Tyrosine promotes cognitive flexibility: Evidence from proactive vs. reactive control during task switching performance
Introduction
One of the most investigated amino acids is tyrosine (TYR). TYR is the biochemical precursor of norepinephrine (NE) and dopamine (DA), which are neurotransmitters of the catecholinergic system. Early research has shown that TYR supplementation, or a TYR-rich diet, increases plasma TYR levels in the blood (Glaeser et al., 1979) and enhances DA and NE release in the brain of rats (Sved and Fernstrom, 1981; Gibson et al., 1983; Acworth et al., 1988) and humans (Growdon et al., 1982; Wurtman, 1992; Deijen, 2005, for a review). Once the optimal level of DA is reached, TYR is no longer transformed to DA because tyrosine hydroxylase, the enzyme that converts TYR into DA, is inhibited (Udenfriend, 1966; Weiner et al., 1977). Previous studies on the effect of TYR on cognition focused mainly on deficits in TYR to DA conversion (e.g. phenylketonuria; Pietz et al., 1995; van Spronsen et al., 1996), on the depletion of TYR (Fernstrom and Fernstrom, 1995; Harmer et al., 2001), or on DA-related diseases (e.g. Parkinson’s disease; Growdon et al., 1982). In healthy individuals, TYR has often been used to reduce the negative effects of conditions that deplete the brain’s dopaminergic resources, such as extreme physical stress. The supply of TYR was found to reduce stress-induced impairments of working memory and attentional tasks, but more so in individuals who were particularly sensitive to the stressors (Deijen and Orlebeke, 1994; Shurtleff et al., 1994; Mahoney et al., 2007).
Only recently, the focus has shifted to the possible beneficial effects of TYR on challenging cognitive performance in the absence of physical stress. Indeed, even without exposure to stress, the supplementation of TYR has been shown to have an acute beneficial effect on challenging task performance thought to be related to DA, such as multitasking (Thomas et al., 1999), the updating and monitoring of working memory (Colzato et al., 2013a), stopping on time (Colzato et al., 2014b), and convergent thinking (Colzato et al. 2014a).
The primary goal of the present study was to examine the effect of TYR on cognitive flexibility, a key cognitive-control function (Miyake et al., 2000). A well-established, reliable indicator of cognitive flexibility is task-switching performance (Monsell, 2003, Miyake et al., 2000). The amount of the time needed to switch between two different tasks can be taken to indicate the efficiency in adapting and restructuring cognitive representations, so that smaller switching costs would reflect a higher level of cognitive flexibility. In this kind of paradigm, the sequence of tasks is often regular and predictable (e.g., AABBAABB…). Accordingly, participants know when to prepare for a task switch, so that the interval between the previous response and the upcoming stimulus (the response-stimulus interval or RSI) represents a preparation interval.
Switching costs in tasks as used in the present study are thought to consist of two major components: a preparatory component and a residual component (e.g., Meiran et al., 2000). In switch trials participants can use the preparation interval (if sufficiently long and sufficiently predictable: Rogers and Monsell, 1995) to reconfigure their cognitive task set to meet the demands of the upcoming task. The shorter the interval the less likely this reconfiguration will be completed before the stimulus is presented, which fits with the observation that switching costs (i.e., the increase of reaction time in task-switching trials relative to task-repetition trials) are more pronounced with short than with long RSIs (Rogers and Monsell, 1995). However, when the RSI is long, the preparatory component is nearly eliminated (Meiran, 1996). What remains is the residual component, the component that is resistant to preparation, e.g., because the stimulus triggers the involuntary activation of the previous task set and/or because completely inhibiting the previous set requires the actual activation of the new task set (see Kiesel et al., 2010). In any case, the residual component reflects processes that occur after target onset on switch trials, regardless of the amount of preparation time (e.g., Monsell, 2003).
According to Cools and D’Esposito (2010), DA modulates cognitive flexibility by facilitating the update of information in working memory such as the current task set. Indeed, the DA-D2 receptor agonist bromocriptine was found to reduce switching costs and was accompanied by a drug-induced potentiation of striatal activity in participants with a low-span baseline in working memory capacity (Cools et al., 2007). The hypothesis that dopaminergic pathways are crucial in driving cognitive flexibility clearly predicts a beneficial effect of TYR, which in our design translates into the prediction of reduced switching costs. However, the existence of multiple DA pathways with to some degree opposite and counter-acting impact on performance (e.g., a frontal pathway associated with goal maintenance and focusing, and a nigrostriatal pathway associated with inhibition and flexibility; Cools, 2008; Cools and D' Esposito, 2010; van Schouwenburg, Aarts and Cools, 2010) makes it difficult to predict whether the preparatory component or the residual component or both would be affected. Accordingly, we manipulated the RSI, so that we were able to dissociate possible effects of TYR on these two components. An effect of TYR on the preparatory component would be visible in a particularly strong TYR effect on switching costs when RSI is short, while an effect of TYR on the residual component would be visible in a particularly strong TYR effect on switching costs when RSI is long.
Section snippets
Participants
Twenty-two undergraduate students of the Leiden University (all females, mean age=19.3 years, SD=1.5, range 17–23; mean Body Mass Index=20.9, SD=1.5, range 19–23; all right-handed) with no cardiac, hepatic, renal, neurological or psychiatric disorders, personal or family history of depression, migraine and medication or drug use participated in the experiment. All participants were selected individually via a phone interview by the same lab-assistant using the Mini International
Task-switching performance
Table 1 provides an overview of the outcomes for reaction times (RTs) and percentage of errors (PEs). RTs revealed a significant main effect of Task Repetition, F(1,21)=112.63, p<0.001, η2p=0.84; and of RSI, F(1,21)=19.53, p<.001, η2p=0.48. These two main effects were involved in two-way interaction, F(1,21)=20.67, p<0.001, η2p=0.50, and in a three-way interaction involving condition, F(1,21)=4.45, p=0.047, η2p=0.18.
Fisher LSD post-hoc tests showed that switching costs differed significantly
Discussion
Our findings show that TYR, the precursor of DA, modulates cognitive flexibility as measured by a task-switching paradigm. Participants showed smaller switching costs after the intake of TYR than of a neutral placebo when the preparation interval to switch was long, but not when it was short. This implies that TYR impacts the residual, but not the preparatory, component of switching costs. An effect on the preparatory component might be due to either the speed of task-set retrieval and
Acknowledgments
The research of L.S. Colzato is supported by a Vidi grant (#452-12-001) of the NWO (Netherlands Organization for Scientific Research). The data reported in this paper are archived in the Open Science Framework (OSF) and are available through https://osf.io/aqrzb/?view_only=906a14b7676145278728a6a2cbfb24ef
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