The physiological foundation of extinction improvement by tDCS over the ventromedial prefrontal cortex (vmPFC) in healthy humans: an fMRI study

A growing body of research highlights the fear extinction model as a key framework for understanding the pathology of anxiety disorders and developing therapeutic interventions. Functional imaging studies link successful extinction recall and reduced amygdala reactivity with ventromedial prefrontal cortex (vmPFC) activity, while dysfunctional vmPFC activity is associated with anxiety pathology. Enhancing vmPFC activity through transcranial direct current stimulation (tDCS) has thus emerged as a promising approach to augment cognitive behavioral therapy (CBT) and therapeutic exposure therapies for anxiety disorders. In this study, anodal tDCS was applied over the vmPFC during the extinction learning phase of a 3-day fear acquisition/extinction paradigm (anodal tDCS: 21, sham tDCS: 23 participants). Skin conductance response (SCR) and Blood Oxygenation Level Dependent (BOLD) brain activity were recorded simultaneously. Healthy participants who received real tDCS showed significantly improved extinction recall compared to the sham tDCS group, as indicated by the SCR. Fear acquisition activated core regions of the fear network, including the anterior cingulate cortex, amygdala, orbitofrontal cortex, and insular cortex. During extinction learning, real tDCS activated both fear and safety networks (particularly the posterior cingulate and middle temporal cortex) during early extinction, while the sham tDCS group showed activity only in the fear network. Furthermore, a decoupling of the vmPFC with fear network regions with real tDCS during extinction was observed, indicating strengthened inhibitory control. These findings suggest that anodal tDCS over the vmPFC promotes early activation of the safety network, enhancing extinction learning and consolidation. This suggests its translational potential as an adjunctive intervention for anxiety disorders.