The effect of dopamine agonists on adaptive and aberrant salience in Parkinson's disease

Clinical evidence suggests that after initiation of dopaminergic medications some patients with Parkinson's disease (PD) develop psychotic symptoms, such as hallucinations and delusions. Here, we tested the hypothesis that the neurocognitive basis of this phenomenon can be defined as the formation of arbitrary and illusory associations between conditioned stimuli and reward signals, called aberrant salience. Young, never-medicated PD patients and matched controls were assessed on a speeded reaction time task in which the probe stimulus was preceded by conditioned stimuli that could signal monetary reward by color or shape. The patients and controls were re-evaluated after 12 weeks during which the patients received a dopamine agonist (pramipexole or ropinirole). Results indicated that dopamine agonists increased both adaptive and aberrant salience in PD patients, that is, formation of real and illusory associations between conditioned stimuli and reward, respectively. This effect was present when associations were assessed by means of faster responding after conditioned stimuli signaling reward (implicit salience) and overt rating of stimulus-reward links (explicit salience). However, unusual feelings and experiences, which are subclinical manifestations of psychotic-like symptoms, were specifically related to irrelevant and illusory stimulus-reward associations (aberrant salience) in PD patients receiving dopamine agonists. The learning of relevant and real stimulus-reward associations (adaptive salience) was not related to unusual experiences. These results suggest that dopamine agonists may increase psychotic-like experiences in young patients with PD, possibly by facilitating dopaminergic transmission in the ventral striatum, which results in aberrant associations between conditioned stimuli and reward

Aversive conditioning, schizotypy, and affective temperament in the framework of the salience hypothesis

During classic conditioning, the processing of conditioned stimuli (CSs+) is enhanced relative to neutral stimuli (CSs-). In patients with psychotic disorders. CSs- become abnormally relevant relative to CSs+, which may lead to the formation of aberrant associations. In this study, we explored how schizotypal and affective personality traits are associated with salience processing in nonclinical individuals. We used aversive conditioning and personality questionnaires in 100 healthy volunteers. The CSs+ were colored circles predicting the unconditioned stimulus (US), which was a loud noise. Circles of another color were the CSs- predicting no US. Conditioning was measured with skin conductance responses (SCRs) and reaction time. Results revealed that higher reality distortion, introvertive anhedonia, and cyclothymic personality negatively correlated with SCRs and positively correlated with reaction time for CSs+, which indicates less efficient conditioning. After taking into account the covariance between these personality traits, only reality distortion and introvertive anhedonia remained significant for CS+ SCRs, and introvertive anhedonia remained significant for CS+ reaction time. Enhanced responses to CSs- were positively predicted only by reality distortion. These results suggest that salience-processing biases are related to schizotypal personality traits in healthy individuals, exhibiting a similar pattern to that observed in psychotic disorders. (C) 2012 Elsevier Ltd. All rights reserved

Drift diffusion model of reward and punishment learning in schizophrenia: Modeling and experimental data.

In this study, we tested reward- and punishment learning performance using a probabilistic classification learning task in patients with schizophrenia (n=37) and healthy controls (n=48). We also fit subjects' data using a Drift Diffusion Model (DDM) of simple decisions to investigate which components of the decision process differ between patients and controls. Modeling results show between-group differences in multiple components of the decision process. Specifically, patients had slower motor/encoding time, higher response caution (favoring accuracy over speed), and a deficit in classification learning for punishment, but not reward, trials. The results suggest that patients with schizophrenia adopt a compensatory strategy of favoring accuracy over speed to improve performance, yet still show signs of a deficit in learning based on negative feedback. Our data highlights the importance of applying fitting models (particularly drift diffusion models) to behavioral data. The implications of these findings are discussed relative to theories of schizophrenia and cognitive processing

General functioning predicts reward and punishment learning in schizophrenia

Previous studies investigating feedback-driven reinforcement learning in patients with schizophrenia have provided mixed results. In this study, we explored the clinical predictors of reward and punishment learning using a probabilistic classification learning task. Patients with schizophrenia (n=40) performed similarly to healthy controls (n=30) on the classification learning task. However, more severe negative and general symptoms were associated with lower reward-learning performance, whereas poorer general psychosocial functioning was correlated with both lower reward- and punishment-learning performances. Multiple linear regression analyses indicated that general psychosocial functioning was the only significant predictor of reinforcement learning performance when education, antipsychotic dose, and positive, negative and general symptoms were included in the analysis. These results suggest a close relationship between reinforcement learning and general psychosocial functioning in schizophrenia