Pupil size as an indicator of neurochemical activity during learning

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. The objective of my research is to understand the role of neurochemicals in human learning. Specifically, I aim to 1) Establish a non-invasive method to study the role of neurochemicals in human learning, 2) Develop methods to monitor learning in real time using pupillometry, and 3) Discover causal relationships between neurochemicals and learning in human subjects. In this article, to address Objective 1, we present evidence that pupil dynamics can be used as a surrogate measure of neurochemical activity during learning. Specifically, we hypothesize that norepinephrine modulates the encoding of memories, the influence of which can be measured with pupil dynamics. To examine this hypothesis a task-irrelevant learning paradigm was used, 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 learning. My ongoing work aims to develop methods to monitor learning in real time by investigating the relationship between, pupil size changes, eye movement and learning in context of a free visual search task. Future work will investigate the causal relationship between neurochemicals, learning and pupil dynamics by using NE specific drugs to up- and down-regulate levels of NE during learning.