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      Dopamine enhances willingness to exert effort for reward in Parkinson's disease

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          Abstract

          Parkinson's disease (PD) is traditionally conceptualised as a disorder of movement, but recent data suggest that motivational deficits may be more pervasive than previously thought. Here, we ask whether subclinical deficits in incentivised decision-making are present in PD and, if so, whether dopaminergic therapy ameliorates such deficits. We devised a novel paradigm in which participants decided whether they were willing to squeeze a hand-held dynamometer at varying levels of force for different magnitudes of reward. For each participant, we estimated the effort level at which the probability of accepting a reward was 50% – the effort ‘indifference point’. Patients with PD ( N = 26) were tested ON and OFF their usual dopaminergic medication, and their performance compared to those of age-matched controls ( N = 26). No participant was clinically apathetic as defined by the Lille Apathy Rating Scale (LARS). Our data show that, regardless of medication status, patients with PD chose to engage less effort than controls for the lowest reward. Overall, however, dopamine had a motivating effect on participants' choice behaviour – patients with PD chose to invest more effort for a given reward when they were in the ON relative to OFF dopamine state. Importantly, this effect could not be attributed to motor facilitation. We conclude that deficits in incentivised decision-making are present in PD even in the absence of a clinical syndrome of apathy when rewards are low, but that dopamine acts to eliminate motivational deficits by promoting the allocation of effort.

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          Most cited references23

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          Dynamic dopamine modulation in the basal ganglia: a neurocomputational account of cognitive deficits in medicated and nonmedicated Parkinsonism.

          Dopamine (DA) depletion in the basal ganglia (BG) of Parkinson's patients gives rise to both frontal-like and implicit learning impairments. Dopaminergic medication alleviates some cognitive deficits but impairs those that depend on intact areas of the BG, apparently due to DA ''overdose.'' These findings are difficult to accommodate with verbal theories of BG/DA function, owing to complexity of system dynamics: DA dynamically modulates function in the BG, which is itself a modulatory system. This article presents a neural network model that instantiates key biological properties and provides insight into the underlying role of DA in the BG during learning and execution of cognitive tasks. Specifically, the BG modulates the execution of ''actions'' (e.g., motor different parts of the frontal cortex. Phasic changes in DA, which occur during error feedback, dynamically modulate the BG threshold for facilitating/suppressing a cortical command in response to particular stimuli. Reduced dynamic range of DA explains Parkinson and DA overdose deficits with a single underlying dysfunction, despite overall differences in raw DA levels. Simulated Parkinsonism and medication effects provide a theoretical basis for behavioral data in probabilistic classification and reversal tasks. The model also provides novel testable predictions for neuropsychological and pharmacological studies, and motivates further investigation of BG/DA interactions with the prefrontal cortex in working memory.
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            Psychometric properties of the Depression Anxiety Stress Scales (DASS) in clinical samples.

            The psychometric properties of the Depression Anxiety Stress Scales (DASS) were evaluated in two studies using large clinical samples (N = 437 and N = 241). In Study 1, the three scales comprising the DASS were shown to have excellent internal consistency and temporal stability. An exploratory factor analysis (principal components extraction with varimax rotation) yielded a solution that was highly consistent with the factor structure previously found in nonclinical samples. Between-groups comparisons indicated that the DASS distinguished various anxiety and mood disorder groups in the predicted direction. In Study 2, the conceptual and empirical latent structure of the DASS was upheld by findings from confirmatory factor analysis. Correlations between the DASS and other questionnaire and clinical rating measures of anxiety, depression, and negative affect demonstrated the convergent and discriminant validity of the scales. In addition to supporting the psychometric properties of the DASS in clinical anxiety and mood disorders samples, the results are discussed in the context of current conceptualizations of the distinctive and overlapping features of anxiety and depression.
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              Reward-learning and the novelty-seeking personality: a between- and within-subjects study of the effects of dopamine agonists on young Parkinson's patients.

              Parkinson's disease is characterized by the degeneration of dopaminergic pathways projecting to the striatum. These pathways are implicated in reward prediction. In this study, we investigated reward and punishment processing in young, never-medicated Parkinson's disease patients, recently medicated patients receiving the dopamine receptor agonists pramipexole and ropinirole and healthy controls. The never-medicated patients were also re-evaluated after 12 weeks of treatment with dopamine agonists. Reward and punishment processing was assessed by a feedback-based probabilistic classification task. Personality characteristics were measured by the temperament and character inventory. Results revealed that never-medicated patients with Parkinson's disease showed selective deficits on reward processing and novelty seeking, which were remediated by dopamine agonists. These medications disrupted punishment processing. In addition, dopamine agonists increased the correlation between reward processing and novelty seeking, whereas these drugs decreased the correlation between punishment processing and harm avoidance. Our finding that dopamine agonist administration in young patients with Parkinson's disease resulted in increased novelty seeking, enhanced reward processing, and decreased punishment processing may shed light on the cognitive and personality bases of the impulse control disorders, which arise as side-effects of dopamine agonist therapy in some Parkinson's disease patients.
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                Author and article information

                Contributors
                Journal
                Cortex
                Cortex
                Cortex; a Journal Devoted to the Study of the Nervous System and Behavior
                Masson
                0010-9452
                1973-8102
                1 August 2015
                August 2015
                : 69
                : 40-46
                Affiliations
                [a ]Department of Experimental Psychology, University of Oxford, Oxford, UK
                [b ]Nuffield Department of Clinical Neurosciences, John Radcliffe Hospital, Oxford, UK
                Author notes
                [] Corresponding author. Nuffield Department of Clinical Neurosciences, John Radcliffe Hospital, Oxford OX3 9DU, United Kingdom. trevor.chong@ 123456ndcn.ox.ac.uk
                Article
                S0010-9452(15)00127-6
                10.1016/j.cortex.2015.04.003
                4533227
                25967086
                adecb887-ca35-4e01-97eb-705724910ef2
                © 2015 The Authors

                This is an open access article under the CC BY license (http://creativecommons.org/licenses/by/4.0/).

                History
                : 8 December 2014
                : 6 March 2015
                : 9 April 2015
                Categories
                Note

                Neurology
                dopamine,effort,reward,decision-making,parkinson's disease,pd, parkinson's disease,moca, montreal cognitive assessment,lars, lille apathy rating scale,dass, depression anxiety stress scale,updrs, unified parkinson's disease rating scale,le, levodopa equivalence,mvc, maximal voluntary contraction,anova, analysis of variance

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