Understanding structural changes in the brain that are caused by a particular disease is a major goal of neuroimaging research. Multivariate pattern analysis (MVPA) comprises a collection of tools that can be used to understand complex disease effects across the brain. We discuss several important issues that must be considered when analyzing data from neuroimaging studies using MVPA. In particular, we focus on the consequences of confounding by non-imaging variables such as age and sex on the results of MVPA. After reviewing current practice to address confounding in neuroimaging studies, we propose an alternative approach based on inverse probability weighting. Although the proposed method is motivated by neuroimaging applications, it is broadly applicable to many problems in machine learning and predictive modeling. We demonstrate the advantages of our approach on simulated and real data examples.
Linn, Kristin A.; Gaonkar, Bilwaj; Doshi, Jimit; Davatzikos, Christos; and Shinohara, Russell T., "Addressing Confounding in Predictive Models with an Application to Neuroimaging" (September 2015). UPenn Biostatistics Working Papers. Working Paper 41.