Opposing roles of primate areas 25 and 32 and their putative rodent homologs in the regulation of negative emotion
Proceedings of the National Academy of Sciences of the United States of America
National Academy of Sciences
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Wallis, C. U., Cardinal, R., Alexander, L., Roberts, A., & Clarke, H. (2017). Opposing roles of primate areas 25 and 32 and their putative rodent homologs in the regulation of negative emotion. Proceedings of the National Academy of Sciences of the United States of America, 114 (20), E4075-E4084. https://doi.org/10.1073/pnas.1620115114
Disorders of dysregulated negative emotion such as depression and anxiety also feature increased cardiovascular mortality and decreased heart-rate variability (HRV). These disorders are correlated with dysfunction within areas 25 and 32 of the ventromedial prefrontal cortex (vmPFC), but a causal relationship between dysregulation of these areas and such symptoms has not been demonstrated. Furthermore, cross-species translation is limited by inconsistent findings between rodent fear extinction and human neuroimaging studies of negative emotion. To reconcile these literatures, we applied an investigative approach to the brain–body interactions at the core of negative emotional dysregulation. We show that, in marmoset monkeys (a nonhuman primate that has far greater vmPFC homology to humans than rodents), areas 25 and 32 have causal yet opposing roles in regulating the cardiovascular and behavioral correlates of negative emotion. In novel Pavlovian fear conditioning and extinction paradigms, pharmacological inactivation of area 25 decreased the autonomic and behavioral correlates of negative emotion expectation, whereas inactivation of area 32 increased them via generalization. Area 25 inactivation also increased resting HRV. These findings are inconsistent with current theories of rodent/primate prefrontal functional similarity, and provide insight into the role of these brain regions in affective disorders. They demonstrate that area 32 hypoactivity causes behavioral generalization relevant to anxiety, and that area 25 is a causal node governing the emotional and cardiovascular symptomatology relevant to anxiety and depression.
marmoset, negative emotion, vmPFC, fear conditioning, depression
This research was funded by Medical Research Council Career Development Award RG62920 (to H.F.C.). It was conducted at the Behavioural and Clinical Neuroscience Institute, which is supported by Joint Award G00001354 from the Medical Research Council and Wellcome Trust.
MEDICAL RESEARCH COUNCIL (G0001354)
External DOI: https://doi.org/10.1073/pnas.1620115114
This record's URL: https://www.repository.cam.ac.uk/handle/1810/270106