Dopamine enhances willingness to exert effort for reward in Parkinson's disease

Abstract

Parkinson's disease (PD) is traditionally conceptualised as a disorder of movement, but recent data suggest that motivational deficits may be more pervasive than previously thought. Here, we ask whether subclinical deficits in incentivised decision-making are present in PD and, if so, whether dopaminergic therapy ameliorates such deficits. We devised a novel paradigm in which participants decided whether they were willing to squeeze a hand-held dynamometer at varying levels of force for different magnitudes of reward. For each participant, we estimated the effort level at which the probability of accepting a reward was 50% - the effort 'indifference point'. Patients with PD (N = 26) were tested ON and OFF their usual dopaminergic medication, and their performance compared to those of age-matched controls (N = 26). No participant was clinically apathetic as defined by the Lille Apathy Rating Scale (LARS). Our data show that, regardless of medication status, patients with PD chose to engage less effort than controls for the lowest reward. Overall, however, dopamine had a motivating effect on participants' choice behaviour - patients with PD chose to invest more effort for a given reward when they were in the ON relative to OFF dopamine state. Importantly, this effect could not be attributed to motor facilitation. We conclude that deficits in incentivised decision-making are present in PD even in the absence of a clinical syndrome of apathy when rewards are low, but that dopamine acts to eliminate motivational deficits by promoting the allocation of effort.

Keywords: Decision-making; Dopamine; Effort; Parkinson's disease; Reward.

Fig. 1

Summary of a typical trial. Stakes were indicated by the number of apples on the tree (1, 3, 6, 9, 12, 15), while the associated effort was indicated by the height of a yellow bar positioned at one of six levels on the tree trunk (corresponding to MVCs of 60%, 70%, 80%, 90%, 100%, 110%). On each trial, participants decided whether they were willing to exert the specified level of effort for the specified stake. If they judged the particular combination of stake and effort to be ‘not worth it,’ they selected the ‘No’ response. If, however, they decided to engage in that trial, they selected the ‘Yes’ response, and then had to squeeze a hand-held dynamometer with a force sufficient to reach the target effort level. Participants received visual feedback of their performance, as indicated by the height of a red force feedback bar. To reduce the effect of fatigue, participants were only required to squeeze the dynamometers on 50% of accepted trials. At the conclusion of each trial, participants were provided with feedback on the number of apples gathered.

Fig. 2

An example of the fitted probability functions for a representative participant. Logistic functions were used to plot the probability of engaging in a trial as a function of the effort level for each of the six stakes. Each participant's effort indifference points – the effort level at which the probability of engaging in a trial for a given stake is 50% (indicated by the dashed line) – were then computed.

Fig. 3

Effort indifference points plotted as a function of stake for healthy controls in Sessions 1 and 2. Effort indifference points divide the stake-effort space into a sector in which participants are willing to engage in an effortful response (below the curve) from a sector that is judged ‘not worth the effort’ (above the curve). Control performance was identical between sessions 1 and 2. Error bars indicate ±1 SEM.

Fig. 4

Effort indifference points plotted as a function of stake for patients and controls. (A) Regardless of medication status, patients had significantly lower effort indifference points than controls for the lowest reward. However, for high rewards, effort indifference points were significantly higher for patients when they were ON medication, relative not only to when they were OFF medication, but even compared to healthy controls. Inset: For clarity, PD data are replotted against control performance for patients (B) ON medication and (C) OFF medication. Shading denotes effort indifference points being greater for patients than controls (orange), or less for patients than controls (yellow). Error bars indicate ±1 SEM.