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

Abstract

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

fMRI as an outcome measure in clinical trials: A systematic review in clinicaltrials.gov

“…In this preregistration, researchers have provided details on the methods and analysis for this fMRI‐based outcome measure, however, there are still details needed to increase the replicability of the outcome measure such as task version, task analysis contrast, and many details in the preprocessing, ROI definition and data analysis pipeline. We believe that higher level of reproducibility could be facilitated with a detailed checklist that should be developed in a consensus process (Ekhtiari, et al., 2020). It is true that clinicaltrial.gov website is not technically designed to provide, encourage or fully support this checklist, however, we should mention that there is still an available space in the clinicaltrial.gov website for each trial to provide detailed descriptions up to 32,000 characters, and also there is a possibility for uploading additional documents for preregistration including structured checklists for methodological details.…”

“…Currently, there is a large gap in harmonized collective efforts with shared fMRI protocols and study designs to help accumulate replicable knowledge in the field over time. Meanwhile, there is a growing effort in the neuroimaging community to develop domain‐specific and domain‐general checklists for better quality reporting of fMRI studies (Ekhtiari et al., 2020). We hope this systematic review and its recommendations will help to move one step forward for this endeavor.…”

Functional evaluation of NK1 antagonism on cue reactivity in opiate dependence; An fMRI study

“…We are adopting the ENIGMA Addiction Cue Reactivity (ACRI) Checklist ( Ekhtiari et al, 2020 ) in our reporting and have added the checklist as supplementary material to highlight where items are addressed in the main body of text.…”

FMRI-based prediction of naltrexone response in alcohol use disorder: a replication study

“…Our trial was pre-registered and designed to investigate neuronal networks in alcoholism, which included analyses of structural and functional connectivity, as well as alcohol cue-induced brain responses (clinical trials id DRKS00003357). Methodological details of the presented alcohol cue-reactivity fMRI study are reported following the recommendations of a recently published ENIGMA consensus paper [13]. Overall, a total of n = 55 abstinent treatment-seeking male patients (100% male) with alcohol dependence were enrolled of whom n = 45 patients with complete follow-up and fMRI baseline data were included in current analyses (n = 5 patients had to be excluded due to fMRI artifacts or due to a different fMRI task version and n = 5 additional patients had to be excluded due to loss to follow-up, because of refusal to continue study procedures)(see Fig.…”