title: Clarifying the role of the rostral dmPFC/dACC in fear/anxiety: learning, appraisal or expression?
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.
authors.affiliation: Department of Psychiatry and Psychotherapy, University Medical Center Freiburg, Freiburg im Breisgau, Germany. simon.maier@uniklinik-freiburg.de
authors.forename: Simon
authors.initials: S
authors.lastname: Maier
authors.forename: Anna
authors.initials: A
authors.lastname: Szalkowski
authors.forename: Susanne
authors.initials: S
authors.lastname: Kamphausen
authors.forename: Evgeniy
authors.initials: E
authors.lastname: Perlov
authors.forename: Bernd
authors.initials: B
authors.lastname: Feige
authors.forename: Jens
authors.initials: J
authors.lastname: Blechert
authors.forename: Alexandra
authors.initials: A
authors.lastname: Philipsen
authors.forename: Ludger Tebartz
authors.initials: LT
authors.lastname: van Elst
authors.forename: Raffael
authors.initials: R
authors.lastname: Kalisch
authors.forename: Oliver
authors.initials: O
authors.lastname: Tüscher
mesh_terms: D000328:Adult; D001007:Anxiety / Q000523:psychology*; D001931:Brain Mapping; D005239:Fear / Q000523:psychology*; D005260:Female; D006179:Gyrus Cinguli / Q000502:physiology*; D006801:Humans; D008279:Magnetic Resonance Imaging; D008297:Male; D008875:Middle Aged; D017397:Prefrontal Cortex / Q000502:physiology*; D055815:Young Adult