Regional inactivations of primate ventral prefrontal cortex reveal two distinct mechanisms underlying negative bias in decision making
National Academy of Sciences
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Clarke, H., Horst, N., & Roberts, A. (2015). Regional inactivations of primate ventral prefrontal cortex reveal two distinct mechanisms underlying negative bias in decision making. PNAS, 112 (13), 4176-4181. https://doi.org/10.1073/pnas.1422440112
Dysregulation of the orbitofrontal and ventrolateral prefrontal cortices is implicated in anxiety and mood disorders, but the specific contributions of each region are unknown, including how they gate the impact of threat on decision making. To address this, the effects of GABAergic inactivation of these regions were studied in marmoset monkeys performing an instrumental approach–avoidance decision-making task that is sensitive to changes in anxiety. Inactivation of either region induced a negative bias away from punishment that could be ameliorated with anxiolytic treatment. However, whereas the effects of ventrolateral prefrontal cortex inactivation on punishment avoidance were seen immediately, those of orbitofrontal cortex inactivation were delayed and their expression was dependent upon an amygdala–anterior hippocampal circuit. We propose that these negative biases result from deficits in attentional control and punishment prediction, respectively, and that they provide the basis for understanding how distinct regional prefrontal dysregulation contributes to the heterogeneity of anxiety disorders with implications for cognitive-behavioral treatment strategies.
anxiety, orbitofrontal cortex, ventrolateral prefrontal cortex, negative bias
All authors contributed extensively to the work presented in this article, and we thank Rudolf Cardinal for helpful advice and discussion and Mercedes Arroyo for histology. This research was funded by a Medical Research Council Programme Grant (to A.C.R.) and Career Development Award (to H.F.C.). The research was conducted at the Behavioural and Clinical Neuroscience Institute, which is supported by a joint award from the Medical Research Council and Wellcome Trust (G00001354).
MEDICAL RESEARCH COUNCIL (G0001354)
Medical Research Council (MR/M023990/1)
Wellcome Trust (093875/Z/10/Z)
External DOI: https://doi.org/10.1073/pnas.1422440112
This record's URL: https://www.repository.cam.ac.uk/handle/1810/247998
Attribution-NonCommercial 2.0 UK: England & Wales
Licence URL: http://creativecommons.org/licenses/by-nc/2.0/uk/
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