In zahlreichen Studien zum Belohnungslernen konnte gezeigt werden, dass Dopamin Verhaltensweisen verstärkt, die für 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-unabhängiges, implizites Lernen unter der grundsätzlichen Annahme analysiert, dass Lernmodulation durch Dopamin allgemein und nicht ausschließlich 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 gleichhäufige Stimuli in pseudorandomisierter Reihenfolge präsentiert. Einer dieser Stimuli fungierte als Zielreiz‚ dem während einer ‚Konditionierungsphase’ zunächst immer der gleiche Stimulus (Precue) vorausging. In der nachfolgenden ‚Dekonditionierungsphase’ 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, während keine Reaktion nach allen anderen Stimuli gefordert war. In der Nogo-Aufgabe sollte nach jedem nicht-Zielreiz ein Tastendruck erfolgen, während nur nach Erscheinen des Zielreizes der Tastendruck unterdrückt werden sollte.
Kernergebnis der Untersuchung war, dass die Aufgabenperformanz von Patienten im OFF der von gesunden Kontrollprobanden ähnelte, sich jedoch deutlich von der Performanz im ON unterschied: Patienten im OFF und Kontrollprobanden zeigten einen Fehleranstieg in der Dekonditionierungsphase der Nogo-Aufgabe, während 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, während dies in der Nogo-Aufgabe nicht der Fall war.
Die Fehleranstiege in der Dekonditionierungsphase können in erster Linie als ‚Carry-Over-Effekte’ im Sinne der Fortführung von in der Konditionierungsphase erlernten Verhaltensmustern verstanden werden. Die Modulation dieser Effekte durch
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Levodopa-Medikation weist darauf hin, dass die Verfügbarkeit von Dopamin das Erlernen ‚neutraler’, 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 Zusammenhängen (Go-Aufgabe) ‚habituelles’ Verhalten verstärken, während sie ─ entsprechend Ergebnissen aus dem Bereich des Belohnungslernens ─ implizite Lernleistungen eher abschwächen, sofern eine inhibitorische Leistung zu erbringen ist (Nogo-Bedingung). Aus klinischer Sicht ist diese Interpretation vor allem hinsichtlich verstärkter Passivität von Parkinsonpatienten von modellhaftem Interesse.
Entsprechenden Verhaltensweisen könnten demnach ─ nebst Krankheits-inhärenten
─ auch erlernte Faktoren zugrunde liegen, da dopaminerge Medikation in allen selektiven Handlungszusammenhängen (in denen auf nur einen aus vielen
‚neutralen’ Reizen zu reagieren bzw. zu handeln ist) das inaktive Grundverhalten verstärken würde.
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Curriculum vitae
Mein Lebenslauf wird aus datenschutzrechtlichen Gründen in der elektronischen Version meiner Arbeit nicht veröffentlicht.
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Publikation
Die Daten der vorliegenden Arbeit bildeten die Grundlage für die folgend genannte Publikation:
Marzinzik, F., Wotka, J., Wahl, M., Krugel, L.K., Kordsachia, C., Klostermann, F.:
Modulation of habit formation by levodopa in Parkinson's disease (PLoS One.
2011;6(11):e27695. Epub 2011 Nov 16.).
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Danksagung
Mein Dank gilt als erstes allen Probanden, die an der Studie teilnahmen. Ein weiterer großer Dank geht an meinen Doktorvater PD Dr. Fabian Klostermann, der mich über die gesamte Dauer des Projekts mit großem persönlichem Engagement und viel Zeit unterstützt hat.
Weiterhin zu Dank verpflichtet bin ich den anderen Mitgliedern der Arbeitsgruppe
„Kognition und Motorik“ des CBF, insbesondere Dr. Frank Marzinzik, Dr. Michael Wahl und Catarina Kordsachia für die Hilfe bei der Erhebung und Auswertung der verwendeten Daten.
Als letztes möchte ich meinen Eltern, Irma und Hans - Erwin Wotka, für ihre großartige Unterstützung nicht nur bei der Entstehung dieser Arbeit, sondern über den Verlauf meines gesamten Medizinstudiums danken.