Group-level functional connectivity analyses often aim to detect the altered connectivity patterns between subgroups with different clinical or psychological experimental conditions, for example, comparing cases and healthy controls. We present a new statistical method to detect differentially expressed connectivity networks with significantly improved power and lower false-positive rates. The goal of our method was to capture most differentially expressed connections within networks of constrained numbers of brain regions (by the rule of parsimony). By virtue of parsimony, the false-positive individual connectivity edges within a network are effectively reduced, whereas the informative (differentially expressed) edges are allowed to borrow strength from each other to increase the overall power of the network. We develop a test statistic for each network in light of combinatorics graph theory, and provide p-values for the networks (in the weak sense) by using permutation test with multiple-testing adjustment. We validate and compare this new approach with existing methods, including false discovery rate and network-based statistic, via simulation studies and a resting-state functional magnetic resonance imaging case–control study. The results indicate that our method can identify differentially expressed connectivity networks, whereas existing methods are limited.

Brain connectivity studies often refer to brain areas as graph nodes and connections between nodes as edges, and aim to identify neuropsychiatric phenotype-related connectivity patterns. When performing group-level brain connectivity alternation analyses, it is critical to model the dependence structure between multivariate connectivity edges to achieve accurate and efficient estimates of model parameters. However, specifying and estimating dependencies between connectivity edges presents formidable challenges because (i) the dimensionality of parameters in the covariance matrix is high (of the order of the fourth power of the number of nodes); (ii) the covariance between a pair of edges involves four nodes with spatial location information; and (iii) the dependence structure between edges can be related to unknown network topological structures. Existing methods for large covariance/precision matrix regularization and spatial closeness-based dependence structure specification/estimation models may not fully address the complexity and challenges. We develop a new Bayesian nonparametric model that unifies information from brain network areas (nodes), connectivity (edges), and covariance between edges by constructing the function of covariance matrix based on the underlying network topological structure. We perform parameter estimation using an efficient Markov chain Monte Carlo algorithm. We apply our method to resting-state functional magnetic resonance imaging data from 60 subjects of a schizophrenia study and simulated data to demonstrate the performance of our method.

Emerging brain connectivity network studies suggest that interactions between various distributed neuronal populations may be characterized by an organized complex topological structure. Many neuropsychiatric disorders are associated with altered topological patterns of brain connectivity. Therefore, a key inquiry of connectivity analysis is to detect group-level differentially expressed connectome patterns from the massive neuroimaging data. Recently, statistical methods have been developed to detect differentially expressed connectivity features at a subnetwork level, extending more commonly applied edge level analysis. However, the graph topological structures in these methods are limited to community/cliques which may not effectively uncover the underlying complex and disease-related brain circuits/subnetworks. Building on these previous subnetwork detection methods, a new statistical approach is developed to automatically identify the latent differentially expressed brain connectivity subnetworks with k-partite graph topological structures from large brain connectivity matrices. In addition, statistical inferential techniques are provided to test the detected topological structure. The new methods are evaluated via extensive simulation studies and then applied to resting state fMRI data (24 cases and 18 controls) for Parkinson's disease research. A differentially expressed connectivity network with the k-partite graph topological structure is detected which reveals underlying neural features distinguishing Parkinson's disease patients from healthy control subjects.

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Autism spectrum disorder (ASD) is associated with disrupted brain networks. Neuroimaging techniques provide noninvasive methods of investigating abnormal connectivity patterns in ASD. In the present study, we compare functional connectivity networks in people with ASD with those in typical controls, using neuroimaging data from the Autism Brain Imaging Data Exchange (ABIDE) project. Specifically, we focus on the characteristics of intrinsic functional connectivity based on data collected by resting-state functional magnetic resonance imaging (rs-fMRI). Our aim was to identify disrupted brain connectivity patterns across all networks, instead of in individual edges, by using advanced statistical methods. Unlike many brain connectome studies, in which networks are prespecified before the edge connectivity in each network is compared between clinical groups, we detected the latent differentially expressed networks automatically. Our network-level analysis identified abnormal connectome networks that (i) included a high proportion of edges that were differentially expressed between people with ASD and typical controls; and (ii) showed highly-organized graph topology. These findings provide new insight into the study of the underlying neuropsychiatric mechanism of ASD.