Machine Learning Models to Predict Cognitive Impairment of Rodents Subjected to Space Radiation
INTRODUCTION We use artificial neural networks (ANNs) as an example machine learning (ML) tool to predict the cognitive performance impairment of rats induced by irradiation. The experimental data in the analyses is attentional set-shifting (ATSET) test scores from a rodent model exposed to ≤15 cGy of individual galactic cosmic radiation (GCR) ions: 4He, 28Si, or 56Fe, expected for a Lunar or Mars mission [1]. This work investigates rats at a subject-based level and uses applied dose and performance scores taken before irradiation to predict whether a rat will be impaired when irradiated. The results of this study are significant to crewed space missions as they support the potential of predicting an astronaut’s impairment in a specific task before spaceflight through the implementation of appropriately trained ML tools. METHODS Data used in this work are scores from the ATSET, a multi-stage constrained cognitive flexibility test [2]. Our computational model utilizes the number of attempts to reach the criterion to pass a stage as a behavioral performance measure for rats. We use the post-irradiation scores, generate thresholds from cumulative distribution plots of non-irradiated rats, and calculate the percent of irradiated rats whose scores fall below the threshold to infer how each radiation type/dose affects a population. Rats scoring above the threshold are labeled impaired while the others are non-impaired. We then employ ANNs as a typical ML technique, and use each subject’s individual scores taken before radiation along with the applied dose, to predict their personal susceptibility to cognitive impairment due to space radiation exposure. RESULTS AND CONCLUSION A significant finding is the exhibition of a dose-dependent increasing probability of impairment for 1 to 10 cGy of 28Si or 56Fe in the simple discrimination (SD) stage of the ATSET, and for 1 to 10 cGy of 56Fe in the compound discrimination (CD) stage. On a subject-based level, implementing ML classifiers such as ANNs identifies rats that have a higher tendency for impairment after GCR exposure [1]. The receiver operating characteristic (ROC) and the precision-recall (PR) curves of the ML models show a better prediction of impairment when 56Fe is the ion in question in both SD (Figure 1) and CD stages. They, however, do not depict impairment due to 4He in SD (Figure 1) and 28Si in CD, suggesting no dose-dependent impairment response in these cases. In this work, “good” prediction pertains to “better-than-random-chance”, due to the limited sample size and the high inter- and intra-individual variabilities in response to brain stimulation paradigms, as applicable to both animals and humans. More behavioral tests and biomarkers should be investigated on the same subjects, to be fed to the ML models to capture the agents responsible for performance alterations of some individuals versus others.