Abnormal Frontostriatal Activity During Unexpected Reward Receipt in Depression and Schizophrenia: Relationship to Anhedonia

Abstract

Alterations in reward processes may underlie motivational and anhedonic symptoms in depression and schizophrenia. However it remains unclear whether these alterations are disorder-specific or shared, and whether they clearly relate to symptom generation or not. We studied brain responses to unexpected rewards during a simulated slot-machine game in 24 patients with depression, 21 patients with schizophrenia, and 21 healthy controls using functional magnetic resonance imaging. We investigated relationships between brain activation, task-related motivation, and questionnaire rated anhedonia. There was reduced activation in the orbitofrontal cortex, ventral striatum, inferior temporal gyrus, and occipital cortex in both depression and schizophrenia in comparison with healthy participants during receipt of unexpected reward. In the medial prefrontal cortex both patient groups showed reduced activation, with activation significantly more abnormal in schizophrenia than depression. Anterior cingulate and medial frontal cortical activation predicted task-related motivation, which in turn predicted anhedonia severity in schizophrenia. Our findings provide evidence for overlapping hypofunction in ventral striatal and orbitofrontal regions in depression and schizophrenia during unexpected reward receipt, and for a relationship between unexpected reward processing in the medial prefrontal cortex and the generation of motivational states.

Figure 1

Example of a ‘win trial' in the fMRI simulated slot-machine game.

Figure 2

fMRI results: receipt of unexpected reward. Left hemisphere is shown in the right side of the image. Coordinates are expressed in mm, and in standard space. Panel a: entire sample pooled analysis. The yellow color indicates significant voxels thresholded at p<0.05 family-wise error (FWE) voxelwise corrected for illustrative purposes. Panel b: between groups analysis using ANOVA. Colored clusters indicate those clusters indicating significant group differences (cluster threshold Z>2.0 p<0.05 FWE whole-brain cluster corrected) and the particular color indicates the results of post hoc tests. Green areas are clusters where the control group has greater activation compared with the depression group and compared with the schizophrenia group; blue areas are clusters where controls have greater activation compared with the depression group and compared with the schizophrenia group, and the depression group has greater activation than the schizophrenia group; red areas are clusters where controls have more activation than the schizophrenia group and the depression group has more activation than the schizophrenia group; lilac areas are clusters those where the control group has more activation than the schizophrenia group.

Figure 3

Left panel: yellow color indicates a significant cluster resulting from the linear regression of brain activation during an unexpected win against subjective ratings of task-related motivation (all participants pooled, adjusted by group). Left hemisphere is shown in the right side of the image. Coordinates are expressed in mm, and in standard space. FWE whole-brain corrected, cluster threshold Z>2.0 p<0.05. Centre panel: scatterplot of the extracted contrast parameter estimates during an unexpected win from the cluster depicted in left panel vs subjective task-related motivation (blue square, controls; green triangle, depression; red circle, schizophrenia). Right panel: scatterplot of SHAPS (Snaith Hamilton pleasure scale) score vs the subjective rating of motivation in the schizophrenia group.

Figure 4

The upper panel shows the mean percent signal change for unexpected reward receipt for the left ventral striatal/orbitofrontal cluster where both patient groups had suppressed activation relative to controls. In contrast, the lower panel shows the mean percent signal change for unexpected reward receipt in the left lateral parietal lobe (angular gyrus and supramarginal gyrus) where activation was suppressed in schizophrenia compared with controls but relatively intact in depression. Error bars are 95% confidence intervals. For graphs of results of other clusters please see Supplementary Material.