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Reviews in the Neurosciences

Editor-in-Chief: Huston, Joseph P.

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Volume 24, Issue 3


Prefrontal dopamine signaling and cognitive symptoms of Parkinson’s disease

Nandakumar S. Narayanan
  • Corresponding author
  • Department of Neurology, University of Iowa Carver College of Medicine, Iowa City, IA 52242, USA
  • Aging Mind and Brain Initiative, University of Iowa Carver College of Medicine, Iowa City, IA 52242, USA
  • Email
  • Other articles by this author:
  • De Gruyter OnlineGoogle Scholar
/ Robert L. Rodnitzky
  • Department of Neurology, University of Iowa Carver College of Medicine, Iowa City, IA 52242, USA
  • Other articles by this author:
  • De Gruyter OnlineGoogle Scholar
/ Ergun Y. Uc
  • Department of Neurology, University of Iowa Carver College of Medicine, Iowa City, IA 52242, USA
  • Veteran’s Administration Medical Center, Iowa City, IA 52246, USA
  • Other articles by this author:
  • De Gruyter OnlineGoogle Scholar
Published Online: 2013-05-25 | DOI: https://doi.org/10.1515/revneuro-2013-0004


Cognitive dysfunction is a common symptom of Parkinson’s disease (PD) that causes significant morbidity and mortality. The severity of these symptoms ranges from minor executive symptoms to frank dementia involving multiple domains. In the present review, we will concentrate on the aspects of cognitive impairment associated with prefrontal dopaminergic dysfunction, seen in non-demented patients with PD. These symptoms include executive dysfunction and disorders of thought, such as hallucinations and psychosis. Such symptoms may go on to predict dementia related to PD, which involves amnestic dysfunction and is typically seen later in the disease. Cognitive symptoms are associated with dysfunction in cholinergic circuits, in addition to the abnormalities in the prefrontal dopaminergic system. These circuits can be carefully studied and evaluated in PD, and could be leveraged to treat difficult clinical problems related to cognitive symptoms of PD.

Keywords: acetylcholine; cognition; cognitive deficits; executive function; frontal cortex; Parkinson’s disease


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About the article

Nandakumar S. Narayanan

Dr. Nandakumar Narayanan is a physician-scientist who is interested in the circuitry of neuropsychiatric disease. In the lab, he studies how dopamine influences prefrontal networks that coordinate goal-directed behavior. Clinically, he sees patients with Parkinson’s disease. He attended Stanford University for his undergraduate training, and received an MD, PhD, and neurology residency training at Yale University prior to joining the faculty at the University of Iowa. He is a recipient of the Lindsley prize for behavioral neuroscience and the S. Weir Mitchell award for residency research.

Robert L. Rodnitzky

Dr. Robert Rodnitzky has been a movement disorders clinician and investigator for over 40 years. He is interested in non-motor symptoms of Parkinson’s disease and the development of new drugs. He is an editor of Parkinsonism and Related Disorders. He received both his undergraduate and medical degrees from the University of Chicago prior to coming to the University of Iowa for residency. He is the division head of Movement Disorders at the University of Iowa and the former chair of the neurology department.

Ergun Y. Uc

Dr. Ergun Uc is an accomplished clinical researcher and movement disorders neurologist who is interested in how Parkinson’s disease impairs performance of real-world tasks (e.g., driving) and in the effect of behavioral (e.g., exercise, cognitive training) or pharmaceutical interventions on function in PD. Dr. Uc has received research support from National Institutes of Health (Prediction of Driver Safety in Parkinson’s disease), Department of Veterans Affairs (Driver Rehabilitation in PD, Effect of Aerobic Exercise on Function and Cognition in PD), as well as American Parkinson Disease Association and Parkinson’s Disease Foundation. He is an Associate Professor at the Department of Neurology, Carver College of Medicine, University of Iowa, with a joint appointment at the Veterans Affairs Medical Center of Iowa City. He is the Associate Director of the Movement Disorders Division at the University of Iowa. He graduated from the University of Istanbul, and did his neurology residency and movement disorders fellowship at the University of Iowa prior to joining the faculty. He was voted as one of America’s best doctors.

Corresponding author: Nandakumar S. Narayanan, Department of Neurology, University of Iowa Carver College of Medicine, Iowa City, IA 52245, USA; and Aging Mind and Brain Initiative, University of Iowa Carver College of Medicine, Iowa City, IA 52242, USA

Received: 2013-02-27

Accepted: 2013-04-09

Published Online: 2013-05-25

Published in Print: 2013-06-01

Citation Information: Reviews in the Neurosciences, Volume 24, Issue 3, Pages 267–278, ISSN (Online) 2191-0200, ISSN (Print) 0334-1763, DOI: https://doi.org/10.1515/revneuro-2013-0004.

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Alex I. Wiesman, Elizabeth Heinrichs-Graham, Timothy J. McDermott, Pamela M. Santamaria, Howard E. Gendelman, and Tony W. Wilson
Human Brain Mapping, 2016, Volume 37, Number 9, Page 3224
Juhyun Song and Jongpil Kim
Frontiers in Aging Neuroscience, 2016, Volume 8
Amrita Biswas, Shantala Hegde, Ketan Jhunjhunwala, and Pramod Kumar Pal
Basal Ganglia, 2016, Volume 6, Number 1, Page 63
Panzao Yang, Darja Pavlovic, Henry Waldvogel, Mike Dragunow, Beth Synek, Clinton Turner, Richard Faull, and Jian Guan
Journal of Parkinson's Disease, 2015, Volume 5, Number 4, Page 821
Krystal L. Parker, Rafael N. Ruggiero, and Nandakumar S. Narayanan
Frontiers in Behavioral Neuroscience, 2015, Volume 9
Patrick Ejlerskov, Jeanette Göransdotter Hultberg, JunYang Wang, Robert Carlsson, Malene Ambjørn, Martin Kuss, Yawei Liu, Giovanna Porcu, Kateryna Kolkova, Carsten Friis Rundsten, Karsten Ruscher, Bente Pakkenberg, Tobias Goldmann, Desiree Loreth, Marco Prinz, David C. Rubinsztein, and Shohreh Issazadeh-Navikas
Cell, 2015, Volume 163, Number 2, Page 324
Maria Vadalà, Annamaria Vallelunga, Lucia Palmieri, Beniamino Palmieri, Julio Cesar Morales-Medina, and Tommaso Iannitti
Behavioral and Brain Functions, 2015, Volume 11, Number 1
Qiang Zhang, Young-Cho Kim, and Nandakumar S. Narayanan
Frontiers in Neuroscience, 2015, Volume 9
Françoise J. Siepel, Ingvild Dalen, Renate Grüner, Jan Booij, Kolbjørn S. Brønnick, Tirza C. Buter, and Dag Aarsland
Movement Disorders, 2016, Volume 31, Number 1, Page 118
Stephanie L. Alberico, Martin D. Cassell, and Nandakumar S. Narayanan
Basal Ganglia, 2015, Volume 5, Number 2-3, Page 51
Young-Cho Kim, Stephanie L. Alberico, Eric Emmons, and Nandakumar S. Narayanan
Frontiers in Biology, 2015, Volume 10, Number 3, Page 230
Laetitia C Schwab, Shaady N Garas, Janelle Drouin-Ouellet, Sarah L Mason, Simon R Stott, and Roger A Barker
Expert Review of Neurotherapeutics, 2015, Volume 15, Number 4, Page 445
Masayuki Matsumoto
Movement Disorders, 2015, Volume 30, Number 4, Page 472
Glenda M. Halliday, James B. Leverenz, Jay S. Schneider, and Charles H. Adler
Movement Disorders, 2014, Volume 29, Number 5, Page 634
M. T. Pellecchia, M. Picillo, G. Santangelo, K. Longo, M. Moccia, R. Erro, M. Amboni, C. Vitale, C. Vicidomini, M. Salvatore, P. Barone, and S. Pappatà
Acta Neurologica Scandinavica, 2015, Volume 131, Number 5, Page 275
Gabriele Cattaneo, Marco Calabria, Paula Marne, Alexandre Gironell, Jubin Abutalebi, and Albert Costa
Neuropsychologia, 2015, Volume 66, Page 99
Michel J. Grothe, Christina Schuster, Florian Bauer, Helmut Heinsen, Johannes Prudlo, and Stefan J. Teipel
Journal of Neurology, 2014, Volume 261, Number 10, Page 1939
Martin Broadstock, Clive Ballard, and Anne Corbett
Expert Review of Clinical Pharmacology, 2014, Volume 7, Number 6, Page 779
Françoise J. Siepel, Kolbjørn S. Brønnick, Jan Booij, Bernard M. Ravina, Alexander V. Lebedev, Joana B. Pereira, Renate Grüner, and Dag Aarsland
Movement Disorders, 2014, Volume 29, Number 14, Page 1802
K.L. Parker, S.L. Alberico, A.D. Miller, and N.S. Narayanan
Neuroscience, 2013, Volume 255, Page 246
M. Victoria Puig, Jonas Rose, Robert Schmidt, and Nadja Freund
Frontiers in Neural Circuits, 2014, Volume 8
J. Schomaker, H.W. Berendse, E.M.J. Foncke, Y.D. van der Werf, O.A. van den Heuvel, J. Theeuwes, and M. Meeter
Neuropsychologia, 2014, Volume 62, Page 124
Santiago Perez-Lloret and Marcelo Merello
Expert Opinion on Pharmacotherapy, 2014, Volume 15, Number 8, Page 1097

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