Pupillary dynamics reflect age-related changes in memory encoding

Abstract

Pupillary dynamics are closely dependent on tonic and phasic activity of the brainstem locus coeruleus (LC), a key neuromodulatory nucleus. LC neurons are the earliest site of hyper-phosphorylated tau accumulation, leading to a decline in nucleus structural integrity in older age that likely impacts long-term memory. While several studies have explored the link between pupil dilation and successful memory encoding, little is known about the effects of aging on this relationship. This study investigated task-evoked pupillary responses (TEPRs) in young and older adults during incidental encoding of neutral visual scenes. Memory performance was assessed 24 hours later using a Remember-Know-Guess recognition task. TEPRs were compared based on recognition performance. Our findings notably revealed attenuated TEPRs in older individuals, supporting the hypothesis of impaired LC-driven modulation with age. Pupil dilation was associated with memory performance in young adults only. In this group, subsequently recognized stimuli elicited greater dilation during encoding compared to forgotten ones. Moreover, among recognized stimuli, recollected ones evoked larger pupillary responses than those remembered with a feeling of familiarity. Importantly, this effect was absent in older adults, suggesting that the benefit provided by LC involvement during encoding declines with advancing age. These findings highlight the crucial role of LC-mediated neuromodulation in episodic memory, and suggest that age-related LC decline can be evidenced using pupillometry.