Neurochemical systems are well studied in animal learning; however, ethical issues limit methodologies to explore these systems in humans. Pupillometry provides a glimpse into the brain's neurochemical systems, where pupil dynamics in monkeys have been linked with locus coeruleus (LC) activity, which releases norepinephrine (NE) throughout the brain. Here, we use pupil dynamics as a surrogate measure of neurochemical activity to explore the hypothesis that NE is involved in modulating memory encoding. We examine this using a task-irrelevant learning paradigm in which learning is boosted for stimuli temporally paired with task targets. We show that participants better recognize images that are paired with task targets than distractors and, in correspondence, that pupil size changes more for target-paired than distractor-paired images. To further investigate the hypothesis that NE nonspecifically guides learning for stimuli that are present with its release, a second procedure was used that employed an unexpected sound to activate the LC–NE system and induce pupil-size changes; results indicated a corresponding increase in memorization of images paired with the unexpected sounds. Together, these results suggest a relationship between the LC–NE system, pupil-size changes, and human memory encoding.

It has been proposed that perceptual learning may occur through a reinforcement process, in which consistently pairing stimuli with reward is sufficient for learning. We tested whether stimulus–reward pairing is sufficient to increase the sensorial representation of a stimulus by recording local field potentials (LFPs) in macaque extrastriate area V4 with chronically implanted electrodes. Two oriented gratings were repeatedly presented; one was paired with a fluid reward, whereas no reward was given at any other time. During the course of conditioning the LFP increased for the rewarded compared to the unrewarded orientation. The time course of the effect of stimulus–reward pairing and its reversal differed between an early and late interval of the LFP response: a fast change in the later part of the neural response that was dissociated from a slower change in the early part of the response. The fast change of the late interval LFP suggests that this late LFP change is related to enhanced attention during the presentation of the rewarded stimulus. The slower time course of the early interval response suggests an effect of sensorial learning. Thus, simple stimulus–reward pairing is sufficient to strengthen stimulus representations in visual cortex and does this by means of two dissociable mechanisms.