Proefschrift_Holstein

Striatal dopamine and motivated cognitive control

Conclusion Imagine again that you are a squirrel. You are still in the forest, alternating between collecting nuts and berries. You have just collected a nut, but now you see a larger berry (i.e. another task) coming up. What happens in your squirrel brain? Well, I would speculate (based on the existent literature and the work in this thesis) that the appearance of the large berry (i.e. a large reward) will elicit a dopamine response in your midbrain. The projections of these dopamine neurons to your ventral striatum will increase the sensitivity of your ventral striatum to input from your prefrontal cortex. These reward-related signals in the ventral striatum will enhance processing in the regions involved in flexible updating. This may occur via a number of routes. First, these reward-related signals will alter signalling in the dorsal parts of the striatum via the spiralling dopamine connections in the midbrain (thereby increasing the stimulation of dopamine D2 receptors in the caudate nucleus, causing a D2-dominated state thereby enabling you to quickly update the new task set). Alternatively (or concurrently) these signals in the striatum act by changing the gating mechanism from the striatum to the ‘cognitive’ prefrontal cortex and subsequently the other regions in the cognitive corticostriatal circuit. If the berry you are about to collect is smaller, then the updating signals in your cognitive control network will also be smaller, leading to less flexible updating of your task sets. In conclusion, the research in this thesis aimed to elucidate the causal role for striatal dopamine and the corticostriatal network during the integration of reward and flexible cognitive control. We showed that dopaminergic manipulation with methylphenidate indeed changed motivation-cognition signalling in the striatum. In addition, a causal role for the ventral striatum in motivated cognitive control was established, followed by evidence for frontal modulation of striatal processing during the integration of signals related to motivation, cognition, and action across subparts of the striatum. Together, these results are in line with a role for striatal dopamine in motivated cognitive control, and they show that integration across corticostriatal circuits is involved in this process.

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