Putaminal dopamine modulates movement motivation in Parkinson's disease

Abstract

The relative inability to produce effortful movements (akinesia) is the most specific motor sign of Parkinsons disease. The motor motivation hypothesis suggests that akinesia 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 Parkinsons disease. A total of 21 patients with Parkinsons 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. Our results demonstrate that patients with Parkinsons 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. Taken together, we provide direct evidence that the reduction of effortful movements in Parkinsons disease depends on motivation and that this effect is associated with putaminal dopaminergic degeneration.