False-positive neuroimaging: Undisclosed flexibility in testing spatial hypotheses allows presenting anything as a replicated finding.

Hypothesis testing in neuroimaging studies relies heavily on treating named anatomical regions (e.g., "the amygdala") as unitary entities. Though data collection and analyses are conducted at the voxel level, inferences are often based on anatomical regions. The discrepancy between the unit of analysis and the unit of inference leads to ambiguity and flexibility in analyses that can create a false sense of reproducibility. For example, hypothesizing effects on "amygdala activity" does not provide a falsifiable and reproducible definition of precisely which voxels or which patterns of activation should be observed. Rather, it comprises a large number of unspecified sub-hypotheses, leaving room for flexible interpretation of findings, which we refer to as "model degrees of freedom." From a survey of 135 functional Magnetic Resonance Imaging studies in which researchers claimed replications of previous findings, we found that 42.2% of the studies did not report any quantitative evidence for replication such as activation peaks. Only 14.1% of the papers used exact coordinate-based or a priori pattern-based models. Of the studies that reported peak information, 42.9% of the 'replicated' findings had peak coordinates more than 15 mm away from the 'original' findings, suggesting that different brain locations were activated, even when studies claimed to replicate prior results. To reduce the flexible and qualitative region-level tests in neuroimaging studies, we recommend adopting quantitative spatial models and tests to assess the spatial reproducibility of findings. Techniques reviewed here include permutation tests on peak distance, Bayesian MANOVA, and a priori multivariate pattern-based models. These practices will help researchers to establish precise and falsifiable spatial hypotheses, promoting a cumulative science of neuroimaging.