Fixing the stimulus-as-fixed-effect fallacy in task fMRI.

Most functional magnetic resonance imaging (fMRI) experiments record the brain's responses to samples of stimulus materials (e.g., faces or words). Yet the statistical modeling approaches used in fMRI research universally fail to model stimulus variability in a manner that affords population generalization, meaning that researchers' conclusions technically apply only to the precise stimuli used in each study, and cannot be generalized to new stimuli. A direct consequence of this stimulus-as-fixed-effect fallacy is that the majority of published fMRI studies have likely overstated the strength of the statistical evidence they report. Here we develop a Bayesian mixed model (the random stimulus model; RSM) that addresses this problem, and apply it to a range of fMRI datasets. Results demonstrate considerable inflation (50-200% in most of the studied datasets) of test statistics obtained from standard "summary statistics"-based approaches relative to the corresponding RSM models. We demonstrate how RSMs can be used to improve parameter estimates, properly control false positive rates, and test novel research hypotheses about stimulus-level variability in human brain responses.