The sympathetic nervous system is a master regulator of cardiovascular function. Over the last two decades there has been renewed interest in identifying the underlying behavior of post-ganglionic sympathetic nerves. By using wavelet-based approaches to isolate underlying action potentials (APs) within multi-unit recordings, tremendous progress has been made to better understand the firing characteristics of individual, and clusters of, sympathetic neurons. These studies, however, have applied these approaches within the context of muscle sympathetic nerve activity recorded from humans, limiting the depth of experimentation into mechanisms that determine sympathetic action potential behaviours and patterns. Here, we extended and refined this wavelet-based approach and uniquely apply it to the measurement of sympathetic nerve activity directed towards the critical splanchnic vascular bed in rodents (i.e., splanchnic sympathetic nerve activity; sSNA). We subsequently quantified AP occurrence within and across bursts and employed k-means clustering on the amplitude of APs and bursts. We first demonstrate that a wavelet-based approach is feasible to implement in rodent recordings. We subsequently show that there is a significant increase in the proportion of large APs and decrease in the proportion of small APs as burst size increases (p < 0.001). Analysis of AP amplitude and latency demonstrated a significant negative association (p < 0.001), indicating that larger APs exhibit shorter latencies. Finally, we demonstrate good agreement between a group-averaged mother wavelet and individual animal mother wavelets. This methodological advance sets the stage for rodent-based mechanistic studies to further understand communication strategies employed by the sympathetic nervous system.

Objective: Functional neuroimaging shows reduced neural activity in the hippocampus (HC), insular cortex (IC) and amygdala during rapid heart rate (HR) responses to brief isometric handgrip exercise (HG). However, the specific electrophysiological mechanisms remain unclear. Hypothesis: This preliminary study tested the hypothesis that cortical stimulation (CS) would reduce HR responses to HG. The a priori expectation was that HR would increase with HG in both healthy control (Control) and drug-resistant epilepsy (DRE) groups. Methods: Two protocols were studied: 1) Control vs DRE: To assess an independent effect of DRE, HR was obtained from the electrocardiogram in groups of Control (n=19; 7F/12M; age: 6±10 years) and DRE (n=18; 5F/13M; age: 34±10 years) participants. Changes in vagal cardiac function were assessed using the root mean square of successive differences (RMSSD). We collected these variables at baseline and the first 10 seconds of HG at 40-50% of maximum voluntary contraction. Changes from baseline to HG were calculated. 2) DRE with CS: We evaluated RMSSD and HR in people with DRE (n=13; 3F/10M; age: 35±11 years; n=10 from above DRE group) at rest and during HG both without and with CS (1 Hz, 5 mA, 10 seconds; delivered by stereoelectroencephalography). Participants received CS in the HC (n=9), IC (n=5), or amygdala (n=2) (n=3 tested 2 CS sites each). The research goal of CS was to minimize regional neural deactivation in each site of interest. Results: 1) Control vs DRE: In response to HG, HR increased in Control from 64±8 beats per minute (bpm) at baseline to 70±10 bpm (p=0.001), while HR only minimally increased in DRE (70±11 bpm at baseline vs 72±11 bpm after HG) (p=0.086). The increase in HR in Control (6.30 ± 4.21 bpm) was greater than in DRE (1.45±3.39 bpm) (p< 0.001). In response to HG, RMSSD decreased in Control from 59±25 to 43±15 ms (p=0.002) and in DRE from 27±14 to 22±12 ms (p=0.002). The reduction in RMSSD in Control (-15.58±19.11 ms) was greater than in DRE (-4.96±5.73 ms) (p=0.030). 2) DRE with CS: Neither HR nor RMSSD changed from baseline pre-CS to CS alone (no HG). In response to HG alone, HR increased ~3 bpm (p=0.038), and RMSSD decreased ~6 ms (p=0.045). In response to HG with CS, HR did not change during stimulation of the HC (80±17 vs 82±15 bpm) (p=0.167), IC (77±9 vs 77±10 bpm) (p=0.370), or amygdala (82±4 vs 83±9 bpm) (p=0.782). In response to HG with CS, RMSSD also did not change with stimulation of the HC (23±19 vs 20±7 ms) (p=0.489), IC (19±12 vs 19±10 ms) (p=0.873), or amygdala (27±7 vs 25±10 ms) (p=0.679). Summary and Conclusions: Compared to Control, DRE participants were marked by impaired HR responses to HG, as well as lower baseline and lower HG-induced changes to RMSSD. These changes in HR during HG were no longer seen with CS, suggesting that the HC, IC, and amygdala have a role in cardiac function, namely vagal activation. However, we note potential limitations that include the short duration of HG, small sample size, and the very small HR response to HG in patients with DRE whereby any effect of CS may be difficult to observe. Funding: Natural Sciences and Engineering Research Council of Canada This abstract was presented at the American Physiology Summit 2026 and is only available in HTML format. There is no downloadable file or PDF version. The Physiology editorial board was not involved in the peer review process.

BACKGROUND:Concussions in adolescents, especially in sports, represent a major public health issue due to prolonged recovery and diagnostic challenges compared to adults. Current clinical assessments often underestimate the true burden and recovery course, highlighting the need for objective physiological biomarkers. OBJECTIVE:To investigate heart rate variability (HRV) as a potential biomarker for monitoring concussion recovery in adolescents through both traditional statistics and machine learning approaches. METHODS:Thirty-seven concussed adolescents (23 females, 14 males; mean age 15 ± 2 years) and 37 age-matched healthy controls (14 females, 23 males; mean age 16 ± 2 years) were enrolled. Concussed participants were evaluated within 1 month post-injury and at clinical discharge (mean interval = 9 ± 4 days). Each session included a 5-minute electrocardiogram and Post-Concussion Symptom Scale (PCSS). Time-domain HRV metrics-standard deviation of normal-to-normal intervals (SDNN) and root mean square of successive differences (RMSSD), were severity-adjusted to PCSS severity (SDNNidx, RMSSDidx). A Boosted Tree algorithm predicted clinical outcomes (Good/Bad) based on raw and severity-adjusted HRV features. RESULTS:Conventional statistics revealed no significant group differences in raw HRV metrics. However, severity-adjusted indices increased with lower symptom severity. The optimized Boosted Tree model achieved promising discriminative performance (AUC = .88), with 82% to 83% sensitivity, 75% to 79% specificity, and 82% to 84% F1 scores, accurately classifying all controls. CONCLUSIONS:Machine learning uncovered nonlinear HRV patterns predictive of clinical recovery where standard analyses failed. HRV-based predictive modeling may provide a noninvasive approach for individualized autonomic monitoring and evidence-based concussion management in adolescents.

This study investigated sympathetic neural blood pressure regulation in humans by quantifying synchronous and asynchronous action potential (AP) discharge. Muscle sympathetic AP discharge was measured (microneurography; continuous wavelet transform) in 21 healthy young adults. Baroreflex functions (central baroreflex component) and diastolic blood pressure (DBP) transduction (peripheral baroreflex component) were quantified for synchronous and asynchronous AP discharge. Analyses were stratified by falling and rising blood pressures to examine hysteresis. Medium-sized synchronous APs exhibited the greatest discharge frequencies (P < 0.001) and baroreflex threshold gains (P < 0.001). Asynchronous AP discharge exhibited weak baroreflex regulation (P = 0.999). Central baroreflex regulation of medium-sized synchronous APs exhibited hysteresis. Medium-sized synchronous APs expressed stronger baroreflex threshold gains (sympathetic AP cluster 3: DBP Fall slope: -5.48 ± 3.07%/mmHg, DBP Rise slope: -4.71 ± 2.91%/mmHg; P < 0.001) and greater discharge frequencies (sympathetic AP cluster 3: DBP Fall: 0.29 ± 0.15 Hz, DBP Rise: 0.25 ± 0.13 Hz; P < 0.001) during falling compared with rising blood pressures. The peripheral baroreflex component exhibited hysteresis. Transduction responses to synchronous AP discharge were larger during rising compared with falling blood pressures (DBP Fall peak: 2.67 ± 1.02 mmHg, DBP Rise peak: 3.14 ± 1.29 mmHg; P = 0.009). Asynchronous AP discharge was associated with attenuated blood pressure reductions compared with cardiac cycles with no AP activity, and more so during rising compared with falling blood pressures (DBP Fall nadir: -2.17 ± 1.09 mmHg, DBP Rise nadir: -1.43 ± 0.68 mmHg; P < 0.001). These data suggest that homeostatic blood pressure regulation is achieved via distinct subpopulations of synchronous and asynchronous APs that receive different central baroreflex and nonbaroreflex inputs. Central and peripheral baroreflex hysteresis may reflect a moment-to-moment compensatory strategy for blood pressure regulation.NEW & NOTEWORTHY 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.

Insulin resistance (IR) may jeopardise cerebral oxygenation and increase perceived exertion during exercise. We investigated whether IR is independently associated with perceived exertion or cerebral oxygenation during exercise and whether perceived exertion is associated with cerebral oxygenation during exercise. 48 premenopausal apparently healthy women underwent a cardiopulmonary exercise test (CPET) in this retrospective cross-sectional study. We assessed IR with the homeostasis model assessment (HOMA-IR). In addition to basic CPET data, we quantified cardiac function (impedance cardiography) and prefrontal cerebral oxygenation (near-infrared spectroscopy [NIRS]) during CPET. We divided the subjects into women with HOMA-IR< 3.0 (HOMALOW) vs. women with HOMA-IR≥ 3.0 (HOMAHIGH), and into women with lower RPE/MET (rating of perceived exertion/metabolic equivalent) slope (RPE/METLOW) vs. women with higher RPE/MET slope (RPE/METHIGH). RPE or NIRS responses to exercise did not differ between HOMA-IR groups. NIRS responses to exercise did not differ between RPE/MET groups. NIRS responses did not correlate with HOMA-IR or RPE/MET slope in all subjects. In multivariate regression analyses, a higher RPE/MET slope was predicted only by higher body mass index and weaker lung function. In conclusion, we found no associations between IR, cerebral oxygenation, and perceived exertion, whereas body mass index and lung function were independently associated with exercise-related perceived exertion.

This study tested the hypothesis that neural and vascular α2-adrenergic mechanisms contribute to sympathetic baroreflex regulation of human blood pressure. Muscle sympathetic nerve activity (MSNA; peroneal microneurography) was measured, and sympathetic action potentials (APs) were extracted from the filtered MSNA neurogram (continuous wavelet transform) in eight participants (5 females; 28 ± 7 yr) during a baseline (BSL) condition and a dexmedetomidine infusion (DEX; α2-adrenergic receptor agonist; 10-min loading dose at 0.225 µg/kg; maintenance dose: 0.1-0.5 µg/kg/h). Sympathetic AP baroreflex threshold and sensitivity gains were measured (spontaneous method). We quantified the transduction of integrated MSNA to diastolic blood pressure (DBP; signal averaging) and calculated an index of transduction gain as the slope of the relationship between maximum DBP and the number of cardiac cycles to maximum DBP. DEX reset the baroreflex operating point for medium APs to lower firing probabilities (AP cluster 4; BSL: 20 ± 6 to DEX: 6 ± 5%, P < 0.0004), lower DBP (72 ± 9 to 65 ± 10 mmHg, P < 0.0001), and reduced gain (AP cluster 4: -6.5 ± 2.0 to -2.0 ± 0.7%/mmHg, P < 0.0001). DEX reset the AP baroreflex sensitivity operating point to fewer AP clusters/burst (3.4 ± 0.7 to 2.9 ± 0.8 clusters/burst, P = 0.0156) but did not change gain. DEX reduced DBP transduction (cardiac cycle 6: 4.3 ± 3.2 to 3.3 ± 2.0 mmHg, P = 0.0032), increased the time to peak DBP (6 ± 1 to 11 ± 3 cardiac cycles, P = 0.0054), and reduced the DBP transduction gain (0.81 ± 0.72 to 0.36 ± 0.37 mmHg/cardiac cycle, P = 0.0012). These data suggest that neural and vascular α2-adrenergic mechanisms contribute to integrative sympathetic baroreflex regulation of blood pressure in humans.NEW & NOTEWORTHY Intravenous dexmedetomidine infusion (selective α2-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 α2-adrenergic mechanisms contribute to sympathetic baroreflex regulation of human BP.

The lack of direct measures of brain blood pressure (BBP) has severely restricted understanding of cerebral pressure-flow relationships and their control. We sought to evaluate the feasibility of directly measuring BBP and its pulsatility between the aorta and middle cerebral artery (MCA) during elective endovascular surgical procedures. We report five case studies (four female, 61 ± 13 yr; means ± SD) of patients undergoing cerebrovascular interventional procedures for aneurysm and stenoses, using direct BBP measures with the COMET 2 pressure guidewire system (Boston Scientific). Patients were supine, intubated, and under anesthesia. The sensor wire was inserted via the femoral artery, measuring, as feasible, blood pressure (BP) in the aorta to MCA vascular segments, referenced to the radial artery BP waveform (arterial catheter). Mean arterial pressure varied between the radial (80 ± 18 mmHg), internal carotid artery (ICA; 70 ± 25 mmHg), and MCA (62 ± 29 mmHg), and marked interindividual heterogeneity was observed. Pulse pressure was higher in the radial artery (68 ± 23 mmHg) compared with the intracranial ICA (ICAi; 43 ± 29 mmHg) and MCA (M1; 25 ± 12 mmHg) segments. Direct measures of BBP in humans are feasible in this interventional surgery model. Although limited by the small sample size, the results suggest a heterogenous pattern of change between systemic and brain measures of blood pressure and pulse pressure.NEW & NOTEWORTHY We explored the feasibility of making direct measures of blood pressure in the large arteries at the base of the brain in humans. Measures were made with an optical sensor positioned in the aorta, common carotid, internal carotid artery external to the cranium, internal carotid artery within the cranium, and/or middle cerebral artery (MCA), M1 segment. Measures varied across individuals, as did the pressure gradient from systemic pressures to those in the MCA.

The compliant nature of cerebral blood vessels may represent an important mechanical protection for sustained cerebral perfusion during reductions in arterial blood pressure (ABP). However, whether the rise in cerebrovascular compliance (Ci) with falling ABP persists and exhibits a threshold effect remains unknown. Therefore, we analyzed Ci changes during graded head-up tilt (HUT) in individuals with autonomic failure (AF), a group that tolerates graded and progressive reductions in ABP. Finger ABP and middle cerebral artery blood velocity (MCAv) were recorded from five patients with AF (61 ± 22 yr) at supine rest and during graded HUT. Tilt gradients increased incrementally between 30, 45, and 60° every 5 min until ABP reached a critically low value. The total time in HUT was 11 ± 4 min. Every 5 s during supine and HUT, individual ABP and MCAv waveforms were assessed for Ci and cerebrovascular resistance (CVR) using a modified Windkessel model. Pulse pressure (PP) was calculated as systolic ABP - diastolic ABP. A threshold value for the increase in Ci was determined using breakpoint analysis of the linear relationship between changes in Ci and PP or ABP across tilt periods. Graded HUT resulted in reduced ABP, PP, CVR, and mean MCAv, and increased Ci (all P < 0.01). Ci began to increase progressively after PP fell by 22 ± 6 mmHg and ABP fell by 20 ± 11 mmHg. In conclusion, the increase in Ci during progressive hypotension exhibited a threshold effect and persisted as ABP continued to fall.NEW & NOTEWORTHY We identify a threshold effect for the increase in cerebrovascular compliance (Ci) during progressive hypotension (baseline vs. end-tilt: 86 ± 18 vs. 50 ± 8 mmHg) in individuals with autonomic failure, such that Ci began to increase progressively after pulse pressure fell by 22 ± 6 mmHg and arterial blood pressure fell by 20 ± 11 mmHg.

This study investigated the impact of long-duration head-down bed rest (HDBR) on the central and peripheral components of the sympathetic baroreflex in males and females. Microneurography was used to measure integrated muscle sympathetic nerve activity (MSNA). Signal averaging was used to quantify sympathetic transduction of mean arterial pressure (MAP) and total peripheral resistance (TPR) in 13 males and 12 females before and after 60 days of 6° HDBR. Under baseline conditions, when analyses were stratified by biological sex, HDBR attenuated transduction of MSNA bursts to MAP responses in males (pre-HDBR: Δ1.4 ± 0.5 mmHg, post-HDBR: Δ1.0 ± 0.4 mmHg; η2 = 0.49, P = 0.005) but not in females (P = 0.143). HDBR did not affect baseline integrated MSNA in males or females. Females performed lower body negative pressure (LBNP) at -20, -30, and -45 mmHg. HDBR reduced stroke volume (η2 = 0.89, P < 0.001) and increased TPR (η2 = 0.56, P < 0.001) across all levels of LBNP but did not affect MSNA burst frequency, burst amplitude, or baroreflex gain indices (all P ≥ 0.191). In females, HDBR augmented sympathetic transduction of TPR at -45 mmHg LBNP (pre-HDBR: Δ0.2 ± 0.2 mmHg/L/min, post-HDBR: Δ0.4 ± 0.4 mmHg/L/min; η2 = 0.25, P < 0.001). These data suggest that: 1) biological sex influences the impact of HDBR on baseline sympathetic transduction of blood pressure, and 2) among females, vasoconstrictor responses to sympathetic bursts elicited by simulated orthostasis are augmented to compensate for reduced stroke volume after long-duration HDBR.NEW & NOTEWORTHY 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.

Cannabis is among the most widely used recreational substances, but the physiological consequences of acute and chronic use remain poorly studied. We recently demonstrated that acute cannabis use reduces muscle sympathetic nerve activity (MSNA). However, MSNA bursts comprise action potentials (APs) of varying size, which exhibit distinct firing and recruitment patterns that represent the communication between the sympathetic nervous system and the circulation. Applying a continuous wavelet transform to the microneurographic MSNA signal, we investigated the hypothesis that sympathetic AP firing patterns would be attenuated following cannabis inhalation at rest and during an end-expiratory apnea in young habitual cannabis users (n = 14; 7 females; 23 ± 3 yr). Following cannabis inhalation, MSNA burst occurrence and amplitude were reduced (all P < 0.001). Cannabis inhalation lowered the firing probability of medium-sized APs (normalized AP cluster 4: 78 ± 34 to 49 ± 31%; P = 0.03) and induced a derecruitment of larger AP clusters (22 ± 11 to 18 ± 9 clusters; P < 0.01). During an end-expiratory apnea following cannabis inhalation, there was an increase in MSNA burst frequency (8 ± 8 to 28 ± 10 bursts/min; P < 0.01), amplitude (51 ± 8 to 94 ± 34 AU; P < 0.01), AP frequency (74 ± 146 to 327 ± 387 spikes/min; P = 0.01), and the number of APs per burst (6 ± 5 to 10 ± 9 APs/burst; P = 0.03). However, the ability to recruit larger AP clusters (15 ± 11 to 16 ± 11 clusters; P = 0.57) and alter AP latency (1.23 ± 0.12 to 1.26 ± 0.17 s; P = 0.50) was absent. These data indicate that cannabis inhalation acutely decreases sympathetic AP firing and disrupts recruitment patterns in humans.NEW & NOTEWORTHY 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.

Chronic exposure to low oxygen (hypoxia) leads to amplification of the hypoxic chemoreflex, increasing breathing and sympathetic nervous system (SNS) activation. Prolonged SNS activation redistributes blood to hypoxia-sensitive tissues, away from muscles. Recent tracking studies have shown that migratory songbirds can fly 5,000 m or higher above sea level, leading us to hypothesize that migratory birds may have a blunted hypoxic chemoreflex to maintain blood flow to muscles during migratory flight at high altitudes. To test this hypothesis, we used a hypobaric wind tunnel and measured circulating plasma catecholamines after maximal altitude flight, flight at 75% of maximal altitude, flight at ground level (~250 m), and after rest at 75% of maximal altitude and ground level in migratory myrtle yellow-rumped warblers ( Setophaga coronata). Yellow-rumped warblers were capable of flying above 4,000 m simulated altitude above sea level (average maximum altitude of ~3,600 m), and would maintain flights at 75% of individual maximum altitudes (~2,700 m). Circulating dopamine and noradrenaline were similar between resting and flight conditions at ground level and with exposure to 75% of maximal altitude, whereas adrenaline significantly increased with flight, but did not change further with flight at 75% of maximal altitude. By contrast, both adrenaline and noradrenaline concentrations increased after maximum altitude flights compared to 75% and ground level flights. Our findings show that exercise increases plasma adrenaline in migratory songbirds, and suggest that warblers flying at high altitudes below their maximum altitude may be minimally hypoxic, allowing them to maintain oxygen transport to flight muscles.

Reductions in cerebral blood flow are associated with Alzheimer's Disease pathological changes and represent a potential therapeutic target. Measuring changes in middle cerebral artery velocity (MCAv) using transcranial Doppler ultrasound measurement of acute changes in MCAv during dynamic maneuvers and uncover relationships with cerebral autoregulation. We tested the hypothesis that changes in cerebral autoregulation are associated with clinical change in patients with mild cognitive impairment. Thirty MCI participants completed a supine-to-stand transition with beat-to-beat MCAv and mean arterial pressure (MAP) collected. Ten patients were cognitively intact and provided control measures. A 30-second supine and standing average were calculated and a standing-induced nadir average of the lowest 3-beats. Dynamic cerebral autoregulation (dCA) was calculated as (MCAv Nadir -MCAv supine /MCAv supine )/(MAP Nadir -MAP supine /MAP supine ). K-means clustering was used to split MCI participants into higher-standing-velocity ( n  = 9) and lower-standing-velocity ( n  = 21) groups. A one-way analysis of variance was employed to determine group differences for MoCA scores and dCA. A two-way repeated measures ANOVA assessed group by position (supine, nadir, standing) effects for cardiorespiratory and cerebrovascular indices. Significance was set to p  <0.05. MoCA scores were significantly higher in controls and the higher-standing-velocity groups compared to the lower-standing-velocity group (Figure 2). dCA was enhanced in the lower-standing-velocity group compared to the higher-standing-velocity group (Figure 2) with an inverse relationship between dCA and standing MCAv at diastole. Interactions were observed for the resistance index, cerebrovascular resistance index, and MCAv at diastole ( p  = 0.045, 0.008, and, 0.004 respectively). Effects of position were observed for all cardiopulmonary and cerebrovascular metrics other than MCAv at systole. This is the first study investigating a supine-to-standing induced dCA response within a cohort of people with MCI. Contrary to our hypothesis, an enhanced dCA was observed in the higher-standing-velocity group compared to the lower-standing-velocity group despite the higher-standing-velocity group having greater cognitive scores. Interestingly, the higher-standing-velocity group with MCI and controls had similar MoCA scores and dCA. An enhanced dCA may be a compensatory mechanism in the neurodegenerative disease processes. The unexpected results highlight the importance of uncovering hemodynamic pathways in clinical populations and identifying the adaptions made to preserve cognitive function in the face of dementia.

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 η 2 = 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.

Monitoring middle cerebral artery blood velocity (MCAv) during maneuvers known to alter cerebral perfusion, such as supine-to-standing transitions or walking, may provide a more comprehensive assessment used to flag individuals susceptible to cerebral hypoperfusion in a way that cannot be achieved at rest. Furthermore, dual-tasks challenge the brain to match MCAv to meet increases in local demands of oxygen and energy in two different functional networks (motor and cognitive), potentially causing cerebral hypoperfusion when competing for shared and/or limited brain resources. We developed a dual-task paradigm comprising of five levels of task complexity, including single-tasks and dual-tasks. The main objective of the study was to evaluate changes in MCAv as task complexity increased, which was demonstrated through cognitive, motor, and combined cognitive-motor tasks in older adults with different cognitive function levels. A secondary objective was to assess the success rate (as a percentage) of obtaining MCAv signals during the dual-task protocol to determine the feasibility of measuring such metrics in older adults with varying levels of cognitive ability. Of the 88 participants (37 females, 75 ± 7 years, 27 ± 4 kg/m2), a MCAv signal was ascertained in 56 participants throughout both single-tasks and both dual-tasks. MCAv increased when transitioning from a simple single-task to a more complex dual-task, while also highlighting a decline in motor and cognitive performance. A full multi-modal signal acquisition (MCAv, blood pressure, and cerebral oxygenation) was acquired for 48 participants. Lower MCAv signal acquisition was observed in females and people with cognitive impairment. We have demonstrated how MCAv changes with increased task complexity, while also uncovering declines in gait and cognitive performance. By establishing the feasibility of obtaining MCAv signals during cognitive stress tests and dynamic movements in older adults with varying cognitive abilities, we can begin to assess cerebral hypoperfusion using a potentially more sensitive indicator linked to neural damage.

Cerebrovascular dysfunction, a risk factor for dementia, is challenging to detect in mild cognitive impairment (MCI). Herein, we used novel, light-based technology to investigate low-frequency hemodynamic oscillations (LFOs; 0.02-0.16 Hz) in cerebral perfusion, oxygenation, and relative metabolic rate of oxygen (rCMRO2) in MCI (n = 13; 74 ± 6 yr) and cognitively intact controls (n = 10; 69 ± 6 yr). Relative cerebral microvascular perfusion and tissue oxygenation changes were recorded using a depth-enhanced optical monitoring system. Continuous wavelet transforms were used to compare average LFO power between groups (α = 0.025). Compared with controls, MCI had lower LFO power in microvascular perfusion, greater power in oxygenation (P ≤ 0.02), and no statistical difference in oscillatory power for rCMRO2. Similar rCMRO2 but opposing changes in oscillatory power for cerebral perfusion and oxygenation associated with MCI suggest an adaptation to maintain energy production.NEW & NOTEWORTHY 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.

Although previous work has demonstrated that oral contraceptive pill (OCP) use does not affect resting muscle sympathetic nerve activity (MSNA), growing evidence indicates that it attenuates neurogenic vasoconstriction. Despite these advances, it remains unknown how OCP use affects the ability of MSNA to dynamically control vascular tone and arterial blood pressure (BP) on a beat-by-beat basis. Thus, we tested the hypothesis that, compared with naturally menstruating females (MC), those using OCPs will exhibit attenuated sympathetic vascular transduction at rest. Forty-three females [MC: n = 21, 26 (4) yrs; OCP: n = 22, 24 (4) yrs; data are presented as means (SD)] completed 10 min of supine rest with continuous measurements of beat-by-beat BP, femoral artery blood flow (26 females; MC: n = 13, OCP: n = 13), and MSNA. Spike-triggered averaging was used to determine sympathetic transduction into leg vascular conductance (LVC) and BP for 12 cardiac cycles following MSNA bursts. Overall sympathetic-BP transduction (P = 0.293), as well as sympathetic-BP transduction of MSNA burst quartiles (P = 0.741) and burst firing patterns (P = 0.452) were not different between the MC and OCP groups. Conversely, sympathetic vascular transduction per unit MSNA burst amplitude (P = 0.026) and burst firing pattern (P = 0.014) were attenuated among females using OCPs. In addition, females using OCPs demonstrated progressively smaller leg vasoconstrictor responses as a function of MSNA burst firing pattern compared with MC females (P = 0.021). Collectively, these data indicate that, in premenopausal females, OCP use attenuates the leg vasoconstrictor responses to bursts of MSNA, particularly during periods of increased sympathetic neural drive, without affecting the transduction of MSNA bursts into beat-by-beat changes in BP. NEW & NOTEWORTHY This study investigated the impact of OCP use on the transduction of MSNA bursts into regional vasoconstriction and blood pressure in premenopausal females. We demonstrated that females using OCPs exhibit attenuated sympathetic transduction into LVC; however, this does not translate to reductions in sympathetic blood pressure transduction. Collectively, these data indicate that OCP use may alter the local vasoconstrictor response to bursts of MSNA; however, compensatory mechanisms may contribute to maintain sympathetic blood pressure transduction.

Altered cerebrovascular hemodynamics and low cerebral perfusion contribute to the development and progression of dementia. Dynamic cerebral autoregulation (dCA), a measure of the cerebral vasculature’s ability to buffer abrupt changes in mean arterial pressure and prevent hypoperfusion, such as during a supine-to-standing transition, have mixed results in people clinically diagnosed with mild cognitive impairment (MCI, people with objective cognitive impairment but maintained functional independence). Therefore, in 30 people with MCI, we tested the hypothesis that participants with a higher standing middle cerebral artery velocity (MCAv) at diastole (higher-velocity group) would have lower dCA values, to confer better cerebrovascular outcomes and enhanced cognitive function compared to participants with a lower MCAv at diastole (lower-velocity group). This study separated people with MCI into different diastolic MCAv groups. dCA was calculated as (MCAv nadir -MCAv supine /MCAv supine )/(MAP MCAnadir -MAP MCAsupine /MAP MCAsupine ). This work led to the identification of a dysregulated dCA in the higher-velocity group (p = 0.009) compared to the lower-velocity group despite having greater cognitive scores (p = 0.008). Elevated levels of cerebral oxygen tissue saturation (p = 0.039) and lower end-tidal carbon dioxide (p = 0.042) suggest that a favourable dCA value may be a compensatory mechanism in the neurodegenerative disease processes. The unexpected results highlight the importance of uncovering hemodynamic pathways in clinical populations.