Assessing inter-individual differences with task-related functional neuroimaging

Explaining and predicting individual behavioural differences induced by clinical and social factors constitutes one of the most promising applications of neuroimaging. In this Perspective, we discuss the theoretical and statistical foundations of the analyses of inter-individual differences in task-related functional neuroimaging. Leveraging a five-year literature review (July 2013–2018), we show that researchers often assess how activations elicited by a variable of interest differ between individuals. We argue that the rationale for such analyses, typically grounded in resource theory, offers an over-large analytical and interpretational flexibility that undermines their validity. We also recall how, in the established framework of the general linear model, inter-individual differences in behaviour can act as hidden moderators and spuriously induce differences in activations. We conclude with a set of recommendations and directions, which we hope will contribute to improving the statistical validity and the neurobiological interpretability of inter-individual difference analyses in task-related functional neuroimaging.