Author(s): ARENALES ARAUZ, Y., OMEJC, N., DE PAUW, K., MARUSIC, U., ROELANDS, B., Institution: VRIJE UNIVERSITEIT BRUSSEL, BELGIUM, Country: BELGIUM, Abstract-ID: 1385

INTRODUCTION:
Physical fatigue impairs cognitive control, with significant consequences for performance (1,2). However, it remains unclear whether fatigue-related inhibitory impairments arise from distinct catecholaminergic mechanisms and how these shape neural control dynamics. By combining pharmacological modulation and electroencephalography (EEG), this study examined whether dopaminergic and noradrenergic systems differentially influence behavioural performance and the neural stages of response execution and inhibition following physical fatigue.
METHODS:
Eighteen healthy adults (9 female; 23.4±2.2 years) completed a randomised, triple-blind, placebo-controlled crossover study. On separate visits, participants received methylphenidate (20 mg MPH; dopaminergic reuptake inhibitor), reboxetine (8 mg REB; selective noradrenaline reuptake inhibitor), or placebo. Physical fatigue was induced by repeated bilateral leg extensions to task failure (3). Cognitive performance was assessed pre- and post-fatigue using a Go/NoGo task. Go trials measured response speed and sustained attention; NoGo trials measured inhibitory control. Outcomes were reaction time and accuracy. EEG was recorded during cognitive task performance, and event-related potentials were derived, with N2 and P3 components quantified from frontal–central and central–parietal clusters. Sample size was supported by an a priori simulation-based sensitivity analysis for drug × time interactions. Data were analysed using mixed-effects models with subject-level random intercepts.
RESULTS:
Go reaction time was faster under MPH than placebo at baseline and post-fatigue (p=0.015), indicating enhanced response execution. Go accuracy declined following fatigue regardless of drug condition (p = 0.017). In NoGo trials, accuracy decreased after fatigue under placebo but was maintained under MPH, resulting in a drug × time interaction (p=0.008). At the neural level, fatigue reduced central–parietal P3 amplitude during Go trials (p=0.031), indicating diminished stimulus evaluation. In NoGo trials, MPH induced shorter frontal–central N2 latencies (p=0.038), reflecting earlier inhibitory processing. A drug × fatigue interaction was observed for frontal–central P3 latency (p = 0.047), showing that MPH prevented fatigue-related delays in later inhibitory stages. REB did not modulate behavioural or neural outcomes.
CONCLUSION:
By dissociating catecholaminergic contributions across neural stages of inhibition, this study provides important mechanistic evidence that dopamine is a key neurochemical for the maintenance of cognitive capacity under physical stress. These findings advance understanding of fatigue-related performance decline and inform strategies to sustain cognitive capacity under high physical demands.

1. Itagi et al. (2018), Ann Neurosci., 25(4):299-304
2. Finkenzeller et al. (2018),J Appl Physiol, 118(12):2509-2521
3. Arauz et al. (2026), Eur J Sport Sci, 26(2):e70119