2008). Response perseveration is an important concept in addiction, because many drug dependent persons are not able to adapt their response to changing unforeseen events, such as the presentation of a drug-related reward, resulting in uncontrolled and compulsive drug use. In addition, response perseveration is of key importance in the treatment of drug dependence, where drug-addicted individuals need to Inhibitors,research,lifescience,medical learn how to change their automated responses following drug cues (i.e., cognitive–behavioral therapy).

In most studies, response perseveration (compulsivity) was assessed with the PRLT, that is, a lack of adequate shifting following nonannounced punishment contingencies. Similarly, heavy smokers earned less money than HCs on the PRLT due to higher response perseveration in smokers (de Ruiter et al. 2009). Also, gambling tasks providing feedback with regard to gains and losses allow group comparisons of reward and punishment sensitivity. Subjects may choose between risky high reward and less risky Inhibitors,research,lifescience,medical lower reward options, and it is assumed that the choice of risky high rewards represents hypersensitivity to reward, hyposensitivity Inhibitors,research,lifescience,medical to punishment, or just risk

taking behavior (Bechara et al. 2001; Clark and Robbins 2002; Tranel et al. 2002). Thus, whereas probabilistic reversal tasks necessitate flexible adaptation of behavior based on (monetary) contingencies, gambling tasks require the subject Inhibitors,research,lifescience,medical to devise a strategy that in the long run proves successful or focus on the level of risk taking with respect to rewards and losses. Cue-exposure tasks also involve (potentially) rewarding stimuli, but these are of a different nature, because they concern drug-related rather than more general natural rewards. In addition, cue-exposure tasks have a much lower cognitive demand and are, therefore, discussed separately in Section 2 (Attentional bias and craving). Imaging

reward and punishment processing: results Inhibitors,research,lifescience,medical and discussion In a study by de Ruiter et al. (2009), heavy smokers showed higher activation in the right insula, right prefrontal cortex (PFC), and parietal regions bilaterally compared with HCs during monetary gain trials, buy PKA inhibitor indicating higher reward sensitivity, while showing significantly lower ventrolateral PFC activation compared with HCs during monetary loss trials, indicating lower punishment sensitivity in heavy smokers compared with HCs (de Ruiter et al. 2009). no In cocaine abusers, however, lower overall brain activity was observed during reward trials compared with HCs, with significant lower activation in left orbitofrontal cortex (OFC) and left cerebellum (Goldstein et al. 2007a). Moreover, during high reward compared with no reward trials, HCs showed significant increases in activation in left OFC, lateral PFC, and mesencephalon, an effect that was not found in cocaine abusers.