BackgroundRecent scientific evidence has challenged the traditional “rest-is-best” approach for concussion management. It is now thought that “exercise-is-medicine” for concussion, owing to dozens of studies which demonstrate that sub-maximal, graded aerobic exercise can reduce symptom burden and time to symptom resolution. However, the primary neuropathology of concussion is altered functional brain activity. To date, no studies have examined the effects of sub-maximal aerobic exercise on resting state functional brain activity in pediatric concussion. In addition, although exercise is now more widely prescribed following concussion, its cardiopulmonary response is not yet well understood in this population. Our study has two main goals. The first is to understand whether there are exercise-induced resting state functional brain activity differences in children with concussion vs. healthy controls. The second is to profile the physiological response to exercise and understand whether it differs between groups.MethodsWe will perform a single-center, controlled, prospective cohort study of pediatric concussion at a large, urban children’s hospital and academic center. Children with sport-related concussion (aged 12–17 years) will be recruited within 4-weeks of injury by our clinical study team members. Key inclusion criteria include: medical clearance to exercise, no prior concussion or neurological history, and no implants that would preclude MRI. Age- and sex-matched healthy controls will be required to meet the same inclusion criteria and will be recruited through the community. The study will be performed over two visits separated by 24–48 h. Visit 1 involves exercise testing (following the current clinical standard for concussion) and breath-by-breath gas collection using a metabolic cart. Visit 2 involves two functional MRI (fMRI) scans interspersed by 10-minutes of treadmill walking at an intensity calibrated to Visit 1 findings. To address sub-objectives, all participants will be asked to self-report symptoms daily and wear a waist-worn tri-axial accelerometer for 28-days after Visit 2.DiscussionOur study will advance the growing exercise-concussion field by helping us understand whether exercise impacts outcomes beyond symptoms in pediatric concussion. We will also be able to profile the cardiopulmonary response to exercise, which may allow for further understanding (and eventual optimization) of exercise in concussion management.Trial registrationNot applicable.