Pavlovian reward prediction and receipt in schizophrenia: relationship to anhedonia

Abstract

Reward processing abnormalities have been implicated in the pathophysiology of negative symptoms such as anhedonia and avolition in schizophrenia. However, studies examining neural responses to reward anticipation and receipt have largely relied on instrumental tasks, which may confound reward processing abnormalities with deficits in response selection and execution. 25 chronic, medicated outpatients with schizophrenia and 20 healthy controls underwent functional magnetic resonance imaging using a pavlovian reward prediction paradigm with no response requirements. Subjects passively viewed cues that predicted subsequent receipt of monetary reward or non-reward, and blood-oxygen-level-dependent signal was measured at the time of cue presentation and receipt. At the group level, neural responses to both reward anticipation and receipt were largely similar between groups. At the time of cue presentation, striatal anticipatory responses did not differ between patients and controls. Right anterior insula demonstrated greater activation for nonreward than reward cues in controls, and for reward than nonreward cues in patients. At the time of receipt, robust responses to receipt of reward vs. nonreward were seen in striatum, midbrain, and frontal cortex in both groups. Furthermore, both groups demonstrated responses to unexpected versus expected outcomes in cortical areas including bilateral dorsolateral prefrontal cortex. Individual difference analyses in patients revealed an association between physical anhedonia and activity in ventral striatum and ventromedial prefrontal cortex during anticipation of reward, in which greater anhedonia severity was associated with reduced activation to money versus no-money cues. In ventromedial prefrontal cortex, this relationship held among both controls and patients, suggesting a relationship between anticipatory activity and anhedonia irrespective of diagnosis. These findings suggest that in the absence of response requirements, brain responses to reward receipt are largely intact in medicated individuals with chronic schizophrenia, while reward anticipation responses in left ventral striatum are reduced in those patients with greater anhedonia severity.

Conflict of interest statement

Competing Interests: The authors have declared that no competing interests exist.

Figures

Figure 1. Cue-related activation in bilateral caudate ROIs.

Activation shown is mean activation across voxels within regions of interest. Error bars represent standard error.

Figure 2. Regions demonstrating a significant main effect of receipt.

All regions showed greater activation for receipt of money than no money. Both ROI results (threshold of p<.01 and voxels within roi mask whole-brain results of p are displayed. graphs represent mean activation magnitudes across example regions among individuals with schizophrenia controls error bars standard error.>

Figure 3. Regions demonstrating a Cue X Receipt interaction.

All regions showed greater activity for unexpected than for expected outcomes. Both ROI results (threshold of p<.01 and voxels within roi mask whole-brain results of p are displayed. graphs represent mean activation magnitudes across example regions among individuals with schizophrenia controls error bars standard error.>

Figure 4. Regions demonstrating correlations between activation and anhedonia severity.

(A) Results of voxelwise correlation between Chapman physical anhedonia score and the Cue Money – No Money contrast in patients, ROI analysis (threshold of p<.01 and voxels within roi mask results of voxelwise correlation between chapman physical anhedonia the receive money no contrast in patients whole brain analysis p voxels. graphs represent mean activation across region.>