Clarifying the role of the rostral dmPFC/dACC in fear/anxiety: learning, appraisal or expression?

PLoS One. 2012;7(11):e50120. doi: 10.1371/journal.pone.0050120. Epub 2012 Nov 26.

Abstract

Recent studies have begun to carve out a specific role for the rostral part of the dorsal medial prefrontal cortex (dmPFC) and adjacent dorsal anterior cingulate cortex (dACC) in fear/anxiety. Within a novel general framework of dorsal mPFC/ACC areas subserving the appraisal of threat and concomitant expression of fear responses and ventral mPFC/ACC areas subserving fear regulation, the rostral dmPFC/dACC has been proposed to specifically mediate the conscious, negative appraisal of threat situations including, as an extreme variant, catastrophizing. An alternative explanation that has not been conclusively ruled out yet is that the area is involved in fear learning. We tested two different fear expression paradigms in separate fMRI studies (study 1: instructed fear, study 2: testing of Pavlovian conditioned fear) with independent groups of healthy adult subjects. In both paradigms the absence of reinforcement precluded conditioning. We demonstrate significant BOLD activation of an identical rostral dmPFC/dACC area. In the Pavlovian paradigm (study 2), the area only activated robustly once prior conditioning had finished. Thus, our data argue against a role of the area in fear learning. We further replicate a repeated observation of a dissociation between peripheral-physiological fear responding and rostral dmPFC/dACC activation, strongly suggesting the area does not directly generate fear responses but rather contributes to appraisal processes. Although we succeeded in preventing extinction of conditioned responding in either paradigm, the data do not allow us to definitively exclude an involvement of the area in fear extinction learning. We discuss the broader implications of this finding for our understanding of mPFC/ACC function in fear and in negative emotion more generally.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Adult
  • Anxiety / psychology*
  • Brain Mapping
  • Fear / psychology*
  • Female
  • Gyrus Cinguli / physiology*
  • Humans
  • Magnetic Resonance Imaging
  • Male
  • Middle Aged
  • Prefrontal Cortex / physiology*
  • Young Adult

Grants and funding

This work was funded by the German Federal Ministry of Education and Research (BMBF 01GV0606) to LTvE, a fellowship grant of the Freiburg University Medical School to OT and the Deutsche Forschungsgemeinschaft (DFG Emmy Noether grant KA 1623/3-1) to RK. The funders had no role in study design, data collection and analysis, decision to publish, or preparation of the manuscript.