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

TY - JOUR

T1 - Clarifying the role of the rostral dmPFC/dACC in fear/anxiety: learning, appraisal or expression?

AU - Maier, Simon

AU - Szalkowski, Anna

AU - Kamphausen, Susanne

AU - Perlov, Evgeniy

AU - Feige, Bernd

AU - Blechert, Jens

AU - Philipsen, Alexandra

AU - Elst, van

AU - Kalisch, Raffael

AU - Kalisch, Raffael

AU - Tüscher, Oliver

PY - 2012

Y1 - 2012

N2 - 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.

AB - 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.

KW - Adult

KW - Humans

KW - Male

KW - Female

KW - Middle Aged

KW - Young Adult

KW - Magnetic Resonance Imaging

KW - Brain Mapping

KW - Prefrontal Cortex/physiology

KW - Anxiety/psychology

KW - Fear/psychology

KW - Gyrus Cinguli/physiology

KW - Adult

KW - Humans

KW - Male

KW - Female

KW - Middle Aged

KW - Young Adult

KW - Magnetic Resonance Imaging

KW - Brain Mapping

KW - Prefrontal Cortex/physiology

KW - Anxiety/psychology

KW - Fear/psychology

KW - Gyrus Cinguli/physiology

U2 - 10.1371/journal.pone.0050120

DO - 10.1371/journal.pone.0050120

M3 - SCORING: Journal article

VL - 7

SP - 50120

JO - PLOS ONE

JF - PLOS ONE

SN - 1932-6203

IS - 11

M1 - 11

ER -