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Dopaminergic influences on risk preferences of Parkinson’s disease patients

  • Shunsuke KobayashiEmail author
  • Kohei Asano
  • Nozomu Matsuda
  • Yoshikazu Ugawa
Article

Abstract

Clinicians are increasingly recognizing impulse control disorders (ICDs) as a complication of dopaminergic treatment in Parkinson’s disease (PD). Considering the pivotal role of dopamine in reward information processing, ICDs may originate from dysregulation of reward-oriented behavior, and the behavioral changes may be reflected in shifts of psychological risk preference during decision-making. We used a behavioral economics paradigm to evaluate quantitatively the risk preferences of PD patients in levodopa on and off states. We also examined age-matched healthy controls. We found that levodopa increased the subjective value and prolonged the decision time in PD patients. These effects are apparently not explained by kinematic improvements but are attributed to psychological shifts of risk preferences and increased attention during risky decision-making. The risk preferences of healthy controls were similar to those of PD on levodopa treatment. The risk preferences of PD patients were not correlated with the scores of routine cognitive batteries, suggesting that dopamine-sensitive risk preferences are independent of cognitive capacities as measured by conventional batteries, including general intelligence, memory, and frontal functioning. By contrast, apathy and ICD partially predicted the risk attitude in PD patients, suggesting a common background of limbic origin behind these properties. The present results demonstrated that dopamine deficiency in off-state PD leads to risk-avoiding behavior and levodopa treatment increases the risk preferences. Behavioral economics framework is useful to evaluate short-term psychological changes in response to levodopa in PD patients.

Keywords

Neuroeconomics Parkinson’s disease Levodopa Impulse control disorders Pathological gambling Coefficient of relative risk aversion 

Notes

Acknowledgements

The authors thank Ms. Ayako Yusa, Ms. Yukiko Akutsu, and Ms. Yumiko Tanji for technical assistance and Dr. Philippe Tobler for discussion. This work was supported by a grant from the Japan Society for the Promotion of Science (JSPS) to S.K.

Funding

Work in the authors’ laboratory was supported by the JSPS grant (KAKENHI #22800052, 23500393)

Compliance with ethical standards

Conflict of interest

The authors declare no competing financial interests.

References

  1. Abler, B., Hahlbrock, R., Unrath, A., Gron, G., & Kassubek, J. (2009). At-risk for pathological gambling: imaging neural reward processing under chronic dopamine agonists. Brain, 132(Pt 9), 2396-2402.Google Scholar
  2. Ahlskog, J. E. (2011). Pathological behaviors provoked by dopamine agonist therapy of Parkinson's disease. Physiol Behav, 104(1), 168-172.Google Scholar
  3. Arrow, K. J. (1965). Aspects of the theory of risk-bearing. Helsinki: Yrjö Jahnssonin Säätiö.Google Scholar
  4. Bates, D., Maechler, M., Bolker, B., & Walker, S. (2014). lme4: Linear mixed-effects models using Eigen and S4. R package version 1.0-6.Google Scholar
  5. Bodi, N., Keri, S., Nagy, H., Moustafa, A., Myers, C. E., Daw, N., Dibo, G., Takats, A., Bereczki, D., & Gluck, M. A. (2009). Reward-learning and the novelty-seeking personality: a between- and within-subjects study of the effects of dopamine agonists on young Parkinson's patients. Brain, 132(Pt 9), 2385-2395.Google Scholar
  6. Brodsky, M. A., Park, B. S., & Nutt, J. G. (2010). Effects of a dopamine agonist on the pharmacodynamics of levodopa in Parkinson disease. Arch Neurol, 67(1), 27-32.Google Scholar
  7. Claassen, D. O., van den Wildenberg, W. P., Ridderinkhof, K. R., Jessup, C. K., Harrison, M. B., Wooten, G. F., & Wylie, S. A. (2011). The risky business of dopamine agonists in Parkinson disease and impulse control disorders. Behav Neurosci, 125(4), 492-500.Google Scholar
  8. Cools, R., Altamirano, L., & D'Esposito, M. (2006). Reversal learning in Parkinson's disease depends on medication status and outcome valence. Neuropsychologia, 44(10), 1663-1673.Google Scholar
  9. R Development Core Team. (2008). R: A language and environment for statistical computing. Vienna, Austria: R Foundation for Statistical Computing.Google Scholar
  10. Djamshidian, A., Jha, A., O'Sullivan, S. S., Silveira-Moriyama, L., Jacobson, C., Brown, P., Lees, A., & Averbeck, B. B. (2010). Risk and learning in impulsive and nonimpulsive patients with Parkinson's disease. Mov Disord, 25(13), 2203-2210.Google Scholar
  11. Djamshidian, A., O'Sullivan, S. S., Lawrence, A. D., Foltynie, T., Aviles-Olmos, I., Magdalinou, N., Tomassini, A., Warner, T. T., Lees, A. J., & Averbeck, B. B. (2014). Perceptual decision-making in patients with Parkinson's disease. J Psychopharmacol, 28(12), 1149-1154.Google Scholar
  12. Evans, A. H., Strafella, A. P., Weintraub, D., & Stacy, M. (2009). Impulsive and compulsive behaviors in Parkinson's disease. Mov Disord, 24(11), 1561-1570.Google Scholar
  13. Goetz, C. G., Tilley, B. C., Shaftman, S. R., Stebbins, G. T., Fahn, S., Martinez-Martin, P., Poewe, W., Sampaio, C., Stern, M. B., Dodel, R., Dubois, B., Holloway, R., Jankovic, J., Kulisevsky, J., Lang, A. E., Lees, A., Leurgans, S., LeWitt, P. A., Nyenhuis, D., Olanow, C. W., Rascol, O., Schrag, A., Teresi, J. A., van Hilten, J. J., LaPelle, N., & Movement Disorder Society, U. R. T. F. (2008). Movement Disorder Society-sponsored revision of the Unified Parkinson's Disease Rating Scale (MDS-UPDRS): scale presentation and clinimetric testing results. Mov Disord, 23(15), 2129-2170.Google Scholar
  14. Johnson, P. S., Madden, G. J., Brewer, A. T., Pinkston, J. W., & Fowler, S. C. (2011). Effects of acute pramipexole on preference for gambling-like schedules of reinforcement in rats. Psychopharmacology (Berl), 213(1), 11-18.Google Scholar
  15. Kapogiannis, D., Mooshagian, E., Campion, P., Grafman, J., Zimmermann, T. J., Ladt, K. C., & Wassermann, E. M. (2011). Reward processing abnormalities in Parkinson's disease. Mov Disord, 26(8), 1451-1457.Google Scholar
  16. Kobayakawa, M., Tsuruya, N., & Kawamura, M. (2010). Sensitivity to reward and punishment in Parkinson's disease: an analysis of behavioral patterns using a modified version of the Iowa gambling task. Parkinsonism Relat Disord, 16(7), 453-457.Google Scholar
  17. Kobayashi, S. (2012). Organization of neural systems for aversive information processing: pain, error, and punishment. Front Neurosci, 6, 136.Google Scholar
  18. Kobayashi, S., & Schultz, W. (2008). Influence of reward delays on responses of dopamine neurons. J Neurosci, 28(31), 7837-7846.Google Scholar
  19. Levin, I. P., Xue, G., Weller, J. A., Reimann, M., Lauriola, M., & Bechara, A. (2012). A neuropsychological approach to understanding risk-taking for potential gains and losses. Front Neurosci, 6, 15.Google Scholar
  20. Ligneul, R., Sescousse, G., Barbalat, G., Domenech, P., & Dreher, J. C. (2013). Shifted risk preferences in pathological gambling. Psychol Med, 43(5), 1059-1068.Google Scholar
  21. Luce, R. D. (2000). Utility of Gains and Losses: Measurement-Theoretical, and Experimental Approaches. Mahwah, NJ: Lawrence Erlbaum Associates.Google Scholar
  22. McElroy, S. L., Keck, P. E., Jr., Pope, H. G., Jr., Smith, J. M., & Strakowski, S. M. (1994). Compulsive buying: a report of 20 cases. J Clin Psychiatry, 55(6), 242-248.Google Scholar
  23. Medic, N., Ziauddeen, H., Vestergaard, M. D., Henning, E., Schultz, W., Farooqi, I. S., & Fletcher, P. C. (2014). Dopamine modulates the neural representation of subjective value of food in hungry subjects. J Neurosci, 34(50), 16856-16864.Google Scholar
  24. von Neumann, J., & Morgenstern, O. (1944). Theory of Games and Economic Behavior. Princeton, NJ: Princeton University Press.Google Scholar
  25. Pagonabarraga, J., Garcia-Sanchez, C., Llebaria, G., Pascual-Sedano, B., Gironell, A., & Kulisevsky, J. (2007). Controlled study of decision-making and cognitive impairment in Parkinson's disease. Mov Disord, 22(10), 1430-1435.Google Scholar
  26. Perretta, J. G., Pari, G., & Beninger, R. J. (2005). Effects of Parkinson disease on two putative nondeclarative learning tasks: probabilistic classification and gambling. Cogn Behav Neurol, 18(4), 185-192.Google Scholar
  27. Peters, J., & Buchel, C. (2010). Neural representations of subjective reward value. Behav Brain Res, 213(2), 135-141.Google Scholar
  28. Pratt, J. W. (1964). Risk aversion in the small and in the large. Econometrica, 32(1/2), 122-136.Google Scholar
  29. Riba, J., Kramer, U. M., Heldmann, M., Richter, S., & Munte, T. F. (2008). Dopamine agonist increases risk taking but blunts reward-related brain activity. PLoS One, 3(6), e2479.Google Scholar
  30. Rokosik, S. L., & Napier, T. C. (2012). Pramipexole-induced increased probabilistic discounting: comparison between a rodent model of Parkinson's disease and controls. Neuropsychopharmacology, 37(6), 1397-1408.Google Scholar
  31. Rossi, M., Gerschcovich, E. R., de Achaval, D., Perez-Lloret, S., Cerquetti, D., Cammarota, A., Ines Nouzeilles, M., Fahrer, R., Merello, M., & Leiguarda, R. (2010). Decision-making in Parkinson's disease patients with and without pathological gambling. Eur J Neurol, 17(1), 97-102.Google Scholar
  32. Starkstein, S. E., Mayberg, H. S., Preziosi, T. J., Andrezejewski, P., Leiguarda, R., & Robinson, R. G. (1992). Reliability, validity, and clinical correlates of apathy in Parkinson's disease. J Neuropsychiatry Clin Neurosci, 4(2), 134-139.Google Scholar
  33. Thiel, A., Hilker, R., Kessler, J., Habedank, B., Herholz, K., & Heiss, W. D. (2003). Activation of basal ganglia loops in idiopathic Parkinson's disease: a PET study. J Neural Transm (Vienna), 110(11), 1289-1301.Google Scholar
  34. Tremblay, M., Silveira, M. M., Kaur, S., Hosking, J. G., Adams, W. K., Baunez, C., & Winstanley, C. A. (2017). Chronic D2/3 agonist ropinirole treatment increases preference for uncertainty in rats regardless of baseline choice patterns. Eur J Neurosci, 45(1), 159-166.Google Scholar
  35. Voon, V., Gao, J., Brezing, C., Symmonds, M., Ekanayake, V., Fernandez, H., Dolan, R. J., & Hallett, M. (2011a). Dopamine agonists and risk: impulse control disorders in Parkinson's disease. Brain, 134(Pt 5), 1438-1446.Google Scholar
  36. Voon, V., Pessiglione, M., Brezing, C., Gallea, C., Fernandez, H. H., Dolan, R. J., & Hallett, M. (2010). Mechanisms underlying dopamine-mediated reward bias in compulsive behaviors. Neuron, 65(1), 135-142.Google Scholar
  37. Voon, V., Sohr, M., Lang, A. E., Potenza, M. N., Siderowf, A. D., Whetteckey, J., Weintraub, D., Wunderlich, G. R., & Stacy, M. (2011b). Impulse control disorders in Parkinson disease: a multicenter case--control study. Ann Neurol, 69(6), 986-996.Google Scholar
  38. Weintraub, D., Papay, K., Siderowf, A., & Parkinson's Progression Markers, I. (2013). Screening for impulse control symptoms in patients with de novo Parkinson disease: a case-control study. Neurology, 80(2), 176-180.Google Scholar
  39. Weintraub, D., Siderowf, A. D., Potenza, M. N., Goveas, J., Morales, K. H., Duda, J. E., Moberg, P. J., & Stern, M. B. (2006). Association of dopamine agonist use with impulse control disorders in Parkinson disease. Arch Neurol, 63(7), 969-973.Google Scholar
  40. Zappia, M., Montesanti, R., Colao, R., & Quattrone, A. (1994). Usefulness of movement time in the assessment of Parkinson's disease. J Neurol, 241(9), 543-550.Google Scholar

Copyright information

© Psychonomic Society, Inc. 2018

Authors and Affiliations

  • Shunsuke Kobayashi
    • 1
    Email author
  • Kohei Asano
    • 2
  • Nozomu Matsuda
    • 1
  • Yoshikazu Ugawa
    • 1
    • 3
    • 4
  1. 1.Department of NeurologyFukushima Medical UniversityFukushima-kenJapan
  2. 2.Kokoro Research CenterKyoto UniversityKyotoJapan
  3. 3.Department of Neural RegenerationFukushima Medical UniversityFukushimaJapan
  4. 4.Department of NeurologyAidu Chuo HospitalFukushimaJapan

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