TY - JOUR T1 - Amygdala contributions to stimulus–reward encoding in the macaque medial and orbital frontal cortex during learning JF - The Journal of Neuroscience JO - J. Neurosci. DO - 10.1523/JNEUROSCI.0933-16.2017 SP - 0933-16 AU - Peter H. Rudebeck AU - Joshua A. Ripple AU - Andrew R. Mitz AU - Bruno B. Averbeck AU - Elisabeth A. Murray Y1 - 2017/01/25 UR - http://www.jneurosci.org/content/early/2017/01/25/JNEUROSCI.0933-16.2017.abstract N2 - 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 following amygdala lesions strongly suggest that the amygdala contributes to the ability to rapidly learn stimulus–reward associations through 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. Taken together, the findings suggest that interactions among amygdala, OFC, and MFC contribute to learning about stimuli that predict rewards. ER -