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  The role of dopamine in positive and negative prediction error utilization during incidental learning: Insights from Positron Emission Tomography, Parkinson’s disease and Huntington’s disease

Mathar, D., Wilkinson, L., Holl, A., Neumann, J., Deserno, L., Villringer, A., et al. (2017). The role of dopamine in positive and negative prediction error utilization during incidental learning: Insights from Positron Emission Tomography, Parkinson’s disease and Huntington’s disease. Cortex, 90, 149-162. doi:10.1016/j.cortex.2016.09.004.

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Mathar, David1, 2, Author              
Wilkinson, Leonora3, Author
Holl, Anna4, Author
Neumann, Jane1, 2, Author              
Deserno, Lorenz1, 5, 6, Author              
Villringer, Arno1, 2, 7, 8, Author              
Jahanshahi, Marjan3, 9, Author
Horstmann, Annette1, 2, Author              
1Department Neurology, MPI for Human Cognitive and Brain Sciences, Max Planck Society, ou_634549              
2Integrated Research and Treatment Center Adiposity Diseases, University of Leipzig, Germany, ou_persistent22              
3Behavioral Neurology Unit, National Institute of Neurological Disorders and Stroke, Bethesda, MD, USA, ou_persistent22              
4Department of Psychiatry, Medical University of Graz, Austria, ou_persistent22              
5Department of Psychiatry and Psychotherapy, Charité University Medicine Berlin, Germany, ou_persistent22              
6Department of Neurology, Otto von Guericke University Magdeburg, Germany, ou_persistent22              
7Clinic for Cognitive Neurology, University of Leipzig, Germany, ou_persistent22              
8Berlin School of Mind and Brain, Humboldt University Berlin, Germany, ou_persistent22              
9Sobell Department of Motor Neuroscience and Movement Disorders, Institute of Neurology, University College London, United Kingdom, ou_persistent22              


Free keywords: Procedural stimulus-response learning; Computational modeling; Dopamine; PET; Parkinson’s disease; Huntington’s disease
 Abstract: Incidental learning of appropriate stimulus-response associations is crucial for optimal functioning within our complex environment. Positive and negative prediction errors (PEs) serve as neural teaching signals within distinct (‘direct’/‘indirect’) dopaminergic pathways to update associations and optimize subsequent behavior. Using a computational reinforcement-learning model, we assessed learning from positive and negative PEs on a probabilistic task (Weather Prediction Task, [WPT]) in three populations that allow different inferences on the role of dopamine (DA) signals: (1) Healthy volunteers that repeatedly underwent [11C]raclopride Positron Emission Tomography, allowing for assessment of striatal DA release during learning, (2) Parkinson’s disease (PD) patients tested both on and off L-DOPA medication, (3) early Huntington’s disease (HD) patients, a disease that is associated with hyper-activation of the ‘direct’ pathway. Our results show that learning from positive and negative feedback on the WPT is intimately linked to different aspects of dopaminergic transmission. In healthy individuals, the difference in [11C]raclopride binding potential (BP) as a measure for striatal DA release was linearly associated with the positive learning rate. Further, asymmetry between baseline DA tone in the left and right ventral striatum was negatively associated with learning from positive PEs. Female patients with early HD exhibited exaggerated learning rates from positive feedback. In contrast, dopaminergic tone predicted learning from negative feedback, as indicated by an inverted-u-shaped association observed with baseline [11C]raclopride BP in healthy controls and the difference between PD patients’ learning rate on and off dopaminergic medication. Thus, the ability to learn from positive and negative feedback is a sensitive marker for the integrity of dopaminergic signal transmission in the ‘direct’ and ‘indirect’ dopaminergic pathways. The present data are interesting beyond clinical context in that imbalances of dopaminergic signaling have not only been observed for neurological and psychiatric conditions but also been proposed for obesity and adolescence.


Language(s): eng - English
 Dates: 2016-04-202016-09-072016-09-192017-05
 Publication Status: Published in print
 Pages: -
 Publishing info: -
 Table of Contents: -
 Rev. Type: Peer
 Identifiers: DOI: 10.1016/j.cortex.2016.09.004
PMID: 27751503
Other: Epub 2016
 Degree: -



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Project name : -
Grant ID : 01E01001
Funding program : -
Funding organization : IFB Adiposity Diseases, German Federal Ministry of Education and Research (BMBF)
Project name : Obesity Mechanisms / SFB 1052
Grant ID : -
Funding program : -
Funding organization : German Research Foundation (DFG)
Project name : -
Grant ID : -
Funding program : -
Funding organization : Fazit-Stiftung
Project name : -
Grant ID : -
Funding program : Landesstipendium
Funding organization : Free State of Saxony

Source 1

Title: Cortex
  Other : Cortex
Source Genre: Journal
Publ. Info: -
Pages: - Volume / Issue: 90 Sequence Number: - Start / End Page: 149 - 162 Identifier: ISSN: 0010-9452
CoNE: https://pure.mpg.de/cone/journals/resource/954925393344