Thesis defense Ruben van den Bosch (Donders series 539)

25 May 2022

Promotors: prof. dr. R. Cools, prof. dr. J. Booij

On the role of striatal dopamine in methylphenidate action on reinforcement learning: A large [18F]DOPA PET/fMRI study

Cognitive control enables the flexible and adaptive behavior that is such a hallmark of the human brain, but lapses of cognitive control are common in both health and disease. Psychostimulants, such as methylphenidate (Ritalin®), can have cognitive control enhancing effects, and their use has drastically increased by both patients and healthy people. However, the drug's effects vary greatly between people and contexts, signaling the need for a better understanding of the neural mechanisms of methylphenidate's effects and the source of the variability therein.
In this thesis, Ruben van den Bosch found that methylphenidate acts on the neurotransmitter dopamine in the striatum to influence how that brain region gates cognitive control signals from the prefrontal cortex. Furthermore, the work established that the effects of dopaminergic drugs in a specific individual depend on the person's baseline state of the striatal dopamine system. This demonstrates the importance of taking the baseline state of the striatal dopamine system into account when interpreting dopaminergic drug effects on cognition, tailoring dopaminergic treatment of psychiatric disorders to the individual patient, and when using psychostimulants for cognitive enhancement.