Connectome spectrum electromagnetic tomography: A method to reconstruct electrical brain source networks at high-spatial resolution.

Connectome spectrum electromagnetic tomography (CSET) combines diffusion MRI-derived structural connectivity data with well-established graph signal processing tools to solve the M/EEG inverse problem. Using simulated EEG signals from fMRI responses, and two EEG datasets on visual-evoked potentials, we provide evidence supporting that (i) CSET captures realistic neurophysiological patterns with better accuracy than state-of-the-art methods, (ii) CSET can reconstruct brain responses more accurately and with more robustness to intrinsic noise in the EEG signal. These results demonstrate that CSET offers high spatio-temporal accuracy, enabling neuroscientists to extend their research beyond the current limitations of low sampling frequency in functional MRI and the poor spatial resolution of M/EEG.

The coupling between the spatial and temporal scales of neural processes revealed by a joint time-vertex connectome spectral analysis.

Brain oscillations are produced by the coordinated activity of large groups of neurons and different rhythms are thought to reflect different modes of information processing. These modes, in turn, are known to occur at different spatial scales. Nevertheless, how these rhythms support different spatial modes of information processing at the brain scale is not yet fully understood. Here we use "Joint Time-Vertex Spectral Analysis" to characterize the joint spectral content of brain activity both in time (temporal frequencies) and in space over the connectivity graph (spatial connectome harmonics). This method allows us to characterize the relationship between spatially localized or distributed neural processes on one side and their respective temporal frequency bands in source-reconstructed M/EEG signals. We explore this approach on two different datasets, an auditory steady-state response (ASSR) and a visual grating task. Our results suggest that different information processing mechanisms are carried out at different frequency bands: while spatially distributed activity (which may also be interpreted as integration) specifically occurs at low temporal frequencies (alpha and theta) and low graph spatial frequencies, localized electrical activity (i.e., segregation) is observed at high temporal frequencies (high and low gamma) over restricted high spatial graph frequencies. Crucially, the estimated contribution of the distributed and localized neural activity predicts performance in a behavioral task, demonstrating the neurophysiological relevance of the joint time-vertex spectral representation.

Structure supports function: Informing directed and dynamic functional connectivity with anatomical priors.

The dynamic repertoire of functional brain networks is constrained by the underlying topology of structural connections. Despite this intrinsic relationship between structural connectivity (SC) and functional connectivity (FC), integrative and multimodal approaches to combine the two remain limited. Here, we propose a new adaptive filter for estimating dynamic and directed FC using structural connectivity information as priors. We tested the filter in rat epicranial recordings and human event-related EEG data, using SC priors from a meta-analysis of tracer studies and diffusion tensor imaging metrics, respectively. We show that, particularly under conditions of low signal-to-noise ratio, SC priors can help to refine estimates of directed FC, promoting sparse functional networks that combine information from structure and function. In addition, the proposed filter provides intrinsic protection against SC-related false negatives, as well as robustness against false positives, representing a valuable new tool for multimodal imaging in the context of dynamic and directed FC analysis.

Four concurrent feedforward and feedback networks with different roles in the visual cortical hierarchy.

Visual stimuli evoke fast-evolving activity patterns that are distributed across multiple cortical areas. These areas are hierarchically structured, as indicated by their anatomical projections, but how large-scale feedforward and feedback streams are functionally organized in this system remains an important missing clue to understanding cortical processing. By analyzing visual evoked responses in laminar recordings from 6 cortical areas in awake mice, we uncovered a dominant feedforward network with scale-free interactions in the time domain. In addition, we established the simultaneous presence of a gamma band feedforward and 2 low frequency feedback networks, each with a distinct laminar functional connectivity profile, frequency spectrum, temporal dynamics, and functional hierarchy. We could identify distinct roles for each of these 4 processing streams, by leveraging stimulus contrast effects, analyzing receptive field (RF) convergency along functional interactions, and determining relationships to spiking activity. Our results support a dynamic dual counterstream view of hierarchical processing and provide new insight into how separate functional streams can simultaneously and dynamically support visual processes.

Source imaging of high-density visual evoked potentials with multi-scale brain parcellations and connectomes.

We describe the multimodal neuroimaging dataset VEPCON (OpenNeuro Dataset ds003505). It includes raw data and derivatives of high-density EEG, structural MRI, diffusion weighted images (DWI) and single-trial behavior (accuracy, reaction time). Visual evoked potentials (VEPs) were recorded while participants (n = 20) discriminated briefly presented faces from scrambled faces, or coherently moving stimuli from incoherent ones. EEG and MRI were recorded separately from the same participants. The dataset contains raw EEG and behavioral data, pre-processed EEG of single trials in each condition, structural MRIs, individual brain parcellations at 5 spatial resolutions (83 to 1015 regions), and the corresponding structural connectomes computed from fiber count, fiber density, average fractional anisotropy and mean diffusivity maps. For source imaging, VEPCON provides EEG inverse solutions based on individual anatomy, with Python and Matlab scripts to derive activity time-series in each brain region, for each parcellation level. The BIDS-compatible dataset can contribute to multimodal methods development, studying structure-function relations, and to unimodal optimization of source imaging and graph analyses, among many other possibilities.

Selective attention involves a feature-specific sequential release from inhibitory gating.

Selective attention is a fundamental cognitive mechanism that allows our brain to preferentially process relevant sensory information, while filtering out distracting information. Attention is thought to flexibly gate the communication of irrelevant information through top-down alpha-rhythmic (8-12 Hz) functional connections, which influence early visual processing. However, the dynamic effects of top-down influence on downstream visual processing remain unknown. Here, we used electroencephalography to investigate local and network effects of selective attention while subjects attended to distinct features of identical stimuli. We found that attention-related changes in the functional brain network organization emerge shortly after stimulus onset, accompanied by an overall decrease of functional connectivity. Signatures of attentional selection were evident from a sequential release from alpha-band parietal gating in feature-selective areas. The directed connectivity paths and temporal evolution of this release from gating were consistent with the sensory effect of each feature, providing a neural basis for how visual processing quickly prioritizes relevant information in functionally specialized areas.

The connectome spectrum as a canonical basis for a sparse representation of fast brain activity.

The functional organization of neural processes is constrained by the brain's intrinsic structural connectivity, i.e., the connectome. Here, we explore how structural connectivity can improve the representation of brain activity signals and their dynamics. Using a multi-modal imaging dataset (electroencephalography, structural MRI, and diffusion MRI), we represent electrical brain activity at the cortical surface as a time-varying composition of harmonic modes of structural connectivity. These harmonic modes are known as connectome harmonics. Here we describe brain activity signal as a time-varying combination of connectome harmonics. We term this description as the connectome spectrum of the signal. We found that: first, the brain activity signal is represented more compactly by the connectome spectrum than by the traditional area-based representation; second, the connectome spectrum characterizes fast brain dynamics in terms of signal broadcasting profile, revealing different temporal regimes of integration and segregation that are consistent across participants. And last, the connectome spectrum characterizes fast brain dynamics with fewer degrees of freedom than area-based signal representations. Specifically, we show that a smaller number of dimensions capture the differences between low-level and high-level visual processing in the connectome spectrum. Also, we demonstrate that connectome harmonics capture more sensitively the topological properties of brain activity. In summary, this work provides statistical, functional, and topological evidence indicating that the description of brain activity in terms of structural connectivity fosters a more comprehensive understanding of large-scale dynamic neural functioning.

The anisotropic field of ensemble coding.

Human observers can accurately estimate statistical summaries from an ensemble of multiple stimuli, including the average size, hue, and direction of motion. The efficiency and speed with which statistical summaries are extracted suggest an automatic mechanism of ensemble coding that operates beyond the capacity limits of attention and memory. However, the extent to which ensemble coding reflects a truly parallel and holistic mode of processing or a non-uniform and biased integration of multiple items is still under debate. In the present work, we used a technique, based on a Spatial Weighted Average Model (SWM), to recover the spatial profile of weights with which individual stimuli contribute to the estimated average during mean size adjustment tasks. In a series of experiments, we derived two-dimensional SWM maps for ensembles presented at different retinal locations, with different degrees of dispersion and under different attentional demands. Our findings revealed strong spatial anisotropies and leftward biases in ensemble coding that were organized in retinotopic reference frames and persisted under attentional manipulations. These results demonstrate an anisotropic spatial contribution to ensemble coding that could be mediated by the differential activation of the two hemispheres during spatial processing and scene encoding.

Nested oscillations and brain connectivity during sequential stages of feature-based attention.

Brain mechanisms of visual selective attention involve both local and network-level activity changes at specific oscillatory rhythms, but their interplay remains poorly explored. Here, we investigate anticipatory and reactive effects of feature-based attention using separate fMRI and EEG recordings, while participants attended to one of two spatially overlapping visual features (motion and orientation). We focused on EEG source analysis of local neuronal rhythms and nested oscillations and on graph analysis of connectivity changes in a network of fMRI-defined regions of interest, and characterized a cascade of attentional effects at multiple spatial scales. We discuss how the results may reconcile several theories of selective attention, by showing how ß rhythms support anticipatory information routing through increased network efficiency, while reactive α-band desynchronization patterns and increased α-γ coupling in task-specific sensory areas mediate stimulus-evoked processing of task-relevant signals.

Neural dynamics of cue reliability in perceptual decisions.

To extract meaningful information from scenes, the visual system must combine local cues that can vary greatly in their degree of reliability. Here, we asked whether cue reliability mostly affects visual or decision-related processes, using visual evoked potentials (VEPs) and a model-based approach to identify when and where stimulus-evoked brain activity reflects cue reliability. Participants performed a shape discrimination task on Gaborized ellipses, while we parametrically and independently, varied the reliability of contour or surface cues. We modeled the expected behavioral performance as a linear function of cue reliability and established at what latencies and electrodes VEP activity reflected behavioral sensitivity to cue reliability. We found that VEPs were linearly related to the individual behavioral predictors at around 400 ms post-stimulus, at electrodes over parietal and lateral temporal cortex. The observed cue reliability effects were similar for variations in contour and surface cues. Notably, effects of cue reliability were absent at earlier latencies where visual shape information is typically reported, and also in data time-locked to the behavioral response, suggesting the effects are not decision-related. These results indicate that reliability of visual cues is reflected in late distributed perceptual processes.

Connectome spectral analysis to track EEG task dynamics on a subsecond scale.

We present an approach for tracking fast spatiotemporal cortical dynamics in which we combine white matter connectivity data with source-projected electroencephalographic (EEG) data. We employ the mathematical framework of graph signal processing in order to derive the Fourier modes of the brain structural connectivity graph, or "network harmonics". These network harmonics are naturally ordered by smoothness. Smoothness in this context can be understood as the amount of variation along the cortex, leading to a multi-scale representation of brain connectivity. We demonstrate that network harmonics provide a sparse representation of the EEG signal, where, at certain times, the smoothest 15 network harmonics capture 90% of the signal power. This suggests that network harmonics are functionally meaningful, which we demonstrate by using them as a basis for the functional EEG data recorded from a face detection task. There, only 13 network harmonics are sufficient to track the large-scale cortical activity during the processing of the stimuli with a 50 â€‹ms resolution, reproducing well-known activity in the fusiform face area as well as revealing co-activation patterns in somatosensory/motor and frontal cortices that an unconstrained ROI-by-ROI analysis fails to capture. The proposed approach is simple and fast, provides a means of integration of multimodal datasets, and is tied to a theoretical framework in mathematics and physics. Thus, network harmonics point towards promising research directions both theoretically - for example in exploring the relationship between structure and function in the brain - and practically - for example for network tracking in different tasks and groups of individuals, such as patients.

Laws of concatenated perception: Vision goes for novelty, decisions for perseverance.

Every instant of perception depends on a cascade of brain processes calibrated to the history of sensory and decisional events. In the present work, we show that human visual perception is constantly shaped by two contrasting forces exerted by sensory adaptation and past decisions. In a series of experiments, we used multilevel modeling and cross-validation approaches to investigate the impact of previous stimuli and decisions on behavioral reports during adjustment and forced-choice tasks. Our results revealed that each perceptual report is permeated by opposite biases from a hierarchy of serially dependent processes: Low-level adaptation repels perception away from previous stimuli, whereas decisional traces attract perceptual reports toward the recent past. In this hierarchy of serial dependence, "continuity fields" arise from the inertia of decisional templates and not from low-level sensory processes. This finding is consistent with a Two-process model of serial dependence in which the persistence of readout weights in a decision unit compensates for sensory adaptation, leading to attractive biases in sequential perception. We propose a unified account of serial dependence in which functionally distinct mechanisms, operating at different stages, promote the differentiation and integration of visual information over time.

Layer 3 Dynamically Coordinates Columnar Activity According to Spatial Context.

To reduce statistical redundancy of natural inputs and increase the sparseness of coding, neurons in primary visual cortex (V1) show tuning for stimulus size and surround suppression. This integration of spatial information is a fundamental, context-dependent neural operation involving extensive neural circuits that span across all cortical layers of a V1 column, and reflects both feedforward and feedback processing. However, how spatial integration is dynamically coordinated across cortical layers remains poorly understood. We recorded single- and multiunit activity and local field potentials across V1 layers of awake mice (both sexes) while they viewed stimuli of varying size and used dynamic Bayesian model comparisons to identify when laminar activity and interlaminar functional interactions showed surround suppression, the hallmark of spatial integration. We found that surround suppression is strongest in layer 3 (L3) and L4 activity, where suppression is established within ∼10 ms after response onset, and receptive fields dynamically sharpen while suppression strength increases. Importantly, we also found that specific directed functional connections were strongest for intermediate stimulus sizes and suppressed for larger ones, particularly for connections from L3 targeting L5 and L1. Together, the results shed light on the different functional roles of cortical layers in spatial integration and on how L3 dynamically coordinates activity across a cortical column depending on spatial context.SIGNIFICANCE STATEMENT Neurons in primary visual cortex (V1) show tuning for stimulus size, where responses to stimuli exceeding the receptive field can be suppressed (surround suppression). We demonstrate that functional connectivity between V1 layers can also have a surround-suppressed profile. A particularly prominent role seems to have layer 3, the functional connections to layers 5 and 1 of which are strongest for stimuli of optimal size and decreased for large stimuli. Our results therefore point toward a key role of layer 3 in coordinating activity across the cortical column according to spatial context.

Directed functional connections underlying spontaneous brain activity.

Neuroimaging studies have shown that spontaneous brain activity is characterized as changing networks of coherent activity across multiple brain areas. However, the directionality of functional interactions between the most active regions in our brain at rest remains poorly understood. Here, we examined, at the whole-brain scale, the main drivers and directionality of interactions that underlie spontaneous human brain activity by applying directed functional connectivity analysis to electroencephalography (EEG) source signals. We found that the main drivers of electrophysiological activity were the posterior cingulate cortex (PCC), the medial temporal lobes (MTL), and the anterior cingulate cortex (ACC). Among those regions, the PCC was the strongest driver and had both the highest integration and segregation importance, followed by the MTL regions. The driving role of the PCC and MTL resulted in an effective directed interaction directed from posterior toward anterior brain regions. Our results strongly suggest that the PCC and MTL structures are the main drivers of electrophysiological spontaneous activity throughout the brain and suggest that EEG-based directed functional connectivity analysis is a promising tool to better understand the dynamics of spontaneous brain activity in healthy subjects and in various brain disorders.

A regularized and smoothed General Linear Kalman Filter for more accurate estimation of time-varying directed connectivity.

Adaptive algorithms based on the Kalman filter are valuable tools to model the dynamic and directed Granger causal interactions between neurophysiological signals simultaneously recorded from multiple cortical regions. Among these algorithms, the General Linear Kalman Filter (GLKF) has proven to be the most accurate and reliable. Here we propose a regularized and smoothed GLKF (spsm-GLKF) with ℓ1 norm penalties based on lasso or group lasso and a fixedinterval smoother. We show that the group lasso penalty promotes sparse solutions by shrinking spurious connections to zero, while the smoothing increases the robustness of the estimates. Overall, our results demonstrate that spsm-GLKF outperforms the original GLKF, and represents a more accurate tool for the characterization of dynamical and sparse functional brain networks.

Assessing the performance of Granger-Geweke causality: Benchmark dataset and simulation framework.

Nonparametric methods based on spectral factorization offer well validated tools for estimating spectral measures of causality, called Granger-Geweke Causality (GGC). In Pagnotta et al. (2018) [1] we benchmarked nonparametric GGC methods using EEG data recorded during unilateral whisker stimulations in ten rats; here, we include detailed information about the benchmark dataset. In addition, we provide codes for estimating nonparametric GGC and a simulation framework to evaluate the effects on GGC analyses of potential problems, such as the common reference problem, signal-to-noise ratio (SNR) differences between channels, and the presence of additive noise. We focus on nonparametric methods here, but these issues also affect parametric methods, which can be tested in our framework as well. Our examples allow showing that time reversal testing for GGC (tr-GGC) mitigates the detrimental effects due to SNR imbalance and presence of mixed additive noise, and illustrate that, when using a common reference, tr-GGC unambiguously detects the causal influence׳s dominant spectral component, irrespective of the characteristics of the common reference signal. Finally, one of our simulations provides an example that nonparametric methods can overcome a pitfall associated with the implementation of conditional GGC in traditional parametric methods.

Benchmarking nonparametric Granger causality: Robustness against downsampling and influence of spectral decomposition parameters.

Brain function arises from networks of distributed brain areas whose directed interactions vary at subsecond time scales. To investigate such interactions, functional directed connectivity methods based on nonparametric spectral factorization are promising tools, because they can be straightforwardly extended to the nonstationary case using wavelet transforms or multitapers on sliding time window, and allow estimating time-varying spectral measures of Granger-Geweke causality (GGC) from multivariate data. Here we systematically assess the performance of various nonparametric GGC methods in real EEG data recorded over rat cortex during unilateral whisker stimulations, where somatosensory evoked potentials (SEPs) propagate over known areas at known latencies and therefore allow defining fixed criteria to measure the performance of time-varying directed connectivity measures. In doing so, we provide a comprehensive benchmark evaluation of the spectral decomposition parameters that might influence the performance of wavelet and multitaper approaches. Our results show that, under the majority of parameter settings, nonparametric methods can correctly identify the contralateral primary sensory cortex (cS1) as the principal driver of the cortical network. Furthermore, we observe that, when properly optimized, the approach based on Morlet wavelet provided the best detection of the preferential functional targets of cS1; while, the best temporal characterization of whisker-evoked interactions was obtained with a sliding-window multitaper. In addition, we find that nonparametric methods provide GGC estimates that are robust against signal downsampling. Taken together our results provide a range of plausible application values for the spectral decomposition parameters of nonparametric methods, and show that they are well suited to characterize time-varying directed causal influences between neural systems with good temporal resolution.

Time-varying MVAR algorithms for directed connectivity analysis: Critical comparison in simulations and benchmark EEG data.

Human brain function depends on directed interactions between multiple areas that evolve in the subsecond range. Time-varying multivariate autoregressive (tvMVAR) modeling has been proposed as a way to help quantify directed functional connectivity strengths with high temporal resolution. While several tvMVAR approaches are currently available, there is a lack of unbiased systematic comparative analyses of their performance and of their sensitivity to parameter choices. Here, we critically compare four recursive tvMVAR algorithms and assess their performance while systematically varying adaptation coefficients, model order, and signal sampling rate. We also compared two ways of exploiting repeated observations: single-trial modeling followed by averaging, and multi-trial modeling where one tvMVAR model is fitted across all trials. Results from numerical simulations and from benchmark EEG recordings showed that: i) across a broad range of model orders all algorithms correctly reproduced patterns of interactions; ii) signal downsampling degraded connectivity estimation accuracy for most algorithms, although in some cases downsampling was shown to reduce variability in the estimates by lowering the number of parameters in the model; iii) single-trial modeling followed by averaging showed optimal performance with larger adaptation coefficients than previously suggested, and showed slower adaptation speeds than multi-trial modeling. Overall, our findings identify strengths and weaknesses of existing tvMVAR approaches and provide practical recommendations for their application to modeling dynamic directed interactions from electrophysiological signals.

Gating by induced Α-Γ asynchrony in selective attention.

Visual selective attention operates through top-down mechanisms of signal enhancement and suppression, mediated by α-band oscillations. The effects of such top-down signals on local processing in primary visual cortex (V1) remain poorly understood. In this work, we characterize the interplay between large-scale interactions and local activity changes in V1 that orchestrates selective attention, using Granger-causality and phase-amplitude coupling (PAC) analysis of EEG source signals. The task required participants to either attend to or ignore oriented gratings. Results from time-varying, directed connectivity analysis revealed frequency-specific effects of attentional selection: bottom-up γ-band influences from visual areas increased rapidly in response to attended stimuli while distributed top-down α-band influences originated from parietal cortex in response to ignored stimuli. Importantly, the results revealed a critical interplay between top-down parietal signals and α-γ PAC in visual areas. Parietal α-band influences disrupted the α-γ coupling in visual cortex, which in turn reduced the amount of γ-band outflow from visual areas. Our results are a first demonstration of how directed interactions affect cross-frequency coupling in downstream areas depending on task demands. These findings suggest that parietal cortex realizes selective attention by disrupting cross-frequency coupling at target regions, which prevents them from propagating task-irrelevant information.