Project Summary
Fatigue, lack of physical and/or mental energy, is a common reported symptom with osteoarthritis (OA) that
may limit physical capacity and contribute to disability. In healthy older adults, muscle fatigue has been
proposed as a key contributor to symptoms of fatigue. Knee extensor muscle dysfunction, including lower
isometric and isokinetic torques and altered muscle activation patterns, are common with knee osteoarthritis
(KOA). Together these changes in neuromuscular function may increase locomotor muscle fatigue in KOA
compared to age-matched controls, as a greater percentage of the muscle’s capacity must be used for daily
activities such as walking. To date, evidence to explain whether and how muscle fatigue may alter control and
coordination of movement in KOA is limited. Our working hypothesis is that KOA-related neuromuscular
changes may exacerbate locomotor muscle fatigue (Aim 1) and alter the neuro-mechanical response to muscle
fatigue during gait (Aim 2), thereby contributing to mobility declines. In healthy adults, central and peripheral
mechanisms can both contribute to muscle fatigue. However, whether the source of fatigue in individuals with
KOA is central or peripheral is unclear which may be due to maladaptive neuroplastic changes that occur with
KOA. To assess and compare the mechanisms for loss of force with a prolonged walk in individuals with KOA
we will use transcranial magnetic stimulation to measure motor cortex excitability and inhibition (Aim 3). To
test these hypotheses, data will be gathered on 2 groups of 10 men and 10 women: KOA (65-80 years) and
older healthy controls (70-80 years). Both groups will be relatively sedentary, which will be verified
quantitatively using accelerometry. In this cross-sectional study design, we will implement our new
physiologically and clinically relevant 30-minute treadmill walk to induce knee extensor muscle fatigue and
then quantify the response with measures of gait mechanics, electromyography, physical performance, and
motor cortex excitability. The problem to be addressed, muscle fatigue in KOA, and its impact on mobility is
significant and currently prevents many older adults from achieving an optimal health span. Understanding
the mechanisms underlying changes in physical function, such as muscle fatigue in individuals with KOA will
allow for a better understanding of how to optimize interventions in this population. The completion of the
project and the proposed training plan activities including skill development in new experimental and
advanced computational approaches as well as professional development activities will have a significant,
positive impact on the development of the PI as an independent researcher, contributing to the stated goals
of the NIH to enhance training of a diverse work force.