Using functional MRI neurofeedback to modulate self-blame in major depressive disorder

Abstract

Background: Major depressive disorder (MDD) is commonly framed as the result of general increases in negative emotion. An alternative theory is that specific increases in self-blaming emotions, relative to other-blaming emotions, is instead what sows vulnerability to depression. Though these two theories likely correspond to dissociable subsyndromes of the disorder deserving of equal attention, academic and clinical efforts have typically given primacy to the former over the latter. Consequently, many current interventions do not address self-blaming biases specifically, resulting in a considerable proportion of patients who respond insufficiently. fMRI neurofeedback is a novel technology well-poised to deliver self-blame-specific interventions. The subgenual cingulate cortex (SCC) is a key hub within the self-blame neural network, representing a potentially potent neurofeedback target. The current study employed a single-session neurofeedback trial harnessing SCC BOLD activity as the sole training target. It involved measures of both feasibility and efficacy to probe the safety and achievability of the protocol, as well as its mechanistic potency and potential clinical value. Methods: 20 participants with current MDD were allocated to two active intervention groups, representing target activation patterns that, though opposite, have both been observed in healthy controls relative to MDD cohorts. By pitting these interventions against each other directly, we hoped to clarify which one possesses the most therapeutic potential. In Intervention A (n=10), participants were encouraged during neurofeedback to upregulate their SCC activity during a ‘guilt’ task and downregulate it during an ‘indignation’ task. In Intervention B (n=10), participants were encouraged to do the opposite. The primary outcome measure was the pre- to post-neurofeedback change in SCC BOLD activity. The secondary outcome measure was the pre- to post-neurofeedback change in clinical profile (self-esteem and symptom severity). Results: Clinical scores improved significantly following neurofeedback, but intervention differences were not observed. Neurofeedback performance was greatest for Intervention B participants while they engaged in the indignation task, suggesting that upregulation of SCC activity for other-blame represents the most achievable training protocol. Neuroimaging analysis revealed one principal cluster of increased activation following neurofeedback (associated with the left temporoparietal region), specifically for indignation (relative to guilt) and Intervention B (relative to Intervention A). Inferences from the results are limited by the small sample size, in addition to other technical issues. Conclusion: The general clinical improvements support feasibility claims by demonstrating that engagement with negative emotions during neurofeedback is safe. The finding that modulation of the SCC is most achievable for indignation contributes to growing evidence that this region is more functionally heterogeneous for causal agency representations than previously assumed. Lastly, the functional neuroimaging observations demonstrate that self-blame-specific neurofeedback likely engages a distributed network beyond the SCC, with implications for future target selection choices. In summary, the results justify more adequately powered investigations into SCC-oriented neurofeedback for depression.

Date of Award	Jan 2026
Original language	English
Awarding Institution	University of Brighton
Supervisor	James Stone (Supervisor), Alessandro Colasanti (Supervisor) & Dr Roland Zahn (Supervisor)