Prolonged deep space missions to planets and asteroids will expose astronauts to galactic cosmic radiation, comprised of low-linear energy transfer (LET) ionizing radiations, high-energy protons and high-Z and energy (HZE) particles, such as (56)Fe nuclei. In prior studies with rodents exposed to HZE particle radiation at doses likely to be encountered during deep space missions (<20 cGy) investigators reported impaired hippocampal-dependent neurocognitive performance and further observed substantial variation among the irradiated animals in neurocognitive impairment, ranging from no observable effects to severe impairment. These findings point to the importance of incorporating quantitative measures of interindividual variations into next generation risk assessment models of radiation risks on neurocognition. In this study, 269 male proven breeder Wistar rats were exposed to 1 GeV/n (56)Fe at doses of 0, 5, 10, 15 and 20 cGy, and tested for spatial memory performance on the Barnes maze at three months after exposure. The radiation response data were compared using changes in mean cohort performance and by the proportion of poor responders using the performance benchmark of two standard deviations below the mean value among the sham-irradiated cohort. Acute exposures to mission-relevant doses of 1 GeV/n (56)Fe reduced the mean spatial memory performance at three months after exposure (P < 0.002) and increased the proportions of poor performers, 2- to 3-fold. However, a substantial fraction of animals in all exposure cohorts showed no detectable change in performance, compared to the distribution of sham-irradiated animals. Our findings suggest that individualized metrics of susceptibility or resistance to radiation-induce changes in neurocognitive performance will be advantageous to the development of probabilistic risk assessment models for HZE-induced neurocognitive impairment.

Prolonged deep space missions to planets and asteroids will expose astronauts to galactic cosmic radiation (GCR), a mixture of low-LET ionizing radiations, high-energy protons and high-Z and energy (HZE) particles. Ground-based experiments are used to determine whether this radiation environment will have an effect on the long-term health of astronauts and their ability to complete various tasks during their mission. Emerging data suggest that mission-relevant HZE doses impair several hippocampus-dependent neurocognitive processes in rodents, but that there is substantial interindividual variation in the severity of neurocognitive impairment, ranging from no observable effects to severe impairment. While the majority of studies have established the effect that the most abundant HZE species (⁵⁶Fe) has on neurocognition, some studies suggest that the lighter ⁴⁸Ti HZE particles may be equally, if not more, potent at impairing neurocognition. In this study, we assessed the effect that exposure to 5-20 cGy 1 GeV/n ⁴⁸Ti had on the spatial memory performance of socially mature male Wistar rats. Acute exposures to mission-relevant doses (≤5 cGy) of 1 GeV/n ⁴⁸Ti significantly (P < 0.05) reduced the mean spatial memory performance of the rats at three months after exposure, and significantly (P < 0.015) increased the percentage of rats that have severe (Z score ≥ 2) impairment, i.e., poor performers. Collectively, these data further support the notion that the LET dependency of neurocognitive impairment may differ from that of cell killing.