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

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dc.contributor.authorAlexander, Laith
dc.contributor.authorWood, Christian M.
dc.contributor.authorGaskin, Philip L. R.
dc.contributor.authorSawiak, Stephen J.
dc.contributor.authorFryer, Tim D.
dc.contributor.authorHong, Young T.
dc.contributor.authorMcIver, Lauren
dc.contributor.authorClarke, Hannah F.
dc.contributor.authorRoberts, Angela C.
dc.contributor.orcidWood, Christian M. [0000-0003-1267-5032]
dc.contributor.orcidGaskin, Philip L. R. [0000-0002-8499-6233]
dc.contributor.orcidRoberts, Angela C. [0000-0003-2873-157X]
dc.date.accessioned2021-10-28T08:07:53Z
dc.date.available2021-10-28T08:07:53Z
dc.date.issued2020-10-26
dc.date.submitted2020-06-01
dc.date.updated2021-10-28T08:07:52Z
dc.description.abstractAbstract: 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.
dc.identifier.doi10.17863/CAM.77421
dc.identifier.eissn2041-1723
dc.identifier.others41467-020-19167-0
dc.identifier.other19167
dc.identifier.urihttps://www.repository.cam.ac.uk/handle/1810/329977
dc.languageen
dc.publisherNature Publishing Group UK
dc.subjectArticle
dc.subject/631/378/1689/1300
dc.subject/631/378/1689/1414
dc.subject/631/378/1689/1831
dc.subject/631/378/1457/1601
dc.subject/631/378/1457/1945
dc.subject/59/78
dc.subject/64
dc.subject/59
dc.subjectarticle
dc.titleOver-activation of primate subgenual cingulate cortex enhances the cardiovascular, behavioral and neural responses to threat
dc.typeArticle
dcterms.dateAccepted2020-09-30
prism.issueIdentifier1
prism.publicationNameNature Communications
prism.volume11
pubs.funder-project-idWellcome Trust (Wellcome) (108089/Z/15/Z)
rioxxterms.licenseref.urihttp://creativecommons.org/licenses/by/4.0/
rioxxterms.versionVoR
rioxxterms.versionofrecord10.1038/s41467-020-19167-0

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