Clarifying the role of the rostral dmPFC/dACC in fear/anxiety: learning, appraisal or expression?
Open accessAbstract
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.
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The dACC is important for both extinction learning and emotion regulation through cognitive reappraisal, and is hypoactivated during emotion regulation in GAD.
“The dACC is a region previously identified as important for both extinction learning (Lang et al., 2009; Maier et al., 2012) and emotion regulation through cognitive reappraisal (Ochsner et al., 2002, 2004), and a region previously shown to be hypoactivated during emotion regulation in GAD (Blair et al., 2012).”
From Neural correlates of emotion acceptance<i>vs</i>worry or suppression in generalized anxiety disorder (2017) · cites this paper as Maier et al., 2012
Maier et al. is cited for the dACC’s role in extinction learning; the reappraisal and GAD claims have separate citations. The Discussion (page unavailable) says the study cannot definitively exclude an extinction-learning role, but points to spared extinction after dorsal mPFC lesions as evidence against that explanation. It does not establish that the dACC is important for extinction learning. (LLM, conf=0.85)
Checked by a reasoning model — may be wrong.
Experimental — accuracy not yet measuredStudies examining the extinction of contextual fear have implicated a larger role for the dACC.
“Although an emphasis has been placed on the role of subgenual and rostral ACC in the modulation of amygdala activation during extinction of cue conditioned fear in studies of human fear conditioning (Delgado et al., 2008; Milad et al., 2007; Phelps et al., 2004), studies examining the extinction of contextual fear have implicated a larger role for the dACC (Lang et al., 2009; Sehlmeyer et al., 201”
From Neural correlates of emotion acceptance<i>vs</i>worry or suppression in generalized anxiety disorder (2017) · cites this paper as Maier et al., 2012
The Introduction describes instructed fear and Pavlovian cue conditioning, not extinction of contextual fear. The Discussion says extinction was not observed during testing and that the data cannot definitively exclude a role for dmPFC/dACC in extinction learning. A search for contextual fear extinction found no passage assessing the claimed larger role for the dACC. (LLM, conf=0.72)
Experimental — accuracy not yet measured
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- Authors
- Maier, S., Szalkowski, A., Kamphausen, S., Perlov, E., Feige, B., Blechert, J., Philipsen, A., van Elst, L. T., Kalisch, R., & Tüscher, O.
- Affiliations
- University of Freiburg (DE)
- University Medical Center Freiburg (DE)
- University of Salzburg (AT)
- Corresponding author
- Maier, Simon
- Szalkowski, Anna
- Kamphausen, Susanne
- Perlov, Evgeniy
- Feige, Bernd
- Blechert, Jens
- Philipsen, Alexandra
- Tüscher, Oliver
- ORCID
- Venue
- PLoS ONE
- Publisher
- Public Library of Science (PLoS)
- Published
- 2012-11-26
- Volume
- 7
- Issue
- 11
- Pages
- e50120
- ISSN
- 1932-6203 (ISSN-L)
- PMC
- PMC3506550
- OpenAlex
- W2031697355
- Cited by
- 77
- References
- 47
- Citations by year
- 2026: 3 · 2025: 3 · 2024: 4 · 2023: 5 · 2022: 2 · 2021: 5 · 2020: 2 · 2019: 4 · 2018: 10 · 2017: 7 · 2016: 10 · 2015: 5 · 2014: 10 · 2013: 7
- FWCI
- 3.14
- Type
- journal article
- Language
- en
- Open access
- gold
- doi.org
- Locations
- PLoS ONE (publishedVersion, cc-by)
- PubMed Central (publishedVersion, cc-by)
- PubMed (publishedVersion)
- DOAJ (DOAJ: Directory of Open Access Journals) (submittedVersion, cc-by-sa)
- Figshare (submittedVersion, cc-by)
- Funders
- Deutsche Forschungsgemeinschaft (KA1623/3-1, 1623/3-1)
- Bundesministerium für Bildung und Forschung (01GV0606)
- Topics
- Life Sciences › Neuroscience › Cognitive Neuroscience › Memory and Neural Mechanisms
- Life Sciences › Neuroscience › Cognitive Neuroscience › Neural and Behavioral Psychology Studies
- Social Sciences › Psychology › Experimental and Cognitive Psychology › Anxiety, Depression, Psychometrics, Treatment, Cognitive Processes
- Keywords
- dorsal anterior cingulate cortex, fear, anxiety, threat appraisal, fear learning, fear expression, fear extinction, catastrophizing, negative emotions, conditioned responding
- MeSH terms
- Adult, Anxiety, Brain Mapping, Fear, Female, Gyrus Cinguli, Humans, Magnetic Resonance Imaging, Male, Middle Aged, Prefrontal Cortex, Young Adult
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