projection of neural activity to multiple electrodes or sensors. Our approach is a combination and extension of existing multivariate source separation methods. We demonstrate that RESS performs well on both simulated and empirical data, and outperforms conventional SSEP analysis methods based on selecting electrodes with the strongest SSEP response, as well as several other linear spatial filters. We also discuss the potential confound of overfitting, whereby the filter captures noise in absence of a signal. Matlab scripts are available to replicate and extend our simulations and methods. We conclude with some practical advice for optimizing SSEP data analyses and interpreting the results.

Determining the number of attributes in the GDINA model.

Exploratory cognitive diagnosis models have been widely used in psychology, education and other fields. This paper focuses on determining the number of attributes in a widely used cognitive diagnosis model, the GDINA model. Under some conditions of cognitive diagnosis models, we prove that there exists a special structure for the covariance matrix of observed data. Due to the special structure of the covariance matrix, an estimator based on eigen-decomposition is proposed for the number of attributes for the GDINA model. The performance of the proposed estimator is verified by simulation studies. Finally, the proposed estimator is applied to two real data sets Examination for the Certificate of Proficiency in English (ECPE) and Big Five Personality (BFP).

Effect of detector placement on joint estimation in X-ray fluorescence emission tomography.

Imaging the spatial distribution of low concentrations of metal is a growing problem of interest with applications in medical and material sciences. X-ray fluorescence emission tomography (XFET) is an emerging metal mapping imaging modality with potential sensitivity improvements and practical advantages over other methods. However, XFET detector placement must first be optimized to ensure accurate metal density quantification and adequate spatial resolution. In this work, we first use singular value decomposition of the imaging model and eigendecomposition of the object-specific Fisher information matrix to study how detector arrangement affects spatial resolution and feature preservation. We then perform joint image reconstructions of a numerical gold phantom. For this phantom, we show that two parallel detectors provide metal quantification with similar accuracy to four detectors, despite the resulting anisotropic spatial resolution in the attenuation map estimate. Two orthogonal detectors provide improved spatial resolution along one axis, but underestimate the metal concentration in distant regions. Therefore, this work demonstrates the minor effect of using fewer, but strategically placed, detectors in the case where detector placement is restricted. This work is a critical investigation into the limitations and capabilities of XFET prior to its translation to preclinical and benchtop uses.

Corrigendum: Complexity changes in functional state dynamics suggest focal connectivity reductions.

[This corrects the article DOI: 10.3389/fnhum.2022.958706.].

Removing dynamic distortions from laser speckle flowgraphy using Eigen-decomposition and spatial filtering.

Laser speckle flowgraphy (LSFG) has been widely used in the investigation of blood flows in ophthalmology. However, the dynamic changes of the ocular optics can impose artificial contrasts to the LSFG, corrupting the detection of both retinal vasculature and blood pulsation at the posterior segment of the human eye. In this study, we propose to use Eigen-decomposition method to separate the spatially and temporally varying speckle patterns from the static tissues. Spatial filtering is further applied to remove the distortion-correlated modulation of the speckle patterns. We experimentally show that with the proposed method, the integrity of blood vessels is significantly improved and the distortions in pulse waveforms can be well corrected.

Complexity changes in functional state dynamics suggest focal connectivity reductions.

The past two decades have seen an explosion in the methods and directions of neuroscience research. Along with many others, complexity research has rapidly gained traction as both an independent research field and a valuable subdiscipline in computational neuroscience. In the past decade alone, several studies have suggested that psychiatric disorders affect the spatiotemporal complexity of both global and region-specific brain activity (Liu et al., 2013; Adhikari et al., 2017; Li et al., 2018). However, many of these studies have not accounted for the distributed nature of cognition in either the global or regional complexity estimates, which may lead to erroneous interpretations of both global and region-specific entropy estimates. To alleviate this concern, we propose a novel method for estimating complexity. This method relies upon projecting dynamic functional connectivity into a low-dimensional space which captures the distributed nature of brain activity. Dimension-specific entropy may be estimated within this space, which in turn allows for a rapid estimate of global signal complexity. Testing this method on a recently acquired obsessive-compulsive disorder dataset reveals substantial increases in the complexity of both global and dimension-specific activity versus healthy controls, suggesting that obsessive-compulsive patients may experience increased disorder in cognition. To probe the potential causes of this alteration, we estimate subject-level effective connectivity via a Hopf oscillator-based model dynamic model, the results of which suggest that obsessive-compulsive patients may experience abnormally high connectivity across a broad network in the cortex. These findings are broadly in line with results from previous studies, suggesting that this method is both robust and sensitive to group-level complexity alterations.

Large-Scale and Multiscale Networks in the Rodent Brain during Novelty Exploration.

Neural activity is coordinated across multiple spatial and temporal scales, and these patterns of coordination are implicated in both healthy and impaired cognitive operations. However, empirical cross-scale investigations are relatively infrequent, because of limited data availability and to the difficulty of analyzing rich multivariate datasets. Here, we applied frequency-resolved multivariate source-separation analyses to characterize a large-scale dataset comprising spiking and local field potential (LFP) activity recorded simultaneously in three brain regions (prefrontal cortex, parietal cortex, hippocampus) in freely-moving mice. We identified a constellation of multidimensional, inter-regional networks across a range of frequencies (2-200 Hz). These networks were reproducible within animals across different recording sessions, but varied across different animals, suggesting individual variability in network architecture. The theta band (∼4-10 Hz) networks had several prominent features, including roughly equal contribution from all regions and strong inter-network synchronization. Overall, these findings demonstrate a multidimensional landscape of large-scale functional activations of cortical networks operating across multiple spatial, spectral, and temporal scales during open-field exploration.

Neural Entrainment Meets Behavior: The Stability Index as a Neural Outcome Measure of Auditory-Motor Coupling.

Understanding rhythmic behavior in the context of coupled auditory and motor systems has been of interest to neurological rehabilitation, in particular, to facilitate walking. Recent work based on behavioral measures revealed an entrainment effect of auditory rhythms on motor rhythms. In this study, we propose a method to compute the neural component of such a process from an electroencephalographic (EEG) signal. A simple auditory-motor synchronization paradigm was used, where 28 healthy participants were instructed to synchronize their finger-tapping with a metronome. The computation of the neural outcome measure was carried out in two blocks. In the first block, we used Generalized Eigendecomposition (GED) to reduce the data dimensionality to the component which maximally entrained to the metronome frequency. The scalp topography pointed at brain activity over contralateral sensorimotor regions. In the second block, we computed instantaneous frequency from the analytic signal of the extracted component. This returned a time-varying measure of frequency fluctuations, whose standard deviation provided our "stability index" as a neural outcome measure of auditory-motor coupling. Finally, the proposed neural measure was validated by conducting a correlation analysis with a set of behavioral outcomes from the synchronization task: resultant vector length, relative phase angle, mean asynchrony, and tempo matching. Significant moderate negative correlations were found with the first three measures, suggesting that the stability index provided a quantifiable neural outcome measure of entrainment, with selectivity towards phase-correction mechanisms. We address further adoption of the proposed approach, especially with populations where sensorimotor abilities are compromised by an underlying pathological condition. The impact of using stability index can potentially be used as an outcome measure to assess rehabilitation protocols, and possibly provide further insight into neuropathological models of auditory-motor coupling.

Does Real-Time Feedback Affect Sensorimotor EEG Patterns in Routine Motor Imagery Practice?

BACKGROUND: Motor imagery engages much of the same neural circuits as an overt movement. Therefore, the mental rehearsal of movements is often used to supplement physical training and might aid motor neurorehabilitation after stroke. One attempt to capture the brain's involvement in imagery involves the use, as a marker, of the depression or event-related desynchronization (ERD) of thalamocortical sensorimotor rhythms found in a human electroencephalogram (EEG). Using fast real-time processing, it is possible to make the subject aware of their own brain reactions or-even better-to turn them into actions through a technology called the brain-computer interface (BCI). However, it remains unclear whether BCI-enabled imagery facilitates a stronger or qualitatively different brain response compared to the open-loop training. METHODS: Seven healthy volunteers who were experienced in both closed and open-loop motor imagery took part in six experimental sessions over a period of 4.5 months, in which they performed kinesthetic imagery of a previously known set of finger and arm movements with simultaneous 30-channel EEG acquisition. The first and the last session mostly consisted of feedback trials in which the subjects were presented with the classification results of the EEG patterns in real time; during the other sessions, no feedback was provided. Spatiotemporal and amplitude features of the ERD patterns concomitant with imagery were compared across experimental days and between feedback conditions using linear mixed-effects modeling. RESULTS: The main spatial sources of ERD appeared to be highly stable across the six experimental days, remaining nearly identical in five of seven subjects (Pearson's ρ > 0.94). Only in one subject did the spatial pattern of activation statistically significantly differ (p = 0.009) between the feedback and no-feedback conditions. Real-time visual feedback delivered through the BCI did not significantly increase the ERD strength. CONCLUSION: The results imply that the potential benefits of MI could be yielded by well-habituated subjects with a simplified open-loop setup, e.g., through at-home self-practice.

Mesoscopic-scale functional networks in the primate amygdala.

The primate amygdala performs multiple functions that may be related to the anatomical heterogeneity of its nuclei. Individual neurons with stimulus- and task-specific responses are not clustered in any of the nuclei, suggesting that single-units may be too-fine grained to shed light on the mesoscale organization of the amygdala. We have extracted from local field potentials recorded simultaneously from multiple locations within the primate (Macaca mulatta) amygdala spatially defined and statistically separable responses to visual, tactile, and auditory stimuli. A generalized eigendecomposition-based method of source separation isolated coactivity patterns, or components, that in neurophysiological terms correspond to putative subnetworks. Some component spatial patterns mapped onto the anatomical organization of the amygdala, while other components reflected integration across nuclei. These components differentiated between visual, tactile, and auditory stimuli suggesting the presence of functionally distinct parallel subnetworks.

Relating the Structure of Noise Correlations in Macaque Primary Visual Cortex to Decoder Performance.

Noise correlations in neuronal responses can have a strong influence on the information available in large populations. In addition, the structure of noise correlations may have a great impact on the utility of different algorithms to extract this information that may depend on the specific algorithm, and hence may affect our understanding of population codes in the brain. Thus, a better understanding of the structure of noise correlations and their interplay with different readout algorithms is required. Here we use eigendecomposition to investigate the structure of noise correlations in populations of about 50-100 simultaneously recorded neurons in the primary visual cortex of anesthetized monkeys, and we relate this structure to the performance of two common decoders: the population vector and the optimal linear estimator. Our analysis reveals a non-trivial correlation structure, in which the eigenvalue spectrum is composed of several distinct large eigenvalues that represent different shared modes of fluctuation extending over most of the population, and a semi-continuous tail. The largest eigenvalue represents a uniform collective mode of fluctuation. The second and third eigenvalues typically show either a clear functional (i.e., dependent on the preferred orientation of the neurons) or spatial structure (i.e., dependent on the physical position of the neurons). We find that the number of shared modes increases with the population size, being roughly 10% of that size. Furthermore, we find that the noise in each of these collective modes grows linearly with the population. This linear growth of correlated noise power can have limiting effects on the utility of averaging neuronal responses across large populations, depending on the readout. Specifically, the collective modes of fluctuation limit the accuracy of the population vector but not of the optimal linear estimator.

Dynamic laser speckle angiography achieved by eigen-decomposition filtering.

A new approach is proposed for statistically analysis of laser speckle signals emerged from a living biological tissue based on eigen-decomposition to separate the dynamic speckle signals due to moving blood cells from the static speckle signals due to static tissue components, upon which to achieve angiography of the interrogated tissue in vivo. The proposed approach is tested by imaging mouse ear pinna in vivo, demonstrating its capability of providing detailed microvascular networks with high contrast, and high temporal and spatial resolutions. It is expected to provide further opportunities for laser speckle imaging in the biomedical and clinical applications where microvascular response to certain stimulus or tissue injury is of interest.

Individual Differences in Frequency and Topography of Slow and Fast Sleep Spindles.

Sleep spindles are transient oscillatory waveforms that occur during non-rapid eye movement (NREM) sleep across widespread cortical areas. In humans, spindles can be classified as either slow or fast, but large individual differences in spindle frequency as well as methodological difficulties have hindered progress towards understanding their function. Using two nights of high-density electroencephalography recordings from 28 healthy individuals, we first characterize the individual variability of NREM spectra and demonstrate the difficulty of determining subject-specific spindle frequencies. We then introduce a novel spatial filtering approach that can reliably separate subject-specific spindle activity into slow and fast components that are stable across nights and across N2 and N3 sleep. We then proceed to provide detailed analyses of the topographical expression of individualized slow and fast spindle activity. Group-level analyses conform to known spatial properties of spindles, but also uncover novel differences between sleep stages and spindle classes. Moreover, subject-specific examinations reveal that individual topographies show considerable variability that is stable across nights. Finally, we demonstrate that topographical maps depend nontrivially on the spindle metric employed. In sum, our findings indicate that group-level approaches mask substantial individual variability of spindle dynamics, in both the spectral and spatial domains. We suggest that leveraging, rather than ignoring, such differences may prove useful to further our understanding of the physiology and functional role of sleep spindles.

Sexual selection and population divergence II. Divergence in different sexual traits and signal modalities in field crickets (Teleogryllus oceanicus).

Sexual selection can target many different types of traits. However, the relative influence of different sexually selected traits during evolutionary divergence is poorly understood. We used the field cricket Teleogryllus oceanicus to quantify and compare how five traits from each of three sexual signal modalities and components diverge among allopatric populations: male advertisement song, cuticular hydrocarbon (CHC) profiles and forewing morphology. Population divergence was unexpectedly consistent: we estimated the among-population (genetic) variance-covariance matrix, D, for all 15 traits, and Dmax explained nearly two-thirds of its variation. CHC and wing traits were most tightly integrated, whereas song varied more independently. We modeled the dependence of among-population trait divergence on genetic distance estimated from neutral markers to test for signatures of selection versus neutral divergence. For all three sexual trait types, phenotypic variation among populations was largely explained by a neutral model of divergence. Our findings illustrate how phenotypic integration across different types of sexual traits might impose constraints on the evolution of mating isolation and divergence via sexual selection.

Comparison of linear spatial filters for identifying oscillatory activity in multichannel data.

BACKGROUND: Large-scale synchronous neural activity produces electrical fields that can be measured by electrodes outside the head, and volume conduction ensures that neural sources can be measured by many electrodes. However, most data analyses in M/EEG research are univariate, meaning each electrode is considered as a separate measurement. Several multivariate linear spatial filtering techniques have been introduced to the cognitive electrophysiology literature, but these techniques are not commonly used; comparisons across filters would be beneficial to the field. NEW METHOD: The purpose of this paper is to evaluate and compare the performance of several linear spatial filtering techniques, with a focus on those that use generalized eigendecomposition to facilitate dimensionality reduction and signal-to-noise ratio maximization. RESULTS: Simulated and empirical data were used to assess the accuracy, signal-to-noise ratio, and interpretability of the spatial filter results. When the simulated signal is powerful, different spatial filters provide convergent results. However, more subtle signals require carefully selected analysis parameters to obtain optimal results. COMPARISON WITH EXISTING METHODS: Linear spatial filters can be powerful data analysis tools in cognitive electrophysiology, and should be applied more often; on the other hand, spatial filters can latch onto artifacts or produce uninterpretable results. CONCLUSIONS: Hypothesis-driven analyses, careful data inspection, and appropriate parameter selection are necessary to obtain high-quality results when using spatial filters.