Making an unknown unknown a known unknown: Missing data in longitudinal neuroimaging studies.

The analysis of longitudinal neuroimaging data within the massively univariate framework provides the opportunity to study empirical questions about neurodevelopment. Missing outcome data are an all-to-common feature of any longitudinal study, a feature that, if handled improperly, can reduce statistical power and lead to biased parameter estimates. The goal of this paper is to provide conceptual clarity of the issues and non-issues that arise from analyzing incomplete data in longitudinal studies with particular focus on neuroimaging data. This paper begins with a review of the hierarchy of missing data mechanisms and their relationship to likelihood-based methods, a review that is necessary not just for likelihood-based methods, but also for multiple-imputation methods. Next, the paper provides a series of simulation studies with designs common in longitudinal neuroimaging studies to help illustrate missing data concepts regardless of interpretation. Finally, two applied examples are used to demonstrate the sensitivity of inferences under different missing data assumptions and how this may change the substantive interpretation. The paper concludes with a set of guidelines for analyzing incomplete longitudinal data that can improve the validity of research findings in developmental neuroimaging research.