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

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

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

Structure Learning in Coupled Dynamical Systems and Dynamic Causal Modelling

Identifying a coupled dynamical system out of many plausible candidates, each of which could serve as the underlying generator of some observed measurements, is a profoundly ill posed problem that commonly arises when modelling real world phenomena. In this review, we detail a set of statistical procedures for inferring the structure of nonlinear coupled dynamical systems (structure learning), which has proved useful in neuroscience research. A key focus here is the comparison of competing models of (ie, hypotheses about) network architectures and implicit coupling functions in terms of their Bayesian model evidence. These methods are collectively referred to as dynamical casual modelling (DCM). We focus on a relatively new approach that is proving remarkably useful; namely, Bayesian model reduction (BMR), which enables rapid evaluation and comparison of models that differ in their network architecture. We illustrate the usefulness of these techniques through modelling neurovascular coupling (cellular pathways linking neuronal and vascular systems), whose function is an active focus of research in neurobiology and the imaging of coupled neuronal systems

Learning Discriminative Bayesian Networks from High-dimensional Continuous Neuroimaging Data

Due to its causal semantics, Bayesian networks (BN) have been widely employed to discover the underlying data relationship in exploratory studies, such as brain research. Despite its success in modeling the probability distribution of variables, BN is naturally a generative model, which is not necessarily discriminative. This may cause the ignorance of subtle but critical network changes that are of investigation values across populations. In this paper, we propose to improve the discriminative power of BN models for continuous variables from two different perspectives. This brings two general discriminative learning frameworks for Gaussian Bayesian networks (GBN). In the first framework, we employ Fisher kernel to bridge the generative models of GBN and the discriminative classifiers of SVMs, and convert the GBN parameter learning to Fisher kernel learning via minimizing a generalization error bound of SVMs. In the second framework, we employ the max-margin criterion and build it directly upon GBN models to explicitly optimize the classification performance of the GBNs. The advantages and disadvantages of the two frameworks are discussed and experimentally compared. Both of them demonstrate strong power in learning discriminative parameters of GBNs for neuroimaging based brain network analysis, as well as maintaining reasonable representation capacity. The contributions of this paper also include a new Directed Acyclic Graph (DAG) constraint with theoretical guarantee to ensure the graph validity of GBN.Comment: 16 pages and 5 figures for the article (excluding appendix

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