Statistical Approaches for Estimation and Comparison of Brain Functional Connectivity

Drug addiction can lead to many health-related problems and social concerns. Functional connectivity obtained from functional magnetic resonance imaging (fMRI) data promotes a variety of fundamental understandings in such association. Due to its complex correlation structure and large dimensionality, the modeling and analysis of the functional connectivity from neuroimage are challenging. By proposing a spatio-temporal model for multi-subject neuroimage data, we incorporate voxel-level spatio-temporal dependencies of whole-brain measurements to improve the accuracy of statistical inference. To tackle large-scale spatio-temporal neuroimage data, we develop a computationally efficient algorithm to estimate the parameters. Our method is used to identify functional connectivity and detect the effect of cocaine use disorder (CUD) on functional connectivity between different brain regions. The functional connectivity identified by our spatio-temporal model matches existing studies on brain networks, and further indicates that CUD may alter the functional connectivity in the medial orbitofrontal cortex subregions and the supplementary motor areas. We further propose a method that jointly estimates the graphical models which share the common structure, while allowing for differences between categories in the data. By assigning different tuning parameters for the contrast of each categorical factor, our method could estimate the effects of multiple treatments or factors across brain regions accurately and achieve computational efficiency at the same time. Simulation studies suggest our method achieves better accuracy in network estimation compared with the joint graphical lasso method. We apply our method to the cocaine-use disorder data and identify functional connectivity in brain affected by cocaine use disorder and gender

Evolution Strategies for Learning Sparse Matrix Representations of Gene Regulatory Networks

Currently, a massive amount of temporal gene expression data is available to researchers, which makes it possible to infer Gene Regulatory Networks (GRNs). Gene regulatory networks are theoretical models to represent excitatory and inhibitory interactions between genes. GRNs are useful in understanding how genes function, and hence they are also useful in pharmaceutical and other applications in biology and medicine. However, despite the importance of GRNs, the process of inferring GRNs from observational data is very difficult. This thesis applies evolutionary algorithms to the problem of GRN inference. We propose a novel evolutionary algorithm: hierarchical evolution strategy (HES) to target the specific difficulties in GRN inference. We propose a sparse matrix representation of GRN to account for sparse connectivity in biological gene interactions. Unlike traditional evolution strategies, we divide our optimization into two concurrent processes: connectivity construction and numerical optimization. In each generation, we first establish connectivity structure of the GRN. Inside the same generation, we apply a secondary ES to find the best numerical values with those fixed connections. We also propose a hybrid crowding method to maintain high population diversity while applying the evolutionary algorithms. High population diversity leads to broader exploration area in the search space, therefore preventing premature convergence. The results obtained show that the proposed HES outperforms other algorithms, and has the potential to scale up to realistic problems with thousands of genes

Revealing networks from dynamics: an introduction

What can we learn from the collective dynamics of a complex network about its interaction topology? Taking the perspective from nonlinear dynamics, we briefly review recent progress on how to infer structural connectivity (direct interactions) from accessing the dynamics of the units. Potential applications range from interaction networks in physics, to chemical and metabolic reactions, protein and gene regulatory networks as well as neural circuits in biology and electric power grids or wireless sensor networks in engineering. Moreover, we briefly mention some standard ways of inferring effective or functional connectivity.Comment: Topical review, 48 pages, 7 figure

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

Advancing functional connectivity research from association to causation

Cognition and behavior emerge from brain network interactions, such that investigating causal interactions should be central to the study of brain function. Approaches that characterize statistical associations among neural time series-functional connectivity (FC) methods-are likely a good starting point for estimating brain network interactions. Yet only a subset of FC methods ('effective connectivity') is explicitly designed to infer causal interactions from statistical associations. Here we incorporate best practices from diverse areas of FC research to illustrate how FC methods can be refined to improve inferences about neural mechanisms, with properties of causal neural interactions as a common ontology to facilitate cumulative progress across FC approaches. We further demonstrate how the most common FC measures (correlation and coherence) reduce the set of likely causal models, facilitating causal inferences despite major limitations. Alternative FC measures are suggested to immediately start improving causal inferences beyond these common FC measures

Uncovering the Temporal Dynamics of Diffusion Networks

Time plays an essential role in the diffusion of information, influence and disease over networks. In many cases we only observe when a node copies information, makes a decision or becomes infected -- but the connectivity, transmission rates between nodes and transmission sources are unknown. Inferring the underlying dynamics is of outstanding interest since it enables forecasting, influencing and retarding infections, broadly construed. To this end, we model diffusion processes as discrete networks of continuous temporal processes occurring at different rates. Given cascade data -- observed infection times of nodes -- we infer the edges of the global diffusion network and estimate the transmission rates of each edge that best explain the observed data. The optimization problem is convex. The model naturally (without heuristics) imposes sparse solutions and requires no parameter tuning. The problem decouples into a collection of independent smaller problems, thus scaling easily to networks on the order of hundreds of thousands of nodes. Experiments on real and synthetic data show that our algorithm both recovers the edges of diffusion networks and accurately estimates their transmission rates from cascade data.Comment: To appear in the 28th International Conference on Machine Learning (ICML), 2011. Website: http://www.stanford.edu/~manuelgr/netrate