Transcranial direct current stimulation (tDCS) has been studied as an add-on enhancer of extinction-based treatments for anxiety disorders. However, previous studies have failed to address one issue of translational significance: the to-be extinguished fear memory must be consolidated. Also, there are conflicting results about the anxiolytic effect of cathodal tDCS delivered to the right dorsolateral prefrontal cortex. To address these issues, we recruited thirty-four female participants to participate in a two-day fear conditioning procedure. In day 1, laboratory fear acquisition was confirmed by self-reported contingency ratings. In day 2, participants were randomly assigned to either the control group (n=18; completed the extinction session) or the tDCS group (n=16; received 20min of cathodal stimulation 1 mA to interfere with the neural activity immediately before extinction).
Functional magnetic resonance imagining data showed that cathodal tDCS modulates the late phase of delayed extinction process. In particular, neural activity of the frontal middle cortex, the left frontal superior cortex, and the left and right paracentral and postcentral cortexes is increased during the processing of the CS-, supporting the processing of uncertainty. Furthermore, during the processing of threat, cathodal tDCS leads to an increased information flow from the contralateral prefrontal cortex along the cortical–amygdalo–hippocampal–cerebellar pathways. Thus, the boosted processing of uncertainty and the stronger coupling during threat processing might well be the mechanisms by which cathodal tDCS boosts stimuli discrimination, leading to decreased symptoms and enhanced clinical gains.