Cathodal tDCS impacts the fear network activity and connectivity patterns during a therapy-like extinction session

Abstract

Background Transcranial direct current stimulation (tDCS) has been studied as an add-on enhancer of extinction-based treatments for anxiety disorders. Previous studies have showed that although anodal tDCS enhances fear extinction it also leads to decreased stimuli discrimination and consequent generalization of the fear response. Here we aim to understand the impact of cathodal tDCS in the neural activity and connectivity patterns between the tDCS target site (the right dorsolateral prefrontal cortex; rDLPFC) and the extant fear network (the bilateral amygdala, bilateral hippocampus, bilateral insula and the ventro medial prefrontal cortex [vmPFC]). Additionally we aim to see if cathodal tDCS leads to adverse effects similar to the ones observed with anodal stimulation. Methods We used a three-day fear conditioning procedure (day 1–fear acquisition; day 2–20-min 1 mA cathodal tDCS (only tDCS group)+ fear extinction; day 3–fear re-instatement and fear re-extinction). Thirty-four female participants where randomly assigned to either the tDCS group (n = 16) or the control group (n = 18). In day 1 fear acquisition was confirmed by self-reported contingency ratings. In day 2 we observed the between group differences in neural activity and connectivity patterns during extinction. In day 3 we observed the self-reported measures of stimuli contingency and reaction times during an approach-avoidance task to tackle the unconscious, automatic and involuntary avoidance responses. Results Functional magnetic resonance imagining (fMRI) group-level maps showed that cathodal tDCS over rDLPFC effectively reduces the right hippocampus activity during the processing of the conditioned stimuli during extinction. Furthermore, group-level psychophysiological interaction analysis (PPI) showed that cathodal tDCS effectively interferes with the fear response neural network. In particular, during the processing of the conditioned stimuli in late extinction phase, tDCS inverts the positive coupling between the vmPFC and a broad range of prefrontal structures, in particular the right and left DLPFC that participate in the regulation of negative emotions. Finally, day 3 measures showed decreased contingency ratings for the neutral cue and increased stimuli discrimination in the tDCS group, suggesting that cathodal tDCS does not lead to increased generalization. Conclusion Our promising results show that 1 mA cathodal tDCS effectively interferes with a large-scale cortico-subcortical fear network during extinction, and confirms that tDCS is a potential add-on strategy to enhance extinction-based treatments. Future studies should observe the adequate parameters of stimulation for the simultaneous enhancement of extinction learning and increased stimuli discrimination.