Regional inactivations of primate ventral prefrontal cortex reveal two distinct mechanisms underlying negative bias in decision making

Proceedings of the National Academy of Sciences of the United States of America
Hannah F ClarkeAngela C Roberts

Abstract

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.

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Citations

Mar 5, 2016·Frontiers in Systems Neuroscience·Yoshiro ShibaAngela C Roberts
Aug 10, 2016·Primates; Journal of Primatology·Marco LucarelliEsterina Pascale
Oct 27, 2016·Developmental Neurobiology·Jeff WalkerNicholas G Hatsopoulos
Sep 3, 2016·Developmental Neurobiology·Lydia OikonomidisAngela C Roberts
Jul 1, 2017·Neuropsychopharmacology : Official Publication of the American College of Neuropsychopharmacology·Kelsey S ZimmermannShannon L Gourley
Nov 6, 2018·Cerebral Cortex·Stacey A W JacksonAngela C Roberts
Aug 30, 2016·Nature Neuroscience·Charles G JenningsGuoping Feng
Sep 26, 2017·Brain and Neuroscience Advances·Emma J BubbJohn P Aggleton
May 4, 2017·Proceedings of the National Academy of Sciences of the United States of America·Chloe U WallisHannah F Clarke
Apr 29, 2018·Neuropsychopharmacology : Official Publication of the American College of Neuropsychopharmacology·Philip Jean-Richard-Dit-BresselGavan P McNally
Oct 18, 2019·Annual Review of Psychology·Angela C. Roberts
Dec 25, 2019·Proceedings of the National Academy of Sciences of the United States of America·Angela C Roberts, Hannah F Clarke
Dec 6, 2016·Learning & Memory·Philip Jean-Richard-Dit-Bressel, Gavan P McNally
Jan 16, 2019·Nihon yakurigaku zasshi. Folia pharmacologica Japonica·Takeshi Enomoto, Kazuhito Ikeda
Jun 6, 2019·Brain Sciences·Laith AlexanderAngela C Roberts
Dec 14, 2018·Proceedings of the National Academy of Sciences of the United States of America·Craig A TaswellBruno B Averbeck
Sep 23, 2020·Proceedings of the National Academy of Sciences of the United States of America·Zuzanna M StawickaAngela C Roberts
Feb 24, 2021·ILAR Journal·Jihane Homman-Ludiye, James A Bourne
Aug 4, 2021·Neuropsychopharmacology : Official Publication of the American College of Neuropsychopharmacology·Diego A Pizzagalli, Angela C Roberts

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