Time-varying Effective Connectivity Research Articles

Characteristic changes in the EEG signals between microsleeps and preceding responsive states.

This work aims at identifying characteristic features of EEG to demarcate a microsleep from preceding responsive states. The EEG signals, after reference electrode standardization technique (REST) re-referencing, were processed through a time-varying general linear Kalman filter (TVGLKF) to derive time-varying auto-regressive (TVAR) parameters. The time-varying effective connectivity measure of orthogonal partial directed coherence (OPDC) was obtained for every instant at 256 Hz. Effective connectivity matrices formed using these OPDC measures, with the scalp electrodes as nodes were processed further using graph theory. Community-based measures were investigated and statistical significances compared. Non-parametric Wilcoxon signed rank test was used for significance analysis, with Cohen-type and Common Language effect size (CLES) as measures of effect sizes. The results showed a decrease in directional modularity from anterior to posterior, in theta, alpha, and beta bands in microsleeps. The alpha band showed the highest significance with a Cohen-type effect size of 1.25 and a median percentage difference of 23% across subjects, with a range of 13-28%. Flexibility and integration also decreased with average percentage of 25% (17-35%) and 20% (16-32%), respectively, while recruitment increased on an average of 11% (3-16%), wherever significant across all bands. These community-based measures can help characterize and explain changes in brain mechanisms, and can also serve as potential biomarkers for microsleep detection.

Transient seizure onset network for localization of epileptogenic zone: effective connectivity and graph theory-based analyses of ECoG data in temporal lobe epilepsy.

Abnormal and dynamic epileptogenic networks cause difficulties for clinical epileptologists in the localization of the seizure onset zone (SOZ) and the epileptogenic zone (EZ) in preoperative assessments of patients with refractory epilepsy. The aim of this study is to investigate the characteristics of time-varying effective connectivity networks in various non-seizure and seizure periods, and to propose a quantitative approach for accurate localization of SOZ and EZ. We used electrocorticogram recordings in the temporal lobe and hippocampus from seven patients with temporal lobe epilepsy to characterize the effective connectivity dynamics at a high temporal resolution using the full-frequency adaptive directed transfer function (ffADTF) measure and five graph metrics, i.e., the out-degree (OD), closeness centrality (CC), betweenness centrality (BC), clustering coefficient (C), and local efficiency (LE). The ffADTF effective connectivity network was calculated and described in five frequency bands (δ, θ, α, β, and γ) and five seizure periods (pre-seizure, early seizure, mid-seizure, late seizure, and post-seizure). The cortical areas with high values of graph metrics in the transient seizure onset network were compared with the SOZ and EZ identified by clinical epileptologists and the results of epilepsy resection surgeries. Origination and propagation of epileptic activity were observed in the high time resolution ffADTF effective connectivity network throughout the entire seizure period. The seizure-specific transient seizure onset ffADTF network that emerged at seizure onset time remained for approximately 20-50ms with strong connections generated from both SOZ and EZ. The values of graph metrics in the SOZ and EZ were significantly larger than that in the other cortical areas. More cortical areas with the highest mean of graph metrics were the same as the clinically determined SOZ in the low-frequency δ and θ bands and in Engel Class I patients than in higher frequency α, β, and γ bands and in Engel Class II and III patients. The OD and C were more likely to localize the SOZ and EZ than CC, BC, and LE in the transient seizure onset network. The high temporal resolution ffADTF effective connectivity analysis combined with the graph theoretical analysis helps us to understand how epileptic activity is generated and propagated during the seizure period. The newly discovered seizure-specific transient seizure onset network could be an important biomarker and a promising tool for more precise localization of the SOZ and EZ in preoperative evaluations.

Estimating EEG Source Dipole Orientation Based on Singular-value Decomposition for Connectivity Analysis.

In the last decade, the use of high-density electrode arrays for EEG recordings combined with the improvements of source reconstruction algorithms has allowed the investigation of brain networks dynamics at a sub-second scale. One powerful tool for investigating large-scale functional brain networks with EEG is time-varying effective connectivity applied to source signals obtained from electric source imaging. Due to computational and interpretation limitations, the brain is usually parcelled into a limited number of regions of interests (ROIs) before computing EEG connectivity. One specific need and still open problem is how to represent the time- and frequency-content carried by hundreds of dipoles with diverging orientation in each ROI with one unique representative time-series. The main aim of this paper is to provide a method to compute a signal that explains most of the variability of the data contained in each ROI before computing, for instance, time-varying connectivity. As the representative time-series for a ROI, we propose to use the first singular vector computed by a singular-value decomposition of all dipoles belonging to the same ROI. We applied this method to two real datasets (visual evoked potentials and epileptic spikes) and evaluated the time-course and the frequency content of the obtained signals. For each ROI, both the time-course and the frequency content of the proposed method reflected the expected time-course and the scalp-EEG frequency content, representing most of the variability of the sources (~ 80%) and improving connectivity results in comparison to other procedures used so far. We also confirm these results in a simulated dataset with a known ground truth.

Studying the effective brain connectivity using multiregression dynamic models

The Multiregression Dynamic Model (MDM) is a multivariate graphical model for a multidimensional time series that allows the estimation of time-varying effective connectivity. An MDM is a state space model where connection weights reflect the contemporaneous interactions between brain regions. Because the marginal likelihood has a closed form, model selection across a large number of potential connectivity networks is easy to perform. With application of the Integer Programming Algorithm, we can quickly find optimal models that satisfy acyclic graph constraints and, due to a factorisation of the marginal likelihood, the search over all possible directed (acyclic or cyclic) graphical structures is even faster. These methods are illustrated using recent resting-state and steady-state task fMRI data.

Identifying disease foci from static and dynamic effective connectivity networks: Illustration in soldiers with trauma

Brain connectivity studies report group differences in pairwise connection strengths. While informative, such results are difficult to interpret since our understanding of the brain relies on region-based properties, rather than on connection information. Given that large disruptions in the brain are often caused by a few pivotal sources, we propose a novel framework to identify the sources of functional disruption from effective connectivity networks. Our approach integrates static and time-varying effective connectivity modeling in a probabilistic framework, to identify aberrant foci and the corresponding aberrant connectomics network. Using resting-state fMRI, we illustrate the utility of this novel approach in U.S. Army soldiers (N = 87) with posttraumatic stress disorder (PTSD), mild traumatic brain injury (mTBI) and combat controls. Additionally, we employed machine-learning classification to identify those significant connectivity features that possessed high predictive ability. We identified three disrupted foci (middle frontal gyrus [MFG], insula, hippocampus), and an aberrant prefrontal-subcortical-parietal network of information flow. We found the MFG to be the pivotal focus of network disruption, with aberrant strength and temporal-variability of effective connectivity to the insula, amygdala and hippocampus. These connectivities also possessed high predictive ability (giving a classification accuracy of 81%); and they exhibited significant associations with symptom severity and neurocognitive functioning. In summary, dysregulation originating in the MFG caused elevated and temporally less-variable connectivity in subcortical regions, followed by a similar effect on parietal memory-related regions. This mechanism likely contributes to the reduced control over traumatic memories leading to re-experiencing, hyperarousal and flashbacks observed in soldiers with PTSD and mTBI. Hum Brain Mapp 39:264-287, 2018. © 2017 Wiley Periodicals, Inc.

Estimation of effective connectivity using multi-layer perceptron artificial neural network.

Studies on interactions between brain regions estimate effective connectivity, (usually) based on the causality inferences made on the basis of temporal precedence. In this study, the causal relationship is modeled by a multi-layer perceptron feed-forward artificial neural network, because of the ANN's ability to generate appropriate input-output mapping and to learn from training examples without the need of detailed knowledge of the underlying system. At any time instant, the past samples of data are placed in the network input, and the subsequent values are predicted at its output. To estimate the strength of interactions, the measure of "Causality coefficient" is defined based on the network structure, the connecting weights and the parameters of hidden layer activation function. Simulation analysis demonstrates that the method, called "CREANN" (Causal Relationship Estimation by Artificial Neural Network), can estimate time-invariant and time-varying effective connectivity in terms of MVAR coefficients. The method shows robustness with respect to noise level of data. Furthermore, the estimations are not significantly influenced by the model order (considered time-lag), and the different initial conditions (initial random weights and parameters of the network). CREANN is also applied to EEG data collected during a memory recognition task. The results implicate that it can show changes in the information flow between brain regions, involving in the episodic memory retrieval process. These convincing results emphasize that CREANN can be used as an appropriate method to estimate the causal relationship among brain signals.

Time-varying dynamic Bayesian network model and its application to brain connectivity using electrocorticograph

Cortical networks for speech production are believed to be widely distributed and highly organized over temporal, parietal, and frontal lobes areas in the human brain cortex. Effective connectivity demonstrates an inherent element of directional information propagation, and is therefore an information dense measure for the relevant activity over different cortical regions. Connectivity analysis of electrocorticographic (ECoG) recordings has been widely studied for its excellent signal-to-noise ratio as well as high temporal and spatial resolutions, providing an important approach to human electrophysiological researches. In this paper, we evaluate two patients undergoing invasive monitoring for seizure localization, in which both micro-electrode and standard clinical electrodes are used for ECoG recordings from speech-related cortical areas during syllable reading test. In order to explore the dynamics of speech processing, we extract the high gamma frequency band (70-110 Hz) power from ECoG signals by the multi-taper method. The trial-averaged results show that there is a consistent task-related increase in high gamma response for micro-ECoG electrodes for patient 1 and standard-ECoG electrodes for both patients 1 and 2. We demonstrate that high gamma response provides reliable speech localization compared with electrocortical stimulation. In addition, a directed connectivity network is built in single trial involving both standard ECoG electrodes and micro-ECoG arrays using time-varying dynamic Bayesian networks (TV-DBN). The TV-DBN is used to model the time-varying effective connectivity between pairs of ECoG electrodes selected by high gamma power, with less parameter optimization required and higher computational simplicity than short-time direct directed transfer function. We observe task-related connectivity modulations of connectivity between large-scale cortical networks (standard ECoG) and local cortical networks (micro-ECoG), as well as between large-scale and local cortical networks. In addition, cortical connectivity is modulated differently before and after response articulation onset. In other words, electrodes located over sensorimotor cortex show higher connectivity before articulation onset, while connectivity appears gradually between sensorimotor and auditory cortex after articulation onset. Also, the connectivity patterns observed during articulation are significantly different for three different places of articulation for the consonants. This study offers insights into preoperative evaluation during epilepsy surgery, dynamic real-time brain connectivity visualization, and assistance to understand the dynamic processing of language pronunciation in the language cortex.

Time-varying effective connectivity of the cortical neuroelectric activity associated with behavioural microsleeps

An episode of complete failure to respond during an attentive task accompanied by behavioural signs of sleep is called a behavioural microsleep. We proposed a combination of high-resolution EEG and an advanced method for time-varying effective connectivity estimation for reconstructing the temporal evolution of the causal relations between cortical regions when microsleeps occur during a continuous visuomotor task. We found connectivity patterns involving left–right frontal, left–right parietal, and left-frontal/right-parietal connections commencing in the interval [−500; −250] ms prior to the onset of microsleeps and disappearing at the end of the microsleeps. Our results from global graph indices derived from effective connectivity analysis have revealed EEG-based biomarkers of all stages of microsleeps (preceding, onset, pre-recovery, recovery). In particular, this raises the possibility of being able to predict microsleeps in real-world tasks and initiate a ‘wake-up’ intervention to avert the microsleeps and, hence, prevent injurious and even multi-fatality accidents.

Time-varying effective connectivity during visual object naming as a function of semantic demands.

Accumulating evidence suggests that visual object understanding involves a rapid feedforward sweep, after which subsequent recurrent interactions are necessary. The extent to which recurrence plays a critical role in object processing remains to be determined. Recent studies have demonstrated that recurrent processing is modulated by increasing semantic demands. Differentially from previous studies, we used dynamic causal modeling to model neural activity recorded with magnetoencephalography while 14 healthy humans named two sets of visual objects that differed in the degree of semantic accessing demands, operationalized in terms of the values of basic psycholinguistic variables associated with the presented objects (age of acquisition, frequency, and familiarity). This approach allowed us to estimate the directionality of the causal interactions among brain regions and their associated connectivity strengths. Furthermore, to understand the dynamic nature of connectivity (i.e., the chronnectome; Calhoun et al., 2014) we explored the time-dependent changes of effective connectivity during a period (200-400 ms) where adding semantic-feature information improves modeling and classifying visual objects, at 50 ms increments. First, we observed a graded involvement of backward connections, that became active beyond 200 ms. Second, we found that semantic demands caused a suppressive effect in the backward connection from inferior frontal cortex (IFC) to occipitotemporal cortex over time. These results complement those from previous studies underscoring the role of IFC as a common source of top-down modulation, which drives recurrent interactions with more posterior regions during visual object recognition. Crucially, our study revealed the inhibitory modulation of this interaction in situations that place greater demands on the conceptual system.

3. Dynamic effective connectivity of epileptic networks determined with high density EEG source analysis

Analyzing the dynamic behaviour of epileptic networks could help to better understand the way pathologic neural activity propagates, and leads to spikes, seizures, and their electro-clinical and cognitive manifestations, with implications for epilepsy surgery candidates. In 6 patients with temporal lobe epilepsy we studied effective connectivity of large-scale cortical networks at high temporal resolution around interictal spikes, recorded with high density (256 channels) EEG. The cortical electric source activity was obtained for 90 cortical regions of interest (ROI) using a distributed inverse solution. Multivariate, time-varying (millisecond resolution), and frequency-resolved (1–50 Hz) Granger causality analysis (Partial Directed Coherence) was applied to the source signal for all ROIs. In all patients subsequent intracranial recording or surgical resection was used for validation. Information flow occurred predominantly in the theta and beta bands. The key driving structures where located in the anterior and medial temporal regions, with peak information transfer before the spike maximum. We found fast-varying connectivity patterns between the antero-medial and lateral temporal lobe and basal frontal lobe, but also transient transfer towards the contralateral temporal lobe. In two patients with a multifocal irritative zone, we found evidence of connectivity from the main anterior temporal driver towards the secondary spike focus remote from the epileptogenic zone. EEG-based time-varying effective connectivity of epileptic spikes provides a clear characterization of the epileptic networks that is concordant with invasive electro-clinical findings. This could have major clinical implications for tailoring resective, disconnective, and functional surgery.

A time-varying source connectivity approach to reveal human somatosensory information processing

Exploration of neural sources and their effective connectivity based on transient changes in electrophysiological activities to external stimuli is important for understanding brain mechanisms of sensory information processing. However, such cortical mechanisms have not yet been well characterized in electrophysiological studies since (1) it is difficult to estimate the stimulus-activated neural sources and their activities and (2) it is difficult to identify transient effective connectivity between neural sources in the order of milliseconds. To address these issues, we developed a time-varying source connectivity approach to effectively capture fast-changing information flows between neural sources from high-density Electroencephalography (EEG) recordings. This time-varying source connectivity approach was applied to somatosensory evoked potentials (SEPs), which were elicited by electrical stimulation of right hand and recorded using 64 channels from 16 subjects, to reveal human somatosensory information processing. First, SEP sources and their activities were estimated, both at single-subject and group level, using equivalent current dipolar source modeling. Then, the functional integration among SEP sources was explored using a Kalman smoother based time-varying effective connectivity inference method. The results showed that SEPs were mainly generated from the contralateral primary somatosensory cortex (SI), bilateral secondary somatosensory cortex (SII), and cingulate cortex (CC). Importantly, we observed a serial processing of somatosensory information in human somatosensory cortices (from SI to SII) at earlier latencies (<150 ms) and a reciprocal processing between SII and CC at later latencies (>200 ms).

Causality in the association between P300 and alpha event-related desynchronization.

Recent findings indicated that both P300 and alpha event-related desynchronization (α-ERD) were associated, and similarly involved in cognitive brain functioning, e.g., attention allocation and memory updating. However, an explicit causal influence between the neural generators of P300 and α-ERD has not yet been investigated. In the present study, using an oddball task paradigm, we assessed the task effect (target vs. non-target) on P300 and α-ERD elicited by stimuli of four sensory modalities, i.e., audition, vision, somatosensory, and pain, estimated their respective neural generators, and investigated the information flow among their neural generators using time-varying effective connectivity in the target condition. Across sensory modalities, the scalp topographies of P300 and α-ERD were similar and respectively maximal at parietal and occipital regions in the target condition. Source analysis revealed that P300 and α-ERD were mainly generated from posterior cingulate cortex and occipital lobe respectively. As revealed by time-varying effective connectivity, the cortical information was consistently flowed from α-ERD sources to P300 sources in the target condition for all four sensory modalities. All these findings showed that P300 in the target condition is modulated by the changes of α-ERD, which would be useful to explore neural mechanism of cognitive information processing in the human brain.

Energy-based stochastic control of neural mass models suggests time-varying effective connectivity in the resting state

Several studies posit energy as a constraint on the coding and processing of information in the brain due to the high cost of resting and evoked cortical activity. This suggestion has been addressed theoretically with models of a single neuron and two coupled neurons. Neural mass models (NMMs) address mean-field based modeling of the activity and interactions between populations of neurons rather than a few neurons. NMMs have been widely employed for studying the generation of EEG rhythms, and more recently as frameworks for integrated models of neurophysiology and functional MRI (fMRI) responses. To date, the consequences of energy constraints on the activity and interactions of ensembles of neurons have not been addressed. Here we aim to study the impact of constraining energy consumption during the resting-state on NMM parameters. To this end, we first linearized the model, then used stochastic control theory by introducing a quadratic cost function, which transforms the NMM into a stochastic linear quadratic regulator (LQR). Solving the LQR problem introduces a regime in which the NMM parameters, specifically the effective connectivities between neuronal populations, must vary with time. This is in contrast to current NMMs, which assume a constant parameter set for a given condition or task. We further simulated energy-constrained stochastic control of a specific NMM, the Wilson and Cowan model of two coupled neuronal populations, one of which is excitatory and the other inhibitory. These simulations demonstrate that with varying weights of the energy-cost function, the NMM parameters show different time-varying behavior. We conclude that constraining NMMs according to energy consumption may create more realistic models. We further propose to employ linear NMMs with time-varying parameters as an alternative to traditional nonlinear NMMs with constant parameters.