Dataset Information

Motivational Deficits in Schizophrenia Are Associated With Reduced Differentiation Between Gain and Loss-Avoidance Feedback in the Striatum.

ABSTRACT: BACKGROUND:The current study was designed to test the hypothesis that motivational deficits in schizophrenia (SZ) are tied to a reduced ability to differentially signal gains and instances of loss-avoidance in the brain, leading to reduced ability to form adaptive representations of expected value. METHODS:We administered a reinforcement learning paradigm to 27 medicated SZ patients and 27 control subjects in which participants learned three probabilistic discriminations. In regions of interest in reward networks identified a priori, we examined contrasts between trial types with different expected values (e.g., expected gain-nonmonetary) and between outcomes with the same prediction error valence but different experienced values (e.g., gain-loss-avoidance outcome, miss-loss outcome). RESULTS:Both whole-brain and region of interest analyses revealed that SZ patients showed reduced differentiation between gain and loss-avoidance outcomes in the dorsal anterior cingulate cortex and bilateral anterior insula. That is, SZ patients showed reduced contrasts between positive prediction errors of different objective values in these areas. In addition, we observed significant correlations between gain-loss-avoidance outcome contrasts in the ventral striatum and ratings for avolition/anhedonia and between expected gain-nonmonetary contrasts in the ventral striatum and ventromedial prefrontal cortex. CONCLUSIONS:These results provide further evidence for intact prediction error signaling in medicated SZ patients, especially with regard to loss-avoidance. By contrast, components of frontostriatal circuits appear to show reduced sensitivity to the absolute valence of expected and experienced outcomes, suggesting a mechanism by which motivational deficits may emerge.

SUBMITTER: Waltz JA

PROVIDER: S-EPMC5833021 | biostudies-literature | 2018 Mar

REPOSITORIES: biostudies-literature

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Motivational Deficits in Schizophrenia Are Associated With Reduced Differentiation Between Gain and Loss-Avoidance Feedback in the Striatum.

Waltz James A JA Xu Ziye Z Brown Elliot C EC Ruiz Rebecca R RR Frank Michael J MJ Gold James M JM

Biological psychiatry. Cognitive neuroscience and neuroimaging 20170812 3

<h4>Background</h4>The current study was designed to test the hypothesis that motivational deficits in schizophrenia (SZ) are tied to a reduced ability to differentially signal gains and instances of loss-avoidance in the brain, leading to reduced ability to form adaptive representations of expected value.<h4>Methods</h4>We administered a reinforcement learning paradigm to 27 medicated SZ patients and 27 control subjects in which participants learned three probabilistic discriminations. In regio ...[more]

PMID: 29486865

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Project description:BackgroundMotivational deficits are a central feature of the negative syndrome in schizophrenia. They have consistently been associated with reduced willingness to expend physical effort in return for monetary rewards on effort based decision making (EBDM) paradigms. Nevertheless, the mechanisms underlying such altered performance are not well characterised, and it remains unclear if they are driven purely by negative symptoms, or also in part by cognitive impairment, antipsychotic treatment or even positive symptoms. Here we investigated the impact of all these factors using a paradigm that has not previously been used to measure EBDM in schizophrenia.MethodsForty treatment resistant schizophrenia (TRS) patients on clozapine and matched controls (N = 80) completed a well validated EBDM task which offers monetary rewards in return for physical effort. Choice and reaction time data was analysed using logistic regressions, as well as Bayesian hierarchical drift diffusion modelling (HDDM). Behavioural parameters were compared between groups and their association with negative symptoms, cognitive function and serum clozapine levels were assessed.ResultsOverall, TRS patients accepted significantly less offers than controls during effort-based decision making, suggesting they were less motivated. They demonstrated reduced sensitivity to increasing rewards, but surprisingly were also less averse to increasing effort. Despite a positive correlation between negative symptoms and cognitive function in TRS, reward sensitivity was associated only with cognitive performance. In contrast, reduced effort aversion correlated with negative symptom severity. Clozapine levels and positive symptoms were not associated with either behavioural parameter.ConclusionMotivational deficits in TRS are characterised by both diminished reward sensitivity and reduced effort aversion during EBDM. Cognitive dysfunction and negative symptom severity account for distinct aspects of these behavioural changes, despite positive associations between themselves. Overall, these findings demonstrate that negative symptoms and cognitive impairment have significant independent contributions to EBDM in TRS, thereby opening the possibility of individualised treatment targeting these mechanisms to improve motivation.

Dataset Information

Motivational Deficits in Schizophrenia Are Associated With Reduced Differentiation Between Gain and Loss-Avoidance Feedback in the Striatum.

Publications

Motivational Deficits in Schizophrenia Are Associated With Reduced Differentiation Between Gain and Loss-Avoidance Feedback in the Striatum.

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