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 estimation error rate. The subsequent multiple testing procedure built on this test statistic is guaranteed to asymptotically control the false discovery rate at the pre-specified level. Both the methodology and theory of the new test are considerably different from the two independent samples framework, owing to the strong correlations of measurements on the same subjects before and after the stimulus activity. We illustrate the efficacy of our proposal through simulations and an analysis of an Alzheimer's Disease Neuroimaing Initiative dataset.
Brain connectivity analysis is now at the foreground of neuroscience research. A connectivity network is characterized by a graph, where nodes represent neural elements such as neurons and brain regions, and links represent statistical dependences that are often encoded in terms of partial correlations. Such a graph is inferred from matrix-valued neuroimaging data such as electroencephalography and functional magnetic resonance imaging. There have been a good number of successful proposals for sparse precision matrix estimation under normal or matrix normal distribution; however, this family o…
Dynamic functional brain connectivity results depend on modeling assumptions: comparing the sliding-window method and the Wishart process for dynamic hypothesis testing
Donders Institute, Radboud University（唐德斯研究所，拉德堡德大学）
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…
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…
In neuroscience, functional brain connectivity describes the connectivity between brain regions that share functional properties. Neuroscientists often characterize it by a time series of covariance matrices between functional measurements of distributed neuron areas. An effective statistical model for functional connectivity and its changes over time is critical for better understanding the mechanisms of brain and various neurological diseases. To this end, we propose a matrix-log mean model with an additive heterogeneous noise for modeling random symmetric positive definite matrices that lie…
Multiple-subject network data are fast emerging in recent years, where a separate connectivity matrix is measured over a common set of nodes for each individual subject, along with subject covariates information. In this article, we propose a new generalized matrix response regression model, where the observed networks are treated as matrix-valued responses and the subject covariates as predictors. The new model characterizes the population-level connectivity pattern through a low-rank intercept matrix, and the effect of subject covariates through a sparse slope tensor. We develop an efficient…
Bayesian Varying-Effects Vector Autoregressive Models for Inference of Brain Connectivity Networks and Covariate Effects in Pediatric Traumatic Brain Injury
Dynamic networks have been increasingly used to characterize brain connectivity that varies during resting and task states. In such characterizations, a connectivity network is typically measured at each time point for a subject over a common set of nodes representing brain regions, together with rich subject-level information. A common approach to analyzing such data is an edge-based method that models the connectivity between each pair of nodes separately. However, such approach may have limited performance when the noise level is high and the number of subjects is limited, as it does not ta…
This paper concerns the modeling of multi-way functional data where double or multiple indices are involved. We introduce a concept of weak separability. The weakly separable structure supports the use of factorization methods that decompose the signal into its spatial and temporal components. The analysis reveals interesting connections to the usual strongly separable covariance structure, and provides insights into tensor methods for multi-way functional data. We propose a formal test for the weak separability hypothesis, where the asymptotic null distribution of the test statistic is a chi-…
Time-varying networks are fast emerging in a wide range of scientific and business disciplines. Most existing dynamic network models are limited to a single-subject and discrete-time setting. In this article, we propose a mixed-effect multi-subject continuous-time stochastic blockmodel that characterizes the time-varying behavior of the network at the population level, meanwhile taking into account individual subject variability. We develop a multi-step optimization procedure for a constrained stochastic blockmodel estimation, and derive the asymptotic property of the estimator. We demonstrate…
Understanding of normal and pathological brain function requires the identification and localization of functional connections between specialized regions. The availability of high time resolution signals of electric neuronal activity at several regions offers information for quantifying the connections in terms of information flow. When the signals cover the whole cortex, the number of connections is very large, making visualization and interpretation very difficult. We introduce here the singular value decomposition of time-lagged multiple signals, which localizes the senders, hubs, and rece…
Alzheimer's disease (AD) is the most common form of dementia, which causes problems with memory, thinking and behavior. Growing evidence has shown that the brain connectivity network experiences alterations for such a complex disease. Network comparison, also known as differential network analysis, is thus particularly powerful to reveal the disease pathologies and identify clinical biomarkers for medical diagnoses (classification). Data from neurophysiological measurements are multi-dimensional and in matrix-form, which poses major challenges in brain connectivity analysis and medical diagnos…
Brain activation and connectivity analyses in task-based functional magnetic resonance imaging (fMRI) experiments with multiple subjects are currently at the forefront of data-driven neuroscience. In such experiments, interest often lies in understanding activation of brain voxels due to external stimuli and strong association or connectivity between the measurements on a set of pre-specified group of brain voxels, also known as regions of interest (ROI). This article proposes a joint Bayesian additive mixed modeling framework that simultaneously assesses brain activation and connectivity patt…
We propose a novel technique to assess functional brain connectivity in EEG/MEG signals. Our method, called Sparsely-Connected Sources Analysis (SCSA), can overcome the problem of volume conduction by modeling neural data innovatively with the following ingredients: (a) the EEG is assumed to be a linear mixture of correlated sources following a multivariate autoregressive (MVAR) model, (b) the demixing is estimated jointly with the source MVAR parameters, (c) overfitting is avoided by using the Group Lasso penalty. This approach allows to extract the appropriate level cross-talk between the ex…
Converging evidence indicates that the heterogeneity of cognitive profiles may arise through detectable alternations in brain functions. Particularly, brain functional connectivity, measured under resting and cognitive states, characterizes the unique neuronal interconnections across large-scale brain networks. Despite an unprecedented opportunity to uncover neurobiological subtypes through clustering or subtyping analyses on multi-state functional connectivity, few existing approaches are applicable here to accommodate the network topology and unique biological architecture of functional conn…
The brain structural connectome is generated by a collection of white matter fiber bundles constructed from diffusion weighted MRI (dMRI), acting as highways for neural activity. There has been abundant interest in studying how the structural connectome varies across individuals in relation to their traits, ranging from age and gender to neuropsychiatric outcomes. After applying tractography to dMRI to get white matter fiber bundles, a key question is how to represent the brain connectome to facilitate statistical analyses relating connectomes to traits. The current standard divides the brain …
Classical scalar-response regression methods treat covariates as a vector and estimate a corresponding vector of regression coefficients. In medical applications, however, regressors are often in a form of multi-dimensional arrays. For example, one may be interested in using MRI imaging to identify which brain regions are associated with a health outcome. Vectorizing the two-dimensional image arrays is an unsatisfactory approach since it destroys the inherent spatial structure of the images and can be computationally challenging. We present an alternative approach - regularized matrix regressi…
