RT Journal Article SR Electronic T1 Neuro-Cognitive Effects of Acute Tyrosine Administration on Reactive and Proactive Response Inhibition in Healthy Older Adults JF eneuro JO eNeuro FD Society for Neuroscience SP ENEURO.0035-17.2018 DO 10.1523/ENEURO.0035-17.2018 A1 Mirjam Bloemendaal A1 Monja Isabel Froböse A1 Joost Wegman A1 Bram Bastiaan Zandbelt A1 Ondine van de Rest A1 Roshan Cools A1 Esther Aarts YR 2018 UL http://www.eneuro.org/content/early/2018/04/18/ENEURO.0035-17.2018.abstract AB The aging brain is characterized by altered dopamine signaling. The amino acid tyrosine, a catecholamine precursor, is known to improve cognitive performance in young adults, especially during high environmental demands. Tyrosine administration might also affect catecholamine transmission in the aging brain, thereby improving cognitive functioning. In healthy older adults, impairments have been demonstrated in two forms of response inhibition: reactive inhibition (outright stopping) and proactive inhibition (anticipatory response slowing) under high information load. However, no study has directly compared the effects of a catecholamine precursor on reactive and load-dependent proactive inhibition. In this study we explored the effects of tyrosine on reactive and proactive response inhibition and signal in dopaminergically innervated fronto-striatal regions. Depending on age, tyrosine might lead to beneficial or detrimental neurocognitive effects. We aimed to address these hypotheses in 24 healthy older human adults (aged 61-72 years) using fMRI in a double blind, counterbalanced, placebo-controlled, within-subject design. Across the group, tyrosine did not alter reactive or proactive inhibition behaviorally, but did increase fronto-parietal proactive inhibition-related activation. When taking age into account, tyrosine affected proactive inhibition both behaviorally and neurally. Specifically, increasing age was associated with a greater detrimental effect of tyrosine compared with placebo on proactive slowing. Moreover, with increasing age, tyrosine decreased fronto-striatal and parietal proactive signal, which correlated positively with tyrosine’s effects on proactive slowing. Concluding, tyrosine negatively affected proactive response slowing and associated fronto-striatal activation in an age-dependent manner, highlighting the importance of catecholamines, perhaps particularly dopamine, for proactive response inhibition in older adults.Significance Statement Healthy aging comes with altered dopamine functioning and is associated with reduced performance on cognitive control tasks, such as response inhibition. However, it is yet unclear whether reactive or proactive response inhibition is modulated by dopamine. We addressed this question by administering the catecholamine precursor tyrosine in a double blind, placebo-controlled, randomized intervention study. Tyrosine decreased proactive response slowing, not reactive stopping, as a function of increasing age. Concurrently, proactive fronto-striatal and parietal BOLD signal decreased after tyrosine with increasing age. These findings, especially in striatum, demonstrate that proactive, rather than reactive response inhibition, is dopamine dependent. Moreover, tyrosine’s effect on brain and cognition became detrimental with increasing age, questioning the cognitive enhancing potential of tyrosine in healthy aging.