Xi Luo

Yi Zhao, Xi Luo

It becomes increasingly popular to perform mediation analysis for complex data from sophisticated experimental studies. In this paper, we present Granger Mediation Analysis (GMA), a new framework for causal mediation analysis of multiple time series. This framework is motivated by a functional magnetic resonance imaging (fMRI) experiment where we are interested in estimating the mediation effects between a randomized stimulus time series and brain activity time series from two brain regions. The stable unit treatment assumption for causal mediation analysis is thus unrealistic for this type of time series data. To address this challenge, our framework integrates two types of models: causal mediation analysis across the variables and vector autoregressive models across the temporal observations. We further extend this framework to handle multilevel data to address individual variability and correlated errors between the mediator and the outcome variables. These models not only provide valid causal mediation for time series data but also model the causal dynamics across time. We show that the modeling parameters in our models are identifiable, and we develop computationally efficient methods to maximize the likelihood-based optimization criteria. Simulation studies show that our method reduces the estimation bias and improve statistical power, compared to existing approaches. On a real fMRI data set, our approach not only infers the causal effects of brain pathways but accurately captures the feedback effect of the outcome region on the mediator region.

Yi Zhao, Xi Luo

In many scientific studies, it becomes increasingly important to delineate the causal pathways through a large number of mediators, such as genetic and brain mediators. Structural equation modeling (SEM) is a popular technique to estimate the pathway effects, commonly expressed as products of coefficients. However, it becomes unstable to fit such models with high dimensional mediators, especially for a general setting where all the mediators are causally dependent but the exact causal relationships between them are unknown. This paper proposes a sparse mediation model using a regularized SEM approach, where sparsity here means that a small number of mediators have nonzero mediation effects between a treatment and an outcome. To address the model selection challenge, we innovate by introducing a new penalty called Pathway Lasso. This penalty function is a convex relaxation of the non-convex product function, and it enables a computationally tractable optimization criterion to estimate and select many pathway effects simultaneously. We develop a fast ADMM-type algorithm to compute the model parameters, and we show that the iterative updates can be expressed in closed form. On both simulated data and a real fMRI dataset, the proposed approach yields higher pathway selection accuracy and lower estimation bias than other competing methods.

Xi Luo

Brain networks has attracted the interests of many neuroscientists. From functional MRI (fMRI) data, statistical tools have been developed to recover brain networks. However, the dimensionality of whole-brain fMRI, usually in hundreds of thousands, challenges the applicability of these methods. We develop a hierarchical graphical model (HGM) to remediate this difficulty. This model introduces a hidden layer of networks based on sparse Gaussian graphical models, and the observed data are sampled from individual network nodes. In fMRI, the network layer models the underlying signals of different brain functional units, and how these units directly interact with each other. The introduction of this hierarchical structure not only provides a formal and interpretable approach, but also enables efficient computation for inferring big networks with hundreds of thousands of nodes. Based on the conditional convexity of our formulation, we develop an alternating update algorithm to compute the HGM model parameters simultaneously. The effectiveness of this approach is demonstrated on simulated data and a real dataset from a stop/go fMRI experiment.