Neuro-Cognitive Effects of Acute Tyrosine Administration on Reactive and Proactive Response Inhibition in Healthy Older Adults

Abstract

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.

Catecholaminergic modulation of the cost of cognitive control in healthy older adults

“…Included participants were also familiarized during the screening session with the cognitive test battery that was administered during the subsequent experimental sessions. This familiarization consisted of practice of a response inhibition task [41], a working memory task [cf. 51,52] and the N-back task [see §2.4, based on 16].…”

“…Sessions started approximately at the same time of the day (maximal deviation was 90 minutes), with an interval of one week to a max of 17 weeks between testing days. After informed consent, participants practiced the response-inhibition task [41], and right after drug administration (see Table 1. Data from questionnaires, neuropsychological assessment (NPA), mood, blood pressure and urine metabolites.…”

“…N-back) task was timed to immediately follow ingestion of the intervention, so that tyrosine was highly unlikely to have taken effect during task execution, given its delay in reaching peak concentrations (±2 hours, see §2.3). Then, after a break of 90 minutes, the response inhibition task [41]) and working memory task [cf. 52] were administered during fMRI.…”

“…Higher doses of tyrosine have been shown to increase plasma tyrosine concentrations to a greater degree in older than younger adults [40], and have been associated with poorer N-back performance than lower tyrosine doses [40]. Furthermore, tyrosine was recently found to reduce proactive response inhibition as a function of age [41]. Although we do not have direct measures of baseline catecholamine function in our sample, we explored in supplemental analyses whether the effects of tyrosine depended on two commonly used proxy measures of baseline dopamine levels: trait impulsivity and working memory capacity [see also 4,42]: trait impulsivity scores for their association with dopamine (auto)receptor availability and striatal dopamine release [24], as well as working memory span, associated with striatal dopamine synthesis capacity [43,44].…”

Catecholaminergic modulation of the cost of cognitive control in healthy older adults

“…Sessions started approximately at the same time of the day (maximal deviation was 90 minutes), with an interval of one week to a max of 17 weeks between testing days. After informed consent, participants practiced the response-inhibition task (see 39), and right after drug administration (see §2.3), each level of the N-back task was rehearsed followed by the practice of another working memory task (cf. 51).…”