Sex-Specific Impact of Stroke on Neuromuscular Fatigability in Older Adults - Project Summary/Abstract Aging is a non-modifiable risk factor of stroke. Notably, females are more likely to experience a stroke at an older age and tend to have worse recovery outcomes than males post stroke, especially in motor recovery. In addition to baseline weakness, increased neuromuscular fatigability (an acute, exercise-induced reduction in maximal voluntary force or power generation) of the paretic musculature following a stroke limits task endurance of activities such as walking. Recently, our laboratory showed that fatigability may be exacerbated in females, but not males, with stroke as compared to neurologically intact controls during a sustained isometric contraction. However, little is known regarding stroke-related sex differences in fatigability during dynamic tasks despite their greater relevance to everyday activities like walking. In people without stroke, older females show a relatively blunted vascular response during dynamic exercise and are more fatigable than older males, but it is unknown if this persists post stroke. The F99 phase research aims to quantify sex differences in fatigability during a dynamic task post stroke and examine the role of sex differences in peripheral muscle perfusion as a mechanism. We propose that impaired muscle perfusion contributes to the greater fatigability during dynamic knee extension contractions in females versus males with chronic stroke. If muscle perfusion is a mechanism, then manipulating blood flow during exercise would modulate sex differences in fatigability among people with chronic stroke. Aim 1 will test the hypothesis that females will have greater fatigability than males post stroke and that fatigability will be negatively correlated with the metrics of blood flow to the exercising musculature. Aim 2 will test the hypothesis that sex differences in fatigability post stroke will be lessened during the same exercise with blood flow occlusion via an inflatable cuff to the exercising limb. Aim 3 will test the hypothesis that sex differences in fatigability post stroke will also be minimized during the same exercise following a single session of ischemic conditioning (IC) procedure. IC is a well-established non-invasive procedure which has been used to enhance blood flow through facilitating vasodilation. Results from the proposed F99 research will contribute to targeted rehabilitative interventions to optimize motor recovery post stroke, especially for females. For the K00 phase, I will shift focus from stroke-related peripheral perfusion impairments to aging-related changes in cortical neurovascular function to better understand the cortical manifestations of neurological disorders on motor performance. With guidance from my K00 mentor, I aim to establish robust quantitative imaging biomarkers of neuromuscular fatigue to study aging-related neurological diseases and the response of individual patients to personalized therapeutic interventions using non-invasive techniques such as functional magnetic resonance imaging and transcranial Doppler ultrasonography. Completion of the proposed F99 and K00 will be a springboard for my future success as an independent extramurally funded aging researcher.
