A Quantitative Assessment of Cerebral Hemodynamic Perturbations Associated with Long R-R Intervals in Atrial Fibrillation: A Pilot-Case-Based Experience.

Background and Objectives: Atrial fibrillation (AF) results in systemic hemodynamic perturbations which impact cerebral circulation, possibly contributing to the development of dementia. However, evidence documenting effects in cerebral perfusion is scarce. The aim of this study is to provide a quantitative characterization of the magnitude and time course of the cerebral hemodynamic response to the short hypotensive events associated with long R-R intervals, as detected by near-infrared spectroscopy (NIRS). Materials and Methods: Cerebral NIRS signals and arterial blood pressure were continuously recorded along with an electrocardiogram in twelve patients with AF undergoing elective electrical cardioversion (ECV). The top 0.5-2.5% longest R-R intervals during AF were identified in each patient and used as triggers to carry out the triggered averaging of hemodynamic signals. The average curves were then characterized in terms of the latency, magnitude, and duration of the observed effects, and the possible occurrence of an overshoot was also investigated. Results: The triggered averages revealed that long R-R intervals produced a significant drop in diastolic blood pressure (-13.7 ± 6.1 mmHg) associated with an immediate drop in cerebral blood volume (THI: -0.92 ± 0.46%, lasting 1.9 ± 0.8 s), followed by a longer-lasting decrease in cerebral oxygenation (TOI: -0.79 ± 0.37%, lasting 5.2 ± 0.9 s, p < 0.01). The recovery of the TOI was generally followed by an overshoot (+1.06 ± 0.12%). These effects were progressively attenuated in response to R-R intervals of a shorter duration. Conclusions: Long R-R intervals cause a detectable and consistent cerebral hemodynamic response which concerns both cerebral blood volume and oxygenation and outlasts the duration of the systemic perturbation. These effects are compatible with the activation of dynamic autoregulatory mechanisms in response to the hypotensive stimulus.

Hemodynamic changes in the temporalis and masseter muscles during acute stress in healthy humans.

PURPOSE: Autonomic control of orofacial areas is an integral part of the stress response, controlling functions such as pupil dilatation, salivation, and skin blood flow. However, the specific control of blood flow in head muscles during stress is unknown. This study aims to investigate the hemodynamic response of temporalis and masseter muscles in response to five different stressors. METHODS: Sixteen healthy individuals were subjected to a randomized series of stressors, including cold pressor test, mental arithmetic test, apnea, isometric handgrip, and post-handgrip muscle ischemia, while in the sitting posture. Finger-pulse photoplethysmography was used to measure arterial blood pressure, heart rate, and cardiac output. Near-infrared spectroscopy was used to measure changes in tissue oxygenation and hemoglobin indices from the temporalis and masseter muscles. RESULTS: All stressors effectively and significantly increased arterial blood pressure. Tissue oxygenation index significantly increased in both investigated head muscles during mental arithmetic test (temporalis: 4.22 ± 3.52%; masseter: 3.43 ± 3.63%) and isometric handgrip (temporalis: 3.45 ± 3.09%; masseter: 3.26 ± 3.07%), suggesting increased muscle blood flow. Neither the masseter nor the temporalis muscles evidenced a vasoconstrictive response to any of the stressors tested. CONCLUSION: In the different conditions, temporalis and masseter muscles exhibited similar hemodynamic patterns of response, which do not include the marked vasoconstriction generally observed in limb muscles. The peculiar sympathetic control of head muscles is possibly related to the involvement of these muscles in aggressive/defensive reactions and/or to their unfavorable position with regard to hydrostatic blood levels.

Hemodynamic monitoring in the human temporalis muscle using near-infrared spectroscopy.

Objective. Altered temporal muscle perfusion is implicated in several painful disorders afflicting orofacial and head regions, including temporomandibular joint dysfunctions, bruxism, and headache. Knowledge about the regulation of blood supply to the temporalis muscle is limited, due to methodological difficulties. The study aimed to test the feasibility of near-infrared spectroscopy (NIRS) monitoring of the human temporal muscle.Approach. Twenty-four healthy subjects were monitored with a 2-channel NIRS: amuscleprobe placed over the temporal muscle and abrainprobe placed on the forehead. A series of teeth clenching at 25, 50, and 75% of maximum voluntary contraction for 20 s and hyperventilation for 90 s at 20 mmHg of end-tidal CO2were performed, to elicit hemodynamic changes in muscle and brain, respectively.Main results. In twenty responsive subjects, NIRS signals from both probes were consistently different during both tasks. The absolute change in tissue oxygenation index (ΔTOI) as detected by muscle and brain probes was -9.40 ± 12.28 and 0.29 ± 1.54% during teeth clenching (p< 0.01) at 50% maximum voluntary contraction, while -1.03 ± 2.70 and -5.11 ± 3.81% during hyperventilation (p< 0.01), respectively.Significance. Distinct response patterns were observed from the temporal muscle and prefrontal cortex which proves that this technique is adequate to monitor tissue oxygenation and hemodynamic changes in human temporal muscle. Noninvasive and reliable monitoring of hemodynamics in this muscle will help to extend basic and clinical investigations about the peculiar control of blood flow in head muscles.

Ischemic Conditioning to Reduce Fatigue in Isometric Skeletal Muscle Contraction.

Ischemic preconditioning (IPC) is a non-invasive protective maneuver that alternates short periods of occlusion and reperfusion of tissue blood flow. Given the heterogeneity in the magnitude and frequency of IPC-induced improvements in physical performance, here we aimed to investigate, in a well-controlled experimental set-up, the local effects of IPC in exposed muscles in terms of tissue oxygenation and muscle fatigue. Nineteen subjects were enrolled in one of the two groups, IPC (3 × 5/5 min right arm ischemia/reperfusion; cuff inflations 250 mmHg) and SHAM (3 × 5/5 min pseudo ischemia/reperfusion; 20 mmHg). The subjects performed a fatiguing contraction protocol before and 30 min after the IPC treatment, consisting of unilateral intermittent isometric elbow flexions (3 s ON/OFF, 80% of maximal voluntary contraction) until exhaustion. While muscle strength did not differ between groups, post- vs. pre-treatment endurance was significantly reduced in the SHAM group (4.1 ± 1.9 vs. 6.4 ± 3.1 repetitions until exhaustion, p < 0.05) but maintained in IPC (7.3 ± 2.0 vs. 7.1 ± 4.3, n.s.). The decrease in tissue oxygenation and the increase in deoxygenated hemoglobin were significantly reduced post- vs. pre-IPC (p < 0.05), but not post- vs. pre-SHAM. The results suggest that IPC delays the onset of fatigue likely through improved metabolic efficiency of muscles.

Cerebrovascular reactivity during visual stimulation: Does hypnotizability matter?

Hypnotizability is a trait associated with several physiological correlates including cardiovascular control. The present study aimed to investigate the posterior cerebral artery flow velocity (PCAv) in basal closed eyes (B) and during visual stimulation (VS) conditions in med-highs and med-lows. Twenty-four healthy volunteers were submitted to the hypnotic assessment through the Stanford Hypnotic Susceptibility Scale, form A which classified 13 low-to-medium (med-lows) and 10 high-to-medium (med-highs) hypnotizable participants. One subject scoring 6 out of 12 was excluded from the comparisons between groups. Arterial blood pressure, heart rate, and partial pressure of end-tidal CO2 were monitored during both B and VS conditions. Simultaneously, PCAv was assessed by transcranial Doppler. Cerebrovascular Reactivity (CVR) was computed as a percentage of the PCAv change occurring during VS with respect to B (ΔPCAv). During VS both groups increased their PCAv (mean ± SD: 7.9 ± 5.2 %) significantly with no significant group difference. However, among med-highs, CVR was negatively correlated with hypnotizability scores. Thus, higher hypnotizability may be associated with lower metabolic demand in response to VS only within med-highs hypnotizable participants.

Does hypnotizability affect neurovascular coupling during cognitive tasks?

Susceptibility to hypnosis is a very pervasive psychophysiological trait characterized by different attentional abilities, information processing, and cardiovascular control. Since near infrared spectroscopy is a good index of neurovascular coupling, we used it during mental computation (MC) and trail making task (TMT) in 13 healthy low-to-medium (med-lows) and 10 healthy medium-to-high (med-highs) hypnotizable participants classified according to the Stanford Hypnotic Susceptibility Scale, form A, and characterized for the level of proneness to be deeply absorbed in related experiences by the Tellegen Absorption Scale. The med-highs reported greater absorption than med-lows. The tissue hemoglobin index (THI) and the tissue oxygenation index (TOI) increased across the tasks only in med-highs who displayed also different time courses of THI and TOI during MC and TMT, which indicates different tasks processing despite the two groups' similar performance. The findings suggest that med-highs' tissue oxygenation is more finely adjusted to metabolic demands than med-lows'.

Differential control of blood flow in masseter and biceps brachii muscles during stress.

OBJECTIVE: The present study aimed to compare sympathetic hemodynamic effects in masticatory and limb muscles in response to different stressors. DESIGN: Twelve healthy participants were subjected to a randomized series of stressors, including cold pressor test (CPT), mental arithmetic test, apnea, isometric handgrip (IHG) and post-handgrip muscle ischemia (PHGMI), while in the supine position. Spatially-resolved near-infrared spectroscopy was used to measure relative changes in blood volume and oxygenation (TOI) of the resting masseter and biceps muscles. Cardiac output, heart rate, and arterial blood pressure (ABP) were also monitored. RESULTS: Except apnea, all tests increased ABP. Different response patterns were observed in the 2 muscles: TOI significantly increased during contralateral IHG (1.24 ± 1.17%) but markedly decreased during CPT (-4.84 ± 4.09%) and PHGMI (-6.65 ± 5.31%) in the biceps muscle, while exhibiting consistent increases in the masseter (1.88 ± 1.85%; 1.60 ± 1.75%; 1.06 ± 3.29%, respectively) (p < 0.05). CONCLUSIONS: The results allow us to infer differential control of blood flow in head and limb muscles. In general, the masseter appears more prone to dilatation than the biceps, exhibiting opposite changes in response to painful stimuli (CPT and PHGMI). Several mechanisms may mediate this effect, including reduced sympathetic outflow to the extracranial vasculature of the head, generally exposed to lower hydrostatic loads than the rest of the body.

Cerebral Blood Flow in Healthy Subjects with Different Hypnotizability Scores.

Hypnotizability is a cognitive trait associated with differences in the brachial artery flow-mediated dilatation of individuals with high hypnotizability (highs) and low hypnotizability scores (lows). The study investigated possible hypnotizability-related cerebrovascular differences. Among 24 healthy volunteers, the Stanford Hypnotic Susceptibility Scale Form A identified 13 medium-to-lows (med-lows), 11 medium-to-highs (med-highs), and 1 medium hypnotizable. Hypnotizability did not influence the significant changes produced by the trail making task (TMT), mental arithmetic task (MAT), hyperventilation (HVT), and rebreathing (RBT) on heart rate (HR), arterial blood pressure (ABP), and partial pressure of end-tidal CO2 (PETCO2), but moderated the correlations between the changes occurring during tasks with respect to basal conditions (Δ) in ABP and PETCO2 with middle cerebral artery flow velocity (MCAv). In HVT, med-lows exhibited a significant correlation between ΔMCAv and ΔPETCO2, and med-highs showed a significant correlation between ΔABP and ΔMCAv. Cerebrovascular reactivity (CVR) and conductance (ΔCVCi) were significantly correlated with ΔMCAv only in med-lows during HVT and RBT. For the first time, cerebrovascular reactivity related to hypnotizability was investigated, evidencing different correlations among hemodynamic variables in med-highs and med-lows.

Use of a wireless ultrasound probe as a portable, noninvasive method for studying reproductive biology in the asp viper, Vipera aspis.

In this study, we investigated the use of wireless ultrasonography as an imaging system to study the reproductive ecology of the asp viper (Vipera aspis), a viviparous snake found in southwestern Europe. Female vipers were captured during the summer and immediately scanned to obtain an estimate of the number of embryos. Ultrasound imaging was performed with a pocket-sized wireless ultrasound probe interfaced with a tablet with a dedicated app. Vipers were then released at the exact capture site after collecting data on body size and weight. We validate wireless ultrasonography as a non-destructive, effective tool for ultrasonic investigations in the field. Wireless probes are light and compact, which facilitates carriage in rugged terrain. Moreover, the absence of cables simplifies the maneuvers to be made on a small, potentially dangerous snake. Importantly, ultrasound scans can be performed at the capture site, thus minimizing restraint time and handling of gravid females.

Inferior Vena Cava Edge Tracking Echocardiography: A Promising Tool with Applications in Multiple Clinical Settings.

Ultrasound (US)-based measurements of the inferior vena cava (IVC) diameter are widely used to estimate right atrial pressure (RAP) in a variety of clinical settings. However, the correlation with invasively measured RAP along with the reproducibility of US-based IVC measurements is modest at best. In the present manuscript, we discuss the limitations of the current technique to estimate RAP through IVC US assessment and present a new promising tool developed by our research group, the automated IVC edge-to-edge tracking system, which has the potential to improve RAP assessment by transforming the current categorical classification (low, normal, high RAP) in a continuous and precise RAP estimation technique. Finally, we critically evaluate all the clinical settings in which this new tool could improve current practice.

Evidence that large vessels do affect near infrared spectroscopy.

The influence of large vessels on near infrared spectroscopy (NIRS) measurement is generally considered negligible. Aim of this study is to test the hypothesis that changes in the vessel size, by varying the amount of absorbed NIR light, could profoundly affect NIRS blood volume indexes. Changes in haemoglobin concentration (tHb) and in tissue haemoglobin index (THI) were monitored over the basilic vein (BV) and over the biceps muscle belly, in 11 subjects (7 M - 4 F; age 31 ± 8 year) with simultaneous ultrasound monitoring of BV size. The arm was subjected to venous occlusion, according to two pressure profiles: slow (from 0 to 60 mmHg in 135 s) and rapid (0 to 40 mmHg maintained for 30 s). Both tHb and THI detected a larger blood volume increase (1.7 to 4 fold; p < 0.01) and exhibited a faster increase and a greater convexity on the BV than on the muscle. In addition, NIRS signals from BV exhibited higher correlation with changes in BV size than from muscle (r = 0.91 vs 0.55, p < 0.001 for THI). A collection of individual relevant recordings is also included. These results challenge the long-standing belief that the NIRS measurement is unaffected by large vessels and support the concept that large veins may be a major determinant of blood volume changes in multiple experimental conditions.

Center of pressure displacement due to graded controlled perturbations to the trunk in standing subjects: the force-impulse paradigm.

PURPOSE: Many studies have investigated postural reactions (PR) to body-delivered perturbations. However, attention has been focused on the descriptive variables of the PR rather than on the characterization of the perturbation. This study aimed to test the hypothesis that the impulse rather than the force magnitude of the perturbation mostly affects the PR in terms of displacement of the center of foot pressure (ΔCoP). METHODS: Fourteen healthy young adults (7 males and 7 females) received 2 series of 20 perturbations, delivered to the back in the anterior direction, at mid-scapular level, while standing on a force platform. In one series, the perturbations had the same force magnitude (40 N) but different impulse (range: 2-10 Ns). In the other series, the perturbations had the same impulse (5 Ns) but different force magnitude (20-100 N). A simple model of postural control restricted to the sagittal plane was also developed. RESULTS: The results showed that ΔCoP and impulse were highly correlated (on average: r = 0.96), while the correlation ΔCoP-force magnitude was poor (r = 0.48) and not statistically significant in most subjects. The normalized response, ΔCoPn = ΔCoP/I, was independent of the perturbation magnitude in a wide range of force amplitude and impulse and exhibited good repeatability across different sets of stimuli (on average: ICC = 0.88). These results were confirmed by simulations. CONCLUSION: The present findings support the concept that the magnitude of the applied force alone is a poor descriptor of trunk-delivered perturbations and suggest that the impulse should be considered instead.

The Cardiac Caval Index: Improving Noninvasive Assessment of Cardiac Preload.

OBJECTIVES: Inferior vena cava (IVC) pulsatility quantified by the Caval Index (CI) is characterized by poor reliability, also due to the irregular magnitude of spontaneous respiratory activity generating the major pulsatile component. The aim of this study was to test whether the IVC cardiac oscillatory component could provide a more stable index (Cardiac CI-CCI) compared to CI or respiratory CI (RCI). METHODS: Nine healthy volunteers underwent long-term monitoring in supine position of IVC, followed by 3 minutes passive leg raising (PLR). CI, RCI, and CCI were extracted from video recordings by automated edge-tracking and CCI was averaged over each respiratory cycle (aCCI). Cardiac output (CO), mean arterial pressure (MAP) and heart rate (HR) were also recorded during baseline (1 minutes prior to PLR) and PLR (first minute). RESULTS: In response to PLR, all IVC indices decreased (P < .01), CO increased by 4 ± 4% (P = .055) while HR and MAP did not vary. The Coefficient of Variation (CoV) of aCCI (13 ± 5%) was lower than that of CI (17 ± 5%, P < .01), RCI (26 ± 7%, P < .001) and CCI (25 ± 7%, P < .001). The mutual correlations in time of the indices were 0.81 (CI-RCI), 0.49 (CI-aCCI) and 0.2 (RCI-aCCI). CONCLUSIONS: Long-term IVC monitoring by automated edge-tracking allowed us to evidence that 1) respiratory and averaged cardiac pulsatility components are uncorrelated and thus carry different information and 2) the new index aCCI, exhibiting the lowest CoV while maintaining good sensitivity to blood volume changes, may overcome the poor reliability of CI and RCI.

Increased beat-to-beat variability of cerebral microcirculatory perfusion during atrial fibrillation: a near-infrared spectroscopy study.

AIMS: Atrial fibrillation (AFib) is associated with cognitive decline/dementia, independently from clinical strokes or transient ischaemic attacks (TIA). Recent in silico data suggested that AFib may induce transient critical haemodynamic events in the cerebral microcirculation. The aim of this study is to use non-invasive spatially resolved cerebral near-infrared spectroscopy (SRS-NIRS) to investigate in vivo beat-to-beat microcirculatory perfusion during AFib and after sinus rhythm (SR) restoration. METHODS AND RESULTS: Cerebral SRS-NIRS with high-frequency sampling (20 Hz) and non-invasive systemic haemodynamic monitoring were recorded before and after elective electrical cardioversion (ECV) for AFib or atrial flutter (AFL). To assess beat-to-beat effects of the rhythm status, the frequency distribution of inter-beat differences in tissue haemoglobin index (THI), a proxy of microcirculatory cerebral perfusion, was compared before and after SR restoration. Fifty-three AFib/AFL patients (mean age 69 ± 8 years, 79% males) were ultimately enrolled. Cardioversion was successful in restoring SR in 51 (96%) patients. In front of a non-significant decrease in arterial blood pressure extreme events between pre- and post-ECV measurements, a significant decrease of both hypoperfusive and hyperperfusive/hypertensive microcirculatory events was observed after SR restoration (P < 0.001 and P = 0.041, respectively). CONCLUSION: The present is the first in vivo demonstration that SR restoration by ECV significantly reduces the burden of extreme single-beat haemodynamic events in cerebral microcirculation. Future studies are needed to assess whether SR maintenance might slow long-term AFib-correlated cognitive decline/dementia.

Decoding overt shifts of attention in depth through pupillary and cortical frequency tagging.

Objective. We have recently developed a prototype of a novel human-computer interface for assistive communication based on voluntary shifts of attention (gaze) from a far target to a near target associated with a decrease of pupil size (Pupillary Accommodative Response, PAR), an automatic vegetative response that can be easily recorded. We report here an extension of that approach based on pupillary and cortical frequency tagging.Approach. In 18 healthy volunteers, we investigated the possibility of decoding attention shifts in depth by exploiting the evoked oscillatory responses of the pupil (Pupillary Oscillatory Response, POR, recorded through a low-cost device) and visual cortex (Steady-State Visual Evoked Potentials, SSVEP, recorded from 4 scalp electrodes). With a simple binary communication protocol (focusing on a far target meaning 'No', focusing on the near target meaning 'Yes'), we aimed at discriminating when observer's overt attention (gaze) shifted from the far to the near target, which were flickering at different frequencies.Main results. By applying a binary linear classifier (Support Vector Machine, SVM, with leave-one-out cross validation) to POR and SSVEP signals, we found that, with only twenty trials and no subjects' behavioural training, the offline median decoding accuracy was 75% and 80% with POR and SSVEP signals, respectively. When the two signals were combined together, accuracy reached 83%. The number of observers for whom accuracy was higher than 70% was 11/18, 12/18 and 14/18 with POR, SVVEP and combined features, respectively. A signal detection analysis confirmed these results.Significance. The present findings suggest that exploiting frequency tagging with pupillary or cortical responses during an attention shift in the depth plane, either separately or combined together, is a promising approach to realize a device for communicating with Complete Locked-In Syndrome (CLIS) patients when oculomotor control is unreliable and traditional assistive communication, even based on PAR, is unsuccessful.

Assessment of Phasic Changes of Vascular Size by Automated Edge Tracking-State of the Art and Clinical Perspectives.

Assessment of vascular size and of its phasic changes by ultrasound is important for the management of many clinical conditions. For example, a dilated and stiff inferior vena cava reflects increased intravascular volume and identifies patients with heart failure at greater risk of an early death. However, lack of standardization and sub-optimal intra- and inter- operator reproducibility limit the use of these techniques. To overcome these limitations, we developed two image-processing algorithms that quantify phasic vascular deformation by tracking wall movements, either in long or in short axis. Prospective studies will verify the clinical applicability and utility of these methods in different settings, vessels and medical conditions.

A Survey on the Use and Barriers of Surface Electromyography in Neurorehabilitation.

Historical, educational, and technical barriers have been reported to limit the use of surface electromyography (sEMG) in clinical neurorehabilitation settings. In an attempt to identify, review, rank, and interpret potential factors that may play a role in this scenario, we gathered information on (1) current use of sEMG and its clinical potential; (2) professional figures primarily dealing with sEMG; (3) educational aspects, and (4) possible barriers and reasons for its apparently limited use in neurorehabilitation. To this aim, an online 30-question survey was sent to 52 experts on sEMG from diverse standpoints, backgrounds, and countries. Participants were asked to respond to each question on a 5-point Likert scale or by ranking items. A cut-off of 75% agreement was chosen as the consensus threshold. Thirty-five invitees (67%) completed the electronic survey. Consensus was reached for 77% of the proposed questions encompassing current trends in sEMG use in neurorehabilitation, educational, technical, and methodological features as well as its translational utility for clinicians and patients. Data evidenced the clinical utility of sEMG for patient assessment, to define the intervention plan, and to complement/optimize other methods used to quantify muscle and physical function. The aggregate opinion of the interviewed experts confirmed that sEMG is more frequently employed in technical/methodological than clinical research. Moreover, the slow dissemination of research findings and the lack of education on sEMG seem to prevent prompt transfer into practice. The findings of the present survey may contribute to the ongoing debate on the appropriateness and value of sEMG for neurorehabilitation professionals and its potential translation into clinical settings.

Multi-directional Assessment of Respiratory and Cardiac Pulsatility of the Inferior Vena Cava From Ultrasound Imaging in Short Axis.

The pulsatility of the inferior vena cava (IVC) reflects the volume status of patients. It can be investigated by ultrasounds (US), offering an important non-invasive tool supporting fluid management. However, the method has limitations attributable to many confounding factors, e.g., related to IVC movements and non-regular shapes. Short- or long-axis views have been used, both having advantages and limitations in counteracting such confounding factors, depending on the specific condition. The aim of this study is to investigate IVC pulsatility in the different directions on the transverse plane and to assess its variability. Moreover, different components of this pulsatility (induced by either respiratory or cardiac activity) are investigated. The method is tested on 10 healthy patients, with large variations across them of IVC section (mean diameters in the range 1 cm to 3 cm), shape and pulsatility (average caval index [CI] ranging from approximately 20% to 70%). The average coefficient of variation of the CI estimated on 10 different directions was 13% (21% and 20% for the respiratory and cardiac components, respectively), with a range that was approximately 50% of the mean CI across different directions (approximately the same for the 2 different components). The minimum and maximum CI were found close to the directions of maximum and minimum IVC diameter, respectively. The investigation of IVC dynamics in the entire cross-section is crucial to obtain a more repeatable and reliable characterization of IVC pulsatility. The calculation of a CI based on the "equivalent" diameter (proportional to the square root of the IVC cross-sectional area) is encouraged.