While baseline weakness is clearly an important factor that contributes to disability post stroke, neuromuscular fatigue (the acute reduction in force production) of the paretic musculature likely compounds strength deficits and further exacerbates disability. For example, neuromuscular fatigue limits the distance a stroke survivor can walk in the community, or their ability to sustain higher walking speeds. The proposed study aims to improve our understanding of the central mechanisms of neuromuscular fatigue in people post stroke in order to optimize strength training. In healthy individuals, both neural and muscular factors are determinants of neuromuscular fatigue. Preliminary data from our laboratory suggests a greater contribution of neural components to neuromuscular fatigue in the paretic musculature. To date, the locus of neuromuscular fatigue is unknown for stroke survivors. Limited neural excitation of paretic muscle not only interferes with the acute force demands of an activity, but also limits strength training, which depends on sufficient muscle activation to initiate muscular hypertrophy. Current rehabilitation strategies, therefore, are likey deficient because they work under the premise that the paretic muscle is optimally activated by the nervous system and adequately fatigued. Locomotor retraining post stroke may be at a particular disadvantage as it requires significant acquisition of both strength and skill, but training frequently occurs with individuals practicing at low force levels. We propose that chronic adaptations in motor unit firing behavior and neural activation of muscle contribute significantly to increased paretic muscle fatigability. We also propose that decreasing the contributions of motor unit firing behavior to central fatigue will improve walking. Accordingly, Aims 1 and 2 will examine spinal and supraspinal contributions to paretic muscle fatigability.
Aim 3 will relate motor unit firing behavior with walking function and identify components of walking most affected by neuromuscular fatigue. This proposal adopts an innovative model of motor impairment post stroke because it implicates the role of motor unit firing behavior in fatigue and is the foundation for future clinical studies that aim to optimize force generating capabilities of leg muscles and walking function.

Public Health Relevance

The purpose of this study is to examine neural mechanisms of neuromuscular fatigue in the chronic stroke population and quantify how muscle fatigue impacts walking function. Evidence from this study will be used to develop therapeutic interventions that optimize strength training and reduce disability in individuals with stroke.

National Institute of Health (NIH)
National Institute of Neurological Disorders and Stroke (NINDS)
Academic Research Enhancement Awards (AREA) (R15)
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Motor Function, Speech and Rehabilitation Study Section (MFSR)
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Chen, Daofen
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Marquette University
Other Health Professions
Sch Allied Health Professions
United States
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Kirking, Meghan; Berrios Barillas, Reivian; Nelson, Philip Andrew et al. (2017) Sex Differences in Neuromuscular Fatigability of the Knee Extensors Post-Stroke. Brain Sci 7: