Abstract
Performance typically peaks at moderate arousal levels, consistent with the Yerkes-Dodson law, as confirmed by recent human and mouse pupillometry studies. Arousal states are influenced by neuromodulators like catecholamines (noradrenaline; NA and dopamine; DA) and acetylcholine (ACh). To explore their causal roles in this law, we pharmacologically enhanced arousal while measuring human decision-making and spontaneous arousal fluctuations via pupil size. The catecholaminergic agent atomoxetine (ATX) increased overall arousal and shifted the entire arousal-performance curve, suggesting a relative arousal mechanism where performance adapts to arousal fluctuations within arousal states. In contrast, the cholinergic agent donepezil (DNP) did not affect arousal or the curve. We modeled these findings in a neurobiologically plausible computational framework, showing how catecholaminergic modulation alters a disinhibitory neural circuit that encodes sensory evidence for decision-making. This work suggests that performance adapts flexibly to arousal fluctuations, ensuring optimal performance in each and every arousal state.
Competing Interest Statement
The authors have declared no competing interest.
Footnotes
↵* Shared first authors
Funding This research was supported by an ERC Starting Grant from the H2020 European Research Council (ERC STG 715605 to S.v.G), a Research Talent Grant from the Dutch Research Council (NWO; 406.17.531 to L.B. and S.v.G.) and a NWO NWA-ORC grant NWA.1292.19.298 (to J. F. M.).
