L-DOPA administration shifts the stability-flexibility balance towards attentional capture by distractors during a visual search task

Abstract

Rationale The cognitive control dilemma describes the necessity to balance two antagonistic modes of attention: stability and flexibility. Stability refers to goal-directed thought, feeling, or action and flexibility refers to the complementary ability to adapt to an ever-changing environment. Their balance is thought to be maintained by neurotransmitters such as dopamine, most likely in a U-shaped rather than linear manner. However, in humans, studies on the stability-flexibility balance using a dopaminergic agent and/or measurement of brain dopamine are scarce. Objective The study aimed to investigate the causal involvement of dopamine in the stability-flexibility balance and the nature of this relationship in humans. Methods Distractibility was assessed as the difference in reaction time (RT) between distractor and non-distractor trials in a visual search task. In a randomized, placebo-controlled, double-blind, crossover study, 65 healthy participants performed the task under placebo and a dopamine precursor (L-DOPA). Using 18F-DOPA-PET, dopamine availability in the striatum was examined at baseline to investigate its relationship to the RT distractor effect and to the L-DOPA-induced change of the RT distractor effect. Results There was a pronounced RT distractor effect in the placebo session that increased under L-DOPA. Neither the RT distractor effect in the placebo session nor the magnitude of its L-DOPA-induced increase were related to baseline striatal dopamine. Conclusions L-DOPA administration shifted the stability-flexibility balance towards attentional capture by distractors, suggesting causal involvement of dopamine. This finding is consistent with current theories of prefrontal cortex dopamine function. Current data can neither confirm nor falsify the inverted U-shaped function hypothesis with regard to cognitive control.

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“…Additionally, L-3,4-dihydroxyphenylalanine (L-DOPA), a DA precursor used as a medication in Parkinson's disease, produces alterations in latent inhibition (Polner et al, 2016;Gy€ orfi et al, 2017), even with only a single dose (Gy€ orfi et al, 2017), which signifies more attention allocated to irrelevant cues. This is unlikely to be a phenomenon specific to those with Parkinson's disease, as L-DOPA in healthy normals causes increases in attentional capture by distractors (Riedel et al, 2022). In contrast, DA depletion has been found to increase attentional control on the Stroop-Color Word task (Scholes et al, 2007), and, intriguingly, the same study also found these results with serotonin depletion.…”