10 research outputs found
Modulation of Habit Formation by Levodopa in Parkinson's Disease
Dopamine promotes the execution of positively reinforced actions, but its role for the formation of behaviour when feedback is unavailable remains open. To study this issue, the performance of treated/untreated patients with Parkinson's disease and controls was analysed in an implicit learning task, hypothesising dopamine-dependent adherence to hidden task rules. Sixteen patients on/off levodopa and fourteen healthy subjects engaged in a Go/NoGo paradigm comprising four equiprobable stimuli. One of the stimuli was defined as target which was first consistently preceded by one of the three non-target stimuli (conditioning), whereas this coupling was dissolved thereafter (deconditioning). Two task versions were presented: in a âGo versionâ, only the target cue required the execution of a button press, whereas non-target stimuli were not instructive of a response; in a âNoGo versionâ, only the target cue demanded the inhibition of the button press which was demanded upon any non-target stimulus. Levodopa influenced in which task version errors grew from conditioning to deconditioning: in unmedicated patients just as controls errors only rose in the NoGo version with an increase of incorrect responses to target cues. Contrarily, in medicated patients errors went up only in the Go version with an increase of response omissions to target cues. The error increases during deconditioning can be understood as a perpetuation of reaction tendencies acquired during conditioning. The levodopa-mediated modulation of this carry-over effect suggests that dopamine supports habit conditioning under the task demand of response execution, but dampens it when inhibition is required. However, other than in reinforcement learning, supporting dopaminergic actions referred to the most frequent, i. e., non-target behaviour. Since this is passive whenever selective actions are executed against an inactive background, dopaminergic treatment could in according scenarios contribute to passive behaviour in patients with Parkinson's disease
Differential Influence of Levodopa on Reward-Based Learning in Parkinson's Disease
The mesocorticolimbic dopamine (DA) system linking the dopaminergic midbrain to the prefrontal cortex and subcortical striatum has been shown to be sensitive to reinforcement in animals and humans. Within this system, coexistent segregated striato-frontal circuits have been linked to different functions. In the present study, we tested patients with Parkinson's disease (PD), a neurodegenerative disorder characterized by dopaminergic cell loss, on two reward-based learning tasks assumed to differentially involve dorsal and ventral striato-frontal circuits. 15 non-depressed and non-demented PD patients on levodopa monotherapy were tested both on and off medication. Levodopa had beneficial effects on the performance on an instrumental learning task with constant stimulus-reward associations, hypothesized to rely on dorsal striato-frontal circuits. In contrast, performance on a reversal learning task with changing reward contingencies, relying on ventral striato-frontal structures, was better in the unmedicated state. These results are in line with the âoverdose hypothesisâ which assumes detrimental effects of dopaminergic medication on functions relying upon less affected regions in PD. This study demonstrates, in a within-subject design, a double dissociation of dopaminergic medication and performance on two reward-based learning tasks differing in regard to whether reward contingencies are constant or dynamic. There was no evidence for a dose effect of levodopa on reward-based behavior with the patientsâ actual levodopa dose being uncorrelated to their performance on the reward-based learning tasks
The impact of Levodopa on implicit learning in patients with Parkinson's disease
In zahlreichen Studien zum Belohnungslernen konnte gezeigt werden, dass
Dopamin Verhaltensweisen verstĂ€rkt, die fĂŒr das Individuum positive
Konsequenzen haben. Ob und, wenn ja, welche Funktionen Dopamin in
Lernsituationen hat, in denen Handlungen weder belohnt noch negativ bewertet
werden, ist allerdings noch unklar. In der vorliegenden Studie wurde der
Einfluss von Dopamin auf Feedback-unabhÀngiges, implizites Lernen unter der
grundsÀtzlichen Annahme analysiert, dass Lernmodulation durch Dopamin
allgemein und nicht ausschlieĂlich im Kontext bewusst erlebter
Verhaltensgratifikation oder -sanktion stattfindet. Dazu bearbeiteten nebst
gesunden Kontrollprobanden Levodopa-behandelte Parkinsonpatienten im
medikamentösen OFF und ON zwei Aufgaben. Den Probanden wurden wiederholt vier
gleichhÀufige Stimuli in pseudorandomisierter Reihenfolge prÀsentiert. Einer
dieser Stimuli fungierte als Zielreizâ dem wĂ€hrend einer
âKonditionierungsphaseâ zunĂ€chst immer der gleiche Stimulus (Precue)
vorausging. In der nachfolgenden âDekonditionierungsphaseâ wurde diese Precue-
Zielreiz-Kopplung aufgehoben, ohne dass dieses Schema den Teilnehmern bewusst
(gemacht) wurde. In der Go-Aufgabe sollte nach Erscheinen des Zielreizes ein
Tastendruck erfolgen, wÀhrend keine Reaktion nach allen anderen Stimuli
gefordert war. In der Nogo-Aufgabe sollte nach jedem nicht-Zielreiz ein
Tastendruck erfolgen, wÀhrend nur nach Erscheinen des Zielreizes der
Tastendruck unterdrĂŒckt werden sollte. Kernergebnis der Untersuchung war, dass
die Aufgabenperformanz von Patienten im OFF der von gesunden Kontrollprobanden
Ă€hnelte, sich jedoch deutlich von der Performanz im ON unterschied: Patienten
im OFF und Kontrollprobanden zeigten einen Fehleranstieg in der
Dekonditionierungsphase der Nogo-Aufgabe, wÀhrend sich im Verlauf der Go-
Aufgabe keine Unterschiede der Fehlerrate entwickelten. Umgekehrt trat ein
Fehleranstieg bei Patienten im Levodopa-ON nur in der Dekonditionierungsphase
der Go-Aufgabe auf, wÀhrend dies in der Nogo-Aufgabe nicht der Fall war. Die
Fehleranstiege in der Dekonditionierungsphase können in erster Linie als
âCarry-Over-Effekteâ im Sinne der FortfĂŒhrung von in der Konditionierungsphase
erlernten Verhaltensmustern verstanden werden. Die Modulation dieser Effekte
durch Levodopa-Medikation weist darauf hin, dass die VerfĂŒgbarkeit von Dopamin
das Erlernen âneutralerâ, also weder belohnter noch sanktionierter,
Verhaltensweisen beeinflusst. Die differentiellen Effekte in Go- versus Nogo-
Aufgabe wurden als Hinweis darauf verstanden, dass hohe Spiegel (in erster
Linie innerhalb des dopaminergen mesokortikalen Systems) in pro-exekutiven
ZusammenhĂ€ngen (Go-Aufgabe) âhabituellesâ Verhalten verstĂ€rken, wĂ€hrend sie â
entsprechend Ergebnissen aus dem Bereich des Belohnungslernens â implizite
Lernleistungen eher abschwÀchen, sofern eine inhibitorische Leistung zu
erbringen ist (Nogo-Bedingung). Aus klinischer Sicht ist diese Interpretation
vor allem hinsichtlich verstÀrkter PassivitÀt von Parkinsonpatienten von
modellhaftem Interesse. Entsprechenden Verhaltensweisen könnten demnach â
nebst Krankheits-inhĂ€renten â auch erlernte Faktoren zugrunde liegen, da
dopaminerge Medikation in allen selektiven HandlungszusammenhÀngen (in denen
auf nur einen aus vielen âneutralenâ Reizen zu reagieren bzw. zu handeln ist)
das inaktive Grundverhalten verstĂ€rken wĂŒrde.Several studies investigating the effect of Levodopa on reward-based learning
in Patients with Parkinsonâs disease (PD) showed a Levodopa-dependent
reinforcement of behaviors resulting in positive consequences for the
individual. Whether an impairment of reward - independent implicit learning in
PD is linked to dopaminergic medication or to the disease itself remains
uncertain. In This study we analyzed the performance of 16 PD patients on and
off Levodopa monotherapy and a healthy control group of 14 volunteers in two
implicit learning tasks. In both tasks, four different stimuli were presented
on a computer screen in pseudorandmized order. One of the stimuli was marked
as a Target - Stimulus. In the first task, called the âGoâ task, participants
were instructed to perform a button press only whenever a Target stimulus
appeared. On the appearance of the other three stimuli the button press had to
be withheld. In the second task, called the âNogoâ task the button press had
to be withheld on the appearance of the target stimulus, whereas it had to be
performed after every non-target stimulus. During a set of 120 stimuli, called
conditioning â sequence, the target was always preceded by the same non-
target, called precue. Thereafter, a set of 40 stimuli, called deconditioning
sequence, without precue-target coupling followed. The overall number of
conditioning - deconditioning blocks was 5, so one task consisted of 800
stimuli. Our results showed that, once off levodopa, Patients did not perform
significantly different than the participants in the control group. However,
on levodopa patients made significantly more omission - mistakes in the
deconditioning â sequence of the Go-task and significantly less commission â
mistakes in the Nogo task than participants in the control group. These
results indicate that the substitution of Levodopa in PD influences implicated
learning in a way that promotes passive behavior under pro-executive
conditions
Errors in the Go version of the task.
<p>In the Go version of the task, erroneous reactions to target signals were response omissions. The average target omission rate is displayed per group over blocks of 40 presentations over the 120 presentations during conditioning (blocks 1 to 3, labelled C1, C2 and C3) and the subsequent 40 presentations during deconditioning (block 4, labelled D). The error bars indicate the standard error of the mean. Note the significant increase of response omissions during deconditioning compared to any of the conditioning blocks in patients with Parkinson's disease on levodopa (indicated by asterisks), which was not found in patients in and patients off levodopa and healthy subjects.</p
Reaction times during conditioning and deconditioning.
<p>Average reaction times are displayed per group over blocks of 40 presentations, exemplified by the responses to non-target cues in the NoGo task version with the highest number of responses (no difference was obtained between task versions). Since conditioning-deconditioning sequences comprised 120 presentations during conditioning followed by 40 presentations during deconditioning, block 1 to 3 (labelled C1, C2 and C3) reflect performance during conditioning, whereas block 4 (labelled D) equates to deconditioning. The error bars indicate the standard error of the mean. Note that reaction times increased significantly during deconditioning compared to any of the conditioning blocks (indicated by asterisks) over all groups.</p
Task structure.
<p>Four neutral and equiprobable symbols were presented in pseudorandomised order, one of which was defined as target signal. During a conditioning phase of 120 signal presentations, the target was always preceded by one of the three non-target signals (precue). Over the subsequent 40 presentations, this precue-target coupling was dissolved (deconditioning phase). The conditioning-deconditioning sequence (comprising 160 presentations) was repeated five times with alternating precues. To avoid conscious recognition of the task structure, one-minute pauses were held every 200 trials. Thus, conditioning and deconditioning phases never appeared at the same point in time with respect to the breaks.</p
Errors in the NoGo version of the task.
<p>In the NoGo version of the task, erroneous reactions to target signals were executed responses (commission errors). The average rate of target commission errors is displayed per group over blocks of 40 presentations over the 120 presentations during conditioning (blocks 1 to 3, labelled C1, C2 and C3) and the subsequent 40 presentations during deconditioning (block 4, labelled D). The error bars indicate the standard error of the mean. Note the significant increase of commission errors during deconditioning compared to any of the conditioning blocks in healthy subjects and patients with Parkinson's disease off levodopa (indicated by asterisks), whereas in patients on levodopa this effect could not be detected.</p
Clinical data.
<p>Patients differed between on and off levodopa states and from controls with respect to the scores in the Unified Parkinson's Disease Rating Scale (UPDRS). Normal values without significant differences between groups were obtained in the Beck Depression Inventory (BDI), the Mini Mental State Examination (MMSE) and the Fatigue Severity Scale (FSS). All data are provided as mean values ± standard deviation.</p