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: 9.2). 06/2011; 134(Pt 6):1751-64. DOI: 10.1093/brain/awr059
Source: PubMed


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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    • "Reward (or positive) vs. neutral codition MNI Gradin et al. 2011 MDD, SZ, CON, MDD vs. "
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    ABSTRACT: Anhedonia is a prominent symptom in neuropsychiatric disorders, most markedly in major depressive disorder (MDD) and schizophrenia (SZ). Emerging evidence indicates an overlap in the neural substrates of anhedonia between MDD and SZ, which supported a transdiagnostic approach. Therefore, we used activation likelihood estimation (ALE) meta-analysis of functional magnetic resonance imaging studies in MDD and SZ to examine the neural bases of three subdomains of anhedonia: consummatory anhedonia, anticipatory anhedonia and emotional processing. ALE analysis focused specifically on MDD or SZ was used later to dissociate specific anhedonia-related neurobiological impairments from potential disease general impairments. ALE results revealed that consummatory anhedonia was associated with decreased activation in ventral basal ganglia areas, while anticipatory anhedonia was associated with more substrates in frontal-striatal networks except the ventral striatum, which included the dorsal anterior cingulate, middle frontal gyrus and medial frontal gyrus. MDD and SZ patients showed similar neurobiological impairments in anticipatory and consummatory anhedonia, but differences in the emotional experience task, which may also involve affective/mood general processing. These results support that anhedonia is characterized by alterations in reward processing and relies on frontal-striatal brain circuitry. The transdiagnostic approach is a promising way to reveal the overall neurobiological framework that contributes to anhedonia and could help to improve targeted treatment strategies.
    Brain Imaging and Behavior 10/2015; DOI:10.1007/s11682-015-9457-6 · 4.60 Impact Factor
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    • "When very high value is attributed to a belief or action, prediction errors of minimal size would not be expected to readjust the value of the belief or action to any meaningful extent (Gradin et al., 2011; Moran, Owen, Crookes, Al-Uzri, & Reveley, 2008). In addition, even when PEs are consciously registered, motivated reasoning that negates the PE as an anomaly further serves to protect the high value of formerly reliable, tried and tested, interpretations, attributions, beliefs, and actions (Kunda, 1990; Westen, Blagov, Harenski, Kilts, & Hamann, 2006). "
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    ABSTRACT: Functional magnetic resonance imaging (fMRI) was used to explore the neural and cognitive basis of literary awareness in 24 participants. The 2 Â 2 design explored the capacity to process and derive meanings in complex poetic and prosaic texts that either did or did not require significant reappraisal during reading. Following this, participants rated each piece on its 'poeticness' and the extent to which it prompted a reappraisal of meaning during reading, providing subjective measures of poetic recognition and the need to reappraise meaning. The substantial shared variance between these 2 subjective measures provided a proxy measure of literary awareness, which was found to modulate activity in regions comprising the central executive and saliency networks. We suggest that enhanced literary awareness is related to increased flexibility of internal models of meaning, enhanced interoceptive awareness of change, and an enhanced capacity to reason about events. In addition, we found that the residual variance in the measure of poetic recognition modulated right dorsal caudate activity, which may be related to tolerance of uncertainty. These findings are consistent with evidence that relates reading to improved mental wellbeing.
    Cortex 09/2015; 73. DOI:10.1016/j.cortex.2015.08.014 · 5.13 Impact Factor
    • "Pavlovian conditioning Holt et al. (2012) Romaniuk et al. (2010) Jensen et al. (2008) Dowd & Barch (2012) Dowd & Barch (2012) Holt et al. (2012) Romaniuk et al. (2010) Instrumental conditioning Gradin et al. (2011) Koch et al. (2010) Gradin et al. (2011) Pavlovian-instrumental transfer Morris et al. (2015) Morris et al. (2015) Delay discounting Avsar et al. (2013) Avsar et al. (2013) a Study in unmedicated psychosis patients b Comparison of patients medicated with first-and second-generation antipsychotics Abbreviations: diff. difference, PFC prefrontal cortex, HC hippocampus, VS ventral striatum, MB midbrain, Neg. "
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    ABSTRACT: Motivational deficits (avolition and anhedonia ) have historically been considered important negative symptoms of schizophrenia (SZ). Numerous studies have attempted to identify the neural substrates of avolition and anhedonia in schizophrenia , but these studies have not produced much agreement. Deficits in various aspects of reinforcement processing have been observed in individuals with schizophrenia, but it is not exactly clear which of these deficits actually engender motivational impairments in SZ. The purpose of this chapter is to examine how various reinforcement-related behavioral and neural signals could contribute to motivational impairments in both schizophrenia and psychiatric illness, in general. In particular, we describe different aspects of the concept of expected value (EV) , such as the distinction between the EV of stimuli and the expected value of actions, the acquisition of value versus the estimation of value, and the discounting of value as a consequence of time or effort required. We conclude that avolition and anhedonia in SZ are most commonly tied to aberrant signals for expected value, in the context of learning. We discuss implications for further research on the neural substrates of motivational impairments in psychiatric illness.
    Current Topics in Behavioral Neurosciences 09/2015; DOI:10.1007/7854_2015_385
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