TY - JOUR
T1 - Dopamine agonist treatment increases sensitivity to gamble outcomes in the hippocampus in de novo Parkinson's disease
AU - van der Vegt, Joyce P.M.
AU - Hulme, Oliver J.
AU - Madsen, Kristoffer H.
AU - Buhmann, Carsten
AU - Bloem, Bastiaan R.
AU - Münchau, Alexander
AU - Helmich, Rick C.
AU - Siebner, Hartwig R.
N1 - Funding Information:
This work was supported by the Netherlands Organisation for Scientific Research (NWO; VIDI grant No. 16.076.352 to B.R.B.) and a grant of excellence by the Lundbeck Foundation on the Control of Action ( ContAct ; grant No. R59 A5399 to H.R.S.). H.R.S. holds a 5-year professorship in precision medicine at the Faculty of Health Sciences and Medicine, University of Copenhagen which is sponsored by the Lundbeck Foundation (Grant Nr. R186-2015–2138).
Funding Information:
The authors declare the following financial interests/personal relationships which may be considered as potential competing interests: Hartwig R. Siebner has received honoraria as speaker from Sanofi Genzyme, Denmark and Novartis, Denmark, as consultant from Sanofi Genzyme, Denmark and as senior editor (NeuroImage) and editor-in-chief (Neuroimage Clinical) from Elsevier Publishers, Amsterdam, The Netherlands. He has received royalties as book editor from Springer Publishers, Stuttgart, Germany. Rick Helmich serves on the clinical advisory board of Cadent Therapeutics and received honoraria from AbbVie. Bas Bloem has received funding from the Parkinson’s Foundation, the Netherlands Organization for Scientific Research, Stichting Internationaal Parkinson Fonds and the Michael J Fox Foundation. The Center of Expertise for Parkinson & Movement Disorders of the Radboud University Medical Center was supported by a center of excellence grant of the Parkinson's Foundation. Prof. Alexander Münchau has received commercial research support from Pharm Allergan, Ipsen, Merz Pharmaceuticals, Actelion and honoraria for lectures from Pharm Allergan, Ipsen, Merz Pharmaceuticals, Actelion, GlaxoSmithKline, Desitin and Teva. He receives royalties for the book Neurogenetics (Oxford University Press).
Publisher Copyright:
© 2020 The Authors
Copyright:
Copyright 2020 Elsevier B.V., All rights reserved.
PY - 2020/1/1
Y1 - 2020/1/1
N2 - Background: Parkinson's disease is associated with severe nigro-striatal dopamine depletion, leading to motor dysfunction and altered reward processing. We previously showed that drug-naïve patients with Parkinson's disease had a consistent attenuation of reward signalling in the mesolimbic and mesocortical system. Here, we address the neurobiological effects of dopaminergic therapy on reward sensitivity in the mesolimbic circuitry, and how this may contribute to neuropsychiatric symptoms. Objectives: We tested the hypothesis that (1) dopaminergic treatment would restore the attenuated, mesolimbic and mesocortical responses to reward; and (2) restoration of reward responsivity by dopaminergic treatment would predict motor performance and the emergence of impulse control symptoms. Methods: In 11 drug-naïve Parkinson patients, we prospectively assessed treatment-induced changes in reward processing before, and eight weeks after initiation of monotherapy with dopamine agonists. They were compared to 10 non-medicated healthy controls who were also measured longitudinally. We used whole-brain functional magnetic resonance imaging at 3 Tesla to assess the reward responsivity of the brain to monetary gains and losses, while participants performed a simple consequential gambling task. Results: In patients, dopaminergic treatment improved clinical motor symptoms without significantly changing task performance. Dopamine agonist therapy induced a stronger reward responsivity in the right hippocampus with higher doses being less effective. None of the patients developed impulse control disorders in the follow-up period of four years. Conclusions: Short-term treatment with first-ever dopaminergic medication partially restores deficient reward-related processing in the hippocampus in de novo Parkinson's disease.
AB - Background: Parkinson's disease is associated with severe nigro-striatal dopamine depletion, leading to motor dysfunction and altered reward processing. We previously showed that drug-naïve patients with Parkinson's disease had a consistent attenuation of reward signalling in the mesolimbic and mesocortical system. Here, we address the neurobiological effects of dopaminergic therapy on reward sensitivity in the mesolimbic circuitry, and how this may contribute to neuropsychiatric symptoms. Objectives: We tested the hypothesis that (1) dopaminergic treatment would restore the attenuated, mesolimbic and mesocortical responses to reward; and (2) restoration of reward responsivity by dopaminergic treatment would predict motor performance and the emergence of impulse control symptoms. Methods: In 11 drug-naïve Parkinson patients, we prospectively assessed treatment-induced changes in reward processing before, and eight weeks after initiation of monotherapy with dopamine agonists. They were compared to 10 non-medicated healthy controls who were also measured longitudinally. We used whole-brain functional magnetic resonance imaging at 3 Tesla to assess the reward responsivity of the brain to monetary gains and losses, while participants performed a simple consequential gambling task. Results: In patients, dopaminergic treatment improved clinical motor symptoms without significantly changing task performance. Dopamine agonist therapy induced a stronger reward responsivity in the right hippocampus with higher doses being less effective. None of the patients developed impulse control disorders in the follow-up period of four years. Conclusions: Short-term treatment with first-ever dopaminergic medication partially restores deficient reward-related processing in the hippocampus in de novo Parkinson's disease.
UR - http://www.scopus.com/inward/record.url?scp=85089265516&partnerID=8YFLogxK
UR - https://www.mendeley.com/catalogue/0f3b5159-64df-3e85-a82e-5561f14a48f7/
U2 - 10.1016/j.nicl.2020.102362
DO - 10.1016/j.nicl.2020.102362
M3 - Journal articles
C2 - 32798910
AN - SCOPUS:85089265516
SN - 2213-1582
VL - 28
SP - 102362
JO - NeuroImage: Clinical
JF - NeuroImage: Clinical
M1 - 102362
ER -