Resting state functional MRI (rs-fMRI) is a widespread and powerful tool for investigating functional connectivity and brain disorders. However, functional connectivity analysis can be seriously affected by random and structured noise from non-neural sources such as physiology. Thus, it is essential to first reduce thermal noise and then correctly identify and remove non-neural artefacts from rs-fMRI signals through optimized data processing methods. However, existing tools that correct for these effects have been developed for human brain and are not readily transposable to rat data. Therefore, the aim of the present study was to establish a data processing pipeline that can robustly remove random and structured noise from rat rs-fMRI data. It includes a novel denoising approach based on the Marchenko-Pastur Principle Component Analysis (MP-PCA) method, FMRIB's ICA-based Xnoiseifier (FIX) for automatic artefact classification and cleaning, and global signal regression. Our results show that: I) MP-PCA denoising substantially improves the temporal signal-to-noise ratio; II) the pre-trained FIX classifier achieves a high accuracy in artefact classification; III) both artefact cleaning and global signal regression are essential steps in minimizing the within-group variability in control animals and identifying functional connectivity changes in a rat model of sporadic Alzheimer's disease, as compared to controls.
Analysis and quantification of brain structural changes, using Magnetic resonance imaging (MRI), are increasingly used to define novel biomarkers of brain pathologies, such as Alzheimer's disease (AD). Network-based models of the brain have shown that both local and global topological properties can reveal patterns of disease propagation. On the other hand, intra-subject descriptions cannot exploit the whole information context, accessible through inter-subject comparisons. To address this, we developed a novel approach, which models brain structural connectivity atrophy with a multiplex netwo…
Anatomical and functional brain studies have converged to the hypothesis that Autism Spectrum Disorders (ASD) are associated with atypical connectivity. Using a modified resting-state paradigm to drive subjects' attention, we provide evidence of a very marked interaction between ASD brain functional connectivity and cognitive state. We show that functional connectivity changes in opposite ways in ASD and typicals as attention shifts from external world towards one's body generated information. Furthermore, ASD subject alter more markedly than typicals their connectivity across cognitive states…
Human learning is a complex process in which future behavior is altered via the reorganization of brain activity and connectivity. It remains unknown whether activity and connectivity differentially reorganize during learning, and, if so, how that differential reorganization tracks stages of learning across distinct brain areas. Here, we address this gap in knowledge by measuring brain activity and functional connectivity in a longitudinal fMRI experiment in which healthy adult human participants learn the values of novel objects over the course of four days. An increasing similarity in activi…
The analysis of brain connectivity aims to understand the emergence of functional networks into the brain. This information can be used in the process of electroencephalographic (EEG) signal analysis and classification for a braincomputer interface (BCI). These systems provide an alternative channel of communication and control to people with motor impairments. In this article, four strategies for using the brain connectivity in a BCI environment as a tool to obtain a deeper understanding of the cerebral mechanisms are proposed, with the principal aim of developing a scheme oriented to neuro-r…
In this paper, we present a novel and versatile method to study the dynamics of resting-state fMRI brain connectivity with a high temporal sensitivity. Whereas most existing methods often rely on dividing the time-series into larger segments of data (i.e. so called sliding window techniques), the point-based method (PBM) proposed here provides an estimate of brain connectivity at the level of individual sampled time-points. The achieved increase in temporal sensitivity, together with temporal graph network theory allowed us to study functional integration between, as well as within, resting-st…
The anatomical structure of the brain can be observed via non-invasive techniques such as diffusion imaging. However, these are imperfect because they miss connections that are actually known to exist, especially long range inter-hemispheric ones. In this paper we formulate the inverse problem of inferring the structural connectivity of brain networks from experimentally observed functional connectivity via functional Magnetic Resonance Imaging (fMRI), by formulating it as a convex optimization problem. We show that structural connectivity can be modeled as an optimal sparse representation der…
A theoretical framework describing the set of interactions between neurons in the brain, or functional connectivity, should include dynamical functions representing the propagation of signal from one neuron to another. Green's functions and response functions are natural candidates for this but, while they are conceptually very useful, they are usually defined only for linear time-translationally invariant systems. The brain, instead, behaves nonlinearly and in a time-dependent way. Here, we use nonequilibrium Green's functions to describe the time-dependent functional connectivity of a contin…
Exploring the human brain networks during rest is a topic of great interest. Several structural and functional studies have previously been conducted to study the intrinsic brain networks. In this paper, we focus on investigating the human brain network topology using dense Electroencephalography (EEG) source connectivity approach. We applied graph theoretical methods on functional networks reconstructed from resting state data acquired using EEG in 14 healthy subjects. Our findings confirmed the existence of sets of brain regions considered as functional hubs. In particular, the isthmus cingu…
In cognitive network neuroscience, the connectivity and community structure of the brain network is related to cognition. Much of this research has focused on two measures of connectivity - modularity and flexibility - which frequently have been examined in isolation. By using resting state fMRI data from 52 young adults, we investigate the relationship between modularity, flexibility and performance on cognitive tasks. We show that flexibility and modularity are highly negatively correlated. However, we also demonstrate that flexibility and modularity make unique contributions to explain task…
In this paper we utilized the concept of stable phase synchronization topography - synchrostates - over the scalp derived from EEG recording for formulating brain connectivity network in Autism Spectrum Disorder (ASD) and typically-growing children. A synchronization index is adapted for forming the edges of the connectivity graph capturing the stability of each of the synchrostates. Such network is formed for 11 ASD and 12 control group children. Comparative analyses of these networks using graph theoretic measures show that children with autism have a different modularity of such networks fr…
Neurofeedback is a non-invasive brain training with long-term medical and non-medical applications. Despite the existence of several emotion regulation studies using neurofeedback, further investigation is needed to understand interactions of the brain regions involved in the process. We implemented EEG neurofeedback with simultaneous fMRI using a modified happiness-inducing task through autobiographical memories to upregulate positive emotion. The results showed increased activity of prefrontal, occipital, parietal, and limbic regions and increased functional connectivity between prefrontal, …
A formula for an average connectivity between cortical areas in mammals is derived. Based on comparative neuroanatomical data, it is found, surprisingly, that this connectivity is either only weakly dependent or independent of brain size. It is discussed how this formula can be used to estimate the average length of axons in white matter. Other allometric relations, such as cortical patches and area sizes vs. brain size, are also provided. Finally, some functional implications, with an emphasis on efficient cortical computation, are discussed as well.
Cognitive states are involving in our daily life, which motivates us to explore them and understand them by a vast variety of perspectives. Among these perspectives, brain connectivity is increasingly receiving attention in recent years. It is the right time to summarize the past achievements, serving as a cornerstone for the upcoming progress in the field. In this chapter, the definition of the cognitive state is first given and the cognitive states that are frequently investigated are then outlined. The introduction of the methods for estimating connectivity strength and graph theoretical me…
Functional brain network has been widely studied to understand the relationship between brain organization and behavior. In this paper, we aim to explore the functional connectivity of brain network under a \emph{multi-step} cognitive task involving with consecutive behaviors, and further understand the effect of behaviors on the brain organization. The functional brain networks are constructed base on a high spatial and temporal resolution fMRI dataset and analyzed via complex network based approach. We find that at voxel level the functional brain network shows robust small-worldness and sca…
Neuroimaging-driven prediction of brain age, defined as the predicted biological age of a subject using only brain imaging data, is an exciting avenue of research. In this work we seek to build models of brain age based on functional connectivity while prioritizing model interpretability and understanding. This way, the models serve to both provide accurate estimates of brain age as well as allow us to investigate changes in functional connectivity which occur during the ageing process. The methods proposed in this work consist of a two-step procedure: first, linear latent variable models, suc…
Understanding brain connectivity in a network-theoretic context has shown much promise in recent years. This type of analysis identifies brain organisational principles, bringing a new perspective to neuroscience. At the same time, large public databases of connectomic data are now available. However, connectome analysis is still an emerging field and there is a crucial need for robust computational methods to fully unravelits potential. This workshop provides a platform to discuss the development of new analytic techniques; methods for evaluating and validating commonly used approaches; as we…
Already two decades passed since the first applications of graph theory to brain neuroimaging. Since that early description, the characterization of the brain as a very large interacting complex network has evolved in several directions. In this brief review we discuss our contributions to this topic and discuss some perspective for future work.
Understanding the human brain remains the Holy Grail in biomedical science, and arguably in all of the sciences. Our brains represent the most complex systems in the world (and some contend the universe) comprising nearly one hundred billion neurons with septillions of possible connections between them. The structure of these connections engenders an efficient hierarchical system capable of consciousness, as well as complex thoughts, feelings, and behaviors. Brain connectivity and network analyses have exploded over the last decade due to their potential in helping us understand both normal an…
Spontaneous brain activity, as observed in functional neuroimaging, has been shown to display reproducible structure that expresses brain architecture and carries markers of brain pathologies. An important view of modern neuroscience is that such large-scale structure of coherent activity reflects modularity properties of brain connectivity graphs. However, to date, there has been no demonstration that the limited and noisy data available in spontaneous activity observations could be used to learn full-brain probabilistic models that generalize to new data. Learning such models entails two mai…
Objective: The coupling between neuronal populations and its magnitude have been shown to be informative for various clinical applications. One method to estimate brain connectivity is with electroencephalography (EEG) from which the cross-spectrum between different sensor locations is derived. We wish to test the efficacy of tensor factorisation in the estimation of brain connectivity. Methods: Complex tensor factorisation based on PARAFAC2 is used to decompose the EEG into scalp components described by the spatial, spectral, and complex trial profiles. An EEG model in the complex domain was …
The human brain is a large-scale network which function depends on dynamic interactions between spatially-distributed regions. In the rapidly-evolving field of network neuroscience, two yet unresolved challenges are potential breakthroughs. First, functional brain networks should be estimated from noninvasive and easy to use neuroimaging techniques. Second, the time/space resolution of these techniques should be high enough to assess the dynamics of identified networks. Emerging evidence suggests that Electroencephalography (EEG) source connectivity method may offer solutions to both issues pr…
Brain network provides important insights for the diagnosis of many brain disorders, and how to effectively model the brain structure has become one of the core issues in the domain of brain imaging analysis. Recently, various computational methods have been proposed to estimate the causal relationship (i.e., effective connectivity) between brain regions. Compared with traditional correlation-based methods, effective connectivity can provide the direction of information flow, which may provide additional information for the diagnosis of brain diseases. However, existing methods either ignore t…
The estimation of sparse hierarchical components reflecting patterns of the brain's functional connectivity from rsfMRI data can contribute to our understanding of the brain's functional organization, and can lead to biomarkers of diseases. However, inter-scanner variations and other confounding factors pose a challenge to the robust and reproducible estimation of functionally-interpretable brain networks, and especially to reproducible biomarkers. Moreover, the brain is believed to be organized hierarchically, and hence single-scale decompositions miss this hierarchy. The paper aims to use cu…
Background: Recent studies have indicated that functional connectivity is dynamic even during rest. A common approach to modeling the dynamic functional connectivity in whole-brain resting-state fMRI is to compute the correlation between anatomical regions via sliding time windows. However, the direct use of the sample correlation matrices is not reliable due to the image acquisition and processing noises in resting-sate fMRI. New method: To overcome these limitations, we propose a new statistical model that smooths out the noise by exploiting the geometric structure of correlation matrices. T…
A variety of resting state neuroimaging data tend to exhibit fractal behavior where its power spectrum follows power-law scaling. Resting state functional connectivity is significantly influenced by fractal behavior which may not directly originate from neuronal population activities of the brain. To describe the fractal behavior, we adopted the fractionally integrated process (FIP) model instead of the fractional Gaussian noise (FGN) since the FIP model covers more general aspects of fractality than the FGN model. We also introduce a novel concept called the nonfractal connectivity which is d…
Today, the human brain can be studied as a whole. Electroencephalography, magnetoencephalography, or functional magnetic resonance imaging techniques provide functional connectivity patterns between different brain areas, and during different pathological and cognitive neuro-dynamical states. In this Tutorial we review novel complex networks approaches to unveil how brain networks can efficiently manage local processing and global integration for the transfer of information, while being at the same time capable of adapting to satisfy changing neural demands.
Human brain anatomy and function display a combination of modular and hierarchical organization, suggesting the importance of both cohesive structures and variable resolutions in the facilitation of healthy cognitive processes. However, tools to simultaneously probe these features of brain architecture require further development. We propose and apply a set of methods to extract cohesive structures in network representations of brain connectivity using multi-resolution techniques. We employ a combination of soft thresholding, windowed thresholding, and resolution in community detection, that e…
Inferring brain connectivity network and quantifying the significance of interactions between brain regions are of paramount importance in neuroscience. Although there have recently emerged some tests for graph inference based on independent samples, there is no readily available solution to test the change of brain network for paired and correlated samples. In this article, we develop a paired test of matrix graphs to infer brain connectivity network when the groups of samples are correlated. The proposed test statistic is both bias corrected and variance corrected, and achieves a small estim…
Functional connectivity of cognitive tasks allows researchers to analyse the interaction mapping occurring between different regions of the brain using electroencephalography (EEG) signals. Standard practice in functional connectivity involve studying the electrode pair interactions across several trials. As the cognitive task always involves the human factor, it is inevitable to have lower quality data from the brain signals influenced by the subject concentration or other mental states which can occur anytime over the whole experimental trials. The connectivity among electrodes are heavily i…
Estimated connectomes by the means of neuroimaging techniques have enriched our knowledge of the organizational properties of the brain leading to the development of network-based clinical diagnostics. Unfortunately, to date, many of those network-based clinical diagnostics tools, based on the mere description of isolated instances of observed connectomes are noisy estimates of the true connectivity network. Modeling brain connectivity networks is therefore important to better explain the functional organization of the brain and allow inference of specific brain properties. In this report, we …
The use of EEG biometrics, for the purpose of automatic people recognition, has received increasing attention in the recent years. Most of current analysis rely on the extraction of features characterizing the activity of single brain regions, like power-spectrum estimates, thus neglecting possible temporal dependencies between the generated EEG signals. However, important physiological information can be extracted from the way different brain regions are functionally coupled. In this study, we propose a novel approach that fuses spectral coherencebased connectivity between different brain reg…
A major challenge in cognitive neuroscience is to evaluate the ability of the human brain to categorize or group visual stimuli based on common features. This categorization process is very fast and occurs in few hundreds of millisecond time scale. However, an accurate tracking of the spatiotemporal dynamics of large-scale brain networks is still an unsolved issue. Here, we show the combination of recently developed method called dense-EEG source connectivity to identify functional brain networks with excellent temporal and spatial resolutions and an algorithm, called SimNet, to compute brain …
Neural network oscillations are a fundamental mechanism for cognition, perception and consciousness. Consequently, perturbations of network activity play an important role in the pathophysiology of brain disorders. When structural information from non-invasive brain imaging is merged with mathematical modeling, then generative brain network models constitute in-silico platforms for the exploration of causal mechanisms of brain function and clinical hypothesis testing. We here demonstrate along the example of drug-resistant epilepsy that patient-specific virtual brain models derived from diffus…
Anatomic connections between brain areas affect information flow between neuronal circuits and the synchronization of neuronal activity. However, such structural connectivity does not coincide with effective connectivity, related to the more elusive question "Which areas cause the present activity of which others?". Effective connectivity is directed and depends flexibly on contexts and tasks. Here we show that a dynamic effective connectivity can emerge from transitions in the collective organization of coherent neural activity. Integrating simulation and semi-analytic approaches, we study me…
TU Dresden（德累斯顿工业大学）；HZDR（亥姆霍兹德累斯顿罗森多夫研究中心）；UKE（汉堡埃彭多夫大学医院）
Functional connectivity plays an essential role in modern neuroscience. The modality sheds light on the brain's functional and structural aspects, including mechanisms behind multiple pathologies. One such pathology is schizophrenia which is often followed by auditory verbal hallucinations. The latter is commonly studied by observing functional connectivity during speech processing. In this work, we have made a step toward an in-depth examination of functional connectivity during a dichotic listening task via deep learning for three groups of people: schizophrenia patients with and without aud…
Assessment of dynamic functional brain connectivity (dFC) based on fMRI data is an increasingly popular strategy to investigate temporal dynamics of the brain's large-scale network architecture. Current practice when deriving connectivity estimates over time is to use the Fisher transform which aims to stabilize the variance of correlation values that fluctuate around varying true correlation values. It is however unclear how well the stabilization of signal variance performed by the Fisher transform works for each connectivity time series, when the true correlation is assumed to be fluctuatin…
Neuroimaging data can be represented as networks of nodes and edges that capture the topological organization of the brain connectivity. Graph theory provides a general and powerful framework to study these networks and their structure at various scales. By way of example, community detection methods have been widely applied to investigate the modular structure of many natural networks, including brain functional connectivity networks. Sparsification procedures are often applied to remove the weakest edges, which are the most affected by experimental noise, and to reduce the density of the gra…
Graph theory provides a powerful framework to investigate brain functional connectivity networks and their modular organization. However, most graph-based methods suffer from a fundamental resolution limit that may have affected previous studies and prevented detection of modules, or communities, that are smaller than a specific scale. Surprise, a resolution-limit-free function rooted in discrete probability theory, has been recently introduced and applied to brain networks, revealing a wide size-distribution of functional modules, in contrast with many previous reports. However, the use of Su…
Current functional Magnetic Resonance Imaging technology is able to resolve billions of individual functional connections characterizing the human connectome. Classical statistical inferential procedures attempting to make valid inferences across this many measures from a reduced set of observations and from a limited number of subjects can be severely underpowered for any but the largest effect sizes. This manuscript discusses fc-MVPA (functional connectivity Multivariate Pattern Analysis), a novel application of multivariate pattern analysis techniques in the context of brain-wide connectome…
Severe traumatic brain injury can lead to disorders of consciousness (DOC) characterized by deficit in conscious awareness and cognitive impairment including coma, vegetative state, minimally consciousness, and lock-in syndrome. Of crucial importance is to find objective markers that can account for the large-scale disturbances of brain function to help the diagnosis and prognosis of DOC patients and eventually the prediction of the coma outcome. Following recent studies suggesting that the functional organization of brain networks can be altered in comatose patients, this work analyzes brain …
High-Order Triadic Functional Connectivity in the Brain and Beyond
Tri-Institutional Center for Translational Research in Neuroimaging and Data Science (TReNDS), Georgia State, Georgia Tech, and Emory University（佐治亚州立大学、佐治亚理工学院和埃默里大学联合转化神经影像与数据科学研究中心）；Department of Psychology, University of Texas at Austin（德克萨斯大学奥斯汀分校心理学系）；Department of Biomedical Engineering, Tulane University（杜兰大学生物医学工程系）；Department of Psychiatry, Yale University（耶鲁大学精神病学系）；Department of Neuroscience, Yale University（耶鲁大学神经科学系）；Olin Neuropsychiatry Research Center, Hartford Hospital（哈特福德医院奥林神经精神病学研究中心）；Neuroscience Institute, Georgia State University（佐治亚州立大学神经科学研究所）
The primary goal of this paper is to develop a method that quantifies how activity in one brain region can explain future activity in another region. Here, we propose the mixed effects spectral vector-autoregressive (ME-SpecVar) model to investigate differences in dynamics of dependence in a brain network between healthy children and those who are diagnosed with ADHD. Specifically, ME-SpecVar model will be used to formally test for significant connectivity structure obtained using filtered EEG signals in delta, theta, alpha, beta, and gamma frequency bands. The suggested model allows one-stage…
Diffusion Magnetic Resonance Imaging (MRI) exploits the anisotropic diffusion of water molecules in the brain to enable the estimation of the brain's anatomical fiber tracts at a relatively high resolution. In particular, tractographic methods can be used to generate whole-brain anatomical connectivity matrix where each element provides an estimate of the connectivity strength between the corresponding voxels. Structural brain networks are built using the connectivity information and a predefined brain parcellation, where the nodes of the network represent the brain regions and the edge weight…
Targeted electrical stimulation of the brain perturbs neural networks and modulates their rhythmic activity both at the site of stimulation and at remote brain regions. Understanding, or even predicting, this neuromodulatory effect is crucial for any therapeutic use of brain stimulation. To this end, we analyzed the stimulation responses in 131 stimulation sessions across 66 patients with focal epilepsy recorded through intracranial EEG (iEEG). We considered functional and structural connectivity features as predictors of the response at every iEEG contact. Taking advantage of multiple recordi…
Intrinsic brain activity is characterized by highly structured co-activations between different regions, whose origin is still under debate. In this paper, we address the question whether it is possible to unveil how the underlying anatomical connectivity shape the brain's spontaneous correlation structure. We start from the assumption that in order for two nodes to exhibit large covariation, they must be exposed to similar input patterns from the entire network. We then acknowledge that information rarely spreads only along an unique route, but rather travels along all possible paths. In real…
Epilepsy is a chronic neurological disorder affecting more than 50 million people globally. An epileptic seizure acts like a temporary shock to the neuronal system, disrupting normal electrical activity in the brain. Epilepsy is frequently diagnosed with electroencephalograms (EEGs). Current methods study the time-varying spectra and coherence but do not directly model changes in extreme behavior. Thus, we propose a new approach to characterize brain connectivity based on the joint tail behavior of the EEGs. Our proposed method, the conditional extremal dependence for brain connectivity (Conex…
Scientists construct connectomes, comprehensive descriptions of neuronal connections across a brain, in order to better understand and model brain function. Interactive visualizations of these pathways would enable exploratory analysis of such information flows. Current tools can be used to see individual tracing experiments which are used to build mesoscale connectomes of the mouse brain, but not the brain network itself. We present a connectivity visualization program called BrainViewer, which we use with a high-resolution mouse cortical connectome. This has the ability to display connectome…
Contemporary neuroimaging methods can shed light on the basis of human neural and cognitive specializations, with important implications for neuroscience and medicine. Different MRI acquisitions provide different brain networks at the macroscale; whilst diffusion-weighted MRI (dMRI) provides a structural connectivity (SC) coincident with the bundles of parallel fibers between brain areas, functional MRI (fMRI) accounts for the variations in the blood-oxygenation-level-dependent T2* signal, providing functional connectivity (FC).Understanding the precise relation between FC and SC, that is, bet…
