Doctor of Philosophy

dissertationFunctional magnetic resonance imaging (fMRI) measures the change of oxygen consumption level in the blood vessels of the human brain, hence indirectly detecting the neuronal activity. Resting-state fMRI (rs-fMRI) is used to identify the intrinsic functional patterns of the brain when there is no external stimulus. Accurate estimation of intrinsic activity is important for understanding the functional organization and dynamics of the brain, as well as differences in the functional networks of patients with mental disorders. This dissertation aims to robustly estimate the functional connectivities and networks of the human brain using rs-fMRI data of multiple subjects. We use Markov random field (MRF), an undirected graphical model to represent the statistical dependency among the functional network variables. Graphical models describe multivariate probability distributions that can be factorized and represented by a graph. By defining the nodes and the edges along with their weights according to our assumptions, we build soft constraints into the graph structure as prior information. We explore various approximate optimization methods including variational Bayesian, graph cuts, and Markov chain Monte Carlo sampling (MCMC). We develop the random field models to solve three related problems. In the first problem, the goal is to detect the pairwise connectivity between gray matter voxels in a rs-fMRI dataset of the single subject. We define a six-dimensional graph to represent our prior information that two voxels are more likely to be connected if their spatial neighbors are connected. The posterior mean of the connectivity variables are estimated by variational inference, also known as mean field theory in statistical physics. The proposed method proves to outperform the standard spatial smoothing and is able to detect finer patterns of brain activity. Our second work aims to identify multiple functional systems. We define a Potts model, a special case of MRF, on the network label variables, and define von Mises-Fisher distribution on the normalized fMRI signal. The inference is significantly more difficult than the binary classification in the previous problem. We use MCMC to draw samples from the posterior distribution of network labels. In the third application, we extend the graphical model to the multiple subject scenario. By building a graph including the network labels of both a group map and the subject label maps, we define a hierarchical model that has richer structure than the flat single-subject model, and captures the shared patterns as well as the variation among the subjects. All three solutions are data-driven Bayesian methods, which estimate model parameters from the data. The experiments show that by the regularization of MRF, the functional network maps we estimate are more accurate and more consistent across multiple sessions

Tensor Analysis and Fusion of Multimodal Brain Images

Current high-throughput data acquisition technologies probe dynamical systems with different imaging modalities, generating massive data sets at different spatial and temporal resolutions posing challenging problems in multimodal data fusion. A case in point is the attempt to parse out the brain structures and networks that underpin human cognitive processes by analysis of different neuroimaging modalities (functional MRI, EEG, NIRS etc.). We emphasize that the multimodal, multi-scale nature of neuroimaging data is well reflected by a multi-way (tensor) structure where the underlying processes can be summarized by a relatively small number of components or "atoms". We introduce Markov-Penrose diagrams - an integration of Bayesian DAG and tensor network notation in order to analyze these models. These diagrams not only clarify matrix and tensor EEG and fMRI time/frequency analysis and inverse problems, but also help understand multimodal fusion via Multiway Partial Least Squares and Coupled Matrix-Tensor Factorization. We show here, for the first time, that Granger causal analysis of brain networks is a tensor regression problem, thus allowing the atomic decomposition of brain networks. Analysis of EEG and fMRI recordings shows the potential of the methods and suggests their use in other scientific domains.Comment: 23 pages, 15 figures, submitted to Proceedings of the IEE

fMRI activation detection with EEG priors

The purpose of brain mapping techniques is to advance the understanding of the relationship between structure and function in the human brain in so-called activation studies. In this work, an advanced statistical model for combining functional magnetic resonance imaging (fMRI) and electroencephalography (EEG) recordings is developed to fuse complementary information about the location of neuronal activity. More precisely, a new Bayesian method is proposed for enhancing fMRI activation detection by the use of EEG-based spatial prior information in stimulus based experimental paradigms. I.e., we model and analyse stimulus influence by a spatial Bayesian variable selection scheme, and extend existing high-dimensional regression methods by incorporating prior information on binary selection indicators via a latent probit regression with either a spatially-varying or constant EEG effect. Spatially-varying effects are regularized by intrinsic Markov random field priors. Inference is based on a full Bayesian Markov Chain Monte Carlo (MCMC) approach. Whether the proposed algorithm is able to increase the sensitivity of mere fMRI models is examined in both a real-world application and a simulation study. We observed, that carefully selected EEG--prior information additionally increases sensitivity in activation regions that have been distorted by a low signal-to-noise ratio

Linking fast and slow: the case for generative models

A pervasive challenge in neuroscience is testing whether neuronal connectivity changes over time due to specific causes, such as stimuli, events, or clinical interventions. Recent hardware innovations and falling data storage costs enable longer, more naturalistic neuronal recordings. The implicit opportunity for understanding the self-organised brain calls for new analysis methods that link temporal scales: from the order of milliseconds over which neuronal dynamics evolve, to the order of minutes, days or even years over which experimental observations unfold. This review article demonstrates how hierarchical generative models and Bayesian inference help to characterise neuronal activity across different time scales. Crucially, these methods go beyond describing statistical associations among observations and enable inference about underlying mechanisms. We offer an overview of fundamental concepts in state-space modeling and suggest a taxonomy for these methods. Additionally, we introduce key mathematical principles that underscore a separation of temporal scales, such as the slaving principle, and review Bayesian methods that are being used to test hypotheses about the brain with multi-scale data. We hope that this review will serve as a useful primer for experimental and computational neuroscientists on the state of the art and current directions of travel in the complex systems modelling literature.Comment: 20 pages, 5 figure