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      A Conditioned Response as a Measure of Impulsive-Compulsive Behaviours in Parkinson's Disease

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          Abstract

          Objectives

          Parkinson's Disease patients wore a device on the wrist that gave reminders to take levodopa and also measured bradykinesia and dyskinesia. Consumption of medications was acknowledged by placing the thumb on the device. Some patients performed this acknowledgement repeatedly and unconsciously. This study examines whether this behaviour reflected increased impulsivity.

          Methods and Results

          Twenty five participants were selected because they had i) excess acknowledgements described above or ii) Impulsive-Compulsive Behaviours or iii) neither of these. A blinded assessor applied clinical scales to measure Impulsive-Compulsive Behaviours, cognition, depression, anxiety and apathy. A Response Ratio, representing the number of acknowledgements/number of doses (expressed as a percentage) was tightly correlated with ratings of Impulsive-Compulsive Behaviours (r 2 = 0.79) in 19/25 subjects. Some of these patients had dyskinesia, which was higher with extraneous responses than with response indicating medication consumption. Six of the 25 subjects had high Impulsive-Compulsive Behaviour Scores, higher apathy scores, low levels of dyskinesia and normal Response Ratios. Patients without ICB (low RR) also had low dyskinesia levels regardless of the relevance of the response.

          Conclusion

          An elevated Response Ratio is a specific measure of a type of ICB where increased incentive salience is attributed to cues by the presence of high striatal dopamine levels, manifested by high levels of dyskinesia. This study also points to a second form of ICBs which occur in the absence of dyskinesia, has normal Response Ratios and higher apathy scores, and may represent prefrontal pathology.

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          Most cited references31

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          The debate over dopamine's role in reward: the case for incentive salience.

          Debate continues over the precise causal contribution made by mesolimbic dopamine systems to reward. There are three competing explanatory categories: 'liking', learning, and 'wanting'. Does dopamine mostly mediate the hedonic impact of reward ('liking')? Does it instead mediate learned predictions of future reward, prediction error teaching signals and stamp in associative links (learning)? Or does dopamine motivate the pursuit of rewards by attributing incentive salience to reward-related stimuli ('wanting')? Each hypothesis is evaluated here, and it is suggested that the incentive salience or 'wanting' hypothesis of dopamine function may be consistent with more evidence than either learning or 'liking'. In brief, recent evidence indicates that dopamine is neither necessary nor sufficient to mediate changes in hedonic 'liking' for sensory pleasures. Other recent evidence indicates that dopamine is not needed for new learning, and not sufficient to directly mediate learning by causing teaching or prediction signals. By contrast, growing evidence indicates that dopamine does contribute causally to incentive salience. Dopamine appears necessary for normal 'wanting', and dopamine activation can be sufficient to enhance cue-triggered incentive salience. Drugs of abuse that promote dopamine signals short circuit and sensitize dynamic mesolimbic mechanisms that evolved to attribute incentive salience to rewards. Such drugs interact with incentive salience integrations of Pavlovian associative information with physiological state signals. That interaction sets the stage to cause compulsive 'wanting' in addiction, but also provides opportunities for experiments to disentangle 'wanting', 'liking', and learning hypotheses. Results from studies that exploited those opportunities are described here. In short, dopamine's contribution appears to be chiefly to cause 'wanting' for hedonic rewards, more than 'liking' or learning for those rewards.
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            Behavioral theories and the neurophysiology of reward.

            The functions of rewards are based primarily on their effects on behavior and are less directly governed by the physics and chemistry of input events as in sensory systems. Therefore, the investigation of neural mechanisms underlying reward functions requires behavioral theories that can conceptualize the different effects of rewards on behavior. The scientific investigation of behavioral processes by animal learning theory and economic utility theory has produced a theoretical framework that can help to elucidate the neural correlates for reward functions in learning, goal-directed approach behavior, and decision making under uncertainty. Individual neurons can be studied in the reward systems of the brain, including dopamine neurons, orbitofrontal cortex, and striatum. The neural activity can be related to basic theoretical terms of reward and uncertainty, such as contiguity, contingency, prediction error, magnitude, probability, expected value, and variance.
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              A cognitive model of drug urges and drug-use behavior: role of automatic and nonautomatic processes.

              Contemporary urge models assume that urges are necessary but not sufficient for the production of drug use in ongoing addicts, are responsible for the initiation of relapse in abstinent addicts, and can be indexed across 3 classes of behavior: verbal report, overt behavior, and somatovisceral response. A review of available data does not provide strong support for these assumptions. An alternative cognitive model of drug use and drug urges is proposed that hypothesizes that drug use in the addict is controlled by automatized action schemata. Urges are conceptualized as responses supported by nonautomatic cognitive processes activated in parallel with drug-use action schemata either in support of the schema or in support of attempts to block the execution of the schema. The implications of this model for the assessment of urge responding and drug-use behavior are presented.
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                Author and article information

                Contributors
                Role: Editor
                Journal
                PLoS One
                PLoS ONE
                plos
                plosone
                PLoS ONE
                Public Library of Science (San Francisco, USA )
                1932-6203
                2014
                24 February 2014
                : 9
                : 2
                : e89319
                Affiliations
                [1 ]Florey Neuroscience Institute, University of Melbourne, Parkville Victoria, Australia
                [2 ]St Vincent's Hospital, Fitzroy, Victoria, Australia
                [3 ]The Royal Melbourne Hospital, Parkville Victoria, Australia
                [4 ]Department of Medicine, St Vincent's Hospital, Fitzroy, Victoria, Australia
                Karolinska Institute, Sweden
                Author notes

                Competing Interests: The authors have read the journal's policy and have the following conflicts: authors AE, RG, MH and KK have a financial interest in GKC, the company that is commercialising the logger and algorithm used in this manuscript. This does not alter the authors' adherence to all the PLOS ONE policies on sharing data and materials.

                Conceived and designed the experiments: AE KK RG MH. Performed the experiments: JK SM. Analyzed the data: MH JK. Contributed reagents/materials/analysis tools: AE KK RG MH. Wrote the paper: AE MH.

                Article
                PONE-D-13-40009
                10.1371/journal.pone.0089319
                3933354
                24586685
                a6c8547c-d563-444e-abbd-7f311606502f
                Copyright @ 2014

                This is an open-access article distributed under the terms of the Creative Commons Attribution License, which permits unrestricted use, distribution, and reproduction in any medium, provided the original author and source are credited.

                History
                : 29 September 2013
                : 17 January 2014
                Page count
                Pages: 7
                Funding
                Funding was provided by the Medical Research Council Funds. MH is a Medical Practitioner Fellow supported by the National Health and Medical Research Council of Australia. The funders had no role in study design, data collection and analysis, decision to publish, or preparation of the manuscript.
                Categories
                Research Article
                Biology
                Neuroscience
                Neurophysiology
                Motor systems
                Medicine
                Mental health
                Psychiatry
                Gambling addiction
                Neurology
                Movement disorders
                Neurodegenerative diseases
                Parkinson disease
                Social and behavioral sciences
                Psychology
                Behavior

                Uncategorized
                Uncategorized

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