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Over-activation of primate subgenual cingulate cortex enhances the cardiovascular, behavioral and neural responses to threat

Published version
Peer-reviewed

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Authors

Alexander, Laith 
Gaskin, Philip L. R.  ORCID logo  https://orcid.org/0000-0002-8499-6233
Sawiak, Stephen J. 
Fryer, Tim D. 

Abstract

Abstract: Stress-related disorders such as depression and anxiety are characterized by enhanced negative emotion and physiological dysfunction. Whilst elevated activity within area 25 of the subgenual anterior cingulate cortex (sgACC/25) has been implicated in these illnesses, it is unknown whether this over-activity is causal. By combining targeted intracerebral microinfusions with cardiovascular and behavioral monitoring in marmosets, we show that over-activation of sgACC/25 reduces vagal tone and heart rate variability, alters cortisol dynamics during stress and heightens reactivity to proximal and distal threat. 18F-FDG PET imaging shows these changes are accompanied by altered activity within a network of brain regions including the amygdala, hypothalamus and dorsolateral prefrontal cortex. Ketamine, shown to have rapid antidepressant effects, fails to reverse elevated arousal to distal threat contrary to the beneficial effects we have previously demonstrated on over-activation induced reward blunting, illustrating the symptom-specificity of its actions.

Description

Keywords

Article, /631/378/1689/1300, /631/378/1689/1414, /631/378/1689/1831, /631/378/1457/1601, /631/378/1457/1945, /59/78, /64, /59, article

Journal Title

Nature Communications

Conference Name

Journal ISSN

2041-1723

Volume Title

11

Publisher

Nature Publishing Group UK
Sponsorship
Wellcome Trust (Wellcome) (108089/Z/15/Z)