Motor System-Dependent Effects of Amygdala and Ventral Striatum Lesions on Explore-Exploit Behaviors.

Deciding whether to forego immediate rewards or explore new opportunities is a key component of flexible behavior and is critical for the survival of the species. Although previous studies have shown that different cortical and subcortical areas, including the amygdala and ventral striatum (VS), are implicated in representing the immediate (exploitative) and future (explorative) value of choices, the effect of the motor system used to make choices has not been examined. Here, we tested male rhesus macaques with amygdala or VS lesions on two versions of a three-arm bandit task where choices were registered with either a saccade or an arm movement. In both tasks we presented the monkeys with explore-exploit tradeoffs by periodically replacing familiar options with novel options that had unknown reward probabilities. We found that monkeys explored more with saccades but showed better learning with arm movements. VS lesions caused the monkeys to be more explorative with arm movements and less explorative with saccades, although this may have been due to an overall decrease in performance. VS lesions affected the monkeys' ability to learn novel stimulus-reward associations in both tasks, while after amygdala lesions this effect was stronger when choices were made with saccades. Further, on average, VS and amygdala lesions reduced the monkeys' ability to choose better options only when choices were made with a saccade. These results show that learning reward value associations to manage explore-exploit behaviors is motor system dependent and they further define the contributions of amygdala and VS to reinforcement learning.

Prefrontal-Amygdala Pathways for Object and Social Value Representation.

This special focus article was prepared to honor the memory of our National Institutes of Health colleague, friend, and mentor Leslie G. Ungerleider, who passed away in December 2020, and is based on a presentation given at a symposium held in her honor at the National Institutes of Health in September 2022. In this article, we describe an extension of Leslie Ungerleider's influential work on the object analyzer pathway in which the inferior temporal visual cortex interacts with the amygdala, and then discuss a broader role for the amygdala in stimulus-outcome associative learning in humans and nonhuman primates. We summarize extant data from our and others' laboratories regarding two distinct frontal-amygdala circuits that subserve nonsocial and social valuation processes. Both neuropsychological and neurophysiological data suggest a role for the OFC in nonsocial valuation and the ACC in social valuation. More recent evidence supports the possibility that the amygdala functions in conjunction with these frontal regions to subserve these distinct, complex valuation processes. We emphasize the dynamic nature of valuation processes and advocate for additional research on amygdala-frontal interactions in these domains.

Interaction between decision-making and interoceptive representations of bodily arousal in frontal cortex.

Decision-making and representations of arousal are intimately linked. Behavioral investigations have classically shown that either too little or too much bodily arousal is detrimental to decision-making, indicating that there is an inverted "U" relationship between bodily arousal and performance. How these processes interact at the level of single neurons as well as the neural circuits involved are unclear. Here we recorded neural activity from orbitofrontal cortex (OFC) and dorsal anterior cingulate cortex (dACC) of macaque monkeys while they made reward-guided decisions. Heart rate (HR) was also recorded and used as a proxy for bodily arousal. Recordings were made both before and after subjects received excitotoxic lesions of the bilateral amygdala. In intact monkeys, higher HR facilitated reaction times (RTs). Concurrently, a set of neurons in OFC and dACC selectively encoded trial-by-trial variations in HR independent of reward value. After amygdala lesions, HR increased, and the relationship between HR and RTs was altered. Concurrent with this change, there was an increase in the proportion of dACC neurons encoding HR. Applying a population-coding analysis, we show that after bilateral amygdala lesions, the balance of encoding in dACC is skewed away from signaling either reward value or choice direction toward HR coding around the time that choices are made. Taken together, the present results provide insight into how bodily arousal and decision-making are signaled in frontal cortex.

Attention to Stimuli of Learned versus Innate Biological Value Relies on Separate Neural Systems.

The neural bases of attention, a set of neural processes that promote behavioral selection, is a subject of intense investigation. In humans, rewarded cues influence attention, even when those cues are irrelevant to the current task. Because the amygdala plays a role in reward processing, and the activity of amygdala neurons has been linked to spatial attention, we reasoned that the amygdala may be essential for attending to rewarded images. To test this possibility, we used an attentional capture task, which provides a quantitative measure of attentional bias. Specifically, we compared reaction times (RTs) of adult male rhesus monkeys with bilateral amygdala lesions and unoperated controls as they made a saccade away from a high- or low-value rewarded image to a peripheral target. We predicted that: (1) RTs will be longer for high- compared with low-value images, revealing attentional capture by rewarded stimuli; and (2) relative to controls, monkeys with amygdala lesions would exhibit shorter RT for high-value images. For comparison, we assessed the same groups of monkeys for attentional capture by images of predators and conspecifics, categories thought to have innate biological value. In performing the attentional capture task, all monkeys were slowed more by high-value relative to low-value rewarded images. Contrary to our prediction, amygdala lesions failed to disrupt this effect. When presented with images of predators and conspecifics, however, monkeys with amygdala lesions showed significantly diminished attentional capture relative to controls. Thus, separate neural pathways are responsible for allocating attention to stimuli with learned versus innate value.SIGNIFICANCE STATEMENT Valuable objects attract attention. The amygdala is known to contribute to reward processing and the encoding of object reward value. We therefore examined whether the amygdala is necessary for allocating attention to rewarded objects. For comparison, we assessed the amygdala's contribution to attending to objects with innate biological value: predators and conspecifics. We found that the macaque amygdala is necessary for directing attention to images with innate biological value, but not for directing attention to recently learned reward-predictive images. These findings indicate that the amygdala makes selective contributions to attending to valuable objects. The data are relevant to mental health disorders, such as social anxiety disorders and small animal phobias, that arise from biased attention to select categories of objects.

Selective prefrontal-amygdala circuit interactions underlie social and nonsocial valuation in rhesus macaques.

Lesion studies in macaques suggest dissociable functions of the orbitofrontal cortex (OFC) and medial frontal cortex (MFC), with OFC being essential for goal-directed decision making and MFC supporting social cognition. Bilateral amygdala damage results in impairments in both of these domains. There are extensive reciprocal connections between these prefrontal areas and the amygdala; however, it is not known whether the dissociable roles of OFC and MFC depend on functional interactions with the amygdala. To test this possibility, we compared the performance of male rhesus macaques (Macaca mulatta) with crossed surgical disconnection of the amygdala and either MFC (MFC x AMY, n=4) or OFC (OFC x AMY, n=4) to a group of unoperated controls (CON, n=5). All monkeys were assessed for their performance on two tasks to measure: (1) food-retrieval latencies while viewing videos of social and nonsocial stimuli in a test of social interest, and (2) object choices based on current food value using reinforcer devaluation in a test of goal-directed decision making. Compared to the CON group, the MFC x AMY group, but not the OFC x AMY group, showed significantly reduced food-retrieval latencies while viewing videos of conspecifics, indicating reduced social valuation and/or interest. By contrast, on the devaluation task, group OFC x AMY, but not group MFC x AMY, displayed deficits on object choices following changes in food value. These data indicate that the MFC and OFC must functionally interact with the amygdala to support normative social and nonsocial valuation, respectively.Significance StatementAscribing value to conspecifics (social) vs. objects (nonsocial) may be supported by distinct but overlapping brain networks. Here we test whether two nonoverlapping regions of the prefrontal cortex, the medial frontal cortex and the orbitofrontal cortex, must causally interact with the amygdala to sustain social valuation and goal-directed decision making, respectively. We found that these prefrontal-amygdala circuits are functionally dissociable, lending support for the idea that medial frontal and orbital frontal cortex make independent contributions to cognitive appraisals of the environment. These data provide a neural framework for distinct value assignment processes and may enhance our understanding of the cognitive deficits observed following brain injury or in the development of mental health disorders.

Reevaluating the role of the hippocampus in memory: A meta-analysis of neurotoxic lesion studies in nonhuman primates.

The hippocampus and perirhinal cortex are both broadly implicated in memory; nevertheless, their relative contributions to visual item recognition and location memory remain disputed. Neuropsychological studies in nonhuman primates that examine memory function after selective damage to medial temporal lobe structures report various levels of memory impairment-ranging from minor deficits to profound amnesia. The discrepancies in published findings have complicated efforts to determine the exact magnitude of visual item recognition and location memory impairments following damage to the hippocampus and/or perirhinal cortex. To provide the most accurate estimate to date of the overall effect size, we use meta-analytic techniques on data aggregated from 26 publications that assessed visual item recognition and/or location memory in nonhuman primates with and without selective neurotoxic lesions of the hippocampus or perirhinal cortex. We estimated the overall effect size, evaluated the relation between lesion extent and effect size, and investigated factors that may account for between-study variation. Grouping studies by lesion target and testing method, separate meta-analyses were conducted. One meta-analysis indicated that impairments on tests of visual item recognition were larger after lesions of perirhinal cortex than after lesions of the hippocampus. A separate meta-analysis showed that performance on tests of location memory was severely impaired by lesions of the hippocampus. For the most part, meta-regressions indicated that greater impairment corresponds with greater lesion extent; paradoxically, however, more extensive hippocampal lesions predicted smaller impairments on tests of visual item recognition. We conclude the perirhinal cortex makes a larger contribution than the hippocampus to visual item recognition, and the hippocampus predominately contributes to spatial navigation.

Specializations for reward-guided decision-making in the primate ventral prefrontal cortex.

The estimated values of choices, and therefore decision-making based on those values, are influenced by both the chance that the chosen items or goods can be obtained (availability) and their current worth (desirability) as well as by the ability to link the estimated values to choices (a process sometimes called credit assignment). In primates, the prefrontal cortex (PFC) has been thought to contribute to each of these processes; however, causal relationships between particular subdivisions of the PFC and specific functions have been difficult to establish. Recent lesion-based research studies have defined the roles of two different parts of the primate PFC - the orbitofrontal cortex (OFC) and the ventral lateral frontal cortex (VLFC) - and their subdivisions in evaluating each of these factors and in mediating credit assignment during reward-based decision-making.

The anterior cingulate cortex is necessary for forming prosocial preferences from vicarious reinforcement in monkeys.

A key feature of most social relationships is that we like seeing good things happen to others. Research has implicated the anterior cingulate cortex (ACC) in attaching value to social outcomes. For example, single neurons in macaque ACC selectively code reward delivery to the self, a partner, both monkeys, or neither monkey. Here, we assessed whether the ACC's contribution to social cognition is causal by testing rhesus monkeys (Macaca mulatta) on a vicarious reinforcement task before and after they sustained ACC lesions. Prior to surgery, actors learned that 3 different visual cues mapped onto 3 distinct reward outcomes: to self ("Self"), to the other monkey ("Other"), or to neither monkey ("Neither"). On each trial, actors saw a cue that predicted one of the 3 juice offers and could accept the offer by making a saccade to a peripheral target or reject the offer by breaking fixation. Preoperatively, all 6 actors displayed prosocial preferences, indicated by their greater tendency to give reward to Other relative to Neither. Half then received selective, bilateral, excitotoxic lesions of the ACC, and the other half served as unoperated controls. After surgery, all monkeys retained the social preferences they had demonstrated with the preoperatively learned cues, but this preference was reduced in the monkeys with ACC lesions. Critically, none of the monkeys in the ACC lesion group acquired social preferences with a new set of cues introduced after surgery. These data indicate that the primate ACC is necessary for acquisition of prosocial preferences from vicarious reinforcement.

Effects of Amygdala Lesions on Object-Based Versus Action-Based Learning in Macaques.

The neural systems that underlie reinforcement learning (RL) allow animals to adapt to changes in their environment. In the present study, we examined the hypothesis that the amygdala would have a preferential role in learning the values of visual objects. We compared a group of monkeys (Macaca mulatta) with amygdala lesions to a group of unoperated controls on a two-armed bandit reversal learning task. The task had two conditions. In the What condition, the animals had to learn to select a visual object, independent of its location. And in the Where condition, the animals had to learn to saccade to a location, independent of the object at the location. In both conditions choice-outcome mappings reversed in the middle of the block. We found that monkeys with amygdala lesions had learning deficits in both conditions. Monkeys with amygdala lesions did not have deficits in learning to reverse choice-outcome mappings. Rather, amygdala lesions caused the monkeys to become overly sensitive to negative feedback which impaired their ability to consistently select the more highly valued action or object. These results imply that the amygdala is generally necessary for RL.

Ventral striatum's role in learning from gains and losses.

Adaptive behavior requires animals to learn from experience. Ideally, learning should both promote choices that lead to rewards and reduce choices that lead to losses. Because the ventral striatum (VS) contains neurons that respond to aversive stimuli and aversive stimuli can drive dopamine release in the VS, it is possible that the VS contributes to learning about aversive outcomes, including losses. However, other work suggests that the VS may play a specific role in learning to choose among rewards, with other systems mediating learning from aversive outcomes. To examine the role of the VS in learning from gains and losses, we compared the performance of macaque monkeys with VS lesions and unoperated controls on a reinforcement learning task. In the task, the monkeys gained or lost tokens, which were periodically cashed out for juice, as outcomes for choices. They learned over trials to choose cues associated with gains, and not choose cues associated with losses. We found that monkeys with VS lesions had a deficit in learning to choose between cues that differed in reward magnitude. By contrast, monkeys with VS lesions performed as well as controls when choices involved a potential loss. We also fit reinforcement learning models to the behavior and compared learning rates between groups. Relative to controls, the monkeys with VS lesions had reduced learning rates for gain cues. Therefore, in this task, the VS plays a specific role in learning to choose between rewarding options.

Amygdala lesions eliminate viewing preferences for faces in rhesus monkeys.

In free-viewing experiments, primates orient preferentially toward faces and face-like stimuli. To investigate the neural basis of this behavior, we measured the spontaneous viewing preferences of monkeys with selective bilateral amygdala lesions. The results revealed that when faces and nonface objects were presented simultaneously, monkeys with amygdala lesions had no viewing preference for either conspecific faces or illusory facial features in everyday objects. Instead of directing eye movements toward socially relevant features in natural images, we found that, after amygdala loss, monkeys are biased toward features with increased low-level salience. We conclude that the amygdala has a role in our earliest specialized response to faces, a behavior thought to be a precursor for efficient social communication and essential for the development of face-selective cortex.

Heightened Defensive Responses Following Subtotal Lesions of Macaque Orbitofrontal Cortex.

Anxiety disorders are characterized by excessive attention to threat. Several brain areas, including the orbitofrontal cortex (OFC), have been associated with threat processing, with more recent work implicating specialized roles for the medial and lateral subregions of the OFC in mediating specific symptoms of anxiety disorders. Virtually no causal work, however, has evaluated the role of these OFC subregions in regulating behavioral responses under threat. To address this gap, we compared male rhesus monkeys (Macaca mulatta) with bilateral excitotoxic lesions restricted to either the lateral OFC (lOFC), targeting Walker's areas 11 and 13, or the medial OFC (mOFC), targeting Walker's area 14, to a group of unoperated controls on behavioral responses to the presentation of a fake rubber snake, fake spider, and neutral stimuli. Both lesion groups showed heightened defensive and reduced approach responses, accompanied by longer latencies to retrieve a food reward, in the presence of the threatening stimuli. Compared to unoperated controls, the mOFC lesion group also showed longer latencies to reach for rewards and a greater proportion of defensive responses (e.g., piloerection) in the presence of neutral stimuli. Thus, monkeys with mOFC lesions displayed a greater tendency to express defensive responses even in the absence of threat. Overall, our data reveal that both the mOFC and lOFC contribute to the attenuation of defensive responses. Notably, these findings, obtained following selective, excitotoxic lesions of the OFC, are diametrically opposed to the effects of aspiration lesions of OFC observed in macaques.SIGNIFICANCE STATEMENT Engaging in adaptive defensive responses under threat promotes biological fitness. The orbitofrontal cortex (OFC) has been implicated in regulating defensive responses to threat, with distinct subregions likely playing different roles. Here we tested the effects of excitotoxic damage restricted to either the lateral or medial subdivisions of the OFC in rhesus macaques. We found significantly heightened defense and reduced approach responses to threatening stimuli in both lesion groups. While lateral OFC lesions led to an increase in defense responses to the threatening stimuli, medial OFC lesions produced increases in defense responses to both threatening and neutral stimuli. Our findings provide insights into the neural regulation of defensive responses to threat and inform the etiology and treatment of anxiety disorders in humans.

Gustatory responses in macaque monkeys revealed with fMRI: Comments on taste, taste preference, and internal state.

Studies of the neural mechanisms underlying value-based decision making typically employ food or fluid rewards to motivate subjects to perform cognitive tasks. Rewards are often treated as interchangeable, but it is well known that the specific tastes of foods and fluids and the values associated with their taste sensations influence choices and contribute to overall levels of food consumption. Accordingly, we characterized the gustatory system in three macaque monkeys (Macaca mulatta) and examined whether gustatory responses were modulated by preferences and hydration status. To identify taste-responsive cortex, we delivered small quantities (0.1 ml) of sucrose (sweet), citric acid (sour), or distilled water in random order without any predictive cues while scanning monkeys using event-related fMRI. Neural effects were evaluated by using each session in each monkey as a data point in a second-level analysis. By contrasting BOLD responses to sweet and sour tastes with those from distilled water in a group level analysis, we identified taste responses in primary gustatory cortex area G, an adjacent portion of the anterior insular cortex, and prefrontal cortex area 12o. Choice tests administered outside the scanner revealed that all three monkeys strongly preferred sucrose to citric acid or water. BOLD responses in the ventral striatum, ventral pallidum, and amygdala reflected monkeys' preferences, with greater BOLD responses to sucrose than citric acid. Finally, we examined the influence of hydration level by contrasting BOLD responses to receipt of fluids when monkeys were thirsty and after ad libitum water consumption. BOLD responses in area G and area 12o in the left hemisphere were greater following full hydration. By contrast, BOLD responses in portions of medial frontal cortex were reduced after ad libitum water consumption. These findings highlight brain regions involved in representing taste, taste preference and internal state.

The Role of Orbitofrontal-Amygdala Interactions in Updating Action-Outcome Valuations in Macaques.

A previous study revealed that, although monkeys with bilateral lesions of either the orbitofrontal cortex (OFC) or the amygdala could learn an action-outcome task, they could not adapt their choices in response to devalued outcomes. Specifically, they could not adjust their choice between two actions after the value of the outcome associated with one of the actions had decreased. Here, we investigated whether OFC needs to interact functionally with the amygdala in mediating such choices. Rhesus monkeys were trained to make two mutually exclusive actions on a touch-sensitive screen: "tap" and "hold." Taps led to the availability of one kind of food outcome; holds produced a different food. On each trial, monkeys could choose either a tap or a hold to earn the corresponding food reward. After consuming one of the two foods to satiety, monkeys were then tested on their ability to adapt their choices in response to the updated relative valuation of the two predicted outcomes. Whereas intact (control) monkeys shifted their choices toward the action associated with the higher value (nonsated) food, monkeys with crossed surgical disconnection of the amygdala and OFC did not. These findings demonstrate that amygdala-OFC interactions are necessary for choices among actions based on the updated value of predicted outcomes and they also have a bearing on the idea that OFC specializes in stimulus- or object-based choices in contrast to action- or response-based choices.SIGNIFICANCE STATEMENT Dysfunctional interactions between orbitofrontal cortex (OFC) and the amygdala underlie several mental health disorders, often related to value-based decision making. Understanding the underlying neural circuitry may help to develop therapies for those suffering from mood and anxiety disorders and provide insight into addiction. Here, we investigated whether the amygdala must interact with OFC to make adaptive choices. Monkeys learned to perform two different actions, "tap" for one kind of food reward and "hold" for another, and then one of the two foods was devalued temporarily. Intact monkeys shifted their choice to whichever action produced the higher-value food; monkeys with crossed surgical disconnection of OFC and the amygdala did not. Therefore, OFC and the amygdala must interact functionally to mediate adaptive choices.

Amygdala Contributions to Stimulus-Reward Encoding in the Macaque Medial and Orbital Frontal Cortex during Learning.

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 STATEMENT Altered 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.

Effects of Ventral Striatum Lesions on Stimulus-Based versus Action-Based Reinforcement Learning.

Learning the values of actions versus stimuli may depend on separable neural circuits. In the current study, we evaluated the performance of rhesus macaques with ventral striatum (VS) lesions on a two-arm bandit task that had randomly interleaved blocks of stimulus-based and action-based reinforcement learning (RL). Compared with controls, monkeys with VS lesions had deficits in learning to select rewarding images but not rewarding actions. We used a RL model to quantify learning and choice consistency and found that, in stimulus-based RL, the VS lesion monkeys were more influenced by negative feedback and had lower choice consistency than controls. Using a Bayesian model to parse the groups' learning strategies, we also found that VS lesion monkeys defaulted to an action-based choice strategy. Therefore, the VS is involved specifically in learning the value of stimuli, not actions.SIGNIFICANCE STATEMENT Reinforcement learning models of the ventral striatum (VS) often assume that it maintains an estimate of state value. This suggests that it plays a general role in learning whether rewards are assigned based on a chosen action or stimulus. In the present experiment, we examined the effects of VS lesions on monkeys' ability to learn that choosing a particular action or stimulus was more likely to lead to reward. We found that VS lesions caused a specific deficit in the monkeys' ability to discriminate between images with different values, whereas their ability to discriminate between actions with different values remained intact. Our results therefore suggest that the VS plays a specific role in learning to select rewarded stimuli.

Learned Value Shapes Responses to Objects in Frontal and Ventral Stream Networks in Macaque Monkeys.

We have an incomplete picture of how the brain links object representations to reward value, and how this information is stored and later retrieved. The orbitofrontal cortex (OFC), medial frontal cortex (MFC), and ventrolateral prefrontal cortex (VLPFC), together with the amygdala, are thought to play key roles in these processes. There is an apparent discrepancy, however, regarding frontal areas thought to encode value in macaque monkeys versus humans. To address this issue, we used fMRI in macaque monkeys to localize brain areas encoding recently learned image values. Each week, monkeys learned to associate images of novel objects with a high or low probability of water reward. Areas responding to the value of recently learned reward-predictive images included MFC area 10 m/32, VLPFC area 12, and inferior temporal visual cortex (IT). The amygdala and OFC, each thought to be involved in value encoding, showed little such effect. Instead, these 2 areas primarily responded to visual stimulation and reward receipt, respectively. Strong image value encoding in monkey MFC compared with OFC is surprising, but agrees with results from human imaging studies. Our findings demonstrate the importance of VLPFC, MFC, and IT in representing the values of recently learned visual images.

A role for primate subgenual cingulate cortex in sustaining autonomic arousal.

The subgenual anterior cingulate cortex (subgenual ACC) plays an important role in regulating emotion, and degeneration in this area correlates with depressed mood and anhedonia. Despite this understanding, it remains unknown how this part of the prefrontal cortex causally contributes to emotion, especially positive emotions. Using Pavlovian conditioning procedures in macaque monkeys, we examined the contribution of the subgenual ACC to autonomic arousal associated with positive emotional events. After such conditioning, autonomic arousal increases in response to cues that predict rewards, and monkeys maintain this heightened state of arousal during an interval before reward delivery. Here we show that although monkeys with lesions of the subgenual ACC show the initial, cue-evoked arousal, they fail to sustain a high level of arousal until the anticipated reward is delivered. Control procedures showed that this impairment did not result from differences in autonomic responses to reward delivery alone, an inability to learn the association between cues and rewards, or to alterations in the light reflex. Our data indicate that the subgenual ACC may contribute to positive affect by sustaining arousal in anticipation of positive emotional events. A failure to maintain positive affect for expected pleasurable events could provide insight into the pathophysiology of psychological disorders in which negative emotions dominate a patient's affective experience.

The Role of Frontal Cortical and Medial-Temporal Lobe Brain Areas in Learning a Bayesian Prior Belief on Reversals.

Reversal learning has been extensively studied across species as a task that indexes the ability to flexibly make and reverse deterministic stimulus-reward associations. Although various brain lesions have been found to affect performance on this task, the behavioral processes affected by these lesions have not yet been determined. This task includes at least two kinds of learning. First, subjects have to learn and reverse stimulus-reward associations in each block of trials. Second, subjects become more proficient at reversing choice preferences as they experience more reversals. We have developed a Bayesian approach to separately characterize these two learning processes. Reversal of choice behavior within each block is driven by a combination of evidence that a reversal has occurred, and a prior belief in reversals that evolves with experience across blocks. We applied the approach to behavior obtained from 89 macaques, comprising 12 lesion groups and a control group. We found that animals from all of the groups reversed more quickly as they experienced more reversals, and correspondingly they updated their prior beliefs about reversals at the same rate. However, the initial values of the priors that the various groups of animals brought to the task differed significantly, and it was these initial priors that led to the differences in behavior. Thus, by taking a Bayesian approach we find that variability in reversal-learning performance attributable to different neural systems is primarily driven by different prior beliefs about reversals that each group brings to the task. SIGNIFICANCE STATEMENT: The ability to use prior knowledge to adapt choice behavior is critical for flexible decision making. Reversal learning is often studied as a form of flexible decision making. However, prior studies have not identified which brain regions are important for the formation and use of prior beliefs to guide choice behavior. Here we develop a Bayesian approach that formally characterizes learning set as a concept, and we show that, in macaque monkeys, the amygdala and medial prefrontal cortex have a role in establishing an initial belief about the stability of the reward environment.

Two-item same/different discrimination in rhesus monkeys (Macaca mulatta).

Almost all nonhuman animals can recognize when one item is the same as another item. It is less clear whether nonhuman animals possess abstract concepts of "same" and "different" that can be divorced from perceptual similarity. Pigeons and monkeys show inconsistent performance, and often surprising difficulty, in laboratory tests of same/different learning that involve only two items. Previous results from tests using multi-item arrays suggest that nonhumans compute sameness along a continuous scale of perceptual variability, which would explain the difficulty of making two-item same/different judgments. Here, we provide evidence that rhesus monkeys can learn a two-item same/different discrimination similar to those on which monkeys and pigeons have previously failed. Monkeys' performance transferred to novel stimuli and was not affected by perceptual variations in stimulus size, rotation, view, or luminance. Success without the use of multi-item arrays, and the lack of effect of perceptual variability, suggests a computation of sameness that is more categorical, and perhaps more abstract, than previously thought.