Effect of Exercise Training on Physical, Cognitive, and Behavioral Function in People With TBI

Traumatic Brain Injury (TBI)

Aerobic Exercise Training, Balance, TBI, Rapid-Resistive Exercise

Background: \- Traumatic brain injury (TBI) often causes problems with moving and balance, and thinking and emotions. Exercise can improve these things in people with other brain damage. Researchers want to look at the effect of exercise on these things in people with TBI. Objectives: \- To study how head injuries affect the brain. To study if exercise can help some symptoms in people with TBI. These include problems thinking, balancing, and moving, and depression or anxiety. Eligibility: * People age between 18 and 79 * Had a non-penetrating TBI at least 12 months ago * Are physically inactive, but can stand and walk without help Design: * Participants will be screened with medical history, physical exam, and blood and urine tests. They may have a balance test. * Participants will be assigned to a high-intensity or a lower-intensity exercise program. * The study is 6 months long. There will be 3 months with exercise on an elliptical machine and 3 months without exercise. * Participants will exercise for 30 minutes on an elliptical machine, 3 days per week for 3 months. * Participants will also have 3 outpatient testing visits lasting approximately 8 hours, once every 3 months. This visit will include: * Blood tests * Tests for memory, attention, and thinking * Tests of walking and balance * Questionnaires * An MRI: they will lie in a machine that takes pictures of their brain, while breathing regular air and air with more carbon dioxide * Test of physical fitness

Objective The broad objective of this study is to examine the effects of moderate and more intense aerobic exercise as an intervention on cognitive performance, physical functioning and health-related quality of life in patients with chronic (more than 12 months post-injury) traumatic brain injury (TBI). Importantly, structural and biological brain changes will be measured to examine whether functional outcomes are related to exercise-induced adaptations. It is hypothesized that in the chronic phase of persons with TBI, there will be improved: 1) cognitive function, 2) physical fitness and fatigue severity, 3) motor performance and balance, and 4) mood and depressive symptoms, in those that performed the exercise intervention compared to a control group. It is also hypothesized that these functional improvements will be related to exercise intensity, improved cortical connectivity, dopamine transmission gene scores, and blood biomarkers related to neuro and angio-genesis. Study Population 80 ambulatory adults with non-penetrating TBI will be enrolled. We will also enroll up to 20 healthy volunteers as a comparison group for some of the outcome measures. Subjects will be recruited from NIH, affiliated hospitals/clinics and the community Design Healthy volunteers will have a limited assessment that includes brain imaging, blood draw for genetic testing, and a subset of the cognitive and behavioral testing at a single time-point. All subjects with TBI will perform baseline assessments including cognitive and behavioral performance, brain imaging, fitness, motor and balance testing, and selected blood and genetic testing. Thereafter, subjects with TBI will be randomized to either a waitlist control, or one of two exercise conditions: 1) 30 minutes at a fast pace, moderate-intensity (rapid-resistive exercise; RET); 2) 30 minutes at higher-intensity (aerobic exercise; AET). Both exercise groups will perform the exercise on an elliptical trainer 3 times a week, for a session duration of 45 minutes including warm-up and cool-down. The RET group will focus on rapid reciprocal motion with minimal resistance, while the AET group will exercise at an elevated intensity known to produce an aerobic effect. After 12 weeks, all groups will repeat the baseline assessments (3 month follow-up). Following this assessment, the waitlist control group will be randomized to either RET or AET and the exercise groups will cease formal supervised exercise sessions. A third assessment visit will be performed after an additional 12 weeks (6 month follow-up). Outcome Measures Cognitive performance will be tested and interpreted compared to norms. Performance on motor and balance tasks will be assessed with the Smart Balance Measurement System and the GAITRite System. Physical fitness will be determined by peak oxygen consumption and aerobic threshold as measured by pulmonary gas exchange during an exercise tolerance test on the treadmill. Structural brain volumes will be determined by magnetic resonance imaging (MRI) and cortical connectivity will be quantified using resting state functional MRI and Diffusion Tensor Imaging (DTI) to evaluate integrity of and changes in white matter tracts in response to exercise and compared to healthy volunteers. Blood will be collected to quantify the presence of biomarkers (such as VEGF, BDNF and IGF-1) and dopamine transmission. Other self-reported measures of quality of life, fatigue severity, depression and sleep quality would also be collected, and compared to healthy volunteers.

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