A Methodological Checklist for fMRI Drug Cue Reactivity Studies: Development and Expert Consensus

Background: Cue reactivity is one of the most frequently used paradigms in functional magnetic resonance imaging (fMRI) studies of substance use disorders (SUDs). Although there have been many promising results elucidating the neurocognitive mechanisms of SUDs and SUD treatments, heterogeneities in participant characteristics, task design, craving assessment, scanning preparation and analysis decisions limit rigor and reproducibility in the field of fMRI of drug cue reactivity (FDCR), hampering clinical translation and synthesis by systematic reviews and meta-analyses. The aim of this consensus paper and Delphi study is to outline the important methodological aspects of FDCR studies and present a list of items and recommendations that should be taken into account when designing FDCR studies and reporting their results. Methods: Fifty-five FDCR scientists from around the world participated. First, an initial checklist of items deemed important in FDCR studies was developed by a group of members from the ENIGMA Addiction Consortium based on a systematic review. Then, using a modified Delphi consensus method, all experts were asked to comment on, revise or add items to the initial checklist. Subsequently, experts were asked to rate the importance of the items. Results: Thirty-seven items were proposed in the first round. After the commenting phase, seven new items suggested by experts were added and six were removed. The final 38 items that reached a defined consensus threshold in the rating phase were classified under seven categories and are considered important for conducting and reporting in any FDCR study. Conclusion: This paper proposes a list of items and additional recommendations that researchers in the field of FDCR are encouraged to note and report when designing an FDCR study and reporting its results. Along with the presentation of a quality control checklist with Yes/No ratable items, various challenges in moving towards greater homogeneity in FDCR research and widespread use of FDCR to investigate SUDs and develop clinically relevant biomarkers are discussed. Key Terms: fMRI, Cue Reactivity, Addiction, Craving, Biomarker, Harmonization, Checklist