Blame-Rebalance fMRI Neurofeedback in Major Depressive Disorder: A Randomised Proof-of-Concept Trial

Excessive self-blame is a core feature of major depressive disorder (MDD), and neuroimaging research has linked it to reduced connectivity between the anterior temporal lobe and the subgenual anterior cingulate cortex — a deficit that persists even after clinical remission. This randomized proof-of-concept trial investigated whether patients with MDD could voluntarily modulate this circuit using real-time fMRI neurofeedback, a technique that provides participants with moment-to-moment information about their own brain activity. The results demonstrated that MDD patients were able to increase anterior temporal–subgenual cingulate connectivity in a single neurofeedback session, representing a meaningful step toward circuit-targeted behavioral interventions for depression. The trial establishes the feasibility of neurofeedback as a non-pharmacological approach to rebalancing the blame-related brain circuitry in MDD.