We first present clinical characteristics of the study cohort. Then we show the effects of DAA (on vs. off), ICD status (PD-ICD, PD-C), and DAA dose (low, moderate, and high), on risk-taking behavior. Of note, session order (off-on agonist, on-off agonist) and levodopa co-therapy did not influence the pattern of results or interact with any experimental factors. The following results collapse across both session order and levodopa co-therapy. See Supplementary data for these analyses.
Of the 41 PD participants, 22 were identified with active symptoms indicative of ICD (PD-ICD) coincident with DAA use. Additionally, 19 patients were classified as PD controls (PD-C). PD-ICD and PD-C patients had similar clinical characteristics (). ICD symptoms included hypersexuality (13/22), compulsive shopping or buying (12/22), compulsive eating (10/22), pathologic gambling (2/22), and compulsive hobbyism (17/22).
Parkinson's Disease (PD) Participant Characteristics
Analysis of Risk-Taking Behavior
Average inflations risked in each risk context are presented in . Patients adjusted risk-taking according to the probability of negative consequences. On average, participants risked more inflations when the chance of the balloon popping with each inflation was lower compared to when it was higher (7.0 versus 3.1) (Risk Context, F(1,39) = 203.9, p < 0.001). This pattern of risk adjustment was uninfluenced by either agonist state or ICD status (Risk Context × Agonist State, F(1,39) = 0.19, p = 0.66; Risk Context × ICD, F(1,39) = 0.14, p = 0.71). Across patients, the average number of inflations risked did not differ between “off” and “on” DAA state (5.0 versus 5.1) (Agonist State, F(1,39) = 0.20, p = 0.66) or between PD-ICD and PD-C (5.3 versus 4.8) (ICD, F(1,39) = 0.84, p = 0.37).
Figure 2 PD control patients without ICD (PD-C; filled markers) and patients with ICD (PD-ICD; open markers) show equivalent balloon inflations risked ‘off’ dopamine agonist medication irrespective of risk context. When on DAA, PD-ICD patients (more ...)
Importantly, agonist state selectively influenced the risk-taking behavior of PD-ICD compared to PD-C patients (Agonist State × ICD, F(1,39) = 5.59, p = 0.02). As depicted in , the average inflations risked by PD-C and by PD-ICD patients was similar in the ‘off’ dopamine agonist state. However, in the ‘on’ agonist state, PD-ICD patients significantly increased their average number of inflations risked as compared to PD-C patients, who showed a slight decrease in inflations risked. This pattern suggests that dopamine agonists induced riskier behavior in a subset of PD patients with active ICD symptoms. Notably, this pattern of increased risk-taking in PD-ICD patients in the ‘on’ agonist state did not depend on the pop risk context (Agonist State × ICD × Risk Context; F(1,39) = 1.34, p = 0.26).
Risk Adjustment after Negative Outcomes
We anticipated that patients would adopt a more cautious risk strategy on trials that followed a popped balloon. This predicted adjustment to negative consequences was measured by comparing the average number of inflations risked for cashed trials that immediately followed a popped balloon to cashed trials immediately preceding a popped balloon. This analysis included Agonist State (on, off), Risk Context (lower risk, higher risk), and Sequence (pre-pop, post-pop) as within-subject factors, as well as ICD status (PD-ICD, PD-C) as a between-subjects factor. Here, we focus on the Sequence effects, as the pattern of effects involving the remaining factors was unchanged from the above analysis.
Patients with and without ICD as well as ‘on’ and ‘off’ of their DAA medication reduced risk-taking similarly following negative outcomes (). Overall, patients risked fewer inflations on trials following a popped balloon (5.1) compared to trials preceding a popped balloon (5.9), (Sequence, F(1, 39) = 65.25, p < .001). This post-pop adjustment in risk-taking depended on the pop risk context (Risk Context × Sequence, F(1, 39) = 11.18, p < .01); that is, the reduction in inflations risked after a pop was greater in the lower risk condition compared to the higher risk condition. Importantly, the reduction in risk-taking following a balloon pop was not influenced by DAA state, ICD status, or their interaction (all ps > 0.10).
Figure 3 PD controls (PD-C) and PD patients with ICD (PD-ICD) showed a similar reduction in balloon inflations risked on trials following a popped balloon compared to trials preceding a popped balloon. This effect was independent of risk context and agonist state. (more ...)
Effects of Daily Dopamine Agonist Dose on Risk Behavior
All patients were subdivided into three equally sized groups based on DAA dose. Expressed in LEDD, 14 patients were taking low doses of a DAA (150 mg or less; range: 37.5 – 150), 13 moderate doses (range: 200 – 300 mg), and 14 high doses (375 mg or higher; range: 375 – 600). The high DAA dose group had a higher ratio of PD-ICD to PD-C patients (10:4) as compared to the moderate (8:5) and low (7:7) groups, but these proportions were not statistically different (χ2 = 3.06, df = 2, p = 0.22). Included in the analysis were within-subject factors of Agonist State (on, off) and Risk Context (lower risk, higher risk) as well as the between-subjects factor of Agonist Dose Group (low, moderate, high) (). Here we focus on the Agonist Dose effect as the main effects involving Agonist State and Risk Context remained unchanged from the above analyses. We predicted a specific interaction between Agonist State and Agonist Dose that would reveal a greater increase in risk-taking among patients taking relatively higher doses of DAA when on compared to off of their DAA.
Balloon Inflations in Dopamine Agonist Subgroups
Overall, the average inflations risked were similar across DAA dose groups (Low = 5.3, Moderate = 4.7, High = 5.2), (Agonist Dose, F(2,38) = 0.52, p = 0.60). However, DAA state differentially influenced risk-taking among the groups, (Agonist State × Agonist Dose Group, F(2,38) = 6.78, p < 0.01), and this effect was sensitive to the risk context (Agonist State × Agonist Dose Group × Risk Context, (F(2,38) = 3.76, p = 0.03) (). In deconstructing this interaction, differences in risk-taking between the groups as a function of DAA state was significant only in the low risk context, (F(2,38) = 6.89, p = 0.003), but not in the high risk context, (F(2,38) = 1.14, p = 0.25). depicts the change in inflations risked between DAA states, on minus off, for each of the DAA dose groups under both high and low risk contexts. As the figure illustrates, the change in inflations risked in the low risk context was greater for patients taking higher doses of DAA compared to the low dose group, (t(26) = −2.25, p = 0.015; one-sided test with Bonferroni corrected alpha = 0.017), and moderate dose group, (t(25) = −3.68, p < 0.001; one-sided test). Patients taking moderate doses of DAA did not risk more inflations than patient taking lower doses in the low risk context, (t(25) = 1.36, p = 0.10; one-sided test).
Figure 4 Depicts the change in average inflations risked when “on” compared to “off” dopamine agonist (DAA) medication for patients taking different doses of DAA. Positive values indicate higher risk-taking while ‘on’ (more ...)
The low dose DAA group had an equal proportion of PD-ICD and PD-C patients. We assessed changes in risk behavior for this group separately as an additional test of the hypothesis that patients with ICD possess a specific vulnerability to the effects of DAA on risk behavior. Specifically, we expected that the PD-ICD patients would still show increased risk-taking ‘on’ DAA compared to the PD-C group despite the fact that both patient groups were taking lower doses of DAA. Using the change in inflations risked (on minus off DAA) as the dependent measure, we used a simple t-test to compare these PD-ICD and PD-C subgroups. Since we established a directional prediction a priori, we used a one-sided hypothesis test. This analysis showed that PD-ICD patients in the low dose group risked more overall inflations ‘on’ compared to ‘off’ DAA (+ 0.8 inflations) than the PD-C patients, who tended to risk slightly fewer inflations ‘on’ versus ‘off’ DAA (−0.5 inflations) (t(12) = −1.89, p = 0.04). This suggests that even among patients taking lower doses of DAA, those with ICD still showed a DAA-induced increase in risk-taking compared to those without ICD.
Associations of Risk Behavior to Key Clinical Features of PD
We examined the association (Pearson correlation) between the change in inflations risked between ‘off’ and ‘on’ DAA states and the following set of clinical features: time on agonist, disease duration, motor symptom severity, and agonist dose in LEDD. After Bonferroni correction for multiple comparisons (adjusted p-value = .006), no clinical features correlated with the change in inflations risked between ‘off’ and ‘on’ DAA states for either low or high risk contexts (all ps > 0.10). Notably, agonist dose (in LEDD) tended to modestly and positively correlate with inflations risked in the low risk context (r = 0.35, p = 0.02), although this fell short of the adjusted significance p-value. This trend, however, is consistent with the results obtained from the agonist dose subgroup analysis that indicated that, relative to patients taking lower doses of DAA, patients taking the highest doses increased risk-taking in situations where risk was less likely to be penalized (i.e., low risk context).