Neuro-Intermuscular Coordination Enhancement (NICE) Rehabilitation Through Human-Machine Interaction in Chronic Stroke

Neuro-Intermuscular Coordination Enhancement (NICE) Rehabilitation

The objective of this study is to develop Neuro-Intermuscular Coordination Enhancement (NICE) rehabilitation, a novel neuromuscular control signal-guided strategy that visually guides stroke patients to individually activate motor modules through human-machine interaction. Ultimately, the development will lead to better clinical motor recovery, better quality of life, and lowered healthcare costs associated with the impairment.

Stroke is the leading cause of severe long-term disability, affecting 9.4 million Americans. Each year around 800,000 people suffer a stroke even in the USA. Chronic upper extremity motor impairment is a major contributing factor to disability; functional use of the affected UE in daily life is a key factor for increased independence, return to work, and overall quality of life. Thus, effective and innovative treatment to address long-term disability is both a major public health need and an economic necessity.

This study is an early-stage, randomized controlled rehabilitation trial designed to evaluate the clinical effects, feasibility, transfer of therapeutic gains, and exploratory neurophysiological correlates of Neuro-Intermuscular Coordination Enhancement (NICE) in individuals with chronic stroke and upper-extremity hemiparesis.

Forty-eight participants will be enrolled to obtain a target analyzable sample of 40 participants. Eligible participants will be randomized to either: (1) NICE, a motor module-guided rehabilitation intervention using isometric human-machine interaction and real-time EMG-based visual feedback to retrain impaired intermuscular coordination patterns; or (2) an active comparator consisting of dose-matched EMG amplitude biofeedback exercise. Both interventions will be delivered three times per week for six weeks (18 total sessions). Participants will complete assessments at baseline, immediately post-intervention, and at 10- and 18-week follow-up time points.

Outcomes will include standardized clinical measures of upper-extremity motor impairment and function, measures of intermuscular coordination derived from surface electromyography, kinematic measures obtained during untrained dynamic motor tasks, and EEG-based measures of brain activity and connectivity.

The primary objective is to determine whether NICE improves upper-extremity motor impairment relative to the active comparator. Secondary objectives are to evaluate intervention-related changes in intermuscular coordination and transfer of therapeutic gains to untrained motor behaviors. Exploratory objectives are to characterize rehabilitation-associated neurophysiological changes and examine relationships among EEG-derived biomarkers, intermuscular coordination, and clinical recovery outcomes.

Inclusion criteria for individuals after stroke are:

• Hemiparetic chronic stroke survivors more than 6 months after stroke onset
• Adults aged 21-80 years, including both female and male participants
• Individuals with a single unilateral ischemic or hemorrhagic stroke
• Individuals with Upper Extremity Fugl-Meyer Assessment score between 10 and 59 out of 66
• Individuals who have not received botulinum toxin injections in the upper extremity within the past 3 months
• Individuals without severe spasticity, defined as Modified Ashworth Scale score ≤3 at the elbow and shoulder

Exclusion criteria for individuals after stroke are:

• Individuals younger than 21 years of age or older than 80 years of age
• Individuals with an orthopedic disorder involving the upper limbs
• Individuals unable to produce voluntary upper-extremity muscle EMG activity;
• Individuals with cognitive impairment sufficient to interfere with informed consent or successful completion of the protocol, assessed using the Montreal Cognitive Assessment or other IRB-approved screening procedures.
• Individuals whose stroke-affected arm has an intermuscular coordination pattern similarity score >0.80 relative to the non-affected arm

Inclusion criteria for healthy individuals are:

• Healthy adults aged 21-80 years, including both female and male participants
• Individuals with no known neurological or orthopedic injuries

Exclusion criteria for healthy individuals are:

• Individuals younger than 21 years of age or older than 80 years of age
• Individuals with known neurological disorders
• Individuals with orthopedic injuries or conditions affecting upper-extremity movement
• Individuals unable to provide informed consent