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INTRODUCTION: Chronic ankle instability (CAI), a common seqeula to ankle injury is characterized by a variety of sensorimotor deficits extending beyond the previously injured limb. Cutaneous reflexes have been identified as a potential contributor to these functional limitations with recent studies identifying alterations in reflex patterns following sural nerve stimulation among those with CAI. To date, no studies have measured cutaneous reflexes of the unaffected limb in this population, therefore, the objective of this study was to measure contralateral cutaneous reflexes during gait in individuals with unilateral CAI and healthy controls. METHODS: Muscle activity of 6 lower limb muscles was measured in nineteen participants while receiving random, non-noxious sural nerve stimulations during a walking task. RESULTS: Control reflex patterns were generally well-aligned with previous literature while CAI patterns varied from controls in several muscles throughout the gait cycle. Namely, a lack of lateral gastrocnemius facilitation during late stance and medial gastrocnemius inhibition at midstance. Additionally, a lack of significant BF facilitation throughout contralateral swing was noted. These results indicate reflex alterations extend beyond the affected limb in those with unilateral CAI indicating changes at the spinal level following lateral ankle sprains (LAS). Considering the symptom variability in CAI, the lack of significant reflexes exhibited by the CAI group may be due to increased variability in motor output between subjects or between stimulation trials. CONCLUSIONS: These findings highlight the importance of identifying reflex alterations arising from LAS and subsequently treating these limitations through rehabilitation targeting systemic neural pathways rather than local deficits.

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PURPOSE: Cough reflex testing (CRT) is an adjunct to the clinical swallowing evaluation (CSE), providing information on patients' risk of silent aspiration. CRT has been shown to influence diet recommendations, but in previous work, the many varied patient characteristics are not controlled. Therefore, the specific role of CRT results in these decisions remains unclear as this relationship has not been directly assessed. METHOD: An online survey was sent to speech language therapists working in dysphagia. Two patient cases were presented that differed only by the presence of risk factors for the development of aspiration pneumonia. For each patient case, there were three assessment scenarios: CSE information only, CSE information with a "pass" CRT result, and CSE information with a "fail" CRT result. Clinicians outlined their patient management plans for each of the six scenarios. RESULTS: Ninety-seven data sets were used in the final analysis. A "fail" result was found to lead to the most restrictive patient management. Decisions made when provided with only CSE information were very similar to decisions made for a CSE with a "pass" result. Aspiration pneumonia risk factors were shown to influence decision making, with the low-risk patient more likely to be recommended a less restrictive diet. CONCLUSIONS: When information was available regarding silent aspiration risk, clinicians factored the results into their decision making. However, in the absence of a CRT result, airway sensation was assumed to be intact in the absence of information. This finding warrants further investigation given the impact this assumption may have on a patient's pulmonary health.

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Introduction: The gag reflex is a protection mechanism that prevents food and unwanted agents from entering the lower airways. It is usually part of the physical examination of swallowing to detect oropharyngeal dysphagia, but it is a potentially ambiguous sign. Objective: To evaluate the diagnostic value of the gag reflex in patients with neurogenic oropharyngeal dysphagia and adults without it. Materials and methods: We conducted an analytical observational study in patients with neurogenic oropharyngeal dysphagia (cases) and patients without dysphagia (controls). We evaluated the absence or presence of the reflex bilaterally, by direct visualization, and adjusted it according to sex, age, and other interaction variables. Results: We included 86 patients with neurogenic oropharyngeal dysphagia and 80 control subjects. The gag reflex on swallowing physical examination showed a positive relationship with the patients (right side: OR = 3.97; 95 % CI: 2.01-7.84; left side: OR = 4.84; 95 % CI: 2.41-9.72), but a negative association with the control group. In both groups, neither sex, nor age, nor other interaction variables modified the gag reflex. Conclusions: The gag reflex absence or presence does not confirm or exclude the existence of oropharyngeal dysphagia due to neurological and neuromuscular causes. Therefore, health professionals must not rely on this reflex. Clinicians must go beyond a simple reflex revision, even in neurological patients where it is supposed to be absent.

Introducción. El reflejo nauseoso es un mecanismo de protección que impide que alimentos y agentes no deseados penetren en la vía aérea inferior. Usualmente, hace parte del examen físico de la deglución para detectar la disfagia orofaríngea, pero es un signo potencialmente ambiguo. Objetivo. Evaluar el valor diagnóstico del reflejo nauseoso en pacientes con disfagia orofaríngea neurogénica y en pacientes sin ella. Materiales y métodos. Se trata de un estudio observacional, analítico, en pacientes con disfagia orofaríngea neurogénica (casos) y en personas sin disfagia (controles), en el cual se evaluó por visualización directa la ausencia o la presencia del reflejo nauseoso de forma bilateral. Este resultado se ajustó por sexo, edad y otras variables de interacción. Resultados. Se evaluaron 86 pacientes con disfagia orofaríngea neurogénica y 80 personas sin ella. En el examen físico de la deglución, la presencia del reflejo mostró una relación positiva con los pacientes (lado derecho: OR = 3,97; IC95%: 2,01-7,84; lado izquierdo: OR = 4,84; IC95%: 2,41-9,72), pero una asociación negativa con los controles. En ambos grupos, ni el sexo ni la edad, ni otras variables de interacción modificaron el reflejo nauseoso. Conclusiones. La ausencia o la presencia del reflejo nauseoso no confirma ni excluye la existencia de una disfagia orofaríngea por causas neurológicas o neuromusculares; por lo tanto, no es recomendable que los profesionales de la salud se fíen del resultado de este reflejo. Los médicos tratantes deben ir más allá de una simple revisión del reflejo nauseoso, incluso en pacientes neurológicos en quienes se supone que debería estar ausente.

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The nociceptive withdrawal reflex (NWR) is a protective limb withdrawal response triggered by painful stimuli, used to assess spinal nociceptive excitability. Conventionally, the NWR is understood as having two reflex responses: a short-latency Aß-mediated response, considered tactile, and a longer-latency Aδ-mediated response, considered nociceptive. However, nociceptors with conduction velocities similar to Aß tactile afferents have been identified in human skin. In this study, we investigated the effect of a preferential conduction block of Aß fibers on pain perception and NWR signaling evoked by intradermal electrical stimulation in healthy participants. We recorded a total of 198 NWR responses in the intact condition, and no dual reflex responses occurred within our latency bandwidth (50-150 ms). The current required to elicit the NWR was higher than the perceptual pain threshold, indicating that NWR did not occur before pain was felt. In the block condition, when the Aß-mediated tuning fork sensation was lost while Aδ-mediated nonpainful cooling was still detectable (albeit reduced), we observed that the reflex was abolished. Further, short-latency electrical pain intensity at pre-block thresholds was greatly reduced, with any residual pain sensation having a longer latency. Although electrical pain was unaffected at suprathreshold current, the reflex could not be evoked despite a two-fold increase in the pre-block current and a five-fold increase in the pre-block pulse duration. These observations lend support to the possible involvement of Aß-fiber inputs in pain and reflex signaling.

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PURPOSE: The goal of this manuscript was to review the biological and clinical evidence that serotonin neurotransmission might play an important role in the  physiology and treatment of vasovagal syncope. METHODS: The authors reviewed PubMed and handsearches of secondary sources for papers related to the Bezold-Jarisch reflex and serotonin, the plausible involvement of the Bezold-Jarisch reflex in vasovagal syncope, and three lines of clinical evidence involving serotonin and the syncope. RESULTS: The Bezold-Jarisch reflex was first described following the infusion of veratrum alkaloids into animals in the 19th century. The reflex is triggered by serotonin stimulation chemoreceptors and mechanoreceptors in the the left ventricle. The afferent component of the reflex is carried by unmyelinated type C vagal nerve fibers, which results in parasympathetic efferent stimulation that causes bradycardia. The similarity of the combination of hypotension and bradycardia in the Bezold-Jarisch reflex and in vasovagal syncope led to the suggestion that the reflex was the cause of the syndrome.  Three lines of evidence implicate the serotonin 5HT3 receptors in the heart in the reflex. There is genetic and physiologic evidence for the serotonin 5HT1A and 5HT3 receptors and the serotonin reuptake transporter (SERT). Acute blockade of SERT induces vasovagal syncope in humans undergoing head-up tilt table testing, and SERT inhibition reduces hypotension and bradycardia during spinal anaesthesia. Finally, three randomized clinical trials of SERT inhibitors uniformly reported that they significantly reduce the likelihood of vasovagal syncope recurrences. CONCLUSION: Multiple lines of evidence implicate serotonin neurotransmission in the cause of vasovagal syncope.

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Oral contraceptive (OC) use can increase resting blood pressure (BP) in females as well as contribute to greater activation of group III/IV afferents during upper body exercise. It is unknown, however, whether an exaggerated BP response occurs during lower limb exercise in OC users. We sought to elucidate the group III/IV afferent activity-mediated BP and heart rate responses while performing lower extremity tasks during early and late follicular phases in young, healthy females. Females not taking OCs (NOC: n = 8; age: 25 ± 4 yr) and those taking OCs (OC: n = 10; age: 23 ± 2 yr) completed a continuous knee extension/flexion passive stretch (mechanoreflex) and cycling exercise with subsystolic cuff occlusion (exercise pressor reflex), which was followed by a 2-min postexercise circulatory occlusion (PECO) (metaboreflex). Data collection occurred on two occasions: once during the early follicular phase (days 1-4) and once during the late follicular phase (days 10-14) of their menstrual cycle (NOC) or during the placebo and active pill phases (OC). Resting mean arterial BP and heart rate were not different between phases in NOC and OC participants (P > 0.05). Hemodynamic responses to metaboreflex, mechanoreflex, and collective exercise pressor reflex activation were not different between phases in both groups (P > 0.05). In conclusion, although OCs are known to increase BP at rest, our findings indicate that neither endogenous nor exogenous (OC) sex hormones modulate BP during large, lower limb muscle exercise with or without group III/IV afferent activation in young, healthy females.NEW & NOTEWORTHY Sex differences in the cardiovascular response to exercise have been demonstrated and may be dependent on sex hormone levels. Furthermore, oral contraceptives (OCs) have been shown to exaggerate the blood pressure response to upper extremity exercise. The results of this study indicate that neither endogenous nor exogenous (OC) sex hormones modulate BP during lower extremity dynamic exercise or with group III/IV afferent activation in young, healthy females.

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Replicating neural responses observed in biological systems using artificial neural networks holds significant promise in the fields of medicine and engineering. In this study, we employ ultra-fast artificial neurons based on antiferromagnetic (AFM) spin Hall oscillators to emulate the biological withdrawal reflex responsible for self-preservation against noxious stimuli, such as pain or temperature. As a result of utilizing the dynamics of AFM neurons, we are able to construct an artificial neural network that can mimic the functionality and organization of the biological neural network responsible for this reflex. The unique features of AFM neurons, such as inhibition that stems from an effective AFM inertia, allow for the creation of biologically realistic neural network components, like the interneurons in the spinal cord and antagonist motor neurons. To showcase the effectiveness of AFM neuron modeling, we conduct simulations of various scenarios that define the withdrawal reflex, including responses to both weak and strong sensory stimuli, as well as voluntary suppression of the reflex.

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Previous research has demonstrated that oral contraceptive (OC) users have enhanced cardiorespiratory responses to arm metaboreflex activation (i.e., postexercise circulatory occlusion, PECO) and attenuated pressor responses to leg passive movement (PM) compared to non-OC users (NOC). We investigated the cardiorespiratory responses to arm or leg metaboreflex and mechanoreflex activation in 32 women (OC, n = 16; NOC, n = 16) performing four trials: 40% handgrip or 80% plantarflexion followed by PECO and arm or leg PM. OC and NOC increased mean arterial pressure (MAP) similarly during handgrip, plantarflexion and arm/leg PECO compared to baseline. Despite increased ventilation (VE) during exercise, none of the women exhibited higher VE during arm or leg PECO. OC and NOC similarly increased MAP and VE during arm or leg PM compared to baseline. Therefore, OC and NOC were similar across pressor and ventilatory responses to arm or leg metaboreflex and mechanoreflex activation. However, some differences due to OC may have been masked by disparities in muscle strength. Since women increase VE during exercise, we suggest that while women do not display a ventilatory response to metaboreflex activation (perhaps due to not reaching a theoretical metabolite threshold to stimulate VE), the mechanoreflex may drive VE during exercise in women.

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The adult turtle spinal cord can generate multiple kinds of limb movements, including swimming, three forms of scratching, and limb withdrawal (flexion reflex), even without brain input and sensory feedback. There are many multifunctional spinal neurons, activated during multiple motor patterns, and some behaviorally specialized neurons, activated during only one. How do multifunctional and behaviorally specialized neurons each contribute to motor output? We analyzed in vivo intracellular recordings of multifunctional and specialized neurons. Neurons tended to spike in the same phase of the hip-flexor (HF) activity cycle during swimming and scratching, though one preferred opposite phases. During both swimming and scratching, a larger fraction of multifunctional neurons than specialized neurons were highly rhythmic. One group of multifunctional neurons was active during the HF-on phase and another during the HF-off phase. Thus, HF-extensor alternation may be generated by a subset of multifunctional spinal neurons during both swimming and scratching. Scratch-specialized neurons and flexion reflex-selective neurons may instead trigger their respective motor patterns, by biasing activity of multifunctional neurons. In phase-averaged membrane potentials of multifunctional neurons, trough phases were more highly correlated between swimming and scratching than peak phases, suggesting that rhythmic inhibition plays a greater role than rhythmic excitation. We also provide the first intracellular recording of a turtle swim-specialized neuron: tonically excited during swimming but inactive during scratching and flexion reflex. It displayed an excitatory postsynaptic potential following each swim-evoking electrical stimulus and thus may be an intermediary between reticulospinal axons and the swimming CPG they activate.

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STUDY DESIGN: Pilot cohort study. OBJECTIVE: To develop and implement a sacral electromyographic (sEMG) technique at bedside to ascertain sparing of sacral motor activity and reflexes in patients hospitalized for acute neurological conditions. SETTING: Hôpital du Sacré-Coeur de Montréal a Canadian Level-1 university trauma center specialized in SCI care. METHODS: Nine patients underwent digital rectal examination (DRE) and sEMG, assessing voluntary anal contraction and sacral spinal reflexes (bulbocavernosus reflex and the anal wink). Our sEMG technique utilized surface recording electrodes and tactile elicitation of reflexes. EMG signal was acquired at bedside through the Noraxon MR3 system. RESULTS: It was quick, well accepted and did no harm. We found that contrary to the DRE, sEMG detected subclinical sacral motor activity and reflexes in 20% of cases for voluntary anal contraction and 40% of cases for the anal wink. CONCLUSION: We believe our sEMG technique is a powerful tool able to enhance management of patients suffering from acute neurological impairments and requiring sacral function assessment.

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Rhythms are the most natural cue for temporal anticipation because many sounds in our living environment have rhythmic structures. Humans have cortical mechanisms that can predict the arrival of the next sound based on rhythm and periodicity. Herein, we showed that temporal anticipation, based on the regularity of sound sequences, modulates peripheral auditory responses via efferent innervation. The medial olivocochlear reflex (MOCR), a sound-activated efferent feedback mechanism that controls outer hair cell motility, was inferred noninvasively by measuring the suppression of otoacoustic emissions (OAE). First, OAE suppression was compared between conditions in which sound sequences preceding the MOCR elicitor were presented at regular (predictable condition) or irregular (unpredictable condition) intervals. We found that OAE suppression in the predictable condition was stronger than that in the unpredictable condition. This implies that the MOCR is strengthened by the regularity of preceding sound sequences. In addition, to examine how many regularly presented preceding sounds are required to enhance the MOCR, we compared OAE suppression within stimulus sequences with 0-3 preceding tones. The OAE suppression was strengthened only when there were at least three regular preceding tones. This suggests that the MOCR was not automatically enhanced by a single stimulus presented immediately before the MOCR elicitor, but rather that it was enhanced by the regularity of the preceding sound sequences.

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Chorea is a hyperkinetic movement disorder associated with various underlyingconditions, including autoimmune diseases such as antiphospholipid syndrome (APS). APS can manifest with a wide range of neurological symptoms, including chorea. We present a case of a 77-year-old man with subacute generalized chorea secondary to primary APS. Notably, the patient exhibited a left patellar crossed-reflex, a phenomenon rarely documented in chorea cases, the pathophysiology of which has not yet been elucidated. In summary, this case challenges the traditional demographics of antiphospholipid syndrome (APS) by suggesting a potential link between APS and late-age patients. It emphasizes the importance of considering APS in late-onset chorea cases.

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The vestigial pinna-orienting system in humans is capable of increasing the activity of several auricular muscles in response to lateralized transient auditory stimuli. For example, transient increases in electromyographic activity in the posterior auricular muscle (PAM) to an attention-capturing stimulus have been documented. For the current study, surface electromyograms (EMGs) were recorded from the PAMs and superior auricular muscles (SAMs) of 10 normal-hearing participants. During the experiments, lateralized transient auditory stimuli, such as a crying baby, a shattering vase, or the participant's first names, were presented. These transient stimuli were either presented in silence or when participants actively listened to a podcast. Although ipsilateral PAM activity increased in response to transient stimuli, the SAM displayed the opposite behavior, i.e., a brief, ipsilateral suppression of activity. This suppression of ipsilateral SAM activity was more frequent on the right (75%) than left side (35%), whereas an ipsilateral PAM increase was roughly equal in prevalence on the two sides (left: 90%, right: 95%). During the active listening task, SAM suppression on the right ear was significantly larger in response to ipsilateral stimuli, compared with contralateral ones (P = 0.002), whereas PAM activity increased significantly (P = 0.002). Overall, this study provides evidence of a systematic transient suppression of the SAM during exogenous attention. This could suggest a more complex system than previously assumed, as the presence of synchronized excitatory and inhibitory components in different auricular muscles points toward a coordinated attempt at reflexively orienting the pinna toward a sound.NEW & NOTEWORTHY This study provides evidence that two auricular muscles in humans, the posterior and superior auricular muscles (PAM, SAM), react fundamentally different to lateralized transient auditory stimuli, especially during active listening. Although the PAM reacts with a transient increase in ipsilateral activity, ongoing ipsilateral SAM activity is briefly suppressed at the same time. This indicates the presence of a more complex and nuanced pinna-orienting system, with synchronized excitatory and inhibitory components in humans, than previously suspected.

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OBJECTIVES: To investigate roles of brain carbon monoxide (CO), an endogenous gasotransmitter, in regulation of the rat micturition reflex. METHODS: In urethane-anesthetized (0.8 g/kg, ip) male rats, evaluation of urodynamic parameters was started 1 h before intracerebroventricular administration of CORM-3 (CO donor) or ZnPP (non-selective inhibitor of heme oxygenase, a CO producing enzyme) and continued for 2 h after the administration. We also investigated effects of centrally pretreated SR95531 (GABAA receptor antagonist) or SCH50911 (GABAB receptor antagonist) on the CORM-3-induced response. RESULTS: CORM-3 significantly prolonged intercontraction intervals (ICIs) without changing maximal voiding pressure (MVP), while ZnPP significantly shortened ICI and reduced single-voided volume and bladder capacity without affecting MVP, post-voided residual volume, or voiding efficiency. The ZnPP-induced ICI shortening was reversed by CORM-3. The CORM-3-induced ICI prolongation was significantly attenuated by centrally pretreated SR95531 or SCH50911, respectively. CONCLUSIONS: Brain CO can suppress the rat micturition reflex through brain γ-aminobutyric acid (GABA) receptors.

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The closure of the urethra under the condition of stress is the result of a reflex contraction of the urethral rhabdosphincter and pelvic floor muscles. This is likely induced by activity of the abdominal muscles due to a sudden increase in abdominal pressure. This reflex contraction with an increase of urethral pressure occurs a few milliseconds before an increase in intraabdominal pressure. The urethral pressure increase during stress is only possible with fixation of the urethra by the pubourethral ligaments (PUL), facilitating urethral kinking. The highest and most important increase in pressure and resistance occurs in the distal urethra due to this kinking of the urethra.

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Intense inspiratory muscle work can evoke a metabolite-stimulated pressor reflex, commonly referred to as the respiratory muscle metaboreflex. When completing similar relative and absolute levels of inspiratory work, females have an attenuated blood pressure response. We sought to test the hypothesis that the lower blood pressure response to the respiratory muscle metaboreflex in females is associated with a reduced sympathetic response. Healthy young (26 ± 4 yr) males (n = 9) and females (n = 7) completed two experimental days. On day 1, participants completed pulmonary function testing and became familiarized with an inspiratory pressure-threshold loading (PTL) task. On the second day, balloon-tipped catheters were placed in the esophagus and stomach to measure pleural and gastric pressures, and transdiaphragmatic pressure was calculated. A microelectrode was inserted into the fibular nerve to quantify muscle sympathetic nerve activity (MSNA), and participants then completed isocapnic PTL to task failure. There was a significant sex-by-time interaction in the mean arterial pressure (MAP, P = 0.015) and burst frequency (P = 0.039) response to PTL. Males had a greater rise in MAP (Δ21 ± 9 mmHg) than females (Δ13 ± 5 mmHg, P = 0.026). Males also demonstrated a greater rise in MSNA burst frequency (Δ18 ± 7 bursts/min) than females (Δ10 ± 5 bursts/min, P = 0.015). The effect of sex was observed despite females and males completing the same magnitude of diaphragm work throughout the task (P = 0.755). Our findings provide novel evidence that the lower blood pressure response to similar relative and absolute inspiratory muscle work in females is associated with lower sympathetic activation.NEW & NOTEWORTHY The blood pressure response to high levels of inspiratory muscle work is lower in females and occurs alongside a reduced sympathetic response. The reduced blood pressure and sympathetic response occur despite males and females performing similar levels of absolute inspiratory work. Our findings provide evidence that sex differences in the respiratory muscle metaboreflex are, in part, sympathetically mediated.

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