Medial orbitofrontal cortex codes relative rather than absolute value of financial rewards in humans

Functional imaging studies in recent years have confirmed the involvement of orbitofrontal cortex (OFC) in human reward processing and have suggested that OFC responses are context-dependent. A seminal electrophysiological experiment in primates taught animals to associate abstract visual stimuli with differently valuable food rewards. Subsequently, pairs of these learned abstract stimuli were presented and firing of OFC neurons to the medium-value stimulus was measured. OFC firing was shown to depend on the relative value context. In this study, we developed a human analogue of this paradigm and scanned subjects using functional magnetic resonance imaging. The analysis compared neuronal responses to two superficially identical events, which differed only in terms of the preceding context. Medial OFC response to the same perceptual stimulus was greater when the stimulus predicted the more valuable of two rewards than when it predicted the less valuable. Additional responses were observed in other components of reward circuitry, the amygdala and ventral striatum. The central finding is consistent with the primate results and suggests that OFC neurons code relative rather than absolute reward value. Amygdala and striatal involvement in coding reward value is also consistent with recent functional imaging data. By using a simpler and less confounded paradigm than many functional imaging studies, we are able to demonstrate that relative financial reward value per se is coded in distinct subregions of an extended reward and decision-making network.     

Inferotemporal-frontal Disconnection: The Uncinate Fascicle and Visual Associative Learning in Monkeys

We report a series of six experiments in which we examined the behavioural effects of disconnecting the inferior temporal cortex from the prefrontal cortex in cynomolgus monkeys by sectioning the direct cortico-cortical pathway between them, the uncinate fascicle. In experiment 1, monkeys with bilateral section of the uncinate fascicle showed a marked deficit in learning visuomotor conditional problems. Experiments 2 and 3 demonstrated that this deficit was not the result of a mild motor impairment, nor of a visual discrimination impairment. However, experiment 4 showed that the impairment extended to visual – visual conditional learning. In contrast, following bilateral section of the uncinate fascicle monkeys were unimpaired at two other tasks of visual associative learning: a reward – visual associative task (experiment 5), in which the presence or absence of a food reward served as a cue to the correct choice between two visual stimuli, and a time – visual associative task (experiment 6), in which the cue to the correct choice was the length of the intertrial interval. Thus, animals with uncinate fascicle section showed no impairment in learning to choose between visual stimuli based on their differential association with food reward or other non-visual cues, but were unable to learn to choose between visual stimuli based on their differential association with another visual stimulus. They were equally unable to choose between two motor responses on the basis of the visual cue.     

A non-reward attractor theory of depression

A non-reward attractor theory of depression is proposed based on the operation of the lateral orbitofrontal cortex and supracallosal cingulate cortex. The orbitofrontal cortex contains error neurons that respond to non-reward for many seconds in an attractor state that maintains a memory of the non-reward. The human lateral orbitofrontal cortex is activated by non-reward during reward reversal, and by a signal to stop a response that is now incorrect. Damage to the human orbitofrontal cortex impairs reward reversal learning. Not receiving reward can produce depression. The theory proposed is that in depression, this lateral orbitofrontal cortex non-reward system is more easily triggered, and maintains its attractor-related firing for longer. This triggers negative cognitive states, which in turn have positive feedback top-down effects on the orbitofrontal cortex non-reward system. Treatments for depression, including ketamine, may act in part by quashing this attractor. The mania of bipolar disorder is hypothesized to be associated with oversensitivity and overactivity in the reciprocally related reward system in the medial orbitofrontal cortex and pregenual cingulate cortex.     

Insights into the nature of fronto-temporal interactions from a biconditional discrimination task in the monkey

Previous work in monkeys has shown that both frontal and inferior temporal cortices are required to solve visual learning tasks. When communication between these cortical areas is prevented within the same hemisphere by crossed lesions of the frontal cortex in one hemisphere and the inferior temporal cortex in the opposite hemisphere, most learning tasks are impaired, but learning of object-reward associations is unimpaired. The current experiment aims to understand further the role of the interaction between the frontal and inferior temporal cortices in learning tasks. We trained monkeys on a biconditional discrimination task, in which different visual cues guided behaviour towards choice objects. One visual cue predicted immediate delivery of reward to a correct response, the other visual cue predicted a delayed delivery of reward to a correct response. Pre-operative behavioural data clearly shows that the monkeys form expectations of the reward outcome for the individual cues and choice objects. Crossed lesions of frontal and inferior temporal cortices, however, produce no impairment on this task. The result suggests (in combination with previous experiments) that task difficulty does not determine the reliance of a task on interactions between the frontal cortex and the inferior temporal cortex within the same hemisphere. Instead, we propose that tasks that can be solved by using expectation of the reward outcome do not require interaction of frontal and inferior temporal cortices within the same hemisphere. The results are discussed in the context of other data on frontal interactions with inferior temporal cortex in learning tasks.     

Delay-period activities in two subdivisions of monkey inferotemporal cortex during pair association memory task

The macaque inferotemporal cortex, which is involved in encoding and retrieval of visual long-term memory, consists of two distinct but mutually interconnected areas: area TE (TE) and area 36 (A36). In the present study, we compared delay-period activities of the two subdivisions in terms of their signal contents. We recorded single-unit activities from TE and A36 during a delayed pair association task, in which monkeys were required to choose the paired associate of a cue stimulus after a delay period. The stimulus-selective delay-period activities of single neurons were characterized by using partial correlation coefficients of delay-period activities for each cue stimulus with the cue-period responses to that stimulus (cue-holding index, CHI) and with the cue-period responses to its paired associate (pair-recall index, PRI). The delay-period activities of TE neurons preferentially represented the paired associate (PRI, median = 0.54) rather than the cue stimulus itself (CHI, 0.23) (P < 0.001, n = 70), while the delay-period activities of A36 neurons retained both the cue stimulus and its paired associate equivalently (CHI, 0.44; PRI, 0.46) (P = 0.78, n = 38). These results indicate that the signal contents of delay-period activities differ between the two subdivisions: TE mostly represents a sought target that is retrieved from long-term memory, while A36 in addition retains cue-stimulus that is transmitted from earlier visual areas.     

Evaluating Visual Cues Modulates Their Representation in Mouse Visual and Cingulate Cortex

Choosing an action in response to visual cues relies on cognitive processes, such as perception, evaluation, and prediction, which can modulate visual representations even at early processing stages. In the mouse, it is challenging to isolate cognitive modulations of sensory signals because concurrent overt behavior patterns, such as locomotion, can also have brainwide influences. To address this challenge, we designed a task, in which head-fixed mice had to evaluate one of two visual cues. While their global shape signaled the opportunity to earn reward, the cues provided equivalent local stimulation to receptive fields of neurons in primary visual (V1) and anterior cingulate cortex (ACC). We found that mice evaluated these cues within few hundred milliseconds. During this period, ∼30% of V1 neurons became cue-selective, with preferences for either cue being balanced across the recorded population. This selectivity emerged in response to the behavioral demands because the same neurons could not discriminate the cues in sensory control measurements. In ACC, cue evaluation affected a similar fraction of neurons; emerging selectivity, however, was stronger than in V1, and preferences in the recorded population were biased toward the cue promising reward. Such a biased selectivity regime might allow the mouse to infer the promise of reward simply by the overall level of activity. Together, these experiments isolate the impact of task demands on neural responses in mouse cerebral cortex, and document distinct neural signatures of cue evaluation in V1 and ACC.SIGNIFICANCE STATEMENT Performing a cognitive task, such as evaluating visual cues, not only recruits frontal and parietal brain regions, but also modulates sensory processing stages. We trained mice to evaluate two visual cues, and show that, during this task, ∼30% of neurons recorded in V1 became selective for either cue, although they provided equivalent visual stimulation. We also show that, during cue evaluation, mice frequently move their eyes, even under head fixation, and that ignoring systematic differences in eye position can substantially obscure the modulations seen in V1 neurons. Finally, we document that modulations are stronger in ACC, and biased toward the reward-predicting cue, suggesting a transition in the neural representation of task-relevant information across processing stages in mouse cerebral cortex.     

Modulation of Behavior by Expected Reward Magnitude Depends on Dopamine in the Dorsomedial Striatum

Reward-predictive cues are important to guide behavioral responding. In a series of experiments, we sought to characterize the role of dopamine in the dorsomedial striatum in modulation of reward-directed responding by visual cues. Different groups of rats subjected to infusion of 6-hydroxydopamine or vehicle into the posterior part of the dorsomedial striatum (pDMS) were tested in three experiments. In experiment 1, rats were examined in an operant task demanding a lever release response. In intact rats, reaction times of responding were reliably shorter on cued large reward trials than on cued small reward trials. Results showed that pDMS dopamine depletion impaired reward-dependent modulation of reaction times, if visual cues predict large versus small reward, but not if visual cues predict reward versus no reward. These observations suggest that dopamine signaling in the pDMS contributes to a process through which reward-directed responses become guided by cues associated with distinct reward magnitudes. Experiment 2 revealed that pDMS dopamine depletion did not compromise the acquisition of a conditional visual discrimination task in an operant box that required learning a rule of the type “if the cue light is bright press left lever for reward, if dim press right lever”. Furthermore, experiment 3 showed that pDMS dopamine depletion did not impair the acquisition of a cross maze task that required learning a visual cue discrimination strategy to obtain food reward. Together results of experiments 2 and 3 indicate that dopamine signaling in the pDMS does not subserve stimulus discrimination per se and stimulus-response learning.     

Re-evaluating the role of the orbitofrontal cortex in reward and reinforcement

The orbitofrontal cortex and adjacent ventromedial prefrontal cortex carry reward representations and mediate flexible behaviour when circumstances change. Here we review how recent experiments in humans and macaques have confirmed the existence of a major difference between the functions of the ventromedial prefrontal cortex and adjacent medial orbitofrontal cortex (mOFC) on the one hand and the lateral orbitofrontal cortex (lOFC) on the other. These differences, however, may not be best accounted for in terms of specializations for reward and error/punishment processing as is commonly assumed. Instead we argue that both lesion and functional magnetic resonance imaging studies reveal that the lOFC is concerned with the assignment of credit for both reward and error outcomes to the choice of specific stimuli and with the linking of specific stimulus representations to representations of specific types of reward outcome. By contrast, we argue that the ventromedial prefrontal cortex/mOFC is concerned with evaluation, value-guided decision-making and maintenance of a choice over successive decisions. Despite the popular view that they cause perseveration of behaviour and inability to inhibit repetition of a previously made choice, we found that lesions in neither orbitofrontal subdivision caused perseveration. On the contrary, lesions in the lOFC made animals switch more rapidly between choices when they were finding it difficult to assign reward values to choices. Lesions in the mOFC caused animals to lose their normal predisposition to repeat previously successful choices, suggesting that the mOFC does not just mediate value comparison in choice but also facilitates maintenance of the same choice if it has been successful.     

Willingness to wait and altered encoding of time-discounted reward in the orbitofrontal cortex with normal aging

Normal aging has been associated with cognitive changes, including shifts in responding for time-discounted rewards. The orbitofrontal cortex, an area previously associated with aging-related cognitive changes, is critical for normal discounting. Previously we have shown in a choice task that rats prefer immediate over delayed reward and that neural representations of delayed reward in orbitofrontal cortex were attenuated, whereas immediate reward elicited strong responses. Changes in choice performance were correlated with changes in firing rate in orbitofrontal neurons, suggesting that these reward representations were critical to the rats' ability to wait for reward. Here we asked whether age-dependent changes in discounting behavior were related to changes in the representation of delayed reward in the orbitofrontal cortex. Young (3-6 months) and aged (22-26 months) rats were trained on the same discounting paradigm used previously. We found that aged rats showed less sensitivity to increasing delay preceding reward delivery, shifting behavior away from the delayed reward more slowly than younger rats. This sensitivity was specific to delay, since choice performance did not differ between the two groups when delay was held constant and reward size varied. Aged rats exhibited a corresponding increase in the prevalence of neurons that fired more strongly for delayed reward. Again this change was specific to delay; there was no change in encoding of different-sized rewards. These results suggest that natural aging results in altered representations of reward in orbitofrontal cortex. These changes may relate to the increased ability to delay gratification and reduced impulsivity associated with aging.     

The anterior insular cortex represents breaches of taste identity expectation

Despite the importance of breaches of taste identity expectation for survival, its neural correlate is unknown. We used fMRI in 16 women to examine brain response to expected and unexpected receipt of sweet taste and tasteless/odorless solutions. During expected trials (70%), subjects heard "sweet" or "tasteless" and received the liquid indicated by the cue. During unexpected trials (30%), subjects heard sweet but received tasteless or they heard tasteless but received sweet. After delivery, subjects indicated stimulus identity by pressing a button. Reaction time was faster and more accurate after valid cuing, indicating that the cues altered expectancy as intended. Tasting unexpected versus expected stimuli resulted in greater deactivation in fusiform gyri, possibly reflecting greater suppression of visual object regions when orienting to, and identifying, an unexpected taste. Significantly greater activation to unexpected versus expected stimuli occurred in areas related to taste (thalamus, anterior insula), reward [ventral striatum (VS), orbitofrontal cortex], and attention [anterior cingulate cortex, inferior frontal gyrus, intraparietal sulcus (IPS)]. We also observed an interaction between stimulus and expectation in the anterior insula (primary taste cortex). Here response was greater for unexpected versus expected sweet compared with unexpected versus expected tasteless, indicating that this region is preferentially sensitive to breaches of taste expectation. Connectivity analyses confirmed that expectation enhanced network interactions, with IPS and VS influencing insular responses. We conclude that unexpected oral stimulation results in suppression of visual cortex and upregulation of sensory, attention, and reward regions to support orientation, identification, and learning about salient stimuli.     

Effective connectivity of a reward network in obese women

Exaggerated reactivity to food cues in obese women appears to be mediated in part by a hyperactive reward system that includes the nucleus accumbens, amygdala, and orbitofrontal cortex. The present study used functional magnetic resonance imaging (fMRI) to investigate whether differences between 12 obese and 12 normal-weight women in reward-related brain activation in response to food images can be explained by changes in the functional interactions between key reward network regions. A two-step path analysis/General Linear Model approach was used to test whether there were group differences in network connections between nucleus accumbens, amygdala, and orbitofrontal cortex in response to high- and low-calorie food images. There was abnormal connectivity in the obese group in response to both high- and low-calorie food cues compared to normal-weight controls. Compared to controls, the obese group had a relative deficiency in the amygdala's modulation of activation in both orbitofrontal cortex and nucleus accumbens, but excessive influence of orbitofrontal cortex's modulation of activation in nucleus accumbens. The deficient projections from the amygdala might relate to suboptimal modulation of the affective/emotional aspects of a food's reward value or an associated cue's motivational salience, whereas increased orbitofrontal cortex to nucleus accumbens connectivity might contribute to a heightened drive to eat in response to a food cue. Thus, it is possible that not only greater activation of the reward system, but also differences in the interaction of regions in this network may contribute to the relatively increased motivational value of foods in obese individuals.     

Early orbitofrontal hyperactivation in obsessive-compulsive disorder

Dysfunctional activity in the orbitofrontal cortex (OFC) is one of the core features in the pathophysiology of obsessive-compulsive disorder (OCD). Neuroimaging studies indicate orbitofrontal hyperactivation during the resting state as well as during symptom provocation, whereas orbitofrontal hypoactivation has been reported during tasks designed to dissociate specific cognitive processes. Combined magnetoencephalic and functional magnetic resonance imaging studies show early involvement of the OFC in stimulus processing in healthy subjects. However, it is unclear whether OFC activation is dysfunctional at an early stage in patients with OCD. We investigated early electrical OFC activation evoked by reward and punishment feedback in a visual probabilistic object reversal task (pORT). Patients with OCD (n=23) and healthy controls (n=27), matched for gender, age and educational level, performed the pORT during a 29-channel electroencephalographic recording. Low resolution brain electromagnetic tomography was applied to localize orbitofrontal sources of neuronal activity at 80 to 200 ms post-stimulus. Group comparison showed significantly higher orbitofrontal activation in OCD patients at 100-120 ms after the reward stimulus. No group differences were found with respect to OFC activation in response to punishment stimuli and in task performance. Results substantiate dysfunctional OFC activity at a very early stage in the processing of reward stimuli in patients with OCD. Our results provide support for the assumption that the OFC plays a more active role in the processing of visual stimuli as previously supposed. As orbitofrontal hyperactivation following rewarding feedback occurred as early as 100 ms after receipt of the visual stimulus in patients with OCD, and as we did not find any OFC dysfunction following negative feedback, our findings may point towards a specific early disturbance of reward processing in OCD. This finding might have implications for cognitive behavioural therapy of this disorder.     

The Representation of Information About Taste and Odor in the Orbitofrontal Cortex

Complementary neurophysiological recordings in macaques and functional neuroimaging in humans show that the primary taste cortex in the rostral insula and adjoining frontal operculum provides separate and combined representations of the taste, temperature, and texture (including viscosity and fat texture) of food in the mouth independently of hunger and thus of reward value and pleasantness. One synapse on, in the orbitofrontal cortex, these sensory inputs are for some neurons combined by learning with olfactory and visual inputs, and these neurons encode food reward in that they only respond to food when hungry and in that activations here correlate with subjective pleasantness and with individual differences in and cognitive modulation of the hedonic value of food. Information theory analysis shows a robust representation of taste in the orbitofrontal cortex, with an average mutual information of 0.45 bits for each neuron about which of six tastants (glucose, NaCl, HCl, quinine-HCl, monosodium glutamate, and water) was present, averaged across 135 gustatory neurons. The information increased with the number of neurons in the ensemble, but less than linearly, reflecting some redundancy. There was less information per neuron about which of six odors was present from orbitofrontal olfactory neurons, but the code was robust in that the information increased linearly with the number of neurons, reflecting independent information encoded by different neurons. Although some neurons were sharply tuned to individual tastants, the average encoding was quite distributed.     

How task demands shape brain responses to visual food cues

Several previous imaging studies have aimed at identifying the neural basis of visual food cue processing in humans. However, there is little consistency of the functional magnetic resonance imaging (fMRI) results across studies. Here, we tested the hypothesis that this variability across studies might – at least in part – be caused by the different tasks employed. In particular, we assessed directly the influence of task set on brain responses to food stimuli with fMRI using two tasks (colour vs. edibility judgement, between‐subjects design). When participants judged colour, the left insula, the left inferior parietal lobule, occipital areas, the left orbitofrontal cortex and other frontal areas expressed enhanced fMRI responses to food relative to non‐food pictures. However, when judging edibility, enhanced fMRI responses to food pictures were observed in the superior and middle frontal gyrus and in medial frontal areas including the pregenual anterior cingulate cortex and ventromedial prefrontal cortex. This pattern of results indicates that task sets can significantly alter the neural underpinnings of food cue processing. We propose that judging low‐level visual stimulus characteristics – such as colour – triggers stimulus‐related representations in the visual and even in gustatory cortex (insula), whereas discriminating abstract stimulus categories activates higher order representations in both the anterior cingulate and prefrontal cortex. Hum Brain Mapp 38:2897–2912, 2017. © 2017 Wiley Periodicals, Inc.     

Context-dependent responses of primate nucleus basalis neurons in a go/no-go task

In previous studies involving monkeys performing behavioral tasks, neurons in the nucleus basalis frequently had significant changes in discharge rate when the animal made a movement in response to a sensory stimulus in order to obtain a reward. To determine whether such responses of basalis neurons are primarily sensory or motor in nature, the activity of single basalis neurons was recorded in monkeys performing a go/no-go (GNG) task which provided a dissociation between sensory and motor neuronal responses. In a sample of 425 basalis neurons, 326 (77%) had significant changes in firing in at least one phase of the GNG task. Most of the task-related neurons (70%) responded in the choice phase in which the animal either made an arm movement (go condition) or kept its arm motionless (no-go condition) in order to obtain a water reward. Of 253 neurons that responded in the choice phase, 88% had changes in firing in the no-go condition that were equal to or, in some cases, greater than the changes in firing in the go condition. Therefore, most responses of basalis neurons in the choice phase could not be specific for the arm movement because they occurred when there was no arm movement at all. The visual stimulus presented in the choice phase was also presented earlier on each trial in the cue phase. Although 70% of the task-related basalis neurons responded in the choice phase, only 5% had detectable changes in firing in the cue phase. Of 251 neurons responding in the cue or choice phase, 59% had significantly larger changes in firing in the choice phase than in the cue phase, whereas only one neuron had a larger response in the cue phase. Therefore, most responses of basalis neurons in the choice phase could not be specific for the visual stimulus because similar responses did not occur when the same stimulus was presented in the cue phase. These results indicate that the frequent responses of basalis neurons in the choice phase are neither purely sensory nor motor in nature, but are highly dependent on the context of the stimulus or movement. The neuronal responses in the choice phase may reflect either transient increases in arousal or decision-making processes.     

Reward sensitivity in impulsivity

Impulsive individuals choose immediate small over delayed larger rewards, suggesting reward hypersensitivity. Single-unit studies have shown increased ventral tegmental activity to rewards and reward predictors and decreased activity when predicted rewards are withheld. The orbitofrontal ventral tegmental cortical target also responds to reward and expectation in single-unit and neuroimaging studies. The anterior P2a event-related potential component is a proposed index of reward-related orbitofrontal activity. In this reward prediction study in high and low impulsive subjects, the P2a localized to orbitofrontal cortex and was largest to non-predicted rewards and smallest in the absence of predicted rewards in subjects higher on self-reported impulsiveness, consistent with a P2a index of orbitofrontal reward processing and with reward hypersensitivity in impulsivity.     

Functional magnetic resonance imaging of reward prediction

PURPOSE OF REVIEW: Technical and conceptual advances in functional magnetic resonance imaging now allow visualization of real-time changes in oxygenation of deep subcortical regions, leading to rapid advances in scientific characterization of the neural substrates that underlie reward prediction in humans. RECENT FINDINGS: Neuroimaging research over the past year has focused on determining the necessary neural substrates for reward prediction. SUMMARY: While the orbitofrontal cortex has long been implicated in modality-specific reward representation, the ventral striatum (particularly the nucleus accumbens) may play a role in modality-independent representations of predicted reward. On the other hand, the mesial prefrontal cortex appears to play a role in representing reward prediction error and the dorsal caudate in linking reward to behavior. Theoretically, future studies will need to establish the specificity of these responses to reward versus punishment and anticipation versus outcome. Clinically, current findings suggest that patients can predict reward without a prefrontal cortex, but should experience difficulty correcting their behavior when reward predictions are violated.     

Sustained activities and retrieval in a computational model of the perirhinal cortex

The perirhinal cortex is involved not only in object recognition and novelty detection but also in multimodal integration, reward association, and visual working memory. We propose a computational model that focuses on the role of the perirhinal cortex in working memory, particularly with respect to sustained activities and memory retrieval. This model describes how different partial informations are integrated into assemblies of neurons that represent the identity of an object. Through dopaminergic modulation, the resulting clusters can retrieve the global information with recurrent interactions between neurons. Dopamine leads to sustained activities after stimulus disappearance that form the basis of the involvement of the perirhinal cortex in visual working memory processes. The information carried by a cluster can also be retrieved by a partial thalamic or prefrontal stimulation. Thus, we suggest that areas involved in planning and memory coordination encode a pointer to access the detailed information encoded in the associative cortex such as the perirhinal cortex.     

Reward breaks through center‐surround inhibition via anterior insula

Focusing attention on a target creates a center‐surround inhibition such that distractors located close to the target do not capture attention. Recent research showed that a distractor can break through this surround inhibition when associated with reward. However, the brain basis for this reward‐based attention is unclear. In this fMRI study, we presented a distractor associated with high or low reward at different distances from the target. Behaviorally the low‐reward distractor did not capture attention and thus did not cause interference, whereas the high‐reward distractor captured attention only when located near the target. Neural activity in extrastriate cortex mirrored the behavioral pattern. A comparison between the high‐reward and the low‐reward distractors presented near the target (i.e., reward‐based attention) and a comparison between the high‐reward distractors located near and far from the target (i.e., spatial attention) revealed a common frontoparietal network, including inferior frontal gyrus and inferior parietal sulcus as well as the visual cortex. Reward‐based attention specifically activated the anterior insula (AI). Dynamic causal modelling showed that reward modulated the connectivity from AI to the frontoparietal network but not the connectivity from the frontoparietal network to the visual cortex. Across participants, the reward‐based attentional effect could be predicted both by the activity in AI and by the changes of spontaneous functional connectivity between AI and ventral striatum before and after reward association. These results suggest that AI encodes reward‐based salience and projects it to the stimulus‐driven attentional network, which enables the reward‐associated distractor to break through the surround inhibition in the visual cortex. Hum Brain Mapp 36:5233–5251, 2015. © 2015 Wiley Periodicals, Inc.     

Differential involvement of the basolateral amygdala and orbitofrontal cortex in the formation of sensory-specific associations in conditioned flavor preference and magazine approach paradigms

Four experiments examined the roles of the basolateral amygdala and orbitofrontal cortex in the formation of sensory-specific associations in conditioned flavor preference and conditioned magazine approach paradigms using unconditioned stimulus (US) devaluation and selective Pavlovian-instrumental transfer procedures in Long Evans rats. Experiment 1 found that pre-training amygdala and orbitofrontal cortex lesions had no detectable effect on the formation or flexible use of sensory-specific flavor-nutrient associations in a US devaluation task, where flavor cues were paired either simultaneously or sequentially with nutrient rewards in water-deprived subjects. In Experiment 2, pre-training amygdala and orbitofrontal cortex lesions both attenuated outcome-specific Pavlovian-instrumental transfer. Experiment 3 indicated that amygdala lesions have no effect on the formation of sensory-specific flavor-nutrient associations in a US devaluation task in food-deprived subjects. Finally, Experiment 4 demonstrated that the outcomes used in Experiment 3 were sufficiently motivationally significant to support conditioned flavor preference. These findings suggest that, although both orbitofrontal cortex and amygdala lesions attenuate the acquisition of sensory-specific associations in magazine approach conditioning, neither lesion reduces the ability to appropriately respond to a flavor cue that was paired with a devalued outcome.