Effective Connectivity Methods Research Articles

Cortex level connectivity between ACT-R modules during EEG-based n-back task

AbstractFinding the synchronization between Electroencephalography (EEG) and human cognition is an essential aspect of cognitive neuroscience. Adaptive Control of Thought-Rational (ACT-R) is a widely used cognitive architecture that defines the cognitive and perceptual operations of the human mind. This study combines the ACT-R and EEG-based cortex-level connectivity to highlight the relationship between ACT-R modules during the EEG-based n-back task (for validating working memory performance). Initially, the source localization method is performed on the EEG signal, and the mapping between ACT-R modules and corresponding brain scouts (on the cortex surface) is performed. Once the brain scouts are identified for ACT-R modules, then those scouts are called ACT-R scouts. The linear (Granger Causality: GC) and non-linear effective connectivity (Multivariate Transfer Entropy: MTE) methods are applied over the scouts’ time series data. From the GC and MTE analysis, for all n-back tasks, information flow is observed from the visual-to-imaginal ACT-R scout for storing the visual stimuli (i.e., input letter) in short-term memory. For 2 and 3-back tasks, causal flow exists from imaginal to retrieval ACT-R scout and vice-versa. Causal flow from procedural to the imaginal ACT-R scout is also observed for all workload levels to execute the set of productions. Identifying the relationship among ACT-R modules through scout-level connectivity in the cortical surface facilitates the effects of human cognition in terms of brain dynamics.

Visual Mental Imagery and Neural Dynamics of Sensory Substitution in the Blindfolded Subjects

Although one can recognize the environment by soundscape substituting vision to auditory signal, whether subjects could perceive the soundscape as visual or visual-like sensation has been questioned. In this study, we investigated hierarchical process to elucidate the recruitment mechanism of visual areas by soundscape stimuli in blindfolded subjects. Twenty-two healthy subjects were repeatedly trained to recognize soundscape stimuli converted by visual shape information of letters. An effective connectivity method called dynamic causal modeling (DCM) was employed to reveal how the brain was hierarchically organized to recognize soundscape stimuli. The visual mental imagery model generated cortical source signals of five regions of interest better than auditory bottom-up, cross-modal perception, and mixed models. Spectral couplings between brain areas in the visual mental imagery model were analyzed. While within-frequency coupling is apparent in bottom-up processing where sensory information is transmitted, cross-frequency coupling is prominent in top-down processing, corresponding to the expectation and interpretation of information. Sensory substitution in the brain of blindfolded subjects derived visual mental imagery by combining bottom-up and top-down processing.

The effective connectivity analysis of fMRI based on asymmetric detection of transfer brain entropy.

It is important to explore causal relationships in functional magnetic resonance imaging study. However, the traditional effective connectivity analysis method is easy to produce false causality, and the detection accuracy needs to be improved. In this paper, we introduce a novel functional magnetic resonance imaging effective connectivity method based on the asymmetry detection of transfer entropy, which quantifies the disparity in predictive information between forward and backward time, subsequently normalizing this disparity to establish a more precise criterion for detecting causal relationships while concurrently reducing computational complexity. Then, we evaluate the effectiveness of this method on the simulated data with different level of nonlinearity, and the results demonstrated that the proposed method outperforms others methods on the detection of both linear and nonlinear causal relationships, including Granger Causality, Partial Granger Causality, Kernel Granger Causality, Copula Granger Causality, and traditional transfer entropy. Furthermore, we applied it to study the effective connectivity of brain functional activities in seafarers. The results showed that there are significantly different causal relationships between different brain regions in seafarers compared with non-seafarers, such as Temporal lobe related to sound and auditory information processing, Hippocampus related to spatial navigation, Precuneus related to emotion processing as well as Supp_Motor_Area associated with motor control and coordination, which reflects the occupational specificity of brain function of seafarers.

Effective Connectivity Estimation by a Hybrid Neural Network, Empirical Wavelet Transform, and Bayesian Optimization.

Accurately measuring nonlinear effective connectivity is a crucial step in investigating brain functions. Brain signals like EEG is nonstationary. Many effective connectivity methods have been proposed but they have drawbacks in their models such as a weakness in proposing a way for hyperparameter and time lag selection as well as dealing with non-stationarity of the time series. This paper proposes an effective connectivity model based on a hybrid neural network model which uses Empirical Wavelet Transform (EWT) and a long short-term memory network (LSTM). The best hyperparameters and time lag are selected using Bayesian Optimization (BO). Due to the importance of generalizability in neural networks and calculating GC, an algorithm was proposed to choose the best generalizable weights. The model was evaluated using simulated and real EEG data consisting of attention deficit hyperactivity disorder (ADHD) and healthy subjects. The proposed model's performance on simulated data was evaluated by comparing it with other neural networks, including LSTM, CNN-LSTM, GRU, RNN, and MLP, using a Blocked cross-validation approach. GC of the simulated data was compared with GRU, linear Granger causality (LGC), Kernel Granger Causality (KGC), Partial Directed Coherence (PDC), and Directed Transfer Function (DTF). Our results demonstrated that the proposed model was superior to the mentioned models. Another advantage of our model is robustness against noise. The results showed that the proposed model can identify the connections in noisy conditions. The comparison of the effective connectivity of ADHD and the healthy group showed that the results are in accordance with previous studies.

Brain Network Evaluation by Functional-Guided Effective Connectivity Reinforcement Learning Method Indicates Therapeutic Effect for Tinnitus.

Using functional connectivity (FC) or effective connectivity (EC) alone cannot effectively delineate brain networks based on functional magnetic resonance imaging (fMRI) data, limiting the understanding of the mechanism of tinnitus and its treatment. Investigating brain FC is a foundational step in exploring EC. This study proposed a functionally guided EC (FGEC) method based on reinforcement learning (FGECRL) to enhance the precision of identifying EC between distinct brain regions. An actor-critic framework with an encoder-decoder model was adopted as the actor network. The encoder utilizes a transformer model; the decoder employs a bidirectional long short-term memory network with attention. An FGEC network was constructed for the enrolled participants per fMRI scan, including 65 patients with tinnitus and 28 control participants healthy at the enrollment time. After 6 months of sound therapy for tinnitus and prospective follow-up, fMRI data were acquired again and retrospectively categorized into an effective group (EG) and an ineffective group (IG) according to the treatment effect. Compared with FC and EC, the FGECRL method demonstrated better accuracy in discriminating between different groups, highlighting the advantage of FGECRL in identifying brain network features. For the FGEC network of the EG and IG per state (before and after treatment) and healthy controls, effective therapy is characterized by a similar pattern of FGEC network between patients with tinnitus after treatment and healthy controls. Deactivated information output in the motor network, somatosensory network, and medioventral occipital cortex may biologically indicate effective treatment. The maintenance of decreased EC in the primary auditory cortex may represent a failure of sound therapy, further supporting the Bayesian inference theory for tinnitus perception. The FGEC network can provide direct evidence for the mechanism of sound therapy in patients with tinnitus with distinct outcomes.

Introduction to Effective Connectivity and Analysis Methods: Psychophysiological Interaction and Dynamic Causal Modeling

Introduction to Effective Connectivity and Analysis Methods: Psychophysiological Interaction and Dynamic Causal Modeling

Time-Lagged Multidimensional Pattern Connectivity (TL-MDPC): An EEG/MEG pattern transformation based functional connectivity metric

Functional and effective connectivity methods are essential to study the complex information flow in brain networks underlying human cognition. Only recently have connectivity methods begun to emerge that make use of the full multidimensional information contained in patterns of brain activation, rather than unidimensional summary measures of these patterns. To date, these methods have mostly been applied to fMRI data, and no method allows vertex-to-vertex transformations with the temporal specificity of EEG/MEG data. Here, we introduce time-lagged multidimensional pattern connectivity (TL-MDPC) as a novel bivariate functional connectivity metric for EEG/MEG research. TL-MDPC estimates the vertex-to-vertex transformations among multiple brain regions and across different latency ranges. It determines how well patterns in ROI X at time point tx can linearly predict patterns of ROI Y at time point ty. In the present study, we use simulations to demonstrate TL-MDPC's increased sensitivity to multidimensional effects compared to a unidimensional approach across realistic choices of number of trials and signal-to-noise ratios. We applied TL-MDPC, as well as its unidimensional counterpart, to an existing dataset varying the depth of semantic processing of visually presented words by contrasting a semantic decision and a lexical decision task. TL-MDPC detected significant effects beginning very early on, and showed stronger task modulations than the unidimensional approach, suggesting that it is capable of capturing more information. With TL-MDPC only, we observed rich connectivity between core semantic representation (left and right anterior temporal lobes) and semantic control (inferior frontal gyrus and posterior temporal cortex) areas with greater semantic demands. TL-MDPC is a promising approach to identify multidimensional connectivity patterns, typically missed by unidimensional approaches.

A Comparative Study on Prominent Connectivity Features for Emotion Recognition From EEG

Classifying distinct human emotions, the fundamental purpose of brain-computer interface research, is essential for providing instant personalized services and assistance to individuals. With such emerging applications for individuals, several techniques have been proposed recently to explore interactions between brain regions, such as correlation, synchronization, and dependence. Notably, functional and effective connectivity methods are applied to assess the relationships between different brain areas. The primary objective of this study is to compare the frequently used functional and effective connectivity methods to recognize emotion using Electroencephalogram (EEG) signals. This paper uses a benchmark emotional EEG dataset consisting of 32 channels of EEG signals collected from 32 subjects while they were watching 40 inspirational music videos. Specifically, correlation, phase synchronization, and mutual information are used to measure functional brain connectivity, and transfer entropy is used to acquire effective brain connectivity. After extracting the features, they are represented in a two-dimensional connectivity feature map (CFM). The CFMs are then used to classify emotions by a convolutional neural network model. The results of classified emotions are analyzed regarding compatible EEG bands, accuracy, and time. Notably, the Gamma band is found as the most compatible band. The comparative study has demonstrated that though the connectivity method named Pearson correlation coefficient requires less time, the normalized mutual information is the most accurate method with advantageous detecting capability of nonlinear dependencies.

Reconfiguration of static and dynamic thalamo-cortical network functional connectivity of epileptic children with generalized tonic-clonic seizures.

ObjectiveA number of studies in adults and children with generalized tonic-clonic seizure (GTCS) have reported the alterations in morphometry, functional activity, and functional connectivity (FC) in the thalamus. However, the neural mechanisms underlying the alterations in the thalamus of patients with GTCS are not well understood, particularly in children. The aim of the current study was to explore the temporal properties of functional pathways connecting thalamus in children with GTCS.MethodsHere, we recruited 24 children with GTCS and 36 age-matched healthy controls. Static and dynamic FC approaches were used to evaluate alterations in the temporal variability of thalamo-cortical networks in children with GTCS. The dynamic effective connectivity (dEC) method was also used to evaluate the directions of the fluctuations in effective connectivity. In addition, the relationships between the dynamic properties and clinical features were assessed.ResultsThe static FC analysis presented significantly decreased connectivity patterns between the bilateral thalamus and between the thalamus and right inferior temporal gyrus. The dynamic connectivity analysis found decreased FC variability in the thalamo-cortical network of children with epilepsy. Dynamic EC analyses identified increased connectivity variability from the frontal gyrus to the bilateral thalamus, and decreased connectivity variability from the right thalamus to the left thalamus and from the right thalamus to the right superior parietal lobe. In addition, correlation analysis revealed that both static FC and connectivity temporal variability in the thalamo-cortical network related to the clinical features (epilepsy duration and epilepsy onset time).SignificanceOur findings of both increased and decreased connectivity variability in the thalamo-cortical network imply a dynamic restructuring of the functional pathways connecting the thalamus in children with GTCS. These alterations in static and temporal dynamic pathways connecting the bilateral thalamus may extend our understanding of the neural mechanisms underlying the GTCS in children.

Neural Correlates of Mental Workload During Multitasking: a Dynamic Causal Modeling Study

The goal of this study is to examine the neural correlates of different mental workload levels. Electroencephalogram (EEG) signals were recorded when participants perform a set of tasks simultaneously with low and high levels of mental workload. Brain connections for each workload level were estimated using Dynamic Causal Modeling (DCM), which is an effective connectivity method to reveal causal relationships between brain sources. The result showed a backward-only, left-lateralized connection pattern for high workload condition, compared to the bidirectional, two-sided connection pattern for low workload condition.These findings of the mental workload effect on neural mechanisms may be utilized in applications of the augmented cognition program.

Acute aerobic exercise enhances cortical connectivity between structures involved in shaping mood and improves self-reported mood: An EEG effective-connectivity study in young male adults

There seems to be a general consensus among researchers that acute aerobic exercise (exercise hereafter) improves mood, but the neural mechanisms which drive these effects are far from being clear. The current study investigated the cortical connectivity patterns that underlie changes in mood after exercise. Twenty male adults underwent three different experimental protocols that were carefully controlled in terms of underlying metabolism and were administered in a randomized order: moderate-intensity continuous exercise, high-intensity interval exercise, and seated rest condition. Before and after each experimental protocol, we collected data on the participants' mood using the UMACL questionnaire and recorded their resting-state EEG. We focused on the effective connectivity patterns exerted by the dorso-lateral prefrontal cortex (dlPFC) over the temporal region (TMP), as these are important cortical structures involved in shaping mood. The cortical connectivity patterns in the resting-state EEG were evaluated using the directed transfer function (DTF), which is an autoregressive effective connectivity method. The results showed that both moderate-intensity exercise and high-intensity interval exercise improved participants' self-reported mood. Crucially, this improvement was accompanied by stronger influences of dlPFC over TMP. The observed changes in the effective connectivity patterns between dlPFC and TMP might help to better understand the effects of exercise on mood.

Does Chronic Cannabis Use Impact Risky Decision-Making: An Examination of fMRI Activation and Effective Connectivity?

With the increase in use of cannabis and its shifting legal status in the United States, cannabis use has become an important research focus. While studies of other drug populations have shown marked increases in risky decision-making, the literature on cannabis users is not as clear. The current study examined the performance of 17 cannabis users and 14 non-users on the Balloon Analog Risk Task (BART) using behavioral, fMRI and effective connectivity methods. Significant attenuation was found in a functional pathway projecting from the dorsal anterior cingulate cortex (dACC) to the nucleus accumbens (NAc) in cannabis users compared to non-using controls as well as decreases in risk-taking behaviors. These findings suggest that cannabis users may process and evaluate risks and rewards differently than non-users.

Measuring the Non-linear Directed Information Flow in Schizophrenia by Multivariate Transfer Entropy.

People living with schizophrenia (SCZ) experience severe brain network deterioration. The brain is constantly fizzling with non-linear causal activities measured by electroencephalogram (EEG) and despite the variety of effective connectivity methods, only few approaches can quantify the direct non-linear causal interactions. To circumvent this problem, we are motivated to quantitatively measure the effective connectivity by multivariate transfer entropy (MTE) which has been demonstrated to be able to capture both linear and non-linear causal relationships effectively. In this work, we propose to construct the EEG effective network by MTE and further compare its performance with the Granger causal analysis (GCA) and Bivariate transfer entropy (BVTE). The simulation results quantitatively show that MTE outperformed GCA and BVTE under varied signal-to-noise conditions, edges recovered, sensitivity, and specificity. Moreover, its applications to the P300 task EEG of healthy controls (HC) and SCZ patients further clearly show the deteriorated network interactions of SCZ, compared to that of the HC. The MTE provides a novel tool to potentially deepen our knowledge of the brain network deterioration of the SCZ.

A new computational approach to estimate whole-brain effective connectivity from functional and structural MRI, applied to language development

Recently introduced effective connectivity methods allow for the in-vivo investigation of large-scale functional interactions between brain regions. However, dynamic causal modeling, the most widely used technique to date, typically captures only a few predefined regions of interest. In this study, we present an alternative computational approach to infer effective connectivity within the entire connectome and show its performance on a developmental cohort with emerging language capacities. The novel approach provides new opportunities to quantify effective connectivity changes in the human brain.

Brain functional connectivity changes in long-term mental stress

Long-term psychological stress can highly influence brain structure and functions. However, there are only a few studies using electroencephalogram (EEG) that have examined this fact. The current study demonstrates a brain-computer interface (BCI) to classify EEG correlates of long-term mental stress in various mental states. The study was performed on 26 healthy right-handed university students and the examination period was considered as a long-term mental stressor. Two groups of subjects were selected based on their stress levels evaluated by the perceived stress scale (PSS-14). The subjects' EEG data were collected during eyes-open resting state and while they exposed to positive and negative emotional stimuli scored by self-assessment manikin questionnaire (SAM). Several types of features were extracted from EEG data including power spectrum density (PSD), laterality index (LI), correlation coefficient (CC), Canonical correlation analysis (CCA), magnitude square coherence estimation (MSCE), mutual information (MI), phase-slope index (PSI), Granger causality (GC) and directed transfer function (DTF). Subsequently, the extracted features were discriminated using several types of classifiers including knearest neighbor (KNN), support vector machine (SVM) and naive Bayesian (NB) classifiers. The proposed BCI was validated by one leave out method and investigation was done in different time windows using low and high-frequency resolutions, 7 and 36 frequency bands respectively. The results showed that the proposed system can accurately recognize the subjects' stress level in various mental states. Moreover, the MI as a functional and DTF as effective connectivity methods yield the highest classification accuracy compared to other feature extraction methods.

A Functional Data Method for Causal Dynamic Network Modeling of Task-Related fMRI.

Functional MRI (fMRI) is a popular approach to investigate brain connections and activations when human subjects perform tasks. Because fMRI measures the indirect and convoluted signals of brain activities at a lower temporal resolution, complex differential equation modeling methods (e.g., Dynamic Causal Modeling) are usually employed to infer the neuronal processes and to fit the resulting fMRI signals. However, this modeling strategy is computationally expensive and remains to be mostly a confirmatory or hypothesis-driven approach. One major statistical challenge here is to infer, in a data-driven fashion, the underlying differential equation models from fMRI data. In this paper, we propose a causal dynamic network (CDN) method to estimate brain activations and connections simultaneously. Our method links the observed fMRI data with the latent neuronal states modeled by an ordinary differential equation (ODE) model. Using the basis function expansion approach in functional data analysis, we develop an optimization-based criterion that combines data-fitting errors and ODE fitting errors. We also develop and implement a block coordinate-descent algorithm to compute the ODE parameters efficiently. We illustrate the numerical advantages of our approach using data from realistic simulations and two task-related fMRI experiments. Compared with various effective connectivity methods, our method achieves higher estimation accuracy while improving the computational speed by from tens to thousands of times. Though our method is developed for task-related fMRI, we also demonstrate the potential applicability of our method (with a simple modification) to resting-state fMRI, by analyzing both simulated and real data from medium-sized networks.

Perspectives on How Human Simultaneous Multi-Modal Imaging Adds Directionality to Spread Models of Alzheimer's Disease.

Previous animal research suggests that the spread of pathological agents in Alzheimer’s disease (AD) follows the direction of signaling pathways. Specifically, tau pathology has been suggested to propagate in an infection-like mode along axons, from transentorhinal cortices to medial temporal lobe cortices and consequently to other cortical regions, while amyloid-beta (Aβ) pathology seems to spread in an activity-dependent manner among and from isocortical regions into limbic and then subcortical regions. These directed connectivity-based spread models, however, have not been tested directly in AD patients due to the lack of an in vivo method to identify directed connectivity in humans. Recently, a new method—metabolic connectivity mapping (MCM)—has been developed and validated in healthy participants that uses simultaneous FDG-PET and resting-state fMRI data acquisition to identify directed intrinsic effective connectivity (EC). To this end, postsynaptic energy consumption (FDG-PET) is used to identify regions with afferent input from other functionally connected brain regions (resting-state fMRI). Here, we discuss how this multi-modal imaging approach allows quantitative, whole-brain mapping of signaling direction in AD patients, thereby pointing out some of the advantages it offers compared to other EC methods (i.e., Granger causality, dynamic causal modeling, Bayesian networks). Most importantly, MCM provides the basis on which models of pathology spread, derived from animal studies, can be tested in AD patients. In particular, future work should investigate whether tau and Aβ in humans propagate along the trajectories of directed connectivity in order to advance our understanding of the neuropathological mechanisms causing disease progression.

Dynamics of the human brain network revealed by time-frequency effective connectivity in fNIRS.

Functional near infrared spectroscopy (fNIRS) is a promising neuroimaging method for investigating networks of cortical regions over time. We propose a directed effective connectivity method (TPDC) allowing the capture of both time and frequency evolution of the brain's networks using fNIRS data acquired from healthy subjects performing a continuous finger-tapping task. Using this method we show the directed connectivity patterns among cortical motor regions involved in the task and their significant variations in the strength of information flow exchanges. Intra and inter-hemispheric connections during the motor task with their temporal evolution are also provided. Characterisation of the fluctuations in brain connectivity opens up a new way to assess the organisation of the brain to adapt to changing task constraints, or under pathological conditions.

Abnormal neural activities of directional brain networks in patients with long-term bilateral hearing loss.

The objective of the study is to provide some implications for rehabilitation of hearing impairment by investigating changes of neural activities of directional brain networks in patients with long-term bilateral hearing loss. Firstly, we implemented neuropsychological tests of 21 subjects (11 patients with long-term bilateral hearing loss, and 10 subjects with normal hearing), and these tests revealed significant differences between the deaf group and the controls. Then we constructed the individual specific virtual brain based on functional magnetic resonance data of participants by utilizing effective connectivity and multivariate regression methods. We exerted the stimulating signal to the primary auditory cortices of the virtual brain and observed the brain region activations. We found that patients with long-term bilateral hearing loss presented weaker brain region activations in the auditory and language networks, but enhanced neural activities in the default mode network as compared with normally hearing subjects. Especially, the right cerebral hemisphere presented more changes than the left. Additionally, weaker neural activities in the primary auditor cortices were also strongly associated with poorer cognitive performance. Finally, causal analysis revealed several interactional circuits among activated brain regions, and these interregional causal interactions implied that abnormal neural activities of the directional brain networks in the deaf patients impacted cognitive function.

Altered neural mechanisms of cognitive control in patients with primary progressive multiple sclerosis: An effective connectivity study.

Primary progressive multiple sclerosis (PPMS) leads to physical and cognitive disability. Specifically, cognitive deficits in PPMS have been explained by both grey matter atrophy and white matter lesions. However, existing research still lacks in the understanding of how the brain of a patient with PPMS functions under cognitive control demands. Thus, the aim of the current study was to examine information integration in patients with PPMS using a search-based effective connectivity method. Fourteen patients with PPMS and 22 age- and gender-matched healthy controls (HC) performed the Stroop task, a cognitively demanding interference task that taxes neural resources required for cognitive control and response inhibition. Results showed that compared to HC, PPMS patients exhibited poor behavioral performance and alterations in information flow, manifested in the form of the loss of top-down connections, reversal of connections, and hyperconnectivity. Significant correlations were observed between connection strengths and behavioral measures. The connection between the posterior parietal cortex (PCC) and left posterior parietal lobule, which was present in both groups, showed a negative correlation with performance accuracy on incongruent trials. The connection between the left dorsolateral prefrontal cortex and PCC showed a positive correlation with performance accuracy on incongruent trials. However, the adaptive nature of this connection was not significant on a behavioral level as the PPMS group performed significantly worse compared to the HC group during the Stroop task. Thus, the current study provides important evidence about effective connectivity patterns that can be characterized as maladaptive cerebral re-organization in the PPMS brain. Hum Brain Mapp 38:2580-2588, 2017. © 2017 Wiley Periodicals, Inc.