PROJECT SUMMARY Sex is an important risk factor to consider in concussion but has been historically under-studied. Computational models of the human head transform external head impacts into regional brain strains that are well believed to be the primary cause for injury. They are thought to offer more effective biomechanical mechanism underpinning concussion. However, current brain injury models do not consider sex differences in morphology, either at the organ level or at the microscale, axon level. Therefore, current brain injury models are not feasible to study the biomechanical basis of sex differences in concussion. This proposal has two specific aims. First, we will develop subject-specific brain injury models of the whole brain and axons. Next, we will use subject-specific head impacts from male and female ice-hockey players to characterize sex differences in brain strain and extent of axonal damage, and then correlate them with a range of biomarkers. Sex differences in both concussion and subconsussion will be studied. The proposed research will provide an initial understanding of the sex-related differences in strains sustained in male and female brains and the extent of axonal structural damages. Ultimately, these efforts will contribute to refined health policymaking and sex-specific concussion mitigation strategies to reduce the growing health-care burden.