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Previous research in patients with psychotic disorder has shown widespread abnormalities in brain activation during reward anticipation. Research at the level of subclinical psychotic experiences in individuals unexposed to antipsychotic medication is limited with inconclusive results. Therefore, brain activation during reward anticipation was examined in a larger sample of individuals with subclinical psychotic experiences (PE). Participants in the PE-group were included based on CAPE scores. A sample of emerging adults aged 16-26 years (n = 47) with PE and healthy controls (HC) (n = 40) underwent fMRI scanning. The Monetary Incentive Delay task was conducted with cues related to win, loss or neutral conditions. fMRI nonparametric tests were used to examine the reward versus neutral cue contrast. A significant main effect of the large win (€3.00) > neutral contrast was found in both groups showing activation in many brain areas, including classic reward regions. Whole brain analysis on the group comparison regarding the large win > neutral contrast showed significantly decreased activation in the right insula, putamen and supramarginal gyrus in the PE-group compared to controls. There was no group difference in the hypothesized reward-related region. Decreased activation in the right insula, putamen and supramarginal gyrus during reward anticipation in individuals with PE may be consistent with altered processing of sensory information, related to decreased emotional valuing and motivational tendencies and/or altered motor-cognitive processes. The absence of group differences in striatal activation suggests that activation here is intact in the earliest stages of psychosis and may exhibit progressive deterioration in as the disease develops., (Copyright © 2019. Published by Elsevier B.V.)

Rationale: Patients with obsessive-compulsive disorder (OCD) have been found to show exaggerated error responses and prediction error learning signals in a variety of EEG and fMRI tasks, with data converging on the anterior cingulate cortex as a key locus of dysfunction. Considerable evidence has linked prediction error processing to dopaminergic function., Objective: In this study, we investigate potential dopaminergic dysfunction during reward processing in the context of OCD., Methods: We studied OCD patients (n = 18) and controls (n = 18) whilst they learned probabilistic associations between abstract stimuli and monetary rewards in the fMRI scanner involving administration (on separate visits) of a dopamine receptor agonist, pramipexole 0.5 mg; a dopamine receptor antagonist, amisulpride 400 mg; and placebo. We fitted a Q-learning computational model to fMRI prediction error responses; group differences were examined in anterior cingulate and nucleus accumbens regions of interest., Results: There were no significant group, drug, or interaction effects in the number of correct choices; computational modeling suggested a marginally significant difference in learning rates between groups (p = 0.089, partial ƞ 2  = 0.1). In the imaging results, there was a significant interaction of group by drug (p = 0.013, partial ƞ 2  = 0.13). OCD patients showed abnormally strong cingulate signaling of prediction errors during omission of an expected reward, with unexpected reduction by both pramipexole and amisulpride (p = 0.014, partial ƞ 2  = 0.26, 1-β error probability = 0.94). Exaggerated cingulate prediction error signaling to omitted reward in placebo was related to trait subjective difficulty in self-regulating behavior in OCD., Conclusions: Our data support cingulate dysfunction during reward processing in OCD, and bidirectional remediation by dopaminergic modulation, suggesting that exaggerated cingulate error signals in OCD may be of dopaminergic origin. The results help to illuminate the mechanisms through which dopamine receptor antagonists achieve therapeutic benefit in OCD. Further research is needed to disentangle the different functions of dopamine receptor agonists and antagonists during bidirectional modulation of cingulate activation.

Abnormal salience processing has been suggested to contribute to the formation of positive psychotic symptoms in schizophrenia and related conditions. Previous research utilising reward learning or anticipation paradigms has demonstrated cortical and subcortical abnormalities in people with psychosis, specifically in the prefrontal cortex, the dopaminergic midbrain and the striatum. In these paradigms, reward prediction errors attribute motivational salience to stimuli. However, little is known about possible abnormalities across different forms of salience processing in psychosis patients, and whether any such abnormalities involve the dopaminergic midbrain. The aim of our study was, therefore, to investigate possible alterations in psychosis in neural activity in response to various forms of salience: novelty, negative emotion, targetness (task-driven salience) and rareness/deviance. We studied 14 antipsychotic naïve participants with first episode psychosis, and 37 healthy volunteers. During fMRI scanning, participants performed a visual oddball task containing these four forms of salience. Psychosis patients showed abnormally reduced signalling in the substantia nigra/ventral tegmental area (SN/VTA) for novelty, negative emotional salience and targetness; reduced striatal and occipital (lingual gyrus) signalling to novelty and negative emotional salience, reduced signalling in the amygdala, anterior cingulate cortex and parahippocamal gyrus to negative emotional salience, and reduced cerebellar signalling to novelty and negative emotional salience. Our results indicate alterations of several forms of salience processing in patients with psychosis in the midbrain SN/VTA, with additional subcortical and cortical regions also showing alterations in salience signalling, the exact pattern of alterations depending on the form of salience in question.

Ongoing research suggests preliminary, though not entirely consistent, evidence of neural abnormalities in signalling prediction errors in schizophrenia. Supporting theories suggest mechanistic links between the disruption of these processes and the generation of psychotic symptoms. However, it is unknown at what stage in the pathogenesis of psychosis these impairments in prediction-error signalling develop. One major confound in prior studies is the use of medicated patients with strongly varying disease durations. Our study aims to investigate the involvement of the meso-cortico-striatal circuitry during reward prediction-error signalling in earliest stages of psychosis. We studied patients with first-episode psychosis (FEP) and help-seeking individuals at-risk for psychosis due to sub-threshold prodromal psychotic symptoms. Patients with either FEP (n = 14), or at-risk for developing psychosis (n = 30), and healthy volunteers (n = 39) performed a reinforcement learning task during fMRI scanning. ANOVA revealed significant (p < 0.05 family-wise error corrected) prediction-error signalling differences between groups in the dopaminergic midbrain and right middle frontal gyrus (dorsolateral prefrontal cortex, DLPFC). FEP patients showed disrupted reward prediction-error signalling compared to controls in both regions. At-risk patients showed intermediate activation in the midbrain that significantly differed from controls and from FEP patients, but DLPFC activation that did not differ from controls. Our study confirms that FEP patients have abnormal meso-cortical signalling of reward-prediction errors, whereas reward-prediction-error dysfunction in the at-risk patients appears to show a more nuanced pattern of activation with a degree of midbrain impairment but preserved cortical function.

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.

Purpose of Review: There has been a resurgence of interest in the field of reward processing in schizophrenia in recent years, aided by insights from functional neuroimaging. We examine how disturbances in reward-related processes relate to the pathophysiology and symptomatology of this disorder., Recent Findings: Behavioural and functional neuroimaging studies in psychosis demonstrate impairments in the representation of reward value and in reward-related learning and a failure to motivate behaviour for incentives. These impairments are linked to abnormal mesocorticolimbic and mesostriatal function., Summary: Abnormalities in reward processing offer insights into the symptomatology of schizophrenia and its underlying neurobiology. Further investigation is required into the specificity of these deficits to particular symptom expression and to what extent they are improved by antipsychotic treatment.

While dopamine systems have been implicated in the pathophysiology of schizophrenia and psychosis for many years, how dopamine dysfunction generates psychotic symptoms remains unknown. Recent theoretical interest has been directed at relating the known role of midbrain dopamine neurons in reinforcement learning, motivational salience and prediction error to explain the abnormal mental experience of psychosis. However, this theoretical model has yet to be explored empirically. To examine a link between psychotic experience, reward learning and dysfunction of the dopaminergic midbrain and associated target regions, we asked a group of first episode psychosis patients suffering from active positive symptoms and a group of healthy control participants to perform an instrumental reward conditioning experiment. We characterized neural responses using functional magnetic resonance imaging. We observed that patients with psychosis exhibit abnormal physiological responses associated with reward prediction error in the dopaminergic midbrain, striatum and limbic system, and we demonstrated subtle abnormalities in the ability of psychosis patients to discriminate between motivationally salient and neutral stimuli. This study provides the first evidence linking abnormal mesolimbic activity, reward learning and psychosis.