Transient Inactivation of Orbitofrontal Cortex Blocks Reinforcer Devaluation in Macaques

Department of Pharmacology and Physiology, Georgetown University Medical Center, Washington, DC 20007, USA.
The Journal of Neuroscience : The Official Journal of the Society for Neuroscience (Impact Factor: 6.34). 10/2011; 31(42):15128-35. DOI: 10.1523/JNEUROSCI.3295-11.2011
Source: PubMed


The orbitofrontal cortex (OFC) and its interactions with the basolateral amygdala (BLA) are critical for goal-directed behavior, especially for adapting to changes in reward value. Here we used a reinforcer devaluation paradigm to investigate the contribution of OFC to this behavior in four macaques. Subjects that had formed associations between objects and two different primary reinforcers (foods) were presented with choices of objects overlying the two different foods. When one of the two foods was devalued by selective satiation, the subjects shifted their choices toward the objects that represented the nonsated food reward (devaluation effect). Transient inactivation of OFC by infusions of the GABA(A) receptor agonist muscimol into area 13 blocked the devaluation effect: the monkeys did not reduce their selection of objects associated with the devalued food. This effect was observed when OFC was inactivated during both satiation and the choice test, and during the choice test only. This supports our hypothesis that OFC activity is required during the postsatiety object choice period to guide the selection of objects. This finding sharply contrasts with the role of BLA in the same devaluation process (Wellman et al., 2005). Whereas activity in BLA was required during the selective satiation procedure, it was not necessary for guiding the subsequent object choice. Our results are the first to demonstrate that transient inactivation of OFC is sufficient to disrupt the devaluation effect, and to document a role for OFC distinct from that of BLA for the conditioned reinforcer devaluation process in monkeys.

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    • "In particular, much work has focused on the computation and representation of subjective values. Lesion studies have shown that value-based decisions are selectively disrupted after lesions to the orbitofrontal cortex (OFC) and/or the amygdala, but effectively spared after lesions to other brain regions (Buckley et al., 2009; Camille et al., 2011; Gallagher et al., 1999; Rudebeck and Murray, 2011; West et al., 2011). Neurophysiology experiments have found that neurons in the primate OFC encode the subjective value of different goods during economic decisions and integrate multiple dimensions on which goods can vary (Kennerley et al., 2009; Padoa-Schioppa and Assad, 2006; Roesch and Olson, 2005). "
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    ABSTRACT: To investigate the mechanisms through which economic decisions are formed, I examined the activity of neurons in the orbitofrontal cortex while monkeys chose between different juice types. Different classes of cells encoded the value of individual offers (offer value), the value of the chosen option (chosen value), or the identity of the chosen juice (chosen juice). Choice variability was partly explained by the tendency to repeat choices (choice hysteresis). Surprisingly, near-indifference decisions did not reflect fluctuations in the activity of offer value cells. In contrast, near-indifference decisions correlated with fluctuations in the preoffer activity of chosen juice cells. After the offer, the activity of chosen juice cells reflected the decision difficulty but did not resemble a race-to-threshold. Finally, chosen value cells presented an "activity overshooting" closely related to the decision difficulty and possibly due to fluctuations in the relative value of the juices. This overshooting was independent of choice hysteresis.
    Preview · Article · Dec 2013 · Neuron
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    • "Changes in instrumental responding after reinforcer devaluation as well as extinction learning, particularly recall, depend critically on input from medial prefrontal cortex to dorsal striatal regions (Corbit and Balleine 2003; Killcross and Coutureau 2003; Milad and Quirk 2002; Quirk et al. 2000; Rhodes and Killcross 2004, 2007; Zapata et al. 2010). Similarly, flexible responding to Pavlovian cues after devaluation and in other settings requires orbitofrontal output that impacts areas in dorsal and ventral striatum (Izquierdo et al. 2004; Machado and Bachevalier 2007; Pickens et al. 2003; West et al. 2011). Altered prefrontal processing would therefore be expected to lead to behavioral deficits in these areas. "
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    ABSTRACT: Addiction is characterized by maladaptive decision-making, in which individuals seem unable to use adverse outcomes to modify their behavior. Adverse outcomes are often infrequent, delayed, and even rare events, especially when compared to the reliable rewarding drug-associated outcomes. As a result, recognizing and using information about their occurrence put a premium on the operation of so-called model-based systems of behavioral control, which allow one to mentally simulate outcomes of different courses of action based on knowledge of the underlying associative structure of the environment. This suggests that addiction may reflect, in part, drug-induced dysfunction in these systems. Here, we tested this hypothesis. This study aimed to test whether cocaine causes deficits in model-based behavior and learning independent of requirements for response inhibition or perception of costs or punishment. We trained rats to self-administer sucrose or cocaine for 2 weeks. Four weeks later, the rats began training on a sensory preconditioning and inferred value blocking task. Like devaluation, normal performance on this task requires representations of the underlying task structure; however, unlike devaluation, it does not require either response inhibition or adapting behavior to reflect aversive outcomes. Rats trained to self-administer cocaine failed to show conditioned responding or blocking to the preconditioned cue. These deficits were not observed in sucrose-trained rats nor did they reflect any changes in responding to cues paired directly with reward. These results imply that cocaine disrupts the operation of neural circuits that mediate model-based behavioral control.
    Full-text · Article · Aug 2013 · Psychopharmacology
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    • "As described above for the amygdala, to dissect the contributions of OFC to different phases of the devaluation task, West and colleagues examined the effects of inactivation of OFC before and after the selective satiation procedure (West et al., 2011). They found that inactivation of OFC either before or after the selective satiation procedure disrupted devaluation effects. "
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    ABSTRACT: Hungry animals are influenced by a multitude of different factors when foraging for sustenance. Much of the work on animal foraging has focused on factors relating to the amount of time and energy animals expend searching for and harvesting foods. Models that emphasize such factors have been invaluable in determining when it is beneficial for an animal to search for pastures new. When foraging, however, animals also have to determine how to direct their search. For what food should they forage? There is no point searching for more of a particular food when you are sated from eating it. Here we review work in macaques and humans that has sought to reveal the neural circuits critical for determining the subjective value of different foods and associated objects in our environment and tracking this value over time. There is mounting evidence that a network composed of the orbitofrontal cortex (OFC), amygdala, and medial thalamus is critical for linking objects in the environment with food value and adjusting those valuations in real time based on current biological needs. Studies using temporary inactivation methods have revealed that the amygdala and OFC play distinct yet complementary roles in this valuation process. Such a network for determining the subjective value of different foods and, by extension, associated objects, must interact with systems that determine where and for how long to forage. Only by efficiently incorporating these two factors into their decisions will animals be able to achieve maximal fitness.
    Full-text · Article · Jun 2013 · Frontiers in Neuroscience
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