Baseline-dependent effect of dopamine’s precursor L-tyrosine on working memory gating but not updating

Abstract

Adaptive goal-directed behavior requires a dynamic balance between maintenance and updating within working memory (WM). This balance is controlled by an input-gating mechanism implemented by dopamine in the basal ganglia. Given that dopaminergic manipulations can modulate performance on WM-related tasks, it is important to gain mechanistic insight into whether such manipulations differentially affect updating (i.e., encoding and removal) and the closely-related gate opening/closing processes that respectively enable/prevent updating. To clarify this issue, 2.0 g of dopamine’s precursor L-tyrosine was administered to healthy young adults (N = 45) in a double-blind, placebo-controlled, within-subjects study. WM processes were empirically distinguished using the reference-back paradigm, which isolates performance related to updating, gate opening, and gate closing. L-tyrosine had a selective, baseline-dependent effect only on gate opening, which was evidenced by markedly reduced variance across subjects in gate opening performance in the L-tyrosine compared with the placebo condition, whereas the whole-sample average performance did not differ between conditions. This indicates a pattern of results whereby low-performing subjects improved, whereas high-performing subjects were impaired on L-tyrosine. Importantly, this inverted U-shaped pattern was not explained by regression to the mean. These results are consistent with an inverted-U relationship between dopamine and WM, and they indicate that updating and gating are differentially affected by a dopaminergic manipulation. This highlights the importance of distinguishing these processes when studying WM, for example, in the context of WM deficits in disorders with a dopaminergic pathophysiology.