A Novel Sparse Group Gaussian Graphical Model for Functional Connectivity Estimation

International audienceThe estimation of intra-subject functional connectivity is greatly complicated by the small sample size and complex noise structure in functional magnetic resonance imaging (fMRI) data. Pooling samples across subjects improves the conditioning of the estimation, but loses subject-specific connectivity information. In this paper, we propose a new sparse group Gaussian graphical model (SGGGM) that facilitates joint estimation of intra-subject and group-level connectivity. This is achieved by casting functional connectivity estimation as a regularized consensus optimization problem, in which information across subjects is aggregated in learning group-level connectivity and group information is propagated back in estimating intra-subject connectivity. On synthetic data, we show that incorporating group information using SGGGM significantly enhances intra-subject connectivity estimation over existing techniques. More accurate group-level connectivity is also obtained. On real data from a cohort of 60 subjects, we show that integrating intra-subject connectivity estimated with SGGGM significantly improves brain activation detection over connectivity priors derived from other graphical modeling approaches

High Dimensional Dependent Data Analysis for Neuroimaging.

This dissertation contains three projects focusing on two major high-dimensional problems for dependent data, particularly neuroimaging data: multiple testing and estimation of large covariance/precision matrices. Project 1 focuses on the multiple testing problem. Traditional voxel-level false discovery rate (FDR) controlling procedures for neuroimaging data often ignore the spatial correlations among neighboring voxels, thus suffer from substantial loss of efficiency in reducing the false non-discovery rate. We extend the one-dimensional hidden Markov chain based local-significance-index procedure to three-dimensional hidden Markov random field (HMRF). To estimate model parameters, a generalized EM algorithm is proposed for maximizing the penalized likelihood. Simulations show increased efficiency of the proposed approach over commonly used FDR controlling procedures. We apply the method to the comparison between patients with mild cognitive impairment and normal controls in the ADNI FDG-PET imaging study. Project 2 considers estimating large covariance and precision matrices from temporally dependent observations, in particular, the resting-state functional MRI (rfMRI) data in brain functional connectivity studies. Existing work on large covariance and precision matrices is primarily for i.i.d. observations. The rfMRI data from the Human Connectome Project, however, are shown to have long-range memory. Assuming a polynomial-decay-dominated temporal dependence, we obtain convergence rates for the generalized thresholding estimation of covariance and correlation matrices, and for the constrained $ell_1$ minimization and the $ell_1$ penalized likelihood estimation of precision matrix. Properties of sparsistency and sign-consistency are also established. We apply the considered methods to estimating the functional connectivity from single-subject rfMRI data. Project 3 extends Project 2 to multiple independent samples of temporally dependent observations. This is motivated by the group-level functional connectivity analysis using rfMRI data, where each subject has a sample of temporally dependent image observations. We use different concentration inequalities to obtain faster convergence rates than those in Project 2 of the considered estimators for multi-sample data. The new proof allows more general within-sample temporal dependence. We also discuss a potential way of improving the convergence rates by using a weighted sample covariance matrix. We apply the considered methods to the functional connectivity estimation for the ADHD-200 rfMRI data.PhDBiostatisticsUniversity of Michigan, Horace H. Rackham School of Graduate Studieshttp://deepblue.lib.umich.edu/bitstream/2027.42/133198/1/haishu_1.pd