Improving effect size estimation and statistical power with multi-echo fMRI and its impact on understanding the neural systems supporting mentalizing

Functional magnetic resonance imaging (fMRI) research is routinely criticized for being statistically underpowered due to characteristically small sample sizes and much larger sample sizes are being increasingly recommended. Additionally, various sources of artifact inherent in fMRI data can have detrimental impact on effect size estimates and statistical power. Here we show how specific removal of non-BOLD artifacts can improve effect size estimation and statistical power in task-fMRI contexts, with particular application to the social-cognitive domain of mentalizing/theory of mind. Non-BOLD variability identification and removal is achieved in a biophysical and statistically principled manner by combining multi-echo fMRI acquisition and independent components analysis (ME-ICA). Group-level effect size estimates on two different mentalizing tasks were enhanced by ME-ICA at a median rate of 24% in regions canonically associated with mentalizing, while much more substantial boosts (40-149%) were observed in non-canonical cerebellar areas. This effect size boosting is primarily a consequence of reduction of non-BOLD noise at the subject-level, which then translates into consequent reductions in between-subject variance at the group-level. Power simulations demonstrate that enhanced effect size enables highly-powered studies at traditional sample sizes. Cerebellar effects observed after applying ME-ICA may be unobservable with conventional imaging at traditional sample sizes. Thus, ME-ICA allows for principled design-agnostic non-BOLD artifact removal that can substantially improve effect size estimates and statistical power in task-fMRI contexts. ME-ICA could help issues regarding statistical power and non-BOLD noise and enable potential for novel discovery of aspects of brain organization that are currently under-appreciated and not well understood.