Article

Expected value and prediction error abnormalities in depression and schizophrenia

Centre for Neuroscience, Department of Psychiatry, University of Dundee, Mail Box 5, Level 5, Ninewells Hospital and Medical School, Dundee DD1 9SY, UK.
Brain (Impact Factor: 10.23). 06/2011; 134(Pt 6):1751-64. DOI: 10.1093/brain/awr059
Source: PubMed

ABSTRACT The dopamine system has been linked to anhedonia in depression and both the positive and negative symptoms of schizophrenia, but it remains unclear how dopamine dysfunction could mechanistically relate to observed symptoms. There is considerable evidence that phasic dopamine signals encode prediction error (differences between expected and actual outcomes), with reinforcement learning theories being based on prediction error-mediated learning of associations. It has been hypothesized that abnormal encoding of neural prediction error signals could underlie anhedonia in depression and negative symptoms in schizophrenia by disrupting learning and blunting the salience of rewarding events, and contribute to psychotic symptoms by promoting aberrant perceptions and the formation of delusions. To test this, we used model based functional magnetic resonance imaging and an instrumental reward-learning task to investigate the neural correlates of prediction errors and expected-reward values in patients with depression (n=15), patients with schizophrenia (n=14) and healthy controls (n=17). Both patient groups exhibited abnormalities in neural prediction errors, but the spatial pattern of abnormality differed, with the degree of abnormality correlating with syndrome severity. Specifically, reduced prediction errors in the striatum and midbrain were found in depression, with the extent of signal reduction in the bilateral caudate, nucleus accumbens and midbrain correlating with increased anhedonia severity. In schizophrenia, reduced prediction error signals were observed in the caudate, thalamus, insula and amygdala-hippocampal complex, with a trend for reduced prediction errors in the midbrain, and the degree of blunting in the encoding of prediction errors in the insula, amygdala-hippocampal complex and midbrain correlating with increased severity of psychotic symptoms. Schizophrenia was also associated with disruption in the encoding of expected-reward values in the bilateral amygdala-hippocampal complex and parahippocampal gyrus, with the degree of disruption correlating with psychotic symptom severity. Neural signal abnormalities did not correlate with negative symptom severity in schizophrenia. These findings support the suggestion that a disruption in the encoding of prediction error signals contributes to anhedonia symptoms in depression. In schizophrenia, the findings support the postulate of an abnormality in error-dependent updating of inferences and beliefs driving psychotic symptoms. Phasic dopamine abnormalities in depression and schizophrenia are suggested by our observation of prediction error abnormalities in dopamine-rich brain areas, given the evidence for dopamine encoding prediction errors. The findings are consistent with proposals that psychiatric syndromes reflect different disorders of neural valuation and incentive salience formation, which helps bridge the gap between biological and phenomenological levels of understanding.

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    • "During reward feedback, VS activation reflects prediction error in response to unexpected rewards (Schultz, 2002) while activity in the ventromedial/medial orbitofrontal cortex (mOFC) signals the updating of reward value (Grabenhorst and Rolls, 2011) and hedonic experience (Kringelbach, 2005). Accordingly, a deficit in the processing of reward receipt on both levels has been associated with anhedonia and depression, although the findings are more consistent for the VS than for the mOFC (McCabe et al., 2009; Pizzagalli et al., 2009; Simon et al., 2010a; Gradin et al., 2011). Dysfunctional activation during both anticipation and outcome in striatal and cortical regions has been associated with negative symptoms (Juckel et al., 2006; Simon et al., 2010a; Waltz et al., 2011). "
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    ABSTRACT: There is growing evidence that reward processing is disturbed in schizophrenia. However, it is uncertain whether this dysfunction predates or is secondary to the onset of psychosis. Studying 21 unmedicated persons at risk for psychosis plus 24 healthy controls (HCs) we used a incentive delay paradigm with monetary rewards during functional magnetic resonance imaging. During processing of reward information, at-risk individuals performed similarly well to controls and recruited the same brain areas. However, while anticipating rewards, the high-risk sample exhibited additional activation in the posterior cingulate cortex, and the medio-and superior frontal gyrus, whereas no significant group differences were found after rewards were administered. Importantly, symptom dimensions were differentially associated with anticipation and outcome of the reward. Positive symptoms were correlated with the anticipation signal in the ventral striatum (VS) and the right anterior insula (rAI). Negative symptoms were inversely linked to outcome-related signal within the VS, and depressive symptoms to outcome-related signal within the medial orbitofrontal cortex (mOFC). Our findings provide evidence for a reward-associated dysregulation that can be compensated by recruitment of additional prefrontal areas. We propose that stronger activations within VS and rAI when anticipating a reward reflect abnormal processing of potential future rewards. Moreover, according to the aberrant salience theory of psychosis, this may predispose a person to positive symptoms. Additionally, we report evidence that negative and depressive symptoms are differentially associated with the receipt of a reward, which might demonstrate a broader vulnerability to motivational and affective symptoms in persons at-risk for psychosis.
    Frontiers in Behavioral Neuroscience 11/2014; 8. DOI:10.3389/fnbeh.2014.00382 · 4.16 Impact Factor
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    • "In turn, the reduced striatal response to fairness in the depression group is consistent with studies reporting reduced striatal activation in response to rewarding events in this population (Eshel & Roiser, 2010; Gradin et al. 2011). The current study therefore contributes to this literature reporting that striatal abnormalities in depression extend to social rewards. "
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    ABSTRACT: Background. Depression is a prevalent disorder that significantly affects the social functioning and interpersonal rela-tionships of individuals. This highlights the need for investigation of the neural mechanisms underlying these social diffi-culties. Investigation of social exchanges has traditionally been challenging as such interactions are difficult to quantify. Recently, however, neuroeconomic approaches that combine multiplayer behavioural economic paradigms and neuroi-maging have provided a framework to operationalize and quantify the study of social interactions and the associated neural substrates. Method. We investigated brain activation using functional magnetic resonance imaging (fMRI) in unmedicated de-pressed participants (n = 25) and matched healthy controls (n = 25). During scanning, participants played a behavioural economic paradigm, the Ultimatum Game (UG). In this task, participants accept or reject monetary offers from other players. Results. In comparison to controls, depressed participants reported decreased levels of happiness in response to 'fair' offers. With increasing fairness of offers, controls activated the nucleus accumbens and the dorsal caudate, regions that have been reported to process social information and responses to rewards. By contrast, participants with depression failed to activate these regions with increasing fairness, with the lack of nucleus accumbens activation correlating with increased anhedonia symptoms. Depressed participants also showed a diminished response to increasing unfairness of offers in the medial occipital lobe. Conclusions. Our findings suggest that depressed individuals differ from healthy controls in the neural substrates involved with processing social information. In depression, the nucleus accumbens and dorsal caudate may underlie ab-normalities in processing information linked to the fairness and rewarding aspects of other people's decisions.
    Psychological Medicine 10/2014; 45(06). DOI:10.1017/S0033291714002347 · 5.43 Impact Factor
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    • "ent and function ( Heinrichs , 2005 ; Woodberry et al . , 2008 ) . Taken together , these results suggest that impaired motivational processes , as assessed by the IGT , may represent a common denomina - tor uniting neuropsychological and clinical expressions of schizophre - nia . Prior research ( Corlett , et al . 2009 ; Fletcher & Frith , 2009 ; Gradin et al . , 2011 ) has proposed disease - related abnormalities in dopamine - Table 1 Neuropsychological scores for participants with schizophrenia and healthy controls . Note . Values are means plus or minus standard deviations . SES = socioeconomic status ;"
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    ABSTRACT: We used the Iowa Gambling Test (IGT) to examine the relationship of reward learning to both neuropsychological functioning and symptom formation in 65 individuals with schizophrenia. Results indicated that compared to controls, participants with schizophrenia showed significantly reduced reward learning, which in turn correlated with reduced intelligence, memory and executive function, and negative symptoms. The current findings suggested that a disease-related disturbance in reward learning may underlie both cognitive and motivation deficits, as expressed by neuropsychological impairment and negative symptoms in schizophrenia.
    Schizophrenia Research 09/2014; 159(2-3). DOI:10.1016/j.schres.2014.08.028 · 4.43 Impact Factor
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