2009; Pine et al. 2009). The specific role each region contributes to DD is still controversial. McClure et al. (2004), for example, have argued that immediate or more impulsive and emotional choices are driven by the limbic system, whereas activation in lateral prefrontal, lateral orbitofrontal, and inferior parietal cortex occurs during all trials requiring a decision, and especially more difficult decisions. The between-group Inhibitors,research,lifescience,medical analysis of all DD task trials versus SMC trials revealed that, in the face of matched performance,

SZ had significantly less activation than HC in putative executive function areas, inferior frontal, dACC, and posterior parietal cortices; as well as in reward regions such as the OSI906 ventral striatum and midbrain. Inhibitors,research,lifescience,medical The results of a recent meta-analysis (Minzenberg et al. 2009) have shown that, in general, executive tasks engage a distributed neural network, prominently including frontal (lateral and medial prefrontal cortex) and posterior parietal cortices and thalamus. The authors of this meta-analysis further report that SZ fail to engage this network to the same extent as HC and speculate

that the findings are consistent with a disruption of a frontal-based cognitive control function. Our data concur with these results and extend Inhibitors,research,lifescience,medical them by additionally showing reduced engagement of regions of the reward system during decision making. SZ appear to lack an integrated neural response when making decisions. Abnormal modulations of Inhibitors,research,lifescience,medical ventral striatum/midbrain regions in SZ have been reported in association with various tasks taping into reward processes such as prediction error (Waltz et al. 2009; Koch et al. 2010), incentive monetary delay (Juckel et al. 2006a,b; Schlagenhauf et al. 2008), and aversive Pavlovian learning (Jensen et al. 2008). However, most of these studies have limited their analyses to regions of the ventral striatum or midbrain, leaving questions of integration with other networks unanswered. Further work will

need to evaluate the specific contribution of cognitive control and reward networks to abnormalities such as those Inhibitors,research,lifescience,medical seen in this study. On the other hand, patients showed greater activation in a limited number of regions such as the precuneus, posterior cingulate Thalidomide gyrus, and insula extending into the frontal operculum and superior temporal gyrus. Perhaps these latter regions of activation served a compensatory role during performance of the DD task, allowing patients to perform similarly to controls in spite of showing blunted activation of putative executive function areas and reward areas. Greater activation in response to other (non-DD) tasks has also been reported in SZ when patient groups were matched on performance and interpreted as compensatory (Callicott et al. 2003; Avsar et al. 2011; Ettinger et al. 2011). On the other hand, the activated regions, the precuneus and posterior cingulate, are regions that are part of the so-called DMN (Gusnard et al. 2001; Raichle et al. 2001; Greicius et al.