Statistical analysis
’, behavioral pain, failure of the equipment, pain
REGRESSION
For the statistical analysis, two participants were excluded, one participant due to the failure to comply with experimental procedures and one due to technical failure of the equipment. For one additional participant, data of one session (levodopa) are missing due to drop-out. Thirty-two out of 3735 single trials of all the remaining sessions were not recorded due to technical failures. In 42 trials, participants did not press a button within the respective interval in the wheel of fortune game. These trials were excluded from the analyses. Note that the NISS questionnaire was missing for two additional subjects due to initial issues at the beginning of the data collection.To test if blinding was successful we fit a mixed effects logistic regression with the subjects’ assumption on the ingested drug (as reported in the exit interview, see above) being correct as dependent variable. We used ‘drug’ as a fixed factor and to account for repeated measures we modeled a random intercept for each subject. Post-hoc general linear hypothesis tests were used to compare estimated proportions of correct assumptions against chance.To confirm that the manipulation of the motivated state (test vs. control trials) of the participants by playing the wheel of fortune game did induce pain modulation as intended in each session, we analyzed the VAS ratings and the behavioral pain measure as outcome measures separately for each session with ‘trial type’ and ‘outcome’ as well as their interaction as fixed effects. Here, the interaction effect indicates that active controllability in test trials has different effects for pain relief and pain increase. We used post-hoc tests to confirm that pain intensity was lower in the test compared to the control condition in win trials and equal or higher in the test compared to control condition in lose trials. We used Bonferroni-Holm method for family-wise error correction of these post-hoc tests across drug conditions. To account for the repeated measures design, we modeled a random intercept for each participant and a random slope for outcome of the wheel within each participant.To obtain an estimate for endogenous pain modulation in each test trial, we subtracted the mean value of all control trials of either the pain relief or the pain increase trials from the value of the winning or losing test trials separately for each session for both the VAS ratings and the behavioral pain measure. Using these differences, negative values indicate pain inhibition and positive values indicate pain facilitation. Estimates for pain modulation were analyzed using linear mixed model procedures with the fixed factors ‘drug’ (levodopa, naltrexone, placebo), ‘outcome’ (win, lose), ‘order’ of sessions (1, 2, 3), and their interaction separately for ratings and behaviorally assessed pain perception as dependent variables. The factor ‘session number’ was added to control for effects of temporal order independent of the drug manipulation that was found to influence pain modulation (see Unbeknown to the subjects, one of the colors in the wheel of fortune was associated with a higher chance to win pain relief. To test whether participants learned to select this color from the implemented reward contingencies we looked at choice behavior in the last 2 blocks of trials only. In this latter phase of the task subjects already had the chance to explore differences in outcomes associated with their choices and were thought show exploitation if they had learned about the contingency. We fitted a mixed effects logistic regression with the subjects’ choices as dependent variable. For a single session, we fit an intercept only model where the intercept represents the group level estimate for the probability to choose the color associated with a higher chance of winning pain relief (To test whether endogenous pain modulation due to winning pain relief was related to participants’ personality trait of novelty seeking, pain modulation represented by the differences between test and control trials in the wheel of fortune in VAS ratings and the behaviorally assessed pain perception of the placebo and the levodopa condition were correlated with the NISS NS scores. To test further whether increases in pain modulation induced by levodopa were associated with novelty seeking, differences in pain modulation between the levodopa and placebo session were also correlated with the NISS NS scores. Before calculating these correlations, multivariate outliers were tested using a chi-square test on the squared Mahalanobis distance using an of 0.025 (The significance level was set to 5% for all analyses. All statistical analyses were performed using statistical computing software R version 3.5.3 (