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Neurofeedback Training versus Treatment-as-Usual for Alcohol Dependence: Results of an Early-Phase Randomized Controlled Trial and Neuroimaging Correlates

Subramanian, Leena; Skottnik, Leon; Cox, W. Miles; Luhrs, Michael; McNamara, Rachel; Hood, Kerry; Watson, Gareth; Whittaker, Joseph R.; Williams, Angharad N.; Sakhuja, Raman; Ihssen, Niklas; Goebel, Rainer; Playle, Rebecca; Linden, David E.J.

Neurofeedback Training versus Treatment-as-Usual for Alcohol Dependence: Results of an Early-Phase Randomized Controlled Trial and Neuroimaging Correlates Thumbnail


Leena Subramanian

Leon Skottnik

W. Miles Cox

Michael Luhrs

Rachel McNamara

Kerry Hood

Gareth Watson

Joseph R. Whittaker

Angharad N. Williams

Raman Sakhuja

Rainer Goebel

Rebecca Playle

David E.J. Linden


Introduction: Alcohol dependence is one of the most common substance use disorders, and novel treatment options are urgently needed. Neurofeedback training (NFT) based on real-time functional magnetic resonance imaging (rtf­MRI) has emerged as an attractive candidate for add-on treatments in psychiatry, but its use in alcohol dependence has not been formally investigated in a clinical trial. We investigated the use of rtfMRI-based NFT to prevent relapse in alcohol dependence. Methods: Fifty-two alcohol-dependent patients from the UK who had completed a detoxification program were randomly assigned to a treatment group (receiving rtfMRI NFT in addition to standard care) or the control group (receiving standard care only). At baseline, alcohol consumption was assessed as the primary outcome measure and a variety of psychological, behavioral, and neural parameters as secondary outcome measures to determine feasibility and secondary training effects. Participants in the treatment group underwent 6 NFT sessions over 4 months and were trained to downregulate their brain activation in the salience network in the presence of alcohol stimuli and to upregulate frontal activation in response to pictures related to positive goals. Four, 8, and 12 months after baseline assessment, both groups were followed up with a battery of clinical and psychometric tests. Results: Primary outcome measures showed very low relapse rates for both groups. Analysis of neural secondary outcome measures indicated that the majority of patients modulated the salience system in the desired directions, by decreasing activity in response to alcohol stimuli and increasing activation in response to positive goals. The intervention had a good safety and acceptability profile. Conclusion: We demonstrated that rtfMRI-neurofeedback targeting hyperactivity of the salience network in response to alcohol cues is feasible in currently abstinent patients with alcohol dependence.


Subramanian, L., Skottnik, L., Cox, W. M., Luhrs, M., McNamara, R., Hood, K., …Linden, D. E. (2021). Neurofeedback Training versus Treatment-as-Usual for Alcohol Dependence: Results of an Early-Phase Randomized Controlled Trial and Neuroimaging Correlates. European Addiction Research, 27(5), 381-394.

Journal Article Type Article
Acceptance Date Oct 20, 2020
Online Publication Date Mar 5, 2021
Publication Date 2021-08
Deposit Date Sep 21, 2021
Publicly Available Date Sep 21, 2021
Journal European Addiction Research
Print ISSN 1022-6877
Electronic ISSN 1421-9891
Publisher Karger Publishers
Peer Reviewed Peer Reviewed
Volume 27
Issue 5
Pages 381-394


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Advanced Online Version This article is licensed under the Creative Commons Attribution-NonCommercial 4.0 International License (CC BY-NC). Usage and distribution for commercial purposes requires written permission. Drug Dosage: The authors and the publisher have exerted every effort to ensure that drug selection and dosage set forth in this text are in accord with current recommendations and practice at the time of publication. However, in view of ongoing research, changes in government regulations, and the constant flow of information relating to drug therapy and drug reactions, the reader is urged to check the package insert for each drug for any changes in indications and dosage and for added warnings and precautions. This is particularly important when the recommended agent is a new and/or infrequently employed drug. Disclaimer: The statements, opinions and data contained in this publication are solely those of the individual authors and contributors and not of the publishers and the editor(s). The appearance of advertisements or/and product references in the publication is not a warranty, endorsement, or approval of the products or services advertised or of their effectiveness, quality or safety. The publisher and the editor(s) disclaim responsibility for any injury to persons or property resulting from any ideas, methods, instructions or products referred to in the content or advertisements.

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