A primary impairment associated with post-stroke hemiparesis is the failure to make rapid graded adjustment of muscle force (i.e. muscle power) within the context of purposeful complex synergies (e.g., coordination during walking). Not surprisingly, the impact of stroke on walking is significant, with less than 50% of survivors progressing to independent community ambulation. Even among those who achieve independent ambulation, significant residual deficits persist in balance and gait speed, with ~75% of persons post-stroke reporting limitations in mobility related to walking. Muscle weakness is the most prominent motor consequence among the nearly 6 million survivors of stroke living in the United States and the strongest predictor of functional disability in this large clinical cohort. To date, the physiological mechanisms that contribute to muscle dysfunction in hemiparetic subjects are largely unstudied. Moreover, evidence regarding the efficacy of interventions aimed at attenuating impaired muscle function and the ensuing functional consequences in the post-stroke population is equivocal and viable therapeutic options to remediate hemiparetic muscle weakness remain among the most pressing challenges for biomedical research. We propose that impaired muscle power (the product of muscle strength and velocity) generation is causal of functional (walking) disability post-stroke. In addition, coordination deficits are also critical determinants of functional performance. We have developed a comprehensive theoretical framework that defines and measures the factors underlying disordered muscle function and coordination and will apply this framework to Post-stroke Optimization of Walking using Explosive Resistance (POWER) training. Our goals over the four year funding period are to 1) quantify neural and muscular adaptations that contribute to impaired muscle power generation post-stroke;2) assess effects of POWER training on neural and muscular adaptations in paretic and non-paretic muscle;and 3) determine the relationship between changes in neural and muscular adaptations following POWER training and locomotor improvements. Innovative aspects of the proposed work include the novel training intervention;the advanced magnetic resonance assessments;as well as the unique measure of the coordination that we propose. It is our belief that: a) neural and muscular adaptations following stroke are associated with impaired muscle power generation as well as locomotor ability, b) POWER training attenuates functional deficits by addressing the underlying neural and muscular elements and c) functional improvements following training are predicated on improving the most prominent neural and muscular contributors to muscle power generation. If correct, the data generated will provide an entirely new level of evidence regarding the effectiveness of this novel intervention strategy on improving functional performance as well as the importance of peripheral muscle properties as predictors of locomotor ability post-stroke.

Public Health Relevance

Hemiparesis, strictly defined as (muscular) weakness affecting one side of the body, is seen in three-quarters of individuals following stroke. Weakness in this population results from both neural and muscular factors which include, respectively, the ability of the central nervous system to activate skeletal muscle as well as the force generating capacity of the muscle. Our overall goal is to improve walking in persons post-stroke by training subjects with an intervention that specifically targets existing neural and muscular impairments, thereby facilitating locomotor recovery.

Agency
National Institute of Health (NIH)
Institute
Veterans Affairs (VA)
Type
Non-HHS Research Projects (I01)
Project #
1I01RX000844-01A3
Application #
8594581
Study Section
Brain Injury: TBI & Stroke (RRD1)
Project Start
2013-10-01
Project End
2017-09-30
Budget Start
2013-10-01
Budget End
2017-09-30
Support Year
1
Fiscal Year
2014
Total Cost
Indirect Cost
Name
Ralph H Johnson VA Medical Center
Department
Type
DUNS #
039807318
City
Charleston
State
SC
Country
United States
Zip Code
29401