Not surprisingly, the hedonic value of a stimulus is substantially influenced by its context. For example, in a decisionmaking situation, unexpected outcomes have greater hedonic impact than expected ones, and any given outcome is perceived as less pleasant if an unobtained outcome is perceived as being better.21 That is, surprise, which strongly activates the ventral striatum,22 and comparison with nonexperienced alternatives, contribute strongly to the experience of pleasure. Similarly, anticipation of pleasure has a profound influence on decisionmaking,

and can explain why individuals make risky choices.23 For example, people feel displeasure when the outcomes #selleck chemicals keyword# of selected actions fall short Inhibitors,research,lifescience,medical of the counterfactual alternative, and increased pleasure when their outcomes exceed the counterfactual alternative.24 Moreover, predictions of future hedonic thoroughly reactions result from a complex interplay between the current state of the individual and the changes that occur as the individual is getting

closer in time to experiencing the stimulus. Specifically, initially the hedonic experience is based on the atemporal imagination of the stimulus, Inhibitors,research,lifescience,medical which is subsequently corrected with information about the time at which the event will actually occur.25 The experience of the hedonic aspects of a rewarding stimulus itself Inhibitors,research,lifescience,medical has profound consequences of subsequent behaviors. In many instances individuals show deteriorating performance when they are anticipating the hedonic quality of a future experience.26,27 Thus, to speak of the pleasurable property of a stimulus without referring to the contextual and individual state is to fundamentally misunderstand the way the brain processes hedonic aspects of reward. Animal experiments have shown that an area within the medial caudal subregion of the nucleus accumbens shell, as well as rostral ventral pallidum, are necessary to process the hedonic reward properties of food.28,29 Moreover, it appears that the ventral pallidum, an area adjacent Inhibitors,research,lifescience,medical to and connected with the insular

cortex, 17 is a key structure in brain mesocorticolimbic reward circuits that mediate “liking” or hedonic reactions. Cilengitide Specifically, firing patterns of neurons within this structure selectively track the hedonic values of tastes, even across hedonic reversals caused by changing the homeostatic state of the animal30 One possible way to examine the brain structures necessary to process the hedonic aspects of reward is to study individuals who are unable to experience pleasure due to an underlying psychiatric condition, ie, depressed subjects with profound anhedonia. In humans, neuroimaging investigations with depressed individuals have shown altered activation in midline cortical structures as well as putamen and thalamus that were directly related to the degree of anhedonia.