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.

Orthogonal Representations of Reward Magnitude, Certainty, and Volatility in the Macaque Orbitofrontal Cortex

“…Lesions of the OFC lead to severe deficits when stimulusoutcome contingencies need to be updated (Jones and Mishkin 1972;Dias et al 1996;Izquierdo et al 2004;Walton et al 2010). Although recent work with selective excitotoxic lesions of the OFC in macaques (Rudebeck et al 2013) has overturned the idea that the OFC is necessary for learning reversals of stimulus-reward contingencies-at least in deterministic settings-recordings from single neurons have shown that OFC neurons change their activity to visual stimuli when the type of their associated outcome changes (Thorpe et al 1983;Rolls et al 1996;Morrison et al 2011) and during learning (Wallis and Miller 2003;Rudebeck et al 2017). Taken together, these results suggest the OFC plays an important role in tracking stimulusreward associations.…”

Value-based Decision Making Takes Place in the Action Domain in the Prefrontal Cortex

“…Many studies have shown that the OFC is important for dynamically updating and tracking stimulus-value association (Morrison et al, 2011;Rolls et al, 1996;Rudebeck et al, 2008Rudebeck et al, , 2017Thorpe et al, 1983). Here we showed that the OFC did not integrate and update value information during decision making.…”

Amygdala input differentially influences prefrontal local field potential and single neuron encoding of reward-based decisions

“…This aids the 374 interpretation of the results; if there had been a behavioral deficit postoperatively it would be 375 difficult to interpret any postoperative changes in neural activity, as effects could be due to 376 either the lesion or the change in behavior. In addition, we confirmed that the lesions were 377 effective in a separate task that required the learning of new stimulus-reward associations 378 (Rudebeck et al, 2017). 379…”

“…By contrast, if the value of stimuli changed unexpectedly or has to be learned, 881 this might trigger a cascade of events throughout the PFC, increasing the need for cognitive 882 control which could potentiate the processing of choice and value information in the MFC and 883 OFC, respectively. This idea would appear to fit with data from the same subjects showing that 884 during stimulus-reward learning, single neuron activity in MFC closely matches stimulus values 885 and is indistinguishable from OFC encoding (Rudebeck et al, 2017). 886 887…”