A DCM for resting state fMRI

This technical note introduces a dynamic causal model (DCM) for resting state fMRI time series based upon observed functional connectivity-as measured by the cross spectra among different brain regions. This DCM is based upon a deterministic model that generates predicted crossed spectra from a biophysically plausible model of coupled neuronal fluctuations in a distributed neuronal network or graph. Effectively, the resulting scheme finds the best effective connectivity among hidden neuronal states that explains the observed functional connectivity among haemodynamic responses. This is because the cross spectra contain all the information about (second order) statistical dependencies among regional dynamics. In this note, we focus on describing the model, its relationship to existing measures of directed and undirected functional connectivity and establishing its face validity using simulations. In subsequent papers, we will evaluate its construct validity in relation to stochastic DCM and its predictive validity in Parkinson's and Huntington's disease

The effect of global signal regression on DCM estimates of noise and effective connectivity from resting state fMRI

The influence of global BOLD fluctuations on resting state functional connectivity in fMRI data remains a topic of debate, with little consensus. In this study, we assessed the effects of global signal regression (GSR) on effective connectivity within and between resting state networks (RSNs) - as estimated with dynamic causal modelling (DCM) for resting state fMRI (rsfMRI). DCM incorporates a forward (generative) model that quantifies the contribution of different types of noise (including global measurement noise), effective connectivity, and (neuro)vascular processes to functional connectivity measurements. DCM analyses were applied to two different designs; namely, longitudinal and cross-sectional designs. In the modelling of longitudinal designs, we considered four extensive longitudinal resting state fMRI datasets with a total number of 20 subjects. In the analysis of cross-sectional designs, we used rsfMRI data from 361 subjects from the Human Connectome Project. We hypothesized that (1) GSR would have no discernible impact on effective connectivity estimated with DCM, and (2) GSR would be reflected in the parameters representing global measurement noise. Additionally, we performed comparative analyses of information gain with and without GSR. Our results showed negligible to small effects of GSR on effective connectivity within small (separately estimated) RSNs. However, although the effect sizes were small, there was substantial to conclusive evidence for an effect of GSR on connectivity parameters. For between-network connectivity, we found two important effects: the effect of GSR on between-network effective connectivity (averaged over all connections) was negligible to small, while the effect of GSR on individual connections was non-negligible. In the cross-sectional (but not in the longitudinal) data, some connections showed substantial to conclusive evidence for an effect of GSR. Contrary to our expectations, we found either no effect (in the longitudinal designs) or a non-specific (cross-sectional design) effect of GSR on parameters characterising (global) measurement noise. Data without GSR were found to be more informative than data with GSR; however, in small resting state networks the precision of posterior estimates was greater after GSR. In conclusion, GSR is a minor concern in DCM studies; however, quantitative interpretation of between-network connections (as opposed to average between-network connectivity) and noise parameters should be treated with some caution. The Kullback-Leibler divergence of the posterior from the prior (i.e., information gain) - together with the precision of posterior estimates - might offer a useful measure to assess the appropriateness of GSR in resting state fMRI

Variability and reliability of effective connectivity within the core default mode network : a multi-site longitudinal spectral DCM study

Dynamic causal modelling (DCM) for resting state fMRI - namely spectral DCM - is a recently developed and widely adopted method for inferring effective connectivity in intrinsic brain networks. Most applications of spectral DCM have focused on group-averaged connectivity within large-scale intrinsic brain networks; however, the consistency of subject- and session-specific estimates of effective connectivity has not been evaluated. Establishing reliability (within subjects) is crucial for its clinical use; e.g., as a neurophysiological phenotype of disease progression. Effective connectivity during rest is likely to vary due to changes in cognitive, and physiological states. Quantifying these variations may help understand functional brain architectures - and inform clinical applications. In the present study, we investigated the consistency of effective connectivity within and between subjects, as well as potential sources of variability (e.g., hemispheric asymmetry). We also addressed the effects on consistency of standard data processing procedures. DCM analyses were applied to four longitudinal resting state fMRI datasets. Our sample comprised 17 subjects with 589 resting state fMRI sessions in total. These data allowed us to quantify the robustness of connectivity estimates for each subject, and to generalise our conclusions beyond specific data features. We found that subjects showed systematic and reliable patterns of hemispheric asymmetry. When asymmetry was taken into account, subjects showed very similar connectivity patterns. We also found that various processing procedures (e.g. global signal regression and ROI size) had little effect on inference and the reliability of connectivity estimates for the majority of subjects. Finally, Bayesian model reduction significantly increased the consistency of connectivity patterns

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

Construct validation of a DCM for resting state fMRI

Recently, there has been a lot of interest in characterising the connectivity of resting state brain networks. Most of the literature uses functional connectivity to examine these intrinsic brain networks. Functional connectivity has well documented limitations because of its inherent inability to identify causal interactions. Dynamic causal modelling (DCM) is a framework that allows for the identification of the causal (directed) connections among neuronal systems - known as effective connectivity. This technical note addresses the validity of a recently proposed DCM for resting state fMRI - as measured in terms of their complex cross spectral density - referred to as spectral DCM. Spectral DCM differs from (the alternative) stochastic DCM by parameterising neuronal fluctuations using scale free (i.e., power law) forms, rendering the stochastic model of neuronal activity deterministic. Spectral DCM not only furnishes an efficient estimation of model parameters but also enables the detection of group differences in effective connectivity, the form and amplitude of the neuronal fluctuations or both. We compare and contrast spectral and stochastic DCM models with endogenous fluctuations or state noise on hidden states. We used simulated data to first establish the face validity of both schemes and show that they can recover the model (and its parameters) that generated the data. We then used Monte Carlo simulations to assess the accuracy of both schemes in terms of their root mean square error. We also simulated group differences and compared the ability of spectral and stochastic DCMs to identify these differences. We show that spectral DCM was not only more accurate but also more sensitive to group differences. Finally, we performed a comparative evaluation using real resting state fMRI data (from an open access resource) to study the functional integration within default mode network using spectral and stochastic DCMs

Causal hierarchy within the thalamo-cortical network in spike and wave discharges

Background: Generalised spike wave (GSW) discharges are the electroencephalographic (EEG) hallmark of absence seizures, clinically characterised by a transitory interruption of ongoing activities and impaired consciousness, occurring during states of reduced awareness. Several theories have been proposed to explain the pathophysiology of GSW discharges and the role of thalamus and cortex as generators. In this work we extend the existing theories by hypothesizing a role for the precuneus, a brain region neglected in previous works on GSW generation but already known to be linked to consciousness and awareness. We analysed fMRI data using dynamic causal modelling (DCM) to investigate the effective connectivity between precuneus, thalamus and prefrontal cortex in patients with GSW discharges. Methodology and Principal Findings: We analysed fMRI data from seven patients affected by Idiopathic Generalized Epilepsy (IGE) with frequent GSW discharges and significant GSW-correlated haemodynamic signal changes in the thalamus, the prefrontal cortex and the precuneus. Using DCM we assessed their effective connectivity, i.e. which region drives another region. Three dynamic causal models were constructed: GSW was modelled as autonomous input to the thalamus (model A), ventromedial prefrontal cortex (model B), and precuneus (model C). Bayesian model comparison revealed Model C (GSW as autonomous input to precuneus), to be the best in 5 patients while model A prevailed in two cases. At the group level model C dominated and at the population-level the p value of model C was ∼1. Conclusion: Our results provide strong evidence that activity in the precuneus gates GSW discharges in the thalamo-(fronto) cortical network. This study is the first demonstration of a causal link between haemodynamic changes in the precuneus - an index of awareness - and the occurrence of pathological discharges in epilepsy. © 2009 Vaudano et al