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Front Behav Neurosci. 2014 Feb 18;8:44. doi: 10.3389/fnbeh.2014.00044. eCollection 2014.

Medial prefrontal cortex stimulation modulates the processing of conditioned fear.

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  • 1Department of Psychiatry, Psychosomatics and Psychotherapy, University of Würzburg Würzburg, Germany.
  • 2Department of Psychiatry and Psychotherapy, University of Tübingen Tübingen, Germany ; LEAD Graduate School, University of Tuebingen Tuebingen, Germany.
  • 3Department of Psychology, University of Würzburg Würzburg, Germany.
  • 4Department of Cognitive Psychology II, University of Frankfurt/Main Frankfurt, Germany.
  • 5Department of Psychiatry, Psychosomatics and Psychotherapy, University of Würzburg Würzburg, Germany ; Institute of Medical Psychology and Systems Neuroscience, University of Münster Münster, Germany.


The extinction of conditioned fear depends on an efficient interplay between the amygdala and the medial prefrontal cortex (mPFC). In rats, high-frequency electrical mPFC stimulation has been shown to improve extinction by means of a reduction of amygdala activity. However, so far it is unclear whether stimulation of homologues regions in humans might have similar beneficial effects. Healthy volunteers received one session of either active or sham repetitive transcranial magnetic stimulation (rTMS) covering the mPFC while undergoing a 2-day fear conditioning and extinction paradigm. Repetitive TMS was applied offline after fear acquisition in which one of two faces (CS+ but not CS-) was associated with an aversive scream (UCS). Immediate extinction learning (day 1) and extinction recall (day 2) were conducted without UCS delivery. Conditioned responses (CR) were assessed in a multimodal approach using fear-potentiated startle (FPS), skin conductance responses (SCR), functional near-infrared spectroscopy (fNIRS), and self-report scales. Consistent with the hypothesis of a modulated processing of conditioned fear after high-frequency rTMS, the active group showed a reduced CS+/CS- discrimination during extinction learning as evident in FPS as well as in SCR and arousal ratings. FPS responses to CS+ further showed a linear decrement throughout both extinction sessions. This study describes the first experimental approach of influencing conditioned fear by using rTMS and can thus be a basis for future studies investigating a complementation of mPFC stimulation to cognitive behavioral therapy (CBT).


fear conditioning; learning; medial prefrontal cortex (mPFC); memory consolidation and extinction; transcranial magnetic stimulation (TMS)

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