Targeting the affective brain—a randomized controlled trial of real-time fMRI neurofeedback in patients with depression
Open accessAbstract
Functional magnetic resonance imaging neurofeedback (fMRI-NF) training of areas involved in emotion processing can reduce depressive symptoms by over 40% on the Hamilton Depression Rating Scale (HDRS). However, it remains unclear if this efficacy is specific to feedback from emotion-regulating regions. We tested in a single-blind, randomized, controlled trial if upregulation of emotion areas (NFE) yields superior efficacy compared to upregulation of a control region activated by visual scenes (NFS). Forty-three moderately to severely depressed medicated patients were randomly assigned to five sessions augmentation treatment of either NFE or NFS training. At primary outcome (week 12) no significant group mean HDRS difference was found (B = -0.415 [95% CI -4.847 to 4.016], p = 0.848) for the 32 completers (16 per group). However, across groups depressive symptoms decreased by 43%, and 38% of patients remitted. These improvements lasted until follow-up (week 18). Both groups upregulated target regions to a similar extent. Further, clinical improvement was correlated with an increase in self-efficacy scores. However, the interpretation of clinical improvements remains limited due to lack of a sham-control group. We thus surveyed effects reported for accepted augmentation therapies in depression. Data indicated that our findings exceed expected regression to the mean and placebo effects that have been reported for drug trials and other sham-controlled high-technology interventions. Taken together, we suggest that the experience of successful self-regulation during fMRI-NF training may be therapeutic. We conclude that if fMRI-NF is effective for depression, self-regulation training of higher visual areas may provide an effective alternative.
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Rt-fMRI NF trainings have been shown to support perceived control and self-efficacy, thus potentially motivating behavioral change.
“Rt-fMRI NF trainings have been shown to support perceived control (Zweerings et al., 2018) and self-efficacy (Mehler et al., 2018), thus potentially motivating behavioral change (MacDuffie et al., 2018).”
From Rt-fMRI neurofeedback-guided cognitive reappraisal training modulates amygdala responsivity in posttraumatic stress disorder (2020) · cites this paper as Mehler et al., 2018
The Discussion (page unavailable) suggests that successful self-regulation during fMRI neurofeedback may increase self-efficacy. The Results report an exploratory association between increased self-efficacy and lower depression severity, but the paper says larger trials are needed to test the proposed mechanism. Thus, the cited source supports a possible benefit for self-efficacy, not that training has definitively been shown to produce it. (LLM, conf=0.82)
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Self-citation
- Authors
- Mehler, D. M. A., Sokunbi, M. O., Habes, I., Barawi, K., Subramanian, L., Range, M., Evans, J., Hood, K., Lührs, M., Keedwell, P., Goebel, R., & Linden, D. E. J.
- Affiliations
- Cardiff University (GB)
- De Montfort University (GB)
- Maastricht University (NL)
- King's College London (GB)
- Corresponding author
- Linden, David E. J.
- ORCID
- Venue
- Neuropsychopharmacology
- Published
- 2018-06-23
- Volume
- 43
- Issue
- 13
- Pages
- 2578-2585
- ISSN
- 0893-133X (ISSN-L)
- 1740-634X
- PMC
- PMC6186421
- OpenAlex
- W2808876118
- Cited by
- 175
- References
- 53
- Citations by year
- 2026: 9 · 2025: 14 · 2024: 16 · 2023: 19 · 2022: 25 · 2021: 54 · 2020: 21 · 2019: 13 · 2018: 4
- FWCI
- 10.35
- Type
- journal article
- Language
- en
- Open access
- hybrid
- doi.org
- Licence
- Locations
- Neuropsychopharmacology (publishedVersion, cc-by)
- Europe PMC (PubMed Central) (publishedVersion, other-oa)
- PubMed Central (publishedVersion, cc-by)
- PubMed (publishedVersion)
- Research Publications (Maastricht University) (publishedVersion, cc-by)
- ORCA Online Research @Cardiff (Cardiff University) (acceptedVersion)
- DMU Open Research Archive (De Montfort University) (submittedVersion)
- Research Publications (Maastricht University) (submittedVersion, other-oa)
- Funders
- National Institute for Social Care and Health Research (HS/10/25)
- Health and Care Research Wales (HS/14/20)
- Cancer Research UK
- European Commission (602186)
- Medical Research Council (MR/L010305/1)
- Topics
- Life Sciences › Neuroscience › Neurology › Transcranial Magnetic Stimulation Studies
- Health Sciences › Medicine › Pharmacology › Treatment of Major Depression
- Life Sciences › Neuroscience › Cognitive Neuroscience › Neural and Behavioral Psychology Studies
- Keywords
- fMRI neurofeedback, depression, emotion regulation, real-time fMRI, visual scene processing, antidepressant augmentation, self-efficacy, placebo effect, regression to the mean, self-regulation training
- MeSH terms
- Adult, Brain, Computer Systems, Depressive Disorder, Female, Follow-Up Studies, Humans, Magnetic Resonance Imaging, Male, Middle Aged, Pilot Projects, Treatment Outcome, Self Efficacy, Neurofeedback
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