An fMRI study might identify reduced activity in an area. But this need not reflect dysfunction in the integrity of that area. Instead, it may reflect reduced input to this area from another region that is dysfunctional in psychopathy. A different

study, using a task that does not rely on the integrity of the dysfunctional region(s) might show no reduced activity in the area. The IES model follows Patrick’s seminal work stressing the importance of the amygdala.28 The amygdala is critical for stimulus-reinforcement learning; both for aversive and appetitive reinforcements.75,76 Stimulus-reinforcement learning, as indexed by aversive conditioning, is impaired in psychopathy.37 Afatinib in vivo Indeed, Inhibitors,research,lifescience,medical adults with psychopathy show reduced amygdala responses during aversive conditioning (though, it should be noted, it is unclear whether the groups were matched Inhibitors,research,lifescience,medical for IQ in this study).77 The emotional expressions of fear, sadness, and happiness are thought to initiate stimulus-reinforcement learning; they allow the individual to learn the value of the object or action to which they are displayed.51 The amygdala is important for processing these expressions (particularly fear).78 In line with the amygdala dysfunction hypothesis, violent patients with psychopathy show reduced amygdala responses Inhibitors,research,lifescience,medical to fearful expressions.68 According to the IES model,

care-based transgressions come to be regarded as “bad” because of the association of representations of these transgressions with the aversive feedback of the distress of the victims of these transgressions.10 Amygdala dysfunction, and consequent impaired stimulus-reinforcement learning and responsiveness to the distress of others, should result in a deficient response to care-based transgressions. At Inhibitors,research,lifescience,medical the neural Inhibitors,research,lifescience,medical level this should be partly manifested as a reduced

amygdala response to care-based transgressions. The data is consistent with this suggestion.65,66 During instrumental learning tasks, where the individual is attempting to learn an action to gain reward or avoid punishment, the amygdala and/ or striatum feeds reinforcement expectancy information to ventromedial frontal cortex where this information is represented.50 Given the diffusion tensor imaging data showing reduced integrity Suplatast tosilate of the white matter tracts between the amygdala and vmPFC in psychopathy,62-64 it is likely that this feed-forward of reinforcement information occurs less successfully. This suggestion is also consistent with data showing reduced amygdala-vmPFC functional connectivity in adults with psychopathy.64 The representation of expected outcome information (how good or bad the action is) within vmPFC is also thought to be dysfunctional.10 This is consistent with the data from Harenski and colleagues’ moral judgment task.65 However, formal fMRI modeling work that would directly address the issue has only been done in youth with psychopathic traits,53 not adult samples.