Modulating Exercise Dosage to Improve Concussion Recovery

Concussions are defined as a mild form of traumatic brain injury that result in acute neurological dysfunction. Recent work suggests post-concussion aerobic exercise at an intensity level below symptom exacerbation is safe. Yet, clinical benefits from existing randomized controlled trials indicate substantial room for improvement. Also, there is currently an incomplete understanding of the neurophysiology underlying changes in response to exercise treatment. Identifying the precise exercise dose (volume/intensity) required to elicit a therapeutic response following concussion will lead to enhanced and more precise post-concussion rehabilitation strategies. Published and pilot data by the investigators indicate light post-concussion exercise was associated with faster symptom resolution time and less severe symptoms, yet this relied on self-reported data and observational designs. Furthermore, the investigators have identified that the optimal exercise volume to differentiate those with/without concussion symptoms after one month was \>160 minutes/week, which is higher than standard exercise volumes prescribed (\>100 minutes/week), and in line with existing recommendations for cardiovascular health (\>150 minutes/week). Beyond this, given the positive effects of regular moderate exercise to reduce inflammation (e.g., interleukin 6) and restore cerebrovascular regulation, these physiological functions represent viable and feasible rehabilitation targets. Thus, using a prospective randomized clinical trial design, the investigators aim to identify if high dose exercise \>(150 minutes/week at an individualized intensity level), relative to standard-of-care, results in: faster/slower symptom resolution, altered physiological function, or reduced secondary sequalae. Our multidisciplinary investigative team has expertise investigating concussion, exercise physiology, fluid biomarkers, cerebrovascular physiology, and psychosocial outcomes. Thus, the investigators will enroll, initially test, and randomize adolescents ages 13-18 years old ≤14 days post-concussion to high dose aerobic exercise or standard-of-care (symptom limited, self-guided physical activity), and reassess upon symptom resolution and 8-weeks post symptom resolution. The investigators will obtain cerebrovascular function and serum biomarker data at each visit, and quantify exercise, symptoms, and secondary sequalae continuously. First, The investigators aim to examine how the dose (intensity, duration, and frequency) of an aerobic exercise program initiated within 10 days of concussion affects time to symptom resolution, relative to standard-of-care, among adolescents. Second, the investigators aim to assess the mechanistic relationship between aerobic exercise, biomarkers of neuroinflammation, and cerebrovascular function. Third, the investigators aim to elucidate how high dose exercise after concussion affects persistent secondary sequalae development (anxiety, depression, kinesiophobia, peer relationships, academic concerns). By challenging the currently accepted, exercise recommendations for sport-related concussion, the investigators will break new ground toward improving rehabilitation strategies.

• Serum biomarker concentration: IL-6 change [Time frame: Baseline, Visit 2 (scheduled after symptoms resolve, about 35 days post-baseline)]
• Serum biomarker concentration: TNF-alpha change [Time frame: Baseline, Visit 2 (scheduled after symptoms resolve, about 35 days post-baseline)]
• Serum biomarker concentration: IL1-RA change [Time frame: Baseline, Visit 2 (scheduled after symptoms resolve, about 35 days post-baseline)]
• Serum biomarker concentration: VEGF change [Time frame: Baseline, Visit 2 (scheduled after symptoms resolve, about 35 days post-baseline)]
• Serum biomarker concentration: MMP-9 change [Time frame: Baseline, Visit 2 (scheduled after symptoms resolve, about 35 days post-baseline)]
• Cerebral autoregulation [Time frame: Baseline, Visit 2 (scheduled after symptoms resolve, about 35 days post-baseline)]
• Cerebral vasoreactivity change [Time frame: Baseline, Visit 2 (scheduled after symptoms resolve, about 35 days post-baseline)]
• Kinesiophobia severity change [Time frame: Baseline, Visit 2 (scheduled after symptoms resolve, about 35 days post-baseline)]
• Peer relationship attitudes change [Time frame: Baseline, Visit 2 (scheduled after symptoms resolve, about 35 days post-baseline)]
• Academic concerns change [Time frame: Baseline, Visit 2 (scheduled after symptoms resolve, about 35 days post-baseline)]