Targeting the affective brain-a randomized controlled trial of real-time fMRI neurofeedback in patients with depression

Abstract

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.

Conflict of interest statement

RG is CEO and ML is an employee of Brain Innovation B.V., the company that makes the Turbo-Brainvoyager software used for the real-time fMRI analyses. The remaining authors declare no competing interests.

Figures

Fig. 1

CONSORT diagram of clinical trial

Fig. 2

Main clinical outcome measure HDRS-17 for NFE and NFS groups at baseline, post-intervention, and follow up. a Mean and standard error of the mean (SEM) HDRS scores, b remission rate in %age based on HDRS, c Robust regression analysis between change in total self-efficacy scores, and residualized HDRS-17 scores at primary endpoint. *p < 0.05

Fig. 3

ROI analysis. Average t-value of target ROIs for each session. Pooled mean shown, as well as means for both groups with error bars showing standard error of the mean (SEM). *p < 0.05 at FDR correction

Fig. 4

Whole-brain analysis. a Probability map (PM) of the localizer. b Activity of intervention groups, shown separately for NF-emotion and NF-scene group. c Group contrast. Key areas are labeled with numbers: (1) Insular cortex/ ventrolateral prefrontal cortex, (2) parahippocampal Place area (PPA), (3) supplementary motor area, (4) lingual gyrus, (5) premotor cortex, (6) superior parietal lobule, and (7) ventrolateral prefrontal cortex. Statistical maps cluster-threshold corrected for multiple comparison (p < 0.001)