Women represent a large proportion of the athletic community in organized sports and they are at increased risk for sustaining a sports-related concussion and to experience worse outcome. The goal of this longitudinal study is to use advanced neuroimaging to investigate underlying differences in brain structure and function between female and male athletes following concussion and during recovery. Neuroimaging findings will be linked to objective measures of neurocognitive and motor function, and possible sex specific risk factors for brain alterations. Findings from this research will lead to new strategies for individualized patient care including diagnosis, prediction, and therapy, and ultimately to prevention of brain alterations following concussion. Findings thus have the potential to impact a major global health problem.

Women are at increased risk for sustaining a sports-related concussion compared to their male counterparts. Moreover, female participation in sports is at an all-time high, with around 210,000 female athletes at the college level in the US, alone. Most importantly, although recent evidence demonstrates worse outcome after concussion in female athletes, women remain understudied in investigations of traumatic brain injury. Hormonal, neuromuscular, and developmental differences may affect recovery from concussion particularly in women. A better understanding of how women are affected initially by concussion and what specific mechanisms contribute to recovery are thus critical for clinicians to make informed and individualized clinical management decisions. Thus, there is an urgent need for a prospective study to investigate the underlying brain structural and functional differences between female and male athletes following concussion in order to provide a scientific basis for individualized injury management. To address this critical need we conduct a five- year longitudinal study of 150 collegiate athletes including: 1) female and 2) male athletes who sustained a concussion along with 3) female and 4) male control athletes who have not sustained a concussion, using advanced neuroimaging, evaluation of clinical symptoms as well as neurocognitive, and motor function. The long-term goal of this research is to understand the effects of sports-related brain trauma, including the possible development of biological markers, for diagnostic, therapeutic and preventive purposes. The specific objectives of the current proposal are to: 1) localize and to characterize sex differences in brain alterations and clinical sequelae immediately after concussion, 2) determine sex differences in the recovery from concussion, and 3) identify sex specific risk factors for immediate and persistent brain alterations. Our central hypothesis is that female athletes are at higher risk for functional and structural alterations and, consequently, at higher risk for worse outcome and prolonged recovery following concussion. Our hypothesis is based on our own preliminary data, as well as based on data presented in the existing literature. The rationale underlying this proposal is that once it is known if and how the female brain is affected differently by concussion and subsequent recovery, we will be able to provide more targeted individualized management guidelines and patient care. This study will be the first to provide insight into sex differences in brain structure and function after concussion and during recovery in collegiate athletes. Results of this investigation will lead to future studies investigating prevention, diagnosis, and treatment strategies of concussion in general.