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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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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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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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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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During quadrupedal locomotion, interactions between spinal and supraspinal circuits and somatosensory feedback coordinate forelimb and hindlimb movements. How this is achieved is not clear. To determine whether forelimb movements modulate hindlimb cutaneous reflexes involved in responding to an external perturbation, we stimulated the superficial peroneal nerve in six intact cats during quadrupedal locomotion and during hindlimb-only locomotion (with forelimbs standing on stationary platform) and in two cats with a low spinal transection (T12-T13) during hindlimb-only locomotion. We compared cutaneous reflexes evoked in six ipsilateral and four contralateral hindlimb muscles. Results showed similar occurrence and phase-dependent modulation of short-latency inhibitory and excitatory responses during quadrupedal and hindlimb-only locomotion in intact cats. However, the depth of modulation was reduced in the ipsilateral semitendinosus during hindlimb-only locomotion. Additionally, longer-latency responses occurred less frequently in extensor muscles bilaterally during hindlimb-only locomotion, whereas short-latency inhibitory and longer-latency excitatory responses occurred more frequently in the ipsilateral and contralateral sartorius anterior, respectively. After spinal transection, short-latency inhibitory and excitatory responses were similar to both intact conditions, whereas mid- or longer-latency excitatory responses were reduced or abolished. Our results in intact cats and the comparison with spinal-transected cats suggest that the absence of forelimb movements suppresses inputs from supraspinal structures and/or cervical cord that normally contribute to longer-latency reflex responses in hindlimb extensor muscles.NEW & NOTEWORTHY During quadrupedal locomotion, the coordination of forelimb and hindlimb movements involves central circuits and somatosensory feedback. To demonstrate how forelimb movement affects hindlimb cutaneous reflexes during locomotion, we stimulated the superficial peroneal nerve in intact cats during quadrupedal and hindlimb-only locomotion as well as in spinal-transected cats during hindlimb-only locomotion. We show that forelimb movement influences the modulation of hindlimb cutaneous reflexes, particularly the occurrence of long-latency reflex responses.

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Hypoxia is a pivotal factor in the pathophysiology of various clinical conditions, including obstructive sleep apnea, which has a strong association with cardiovascular diseases like hypertension, posing significant health risks. Although the precise mechanisms linking hypoxemia-associated clinical conditions with hypertension remains incompletely understood, compelling evidence suggests that hypoxia induces plasticity of the neurocirculatory control system. Despite variations in experimental designs and the severity, frequency, and duration of hypoxia exposure, evidence from animal and human models consistently demonstrates the robust effects of hypoxemia in triggering reflex-mediated sympathetic activation. Both acute and chronic hypoxia alters neurocirculatory regulation and, in some circumstances, leads to sympathetic outflow and elevated blood pressures that persist beyond the hypoxic stimulus. Dysregulation of autonomic control could lead to adverse cardiovascular outcomes and increase the risk of developing hypertension.

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Animal models are instrumental to understanding the mechanisms underlying autism spectrum disorder, yet translating human behavioral phenotypes remains challenging. Wang et al. leverage a conserved sensorimotor reflex to elucidate synaptic deficits in Scn2a haploinsufficiency and pilot novel rescue strategies.

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BACKGROUND: Gait deficits are very common after stroke and therefore an important aspect in poststroke rehabilitation. A currently little used method in gait rehabilitation after stroke is the activation of the flexor reflex (FR) by electrical stimulation of the sole of foot while walking. The aim of this study was to investigate the effect of FR stimulation on gait performance and gait parameters in participants with stroke within a single session of flexor reflex stimulation using Incedo™. METHODS: Twenty-five participants with subacute (n = 14) and chronic (n = 11) stroke were enrolled in the study. Motor functions were tested with a 10-m walk test (10mWT), a 2-min walk test (2minWT), and a gait analysis. These tests were performed with and without Incedo™ within a single session in randomized order. RESULTS: In the 10mWT, a significant difference was found between walking with Incedo™ (15.0 ± 8.5 s) versus without Incedo™ (17.0 ± 11.4 s, p = 0.01). Similarly, the 2minWT showed a significant improvement with Incedo™ use (90.0 ± 36.4 m) compared to without Incedo™ (86.3 ± 36.8 m, p = 0.03). These results indicate that while the improvements are statistically significant, they are modest and should be considered in the context of their clinical relevance. The gait parameters remained unchanged except for the step length. A subgroup analysis indicated that participants with subacute and chronic stroke responded similarly to the stimulation. There was a correlation between the degree of response to electrostimulation while walking and degree of improvement in 2minWT (r = 0.50, p = 0.01). CONCLUSIONS: This study is the first to examine FR activation effects in chronic stroke patients and suggests that stimulation effects are independent of the time since stroke. A larger controlled clinical trial is warranted that addresses issues as the necessary number of therapeutical sessions and for how long stimulation-induced improvements outlast the treatment period. TRIAL REGISTRATION: The trial was retrospectively registered in German Clinical Trials Register. CLINICAL TRIAL REGISTRATION NUMBER: DRKS00021457. Date of registration: 29 June 2020.

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Sensory feedback for prosthesis control is typically based on encoding sensory information in specific types of sensory stimuli that the users interpret to adjust the control of the prosthesis. However, in physiological conditions, the afferent feedback received from peripheral nerves is not only processed consciously but also modulates spinal reflex loops that contribute to the neural information driving muscles. Spinal pathways are relevant for sensory-motor integration, but they are commonly not leveraged for prosthesis control. We propose an approach to improve sensory-motor integration for prosthesis control based on modulating the excitability of spinal circuits through the vibration of tendons in a closed loop with muscle activity. We measured muscle signals in healthy participants and amputees during different motor tasks, and we closed the loop by applying vibration on tendons connected to the muscles, which modulated the excitability of motor neurons. The control signals to the prosthesis were thus the combination of voluntary control and additional spinal reflex inputs induced by tendon vibration. Results showed that closed-loop tendon vibration was able to modulate the neural drive to the muscles. When closed-loop tendon vibration was used, participants could achieve similar or better control performance in interfaces using muscle activation than without stimulation. Stimulation could even improve prosthetic grasping in amputees. Overall, our results indicate that closed-loop tendon vibration can integrate spinal reflex pathways in the myocontrol system and open the possibility of incorporating natural feedback loops in prosthesis control.

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