Sleep Fragmentation Exacerbates Executive Function Impairments Induced by Low Doses of Si Ions

Abstract

Astronauts on deep space missions will be required to work autonomously and thus their ability to perform executive functions could be critical to mission success. Ground-based rodent experiments have shown that low (<25 cGy) doses of several space radiation (SR) ions impair various aspects of executive function. Translating ground-based rodent studies into tangible risk estimates for astronauts remains an enormous challenge, but should similar neurocognitive impairments occur in astronauts exposed to low-SR doses, a Numbers-Needed-to-Harm analysis (of the rodent data) predicts that approximately 30% of the astronauts could develop severe cognitive flexibility decrements. In addition to the health risks associated with SR exposure, astronauts have to contend with other stressors, of which inadequate sleep quantity and quality are considered to be major concerns. We have shown that a single session of fragmented sleep uncovered latent attentional set-shifting (ATSET) performance deficits in rats exposed to protracted neutron radiation that had no obvious defects in performance under rested wakefulness conditions. It is unclear if the exacerbating effect of sleep fragmentation (SF) only occurs in rats receiving protracted low-dose-rate-neutron radiation. In this study, we assessed whether SF also unmasks latent ATSET deficits in rats exposed to 5 cGy 600 MeV/n 28Si ions. Only sham and Si-irradiated rats that had good ATSET performance (passing every stage of the test on their first attempt) were selected for study. Sleep fragmentation selectively impaired performance in the more complex IDR, EDS and EDR stages of the ATSET test in the Si-irradiated rats. Set-shifting performance has rarely been affected by SR exposure in our studies conducted with rats tested under rested wakefulness conditions. The consistent SF-related unmasking of latent set-shifting deficits in both Si- and neutron-irradiated rats suggests that there is a unique interaction between sleep fragmentation and space radiation on the functionality of the brain regions that regulate performance in the IDR, EDS and EDR stages of ATSET. The uncovering of these latent SR-induced ATSET performance deficits in both Si- and neutron-irradiated rats suggests that the true impact of SR-induced cognitive impairment may not be fully evident in normally rested rats, and thus cognitive testing needs to be conducted under both rested wakefulness and sleep fragmentation conditions.