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

Fast joint detection-estimation of evoked brain activity in event-related fMRI using a variational approach

In standard clinical within-subject analyses of event-related fMRI data, two steps are usually performed separately: detection of brain activity and estimation of the hemodynamic response. Because these two steps are inherently linked, we adopt the so-called region-based Joint Detection-Estimation (JDE) framework that addresses this joint issue using a multivariate inference for detection and estimation. JDE is built by making use of a regional bilinear generative model of the BOLD response and constraining the parameter estimation by physiological priors using temporal and spatial information in a Markovian modeling. In contrast to previous works that use Markov Chain Monte Carlo (MCMC) techniques to approximate the resulting intractable posterior distribution, we recast the JDE into a missing data framework and derive a Variational Expectation-Maximization (VEM) algorithm for its inference. A variational approximation is used to approximate the Markovian model in the unsupervised spatially adaptive JDE inference, which allows fine automatic tuning of spatial regularisation parameters. It follows a new algorithm that exhibits interesting properties compared to the previously used MCMC-based approach. Experiments on artificial and real data show that VEM-JDE is robust to model mis-specification and provides computational gain while maintaining good performance in terms of activation detection and hemodynamic shape recovery

A Bayesian Heteroscedastic GLM with Application to fMRI Data with Motion Spikes

We propose a voxel-wise general linear model with autoregressive noise and heteroscedastic noise innovations (GLMH) for analyzing functional magnetic resonance imaging (fMRI) data. The model is analyzed from a Bayesian perspective and has the benefit of automatically down-weighting time points close to motion spikes in a data-driven manner. We develop a highly efficient Markov Chain Monte Carlo (MCMC) algorithm that allows for Bayesian variable selection among the regressors to model both the mean (i.e., the design matrix) and variance. This makes it possible to include a broad range of explanatory variables in both the mean and variance (e.g., time trends, activation stimuli, head motion parameters and their temporal derivatives), and to compute the posterior probability of inclusion from the MCMC output. Variable selection is also applied to the lags in the autoregressive noise process, making it possible to infer the lag order from the data simultaneously with all other model parameters. We use both simulated data and real fMRI data from OpenfMRI to illustrate the importance of proper modeling of heteroscedasticity in fMRI data analysis. Our results show that the GLMH tends to detect more brain activity, compared to its homoscedastic counterpart, by allowing the variance to change over time depending on the degree of head motion

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

The MVGC multivariate Granger causality toolbox: a new approach to Granger-causal inference

Background: Wiener-Granger causality (“G-causality”) is a statistical notion of causality applicable to time series data, whereby cause precedes, and helps predict, effect. It is defined in both time and frequency domains, and allows for the conditioning out of common causal influences. Originally developed in the context of econometric theory, it has since achieved broad application in the neurosciences and beyond. Prediction in the G-causality formalism is based on VAR (Vector AutoRegressive) modelling. New Method: The MVGC Matlab c Toolbox approach to G-causal inference is based on multiple equivalent representations of a VAR model by (i) regression parameters, (ii) the autocovariance sequence and (iii) the cross-power spectral density of the underlying process. It features a variety of algorithms for moving between these representations, enabling selection of the most suitable algorithms with regard to computational efficiency and numerical accuracy. Results: In this paper we explain the theoretical basis, computational strategy and application to empirical G-causal inference of the MVGC Toolbox. We also show via numerical simulations the advantages of our Toolbox over previous methods in terms of computational accuracy and statistical inference. Comparison with Existing Method(s): The standard method of computing G-causality involves estimation of parameters for both a full and a nested (reduced) VAR model. The MVGC approach, by contrast, avoids explicit estimation of the reduced model, thus eliminating a source of estimation error and improving statistical power, and in addition facilitates fast and accurate estimation of the computationally awkward case of conditional G-causality in the frequency domain. Conclusions: The MVGC Toolbox implements a flexible, powerful and efficient approach to G-causal inference. Keywords: Granger causality, vector autoregressive modelling, time series analysi

Algorithms of causal inference for the analysis of effective connectivity among brain regions

In recent years, powerful general algorithms of causal inference have been developed. In particular, in the framework of Pearl’s causality, algorithms of inductive causation (IC and IC*) provide a procedure to determine which causal connections among nodes in a network can be inferred from empirical observations even in the presence of latent variables, indicating the limits of what can be learned without active manipulation of the system. These algorithms can in principle become important complements to established techniques such as Granger causality and Dynamic Causal Modeling (DCM) to analyze causal influences (effective connectivity) among brain regions. However, their application to dynamic processes has not been yet examined. Here we study how to apply these algorithms to time-varying signals such as electrophysiological or neuroimaging signals. We propose a new algorithm which combines the basic principles of the previous algorithms with Granger causality to obtain a representation of the causal relations suited to dynamic processes. Furthermore, we use graphical criteria to predict dynamic statistical dependencies between the signals from the causal structure. We show how some problems for causal inference from neural signals (e.g., measurement noise, hemodynamic responses, and time aggregation) can be understood in a general graphical approach. Focusing on the effect of spatial aggregation, we show that when causal inference is performed at a coarser scale than the one at which the neural sources interact, results strongly depend on the degree of integration of the neural sources aggregated in the signals, and thus characterize more the intra-areal properties than the interactions among regions. We finally discuss how the explicit consideration of latent processes contributes to understand Granger causality and DCM as well as to distinguish functional and effective connectivity