2024
Banwinkler, Magdalena; Dzialas, Verena; Rigoux, Lionel; Asendorf, Adrian L; Theis, Hendrik; Giehl, Kathrin; Tittgemeyer, Marc; Hoenig, Merle C; van Eimeren, Thilo
Putaminal dopamine modulates movement motivation in Parkinson’s disease Journal Article
In: Brain, vol. 147, no. 10, pp. 3352–3357, 2024, ISSN: 1460-2156.
Abstract | Links | BibTeX | Tags: DaT imaging, Motivation, Parkinson
@article{Banwinkler2024,
title = {Putaminal dopamine modulates movement motivation in Parkinson’s disease},
author = {Magdalena Banwinkler and Verena Dzialas and Lionel Rigoux and Adrian L Asendorf and Hendrik Theis and Kathrin Giehl and Marc Tittgemeyer and Merle C Hoenig and Thilo van Eimeren},
doi = {10.1093/brain/awae214},
issn = {1460-2156},
year = {2024},
date = {2024-10-03},
urldate = {2024-10-03},
journal = {Brain},
volume = {147},
number = {10},
pages = {3352--3357},
publisher = {Oxford University Press (OUP)},
abstract = {<jats:title>Abstract</jats:title>
<jats:p>The relative inability to produce effortful movements is the most specific motor sign of Parkinson’s disease, which is primarily characterized by loss of dopaminergic terminals in the putamen. The motor motivation hypothesis suggests that this motor deficit may not reflect a deficiency in motor control per se, but a deficiency in cost-benefit considerations for motor effort. For the first time, we investigated the quantitative effect of dopamine depletion on the motivation of motor effort in Parkinson’s disease.</jats:p>
<jats:p>A total of 21 early-stage, unmedicated patients with Parkinson’s disease and 26 healthy controls were included. An incentivized force task was used to capture the amount of effort participants were willing to invest for different monetary incentive levels and dopamine transporter depletion in the bilateral putamen was assessed.</jats:p>
<jats:p>Our results demonstrate that patients with Parkinson’s disease applied significantly less grip force than healthy controls, especially for low incentive levels. Congruously, decrease of motor effort with greater loss of putaminal dopaminergic terminals was most pronounced for low incentive levels. This signifies that putaminal dopamine is most critical to motor effort when the trade-off with the benefit is poor.</jats:p>
<jats:p>Taken together, we provide direct evidence that the reduction of effortful movements in Parkinson’s disease depends on motivation and that this effect is associated with putaminal dopaminergic degeneration.</jats:p>},
keywords = {DaT imaging, Motivation, Parkinson},
pubstate = {published},
tppubtype = {article}
}
<jats:title>Abstract</jats:title>
<jats:p>The relative inability to produce effortful movements is the most specific motor sign of Parkinson’s disease, which is primarily characterized by loss of dopaminergic terminals in the putamen. The motor motivation hypothesis suggests that this motor deficit may not reflect a deficiency in motor control per se, but a deficiency in cost-benefit considerations for motor effort. For the first time, we investigated the quantitative effect of dopamine depletion on the motivation of motor effort in Parkinson’s disease.</jats:p>
<jats:p>A total of 21 early-stage, unmedicated patients with Parkinson’s disease and 26 healthy controls were included. An incentivized force task was used to capture the amount of effort participants were willing to invest for different monetary incentive levels and dopamine transporter depletion in the bilateral putamen was assessed.</jats:p>
<jats:p>Our results demonstrate that patients with Parkinson’s disease applied significantly less grip force than healthy controls, especially for low incentive levels. Congruously, decrease of motor effort with greater loss of putaminal dopaminergic terminals was most pronounced for low incentive levels. This signifies that putaminal dopamine is most critical to motor effort when the trade-off with the benefit is poor.</jats:p>
<jats:p>Taken together, we provide direct evidence that the reduction of effortful movements in Parkinson’s disease depends on motivation and that this effect is associated with putaminal dopaminergic degeneration.</jats:p>
<jats:p>The relative inability to produce effortful movements is the most specific motor sign of Parkinson’s disease, which is primarily characterized by loss of dopaminergic terminals in the putamen. The motor motivation hypothesis suggests that this motor deficit may not reflect a deficiency in motor control per se, but a deficiency in cost-benefit considerations for motor effort. For the first time, we investigated the quantitative effect of dopamine depletion on the motivation of motor effort in Parkinson’s disease.</jats:p>
<jats:p>A total of 21 early-stage, unmedicated patients with Parkinson’s disease and 26 healthy controls were included. An incentivized force task was used to capture the amount of effort participants were willing to invest for different monetary incentive levels and dopamine transporter depletion in the bilateral putamen was assessed.</jats:p>
<jats:p>Our results demonstrate that patients with Parkinson’s disease applied significantly less grip force than healthy controls, especially for low incentive levels. Congruously, decrease of motor effort with greater loss of putaminal dopaminergic terminals was most pronounced for low incentive levels. This signifies that putaminal dopamine is most critical to motor effort when the trade-off with the benefit is poor.</jats:p>
<jats:p>Taken together, we provide direct evidence that the reduction of effortful movements in Parkinson’s disease depends on motivation and that this effect is associated with putaminal dopaminergic degeneration.</jats:p>
2023
Theis, Hendrik; Prange, Stéphane; Bischof, Gérard N.; Hoenig, Merle C.; Tittgemeyer, Marc; Timmermann, Lars; Fink, Gereon R.; Drzezga, Alexander; Eggers, Carsten; van Eimeren, Thilo
Impulsive-compulsive behaviour in early Parkinson’s disease is determined by apathy and dopamine receptor D3 polymorphism Journal Article
In: npj Parkinsons Dis., vol. 9, no. 1, 2023, ISSN: 2373-8057.
Abstract | Links | BibTeX | Tags: Impulse control disorder, Motivation, Parkinson
@article{Theis2023,
title = {Impulsive-compulsive behaviour in early Parkinson’s disease is determined by apathy and dopamine receptor D3 polymorphism},
author = {Hendrik Theis and Stéphane Prange and Gérard N. Bischof and Merle C. Hoenig and Marc Tittgemeyer and Lars Timmermann and Gereon R. Fink and Alexander Drzezga and Carsten Eggers and Thilo van Eimeren},
doi = {10.1038/s41531-023-00596-9},
issn = {2373-8057},
year = {2023},
date = {2023-12-00},
urldate = {2023-12-00},
journal = {npj Parkinsons Dis.},
volume = {9},
number = {1},
publisher = {Springer Science and Business Media LLC},
abstract = {<jats:title>Abstract</jats:title><jats:p>Impulsive-compulsive behaviour (ICB) is a frequently observed non-motor symptom in early Parkinson’s disease after initiating dopamine replacement therapy. At the opposite end of the motivated behaviour spectrum, apathy occurs in early Parkinson’s disease even before dopamine replacement is started. The co-occurrence of these behavioural conditions in Parkinson’s disease raises questions about their relationship and underlying pathophysiological determinants. In previous imaging or genetic studies, both conditions have been associated with the limbic dopaminergic system. The risk variant of the Ser9Gly polymorphism of the dopamine receptor D3 (DRD3) is linked to increased dopamine affinity in the limbic striatum. With this in mind, we investigated how ICB expression is explained by apathy and DRD3 polymorphisms and their effects on grey matter volume and dopamine synthesis capacity. Fifty-four patients with early Parkinson’s disease took part in anatomical T1-weighted MRI. Forty of them also underwent dynamic PET imaging using [18F]DOPA to measure striatal dopamine synthesis capacity. Further, Ser9Gly (rs6280) gene polymorphism influencing the DRD3 dopamine-binding affinity was determined in all patients. The severity of impulsive-compulsive behaviour and apathy was assessed using the Questionnaire for Impulsive-Compulsive Disorders Rating Scale and the Apathy Evaluation Scale. ICB and the severity of apathy were indeed positively correlated. Apathy and the DRD3 polymorphism were interactive risk factors for ICB severity. Apathy was significantly linked to atrophy of the bilateral putamen. Patients with the DRD3 risk type had reduced dopamine synthesis capacity in the putamen and limbic striatum, apathy was associated with reduced dopamine synthesis capacity in the limbic striatum. The results of [18F]DOPA reached only trend significance. Apathy in drug-naïve PD patients might be a consequence of impaired striatal dopaminergic tone. This may represent a predisposing factor for the development of ICB after the initiation of dopamine replacement therapy. The risk type of DRD3 could further amplify this predisposition due to its higher affinity to dopamine.</jats:p>},
keywords = {Impulse control disorder, Motivation, Parkinson},
pubstate = {published},
tppubtype = {article}
}
<jats:title>Abstract</jats:title><jats:p>Impulsive-compulsive behaviour (ICB) is a frequently observed non-motor symptom in early Parkinson’s disease after initiating dopamine replacement therapy. At the opposite end of the motivated behaviour spectrum, apathy occurs in early Parkinson’s disease even before dopamine replacement is started. The co-occurrence of these behavioural conditions in Parkinson’s disease raises questions about their relationship and underlying pathophysiological determinants. In previous imaging or genetic studies, both conditions have been associated with the limbic dopaminergic system. The risk variant of the Ser9Gly polymorphism of the dopamine receptor D3 (DRD3) is linked to increased dopamine affinity in the limbic striatum. With this in mind, we investigated how ICB expression is explained by apathy and DRD3 polymorphisms and their effects on grey matter volume and dopamine synthesis capacity. Fifty-four patients with early Parkinson’s disease took part in anatomical T1-weighted MRI. Forty of them also underwent dynamic PET imaging using [18F]DOPA to measure striatal dopamine synthesis capacity. Further, Ser9Gly (rs6280) gene polymorphism influencing the DRD3 dopamine-binding affinity was determined in all patients. The severity of impulsive-compulsive behaviour and apathy was assessed using the Questionnaire for Impulsive-Compulsive Disorders Rating Scale and the Apathy Evaluation Scale. ICB and the severity of apathy were indeed positively correlated. Apathy and the DRD3 polymorphism were interactive risk factors for ICB severity. Apathy was significantly linked to atrophy of the bilateral putamen. Patients with the DRD3 risk type had reduced dopamine synthesis capacity in the putamen and limbic striatum, apathy was associated with reduced dopamine synthesis capacity in the limbic striatum. The results of [18F]DOPA reached only trend significance. Apathy in drug-naïve PD patients might be a consequence of impaired striatal dopaminergic tone. This may represent a predisposing factor for the development of ICB after the initiation of dopamine replacement therapy. The risk type of DRD3 could further amplify this predisposition due to its higher affinity to dopamine.</jats:p>