Joel Kevin Shoemaker

The exercise intensity at which muscle sympathetic nerve activity (MSNA) recorded in the inactive limb begins to rise during rhythmic handgrip (RHG) exercise remains unknown. Forearm blood flow during RHG exhibits an attenuated rate of increase at ∼50% maximal voluntary contraction force (MVC), although whether this occurs in parallel with sympathetic activation remains unknown. Therefore, we tested the hypotheses that MSNA increases at intensities <50% MVC and coincides with an attenuation in forearm vascular conductance (FVC) during incremental RHG. Twenty-nine young adults (11 males; 26 [4] yrs; mean [SD]) underwent assessments of blood pressure (photoplethysmography), cardiac output and total peripheral resistance (TPR; Modelflow), brachial artery blood flow of the exercising arm (doppler ultrasound), and MSNA (microneurography) during incremental RHG exercise to fatigue. An operational onset threshold (deviation beyond baseline variability) for MSNA burst frequency, amplitude, and total activity occurred between 36-41% MVC. Cardiac output began to rise at 37% MVC, whereas mean arterial pressure began to rise at 45% MVC. TPR demonstrated a linear decline. FVC and brachial artery diameter increased rapidly at low intensities, with attenuation in the rate of rise at ∼20% MVC, whereas forearm blood flow and shear rate increased linearly. Collectively, these data challenge the prior view that during RHG, MSNA increases only at intensities above 50% MVC, and indicate that sympathetic recruitment occurs during light-to-moderate stages of incremental exercise. Moreover, the dissociation between MSNA and FVC indicates that resting limb MSNA does not predict direct efferent sympathetic vasoconstrictor signalling within contracting skeletal muscle.

This study found that 1) medium-sized synchronous APs exhibit central and peripheral baroreflex hysteresis and 2) despite negligible baroreflex regulation, asynchronous APs attenuate reductions in blood pressure during cardiac cycles with no synchronous AP activity. These findings suggest that blood pressure regulation is achieved via subpopulations of synchronous and asynchronous postganglionic neurons that receive different central baroreflex and nonbaroreflex inputs. Central and peripheral sympathetic baroreflex hysteresis may reflect a moment-to-moment compensatory strategy regulating blood pressure.

Intravenous dexmedetomidine infusion (selective α ₂ -adrenergic receptor agonist) 1) reduced the firing probability and strength of baroreflex control over medium-sized sympathetic action potentials in muscle sympathetic nerve activity (MSNA) and 2) attenuated the transduction of MSNA bursts to changes in blood pressure (BP) by reducing the magnitude of BP responses and increasing the time to peak BP. These data suggest that neural and vascular α ₂ -adrenergic mechanisms contribute to sympathetic baroreflex regulation of human BP.

Our knowledge remains incomplete regarding the impact of microgravity exposure on the central and peripheral components of the sympathetic baroreflex in males and females. Using long-duration head-down bed rest as a model of simulated microgravity in humans, we found that microgravity exposure: 1) impairs the peripheral component of the sympathetic baroreflex at rest in all individuals and 2) augments the vascular response to postural stress in females to maintain blood pressure homeostasis.

INTRODUCTION: We tested the hypothesis that increased middle cerebral artery velocity (MCA velocity) during complex motor (overground walking) and cognitive tasks (e.g., dual task) is associated with cognitive performance in older adults with varying levels of cognitive ability. METHODS: Fifty‐six participants (19 females, 75 ± 7 years old) completed a seated single task that assessed working memory performance; a walking single task, assessing overground walking gait speed; and a dual task, combining both. Continuous MCA velocity was collected, and participants completed a Montreal Cognitive Assessment (MoCA). RESULTS: Higher MCA velocity was associated with faster gait speed, better working memory performance, and greater MoCA scores (all p < 0.05). Participants with lower MoCA scores had lower MCA velocity ( p = 0.052), slower gait speed ( p = 0.035), and lower working memory performance ( p = 0.016) than people with higher MoCA scores. The hyperemic response of MCA velocity from single task walking to the dual task with increased cognitive load significantly contributed to MoCA scores ( p = 0.017). DISCUSSION: The functional response of cerebral blood flow with these tests suggests vascular properties may be considered a biomarker indicative of subclinical cognitive function during walking tasks. Highlights: Mobile devices simultaneously assessed neurovascular coupling and dual‐task cost. Middle cerebral artery velocity (MCA velocity) is negatively associated with dual‐task cost. MCA velocity is associated with gait speed, working memory, and Montreal Cognitive Assessment scores. MCA velocity decreased from controls to mild cognitive impairment to dementia. Novel methodological approach to utilize MCA velocity during overground walking, single‐tasks, and dual‐tasks.

Background: Older adults with mild cognitive impairment (MCI) have a higher risk of gait impairments and falls; yet, the effects of multimodal interventions, including combinations of exercises with cognitive training, on improving their mobility remain unclear. Objectives: To investigate the synergistic effects of aerobic-resistance exercise combined with cognitive training, with or without vitamin D supplementation, on gait performance and falls risk in older adults with MCI. Methods: The effect of 20 weeks of aerobic-resistance exercise, cognitive training, and Vitamin D supplementation (10 000 IU 3×/week) on gait and falls in older adults with MCI was evaluated in the SYNERGIC trial, using a fractional factorial design. Assessments were conducted at baseline, 6-month endpoint (after intervention) and 12-month endpoint (follow-up). Eligible participants were between the ages of 65 and 84 years with MCI enrolled from 19 September 2016 to 7 April 2020. Main outcomes of interest for gait performance were gait speed and gait variability changes, whilst for falls were incidental falls and incidental injurious falls. Results: Amongst 161 participants, the four exercise-based arms improved gait speed (+7.5 cm/s, P < .001) and reduced falls (incidence rate ratios (IRR) = 0.65, 95% confidence interval (CI): 0.32–1.42, P = .25) and injurious falls (IRR = 0.38, 95% CI: 0.15–1.05, P = .05) at 6-month endpoint. Falls reduction reached statistical significance (IRR = 0.28, 95% CI: 0.13–0.64, P = .002) at 12-month endpoint. Exercises combined with cognitive training showed the greatest gains in gait speed at 6-month endpoint (P < .001) and in reducing falls at 12-month endpoint (IRR = 0.24, 95% CI: 0.05–0.77, P = .02) compared to the control. Vitamin D did not enhance outcomes and increased gait variability, a marker of instability. Conclusion: Aerobic-resistance exercise combined with sequential computerised cognitive training improved gait performance at 6 months and decreased the risk of falls and injuries at 12 months in older adults with MCI. The addition of vitamin D did not produce benefits.

We examined the impact of cannabis inhalation on the firing and recruitment patterns of postganglionic muscle sympathetic action potentials (APs) in humans. We found that cannabis inhalation induced a derecruitment of larger, high-threshold APs, reduced the discharge probability and baroreflex control of medium-sized APs at rest, and impaired sympathetic AP recruitment during an end-expiratory apnea. Collectively, these data indicate that cannabis impairs the fundamental, homeostatic communication between the sympathetic nervous system and cardiovascular system.

We used a novel, depth-enhanced optical monitoring system to investigate low-frequency hemodynamic oscillations (0.02–0.16 Hz) in cerebral microvascular perfusion, oxygenation, and relative metabolic rate of oxygen in patients with MCI and cognitively intact controls. Our findings indicate cerebrovascular dysfunction in MCI, wherein the regulation of oxygenation is altered to maintain metabolism in an environment with attenuated vascular control. These findings highlight the potential of using optical technology to assess cerebrovascular function in MCI.

Central artery stiffening increases the haemodynamic pulsations transmitted downstream towards target organs, including the brain. While recent evidence suggests that long duration spaceflight is associated with reduced common carotid artery (CCA) distensibility, cerebrovascular pulsatility has not been extensively characterized in astronauts. This study investigated changes in pulsatility from pre‐flight to after 6 months in space, using a secondary analysis of data from four separate experiments. Middle cerebral artery blood velocity (MCAv) was measured during supine rest in 27 astronauts (20 men, 7 women). In subsets of this cohort, we measured CCA distensibility and β stiffness (n = 20), and CCA wave intensity (n = 12). The overall increase in MCAv pulsatility index (PI_mca) from pre‐flight to post‐flight was not significant (0.73 ± 0.12 vs. 0.77 ± 0.11, P = 0.060, partial η² = 0.13). However, individual changes in PI_mca were directly associated with changes in estimated aortic pulse pressure (r = 0.51, P = 0.007) and β stiffness (r = 0.54, P = 0.015), and inversely associated with changes in distensibility (r = −0.62, P = 0.003), in separate bivariate analyses. Wave intensity analysis suggested a reduction in normalized wave reflection (P = 0.07), and that forward compression wave amplitude was directly related to PI_mca (r = 0.64, P = 0.025). These findings suggest that PI_mca in the days immediately following spaceflight is a function of lower carotid distensibility, highlighting the interplay between arterial stiffness and cerebrovascular pulsatility.

Yellow-rumped warblers, a small songbird that conducts migratory flights, were found to fly to altitudes above 4,000 m above sea level in simulated flights using a hypobaric wind tunnel. Circulating adrenaline suggests that warblers flying at 75% of individual maximum altitudes are not experiencing arterial hypoxia, allowing them to maintain aerobically demanding migratory flight at high altitudes.