Comprehensive White-matter Microstructure-informed Analytical Methods to Elucidate Neurobiological Mechanisms of Sports-related Concussion (SRC)

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Project Abstract Sports-related concussion (SRC), while often regarded as the mildest form of traumatic brain injury (TBI), is nevertheless a significant public health issue. Based on the estimates by the Centers for Disease Control, 1.6 to 3.8 million SRCs occur annually among high school and collegiate athletes. Athletes sustaining acute concussion have a wide spectrum of clinical signs and symptoms including psychological distress, cognitive impairment, and somatic symptoms. In some cases, these symptoms persist, and people with mild TBI may be at higher risk for neurodegenerative diseases, future TBI, and, in cases of repetitive injuries, chronic traumatic encephalopathy. While standardized assessment tools are useful in the clinical management of acute concussion, the underlying pathophysiology of SRC and the time course of physiological recovery after injury remain unclear. There is an immediate need to address the heterogeneity in the long-term consequences of SRC to facilitate concussion management. The proposed research aims to understand why some concussed athletes have prolonged recovery time and, more importantly, how to detect such extreme cases. Diffuse axonal injury is generally believed to be the initial white matter neuropathology associated with mild TBI. Nevertheless, this microscopic injury is more difficult to detect in human mild TBI. Modern diffusion MRI techniques offer increased biological specificity for describing white-matter alterations. Therefore, the goal of the proposed research is to determine whether these novel axonal metrics: (1) provide indirect evidence of diffuse axonal injury in human SRC; (2) help to explain heterogeneity in individual recovery trajectories; and (3) inform our understanding of the relationship between axonal injury in SRC and clinical manifestations of SRC.