Offline tDCS modulates prefrontal cortical-subcortical cerebellar fear pathways in delayed fear extinction

Abstract

Transcranial direct current stimulation (tDCS) has been studied to enhance extinction-based treatments for anxiety disorders. However, the field shows conflicting results about the anxiolytic effect of tDCS and only a few studies have previously observed the extinction of consolidated memories. Off-line tDCS modulates subsequent fear response (fear recall and fear extinction) neural activity and connectivity, throughout changes in the fear pathway that is critically involved in the pathogenesis of anxiety disorders. Thirty-four women participated in a two-day fear conditioning procedure. On day 1, women were randomly assigned to the control group (n=18) or the tDCS group (n=16) and went through a fear acquisition procedure. On day 2, the tDCS group received 20min tDCS at 1mA [cathode - F4; anode - contralateral deltoid] immediately before extinction and while inside the MRI scanner. The control group completed the extinction procedure only. fMRI whole brain contrast analysis showed stimulation dependent activity patterns with the tDCS group showing decreased neural activity during the processing of the CS+ and increased activity during the processing of the CS, in prefrontal, postcentral and paracentral regions, during late extinction. PPI analysis showed tDCS impact on the connectivity between the left dorsolateral prefrontal cortex and three clusters along the cortical-amygdalo-hippocampal- cerebellar pathway, during the processing of the CS+ in late extinction (TFCE corrected at p <.05). The increased neuronal activity during the processing of safety cues and the stronger coupling during the processing of threat cues might well be the mechanisms by which tDCS contributes to stimuli discrimination. HighlightsO_LIThe anxiolytic effect of cathodal tDCS is controversial. C_LIO_LIWe show cathodal tDCS modulatory effect on delayed extinction of the fear response. C_LIO_LICathodal tDCS modulates the processing of safe and threatening cues. C_LIO_LICathodal tDCS modulates the activity and connectivity of the fear network. C_LI