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

Analysis of Dynamic Brain Imaging Data

Modern imaging techniques for probing brain function, including functional Magnetic Resonance Imaging, intrinsic and extrinsic contrast optical imaging, and magnetoencephalography, generate large data sets with complex content. In this paper we develop appropriate techniques of analysis and visualization of such imaging data, in order to separate the signal from the noise, as well as to characterize the signal. The techniques developed fall into the general category of multivariate time series analysis, and in particular we extensively use the multitaper framework of spectral analysis. We develop specific protocols for the analysis of fMRI, optical imaging and MEG data, and illustrate the techniques by applications to real data sets generated by these imaging modalities. In general, the analysis protocols involve two distinct stages: `noise' characterization and suppression, and `signal' characterization and visualization. An important general conclusion of our study is the utility of a frequency-based representation, with short, moving analysis windows to account for non-stationarity in the data. Of particular note are (a) the development of a decomposition technique (`space-frequency singular value decomposition') that is shown to be a useful means of characterizing the image data, and (b) the development of an algorithm, based on multitaper methods, for the removal of approximately periodic physiological artifacts arising from cardiac and respiratory sources.Comment: 40 pages; 26 figures with subparts including 3 figures as .gif files. Originally submitted to the neuro-sys archive which was never publicly announced (was 9804003

Dynamic Construction of Stimulus Values in the Ventromedial Prefrontal Cortex

Signals representing the value assigned to stimuli at the time of choice have been repeatedly observed in ventromedial prefrontal cortex (vmPFC). Yet it remains unknown how these value representations are computed from sensory and memory representations in more posterior brain regions. We used electroencephalography (EEG) while subjects evaluated appetitive and aversive food items to study how event-related responses modulated by stimulus value evolve over time. We found that value-related activity shifted from posterior to anterior, and from parietal to central to frontal sensors, across three major time windows after stimulus onset: 150–250 ms, 400–550 ms, and 700–800 ms. Exploratory localization of the EEG signal revealed a shifting network of activity moving from sensory and memory structures to areas associated with value coding, with stimulus value activity localized to vmPFC only from 400 ms onwards. Consistent with these results, functional connectivity analyses also showed a causal flow of information from temporal cortex to vmPFC. Thus, although value signals are present as early as 150 ms after stimulus onset, the value signals in vmPFC appear relatively late in the choice process, and seem to reflect the integration of incoming information from sensory and memory related regions

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

Nonlinear ICA of fMRI reveals primitive temporal structures linked to rest, task, and behavioral traits

Accumulating evidence from whole brain functional magnetic resonance imaging (fMRI) suggests that the human brain at rest is functionally organized in a spatially and temporally constrained manner. However, because of their complexity, the fundamental mechanisms underlying time-varying functional networks are still not well under-stood. Here, we develop a novel nonlinear feature extraction framework called local space-contrastive learning (LSCL), which extracts distinctive nonlinear temporal structure hidden in time series, by training a deep temporal convolutional neural network in an unsupervised, data-driven manner. We demonstrate that LSCL identifies certain distinctive local temporal structures, referred to as temporal primitives, which repeatedly appear at different time points and spatial locations, reflecting dynamic resting-state networks. We also show that these temporal primitives are also present in task-evoked spatiotemporal responses. We further show that the temporal primitives capture unique aspects of behavioral traits such as fluid intelligence and working memory. These re-sults highlight the importance of capturing transient spatiotemporal dynamics within fMRI data and suggest that such temporal primitives may capture fundamental information underlying both spontaneous and task-induced fMRI dynamics.Peer reviewe

The shuffle estimator for explainable variance in fMRI experiments

In computational neuroscience, it is important to estimate well the proportion of signal variance in the total variance of neural activity measurements. This explainable variance measure helps neuroscientists assess the adequacy of predictive models that describe how images are encoded in the brain. Complicating the estimation problem are strong noise correlations, which may confound the neural responses corresponding to the stimuli. If not properly taken into account, the correlations could inflate the explainable variance estimates and suggest false possible prediction accuracies. We propose a novel method to estimate the explainable variance in functional MRI (fMRI) brain activity measurements when there are strong correlations in the noise. Our shuffle estimator is nonparametric, unbiased, and built upon the random effect model reflecting the randomization in the fMRI data collection process. Leveraging symmetries in the measurements, our estimator is obtained by appropriately permuting the measurement vector in such a way that the noise covariance structure is intact but the explainable variance is changed after the permutation. This difference is then used to estimate the explainable variance. We validate the properties of the proposed method in simulation experiments. For the image-fMRI data, we show that the shuffle estimates can explain the variation in prediction accuracy for voxels within the primary visual cortex (V1) better than alternative parametric methods.Comment: Published in at http://dx.doi.org/10.1214/13-AOAS681 the Annals of Applied Statistics (http://www.imstat.org/aoas/) by the Institute of Mathematical Statistics (http://www.imstat.org

AM-FM Analysis of Structural and Functional Magnetic Resonance Images

This thesis proposes the application of multi-dimensional Amplitude-Modulation Frequency-Modulation (AM-FM) methods to magnetic resonance images (MRI). The basic goal is to provide a framework for exploring non-stationary characteristics of structural and functional MRI (sMRI and fMRI). First, we provide a comparison framework for the most popular AM-FM methods using different filterbank configurations that includes Gabor, Equirriple and multi-scale directional designs. We compare the performance and robustness to Gaussian noise using synthetic FM image examples. We show that the multi-dimensional quasi-local method (QLM) with an equiripple filterbank gave the best results in terms of instantaneous frequency (IF) estimation. We then apply the best performing AM-FM method to sMRI to compute the 3D IF features. We use a t-test on the IF magnitude for each voxel to find evidence of significant differences between healthy controls and patients diagnosed with schizophrenia (n=353) can be found in the IF. We also propose the use of the instantaneous phase (IP) as a new feature for analyzing fMRI images. Using principal component analysis and independent component analysis on the instantaneous phase from fMRI, we built spatial maps and identified brain regions that are biologically coherent with the task performed by the subject. This thesis provides the first application of AM-FM models to fMRI and sMRI