A Pilot Study of Home-Based Rhythmic Auditory Stimulation to Evaluate Mobility, Balance, and Patient-Reported Outcomes After Traumatic Brain Injury

1. PURPOSE, BACKGROUND, SCIENTIFIC RATIONALE Traumatic brain injury (TBI) affects approximately 2.8 million people annually in the United States and remains a major public health concern due to its high rates of disability and long-term functional impairment.1 TBI commonly results from falls, motor vehicle collisions, sports -related injuries, and assaults, and can lead to persistent deficits in mobility, balance, cognition, and overall functional independence.2 Even after acute recovery, many individuals experience prolonged limitations that interfere with community participation and quality of life.3,4 As survival rates improve, optimizing rehabilitation strategies that support functional recovery has become increasingly important.

Impaired mobility and balance are two common long-term sequelae of TBI5-7 that have substantial negative life impacts and often persist for years post injury.8 Individuals with TBI walk more slowly,9-13 demonstrate greater imbalance,11-13 and have reduced endurance14 compared to nondisabled counterparts; evidence suggests that improving mobility and balance after TBI is associated with improved quality of life and community participation.15 Despite clinical guidelines emphasizing the importance of ongoing, task-specific rehabilitation to promote neuroplasticity, access to sustained outpatient therapy for individuals with chronic TBI is limited by cost, transportation barriers, workforce constraints, and insurance coverage.16 As a result, there is a critical need for scalable, home-based rehabilitation approaches that can safely deliver high-quality, progressive mobility training while supporting adherence and engagement over time.

Rhythmic auditory stimulation (RAS) is a well established, evidence based neuromodulation approach that uses rhythmic auditory cues, such as music, to synchronize and support motor activity through auditory-motor entrainment..17,18 This synchronization can enhance gait neuromotor control by activating intact motor networks to facilitate recovery after neurologic injury.19,20 Stroke literature demonstrates that RAS improves walking speed, cadence, symmetry, endurance, and functional mobility, with emerging evidence that music-based cueing may also enhance motivation, enjoyment, and engagement relative to metronome-only cueing.17 A growing body of literature suggests that music-based interventions may offer multi-domain benefits for individuals with TBI, extending beyond motor recovery to cognitive, emotional, and psychosocial outcomes.21,22 Randomized controlled trials of neurological music therapy in moderate-to-severe TBI have demonstrated improvements in executive function, behavioral regulation, and attentional control.22,23 Complementary neuroimaging analyses provide preliminary evidence that these functional gains may be supported by music-induced neuroplasticity, including structural and network-level changes within prefrontal and frontotemporal circuits implicated in cognitive control and emotional regulation. Systematic reviews further indicate that music-based interventions are associated with improvements in mood, agitation, stress, social interaction, and sleep quality in TBI populations, supporting their potential relevance for quality-of-life outcomes. However, despite these promising findings, the evidence base remains limited by small sample sizes, heterogeneous intervention protocols, variable outcome measures, and inconsistent reporting of dose, timing, and treatment fidelity. Recent reviews emphasize the need for larger, methodologically rigorous trials with standardized outcomes and clearer mechanistic frameworks to support translation into routine neurorehabilitation practice.

MedRhythms' MR-001 represents a significant advancement in the delivery of RAS. The system integrates wearable inertial sensors with proprietary, closed-loop algorithms to autonomously deliver individualized, progressive, music-based rhythmic cueing during walking in the home environment. Specifically, the MR-001 neurorehabilitation system consists of three components: two shoe-worn wearable inertial sensors that measure walking patterns and gait parameters in real time, a bluetooth headset to deliver RAS via music, and a touchscreen control unit preloaded with intervention software to deliver personalized therapy. The MR-001 neurorehabilitation system continuously assesses the user's entrainment to the target tempo and evaluates gait symmetry and variability, while safely and autonomously adjusting the target walking speed without direct clinician input.

Unlike traditional RAS approaches that require in-person clinician oversight, this technology adapts tempo and cueing in real time based on gait quality and entrainment, enabling safe, unsupervised home use. A large-scale study (n=204) in the stroke population provides strong preliminary evidence supporting the feasibility, safety, and effectiveness of this approach. In the OrcHESTRAS single arm, pragmatic home-based trial, over 81.9% (95% confidence interval \[CI\] 0.76-0.87) achieved moderate to high weekly use \> 4 weeks meeting the primary endpoint (p\<0.001) over 12 weeks, exceeding the predefined feasibility benchmark of 60%. Additionally, participants demonstrated significant improvements in walking endurance (6-minute walk test \[6minWT\] 26.1 ± 5.6m; 95% CI 14.99, 37.22) and functional mobility (Timed Up and Go \[TUG\] -1.45 ± 0.31s; 95% CI -2.06, -0.84 p\< 0.001). Weekly use influenced effectiveness with each additional week of use predicting a 5.82m greater gain in the 6minWT (standard error \[SE\] = 2.05; 95% CI 1.77, 9.87\], p\<0.005. Importantly, the intervention exhibited an acceptable safety profile across more than 100,000 minutes of autonomous use, with adverse events and falls largely consistent with baseline risk in chronic stroke populations (preprint doi.org/10.64898/2026.03.13.26348352)

Brain derived neurotrophic factor (BDNF) is a growth factor known to be important for both neuronal and cognitive plasticity. Increased BDNF levels improves cell signaling promoting synaptic plasticity and neurogenesis .37,38 High intensity interval training and continuous moderate to high intensity exercise are both associated with increased BDNF levels in animal models,39 but the impact of high-intensity training on BDNF has not been tested in individuals with moderate to severe TBI. We propose to evaluate changes in BDNF levels after 6 weeks of training interventions (including high-intensity training) in individuals with moderate to severe TBI.

Although a growing body of literature supports RAS in brain injury, the neural mechanisms underlying RAS remain poorly characterized. Functional near-infrared spectroscopy (fNIRS) offers a portable, ecologically valid method for assessing cortical activation during auditory and motor tasks and is particularly well suited for rehabilitation research involving movement. Emerging fNIRS evidence in acquired brain injury demonstrates altered and exaggerated prefrontal cortical hemodynamic responses to musical and rhythmic auditory stimuli, suggesting inefficient or compensatory neural processing during auditory-cognitive integration tasks.24 These findings support the feasibility of using fNIRS to objectively quantify brain responses to rhythmic auditory input after brain injury and highlight a critical gap in understanding how RAS modulates cortical networks during motor rehabilitation in individuals with TBI. Additionally, while RAS is supported by a robust evidence base in stroke, comparable data are lacking in individuals with TBI despite shared mechanisms of motor control impairment and neuroplastic potential. Individuals with TBI may demonstrate even greater benefit from music-based, home-delivered interventions that reduce cognitive load, enhance enjoyment, and support sustained engagement in rehabilitation. However, foundational data are needed to establish feasibility, adherence, safety, and preliminary signal of benefit before larger efficacy trials in this population are warranted.

Study Objective and Design The purpose of this pilot randomized controlled trial with a waitlist control study is to determine the safety, feasibility, and adherence of a home-based, music-guided RAS intervention using the MR-001 for individuals with TBI, and to explore preliminary effects on mobility, cognition, mood, enjoyment, perceived change, and cortical excitation. This work addresses critical barriers to long-term rehabilitation by evaluating a home-based approach to gait recovery in the chronic TBI population.

Aim 1:

To determine the safety, feasibility, and adherence of a home-based, music-guided RAS intervention delivered via the MR-001 in individuals with TBI.

Hypothesis 1:

The MR-001 intervention will be safe and feasible for individuals with chronic TBI (\>6 months). Safety will be demonstrated by the absence of serious device-related adverse events. Feasibility will be demonstrated by the ability to enroll and retain 30 individuals with TBI; and adherence will be defined as enrolled individuals will complete \> 60% of scheduled training sessions (30-minute sessions three times per week) over the 8-week intervention period.

Aim 2:

Evaluate the preliminary effects of using home-based RAS (MR-001) on the change in walking endurance, gait speed, and balance, both between groups and within the waitlist control group.

Hypothesis 2a:

Participants will demonstrate clinically meaningful improvements in walking endurance (6-Minute Walk Test \[6minWT\]), gait speed (10-Meter Walk Test \[10MWT\]), and balance (Berg Balance Scale \[BBS\]; Timed Up and Go \[TUG\]; Functional Gait Assessment \[FGA\]; High Level Mobility Assessment Tool \[HiMAT\]) over the intervention period (eight weeks) compared to the waitlist control group.

Hypothesis 2b:

Participants within the waitlist control group will demonstrate clinically meaningful improvements in walking endurance, gait speed, and balance over the intervention period (eight weeks) compared to the eight-week waitlist control period.

Aim 3:

Evaluate the preliminary effects of using home-based RAS (MR-001) on the change in cognition, mood, fatigue, and impression of change, both between groups and within the waitlist control group while also assessing activity enjoyment in both groups after training.

Hypothesis 3a:

Participants will demonstrate clinically meaningful improvements in cognition (Brief Test of Adult Cognition by Telephone \[BTACT\]), mood (Brief symptom Inventory, \[BSI-18\]), fatigue (Modified Fatigue Impact Scale \[MFIS\]), and participant global impression of change (PGIC) over the intervention period (eight weeks) compared to the waitlist control group.

Hypothesis 3b:

Participants within the waitlist control group will demonstrate clinically meaningful improvements in cognition, mood, fatigue, and impression of change over the intervention period (eight weeks) compared to the eight-week waitlist control period.

Hypothesis 3C: Participants in both groups will report greater enjoyment (PACES) with training using the MR-001.

Exploratory Aim:

Explore within participant changes in global cortical excitation (fNIRS) when walking overground with MR-001 compared to walking overground without MR-001

PARTICIPANT SELECTION CRITERIA

Inclusion and exclusion criteria for participation are provided in Table 1 below:

Table 1. Eligibility criteria for participants Inclusion Exclusion 1) have a moderate to severe TBI that required inpatient rehabilitation; 2) able to ambulate independently, with or without an assistive device.; 3) ambulating \< 1.4 m/s (comfortable walking speed) 4) demonstrate a reciprocal gait pattern; 5) ability to follow directions/standardized instructions; 6) minimum 18 years of age at consent. 1) Uncontrolled cardiopulmonary, metabolic, or infectious disorder

• 10MWT [Срок оценки: Baseline, 8 weeks, 16 weeks]
• Berg Balance Scale [Срок оценки: Baseline, 8-weeks, 16-weeks]
• 6minWT [Срок оценки: Baseline, 8 weeks, 16 weeks]
• Functional Gait Assessment (FGA) [Срок оценки: Baseline, 8 week, 16 week]
• High-Level Mobility Assessment Tool (HiMAT) [Срок оценки: Baseline, 8 week, 16 week]