Biomechanical and Neural Mechanisms of Post-stroke Gait Training

The study seeks to develop an understanding of how, why, and for whom fast treadmill walking (Fast) and Fast with functional electrical stimulation (FastFES) induce clinical benefits, allowing future development of cutting-edge, individually-tailored gait treatments that enhance both gait quality and gait function.

Stroke is the leading cause of adult disability in the United States, with stroke prevalence expected to increase by 20% in the next 20 years. Stroke induces a cascade of neurophysiologic changes in cortical and spinal circuits that result in biomechanical impairments (reduced paretic propulsion, footdrop) and gait dysfunction (reduced speed and endurance). This study evaluates neurobiological and biomechanics mechanisms of two gait (walking) rehabilitation treatments. Gait impairments persist at discharge from rehabilitation in over two thirds of stroke survivors, reducing community participation and quality of life.

Stroke gait deficits are complex and multi-factorial, posing a problem well-matched to the NIH precision medicine initiative. Stroke gait impairments adversely affect kinematics and kinetics in all paretic lower limb joints, disrupt stance and swing phases, and are marked by inter-limb asymmetry. One intervention cannot target all post-stroke gait deficits. Multiple factors, including biomechanics, energy cost, and functioning and integrity of corticomotor neural pathways can influence stroke gait function and training-induced gait improvements.

Fast treadmill walking (Fast) is an evidence-based, clinically-used intervention, comprising high-intensity, high-repetition, bilateral stepping practice. High-intensity treadmill training was recommended by clinical practice guidelines for locomotor training at the 2018 American Physical Therapy Association (APTA) conference. Fast provides practice of thousands of steps and aerobic exercise, which may induce bilateral neuroplasticity. However, without adjunctive feedback or cues (verbal, biofeedback, stimulation), Fast is not targeted to specific gait deficits or the paretic leg. Importantly, neural correlates underlying Fast are unclear. A single session of high-intensity interval treadmill walking exacerbated already suppressed ankle muscle corticospinal excitability in the paretic leg post-stroke. Four weeks of treadmill training in chronic stroke improved gait speed compared to control treatment, but increased cortical excitability in the non-lesioned hemisphere. Despite Fast and treadmill-based interventions gaining clinical popularity, important questions pertaining to neural mechanisms of Fast are unknown.

Recent work has demonstrated that combining Fast with functional electrical stimulation (FastFES) not only leads to improvements in gait speed but also reduces energy cost (EC) of stroke gait. FastFES is an intervention combining fast treadmill training and functional electrical stimulation (FES) to ankle plantar- and dorsi-flexor muscles during paretic terminal stance and swing phases, respectively. As a paradigm for studying gait training mechanisms, FastFES offers several advantages including using hypothesis-based biomechanical approach to improve gait function by targeting impairments in paretic propulsion, and is delivered only to the paretic leg.

The study seeks to develop an understanding of how, why, and for whom fast treadmill walking (Fast) and Fast with functional electrical stimulation (FastFES) induce clinical benefits, allowing future development of cutting-edge, individually-tailored gait treatments that enhance both gait quality and gait function.

This mechanism-focused randomized clinical investigation will compare the effects of 12 sessions of Fast and FastFES in individuals with post-stroke hemiparesis. Gait biomechanics, EC, corticospinal excitability, and gait function will be evaluated at two baseline visits,after 3 gait training sessions, after 12 gait training sessions, and at two follow-ups (3 and 6 weeks post-training).

Eligibility Criteria:
Inclusion Criteria:

* at least 6 months since stroke
* single cortical or subcortical ischemic stroke
* able to walk 10-meters with or without assistive device
* sufficient cardiovascular health and ankle stability to walk on treadmill for 2-minutes at self-selected speed without orthosis
* resting heart rate 40-100 bpm

Exclusion Criteria:

* hemorrhagic stroke
* cerebellar signs (ataxic ("drunken") gait or decreased coordination during rapid alternating hand or foot movements
* score of \>1 on question 1b and \>0 on question 1c on NIH Stroke Scale
* inability to communicate with investigators
* musculoskeletal conditions or pain that limit walking
* neglect/hemianopia, or unexplained dizziness in last 6 months
* neurologic conditions or diagnoses other than stroke
* lack of sensation in lower limb affected by stroke
* any medical diagnosis that would hinder the participant from completing the experimental trial
* additional exclusion criteria due to contra-indications to TMS (measurement of corticospinal excitability) are: history of seizures, metal implants in the head or face, history of recurring or severe headaches/migraine, headache within the past 24 hours, presence of skull abnormalities or fractures, hemorrhagic stroke, history of dizziness, syncope, nausea, or loss of consciousness in the past 6 months