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

Physiological Gaussian Process Priors for the Hemodynamics in fMRI Analysis

Background: Inference from fMRI data faces the challenge that the hemodynamic system that relates neural activity to the observed BOLD fMRI signal is unknown. New Method: We propose a new Bayesian model for task fMRI data with the following features: (i) joint estimation of brain activity and the underlying hemodynamics, (ii) the hemodynamics is modeled nonparametrically with a Gaussian process (GP) prior guided by physiological information and (iii) the predicted BOLD is not necessarily generated by a linear time-invariant (LTI) system. We place a GP prior directly on the predicted BOLD response, rather than on the hemodynamic response function as in previous literature. This allows us to incorporate physiological information via the GP prior mean in a flexible way, and simultaneously gives us the nonparametric flexibility of the GP. Results: Results on simulated data show that the proposed model is able to discriminate between active and non-active voxels also when the GP prior deviates from the true hemodynamics. Our model finds time varying dynamics when applied to real fMRI data. Comparison with Existing Method(s): The proposed model is better at detecting activity in simulated data than standard models, without inflating the false positive rate. When applied to real fMRI data, our GP model in several cases finds brain activity where previously proposed LTI models does not. Conclusions: We have proposed a new non-linear model for the hemodynamics in task fMRI, that is able to detect active voxels, and gives the opportunity to ask new kinds of questions related to hemodynamics.Comment: 18 pages, 14 figure

Synergetic and redundant information flow detected by unnormalized Granger causality: application to resting state fMRI

Objectives: We develop a framework for the analysis of synergy and redundancy in the pattern of information flow between subsystems of a complex network. Methods: The presence of redundancy and/or synergy in multivariate time series data renders difficult to estimate the neat flow of information from each driver variable to a given target. We show that adopting an unnormalized definition of Granger causality one may put in evidence redundant multiplets of variables influencing the target by maximizing the total Granger causality to a given target, over all the possible partitions of the set of driving variables. Consequently we introduce a pairwise index of synergy which is zero when two independent sources additively influence the future state of the system, differently from previous definitions of synergy. Results: We report the application of the proposed approach to resting state fMRI data from the Human Connectome Project, showing that redundant pairs of regions arise mainly due to space contiguity and interhemispheric symmetry, whilst synergy occurs mainly between non-homologous pairs of regions in opposite hemispheres. Conclusions: Redundancy and synergy, in healthy resting brains, display characteristic patterns, revealed by the proposed approach. Significance: The pairwise synergy index, here introduced, maps the informational character of the system at hand into a weighted complex network: the same approach can be applied to other complex systems whose normal state corresponds to a balance between redundant and synergetic circuits.Comment: 6 figures. arXiv admin note: text overlap with arXiv:1403.515

A blind deconvolution approach to recover effective connectivity brain networks from resting state fMRI data

A great improvement to the insight on brain function that we can get from fMRI data can come from effective connectivity analysis, in which the flow of information between even remote brain regions is inferred by the parameters of a predictive dynamical model. As opposed to biologically inspired models, some techniques as Granger causality (GC) are purely data-driven and rely on statistical prediction and temporal precedence. While powerful and widely applicable, this approach could suffer from two main limitations when applied to BOLD fMRI data: confounding effect of hemodynamic response function (HRF) and conditioning to a large number of variables in presence of short time series. For task-related fMRI, neural population dynamics can be captured by modeling signal dynamics with explicit exogenous inputs; for resting-state fMRI on the other hand, the absence of explicit inputs makes this task more difficult, unless relying on some specific prior physiological hypothesis. In order to overcome these issues and to allow a more general approach, here we present a simple and novel blind-deconvolution technique for BOLD-fMRI signal. Coming to the second limitation, a fully multivariate conditioning with short and noisy data leads to computational problems due to overfitting. Furthermore, conceptual issues arise in presence of redundancy. We thus apply partial conditioning to a limited subset of variables in the framework of information theory, as recently proposed. Mixing these two improvements we compare the differences between BOLD and deconvolved BOLD level effective networks and draw some conclusions