Frontal-striatum dysfunction during reward processing: Relationships to amotivation in schizophrenia

Abstract

Schizophrenia is characterized by deficits of context processing, thought to be related to dorsolateral prefrontal cortex (DLPFC) impairment. Despite emerging evidence suggesting a crucial role of the DLPFC in integrating reward and goal information, we do not know whether individuals with schizophrenia can represent and integrate reward-related context information to modulate cognitive control. To address this question, 36 individuals with schizophrenia (n = 29) or schizoaffective disorder (n = 7) and 27 healthy controls performed a variant of a response conflict task (Padmala & Pessoa, 2011) during fMRI scanning, in both baseline and reward conditions, with monetary incentives on some reward trials. We used a mixed state-item design that allowed us to examine both sustained and transient reward effects on cognitive control. Different from predictions about impaired DLPFC function in schizophrenia, we found an intact pattern of increased sustained DLPFC activity during reward versus baseline blocks in individuals with schizophrenia at a group level but blunted sustained activations in the putamen. Contrary to our predictions, individuals with schizophrenia showed blunted cue-related activations in several regions of the basal ganglia responding to reward-predicting cues. Importantly, as predicted, individual differences in anhedonia/amotivation symptoms severity were significantly associated with reduced sustained DLPFC activation in the same region that showed overall increased activity as a function of reward. These results suggest that individual differences in motivational impairments in schizophrenia may be related to dysfunction of the DLPFC and striatum in motivationally salient situations.

Figure 1

Task Stimuli and Paradigm Note. During reward blocks, Reward-cue (REW, “$20”) and Reward-Context cue (RCTX, “XX”) were intermixed with equal number of trials across trial-type

Figure 2

Behavioral Data: Median Correct Reaction Times Note. BASE-CUE = Baseline cue trials, HC = healthy controls, REW-CUE= Reward cue, RCTX-CUE = Reward-Context cue, SCZ = Schizophrenia.

Figure 3

Regions Displaying Sustained Reward x Group Interaction Note. Error bars represent ± SEM

Figure 4

Relationship between Sustained DLPFC Activation and Amotivation Note. DLPFC= dorsolateral prefrontal cortex, L = left, R= right, SANS = The Scales for the Assessment of Negative Symptoms (Andreasen, 1983b). ** p < 0.02.

Figure 5

Time Courses for Regions showing Reward Cue Type x Group x Time Point Interactions During Cue Phase Note. R= Right, L= Left

Figure 6

Time courses for the Right DLPFC Region Displaying a Reward x Trial type x Group Interaction During Target Phase Note. BASE-CUE= Baseline cue, RCTX-CUE=Reward-Context cue, REW-CUE = Reward Cue

Figure 7

Relationship between Cue-Related DLPFC Activation and Negative Symptoms Note. BNSS: Brief Negative Symptom Scale, DLPFC = Dorsolateral Prefrontal Cortex.