Five years of harmonized fMRI data analysis with HALFpipe in the ENIGMA consortium

Brisbane Convention & Exhibition Centre 

Finding and validating biomarkers for mental health and behavior using neuroimaging requires combining many diverse cohorts in large-scale meta- and mega-analyses. In such studies, ensuring computational and analytic reproducibility becomes a core challenge. Five years ago, we released ENIGMA HALFpipe, a software built for collaborative projects creating such global benchmarks of biomarker discovery. HALFpipe is based on fMRIPrep for preprocessing and makes extensive use of other tools from the neuroimaging and open science ecosystem. At time of writing, more than ten resting state fMRI projects and three task-based fMRI projects are using HALFpipe within the consortium, with more than fifty thousand participants included across various psychiatric diagnoses and controls. Across these projects, we have encountered a number of important lessons that we will describe in this talk. Some examples of considerations include, for resting-state fMRI, the problem of analytic flexibility, and for task-based fMRI, how to model tasks on the individual level. For any task-based fMRI study, there are various ways in which researchers can operationalize a single psychological construct or cognitive domain into a concrete fMRI paradigm. We rely on an ontology-based protocol that standardizes design matrices and contrasts across sites. This ensures the interpretability of meta- and mega-analytic results. Another consideration involves the proportion of missing data we have encountered in meta- and mega-analyses. The brain coverage for different MRI scanners and acquisition protocols lead to missing parts of the brain in most multi-site datasets for at least some participants. This data is not missing at random, but is associated with head size and gender, meaning that statistics need to be carefully considered to avoid biased results. In this talk, I will discuss these and other challenges, as well as our roadmap for continuing to support large-scale collaborative investigations within ENIGMA and beyond.