The midbrain is biomechanically susceptible to force loading from repetitive subconcussive head impacts (RSHI), is a site of tauopathy in chronic traumatic encephalopathy (CTE), and regulates functions (e.g., eye movements) often disrupted in concussion. In a prospective longitudinal design, we demonstrate there are reductions in midbrain white matter integrity due to a single season of collegiate football, and that the amount of reduction in midbrain white matter integrity is related to the amount of rotational acceleration to which players’ brains are exposed. We then replicate the observation of reduced midbrain white matter integrity in a retrospective cohort of individuals with frank concussion, and further show that variance in white matter integrity is correlated with levels of serum-based tau, a marker of blood-brain barrier disruption. These findings mean that noninvasive structural MRI of the midbrain is a succinct index of both clinically silent white matter injury as well as frank concussion.

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