Previous studies have shown that dopaminergic replacement improves learning from positive feedback but impairs learning from negative feedback while withdrawal from anti-Parkinsonian medication leads to the reverse profile10, 19
. Contrary to this, we found that PD+ ICB patients showed increased learning from positive vs. negative feedback off medication compared to on medication, whereas PD patients without ICB in our study showed a trend towards the previously described learning effects10
. Furthermore, the group by session by valence interaction was significant, such that these learning effects were significantly complimentary.
PET studies of dopamine release have shown that dopamine medication leads to elevated ventral striatal dopamine release in PD+ ICB patients relative to PD patients without ICB 20, 21
. Furthermore, studies in healthy human subjects have shown that PET measures of dopamine synthesis rates in the striatum correlate with increased learning from positive feedback relative to negative feedback and deleterious effects of dopamine agonists in normal subjects with high baseline dopamine synthesis rates have also been reported 22
. These observations and our results are consistent with the hypothesis that PD+ ICB patients have elevated baseline dopamine levels in the ventral striatum, and that dopamine replacement therapy increases the levels further, causing reduced learning from positive feedback. This might be explained by the “inverted U” shape hypothesis 23, 24
where cognitive performance and the ability to pick the rewarded stimulus might be impaired when PD+ ICB subjects are pushed off the upper end of the curve by their medication.
Previous authors have described the premorbid Parkinsonian personality
as one characterised by caution, risk aversion and anhedonia 25
. In contrast PD+ ICB patients have a behavioural profile characterized by increased impulsiveness or novelty seeking 26
similar to subjects prone to substance abuse and behavioural addictions 27
. Impulsive individuals are more sensitive to reward than punishment 28
and resemble the unmedicated PD+ ICB patients in this study.
The risk task was designed to test the hypothesis that patients with ICB are more risk-prone than non- ICB patients 26
. Overall PD+ ICB patients showed a trend to be more risk prone relative to normal PD, which did not reach significance. However those PD+ ICB patients who had PG were significantly more risk prone compared to the PD group. Impaired decision making with an increased tendency towards risky behaviour has also been found in pathological gamblers 29
. Furthermore dopaminergic medication led to increased risk preference in the PD patients relative to the healthy controls, and just missed significance in the ICB patients vs. healthy controls. This is particularly interesting since risk taking decreases with age 30
and the PD group without ICB showed a trend to be older compared to the other two groups. These findings are consistent with two recently published studies which showed that dopamine agonist treatment lead to an increased novelty and reward seeking behaviour and in a reduction of negative feedback learning 31, 32
Working memory in the forward and backward digit span was significantly reduced in PD+ ICB patients compared to the PD and the control group. PD patients without impulsive behaviour showed impairment in the digit backward span test compared to healthy controls, which is in agreement with a recent publication 33
. We did not find any improvement of WM after L-dopa administration. Previous studies have shown that working memory is reduced in impulsive patients with attention deficit/hyperactivity disorder and healthy controls who scored highly on an impulsivity questionnaire and that these subjects had lower total striatal dopamine levels which seem to be associated with lower working memory capacity 34, 35
. These Other studies have shown impaired spatial memory in patients with impulse control disorders36
We have demonstrated a different learning profile between PD patients with and without ICB and healthy controls. These differences could be explained by higher ventral striatal dopamine levels in PD+ ICB patients. In addition PD patients with pathological gambling were more risk prone compared to normal PD patients and healthy controls. These findings may have therapeutic and clinical implications. The reduction in the overall anti- parkinsonian medication with positive reinforcement of non impulsive behaviour is likely to be more beneficial than aversion therapy in PD patients with impulsive compulsive behaviours.