Effects of adult age and functioning of the locus coeruleus norepinephrinergic system on reward-based learning.

Age-related impairments in value representations and updating during decision-making and reward-based learning are often related to age-related attenuation in the catecholamine system such as dopamine (DA) and norepinephrine (NE). However, it is unclear to what extent age-related declines in NE functioning in humans affect reward-based decision-making. We conducted a probabilistic decision-making task and applied a Q-learning model to investigate participants' anticipatory values and value sensitivities. Task-related pupil dilations and locus coeruleus (LC)-magnetic resonance imaging (MRI) contrast, which served as a potential window of the LC-NE functions, were assessed in younger and older adults. Results showed that in both choice and feedback phases, younger adults' (N = 42; 22 males) pupil dilations negatively correlated with anticipatory values, indicating uncertainty about outcome probabilities. Uncertainty-evoked pupil dilations in older adults (N = 41; 27 males) were smaller, indicating age-related impairments in value estimation and updating. In both age groups, participants who showed a larger uncertainty-evoked pupil dilation exhibited a higher value sensitivity as reflected in the β parameter of the reinforcement Q-learning model. Furthermore, older adults (N = 34; 29 males) showed a lower LC-MRI contrast than younger adults (N = 25; 15 males). The LC-MRI contrast positively correlated with value sensitivity only in older but not in younger adults. These findings suggest that task-related pupillary responses can reflect age-related deficits in value estimation and updating during reward-based decision-making. Our evidence with the LC-MRI contrast further showed the age-related decline of the LC structure in modulating value representations during reward-based learning. Significance Statement: Age-related impairments in value representation and updating during reward-based learning are associated with declines in the catecholamine modulation with age. However, it is unclear how age-related declines in the locus coeruleus norepinephrine (LC-NE) system may affect reward-based learning. Here, we show that compared to younger adults, older adults exhibited reduced uncertainty-induced pupil dilations, suggesting age-related deficits in value estimation and updating. Older adults showed a lower structural magnetic resonance imaging (MRI) of the LC contrast than younger adults, indicating age-related degeneration of the LC structure. The association between the LC-MRI contrast and value sensitivity was only observed in older adults. Our findings may demonstrate a pioneering model to unravel the role of the LC-NE system in reward-based learning in aging.