Intermittent theta burst stimulation to the left prefrontal cortex enhances extinction learning but not extinction recall

Background: Non-invasive brain stimulation targeting the left ventromedial prefrontal cortex (vmPFC) has shown potential in enhancing fear extinction. However, optimal stimulation parameters for clinical application remain unclear. Methods: This study investigated the effects of intermittent theta burst stimulation (iTBS) on fear extinction using a three-day paradigm. Fifty healthy participants underwent fear acquisition (day 1), extinction learning (day 2), and both a spontaneous recovery and reinstatement test (day 3). Active or sham iTBS was applied before extinction learning to the left posterior PFC (MNI: -56, 2, 40), previously shown to be functionally connected to the vmPFC. Fear responses were measured using skin conductance responses (SCR) during CS+ and CS- presentations, along with arousal, valence, and contingency awareness ratings. Results: A significant time x group interaction was found for iTBS administered before extinction learning, with the active group showing reduced SCR during extinction learning compared to sham. However, no TMS effects were observed during the spontaneous recovery or reinstatement tests. Conclusion: These findings suggest limited therapeutic potential for iTBS targeting the left posterior PFC in enhancing extinction memory consolidation. Further research is needed to determine optimal stimulation parameters for clinical application.