Proefschrift_Holstein

Chapter 8

striatum and a cortical region involved in attention processing, i.e. the intraparietal sulcus (Padmala and Pessoa, 2011). This is illustrated further (and causally) in chapter 7 , where we show that manipulating the prefrontal cortex with TMS has effects on the integration across task-related goals in the striatum without directly altering processing in the cortex. In fact, activity in chapter 4 was not restricted to the striatum, but was also revealed in the posterior cingulate cortex, an area that is connected to the dorsal striatum (Di Martino et al., 2008; Beckmann et al., 2009), suggesting indeed that processing in the corticostriatal network was altered during motivated cognitive control in these patients. The absence of significant effects in the striatum in studies that report prefrontal effects does not necessarily imply that the striatum is not playing a role in the underlying process. Instead, the measurement technique in studies that report effects in the prefrontal cortex may simply not be sufficiently sensitive to detect changes in striatal BOLD response. The BOLD signal in the ventral part of the brain, including the striatum is more susceptible to signal drop out. Functional MRI may therefore generally be more sensitive to changes in signal in ‘cognitive’ dorsal cortical regions. Taking into account the DAT1 genotype to account for inter-individual differences in dopamine signalling in our work (e.g. chapter 4 and (Aarts et al., 2010)) can increase the sensitivity to detect changes in the striatum. These studies are generally in line with the idea that reward changes processing in the cognitive control region involved in the task at hand. And they suggest that the prefrontal cortex and striatumcan act in concert tomediate the interaction between different task aspects. However, in chapter 1 we argued and illustrated that reward motivation can have opposite effects on cognitive flexibility and stability and we argued that this effect may be due to opposing effect of dopamine on cognitive flexibility and stability (Durstewitz and Seamans, 2008). The idea that dopamine can be detrimental for cognitive focussing was demonstrated recently in a study using a Stroop task (Aarts et al., 2014b), for which good task performance requires a stable task representation (i.e. not be distracted by the irrelevant dimension in the incongruent condition). Importantly, rewarded Stroop performance was associated with dopamine levels (i.e. dopamine synthesis capacity). More specifically, increased dopamine levels in this study were associated with a detrimental effect of reward on cognitive performance. The work in this thesis focused on cognitive flexibility, and did not formally manipulate stability. However, whereas one may think of switch trials as a form of cognitive flexibility, performance on repeat trials will likely benefit from stable task representations. The results in chapter 5 revealed opposing age-related effect of reward motivation on switch and repeat trials, suggesting that (reward and age-induced changes in) dopamine can have opposite effects on cognitive flexibility and cognitive focussing ( limitations ). The number of studies that assessed the role of striatal dopamine in mediating the integration between reward and cognitive control (whether it is flexible control or maintaining stable task representations) is scarce. Therefore it remains unclear which factors determine whether the effects of dopamine are beneficial or detrimental for cognitive control. Reward-induced changes in dopamine may modulate how susceptible the cognitive (dorsal) striatum is for input from the reward (ventral) striatum or

170