Effects of repeated tDCS on fear extinction in mice

Symposium title: Brain stimulation in fear and anxiety disorders Symposium description: Anxiety disorders, together with depression, are the most common mental health disorders in the world. Although evidence-based treatments for anxiety disorders exist, more than half of treated individuals do not show sufficient improvement in clinical symptoms after therapy or show a relapse after successful therapy. Therefore there is a continuing need to develop novel and effective treatments for anxiety. The use of non-invasive brain stimulation represents a promising approach to complement current evidence-based treatments as therapeutic tools. This symposium takes a bench-to-bedside approach covering both basic and clinical studies using the two most common non-invasive brain stimulation techniques, transcranial direct current stimulation (tDCS) and repetitive transcranial magnetic stimulation (rTMS), in the context of fear and anxiety disorders. First, Dimitri de Bundel will demonstrate in an animal model that tDCS is capable of modulating fear extinction in mice. Next, Mascha van 't Wout-Frank will cover the use of tDCS to modulate fear extinction and anxious habituation during exposure in individuals with posttraumatic stress disorder (PTSD). This will be followed by Martin Herrmann who will present a clinical study investigating whether rTMS can be used to improve exposure therapy in phobic patients. The symposium will conclude with a lecture by Sara Borgomaneri who will demonstrate that rTMS can be used to disrupt the consolidationand reconsolidation of fear memory, providing a novel option for the treatment of anxiety disorders. Abstract Exposure-based psychotherapy is a first line treatment for fear-related disorders. Not all patients achieve long-term remission but adjunctive non-invasive neuromodulation may be a promising strategy to enhance the efficacy of exposure therapy. In a proof of concept study, we explored whether tDCS over the prefrontal cortex (PFC) could enhance fear extinction in mice. While this preclinical model of exposure therapy is appealing for in-depth exploration of mechanisms of action, it comes with technical challenges that may hamper direct comparisons of online with offline tDSC effects and the translation towards applications in humans. Nevertheless, we found that repeated offline anodal tDCS (0.2 mA, 20 min, twice daily for five consecutive days) over the PFC resulted in enhanced fear extinction when extinction training followed one day after the last stimulation session. We found that tDCS was most effective in experimental conditions corresponding to high fear expression. Our data provide a rationale to further explore anodal tDCS over the PFC as potential support for exposure-based psychotherapy. Research Category and Technology and Methods Basic Research: 9. Transcranial Direct Current Stimulation (tDCS) Keywords: Fear extinction, mice, tDCS