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

Fluctuations between high- and low-modularity topology in time-resolved functional connectivity

Modularity is an important topological attribute for functional brain networks. Recent studies have reported that modularity of functional networks varies not only across individuals being related to demographics and cognitive performance, but also within individuals co-occurring with fluctuations in network properties of functional connectivity, estimated over short time intervals. However, characteristics of these time-resolved functional networks during periods of high and low modularity have remained largely unexplored. In this study we investigate spatiotemporal properties of time-resolved networks in the high and low modularity periods during rest, with a particular focus on their spatial connectivity patterns, temporal homogeneity and test-retest reliability. We show that spatial connectivity patterns of time-resolved networks in the high and low modularity periods are represented by increased and decreased dissociation of the default mode network module from task-positive network modules, respectively. We also find that the instances of time-resolved functional connectivity sampled from within the high (low) modularity period are relatively homogeneous (heterogeneous) over time, indicating that during the low modularity period the default mode network interacts with other networks in a variable manner. We confirmed that the occurrence of the high and low modularity periods varies across individuals with moderate inter-session test-retest reliability and that it is correlated with previously-reported individual differences in the modularity of functional connectivity estimated over longer timescales. Our findings illustrate how time-resolved functional networks are spatiotemporally organized during periods of high and low modularity, allowing one to trace individual differences in long-timescale modularity to the variable occurrence of network configurations at shorter timescales.Comment: Reorganized the paper; to appear in NeuroImage; arXiv abstract shortened to fit within character limit

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

Characterization of Large Scale Functional Brain Networks During Ketamine-Medetomidine Anesthetic Induction

Several experiments evidence that specialized brain regions functionally interact and reveal that the brain processes and integrates information in a specific and structured manner. Networks can be used to model brain functional activities constituting a way to characterize and quantify this structured form of organization. Reports state that different physiological states or even diseases that affect the central nervous system may be associated to alterations on those networks, that might reflect in graphs of different architectures. However, the relation of their structure to different states or conditions of the organism is not well comprehended. Thus, experiments that involve the estimation of functional neural networks of subjects exposed to different controlled conditions are of great relevance. Within this context, this research has sought to model large scale functional brain networks during an anesthetic induction process. The experiment was based on intra-cranial recordings of neural activities of an old world macaque of the species Macaca fuscata. Neural activity was recorded during a Ketamine-Medetomidine anesthetic induction process. Networks were serially estimated in time intervals of five seconds. Changes were observed in various networks properties within about one and a half minutes after the administration of the anesthetics. These changes reveal the occurrence of a transition on the networks architecture. During general anesthesia a reduction in the functional connectivity and network integration capabilities were verified in both local and global levels. It was also observed that the brain shifted to a highly specific and dynamic state. The results bring empirical evidence and report the relation of the induced state of anesthesia to properties of functional networks, thus, they contribute for the elucidation of some new aspects of neural correlates of consciousness.Comment: 28 pages , 9 figures, 7 tables; - English errors were corrected; Figures 1,3,4,5,6,8 and 9 were replaced by (exact the same)figures of higher resolution; Three(3) references were added on the introduction sectio