Showing papers on "Reflex published in 2020"

An Artificial Somatic Reflex Arc

Abstract: The emulation of human sensation, perception, and action processes has become a major challenge for bioinspired intelligent robotics, interactive human-machine interfacing, and advanced prosthetics. Reflex actions, enabled through reflex arcs, are important for human and higher animals to respond to stimuli from environment without the brain processing and survive the risks of nature. An artificial reflex arc system that emulates the functions of the reflex arc simplifies the complex circuit design needed for "central-control-only" processes and becomes a basic electronic component in an intelligent soft robotics system. An artificial somatic reflex arc that enables the actuation of electrochemical actuators in response to the stimulation of tactile pressures is reported. Only if the detected pressure by the pressure sensor is above the stimulus threshold, the metal-organic-framework-based threshold controlling unit (TCU) can be activated and triggers the electrochemical actuators to complete the motion. Such responding mechanism mimics the all-or-none law in the human nervous system. As a proof of concept, the artificial somatic reflex arc is successfully integrated into a robot to mimic the infant grasp reflex. This work provides a unique and simplifying strategy for developing intelligent soft robotics, next-generation human-machine interfaces, and neuroprosthetics.

Middle Ear Muscle Reflex and Word Recognition in "Normal-Hearing" Adults: Evidence for Cochlear Synaptopathy?

Abstract: Objectives Permanent threshold elevation after noise exposure, ototoxic drugs, or aging is caused by loss of sensory cells; however, animal studies show that hair cell loss is often preceded by degeneration of synapses between sensory cells and auditory nerve fibers. The silencing of these neurons, especially those with high thresholds and low spontaneous rates, degrades auditory processing and may contribute to difficulties in understanding speech in noise. Although cochlear synaptopathy can be diagnosed in animals by measuring suprathreshold auditory brainstem responses, its diagnosis in humans remains a challenge. In mice, cochlear synaptopathy is also correlated with measures of middle ear muscle (MEM) reflex strength, possibly because the missing high-threshold neurons are important drivers of this reflex. The authors hypothesized that measures of the MEM reflex might be better than other assays of peripheral function in predicting difficulties hearing in difficult listening environments in human subjects. Design The authors recruited 165 normal-hearing healthy subjects, between 18 and 63 years of age, with no history of ear or hearing problems, no history of neurologic disorders, and unremarkable otoscopic examinations. Word recognition in quiet and in difficult listening situations was measured in four ways: using isolated words from the Northwestern University auditory test number six corpus with either (a) 0 dB signal to noise, (b) 45% time compression with reverberation, or (c) 65% time compression with reverberation, and (d) with a modified version of the QuickSIN. Audiometric thresholds were assessed at standard and extended high frequencies. Outer hair cell function was assessed by distortion product otoacoustic emissions (DPOAEs). Middle ear function and reflexes were assessed using three methods: the acoustic reflex threshold as measured clinically, wideband tympanometry as measured clinically, and a custom wideband method that uses a pair of click probes flanking an ipsilateral noise elicitor. Other aspects of peripheral auditory function were assessed by measuring click-evoked gross potentials, that is, summating potential (SP) and action potential (AP) from ear canal electrodes. Results After adjusting for age and sex, word recognition scores were uncorrelated with audiometric or DPOAE thresholds, at either standard or extended high frequencies. MEM reflex thresholds were significantly correlated with scores on isolated word recognition, but not with the modified version of the QuickSIN. The highest pairwise correlations were seen using the custom assay. AP measures were correlated with some of the word scores, but not as highly as seen for the MEM custom assay, and only if amplitude was measured from SP peak to AP peak, rather than baseline to AP peak. The highest pairwise correlations with word scores, on all four tests, were seen with the SP/AP ratio, followed closely by SP itself. When all predictor variables were combined in a stepwise multivariate regression, SP/AP dominated models for all four word score outcomes. MEM measures only enhanced the adjusted r values for the 45% time compression test. The only other predictors that enhanced model performance (and only for two outcome measures) were measures of interaural threshold asymmetry. Conclusions Results suggest that, among normal-hearing subjects, there is a significant peripheral contribution to diminished hearing performance in difficult listening environments that is not captured by either threshold audiometry or DPOAEs. The significant univariate correlations between word scores and either SP/AP, SP, MEM reflex thresholds, or AP amplitudes (in that order) are consistent with a type of primary neural degeneration. However, interpretation is clouded by uncertainty as to the mix of pre- and postsynaptic contributions to the click-evoked SP. None of the assays presented here has the sensitivity to diagnose neural degeneration on a case-by-case basis; however, these tests may be useful in longitudinal studies to track accumulation of neural degeneration in individual subjects.

Long-Term Evaluation of the Vagal Denervation by Cardioneuroablation Using Holter and Heart Rate Variability.

Abstract: Background: Several disorders present reflex or persistent increase in vagal tone that may cause refractory symptoms even in a normal heart patient. Cardioneuroablation, the vagal denervation by ra...

Prepulse Inhibition of the Auditory Startle Reflex Assessment as a Hallmark of Brainstem Sensorimotor Gating Mechanisms.

Abstract: When a low-salience stimulus of any type of sensory modality—auditory, visual, tactile—immediately precedes an unexpected startle-like stimulus, such as the acoustic startle reflex, the startle motor reaction becomes less pronounced or is even abolished. This phenomenon is known as prepulse inhibition (PPI), and it provides a quantitative measure of central processing by filtering out irrelevant stimuli. As PPI implies plasticity of a reflex and is related to automatic or attentional processes, depending on the interstimulus intervals, this behavioral paradigm might be considered a potential marker of short- and long-term plasticity. Assessment of PPI is directly related to the examination of neural sensorimotor gating mechanisms, which are plastic-adaptive operations for preventing overstimulation and helping the brain to focus on a specific stimulus among other distracters. Despite their obvious importance in normal brain activity, little is known about the intimate physiology, circuitry, and neurochemistry of sensorimotor gating mechanisms. In this work, we extensively review the current literature focusing on studies that used state-of-the-art techniques to interrogate the neuroanatomy, connectomics, neurotransmitter-receptor functions, and sex-derived differences in the PPI process, and how we can harness it as biological marker in neurological and psychiatric pathology.

Recent advances in exercise pressor reflex function in health and disease.

Abstract: Autonomic alterations at the onset of exercise are critical to redistribute cardiac output towards the contracting muscles while preventing a fall in arterial pressure due to excessive vasodilation within the contracting muscles. Neural mechanisms responsible for these adjustments include central command, the exercise pressor reflex, and arterial and cardiopulmonary baroreflexes. The exercise pressor reflex evokes reflex increases in sympathetic activity to the heart and systemic vessels and decreases in parasympathetic activity to the heart, which increases blood pressure (BP), heart rate, and total peripheral resistance through vasoconstriction of systemic vessels. In this review, we discuss recent advancements in our understanding of exercise pressor reflex function in health and disease. Specifically, we discuss emerging evidence suggesting that sympathetic vasoconstrictor drive to the contracting and non-contracting skeletal muscle is differentially controlled by central command and the metaboreflex in healthy conditions. Further, we discuss evidence from animal and human studies showing that cardiovascular diseases, including hypertension, diabetes, and heart failure, lead to an altered exercise pressor reflex function. We also provide an update on the mechanisms thought to underlie this altered exercise pressor reflex function in each of these diseases. Although these mechanisms are complex, multifactorial, and dependent on the etiology of the disease, there is a clear consensus that several mechanisms are involved. Ultimately, approaches targeting these mechanisms are clinically significant as they provide alternative therapeutic strategies to prevent adverse cardiovascular events while also reducing symptoms of exercise intolerance.

Principles of Electrophysiological Assessments for Movement Disorders.

Abstract: Electrophysiological studies can provide objective and quantifiable assessments of movement disorders. They are useful in the diagnosis of hyperkinetic movement disorders, particularly tremors and myoclonus. The most commonly used measures are surface electromyography (sEMG), electroencephalography (EEG) and accelerometry. Frequency and coherence analyses of sEMG signals may reveal the nature of tremors and the source of the tremors. The effects of voluntary tapping, ballistic movements and weighting of the limbs can help to distinguish between organic and functional tremors. The presence of Bereitschafts-potentials and beta-band desynchronization recorded by EEG before movement onset provide strong evidence for functional movement disorders. EMG burst durations, distributions and muscle recruitment orders may identify and classify myoclonus to cortical, subcortical or spinal origins and help in the diagnosis of functional myoclonus. Organic and functional cervical dystonia can potentially be distinguished by EMG power spectral analysis. Several reflex circuits, such as the long latency reflex, blink reflex and startle reflex, can be elicited with different types of external stimuli and are useful in the assessment of myoclonus, excessive startle and stiff person syndrome. However, limitations of the tests should be recognized, and the results should be interpreted together with clinical observations.

Safety of local anesthetics.

Abstract: Local anesthetics are essential medications for the conduction of dermatological procedures. They stop the depolarization of nerve fibers and are divided into two main categories, the amide and ester types. Systemic toxicity with reflex on the central nervous and cardiovascular systems is their most feared adverse reactions, and the anaphylactic reaction is the most concerning one. Although potentially fatal, these events are extremely rare, so local anesthetics are considered safe for use in in-office procedures.

Relation of Fractionated Atrial Potentials With the Vagal Innervation Evaluated by Extracardiac Vagal Stimulation During Cardioneuroablation.

Abstract: Background: Vagal hyperactivity is directly related to several clinical conditions as reflex/functional bradyarrhythmias and vagal atrial fibrillation (AF). Cardioneuroablation provides therapeutic...

The potential role of the carotid body in COVID-19.

Abstract: The carotid body (CB) plays a contributory role in the pathogenesis of various respiratory, cardiovascular, renal, and metabolic diseases through reflex changes in ventilation and sympathetic output. On the basis of available data about peripheral arterial chemoreception and severe acute respiratory syndrome-coronavirus 2 (SARS-CoV-2), a potential involvement in the coronavirus disease 2019 (COVID-19) may be hypothesized through different mechanisms. The CB could be a site of SARS-CoV-2 invasion, due to local expression of its receptor [angiotensin-converting enzyme (ACE) 2] and an alternative route of nervous system invasion, through retrograde transport along the carotid sinus nerve. The CB function could be affected by COVID-19-induced inflammatory/immune reactions and/or ACE1/ACE2 imbalance, both at local or systemic level. Increased peripheral arterial chemosensitivity and reflex sympatho-activation may contribute to the increased morbidity and mortality in COVID-19 patients with respiratory, cardiovascular, renal, or metabolic comorbidities.

The exercise pressor reflex and chemoreflex interaction: cardiovascular implications for the exercising human

Abstract: Key points Although the exercise pressor reflex (EPR) and the chemoreflex (CR) are recognized for their sympathoexcitatory effect, the cardiovascular implication of their interaction remains elusive. We quantified the individual and interactive cardiovascular consequences of these reflexes during exercise and revealed various modes of interaction. The EPR and hypoxia-induced CR interaction is hyper-additive for blood pressure and heart rate (responses during co-activation of the two reflexes are greater than the summation of the responses evoked by each reflex) and hypo-additive for peripheral haemodynamics (responses during co-activation of the reflexes are smaller than the summated responses). The EPR and hypercapnia-induced CR interaction results in a simple addition of the individual responses to each reflex (i.e. additive interaction). Collectively, EPR:CR co-activation results in significant cardiovascular interactions with restriction in peripheral haemodynamics, resulting from the EPR:CR interaction in hypoxia, likely having the most crucial impact on the functional capacity of an exercising human. Abstract We investigated the interactive effect of the exercise pressor reflex (EPR) and the chemoreflex (CR) on the cardiovascular response to exercise. Eleven healthy participants (5 females) completed a total of six bouts of single-leg knee-extension exercise (60% peak work rate, 4 min each) either with or without lumbar intrathecal fentanyl to attenuate group III/IV afferent feedback from lower limbs to modify the EPR, while breathing either ambient air, normocapnic hypoxia (Sa O2 ∼79%, Pa O2 ∼43 mmHg, Pa CO2 ∼33 mmHg, pH ∼7.39), or normoxic hypercapnia (Sa O2 ∼98%, Pa O2 ∼105 mmHg, Pa CO2 ∼50 mmHg, pH ∼7.26) to modify the CR. During co-activation of the EPR and the hypoxia-induced CR (O2 -CR), mean arterial pressure and heart rate were significantly greater, whereas leg blood flow and leg vascular conductance were significantly lower than the summation of the responses evoked by each reflex alone. During co-activation of the EPR and the hypercapnia-induced CR (CO2 -CR), the haemodynamic responses were not different from the summated responses to each reflex response alone (P ≥ 0.1). Therefore, while the interaction resulting from the EPR:O2 -CR co-activation is hyper-additive for blood pressure and heart rate, and hypo-additive for peripheral haemodynamics, the interaction resulting from the EPR:CO2 -CR co-activation is simply additive for all cardiovascular parameters. Thus, EPR:CR co-activation results in significant interactions between cardiovascular reflexes, with the impact differing when the CR activation is achieved by hypoxia or hypercapnia. Since the EPR:CR co-activation with hypoxia potentiates the pressor response and restricts blood flow to contracting muscles, this interaction entails the most functional impact on an exercising human.

The Mammalian Diving Response: Inroads to Its Neural Control.

Abstract: The mammalian diving response (DR) is a remarkable behavior that was first formally studied by Laurence Irving and Per Scholander in the late 1930s. The DR is called such because it is most prominent in marine mammals such as seals, whales, and dolphins, but nevertheless is found in all mammals studied. It consists generally of breathing cessation (apnea), a dramatic slowing of heart rate (bradycardia), and an increase in peripheral vasoconstriction. The DR is thought to conserve vital oxygen stores and thus maintain life by directing perfusion to the two organs most essential for life-the heart and the brain. The DR is important, not only for its dramatic power over autonomic function, but also because it alters normal homeostatic reflexes such as the baroreceptor reflex and respiratory chemoreceptor reflex. The neurons driving the reflex circuits for the DR are contained within the medulla and spinal cord since the response remains after the brainstem transection at the pontomedullary junction. Neuroanatomical and physiological data suggesting brainstem areas important for the apnea, bradycardia, and peripheral vasoconstriction induced by underwater submersion are reviewed. Defining the brainstem circuit for the DR may open broad avenues for understanding the mechanisms of suprabulbar control of autonomic function in general, as well as implicate its role in some clinical states. Knowledge of the proposed diving circuit should facilitate studies on elite human divers performing breath-holding dives as well as investigations on sudden infant death syndrome (SIDS), stroke, migraine headache, and arrhythmias. We have speculated that the DR is the most powerful autonomic reflex known.

Sympathetic nerves control bacterial clearance.

Abstract: A neural reflex mediated by the splanchnic sympathetic nerves regulates systemic inflammation in negative feedback fashion, but its consequences for host responses to live infection are unknown. To test this, conscious instrumented sheep were infected intravenously with live E. coli bacteria and followed for 48 h. A month previously, animals had undergone either bilateral splanchnic nerve section or a sham operation. As established for rodents, sheep with cut splanchnic nerves mounted a stronger systemic inflammatory response: higher blood levels of tumor necrosis factor alpha and interleukin-6 but lower levels of the anti-inflammatory cytokine interleukin-10, compared with sham-operated animals. Sequential blood cultures revealed that most sham-operated sheep maintained high circulating levels of live E. coli throughout the 48-h study period, while all sheep without splanchnic nerves rapidly cleared their bacteraemia and recovered clinically. The sympathetic inflammatory reflex evidently has a profound influence on the clearance of systemic bacterial infection.

Direct evidence for decreased presynaptic inhibition evoked by PBSt group I muscle afferents after chronic SCI and recovery with step-training in rats

Abstract: Key points Presynaptic inhibition is modulated by supraspinal centres and primary afferents in order to filter sensory information, adjust spinal reflex excitability, and ensure smooth movement. After spinal cord injury (SCI), the supraspinal control of primary afferent depolarization (PAD) interneurons is disengaged, suggesting an increased role for sensory afferents. While increased H-reflex excitability in spastic individuals indicates a possible decrease in presynaptic inhibition, it remains unclear whether a decrease in sensory-evoked PAD contributes to this effect. We investigated whether the PAD evoked by hindlimb afferents contributes to the change in presynaptic inhibition of the H-reflex in a decerebrated rat preparation. We found that chronic SCI decreases presynaptic inhibition of the plantar H-reflex through a reduction in PAD evoked by posterior biceps-semitendinosus (PBSt) muscle group I afferents. We further found that step-training restored presynaptic inhibition of the plantar H-reflex evoked by PBSt, suggesting the presence of activity-dependent plasticity of PAD pathways activated by flexor muscle group I afferents. Abstract Spinal cord injury (SCI) results in the disruption of supraspinal control of spinal networks and an increase in the relative influence of afferent feedback to sublesional neural networks, both of which contribute to enhancing spinal reflex excitability. Hyperreflexia occurs in ∼75% of individuals with a chronic SCI and critically hinders functional recovery and quality of life. It is suggested that it results from an increase in motoneuronal excitability and a decrease in presynaptic and postsynaptic inhibitory mechanisms. In contrast, locomotor training decreases hyperreflexia by restoring presynaptic inhibition. Primary afferent depolarization (PAD) is a powerful presynaptic inhibitory mechanism that selectively gates primary afferent transmission to spinal neurons to adjust reflex excitability and ensure smooth movement. However, the effect of chronic SCI and step-training on the reorganization of presynaptic inhibition evoked by hindlimb afferents, and the contribution of PAD has never been demonstrated. The objective of this study is to directly measure changes in presynaptic inhibition through dorsal root potentials (DRPs) and its association with plantar H-reflex inhibition. We provide direct evidence that H-reflex hyperexcitability is associated with a decrease in transmission of PAD pathways activated by posterior biceps-semitendinosus (PBSt) afferents after chronic SCI. More precisely, we illustrate that the pattern of inhibition evoked by PBSt group I muscle afferents onto both L4-DRPs and plantar H-reflexes evoked by the distal tibial nerve is impaired after chronic SCI. These changes are not observed in step-trained animals, suggesting a role for activity-dependent plasticity to regulate PAD pathways activated by flexor muscle group I afferents.

Corneal Reflex Testing in the Evaluation of a Comatose Patient: An Ode to Precise Semiology and Examination Skills

Abstract: The corneal reflex assesses the integrity of the trigeminal and facial cranial nerves. This brainstem reflex is fundamental in neuroprognostication after cardiac arrest and in brain death determination. We sought to investigate corneal reflex testing methods among neurologists and general critical care providers in the context of neuroprognostication following cardiac arrest. This is an international cross-sectional study disseminated to members of the Neurocritical Care Society, Society of Critical Care Medicine, and American Academy of Neurology. We utilized an open Web-based survey (Qualtrics®, Provo, UT, USA) to disseminate 26 questions regarding neuroprognostication practices following cardiac arrest, in which 3 questions pertained to corneal reflex testing. Descriptive statistical measures were used, and subgroup analyses performed between neurologists and non-neurologists. Questions were not mandatory; therefore, the percentages were relative to the number of respondents for each question. There were 959 respondents in total. Physicians comprised 85.1% of practitioners (762 out of 895), of which 55% (419) identified themselves as non-neurologists and 45% (343) as neurologists. Among physicians, 85.9% (608 out of 708) deemed corneal reflex relevant for prognostication following cardiac arrest (neurologists 84.4% versus non-neurologists 87.0%). A variety of techniques were employed for corneal reflex testing, the most common being “light cotton touch” (59.2%), followed by “cotton-tipped applicator with pressure” (23.9%), “saline or water squirt” (15.9%), and “puff of air” (1.0%). There were no significant differences in the methods for testing between neurologists and non-neurologists (p = 0.52). The location of stimulus application was variable, and 26.1% of physicians (148/567) apply the stimulus on the temporal conjunctiva rather than on the cornea itself. Corneal reflex testing remains a cornerstone of the coma exam and is commonly used in neuroprognostication of unconscious cardiac arrest survivors and in brain death determination. A wide variability of techniques is noted among practitioners, including some that may provide suboptimal stimulation of corneal nerve endings. Imprecise testing in this setting may lead to inaccuracies in critical settings, which carries significant consequences such as guiding decisions of care limitations, misdiagnosis of brain death, and loss of public trust.

Machine learning analysis to automatically measure response time of pharyngeal swallowing reflex in videofluoroscopic swallowing study.

Abstract: To evaluate clinical features and determine rehabilitation strategies of dysphagia, it is crucial to measure the exact response time of the pharyngeal swallowing reflex in a videofluoroscopic swallowing study (VFSS). However, measuring the response time of the pharyngeal swallowing reflex is labor-intensive and particularly for inexperienced clinicians, it can be difficult to measure the brief instance of the pharyngeal swallowing reflex by VFSS. To accurately measure the response time of the swallowing reflex, we present a novel framework, able to detect quick events. In this study, we evaluated the usefulness of machine learning analysis of a VFSS video for automatic measurement of the response time of a swallowing reflex in a pharyngeal phase. In total, 207 pharyngeal swallowing event clips, extracted from raw VFSS videos, were annotated at the starting point and end point of the pharyngeal swallowing reflex by expert clinicians as ground-truth. To evaluate the performance and generalization ability of our model, fivefold cross-validation was performed. The average success rates of detection of the class "during the swallowing reflex" for the training and validation datasets were 98.2% and 97.5%, respectively. The average difference between the predicted detection and the ground-truth at the starting point and end point of the swallowing reflex was 0.210 and 0.056 s, respectively. Therefore, the response times during pharyngeal swallowing reflex are automatically detected by our novel framework. This framework can be a clinically useful tool for estimating the absence or delayed response time of the swallowing reflex in patients with dysphagia and improving poor inter-rater reliability of evaluation of response time of pharyngeal swallowing reflex between expert and unskilled clinicians.

Reflexes that impact spontaneous breathing of preterm infants at birth: a narrative review

Abstract: Some neural circuits within infants are not fully developed at birth, especially in preterm infants. Therefore, it is unclear whether reflexes that affect breathing may or may not be activated during the neonatal stabilisation at birth. Both sensory reflexes (eg, tactile stimulation) and non-invasive ventilation (NIV) can promote spontaneous breathing at birth, but the application of NIV can also compromise breathing by inducing facial reflexes that inhibit spontaneous breathing. Applying an interface could provoke the trigeminocardiac reflex (TCR) by stimulating the trigeminal nerve resulting in apnoea and a reduction in heart rate. Similarly, airflow within the nasopharynx can elicit the TCR and/or laryngeal chemoreflex (LCR), resulting in glottal closure and ineffective ventilation, whereas providing pressure via inflations could stimulate multiple receptors that affect breathing. Stimulating the fast adapting pulmonary receptors may activate Head's paradoxical reflex to stimulate spontaneous breathing. In contrast, stimulating the slow adapting pulmonary receptors or laryngeal receptors could induce the Hering-Breuer inflation reflex or LCR, respectively, and thereby inhibit spontaneous breathing. As clinicians are most often unaware that starting primary care might affect the breathing they intend to support, this narrative review summarises the currently available evidence on (vagally mediated) reflexes that might promote or inhibit spontaneous breathing at birth.

Noninvasive vagus nerve stimulation and the trigeminal autonomic reflex: An fMRI study

Abstract: Objective The trigeminal autonomic reflex is a physiologic reflex that plays a crucial role in primary headache and particularly in trigeminal autonomic cephalalgias, such as cluster headache. Previous studies have shown that this reflex can be modulated by the vagus nerve, leading to an inhibition of the parasympathetic output of the reflex in healthy participants. The aim of the present study was to characterize neural correlates of the modulatory effect of noninvasive vagus nerve stimulation (nVNS) on the trigeminal autonomic reflex. Methods Twenty-one healthy participants were included in a 2-day, randomized, single-blind, within-subject design. The reflex was activated inside the MRI scanner using kinetic oscillation stimulation placed in the left nostril, resulting in an increase in lacrimation. After the first fMRI session, the participants received either sham vagus nerve stimulation or nVNS outside the scanner and underwent a subsequent fMRI session. Results nVNS prompted an increase in activation of the left pontine nucleus and a decreased activation of the right parahippocampal gyrus. Psychophysiologic interaction analyses revealed an increased functional connectivity between the left pontine nucleus and the right hypothalamus and a decreased functional connectivity between the right parahippocampal gyrus and the bilateral spinal trigeminal nuclei (sTN). Conclusions These findings indicate a complex network involved in the modulatory effect of nVNS including the hypothalamus, the sTN, the pontine nucleus, and the parahippocampal gyrus.

Cardiovascular Control During Exercise: The Connectivity of Skeletal Muscle Afferents to the Brain.

Abstract: The exercise pressor reflex (EPR) is engaged upon the activation of group III/IV skeletal muscle afferents and is one of the principal mediators of cardiovascular responses to exercise. This review explores the hypothesis that afferent signals from EPR communicate via GABAergic contacts within the brain stem to evoke parasympathetic withdrawal and sympathoexcitation to increase cardiac output, peripheral resistance, and blood pressure during exercise.

Evidence for a physiological role of pulmonary arterial baroreceptors in sympathetic neural activation in healthy humans

Abstract: KEY POINTS In an anaesthetised animal model, independent stimulation of baroreceptors in the pulmonary artery elicits reflex sympathoexcitation. In humans, pulmonary arterial pressure is positively related to basal muscle sympathetic nerve activity (MSNA) under conditions where elevated pulmonary pressure is evident (e.g. high altitude); however, a causal link is not established. Using a novel experimental approach, we demonstrate that reducing pulmonary arterial pressure lowers basal MSNA in healthy humans. This response is distinct from the negative feedback reflex mediated by aortic and carotid sinus baroreceptors when systemic arterial pressure is lowered. Afferent input from pulmonary arterial baroreceptors may contribute to sympathetic neural activation in healthy lowland natives exposed to high altitude. ABSTRACT In animal models, distension of baroreceptors located in the pulmonary artery induces a reflex increase in sympathetic outflow; however, this has not been examined in humans. Therefore, we investigated whether reductions in pulmonary arterial pressure influenced sympathetic outflow and baroreflex control of muscle sympathetic nerve activity (MSNA). Healthy lowlanders (n = 13; 5 females) were studied 4-8 days following arrival at high altitude (4383 m; Cerro de Pasco, Peru), a setting that increases both pulmonary arterial pressure and sympathetic outflow. MSNA (microneurography) and blood pressure (BP; photoplethysmography) were measured continuously during ambient air breathing (Amb) and a 6 min inhalation of the vasodilator nitric oxide (iNO; 40 ppm in 21% O2 ), to selectively lower pulmonary arterial pressure. A modified Oxford test was performed under both conditions. Pulmonary artery systolic pressure (PASP) was determined using Doppler echocardiography. iNO reduced PASP (24 ± 3 vs. 32 ± 5 mmHg; P < 0.001) compared to Amb, with a similar reduction in MSNA total activity (1369 ± 576 to 994 ± 474 a.u min-1 ; P = 0.01). iNO also reduced the MSNA operating point (burst incidence; 39 ± 16 to 33 ± 17 bursts·100 Hb-1 ; P = 0.01) and diastolic operating pressure (82 ± 8 to 80 ± 8 mmHg; P < 0.001) compared to Amb, without changing heart rate (P = 0.6) or vascular-sympathetic baroreflex gain (P = 0.85). In conclusion, unloading of pulmonary arterial baroreceptors reduced basal sympathetic outflow to the skeletal muscle vasculature and reset vascular-sympathetic baroreflex control of MSNA downward and leftward in healthy humans at high altitude. These data suggest the existence of a lesser-known reflex input involved in sympathetic activation in humans.

Establishing critical differences in ear-canal stimulus amplitude for detecting middle ear muscle reflex activation during olivocochlear efferent measurements

Abstract: Objective: Assessments of the medial olivocochlear reflex (MOCR) may have clinical utility. The MOCR is measured using contralateral inhibition of otoacoustic emissions but concurrent activ...

Chemical Stimulation of Renal Tissue Induces Sympathetic Activation and a Pressor Response via the Paraventricular Nucleus in Rats.

Abstract: Sympathetic activation and the kidney play critical roles in hypertension and chronic heart failure. The role of the kidney in sympathetic activation is still not well known. In this study, we revealed an excitatory renal reflex (ERR) in rats induced by chemical stimulation of the kidney that regulated sympathetic activity and blood pressure. The ERR was induced by renal infusion of capsaicin, and evaluated by the changes in renal sympathetic outflow, blood pressure, and heart rate. Renal infusion of capsaicin dose-dependently increased the contralateral renal sympathetic nerve activity, mean arterial pressure, and heart rate. Capsaicin in the cortico-medullary border had greater effects than in the cortex or medulla. Intravenous infusion of capsaicin had no significant effects. The effects of renal infusion of capsaicin were abolished by ipsilateral renal denervation, but were not affected by bilateral sinoaortic denervation. Renal infusion of capsaicin increased the ipsilateral renal afferent activity. The ERR was also induced by renal infusion of bradykinin, adenosine, and angiotensin II, but not by ATP. Renal infusion of capsaicin increased c-Fos expression in the paraventricular nucleus (PVN) of hypothalamus. Lesion of neurons in the PVN with kainic acid abolished the capsaicin-induced ERR. These findings indicate that chemical stimulation of kidney causes an excitatory reflex, leading to sympathetic activation, pressor response, and accelerated heart rate. The PVN is an important central nucleus in the pathway of the ERR.

Long-latency Responses to a Mechanical Perturbation of the Index Finger Have a Spinal Component.

Abstract: In an uncertain external environment, the motor system may need to respond rapidly to an unexpected stimulus. Limb displacement causes muscle stretch; the corrective response has multiple activity bursts, which are suggested to originate from different parts of the neuraxis. The earliest response is so fast, it can only be produced by spinal circuits; this is followed by slower components thought to arise from primary motor cortex (M1) and other supraspinal areas. Spinal cord (SC) contributions to the slower components are rarely considered. To address this, we recorded neural activity in M1 and the cervical SC during a visuomotor tracking task, in which 2 female macaque monkeys moved their index finger against a resisting motor to track an on-screen target. Following the behavioral trial, an increase in motor torque rapidly returned the finger to its starting position (lever velocity >200°/s). Many cells responded to this passive mechanical perturbation (M1: 148 of 211 cells, 70%; SC: 67 of 119 cells, 56%). The neural onset latency was faster for SC compared with M1 cells (21.7 ± 11.2 ms vs 25.5 ± 10.7 ms, respectively, mean ± SD). Using spike-triggered averaging, some cells in both regions were identified as likely premotor cells, with monosynaptic connections to motoneurons. Response latencies for these cells were compatible with a contribution to the muscle responses following the perturbation. Comparable fractions of responding neurons in both areas were active up to 100 ms after the perturbation, suggesting that both SC circuits and supraspinal centers could contribute to later response components.SIGNIFICANCE STATEMENT Following a limb perturbation, multiple reflexes help to restore limb position. Given conduction delays, the earliest part of these reflexes can only arise from spinal circuits. By contrast, long-latency reflex components are typically assumed to originate from supraspinal centers. We recorded from both spinal and motor cortical cells in monkeys responding to index finger perturbations. Many spinal interneurons, including those identified as projecting to motoneurons, responded to the perturbation; the timing of responses was compatible with a contribution to both short- and long-latency reflexes. We conclude that spinal circuits also contribute to long-latency reflexes in distal and forearm muscles, alongside supraspinal regions, such as the motor cortex and brainstem.

Neurological Disorders Identified during Treatment of a SARS-CoV-2 Infection.

Abstract: A 69-year-old man was admitted to our hospital under diagnosis of pneumonia due to severe acute respiratory syndrome-corona virus 2 (SARS-CoV-2) (Day 0). He underwent endotracheal intubation from Day 3. Although his respiratory condition improved and anesthetic drugs were discontinued, no cough reflex was observed despite intubation having been performed until Day 17. His tendon reflexes were also diminished. We suspected that he had developed Guillain-Barre syndrome (GBS), and administered intravenous immunoglobulin from Day 18. The absence of cough reflex improved and extubation was successfully performed on Day 23. Neurological disorders including GBS should be considered when intubated SARS-CoV-2 patients present with a loss of cough reflex during the treatment period.

Neural Mechanisms Underlying High-Frequency Vestibulocollic Reflexes In Humans And Monkeys.

Abstract: The vestibulocollic reflex is a compensatory response that stabilizes the head in space. During everyday activities, this stabilizing response is evoked by head movements that typically span frequencies from 0 to 30 Hz. Transient head impacts, however, can elicit head movements with frequency content up to 300-400 Hz, raising the question whether vestibular pathways contribute to head stabilization at such high frequencies. Here, we first established that electrical vestibular stimulation modulates human neck motor unit (MU) activity at sinusoidal frequencies up to 300 Hz, but that sensitivity increases with frequency up to a low-pass cutoff of ∼70-80 Hz. To examine the neural substrates underlying the low-pass dynamics of vestibulocollic reflexes, we then recorded vestibular afferent responses to the same electrical stimuli in monkeys. Vestibular afferents also responded to electrical stimuli up to 300 Hz, but in contrast to MUs their sensitivity increased with frequency up to the afferent resting firing rate (∼100-150 Hz) and at higher frequencies afferents tended to phase-lock to the vestibular stimulus. This latter nonlinearity, however, was not transmitted to neck motoneurons, which instead showed minimal phase-locking that decreased at frequencies >75 Hz. Similar to human data, we validated that monkey muscle activity also exhibited low-pass filtered vestibulocollic reflex dynamics. Together, our results show that neck MUs are activated by high-frequency signals encoded by primary vestibular afferents, but undergo low-pass filtering at intermediate stages in the vestibulocollic reflex. These high-frequency contributions to vestibular-evoked neck muscle responses could stabilize the head during unexpected head transients.SIGNIFICANCE STATEMENT Vestibular-evoked neck muscle responses rely on accurate encoding and transmission of head movement information to stabilize the head in space. Unexpected transient events, such as head impacts, are likely to push the limits of these neural pathways since their high-frequency features (0-300 Hz) extend beyond the frequency bandwidth of head movements experienced during everyday activities (0-30 Hz). Here, we demonstrate that vestibular primary afferents encode high-frequency stimuli through frequency-dependent increases in sensitivity and phase-locking. When transmitted to neck motoneurons, these signals undergo low-pass filtering that limits neck motoneuron phase-locking in response to stimuli >75 Hz. This study provides insight into the neural dynamics producing vestibulocollic reflexes, which may respond to high-frequency transient events to stabilize the head.

Voluntary Activation and Reflex Responses after Hamstring Strain Injury.

Abstract: Introduction There is a lack of definitive evidence supporting deficits in voluntary activation in participants with prior hamstring injury; moreover, it remains unknown if spinal mechanisms contribute to suspected deficits. Purpose This study aimed to determine the effect of prior hamstring strain injury on knee flexor concentric and eccentric strength, voluntary activation, surface electromyographic (sEMG) activity, and stretch and tendon reflex amplitudes. Methods Twenty-five participants were recruited, 12 with a history of unilateral hamstring strain injury of at least moderate severity. Voluntary activation, strength, and sEMG activity were recorded during maximal eccentric and concentric knee flexor contractions at 60°·s-1. Stretch and tendon reflexes were also recorded at rest. Results Previously injured limbs exhibited lower levels of voluntary activation (mean difference = -24.1%, 95% confidence interval [CI] = -34.1% to -14.0%, P

Molecular/Ionic Basis of Vagal Bronchopulmonary C-Fiber Activation by Inflammatory Mediators

Abstract: Stimulation of bronchopulmonary vagal afferent C fibers by inflammatory mediators can lead to coughing, chest tightness, and changes in breathing pattern, as well as reflex bronchoconstriction and ...

Linking environmental factors with reflex action mortality predictors, physiological stress, and post-release movement behaviour to evaluate the response of white sturgeon (Acipenser transmontanus Richardson, 1836) to catch-and-release angling.

Abstract: White sturgeon are the largest freshwater fish in North America and are the focus of an intense catch-and-release (CR the effects are largely unknown. We assessed the effect of fight and handling time, water temperature, river discharge rate, and fish size on physiological and reflex impairment responses of wild white sturgeon to angling. Sixty of these fish were tagged with acoustic transmitters to assess survival and post-release behaviour. Survival was high (100%). Water temperature and discharge influenced post-capture blood physiology. Specifically, lactate, chloride, and cortisol concentrations were elevated in individuals fought longer, and captured at higher water temperatures and river discharge. Cortisol was affected by fish size, with lower concentrations found in larger individuals. Only lactate and chloride were positively related to reflex impairment scores. Post-release movements were correlated with physiological state, fight characteristics and the environment. Specifically, higher blood lactate and chloride and those with longer fight times moved shorter distances after release. Contrastingly, higher levels of circulating glucose and potassium, as well as larger fish captured during periods of high discharge moved longer distances. Sturgeon tended to move shorter distances and at slower rates when reflex impairment was high, although reflex impairment in general did not explain a significant proportion of the variance in any movement metric. Our results show intriguing variance in the physiological and behavioural response of individual white sturgeon to C&R angling, with some degree of environmental dependence, and highlights the importance of understanding drivers of such variation when managing fisheries.

Angiotensin Type 1 Receptors and Superoxide Anion Production in Hypothalamic Paraventricular Nucleus Contribute to Capsaicin-Induced Excitatory Renal Reflex and Sympathetic Activation.

Abstract: Chemical stimulation of the kidney increases sympathetic activity and blood pressure in rats. The hypothalamic paraventricular nucleus (PVN) is important in mediating the excitatory renal reflex (ERR). In this study, we examined the role of molecular signaling in the PVN in mediating the capsaicin-induced ERR and sympathetic activation. Bilateral PVN microinjections were performed in rats under anesthesia. The ERR was elicited by infusion of capsaicin into the cortico-medullary border of the right kidney. The reflex was evaluated as the capsaicin-induced changes in left renal sympathetic nerve activity and mean arterial pressure. Blockade of angiotensin type 1 receptors with losartan or inhibition of angiotensin-converting enzyme with captopril in the PVN abolished the capsaicin-induced ERR. Renal infusion of capsaicin significantly increased NAD(P)H oxidase activity and superoxide anion production in the PVN, which were prevented by ipsilateral renal denervation or microinjection of losartan into the PVN. Furthermore, either scavenging of superoxide anions or inhibition of NAD(P)H oxidase in the PVN abolished the capsaicin-induced ERR. We conclude that the ERR induced by renal infusion of capsaicin is mediated by angiotensin type 1 receptor-related NAD(P)H oxidase activation and superoxide anion production within the PVN.