Estimating Time-Varying Effective Connectivity in High-Dimensional fMRI Data Using Regime-Switching Factor Models

Recent studies on analyzing dynamic brain connectivity rely on sliding-window analysis or time-varying coefficient models which are unable to capture both smooth and abrupt changes simultaneously. Emerging evidence suggests state-related changes in brain connectivity where dependence structure alternates between a finite number of latent states or regimes. Another challenge is inference of full-brain networks with large number of nodes. We employ a Markov-switching dynamic factor model in which the state-driven time-varying connectivity regimes of high-dimensional fMRI data are characterized by lower-dimensional common latent factors, following a regime-switching process. It enables a reliable, data-adaptive estimation of change-points of connectivity regimes and the massive dependencies associated with each regime. We consider the switching VAR to quantity the dynamic effective connectivity. We propose a three-step estimation procedure: (1) extracting the factors using principal component analysis (PCA) and (2) identifying dynamic connectivity states using the factor-based switching vector autoregressive (VAR) models in a state-space formulation using Kalman filter and expectation-maximization (EM) algorithm, and (3) constructing the high-dimensional connectivity metrics for each state based on subspace estimates. Simulation results show that our proposed estimator outperforms the K-means clustering of time-windowed coefficients, providing more accurate estimation of regime dynamics and connectivity metrics in high-dimensional settings. Applications to analyzing resting-state fMRI data identify dynamic changes in brain states during rest, and reveal distinct directed connectivity patterns and modular organization in resting-state networks across different states.Comment: 21 page

Disentangling causal webs in the brain using functional Magnetic Resonance Imaging: A review of current approaches

In the past two decades, functional Magnetic Resonance Imaging has been used to relate neuronal network activity to cognitive processing and behaviour. Recently this approach has been augmented by algorithms that allow us to infer causal links between component populations of neuronal networks. Multiple inference procedures have been proposed to approach this research question but so far, each method has limitations when it comes to establishing whole-brain connectivity patterns. In this work, we discuss eight ways to infer causality in fMRI research: Bayesian Nets, Dynamical Causal Modelling, Granger Causality, Likelihood Ratios, LiNGAM, Patel's Tau, Structural Equation Modelling, and Transfer Entropy. We finish with formulating some recommendations for the future directions in this area

A nonstationary nonparametric Bayesian approach to dynamically modeling effective connectivity in functional magnetic resonance imaging experiments

Effective connectivity analysis provides an understanding of the functional organization of the brain by studying how activated regions influence one other. We propose a nonparametric Bayesian approach to model effective connectivity assuming a dynamic nonstationary neuronal system. Our approach uses the Dirichlet process to specify an appropriate (most plausible according to our prior beliefs) dynamic model as the "expectation" of a set of plausible models upon which we assign a probability distribution. This addresses model uncertainty associated with dynamic effective connectivity. We derive a Gibbs sampling approach to sample from the joint (and marginal) posterior distributions of the unknowns. Results on simulation experiments demonstrate our model to be flexible and a better candidate in many situations. We also used our approach to analyzing functional Magnetic Resonance Imaging (fMRI) data on a Stroop task: our analysis provided new insight into the mechanism by which an individual brain distinguishes and learns about shapes of objects.Comment: Published in at http://dx.doi.org/10.1214/11-AOAS470 the Annals of Applied Statistics (http://www.imstat.org/aoas/) by the Institute of Mathematical Statistics (http://www.imstat.org

Estimating effective connectivity in linear brain network models

Contemporary neuroscience has embraced network science to study the complex and self-organized structure of the human brain; one of the main outstanding issues is that of inferring from measure data, chiefly functional Magnetic Resonance Imaging (fMRI), the so-called effective connectivity in brain networks, that is the existing interactions among neuronal populations. This inverse problem is complicated by the fact that the BOLD (Blood Oxygenation Level Dependent) signal measured by fMRI represent a dynamic and nonlinear transformation (the hemodynamic response) of neuronal activity. In this paper, we consider resting state (rs) fMRI data; building upon a linear population model of the BOLD signal and a stochastic linear DCM model, the model parameters are estimated through an EM-type iterative procedure, which alternately estimates the neuronal activity by means of the Rauch-Tung-Striebel (RTS) smoother, updates the connections among neuronal states and refines the parameters of the hemodynamic model; sparsity in the interconnection structure is favoured using an iteratively reweighting scheme. Experimental results using rs-fMRI data are shown demonstrating the effectiveness of our approach and comparison with state of the art routines (SPM12 toolbox) is provided

Nonparametric Modeling of Dynamic Functional Connectivity in fMRI Data

Dynamic functional connectivity (FC) has in recent years become a topic of interest in the neuroimaging community. Several models and methods exist for both functional magnetic resonance imaging (fMRI) and electroencephalography (EEG), and the results point towards the conclusion that FC exhibits dynamic changes. The existing approaches modeling dynamic connectivity have primarily been based on time-windowing the data and k-means clustering. We propose a non-parametric generative model for dynamic FC in fMRI that does not rely on specifying window lengths and number of dynamic states. Rooted in Bayesian statistical modeling we use the predictive likelihood to investigate if the model can discriminate between a motor task and rest both within and across subjects. We further investigate what drives dynamic states using the model on the entire data collated across subjects and task/rest. We find that the number of states extracted are driven by subject variability and preprocessing differences while the individual states are almost purely defined by either task or rest. This questions how we in general interpret dynamic FC and points to the need for more research on what drives dynamic FC.Comment: 8 pages, 1 figure. Presented at the Machine Learning and Interpretation in Neuroimaging Workshop (MLINI-2015), 2015 (arXiv:1605.04435

Towards a Multi-Subject Analysis of Neural Connectivity

Directed acyclic graphs (DAGs) and associated probability models are widely used to model neural connectivity and communication channels. In many experiments, data are collected from multiple subjects whose connectivities may differ but are likely to share many features. In such circumstances it is natural to leverage similarity between subjects to improve statistical efficiency. The first exact algorithm for estimation of multiple related DAGs was recently proposed by Oates et al. 2014; in this letter we present examples and discuss implications of the methodology as applied to the analysis of fMRI data from a multi-subject experiment. Elicitation of tuning parameters requires care and we illustrate how this may proceed retrospectively based on technical replicate data. In addition to joint learning of subject-specific connectivity, we allow for heterogeneous collections of subjects and simultaneously estimate relationships between the subjects themselves. This letter aims to highlight the potential for exact estimation in the multi-subject setting.Comment: to appear in Neural Computation 27:1-2