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Ventromedial prefrontal area 14 provides opposing regulation of threat and reward-elicited responses in the common marmoset.

Accepted version
Peer-reviewed

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Authors

Stawicka, Zuzanna M 
Massoudi, Roohollah 
Horst, Nicole K 
Koda, Ken 

Abstract

The ventromedial prefrontal cortex (vmPFC) is a key brain structure implicated in mood and anxiety disorders, based primarily on evidence from correlational neuroimaging studies. Composed of a number of brain regions with distinct architecture and connectivity, dissecting its functional heterogeneity will provide key insights into the symptomatology of these disorders. Focusing on area 14, lying on the medial and orbital surfaces of the gyrus rectus, this study addresses a key question of causality. Do changes in area 14 activity induce changes in threat- and reward-elicited responses within the nonhuman primate, the common marmoset, similar to that seen in mood and anxiety disorders? Area 14 overactivation was found to induce heightened responsivity to uncertain, low-imminence threat while blunting cardiovascular and behavioral anticipatory arousal to high-value food reward. Conversely, inactivation enhanced the arousal to high-value reward cues while dampening the acquisition of cardiovascular and behavioral responses to a Pavlovian threat cue. Basal cardiovascular activity, including heart rate variability and sympathovagal balance, which are dysfunctional in mood and anxiety disorders, are insensitive to alterations in area 14 activity as is the extinction of conditioned threat responses. The distinct pattern of dysregulation compared to neighboring region area 25 highlights the heterogeneity of function within vmPFC and reveals how the effects of area 14 overactivation on positive and negative reactivity mirror symptoms of anhedonia and anxiety that are so often comorbid in mood disorders.

Description

Keywords

anhedonia, anxiety, area 14, orbitofrontal, ventromedial, Animals, Anxiety, Brain Mapping, Callithrix, Conditioning, Classical, Heart Rate, Humans, Magnetic Resonance Imaging, Prefrontal Cortex, Reward

Journal Title

Proc Natl Acad Sci U S A

Conference Name

Journal ISSN

0027-8424
1091-6490

Volume Title

117

Publisher

Proceedings of the National Academy of Sciences

Rights

All rights reserved
Sponsorship
Medical Research Council (MR/M023990/1)