Dual-Task Exercise for Mild Traumatic Brain Injury (mTBI)

There is a critical need to develop an effective intervention for a chronic concussion or mild traumatic brain injury (mTBI) that presents persistent post-injury functional declines. Up to 40% of mTBIs cause multifaceted and long-term functional declines, including cognitive declines, psychosocial or sensorimotor problems, which results in $17B medical costs each year. Long-term functional impairments have been reported even 5 to 19 years post-injury, which exacerbate neurodegeneration, such as chronic traumatic encephalopathy or Parkinson's disease. Yet, only a very limited or few studies have investigated a followup screening or intervention for long-term and persistent functional declines, suggesting important deficiencies in long-term care for mTBI. The investigators previously developed a virtual 14-day dual-task walking exercise program and tested its feasibility with Asian and Pacific Islanders (API), including those with mTBI history. The investigators will test the feasibility and efficacy of a mobile app-version (Uplode) of the same 14-day exercise program (Brain \& Walk Exercise Every Day [BraW-Day]), on cognition, sensorimotor, and other functions in a group of voluntary young adults with an mTBI between last three months to two years, including student athletes, Veterans, and ethnic minorities. The specific aims of the current study are:

Aim 1: Examine if the mobile app, home-based BraW-Day program is acceptable to young adults with an mTBI. H1. BraW-Day program will (a) be acceptable to the participants, (b) fit with their daily life, and (c) demonstrate feasible and suitable data collection of the daily participation.

Aim 2: Test the efficacy of the BraW-Day program on functions after mTBI. H2. BraW-Day program will improve (a) cognitive (measured by a computerized CNS-VS), (b) psychosocial (by Neuro QoL, a standardized self-report tool for neuro-psychosocial conditions), or (c) sensorimotor functions (by walking movement measuring app, 3D kinematic and kinetic gait analysis, and EyeLink rapid eye movement tracker) in mTBI at post-intervention (T2), compared to wait-list controls.

Aim 3: Examine the sustained effect of the BraW-Day program on function after mTBI. H3. Functional levels one month after intervention (T3) will be equivalent to or higher than baseline (T1) and postintervention (T2) levels.

We will conduct a nonblinded randomized trial with a wait-list control design to test the efficacy of a 2-week (14 consecutive days) BraW-Day, which is daily home-based mobile app-based cognitive-walking exercise program on overall functions in individuals with a recent history of mTBI. Both male and female voluntary young adults aged 18 to 40 years with diverse ethnic backgrounds who report a recent history of mTBI, including student athletes and Veterans, will be invited to our exercise intervention. The participants will be randomly assigned to either the intervention group or the control group. Intervention group will have a 3 study visits to ULNV for assessing the baseline (T1), post-intervention (T2), and 1-month post-intervention (T3) functional levels to test the efficacy of the program. The waitlist control group will have an additional study visit at pre-baseline (T0), so will have a total of 4 study visits (T0, T1, T2, \& T3). The BraW-Day intervention program consists of 15-minute-long daily brain exercise and walking at the same time (i.e., cognitive-walking tasks) for 14 consecutive days, targeting persistent mTBI symptoms and functional declines, including cognitive, psychosocial, and sensorimotor functions. The BraW Day program will be delivered on a mobile app, Uplode. All subjects will be introduced to the BraW-Day program and the Uplode app. They will be guided to download the Uplode app on their mobile phone with the app's notification enabled for the next day when they will start the BraW-Day program as Day 1. From Day 1, daily reminder notifications from the app will be sent to each participant's mobile phone. They will then follow the schedule for the daily exercise as guided by the app. Each participant will be asked to perform three different 5-minute-long cognitive tasks (e.g., subtracting numbers or remembering long phrases) and one physical task (i.e., tandem walking or 8-shape walking) either indoor or outdoor at the same time for 15 minutes every day, which they will repeat daily for the next 13 days (2 weeks in total). Participants will be asked to mark the start time and the end time of the 15-minute dual-task exercise every day and also to mark off each of the 3 different cognitive tasks every time they finish on that day. Once each participant hits the "Submit" button when they complete each 15-minute-long exercise every day. Post-injury functional levels will be measured by the Rivermead Post-concussion Symptom Questionnaire (RPQ) and the Neurobehavioral symptom inventory (NSI). At each site visit, participants will complete functional assessments (cognitive, psychosocial, sensorimotor function) and collect a saliva sample, which will take est. 1.5 hours per visit. More specifically, cognitive functional assessment will be by a computerized CNS-VS, psychosocial by Neuro QoL (a standardized self-report tool for neuro-psychosocial conditions), and sensorimotor by the mHealth-WB app, 3D kinematic and kinetic gait analysis, and EyeLink rapid eye movement tracker. T2 visit will include a semi-structured interview (max. 20 mins) based on components of the System Usability Scale (SUS) focusing on acceptability, feasibility, and barriers and facilitators for the BraW-Day exercise program on the Uplode app. Saliva samples will be collected and saved for future profiling of peripheral epigenetic markers (i.e., saliva exosomal microRNA). This will be explained as part of informed consent process.

No adverse events are expected from the implementation of the project, including the BraW-Day home-based exercise intervention, based on our previous virtual format of the same intervention. All healthcare providers in the proposed project are board-certified and credentialed in each of their states. All participants will be strongly encouraged to contact and report any adverse event during the study participation. The PI's contact information and a list of campus resources, primary care, and urgent care settings will be shared with every participant in their first site visit. If any adverse events happen during the project, within 24 hours of the discovery of the occurrence, the PI will submit adverse event reports to the UNLV IRB and the CTR-IN Pilot Program committee.