Thesis defense Mirjam Bloemendaal (Donders series 265)

8 May 2017

Promotor: Prof. dr. R. Cools, copromotor: dr. E. Aarts

Neural mechanisms of cognitive control: modulation by age and dopamine

In this thesis, the neural mechanisms of cognitive control processes were probed by dopamine, cognitive load and age. The work in this thesis extends knowledge on cognitive control processes such as working memory and response inhibition in several ways. Firstly, I provided evidence for the role of the dopamine D2 receptor stimulation in working memory distractibility, its accompanying delay-related PFC signal and connectivity with posterior sensory areas. Secondly, both working memory maintenance and updating were shown to be impaired in aging. Third, working memory performance in older adults decreased as a function of increasing doses of the dopamine precursor tyrosine, associated with increased plasma tyrosine responses, suggesting that altered intestinal processing with age contributes to over-stimulation of dopaminergic neurons. Fourth, aging was associated with impaired reactive as well as proactive response inhibition, specifically under increasing information load and associated with load dependent BOLD signal alterations in fronto-striatal regions. Fifth, the effects of tyrosine administration in healthy older adults implicate dopamine in proactive response inhibition, influencing fronto-striatal regions. Furthermore, I showed that tyrosine can enhance as well as impair proactive control in healthy older adults, depending on age.

In sum, cognitive control processes, such as working memory and proactive response inhibition, are challenged by cognitive load and age and affect cortical as well as subcortical cognitive control regions. Beneficial effects of the dopamine precursor tyrosine depend on dose and age, where a high dose and high age result in negative effects on neurocognitive measures.