A Two-Hit Model of Executive Dysfunction: Simulated Galactic Cosmic Radiation Primes Latent Deficits Revealed by Sleep Fragmentation.

Future Artemis-class missions to Mars will expose astronauts to prolonged space radiation (SR), sleep disruption, and operational demands requiring greater autonomy, placing decision making and executive function at heightened risk. Both SR and sleep fragmentation (SF) independently impair cognition, yet their combined effects remain poorly understood. Using the Associative Recognition Memory and Interference (ARMIT) task, we assessed cognitive performance in male rats exposed to 10 cGy of Galactic Cosmic Ray simulation (GCRsim), SF, or both. Under well-rested conditions, GCRsim-exposed rats exhibited overt deficits in the C.1.2 stage, performing at chance when reinforcement contingencies shifted, consistent with impaired cognitive flexibility. In contrast, high-performing GCRsim-exposed rats that initially performed comparably to Sham s revealed latent deficits following a single night of SF. Specifically, the SF-induced loss of C.1.3 performance was accompanied by perseverative errors (persistently selecting outdated cues despite negative feedback), reflecting impaired attentional control and decision updating. Sham s maintained stable performance after SF. These findings support a two-hit vulnerability model in which SR primes corticostriatal and frontoparietal networks for collapse under subsequent sleep disruption. Operationally, this suggests that astronauts may display either persistent or stress-induced deficits, with both modes threatening mission success. Identifying mechanisms of such vulnerabilities is essential for countermeasure development.