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

Charpentier, Caroline J. and Faulkner, Paul and Pool, Eva R. and Ly, Verena and Tollenaar, Marieke S. and Kluen, Lisa M. and Fransen, Aniek and Yamamori, Yumeya and Lally, Níall and Mkrtchian, Anahit and Valton, Vincent and Huys, Quentin J. M. and Sarigiannidis, Ioannis and Morrow, Kelly A. and Krenz, Valentina and Kalbe, Felix and Cremer, Anna and Zerbes, Gundula and Kausche, Franziska M. and Wanke, Nadine and Giarrizzo, Alessio and Pulcu, Erdem and Murphy, Susannah and Kaltenboeck, Alexander and Browning, Michael and Paul, Lynn K. and Cools, Roshan and Roelofs, Karin and Pessoa, Luiz and Harmer, Catherine J. and Chase, Henry W. and Grillon, Christian and Schwabe, Lars and Roiser, Jonathan P. and Robinson, Oliver J. and O'Doherty, John P. (2021) How representative are neuroimaging samples? Large-scale evidence for trait anxiety differences between fMRI and behaviour-only research participants. Social Congnitive and Affective Neuroscience, 16 (10). pp. 1057-1070. ISSN 1749-5016. PMCID PMC8483285. doi:10.1093/scan/nsab057.

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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.

Item Type:Article
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URLURL TypeDescription CentralArticle
Charpentier, Caroline J.0000-0002-7283-0738
Giarrizzo, Alessio0000-0001-9455-7544
Paul, Lynn K.0000-0002-3128-8313
Schwabe, Lars0000-0003-4429-4373
O'Doherty, John P.0000-0003-0016-3531
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 (, 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.
Funding AgencyGrant Number
Wellcome Trust218642/Z/19/Z
Caltech Conte Center for the Neurobiology of Social Decision MakingUNSPECIFIED
NIHR01 DA040011
Medical Research FoundationC0497
Medical Research Council (UK)MR/K024280/1
Wellcome Trust200934/Z/16/Z
Deutsche Forschungsgemeinschaft (DFG)SFB/TRR 58
Deutsche Forschungsgemeinschaft (DFG)SCHW1357/14-1
Deutsche Forschungsgemeinschaft (DFG)SCHW1357/16-1
Swiss Centre for Affective SciencesUNSPECIFIED
Wellcome Trust101798/Z/13/Z
University College LondonUNSPECIFIED
Max Planck SocietyUNSPECIFIED
Oxford Health Biomedical Research CentreUNSPECIFIED
NIHR01 MH071589
NIHR01 MH112517
Nederlandse Organisatie voor Wetenschappelijk Onderzoek (NWO)453-14-015
Ammodo Science AwardUNSPECIFIED
Human Brain ProjectUNSPECIFIED
European Research Council (ERC)772337
Subject Keywords:trait anxiety, neuroimaging, behaviour, sampling bias
Issue or Number:10
PubMed Central ID:PMC8483285
Record Number:CaltechAUTHORS:20211005-142053310
Persistent URL:
Official Citation:Caroline J Charpentier, Paul Faulkner, Eva R Pool, Verena Ly, Marieke S Tollenaar, Lisa M Kluen, Aniek Fransen, Yumeya Yamamori, Níall Lally, Anahit Mkrtchian, Vincent Valton, Quentin J M Huys, Ioannis Sarigiannidis, Kelly A Morrow, Valentina Krenz, Felix Kalbe, Anna Cremer, Gundula Zerbes, Franziska M Kausche, Nadine Wanke, Alessio Giarrizzo, Erdem Pulcu, Susannah Murphy, Alexander Kaltenboeck, Michael Browning, Lynn K Paul, Roshan Cools, Karin Roelofs, Luiz Pessoa, Catherine J Harmer, Henry W Chase, Christian Grillon, Lars Schwabe, Jonathan P Roiser, Oliver J Robinson, John P O’Doherty, How representative are neuroimaging samples? Large-scale evidence for trait anxiety differences between fMRI and behaviour-only research participants, Social Cognitive and Affective Neuroscience, Volume 16, Issue 10, October 2021, Pages 1057–1070,
Usage Policy:No commercial reproduction, distribution, display or performance rights in this work are provided.
ID Code:111214
Deposited By: Tony Diaz
Deposited On:05 Oct 2021 15:09
Last Modified:05 Oct 2021 15:09

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