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Published October 2021 | Published + Supplemental Material
Journal Article Open

How representative are neuroimaging samples? Large-scale evidence for trait anxiety differences between fMRI and behaviour-only research participants


Over the past three decades, functional magnetic resonance imaging (fMRI) has become crucial to study how cognitive processes are implemented in the human brain. However, the question of whether participants recruited into fMRI studies differ from participants recruited into other study contexts has received little to no attention. This is particularly pertinent when effects fail to generalize across study contexts: for example, a behavioural effect discovered in a non-imaging context not replicating in a neuroimaging environment. Here, we tested the hypothesis, motivated by preliminary findings (N = 272), that fMRI participants differ from behaviour-only participants on one fundamental individual difference variable: trait anxiety. Analysing trait anxiety scores and possible confounding variables from healthy volunteers across multiple institutions (N = 3317), we found robust support for lower trait anxiety in fMRI study participants, consistent with a sampling or self-selection bias. The bias was larger in studies that relied on phone screening (compared with full in-person psychiatric screening), recruited at least partly from convenience samples (compared with community samples), and in pharmacology studies. Our findings highlight the need for surveying trait anxiety at recruitment and for appropriate screening procedures or sampling strategies to mitigate this bias.

Additional Information

© The Author(s) 2021. Published by Oxford University Press. This is an Open Access article distributed under the terms of the Creative Commons Attribution License (https://creativecommons.org/licenses/by/4.0/), which permits unrestricted reuse, distribution, and reproduction in any medium, provided the original work is properly cited. Received: 20 April 2020; Revision received: 13 March 2021; Editorial decision: 30 April 2021; Accepted: 04 May 2021; Published: 05 May 2021; Corrected and typeset: 28 September 2021. C.J.C. is supported by Wellcome Trust's Sir Henry Wellcome Postdoctoral Fellowship (218642/Z/19/Z). J.O.D. and L.K.P. are supported by the Caltech Conte Center for the Neurobiology of Social Decision-Making (NIMH award: P50MH094258). J.O.D. is supported by a National Institute on Drug Abuse R01 DA040011. O.J.R. and Y.Y. were funded by a Medical Research Foundation Equipment Competition Grant (C0497, Principal Investigator O.J.R.); a Medical Research Council Career Development Award to O.J.R. (MR/K024280/1). A.M. is supported by Wellcome Trust-NIH PhD Studentship (200934/Z/16/Z). L.S. was supported by the German Research Foundation (DFG; grants: SFB/TRR 58, project B10; SCHW1357/14-1; SCHW1357/16-1). E.P. and A.G. are supported by the Swiss Centre for Affective Sciences. J.P.R. and V.V. are supported by the Wellcome Trust (101798/Z/13/Z). V.V. is supported by an NIHR UCLH Biomedical Research Centre Fellowship. Q.J.M.H. acknowledges support by the Max Planck Society and the UCL NIHR BRC. M.B. is supported by the NIHR Oxford Health Biomedical Research Centre and the NIHR Oxford cognitive health Clinical Research Facility. C.J.H. and S.E.M. are supported by the NIHR Oxford Health Biomedical Research Centre. L.P. was supported by the National Institute of Mental Health (R01 MH071589 and R01 MH112517). R.C. is supported by a Vici award from the Netherlands Organisation for Scientific Research (453-14-015), an Ammodo Science Award and a lead scientist voucher from the Human Brain Project. C.G. is supported by the Intramural Research Program, National Institute of Mental Health (grant number ZIAMH002798, NCT00026559). K.R. is supported by a consolidator grant from the European Research Council (ERC_CoG-2017_772337). The funders had no role in study design, data analysis, decision to publish or preparation of the manuscript. Conflict of interest: O.J.R.'s current MRC senior fellowship is partially in collaboration with Cambridge Cognition (who plan to provide in kind contribution). He is running an investigator-initiated trial with medication donated by Lundbeck (escitalopram and placebo, no financial contribution), holds an MRC-Proximity to discovery award with Roche (in kind contributions, sponsor travel) and has completed consultancy work for Peak and IESO digital health. J.P.R. has performed consultancy work for Cambridge Cognition, Takeda and GE Healthcare. M.B. has received travel expenses from Lundbeck for attending conferences, and has acted as a consultant for J&J and for CHDR. C.J.H. has received consultancy fees from P1vital Ltd., Sage Pharmaceuticals, Zogenix, J&J and Pfizer. S.E.M. has received consultancy fees from Janssen Pharmaceuticals, Zogenix and Sumitomo Dainippon Pharma and holds grant income from UCB Pharma, Janssen Pharmaceuticals and Zogenix and from a collaborative research project with Pfizer. These disclosures are made in the interest of full transparency and do not constitute a direct conflict of interest with the current work. Authors' contributions: C.J.C., O.J.R., H.W.C., J.P.R. and J.O.D. were involved in the conception of the study. C.J.C., P.F., E.R.P., V.L., M.S.T., L.M.K., A.F., Y.Y., N.L., A.M., V.V., Q.J.M.H., I.S., K.A.M., V.K., F.K., A.C., G.Z., F.M.K., N.W., A.G., E.P., S.M., A.K., M.B. and L.K.P. collected and contributed data to the large-scale data set. C.J.C. performed data analysis and wrote the manuscript. P.F., E.R.P., V.L., M.S.T., L.M.K., A.F., N.L., V.V., Q.J.M.H., K.A.M., F.K., F.M.K, L.K.P., R.C., K.R., L.P., C.J.H., H.W.C., C.G., L.S., O.J.R. and J.O.D. commented on the manuscript and contributed to the interpretation of the results and revisions.

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August 20, 2023
October 23, 2023