Effort-based decision making in narcolepsy-cataplexy

Abstract

Introduction Narcolepsy-cataplexy (NC) is caused by the loss of hypothalamic neurons that produce hypocretins. By interacting with the mesolimbic dopamine structures (i.e. amygdala, prefrontal cortex, nucleus accumbens), hypocretins are involved in modulation of the reward system. Nucleus accumbens dopamine activity is crucially involved in valuing effort and probability costs. Thereby, NC represents an interesting model to study the implication of the hypocretin system in reward-based effort expenditure in humans. Materials and methods Eighty-nine adult participants were included, 7 drug-free patients with NC, 32 patients medicated with psychostimulant (including 17 with antidepressant), and 40 matched healthy controls (HC). All completed the Effort Expenditure for Rewards Task (EEfRT). In this task running approximately 20 min, participants are given an opportunity to choose between two different task difficulty levels: (1) easy trials (less motoric effort) for a small, stable reward; (2) hard trials (more motoric effort) for a variable but consistently larger reward. Trials (n = 40) had three levels of probability of receiving a monetary reward (i.e. 12%, 50%, and 88%). Intrinsic Motivation Inventory was administered in order to assess participants subjective experience of this task. The Karolinska Sleepiness Scale (KSS) was fulfilled by participants before and after the EEfRT completion. Results There was no difference in the percentage of trials successfully completed by patients with NC (99.1%) or controls (99.5%, p = 0.92). There were no group differences in average responses times for choosing between the easy and hard task (respectively, p = 0.24 and p = 0.19). No group effect was observed for reward magnitude (p = 0.98). However, we found that patients with NC were less willing to expend effort for rewards than HC when probability of winning was low (12%, p = 0.016) compared to medium (50%) and high (80%) probabilities. Patients with NC had higher level of intrinsic motivation (p = 0.019) with no association with the EEfRT performances. Finally, groups did not differ on the KSSs (p = 0.73 and p = 0.82). Conclusion This is the first demonstration in humans that patients with NC showed decrease willingness to incur effort costs when probability of reward receipt was low. This study provides a starting point for exploring contributions of hypocretin system to motivation in humans.