Interplay of pupil-linked arousal and cortical decision computations in mice

Influential frameworks hold that brainstem neuromodulatory systems are rapidly recruited in a top-down manner during decision-making, adapting brain-wide activity and cognitive behavior in real time. Here, we examined the relationship between decision-related frontal cortical activity and pupil responses (a peripheral proxy of neuromodulatory activity) in mice accumulating fluctuating auditory evidence to choose among two options. We found two components of preparatory activity during decision formation, prior to motor action: a non-selective component shared between hemispheres and a choice-selective component that reflected decision uncertainty. Both components were mirrored in pupil responses during the task, which, in turn, scaled with decision uncertainty during decision formation and with uncertainty-modulated prediction errors after experiencing the outcome. Pupil responses also predicted an adjustment of choice behavior at the next trial. Our results point to a recurrent interplay between cortical decision computation and pupil-linked neuromodulation. HIGHLIGHTSO_LIMice switch between evidence integration and heuristic strategies during auditory-informed decisions C_LIO_LIPupil responses track decision uncertainty and uncertainty-modulated prediction errors C_LIO_LIDecision-related frontal cortical activity is coupled with pupil responses C_LIO_LIPupil responses predict an adjustment of future choice behavior C_LI IN SHORTMaheu et al. show that the phasic transitions in the arousal state mirror distinct components of cortical activity, including one directly involved in decision computations. In turn, these pupil-linked arousal responses predicted the strategy adopted at the next trial.