The role of reward processing in the pathophysiology of schizophrenia has garnered significant attention in recent years. Aberrant reward processing has been implicated in both positive 
and negative 
symptomatology, and advances in neuroimaging techniques have allowed new insights into the mechanisms of reward processing that may be disrupted in this illness. One such process is reward prediction, or the ability to anticipate a reward when presented with a predictive cue. Reward prediction is strongly associated with dopaminergic activity in the midbrain and striatum 
, which is thought to be dysregulated in schizophrenia 
. If disruptions in reward signaling prevent predictive stimuli from taking on the appropriate significance, they could contribute to important negative symptoms of schizophrenia such as decreased motivation and anhedonia (a reduced ability to experience pleasure) 
. Here, we examine this possibility using a Pavlovian reward prediction task to examine functional activity during reward anticipation and receipt in schizophrenia and its relationship to symptoms of anhedonia and amotivation.
A number of previous neuroimaging studies have examined reward prediction in schizophrenia. Studies using monetary incentive delay paradigms have shown reduced ventral striatal responses to reward-predictive cues in patients who are unmedicated 
, or taking typical, but not atypical, antipsychotics 
. Notably, this reduction in anticipatory activation was associated with negative symptom severity. Several studies in patients taking atypical antipsychotics have shown intact striatal anticipatory activation 
, though some of these studies also demonstrated negative correlations between ventral striatal activation and negative symptoms 
Work examining brain responses to reward receipt has also revealed alterations in schizophrenia. Some studies have shown blunted striatal reward responses or prediction errors (responses to outcomes that do not match expectation) 
, while others have shown intact responses 
. Notably, several of these studies also found inverse relationships between striatal responses to reward receipt and negative or depressive symptoms 
. In addition, abnormal outcome or prediction error responses have been reported in cortical regions including insula 
and medial 
, ventrolateral 
, and dorsolateral 
prefrontal cortex. In several of these studies, attenuated cortical prediction errors or outcome responses were associated with increased severity of either positive 
or negative 
Importantly, the literature examining reward processing in schizophrenia has largely relied on instrumental learning tasks, in which rewards must be earned via correct and/or rapid response execution. In these tasks, the ability to anticipate a reward depends upon the ability to earn the reward by responding appropriately. This requires not only reward prediction, but also action selection and response execution, any of which may be impaired in schizophrenia. Here, we examined reward prediction in schizophrenia in the absence of requirements for response selection and execution. Using a passive Pavlovian paradigm, we examined functional activation in response to rewarding stimuli and to predictive cues that had been associated with rewards based on pre-scan instructions.
Previous work using aversive Pavlovian conditioning has revealed abnormal brain responses among individuals with schizophrenia. Using a task in which colored cues were associated with affectively negative or neutral pictures, Romaniuk et al 
demonstrated reduced responses to aversive cues in bilateral amygdala, as well as decreased prediction error responses in the midbrain. Further, inappropriate midbrain activation to neutral stimuli correlated with delusional symptom severity. Similarly, work by Jensen et al 
using aversive noise stimuli revealed increased right ventral striatum activation to neutral cues in patients. These studies suggest that even in the absence of response requirements, brain responses to neutral cues in an aversive context may be augmented among individuals with schizophrenia. In addition, two studies have examined functional activity using Pavlovian paradigms with appetitive rewards in schizophrenia 
. Waltz et al used a timing-sensitive paradigm to examine anticipation and receipt of primary reward (juice), and found reduced positive (but not negative) prediction errors and reward responses in schizophrenia in widespread regions throughout the brain. However, integrating these results with others in the literature is challenging because the timing-sensitive paradigm and primary reward differ greatly from the tasks typically used in instrumental studies. Morris et al used a Pavlovian prediction error task to examine responses to expected and unexpected rewards and omissions. In this study, ventral striatal responses in patients were intact for reward receipt vs. omission, but failed to differentiate between expected and unexpected rewards. However, this study did not examine brain activity at the time of cue presentation. Here, we used a Pavlovian monetary reward prediction task to examine whether functional activation during reward anticipation and receipt is altered in schizophrenia even in the absence of response requirements, and whether it relates to symptoms of anhedonia and amotivation.