Effective Connectivity Network Research Articles

Author Correction: Early detection of dementia with default-mode network effective connectivity

Author Correction: Early detection of dementia with default-mode network effective connectivity

Improved brain effective connectivity modelling by dynamic Bayesian networks

Background:If brain effective connectivity network modelling (ECN) could be accurately achieved, early diagnosis of neurodegenerative diseases would be possible. It has been observed in the literature that Dynamic Bayesian Network (DBN) based methods are more successful than others. However, DBNs have not been applied easily and tested much due to computational complexity problems in structure learning. New method:This study introduces an advanced method for modelling brain ECNs using improved discrete DBN (Improved- dDBN) which addresses the computational challenges previously limiting DBN application, offering solutions that enable accurate and fast structure modelling. Results:The practical data and prior sizes needed for the convergence to the globally correct network structure are proved to be much smaller than the theoretical ones using simulated dDBN data. Besides, Hill Climbing is shown to converge to the true structure at a reasonable iteration step size when the appropriate data and prior sizes are used. Finally, importance of data quantization methods are analysed. Comparison with existing methods:The Improved-dDBN method performs better and robust, when compared to the existing methods for realistic scenarios such as varying graph complexity, various input conditions, noise cases and non-stationary connections. The data used in these tests is the simulated fMRI BOLD time series proposed in the literature. Conclusions:Improved-dDBN is a good candidate to be used on real datasets to accelerate developments in brain ECN modelling and neuroscience. Appropriate data and prior sizes can be identified based on the approach proposed in this study for global and fast convergence.

Early detection of dementia with default-mode network effective connectivity

Altered functional connectivity precedes structural brain changes and symptoms in dementia. Alzheimer’s disease is the largest contributor to dementia at the population level, and disrupts functional connectivity in the brain’s default-mode network (DMN). We investigated whether a neurobiological model of DMN effective connectivity could predict a future dementia diagnosis at the single-participant level. We applied spectral dynamic causal modeling to resting-state functional magnetic resonance imaging data in a nested case–control group from the UK Biobank, including 81 undiagnosed individuals who developed dementia up to nine years after imaging, and 1,030 matched controls. Dysconnectivity predicted both future dementia incidence (AUC = 0.82) and time to diagnosis (R = 0.53), outperforming models based on brain structure and functional connectivity. We also evaluated associations between DMN dysconnectivity and major risk factors for dementia, revealing strong relationships with polygenic risk for Alzheimer’s disease and social isolation. Neurobiological models of effective connectivity may facilitate early detection of dementia at population level, supporting rational deployment of targeted dementia-prevention strategies.

Event segmentation in ADHD: neglect of social information and deviant theta activity point to a mechanism underlying ADHD

BackgroundAttention-deficit/hyperactivity disorder (ADHD) is one of the most frequently diagnosed psychiatric conditions in children and adolescents. Although the symptoms appear to be well described, no coherent conceptual mechanistic framework integrates...

Exploring Brain Effective Connectivity Networks Through Spatiotemporal Graph Convolutional Models.

Learning brain effective connectivity networks (ECN) from functional magnetic resonance imaging (fMRI) data has gained much attention in recent years. With the successful applications of deep learning in numerous fields, several brain ECN learning methods based on deep learning have been reported in the literature. However, current methods ignore the deep temporal features of fMRI data and fail to fully employ the spatial topological relationship between brain regions. In this article, we propose a novel method for learning brain ECN based on spatiotemporal graph convolutional models (STGCM), named STGCMEC, in which we first adopt the temporal convolutional network to extract the deep temporal features of fMRI data and utilize the graph convolutional network to update the spatial features of each brain region by aggregating information from neighborhoods, which makes the features of brain regions more discriminative. Then, based on such features of brain regions, we design a joint loss function to guide STGCMEC to learn the brain ECN, which includes a task prediction loss and a graph regularization loss. The experimental results on a simulated dataset and a real Alzheimer's disease neuroimaging initiative (ADNI) dataset show that the proposed STGCMEC is able to better learn brain ECN compared with some state-of-the-art methods.

Motor network dynamic resting state fMRI connectivity of neurotypical children in regions affected by cerebral palsy.

Normative childhood motor network resting-state fMRI effective connectivity is undefined, yet necessary for translatable dynamic resting-state-network-informed evaluation in pediatric cerebral palsy. Cross-spectral dynamic causal modeling of resting-state-fMRI was investigated in 50 neurotypically developing 5- to 13-year-old children. Fully connected six-node network models per hemisphere included primary motor cortex, striatum, subthalamic nucleus, globus pallidus internus, thalamus, and contralateral cerebellum. Parametric Empirical Bayes with exhaustive Bayesian model reduction and Bayesian modeling averaging informed the model; Purdue Pegboard Test scores of hand motor behavior were the covariate at the group level to determine the effective-connectivity-functional behavior relationship. Although both hemispheres exhibited similar effective connectivity of motor cortico-basal ganglia-cerebellar networks, magnitudes were slightly greater on the right, except for left-sided connections of the striatum which were more numerous and of opposite polarity. Inter-nodal motor network effective connectivity remained consistent and robust across subjects. Age had a greater impact on connections to the contralateral cerebellum, bilaterally. Motor behavior, however, affected different connections in each hemisphere, exerting a more prominent effect on the left modulatory connections to the subthalamic nucleus, contralateral cerebellum, primary motor cortex, and thalamus. This study revealed a consistent pattern of directed resting-state effective connectivity in healthy children aged 5-13 years within the motor network, encompassing cortical, subcortical, and cerebellar regions, correlated with motor skill proficiency. Both hemispheres exhibited similar effective connectivity within motor cortico-basal ganglia-cerebellar networks reflecting inter-nodal signal direction predicted by other modalities, mainly differing from task-dependent studies due to network differences at rest. Notably, age-related changes were more pronounced in connections to the contralateral cerebellum. Conversely, motor behavior distinctly impacted connections in each hemisphere, emphasizing its role in modulating left sided connections to the subthalamic nucleus, contralateral cerebellum, primary motor cortex, and thalamus. Motor network effective connectivity was correlated with motor behavior, validating its physiological significance. This study is the first to evaluate a normative effective connectivity model for the pediatric motor network using resting-state functional MRI correlating with behavior and serves as a foundation for identifying abnormal findings and optimizing targeted interventions like deep brain stimulation, potentially influencing future therapeutic approaches for children with movement disorders.

The increased effective connectivity from left middle occipital gyrus to right medial septum/diagonal bands in AD patients after donepezil intervention.

Donepezil enhances the function of cholinergic nerves by increasing the concentration of acetylcholine, thereby improving clinical symptoms in patients with Alzheimer's disease (AD). However, the neural mechanisms of how donepezil modulates the effective connectivity (EC) network of cholinergic system in AD patients remain unknown. We speculated that the effective network of the cholinergic system changes in AD patients after donepezil intervention. We employed resting-state functional magnetic resonance imaging and Granger causality analysis approach to explore changes in the effective connectivity network of the basal forebrain in AD patients before and after donepezil intervention. This study included 32 participants, including 16 healthy controls (HCs) and 16 AD patients. In a 3T MRI scanner, the 16 AD patients were scanned before and after the donepezil intervention. To compare EC differences between the three groups of participants, ANOVA and post-hoc t-tests analysis were employed. Compared to baseline status, AD patients after donepezil intervention had an increased EC from left middle occipital gyrus to right medial septum/diagonal bands. Compared to HCs, AD patients after donepezil intervention had an increased EC from right inferior frontal gyrus/orbit part to right medial septum/diagonal bands, AD patients before donepezil intervention had a reduced EC from right precuneus to right medial septum/diagonal bands. A significant positive correlation was found between EC values in right precuneus and Mini-Mental State Examination in pre-intervention AD patients (r = 0.7338, p = 0.0012). Our study showed that effective connectivity of brain regions associated with the default mode network in the cholinergic pathway was enhanced after donepezil intervention. The results of this study will help us to better understand the neural mechanisms of donepezil intervention in AD and to find clinical targets for intervention.

MetaRLEC: Meta-Reinforcement Learning for Discovery of Brain Effective Connectivity

In recent years, the discovery of brain effective connectivity (EC) networks through computational analysis of functional magnetic resonance imaging (fMRI) data has gained prominence in neuroscience and neuroimaging. However, owing to the influence of diverse factors during data collection and processing, fMRI data typically exhibits high noise and limited sample characteristics, consequently leading to suboptimal performance of current methods. In this paper, we propose a novel brain effective connectivity discovery method based on meta-reinforcement learning, called MetaRLEC. The method mainly consists of three modules: actor, critic, and meta-critic. MetaRLEC first employs an encoder-decoder framework: the encoder utilizing a Transformer, converts noisy fMRI data into a state embedding; the decoder employing bidirectional LSTM, discovers brain region dependencies from the state and generates actions (EC networks). Then a critic network evaluates these actions, incentivizing the actor to learn higher-reward actions amidst the high-noise setting. Finally, a meta-critic framework facilitates online learning of historical state-action pairs, integrating an action-value neural network and supplementary training losses to enhance the model's adaptability to small-sample fMRI data. We conduct comprehensive experiments on both simulated and real-world data to demonstrate the efficacy of our proposed method.

A biophysically constrained brain connectivity model based on stimulation-evoked potentials.

BackgroundSingle-pulse electrical stimulation (SPES) is an established technique used to map functional effective connectivity networks in treatment-refractory epilepsy patients undergoing intracranial-electroencephalography monitoring. While the connectivity path between stimulation and recording sites has been explored through the integration of structural connectivity, there are substantial gaps, such that new modeling approaches may advance our understanding of connectivity derived from SPES studies. New methodUsing intracranial electrophysiology data recorded from a single patient undergoing stereo-electroencephalography (sEEG) evaluation, we employ an automated detection method to identify early response components, C1, from pulse-evoked potentials (PEPs) induced by SPES. C1 components were utilized for a novel topology optimization method, modeling 3D electrical conductivity to infer neural pathways from stimulation sites. Additionally, PEP features were compared with tractography metrics, and model results were analyzed with respect to anatomical features. ResultsThe proposed optimization model resolved conductivity paths with low error. Specific electrode contacts displaying high error correlated with anatomical complexities. The C1 component strongly correlated with additional PEP features and displayed stable, weak correlations with tractography measures. Comparison with existing methodExisting methods for estimating neural signal pathways are imaging-based and thus rely on anatomical inferences. ConclusionsThese results demonstrate that informing topology optimization methods with human intracranial SPES data is a feasible method for generating 3D conductivity maps linking electrical pathways with functional neural ensembles. PEP-estimated effective connectivity is correlated with but distinguished from structural connectivity. Modeled conductivity resolves connectivity pathways in the absence of anatomical priors.

Reduced default mode network effective connectivity in healthy aging is modulated by years of education

Aging is a major risk factor for neurodegenerative diseases like dementia and Alzheimer's disease. Even in non-pathological aging, decline in cognitive functioning is observed in the majority of the elderly population, necessitating the importance of studying the processes involved in healthy aging in order to identify brain biomarkers that promote the conservation of functioning. The default mode network (DMN) has been of special interest to aging research due to its vulnerability to atrophy and functional decline over the course of aging. Prior work has focused almost exclusively on functional (i.e. undirected) connectivity, yet converging findings are scarce. Therefore, we set out to use spectral dynamic causal modeling to investigate changes in the effective (i.e. directed) connectivity within the DMN and to discover changes in information flow in a sample of cognitively normal adults spanning from 48 to 89 years (n = 63). Age was associated to reduced verbal memory performance. Modeling of effective connectivity revealed a pattern of age-related downregulation of posterior DMN regions driven by inhibitory connections from the hippocampus and middle temporal gyrus. Additionally, there was an observed decline in the hippocampus’ susceptibility to network inputs with age, effectively disconnecting itself from other regions. The estimated effective connectivity parameters were robust and able to predict the age in out of sample estimates in a leave-one-out cross-validation. Attained education moderated the effects of aging, largely reversing the observed pattern of inhibitory connectivity. Thus, medial prefrontal cortex, hippocampus and posterior DMN regions formed an excitatory cycle of extrinsic connections related to the interaction of age and education. This suggests a compensatory role of years of education in effective connectivity, stressing a possible target for interventions. Our findings suggest a connection to the concept of cognitive reserve, which attributes a protective effect of educational level on cognitive decline in aging (Stern, 2009).

MetaCAE: Causal autoencoder with meta-knowledge transfer for brain effective connectivity estimation

Using machine learning methods to estimate brain effective connectivity networks from functional magnetic resonance imaging (fMRI) data has gradually become one of the hot subjects in the fields of neuroscience. In particular, the encoder–decoder based methods can effectively extract the connections in fMRI time series, which have achieved promising performance. However, these methods generally use Granger causality model, which may identify false directions due to the non-stationary characteristic of fMRI data. Additionally, fMRI datasets have limited sample sizes, which significantly constrains the development of these methods. In this paper, we propose a novel brain effective connectivity estimation method based on causal autoencoder with meta-knowledge transfer, called MetaCAE. The proposed approach employs a causal autoencoder (CAE) to extract causal dependencies from non-stationary fMRI time series, and leverages meta-knowledge transfer to improve the estimation accuracy on small-sample data. More specifically, MetaCAE first employs a temporal convolutional encoder to extract non-stationary temporal information from fMRI time series. Then it uses a structural equation model-based decoder to decode causal relationships between brain regions. Finally, it utilizes a model-agnostic meta-learning method to learn the meta-knowledge of the shared brain effective connectivity among different subjects, and transfers the meta-knowledge to the CAE to enhance its estimation ability on small-sample fMRI data. Comprehensive experiments on both simulated and real-world data demonstrate the efficacy of MetaCAE in estimating brain effective connectivity.

Creativity Stimulation by Idea Generation: A Resting-state fMRI Study on Effective Connectivity

Studies on creativity have bloomed in the past decade. However, little is known about the effective connectivity (EC) between default-mode network (DMN) regions after creativity stimulation. This study aimed to measure the brain connectivity induced by creativity stimulation and to relate it with creativity score. A total of 50 participants were recruited and assigned to control and experimental groups. The experimental participants underwent a two-day creativity stimulation session. Resting state functional magnetic resonance imaging (rs-fMRI) scans were performed on all participants after the session. The rs-fMRI data were analysed using statistical parametric mapping and spectral dynamic causal modelling. A fully connected model comprising angular gyrus (AG), medial pre-frontal cortex (mPFC) and pre-cuneus (PCU) as regions-of-interest (ROIs) was fitted for every participant’s data. The model underwent Bayesian parameter averaging to determine the average strength of connection between ROIs. There was a significant increase in creativity score for the experimental group in the aspect of fluency (p=0.018) and flexibility (p=0.048) except in originality (p>0.05). No difference in brain activation was observed between groups. All the EC between ROIs in the left and right hemisphere for both groups were significant (P>0.9). Symmetrical EC networks for the experimental group were observed with left hemisphere PCU→PCU, PCU→mPFC and AG→PCU connections which were more significant in the experimental group. These findings suggested that creativity stimulation as short as two days was able to evoke changes in creativity score and network connectivity but insufficient to cause convincing differences in the brain activation.

Large-scale effective connectivity analysis reveals the existence of two mutual inhibitory systems in patients with major depression

It is posited that cognitive and affective dysfunction in patients with major depression disorder (MDD) may be caused by dysfunctional signal propagation in the brain. By leveraging dynamic causal modeling, we investigated large-scale directed signal propagation (effective connectivity) among distributed large-scale brain networks with 43 MDD patients and 56 healthy controls. The results revealed the existence of two mutual inhibitory systems: the anterior default mode network, auditory network, sensorimotor network, salience network and visual networks formed an “emotional” brain, while the posterior default mode network, central executive networks, cerebellum and dorsal attention network formed a “rational brain”. These two networks exhibited excitatory intra-system connectivity and inhibitory inter-system connectivity. Patients were characterized by potentiated intra-system connections within the “emotional/sensory brain”, as well as over-inhibition of the “rational brain” by the “emotional/sensory brain”. The hierarchical architecture of the large-scale effective connectivity networks was then analyzed using a PageRank algorithm which revealed a shift of the controlling role of the “rational brain” to the “emotional/sensory brain” in the patients. These findings inform basic organization of distributed large-scale brain networks and furnish a better characterization of the neural mechanisms of depression, which may facilitate effective treatment.

An amygdala-centered effective connectivity networkin trait anxiety.

Previous studies have established that the amygdala plays an important role in trait anxiety. However, there remains limited knowledge regarding the changes in amygdala-centered effective connectivity network associated with this trait. The current study employed the Granger Causal analysis to investigate the directional connectivity patterns involving the amygdala in relation to trait anxiety in a large cohort of young adults (N = 424). The results revealed a negative association between trait anxiety scores and the Granger causality from the left middle frontal gyrus and right superior frontal gyrus to the right amygdala. Conversely, higher trait anxiety levels were found to be associated with increased effective connectivity from the left amygdala to the left hippocampus. These results demonstrated the significance of the prefrontal cortex-amygdala-hippocampus neural circuitry in the neurobiological mechanisms underlying trait anxiety. Our findings advance the comprehension of this characteristic, holding promise for informing strategies in the prevention and treatment of related mental disorders.

Longitudinal assessment of the effects of passive training on stroke rehabilitation using fNIRS technology

For patients with severe conditions such as stroke, passive exercise is commonly used in the early stages of their rehabilitation training. This study aimed to assess the effect of passive training on stroke rehabilitation and track brain function changes and the patient's rehabilitation progress, by employing a robot glove to perform a passive flexion-extension task. Specifically, functional near-infrared spectroscopy data from 26 patients under resting and right-hand passive interactions (task state) were recorded before and after a one-week interval, respectively, to explore the variations in the brain network of the patients. The results showed a stronger functional connectivity in both states of the two experiments in the left and right homotopic brain regions (p < 0.01). The effective connectivity network between brain regions maintained a consistent trend during the same test. Changes in functional connectivity and effective connectivity networks may represent the advantages of motor rehabilitation tasks and patient treatment duration, providing a perspective for an easy understanding of the mechanisms of stroke-related brain changes. This study demonstrates the feasibility of passive training strategies in the field of intelligent rehabilitation by applying neuroscientific diagnostic methods based on physiological data to the field of human-computer interaction.

Graph Analysis of TMS-EEG Connectivity Reveals Hemispheric Differences following Occipital Stimulation.

(1) Background: Transcranial magnetic stimulation combined with electroencephalography (TMS-EEG) provides a unique opportunity to investigate brain connectivity. However, possible hemispheric asymmetries in signal propagation dynamics following occipital TMS have not been investigated. (2) Methods: Eighteen healthy participants underwent occipital single-pulse TMS at two different EEG sites, corresponding to early visual areas. We used a state-of-the-art Bayesian estimation approach to accurately estimate TMS-evoked potentials (TEPs) from EEG data, which has not been previously used in this context. To capture the rapid dynamics of information flow patterns, we implemented a self-tuning optimized Kalman (STOK) filter in conjunction with the information partial directed coherence (iPDC) measure, enabling us to derive time-varying connectivity matrices. Subsequently, graph analysis was conducted to assess key network properties, providing insight into the overall network organization of the brain network. (3) Results: Our findings revealed distinct lateralized effects on effective brain connectivity and graph networks after TMS stimulation, with left stimulation facilitating enhanced communication between contralateral frontal regions and right stimulation promoting increased intra-hemispheric ipsilateral connectivity, as evidenced by statistical test (p < 0.001). (4) Conclusions: The identified hemispheric differences in terms of connectivity provide novel insights into brain networks involved in visual information processing, revealing the hemispheric specificity of neural responses to occipital stimulation.

Discovering a change point and piecewise linear structure in a time series of organoid networks via the iso-mirror

Recent advancements have been made in the development of cell-based in-vitro neuronal networks, or organoids. In order to better understand the network structure of these organoids, a super-selective algorithm has been proposed for inferring the effective connectivity networks from multi-electrode array data. In this paper, we apply a novel statistical method called spectral mirror estimation to the time series of inferred effective connectivity organoid networks. This method produces a one-dimensional iso-mirror representation of the dynamics of the time series of the networks which exhibits a piecewise linear structure. A classical change point algorithm is then applied to this representation, which successfully detects a change point coinciding with the neuroscientifically significant time inhibitory neurons start appearing and the percentage of astrocytes increases dramatically. This finding demonstrates the potential utility of applying the iso-mirror dynamic structure discovery method to inferred effective connectivity time series of organoid networks.

Schizophrenia MEG Network Analysis Based on Kernel Granger Causality.

Network analysis is an important approach to explore complex brain structures under different pathological and physiological conditions. In this paper, we employ the multivariate inhomogeneous polynomial kernel Granger causality (MKGC) to construct directed weighted networks to characterize schizophrenia magnetoencephalography (MEG). We first generate data based on coupled autoregressive processes to test the effectiveness of MKGC in comparison with the bivariate linear Granger causality and bivariate inhomogeneous polynomial kernel Granger causality. The test results suggest that MKGC outperforms the other two methods. Based on these results, we apply MKGC to construct effective connectivity networks of MEG for patients with schizophrenia (SCZs). We measure three network features, i.e., strength, nonequilibrium, and complexity, to characterize schizophrenia MEG. Our results suggest that MEG of the healthy controls (HCs) has a denser effective connectivity network than that of SCZs. The most significant difference in the in-connectivity strength is observed in the right frontal network (p=0.001). The strongest out-connectivity strength for all subjects occurs in the temporal area, with the most significant between-group difference in the left occipital area (p=0.0018). The total connectivity strength of the frontal, temporal, and occipital areas of HCs exhibits higher values compared with SCZs. The nonequilibrium feature over the whole brain of SCZs is significantly higher than that of the HCs (p=0.012); however, the results of Shannon entropy suggest that healthy MEG networks have higher complexity than schizophrenia networks. Overall, MKGC provides a reliable approach to construct MEG brain networks and characterize the network characteristics.

Characterizing heterogeneity in early adolescent reward networks and individualized associations with behavioral and clinical outcomes.

Associations between connectivity networks and behavioral outcomes such as depression are typically examined by comparing average networks between known groups. However, neural heterogeneity within groups may limit the ability to make inferences at the individual level as qualitatively distinct processes across individuals may be obscured in group averages. This study characterizes the heterogeneity of effective connectivity reward networks among 103 early adolescents and examines associations between individualized features and multiple behavioral and clinical outcomes. To characterize network heterogeneity, we used extended unified structural equation modeling to identify effective connectivity networks for each individual and an aggregate network. We found that an aggregate reward network was a poor representation of individuals, with most individual-level networks sharing less than 50% of the group-level network paths. We then used Group Iterative Multiple Model Estimation to identify a group-level network, subgroups of individuals with similar networks, and individual-level networks. We identified three subgroups that appear to reflect differences in network maturity, but this solution had modest validity. Finally, we found numerous associations between individual-specific connectivity features and behavioral reward functioning and risk for substance use disorders. We suggest that accounting for heterogeneity is necessary to use connectivity networks for inferences precise to the individual.

Amortization Transformer for Brain Effective Connectivity Estimation from fMRI Data.

Using machine learning methods to estimate brain effective connectivity networks from functional magnetic resonance imaging (fMRI) data has garnered significant attention in the fields of neuroinformatics and bioinformatics. However, existing methods usually require retraining the model for each subject, which ignores the knowledge shared across subjects. In this paper, we propose a novel framework for estimating effective connectivity based on an amortization transformer, named AT-EC. In detail, AT-EC first employs an amortization transformer to model the dynamics of fMRI time series and infer brain effective connectivity across different subjects, which can train an amortized model that leverages the shared knowledge from different subjects. Then, an assisted learning mechanism based on functional connectivity is designed to assist the estimation of the brain effective connectivity network. Experimental results on both simulated and real-world data demonstrate the efficacy of our method.