Evaluating the effects of high-throughput structural neuroimaging predictors on whole-brain functional connectome outcomes via network-based vector-on-matrix regression

The joint analysis of multimodal neuroimaging data is critical in the field of brain research because it reveals complex interactive relationships between neurobiological structures and functions. In this study, we focus on investigating the effects of structural imaging (SI) features, including white matter micro-structure integrity (WMMI) and cortical thickness, on the whole brain functional connectome (FC) network. To achieve this goal, we propose a network-based vector-on-matrix regression model to characterize the FC-SI association patterns. We have developed a novel multi-level dense bipartite and clique subgraph extraction method to identify which subsets of spatially specific SI features intensively influence organized FC sub-networks. The proposed method can simultaneously identify highly correlated structural-connectomic association patterns and suppress false positive findings while handling millions of potential interactions. We apply our method to a multimodal neuroimaging dataset of 4,242 participants from the UK Biobank to evaluate the effects of whole-brain WMMI and cortical thickness on the resting-state FC. The results reveal that the WMMI on corticospinal tracts and inferior cerebellar peduncle significantly affect functional connections of sensorimotor, salience, and executive sub-networks with an average correlation of 0.81 (p<0.001).Comment: 20 pages, 5 figures, 2 table

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

Mapping hybrid functional-structural connectivity traits in the human connectome

One of the crucial questions in neuroscience is how a rich functional repertoire of brain states relates to its underlying structural organization. How to study the associations between these structural and functional layers is an open problem that involves novel conceptual ways of tackling this question. We here propose an extension of the Connectivity Independent Component Analysis (connICA) framework, to identify joint structural-functional connectivity traits. Here, we extend connICA to integrate structural and functional connectomes by merging them into common hybrid connectivity patterns that represent the connectivity fingerprint of a subject. We test this extended approach on the 100 unrelated subjects from the Human Connectome Project. The method is able to extract main independent structural-functional connectivity patterns from the entire cohort that are sensitive to the realization of different tasks. The hybrid connICA extracted two main task-sensitive hybrid traits. The first, encompassing the within and between connections of dorsal attentional and visual areas, as well as fronto-parietal circuits. The second, mainly encompassing the connectivity between visual, attentional, DMN and subcortical networks. Overall, these findings confirms the potential ofthe hybrid connICA for the compression of structural/functional connectomes into integrated patterns from a set of individual brain networks.Comment: article: 34 pages, 4 figures; supplementary material: 5 pages, 5 figure

Testing for Differences in Gaussian Graphical Models: Applications to Brain Connectivity

Functional brain networks are well described and estimated from data with Gaussian Graphical Models (GGMs), e.g. using sparse inverse covariance estimators. Comparing functional connectivity of subjects in two populations calls for comparing these estimated GGMs. Our goal is to identify differences in GGMs known to have similar structure. We characterize the uncertainty of differences with confidence intervals obtained using a parametric distribution on parameters of a sparse estimator. Sparse penalties enable statistical guarantees and interpretable models even in high-dimensional and low-sample settings. Characterizing the distributions of sparse models is inherently challenging as the penalties produce a biased estimator. Recent work invokes the sparsity assumptions to effectively remove the bias from a sparse estimator such as the lasso. These distributions can be used to give confidence intervals on edges in GGMs, and by extension their differences. However, in the case of comparing GGMs, these estimators do not make use of any assumed joint structure among the GGMs. Inspired by priors from brain functional connectivity we derive the distribution of parameter differences under a joint penalty when parameters are known to be sparse in the difference. This leads us to introduce the debiased multi-task fused lasso, whose distribution can be characterized in an efficient manner. We then show how the debiased lasso and multi-task fused lasso can be used to obtain confidence intervals on edge differences in GGMs. We validate the techniques proposed on a set of synthetic examples as well as neuro-imaging dataset created for the study of autism

Brain covariance selection: better individual functional connectivity models using population prior

Spontaneous brain activity, as observed in functional neuroimaging, has been shown to display reproducible structure that expresses brain architecture and carries markers of brain pathologies. An important view of modern neuroscience is that such large-scale structure of coherent activity reflects modularity properties of brain connectivity graphs. However, to date, there has been no demonstration that the limited and noisy data available in spontaneous activity observations could be used to learn full-brain probabilistic models that generalize to new data. Learning such models entails two main challenges: i) modeling full brain connectivity is a difficult estimation problem that faces the curse of dimensionality and ii) variability between subjects, coupled with the variability of functional signals between experimental runs, makes the use of multiple datasets challenging. We describe subject-level brain functional connectivity structure as a multivariate Gaussian process and introduce a new strategy to estimate it from group data, by imposing a common structure on the graphical model in the population. We show that individual models learned from functional Magnetic Resonance Imaging (fMRI) data using this population prior generalize better to unseen data than models based on alternative regularization schemes. To our knowledge, this is the first report of a cross-validated model of spontaneous brain activity. Finally, we use the estimated graphical model to explore the large-scale characteristics of functional architecture and show for the first time that known cognitive networks appear as the integrated communities of functional connectivity graph.Comment: in Advances in Neural Information Processing Systems, Vancouver : Canada (2010

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