Self-blaming emotions in major depression: a randomised pilot trial comparing fMRI neurofeedback training with self-guided psychological strategies (NeuroMooD)

Abstract

Background: Overgeneralised self-blame and worthlessness are key symptoms of major depressive disorder (MDD) and were previously associated with self-blame-selective changes in connectivity between right superior anterior temporal lobe (rSATL) and subgenual frontal areas. In a previous study, remitted MDD patients successfully modulated guilt-selective rSATL-subgenual cingulate connectivity using real-time functional magnetic resonance imaging (rtfMRI) neurofeedback training, thereby increasing their self-esteem. The feasibility and potential of using this approach in symptomatic MDD were unknown. Methods: This single-blind pre-registered randomised controlled pilot trial tested the clinical potential of a novel self-guided psychological intervention with and without additional rSATL-posterior subgenual cortex (SC) rtfMRI neurofeedback, targeting self-blaming emotions in insufficiently recovered people with MDD and early treatment-resistance (n=43, n=35 completers). Following a diagnostic baseline assessment, patients completed three self-guided sessions to rebalance self-blaming biases and a post-treatment assessment. The fMRI neurofeedback software FRIEND was used to measure rSATL-posterior SC connectivity, while the BDI-II was administered to assess depressive symptom severity as a primary outcome measure. Results: Both interventions were demonstrated to be safe and beneficial, resulting in a mean reduction of MDD symptom severity by 46% and response rates of more than 55%, with no group difference. Secondary analyses, however, revealed a differential response on our primary outcome measure between MDD patients with and without DSM-5 defined anxious distress. Stratifying by anxious distress features was investigated, because this was found to be the most common subtype in our sample. MDD patients without anxious distress showed a higher response to rtfMRI neurofeedback training compared to the psychological intervention, with the opposite pattern found in anxious MDD. We explored potentially confounding clinical differences between subgroups and found that anxious MDD patients were much more likely to experience anger towards others as measured on our psychopathological interview which might play a role in their poorer response to neurofeedback. In keeping with the hypothesis that self-worth plays a key role in MDD, improvement on our primary outcome measure was correlated with increases in self-esteem after the intervention and this correlated with the frequency with which participants employed the strategies to tackle self-blame outside of the treatment sessions. Conclusions: These findings suggest that self-blame-selective rtfMRI neurofeedback training may be superior over a solely psychological intervention in non-anxious MDD, although further confirmatory studies are needed. The self-guided psychological intervention showed a surprisingly high clinical potential in the anxious MDD group which needs further confirmation compared vs treatment-as-usual. Future studies need to investigate whether self-blame-selective rSATL-SC connectivity changes are irrelevant in anxious MDD, which could explain their response being better to the psychological intervention without interfering neurofeedback.

Neurofeedback training in major depressive disorder: A systematic review of clinical efficacy, study quality and reporting practices

“…While this design controls for natural effects (e.g., regression to the mean), it does not control for any general or neurofeedback training related non-specific effects.  Active control outside the scanner: this category includes control conditions where the participant is engaging in a similar mental task, but outside of the neuroimaging scanner (Jaeckle et al, 2019;Linden et al, 2012). This condition is also referred to as a mental-rehearsal control (Sorger et al, 2019).…”

“…Thus, the majority of neurofeedback protocols for MDD aim to directly or indirectly rebalance these networks. For instance, in fMRI-based protocols these areas are the ones commonly targeted for self-regulation, as individual ROIs (Jaeckle et al, 2019;Young et al, 2017b;Young et al, 2014) or as multi-ROI networks (Linden et al, 2012;. Although some studies using EEG-based neurofeedback claim to target some of these brain structures (e.g.…”

Development and validation of the Maudsley Modified Patient Health Questionnaire (MM-PHQ-9)

“…The NeuroMooD trial examined a novel real-time fMRI neurofeedback method in MDD, and also included a case–control cross-sectional study recruiting healthy controls. 24 Both MDD and control samples were included in this analysis. The SiG study aimed to use a method of emotion reappraisal to train healthy participants with a tendency for self-blame to convert their self-blame to sadness, as a more adaptive emotion.…”

Neurofeedback training in major depressive disorder: a systematic review of clinical efficacy, study quality and reporting practices

“…More recently, Jaeckle and colleagues [112] conducted a randomized, single-blinded trial that consisted of three training sessions. Patients (majority of them under medication) were either allocated to the experimental group (N=19) that trained up-regulation of functional connectivity between the right superior anterior temporal lobe and the right subgenual cingulate, or to a control group (N=16) that trained cognitive reappraisal techniques outside the fMRI scanner.…”