A hierarchical independent component analysis model for longitudinal neuroimaging studies.

In recent years, longitudinal neuroimaging study has become increasingly popular in neuroscience research to investigate disease-related changes in brain functions, to study neurodevelopment or to evaluate treatment effects on neural processing. One of the important goals in longitudinal imaging analysis is to study changes in brain functional networks across time and how the changes are modulated by subjects' clinical or demographic variables. In current neuroscience literature, one of the most commonly used tools to extract and characterize brain functional networks is independent component analysis (ICA), which separates multivariate signals into linear mixture of independent components. However, existing ICA methods are only applicable to cross-sectional studies and not suited for modeling repeatedly measured imaging data. In this paper, we propose a novel longitudinal independent component model (L-ICA) which provides a formal modeling framework for extending ICA to longitudinal studies. By incorporating subject-specific random effects and visit-specific covariate effects, L-ICA is able to provide more accurate estimates of changes in brain functional networks on both the population- and individual-level, borrow information across repeated scans within the same subject to increase statistical power in detecting covariate effects on the networks, and allow for model-based prediction for brain networks changes caused by disease progression, treatment or neurodevelopment. We develop a fully traceable exact EM algorithm to obtain maximum likelihood estimates of L-ICA. We further develop a subspace-based approximate EM algorithm which greatly reduce the computation time while still retaining high accuracy. Moreover, we present a statistical testing procedure for examining covariate effects on brain network changes. Simulation results demonstrate the advantages of our proposed methods. We apply L-ICA to ADNI2 study to investigate changes in brain functional networks in Alzheimer disease. Results from the L-ICA provide biologically insightful findings which are not revealed using existing methods.