A simple and objective method for reproducible resting state network (RSN) detection in fMRI

Spatial Independent Component Analysis (ICA) decomposes the time by space functional MRI (fMRI) matrix into a set of 1-D basis time courses and their associated 3-D spatial maps that are optimized for mutual independence. When applied to resting state fMRI (rsfMRI), ICA produces several spatial independent components (ICs) that seem to have biological relevance - the so-called resting state networks (RSNs). The ICA problem is well posed when the true data generating process follows a linear mixture of ICs model in terms of the identifiability of the mixing matrix. However, the contrast function used for promoting mutual independence in ICA is dependent on the finite amount of observed data and is potentially non-convex with multiple local minima. Hence, each run of ICA could produce potentially different IC estimates even for the same data. One technique to deal with this run-to-run variability of ICA was proposed by Yang et al. (2008) in their algorithm RAICAR which allows for the selection of only those ICs that have a high run-to-run reproducibility. We propose an enhancement to the original RAICAR algorithm that enables us to assign reproducibility p-values to each IC and allows for an objective assessment of both within subject and across subjects reproducibility. We call the resulting algorithm RAICAR-N (N stands for null hypothesis test), and we have applied it to publicly available human rsfMRI data (http://www.nitrc.org). Our reproducibility analyses indicated that many of the published RSNs in rsfMRI literature are highly reproducible. However, we found several other RSNs that are highly reproducible but not frequently listed in the literature.Comment: 54 pages, 13 figure

Modeling Covariate Effects in Group Independent Component Analysis with Applications to Functional Magnetic Resonance Imaging

Independent component analysis (ICA) is a powerful computational tool for separating independent source signals from their linear mixtures. ICA has been widely applied in neuroimaging studies to identify and characterize underlying brain functional networks. An important goal in such studies is to assess the effects of subjects' clinical and demographic covariates on the spatial distributions of the functional networks. Currently, covariate effects are not incorporated in existing group ICA decomposition methods. Hence, they can only be evaluated through ad-hoc approaches which may not be accurate in many cases. In this paper, we propose a hierarchical covariate ICA model that provides a formal statistical framework for estimating and testing covariate effects in ICA decomposition. A maximum likelihood method is proposed for estimating the covariate ICA model. We develop two expectation-maximization (EM) algorithms to obtain maximum likelihood estimates. The first is an exact EM algorithm, which has analytically tractable E-step and M-step. Additionally, we propose a subspace-based approximate EM, which can significantly reduce computational time while still retain high model-fitting accuracy. Furthermore, to test covariate effects on the functional networks, we develop a voxel-wise approximate inference procedure which eliminates the needs of computationally expensive covariance estimation. The performance of the proposed methods is evaluated via simulation studies. The application is illustrated through an fMRI study of Zen meditation.Comment: 36 pages, 5 figure