Low-frequency parietal repetitive transcranial magnetic stimulation reduces fear and anxiety

Anxiety disorders are the most prevalent mental disorders, with few effective neuropharmacological treatments, making treatments development critical. While noninvasive neuromodulation can successfully treat depression, few treatment targets have been identified specifically for anxiety disorders. Previously, we showed that shock threat increases excitability and connectivity of the intraparietal sulcus (IPS). Here we tested the hypothesis that inhibitory repetitive transcranial magnetic stimulation (rTMS) targeting this region would reduce induced anxiety. Subjects were exposed to neutral, predictable, and unpredictable shock threat, while receiving double-blinded, 1 Hz active or sham IPS rTMS. We used global brain connectivity and electric-field modelling to define the single-subject targets. We assessed subjective anxiety with online ratings and physiological arousal with the startle reflex. Startle stimuli (103 dB white noise) probed fear and anxiety during the predictable (fear-potentiated startle, FPS) and unpredictable (anxiety-potentiated startle, APS) conditions. Active rTMS reduced both FPS and APS relative to both the sham and no stimulation conditions. However, the online anxiety ratings showed no difference between the stimulation conditions. These results were not dependent on the laterality of the stimulation, or the subjects' perception of the stimulation (i.e. active vs. sham). Results suggest that reducing IPS excitability during shock threat is sufficient to reduce physiological arousal related to both fear and anxiety, and are consistent with our previous research showing hyperexcitability in this region during threat. By extension, these results suggest that 1 Hz parietal stimulation may be an effective treatment for clinical anxiety, warranting future work in anxiety patients.