NEUROBALANCE Training to Improve Postural Control in Individuals With Traumatic Brain Injury

Background: Traumatic Brain Injury (TBI) is one of the severe health conditions with debilitating consequences, affecting more than 2.5 million individuals in the US alone. Balance dysfunction is one of the most disabling outcomes of TBI, affecting roughly half of those who have TBI even after ten years have passed after their accident, and further, it increases the risk of falls due to poor postural control. The current challenges are that there are currently no well-established rehabilitation treatments that have been shown to have long-term retention of balance recovery in TBI survivors with chronic balance complaints. Therefore, we need novel therapeutic strategies using rehabilitation engineering that can target sensorimotor integration and improved proprioceptive control to improve balance function, thereby alleviating the long-term burden on TBI survivors and their caregivers.

Hypothesis and Rationale: We hypothesize that the balance and postural control recovery requires a multimodal strategy, and we propose robotic balance training (RBT) using the Hunova platform (Movendo Technology, Italy), as it has an advantage of supporting dynamic balance in not only sagittal plane but also transverse plane (mediolateral and anterior-posterior directions), and allows for core stability and trunk control with its unique seated balance exercises. In addition, we hypothesize that by using high-definition transcranial direct current stimulation (HD-tDCS) as an adjuvant to RBT, HD-tDCS will facilitate top-down neuromuscular control of balance through corticospinal circuits, whereas the robotic platform will enable bottom-up feedback of response to platform perturbations. Overall, we anticipate that the combined intervention will improve reactive and anticipatory postural control, position sense, and proprioceptive control, gain lower-limb strength, increase ankle range of motion, and stimulate attention through game-like exercises.

Study Design: We propose a single-center, investigator-blinded, randomized, sham-controlled triple-arm parallel-group, superiority trial study. Forty-five adult individuals with chronic TBI with complaints of balance dysfunction (injury onset \> 6 months before screening) will be randomized into one of the three groups: (1) Real HD-tDCS + RBT, (2) Sham HD-tDCS + RBT, and (3) Control group receiving dose-matched standard of care rehabilitation treatment. All participants will undergo 12 sessions (3 days × 4 weeks) of intervention. A total of 3 assessment visits (before training, immediately after 4-week training, and 2-months after the last training visit) will be conducted to evaluate the functional recovery and neurophysiological changes due to intervention.

Specific Aim-1: To determine whether there is an overall treatment effect of targeted neuromodulation combined with robotic balance training on balance outcomes immediately after 4-week training function in people with TBI. The change in Berg Balance Scale score from baseline to 4-week post-training will be the primary outcome measure. The secondary outcome measures of balance recovery will be the changes in Mini BESTest, Functional Gait Assessment, and Trunk Impairment Scale scores from baseline to 4-week post-training. We hypothesize that the Real HD-tDCS + RBT will show the largest improvement in the balance outcomes.

Secondary Aim-2: To characterize the top-down and bottom-up neurophysiological mechanisms of balance control due to neuromodulation-enhanced robotic training. We will measure the neurophysiological outcomes of EEG and EMG activity, and posturography outcomes of body sway during platform perturbation task at baseline, 4-week post-training, and 2-month follow-up. Specifically, the intervention-induced changes in the cortical reactivity amplitude, muscle coactivation, and center of displacement will be compared across groups.

Secondary Aim-3: To study the association between the intervention-related changes in the balance function endpoints and graph-theoretic measures of cortical functional connectivity. We will use a multivariate statistical approach-partial least squares correlation-to identify a latent component that characterizes the correlation between the 4-week intervention-related changes in balance outcome measures and EEG corticocortical functional connectivity features measured during platform perturbation task.

• Functional Gait Assessment (FGA) [Срок оценки: Baseline, post 4-week training, and 2-month follow-up]
• Mini Balance Evaluation Systems Test (MBT) [Срок оценки: Baseline, post 4-week training, and 2-month follow-up]
• Trunk Impairment Scale (TIS) [Срок оценки: Baseline, post 4-week training, and 2-month follow-up]
• Center of Pressure (COP) Displacement [Срок оценки: Baseline, post 4-week training, and 2-month follow-up]
• TMS-evoked EEG Potentials (TEP) [Срок оценки: Baseline, post 4-week training, and 2-month follow-up]
• EEG Corticocortical Functional Connectivity [Срок оценки: Baseline, post 4-week training, and 2-month follow-up]
• EEG-to-EMG Corticomuscular Connectivity [Срок оценки: Baseline, post 4-week training, and 2-month follow-up.]
• EMG Muscle Coactivation [Срок оценки: Baseline, post 4-week training, and 2-month follow-up.]
• Quality of Life after Brain Injury (QOLIBRI) [Срок оценки: Baseline, post 4-week training, and 2-month follow-up.]
• Physical Activity Enjoyment Scale (PACES) [Срок оценки: Post 4-week training]
• Dizziness Handicap Inventory (DHI) [Срок оценки: Baseline, post 4-week training, and 2-month follow-up.]