Effects of dopamine on reinforcement learning and consolidation in Parkinson’s disease
- University of Bristol, United Kingdom
- North Bristol NHS Trust, United Kingdom
- University of Oxford, United Kingdom
Figures
Figure 1
Diagram of the learning trials of the Probabilistic Selection Task.
In each pair one card is more likely to be rewarded (shown ‘Correct’ feedback) than the other, with card A in pair AB rewarded 80% of trials, and card B on 20% of trials. For pairs CD and EF, the probabilities are 70–30% and 60–40%.
Figure 2
Mean difference in memory block accuracy between 24 hr and 30 min, for each condition in experiment 1.
ON-OFF had significantly greater increases in memory score over this time than OFF-OFF (* = p=0.0106) and indeed both day 1 ON conditions (blue bars) had a mean increase in accuracy while both day 1 OFF conditions (red bars) and HC (black bars) had a decrease. Error bars are SEM. Figure 2—source data 1 shows the summary statistics.
-
Figure 2—source data 1
Summary statistics for Figure 2, the difference in memory scores between 30 min and 24 hr tests for each condition.
- https://doi.org/10.7554/eLife.26801.005
Figure 3 with 2 supplements
The mean percentages of choose-A and avoid-B selections at the 24 hr novel pairs tests in experiment 1, split by a) day 1 and b) day 2 conditions.
There were no significant effects of day 1 or day 2 medication state (p>0.28). Error bars are SEM. Figure 3—figure supplement 1 shows the data when filtered by performance on the 80–20% pair for day 1 conditions, and Figure 3—figure supplement 2 shows the filtered day 2 conditions. Figure 3—source data 1 shows the summary statistics.
-
Figure 3—source data 1
Summary statistics for Figure 3, the percentages of choose-A and avoid-B selections in the experiment 1 novel pairs test.
- https://doi.org/10.7554/eLife.26801.007
Figure 3—figure supplement 1
The mean percentages of choose-A and avoid-B selections for the filtered data in the experiment 1 novel pairs test split by day 1 conditions.
As the filtering removed data from different participants, paired samples statistics were no longer suitable. Independent-samples t-tests showed no significant effects of day 1 medication state (df = 57, p=0.975, d = 0.0956; p=0.265, d = 0.2010), nor an effect of disease state (df = 72, p=0.315, d = 0.1269; p=0.939, 0.1169) on choose-A or avoid-B. Error bars are SEM.
-
Figure 3—figure supplement 1—source data 1
Summary statistics for Figure 3—figure supplement 1, percentages of choose-A and avoid-B behaviours for experiment 1 split by Day 1 condition, after data filtering.
- https://doi.org/10.7554/eLife.26801.009
Figure 3—figure supplement 2
The mean percentages of choose-A and avoid-B selections for the filtered data in the experiment 1 novel pairs test split by day 2 conditions.
Between-subjects t-tests showed no effect of day 2 medication state (df = 57, p=0.151, d = 0.1780; p=0.928, d = 0.0061). Error bars are SEM.
-
Figure 3—figure supplement 2—source data 1
Summary statistics for Figure 3—figure supplement 2, percentages of choose-A and avoid-B behaviours for experiment 1 split by day 2 condition, after data filtering.
- https://doi.org/10.7554/eLife.26801.011
Figure 4 with 2 supplements
The mean percentages of selections on the novel pairs test for a) experiment 2 and b) experiment 3.
There were no significant effects of disease state or medication condition on either selection in either experiment 2 (p>0.2) or experiment 3 (p>0.3). Error bars are SEM. Figure 4—figure supplement 1 shows the data after filtering was applied to experiment 2, and Figure 4—figure supplement 2 shows the filtered data for experiment 3. Figure 4—source data 1 shows the summary statistics.
-
Figure 4—source data 1
Summary statistics for Figure 4, the percentages of choose-A and avoid-B selections in experiments 2 and 3 novel pairs tests.
- https://doi.org/10.7554/eLife.26801.013
Figure 4—figure supplement 1
The mean percentage of selections for the filtered data for experiment 2.
Independent-samples t-tests showed no significant effects on choose-A or avoid-B for disease state (df = 47, p=0.361, d = 0.2768; p=0.126, d = 0.4681) or medication state (df = 30, p=0.473, d = 0.2575; p=0.825, d = 0.0792). Error bars are SEM.
-
Figure 4—figure supplement 1—source data 1
Summary statistics for Figure 4—figure supplement 1, percentages of choose-A and avoid-B behaviours for experiment 3, after data filtering.
- https://doi.org/10.7554/eLife.26801.015
Figure 4—figure supplement 2
The mean percentage of selections for the filtered data for experiment 3.
Independent-samples t-tests showed no effects of disease state (df = 31, p=0.509, d = 0.2465; p=0.926, d = 0.0345) or medication state (df = 20, p=0.579, d = 0.2415; p=0.555, d = 0.25658). Error bars are SEM.
-
Figure 4—figure supplement 2—source data 1
Summary statistics for Figure 4—figure supplement 2, percentages of choose-A and avoid-B behaviours for experiment 2, after data filtering.
- https://doi.org/10.7554/eLife.26801.017
Figure 5
Mean final learning block accuracies across the three experiments.
Experiment 3’s final accuracy was significantly lower than experiments 1 and 2’s (p<0.000001). Error bars are SEM. Figure 5—source data 1 shows the summary statistics.
-
Figure 5—source data 1
Summary statistics for Figure 5, the mean final learning block accuracies across the three experiments.
- https://doi.org/10.7554/eLife.26801.019
Figure 6
A diagram of the timing of PD medication withdrawal for all four conditions in experiment 1.
Blue is when patients were ON medication, red hatched bars when they were OFF, and yellow bars the PST phases. In order for patients to be fully OFF medication during testing, they were withdrawn from their dopaminergic medications a minimum of 15 hr prior to testing (>24 hr for long-lasting medications). Note that in all conditions, patients were ON medication for a few hours after the day 1 session, to minimise the time spent OFF medication.
Figure 7
The modified Probabilistic Selection Task procedure.
Participants saw two symbols on the screen, and selected one with a button press. If no response was made within 2 s, they were shown a ‘GO’ prompt. Feedback was determined probabilistically, was shown for 2 s, and was either the smiling or frowning face.
Appendix 1—figure 1
The mean percentages of win-stay and lose-shift during the learning trials for experiments 1 (a), 2 (b) and 3 (c), each split by day 1 condition.
Appendix 1—figure 1—source data 1 shows the summary statistics.
-
Appendix 1—figure 1—source data 1
Summary statistics for the percentage of win-stay and lose-shift behaviours during learning trials for each experiment.
- https://doi.org/10.7554/eLife.26801.024
Tables
Table 1
The means and SEM for each experiment for PD patients and HC on all measures taken. Within each experiment, one-way ANOVAs were run between PD patients and HC (χ2 for the genders), and paired t-tests for the comparisons between patients ON and OFF medication for the UPDRS. MMSE scores from experiment 1 were converted to MoCA scores for comparison. *p<0.05, **p<0.01, ***p<0.001.
| Experiment | 1 | 2 | 3 | |||
|---|---|---|---|---|---|---|
| Measure | PD patients | HC | PD patients | HC | PD patients | HC |
| Number | 18 | 18 | 18 | 20 | 18 | 18 |
| Gender (M/F) | 15/3** | 7/11 | 16/2*** | 5/15 | 11/7 | 11/7 |
| Age | 71.56 (2.06) | 71.19 (2.52) | 67.39 (2.10) | 66.05 (2.05) | 69.11 (1.44) | 71.61 (2.05) |
| Years Education | 13.50 (0.66) | 12.93 (0.89) | 14.83 (0.91) | 13.75 (0.56) | 11.94 (0.52)* | 14.72 (0.65) |
| MoCA | 29.44 (0.12) | 29.63 (0.13) | 28.72 (0.50)* | 26.85 (0.53) | 27.61 (0.54) | 26.78 (0.56) |
| DASS | 21.71 (2.85)* | 12.19 (2.76) | 15.39 (2.54) | 20.05 (5.50) | 29.13 (4.53)** | 10.44 (2.29) |
| Depression | 6.35 (0.81)** | 2.88 (0.87) | 4.94 (1.13) | 5.55 (1.958) | 7.13 (1.71)*** | 2.78 (0.75) |
| Anxiety | 7.88 (1.27)** | 3.25 (0.88) | 5.67 (0.84) | 5.50 (1.80) | 10.33 (1.58)*** | 2.61 (0.69) |
| Stress | 7.47 (1.41) | 6.06 (1.32) | 4.78 (1.09) | 9.00 (2.02) | 11.67 (1.73)** | 5.06 (1.25) |
| BIS | 14.94 (2.36) | 15.31 (3.07) | 53.50 (2.47) | 51.90 (2.35) | 53.56 (2.70) | 51.00 (1.88) |
| LARS | −20.22 (1.36)*** | −27.44 (1.24) | −23.50 (1.71)* | −30.00 (1.58) | −22.44 (2.06)* | −27.06 (1.16) |
| UPDRS ON | 18.67 (2.69) | 18.78 (2.85) | 26.50 (2.73) | |||
| UPDRS OFF | 24.56 (3.41)*** | 23.28 (2.97) | 30.44 (2.52)*** | |||
| Years since diagnosis | 4.44 (1.21) | 4.39 (0.90) | 5.00 (1.02) | |||
| Years since symptoms | 5.18 (1.28) | 4.78 (0.86) | 6.44 (1.10) | |||
| LDE (mg) | 566.41 (61.18) | 543.70 (67.36) | 653.00 (93.96) | |||
| # levodopa/ dopamine agonists/both | 12/1/5 | 10/2/6 | 10/0/8 | |||
| # on XL meds | 3 | 10 | 9 | |||
-
MoCA=Montreal Cognitive Assessment, DASS=Depression, Anxiety and Stress Scale, BIS=Barratt Impulsivity Scale, LARS=Lille Apathy Rating Scale, UPDRS=Unified Parkinson’s Disease Rating Scale, LDE=Levodopa Dose Equivalence.
Appendix 2—table 1
The mean BIC and model parameter values for each model for each experiment. The bolded lines show the models with the smallest BIC, which was model number 2, the dual-learning rate model without separate parameters for day 1 conditions.
| Experiment | Model | BIC | on | off | α+ON | α+OFF | α-ON | α-OFF | β |
|---|---|---|---|---|---|---|---|---|---|
| 1 | 1 | 996.243 | 0.1006 | 60.8972 | |||||
| 2 | 885.9434 | 0.1024 | 0.0041 | 9.678 | |||||
| 3 | 992.3985 | 0.0808 | 0.0988 | 36.866 | |||||
| 4 | 891.5522 | 0.1184 | 0.1593 | 0.0184 | 0.0097 | 7.3885 | |||
| 2 | 1 | 520.6029 | 0.1131 | 231.6615 | |||||
| 2 | 485.0105 | 0.1922 | 0.0319 | 21.278 | |||||
| 3 | 510.5098 | 0.1248 | 0.0616 | 116.4691 | |||||
| 4 | 487.6825 | 0.3144 | 0.1825 | 0.0438 | 0.1273 | 7.2812 | |||
| 3 | 1 | 807.0322 | 0.132 | 101.1408 | |||||
| 2 | 737.4145 | 0.2069 | 0.0253 | 5.9512 | |||||
| 3 | 802.9193 | 0.1059 | 0.0624 | 163.4829 | |||||
| 4 | 746.7926 | 0.2918 | 0.1846 | 0.0521 | 0.0555 | 4.104 | |||
Additional files
-
Appendix 1—figure 1—source data 1
Summary statistics for the percentage of win-stay and lose-shift behaviours during learning trials for each experiment.
- https://doi.org/10.7554/eLife.26801.024
Download links
A two-part list of links to download the article, or parts of the article, in various formats.
Downloads (link to download the article as PDF)
Open citations (links to open the citations from this article in various online reference manager services)
Cite this article (links to download the citations from this article in formats compatible with various reference manager tools)
Effects of dopamine on reinforcement learning and consolidation in Parkinson’s disease
eLife 6:e26801.
https://doi.org/10.7554/eLife.26801
