title: Regional inactivations of primate ventral prefrontal cortex reveal two distinct mechanisms underlying negative bias in decision making.
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.
authors.affiliation: Department of Physiology, Development and Neuroscience, University of Cambridge, Cambridge, Cambridgeshire, CB2 3DY, United Kingdom; and Behavioural and Clinical Neurosciences Institute and hfc23@cam.ac.uk.
authors.forename: Hannah F
authors.initials: HF
authors.lastname: Clarke
authors.affiliation: Behavioural and Clinical Neurosciences Institute and Department of Psychology, University of Cambridge, Cambridge, Cambridgeshire, CB2 3EB, United Kingdom.
authors.forename: Nicole K
authors.initials: NK
authors.lastname: Horst
authors.affiliation: Department of Physiology, Development and Neuroscience, University of Cambridge, Cambridge, Cambridgeshire, CB2 3DY, United Kingdom; and Behavioural and Clinical Neurosciences Institute and.
authors.forename: Angela C
authors.initials: AC
authors.lastname: Roberts
mesh_terms: D000679:Amygdala / Q000502:physiology; D000818:Animals; D014151:Anti-Anxiety Agents / Q000737:chemistry; D001008:Anxiety Disorders / Q000503:physiopathology; D001288:Attention; D001522:Behavior, Animal; D015982:Bias; D002144:Callithrix; D003657:Decision Making; D005260:Female; D006624:Hippocampus / Q000502:physiology; D008279:Magnetic Resonance Imaging; D008297:Male; D059906:Neuroimaging / Q000379:methods; D017397:Prefrontal Cortex / Q000502:physiology*; D014785:Vision, Ocular
chemical_list: D014151:Anti-Anxiety Agents
keywords: anxiety; negative bias; orbitofrontal cortex; ventrolateral prefrontal cortex