title: Amygdala Contributions to Stimulus-Reward Encoding in the Macaque Medial and Orbital Frontal Cortex during Learning.
abstract: Orbitofrontal cortex (OFC), medial frontal cortex (MFC), and amygdala mediate stimulus-reward learning, but the mechanisms through which they interact are unclear. Here, we investigated how neurons in macaque OFC and MFC signaled rewards and the stimuli that predicted them during learning with and without amygdala input. Macaques performed a task that required them to evaluate two stimuli and then choose one to receive the reward associated with that option. Four main findings emerged. First, amygdala lesions slowed the acquisition and use of stimulus-reward associations. Further analyses indicated that this impairment was due, at least in part, to ineffective use of negative feedback to guide subsequent decisions. Second, the activity of neurons in OFC and MFC rapidly evolved to encode the amount of reward associated with each stimulus. Third, amygdalectomy reduced encoding of stimulus-reward associations during the evaluation of different stimuli. Reward encoding of anticipated and received reward after choices were made was not altered. Fourth, amygdala lesions led to an increase in the proportion of neurons in MFC, but not OFC, that encoded the instrumental response that monkeys made on each trial. These correlated changes in behavior and neural activity after amygdala lesions strongly suggest that the amygdala contributes to the ability to learn stimulus-reward associations rapidly by shaping encoding within OFC and MFC.SIGNIFICANCE STATEMENTAltered functional interactions among orbital frontal cortex (OFC), medial frontal cortex (MFC), and amygdala are thought to underlie several psychiatric conditions, many related to reward learning. Here, we investigated the causal contribution of the amygdala to the development of neuronal activity in macaque OFC and MFC related to rewards and the stimuli that predict them during learning. Without amygdala inputs, neurons in both OFC and MFC showed decreased encoding of stimulus-reward associations. MFC also showed increased encoding of the instrumental responses that monkeys made on each trial. Behaviorally, changes in neural activity were accompanied by slower stimulus-reward learning. The findings suggest that interactions among amygdala, OFC, and MFC contribute to learning about stimuli that predict rewards.
authors.affiliation: Friedman Brain Institute, Icahn School of Medicine at Mount Sinai, New York, New York 10029, and peter.rudebeck@mssm.edu.|Section on the Neurobiology of Learning and Memory, Laboratory of Neuropsychology, National Institutes of Health, Bethesda, Maryland 20892.
authors.forename: Peter H
authors.initials: PH
authors.lastname: Rudebeck
authors.affiliation: Section on the Neurobiology of Learning and Memory, Laboratory of Neuropsychology, National Institutes of Health, Bethesda, Maryland 20892.
authors.forename: Joshua A
authors.identifier: 0000-0001-6267-2791
authors.initials: JA
authors.lastname: Ripple
authors.affiliation: Section on the Neurobiology of Learning and Memory, Laboratory of Neuropsychology, National Institutes of Health, Bethesda, Maryland 20892.
authors.forename: Andrew R
authors.identifier: 0000-0002-8045-0970
authors.initials: AR
authors.lastname: Mitz
authors.affiliation: Section on the Neurobiology of Learning and Memory, Laboratory of Neuropsychology, National Institutes of Health, Bethesda, Maryland 20892.
authors.forename: Bruno B
authors.initials: BB
authors.lastname: Averbeck
authors.affiliation: Section on the Neurobiology of Learning and Memory, Laboratory of Neuropsychology, National Institutes of Health, Bethesda, Maryland 20892.
authors.forename: Elisabeth A
authors.identifier: 0000-0003-1450-1642
authors.initials: EA
authors.lastname: Murray
mesh_terms: D000200:Action Potentials / Q000502:physiology; D000679:Amygdala / Q000166:cytology / Q000000981:diagnostic imaging / Q000293:injuries / Q000502:physiology*; D000704:Analysis of Variance; D000818:Animals; D002755:Choice Behavior; D004193:Discrimination Learning / Q000502:physiology; D018690:Excitatory Amino Acid Agonists / Q000633:toxicity; D007051:Ibotenic Acid / Q000633:toxicity; D007858:Learning / Q000502:physiology*; D008253:Macaca mulatta; D008279:Magnetic Resonance Imaging; D008297:Male; D016202:N-Methylaspartate / Q000633:toxicity; D009474:Neurons / Q000502:physiology*; D017397:Prefrontal Cortex / Q000166:cytology / Q000000981:diagnostic imaging / Q000502:physiology*; D011930:Reaction Time / Q000502:physiology; D012201:Reward; D013997:Time Factors
chemical_list: D018690:Excitatory Amino Acid Agonists; D007051:Ibotenic Acid; D016202:N-Methylaspartate
keywords: amygdala; learning; macaque; prefrontal; reward