Article Figures & Data
Figures
- Figure 1.
Task design and performance on placebo and l-DOPA. A, In each of 300 trials, subjects made choices between safe and risky options. In 100 gain trials, the worst gamble outcome was zero. In 100 loss trials, the best gamble outcome was zero. In 100 mixed trials, both gamble outcome gains and losses were possible. Chosen gambles were resolved after a brief delay period. Subjects were also asked after every 3–4 choice trials “how happy are you at this moment?” and indicated their responses by moving a slider. B, On average, subjects (n = 30) gambled most in gain trials, less in mixed trials, and least in loss trials on both placebo and l-DOPA. Error bars indicate SEM. C, Subjects did not gamble more in mixed and loss trials on l-DOPA compared with placebo, but did gamble more in gain trials. *p < 0.05. D, Subjects who received higher effective drug doses chose more gain gambles on l-DOPA than placebo (p < 0.01).
- Figure 2.
Choice behavior and economic decision model fits. A, Parametric model based on prospect theory explained choice behavior. Error bars indicate SEM. B, Parameter estimates were similar on placebo and l-DOPA. C, Gain gamble value was determined relative to the value of the certain option. Deciles 1–2 corresponded to lower expected reward for the gamble than the certain option. Decile 3 corresponded to equal expected reward for the gamble and certain option. Deciles 4–10 corresponded to higher expected reward for the gamble than the certain option. As gain gamble value increased, subjects gambled more on both placebo and l-DOPA, as expected. D, Average model fit across subjects for the prospect theory model, which cannot account for the observed difference in choice behavior on l-DOPA compared with placebo.
- Figure 3.
Approach–avoidance model fits. A, Our approach–avoidance model incorporates an additional value-independent, valence-dependent effect on choice probability that accounts for the increased gambling on l-DOPA across gamble value deciles. B, Risk aversion parameters αgain and αloss for both placebo and l-DOPA sessions were <1, indicating risk aversion in the gain domain and risk seeking in the loss domain. Approach–avoidance parameter βgain was positive (“approach”) and βloss was negative (“avoid”) in placebo and l-DOPA sessions. Error bars indicate SEM. *p < 0.05. C, βgain was higher on l-DOPA than placebo, indicating an increased tendency to choose gain gambles independent of value. D, Subjects that received higher effective drug doses had a greater increase in βgain on l-DOPA than placebo (p < 0.05).
- Figure 4.
Choice behavior and approach–avoidance model fits for mixed and loss trials. A, Mixed gamble value was determined by the ratio of the potential gain to the potential loss. As mixed gamble value increased, subjects gambled more, as expected. B, Average model fit across subjects for the approach–avoidance model. C, Subjects who received higher effective doses did not have a larger change in the number of mixed gambles chosen on l-DOPA than placebo (Spearman's ρ = 0.02, p = 0.91), a relationship that would be negative if l-DOPA decreased risk taking. D, Loss gamble value was determined relative to the value of the certain option. As loss gamble value increased, subjects gambled more, as expected. E, Average model fit across subjects for the approach–avoidance model, which can account for the low probability of gambling for even the highest gamble values in placebo and l-DOPA sessions. F, Subjects who received higher effective doses did not have a larger change in the number of loss gambles chosen on l-DOPA than placebo (Spearman's ρ = 0.19, p = 0.32), a relationship that would be negative if l-DOPA decreased risk taking.
- Figure 5.
Happiness ratings across sessions. A, l-DOPA did not affect the mean or SD of happiness ratings. Error bars indicate SEM. B, Mean happiness ratings were uncorrelated across placebo and l-DOPA sessions (p = 0.27). C, SD of happiness ratings was correlated across placebo and l-DOPA sessions (p < 0.001). D, l-DOPA did not affect initial or final happiness ratings or how happy subjects remembered being the day after the session (all p > 0.2). Error bars indicate SEM. E, Mean happiness ratings were correlated with how happy subjects remembered being the day after the session (both Spearman's ρ > 0.5, p < 0.01). F, Remembered happiness was uncorrelated between placebo and l-DOPA sessions (Spearman's ρ = −0.21, p = 0.27).
- Figure 6.
Rewards and expectations explain momentary subjective well-being. A, B, Happiness ratings and cumulative task earnings across subjects (n = 30) on placebo (A) and l-DOPA (B) (placebo: r2 = 0.49 ± 0.25; l-DOPA: r2 = 0.45 ± 0.25). Happiness model fits are displayed for the model in C. Subjects completed 300 choice trials and made a rating after every 3–4 trials for a total of 90 ratings. C, The computational model that best explained momentary happiness had positive weights for certain rewards, gamble EVs, and gamble RPEs. Error bars indicate SEM. D, An alternative computational model included separate positive and negative RPE terms. E, F, In trials with potential gains but not losses, happiness was higher after gamble wins than losses on both placebo and l-DOPA (both p < 0.05). Happiness was higher after the small rewards from low-value gain gambles on l-DOPA compared with placebo (E), but not for the large rewards from high-value gain gambles (F). Error bars indicate SEM. *p < 0.05.
Tables
Model Parameters per subject Mean r2 Median r2 Model BIC BIC- BICa-a Prospect theory 7 0.51 0.50 13620 883 Approach–avoidance 11 0.57 0.58 12737 0 Dual-inverse-temperature 10 0.54 0.52 13363 626 Gain-loss learning 11 0.52 0.51 14160 1423 Approach–avoidance-mixed 13 0.60 0.59 12596 −141 BIC measures are summed across the 30 subjects. Parameters per subject are across both placebo and l-DOPA sessions. All models include separate parameters for placebo and l-DOPA sessions that capture the weighting of losses relative to equivalent gains (loss aversion, λ), risk aversion in the gain domain (αgain), and risk aversion in the loss domain (αloss). All models except the dual-inverse-temperature model included a shared parameter across sessions for stochasticity in choice (inverse temperature, μ). The final column is the difference between the model BIC and BICa-a, the BIC for the approach–avoidance model. The approach–avoidance model was preferred (lower BIC) to the prospect theory model, dual-inverse-temperature model, and gain-loss learning model. The more complex approach-avoidance-mixed model included additional approach–avoidance parameters for the mixed trials and had the lowest BIC of the models tested.
Subjective state questionnaire Placebo start l-DOPA start p-value Placebo end l-DOPA end p-value Alert to drowsy 0.18 1.20 0.15 0.12 0.82 0.62 Calm to excited −0.29 −0.22 0.42 −0.36 −0.06 0.72 Strong to feeble −0.17 0.68 0.06 0.06 0.51 0.96 Muzzy to clear headed 0.04 −0.94 0.12 −0.60 −1.12 0.86 Coordinated to clumsy −0.75 0.25 0.11 −0.34 0.33 0.78 Lethargic to energetic −0.15 −0.67 0.19 −0.17 −0.91 0.21 Contented to discontented −0.05 0.65 0.20 0.40 0.51 0.85 Troubled to tranquil −0.23 0.05 0.70 −0.71 −0.32 0.62 Slow to quick witted −0.05 −0.64 0.04 −0.44 −0.68 0.40 Tense to relaxed −0.04 −0.54 0.22 −0.74 −0.93 0.44 Attentive to dreamy 0.11 0.83 0.14 0.01 0.94 0.09 Incompetent to proficient −0.26 −0.32 0.67 −0.48 −0.71 0.95 Happy to sad −0.08 0.06 0.87 0.28 0.16 0.62 Antagonistic to friendly −0.09 −0.24 0.95 −0.64 −1.04 0.26 Interested to bored 0.14 0.40 0.53 0.52 0.64 1.00 Withdrawn to sociable 0.52 0.41 0.75 −0.06 −0.02 0.88 Scores represent differences in ratings in a subjective state questionnaire between baseline (before placebo or l-DOPA administration) and the start of the task or the end of the task. Questions were answered by marking a point on a line and responses were converted to a 0–10 scale. We used a Wilcoxon signed-rank test and the p-values listed are not corrected for multiple comparisons. We found no evidence for an overall effect of l-DOPA on any subjective state report because no test would survive any correction for multiple comparisons. However, many such corrections might be considered too conservative. For three variables, we identified trends at the 10% significance level (uncorrected) for a difference in subjective ratings between placebo and l-DOPA. For those three cases, we then tested for a dose-dependent relationship between l-DOPA and the size of the change in subjective responses because heavier subjects may not be affected and lighter subjects would be. We found no evidence for a relationship at the 10% significance level for these three tests, and therefore found no evidence supporting a dose-dependent effect of l-DOPA on these subjective state reports.
