OFC is thought to be essential for at least two aspects of stimulus-reward learning: 1) representing the current value of anticipated outcomes and 2) learning to choose based on the relationship between particular choices and the probability of receiving a reward. These two aspects might be considered to reflect the desirability and availability of reward outcomes. Yet the ventrolateral prefrontal cortex (VLPFC), a region adjacent to OFC, has also been implicated in learning about the availability of outcomes. To explore the functional specializations of these two frontal cortex regions, we trained animals on two tasks: one required updating representations of a predicted outcomes desirability, as measured by the devaluation task; the other required updating representations of an outcomes availability, as indexed by performance on a probabilistic 3-choice visual discrimination. We evaluated performance on both tasks in three groups of animals: unoperated controls and those with selective, fiber-sparing lesions of either OFC or VLPFC. We found that VLPFC but not OFC plays an essential role in making choices based on outcome availability; in contrast, OFC but not VLPFC is essential for making choices based on outcome desirability. The separate processing of outcome availability and desirability in VLPFC and OFC, respectively, has implications for models of prefrontal cortex function during choice behavior. A considerable body of evidence suggests a role for the amygdala in processing emotionally salient information in faces. For example, patients with amygdala damage fix their gaze on the eye region of faces to a lesser extent than controls. In our earlier work we used an attentional capture task to assess the role of the amygdala in attending to different aspects of facial expressions of emotion. Attentional capture is a phenomenon whereby irrelevant stimuli in the field of view detract from ongoing cognitive processes. We found that subjects with amygdala lesions showed reduced attentional capture by face stimuli, and that this effect was driven by the mouth region more than the eyes. Thus, the amygdala contributes to the processing of, and attention to, certain social cues. Rewarded stimuli are also known to capture attention. Because the amygdala is essential for processing reward outcomes, this raised the possibility that it is important for attending to rewarded stimuli. To test this, animals with amygdala lesions and intact controls were trained to acquire stimulus-reward associations, and then probed for attentional capture by those rewarded stimuli. Both groups showed robust attentional capture by the rewarded stimuli, measured by the latency to look away from a valuable, rewarded image. Importantly, there was no effect of the lesion on attentional capture. The same groups of animals were tested for attentional capture by innately valuable stimuli, including predators (e.g., snakes, crocodiles) and positive social cues (e.g., female perineum). Here, attentional capture was attenuated in the animals with amygdala lesions relative to controls. These data indicate that the amygdala is essential for attending to innately valuable but not learned reward-predictive stimuli. We have also studied the neural basis of reward processing in a social context. Previous research shows that animals choose to deliver rewards to their conspecifics under some conditions. This apparent prosocial preference suggests that the sight of another animal receiving reward is vicariously reinforcing. Here, we evaluated how pupil size, an autonomic correlate of arousal, changed when animals anticipated that juice would be delivered to themselves, another conspecific animal, or not at all. Two animals sat opposite each other while one, the actor, was visually cued to the upcoming juice delivery outcome and could choose to complete or abort the trial. Consistent with previous research, actors chose to complete most self-reward trials, a moderate number of other-reward trials, and the fewest neither-reward trials, suggesting that they did prefer juice delivery to the other animal over juice delivery to nobody. As expected, pupil size was widest in anticipation of the animals own reward. Paradoxically, pupil size was more constricted in anticipation of reward to the other animal than in anticipation of reward to nobody. Thus, trial completion rates suggest animals find reward delivery to another animal reinforcing, but pupil size suggests they find it aversive. Thus, there may be both positive and negative affect associated with vicarious reinforcement. Studies examining the effects of focal brain lesions provide critical insights on the relationships between brain structure and behavior. Current techniques allow researchers to damage cell bodies selectively, while sparing fibers of passage. A major challenge of the lesion method is documenting the degree to which the lesion is both complete and selective for the region of interest. Currently, lesion extent is manually drawn on a series of sections of a reference brain from visual inspection of a postoperative T1 MRI scan (in which damage appears as relative hyposignal), T2 MRI scan (in which damage appears as relative hypersignal), or histology slides. However, this approach is time-consuming and difficult to standardize. Recent advances in automated nonlinear registration algorithms and the advent of a standard brain template may improve the speed and standardization of lesion mapping. Here, we employ a semi-automated method to map cortical lesion boundaries (e.g., orbitofrontal cortex, prelimbic cortex, premotor cortex) from multiple subjects to a single standard template. This two-step process involves: 1) manually tracing the lesions in native space on the subjects postoperative MRI scan, and 2) warping the traced lesion mask and postoperative scan to template space using a nonlinear algorithm provided by a validated neuroimaging software package, ANTs. We further evaluate the extent to which the damage registered in the in vivo scans are representative of the actual surgical damage by comparing these digitized masks to traditional Nissl-stained histological material. This approach provides an improved method for lesion mapping that saves time, standardizes results, and provides multiple options for quantifying lesion extent and generating informative 2D and 3D visualizations. Selective, fiber-sparing excitotoxic lesions are a state-of-the-art tool for studying the causal contributions of different brain areas to behavior. We routinely use MRI to plan and to guide injections of excitotoxins into specific regions to produce selective cell loss (i.e., lesions). In addition, we routinely assess the extent of excitotoxic lesions in vivo, using MRI-based methods, within a few weeks of the operation. To determine whether in vivo T2-weighted MRI accurately estimates damage following selective excitotoxic lesions of the amygdala, we compared lesion volume estimates for the amygdala obtained from MRI and traditional histology. Across 19 hemispheres from 13 subjects, MRI assessment consistently overestimated amygdala damage compared to microscopic examination of Nissl-stained histological material. Two outliers suggested that near-complete MRI-estimated damage may predict actual damage of at least 45%, but more data are necessary to evaluate this hypothesis. However, excitotoxins routinely produce extensive damage (median = 82%) that correlates with total injection volume, validating the general success of the technique. The field will benefit from more research into these assessment methods, and the accuracy of MRI assessment in different brain areas. For now, in vivo MRI assessment of lesions of the amygdala can be used to confirm successful injections, but estimates of lesion extent should be interpreted with caution.
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