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Communication is commonly viewed as connecting people through conscious symbolic processes. Infants have an immature communication toolbox, raising the question of how they form a sense of connectedness. In this article, we propose a framework for infants' communication, emphasizing the subtle unconscious behaviors and autonomic contingent signals that convey drives, emotions, and a sense of connection, facilitating the formation of primal social bonds. Our developmental model emphasizes the importance of diverse modes of communication and their interplay in social interactions during infancy. The framework leverages three levels of communication—autonomic, behavioral, and symbolic—and their different maturational pathways. Initially, infants' social communication relies on autonomic responses and a dynamic behavioral repertoire, which evolve during the first year of life, supporting the emergence of symbolic communication. This extended communication framework highlights infants' role as proactive communicating agents and allows for tracing communicative developmental cascades back to their origins. [ABSTRACT FROM AUTHOR]

Diabetes mellitus affects over half a billion people worldwide and is associated with numerous complications, including diabetic gastroparesis, characterized by delayed gastric emptying without mechanical obstruction. Although diabetic gastroparesis does not affect life expectancy, it significantly impairs digestion and medication absorption, complicating glucose metabolism and health management, thus reducing quality of life. The etiology of diabetic gastroparesis is multifactorial, involving autonomic neuropathy, vagus nerve dysfunction, disturbances in interstitial cells of Cajal, nitric oxide synthesis, hyperglycemia, and oxidative stress. Symptoms include early satiety, bloating, nausea, vomiting, dysphagia, and unintentional weight loss, which complicate diabetes management by causing unpredictable glycemic control. Despite advancements in understanding diabetic gastroparesis, it remains underdiagnosed due to its often asymptomatic nature. Further research is needed to elucidate its epidemiology and pathophysiology, particularly in asymptomatic patients. This review discusses the epidemiology, pathophysiology, symptoms, and clinical consequences of diabetic gastroparesis, highlighting the need for improved diagnostic and management strategies.

The Valsalva maneuver, named after Antonio Maria Valsalva, is one of the vagal maneuvers. It is defined as a forced expiration against a closed glottis, leading to an increase in intrathoracic and intra-abdominal pressure. Over the years it has become a subject of interest to many clinical researchers who have comprehensively studied its physiology and clinical significance. As a result, the application of the Valsalva maneuver has expanded to become a versatile technique applied across a wide range of medical specialties as a diagnostic and therapeutic tool. Additionally, it has found its use in sport among athletes. The aim of this article is to present the current state of knowledge about the clinical significance of the Valsalva maneuver and show that this simple physiological technique described in the 18th century remains a valuable tool in modern clinical practice and has found its use in sport. The review was based on chosen literature obtained from the PubMed electronic database, Google Scholar electronic database, and other scientific articles. Search terms included keywords listed below. Keywords: Valsalva maneuver; vagal maneuver; respiratory maneuver; autonomic system

Objective: This study evaluated the antihyperalgesic and anti-inflammatory effects of percutaneous vagus nerve electrical stimulation (pVNS) associated with physical exercise, i.e., swimming, in mice with peripheral inflammation. Methods: The pain model was induced by intraplantar (i.pl.) injection of Freund's complete adjuvant (CFA). Sixty-four male Swiss mice (35-40 g) received an i.pl. of CFA and underwent behavioral tests, i.e., mechanical hyperalgesia, edema, and paw temperature tests. Additionally, cytokine levels, specifically interleukin-6 (IL-6) and interleukin-10 (IL-10), were determined by enzyme-linked immunosorbent assay. Mice were treated with swimming exercise for 30 min alone or associated with different time protocols (10, 20, or 30 min) of stimulation in the left ear with random frequency during four consecutive days. Results: pVNS for 20 min prolonged the antihyperalgesic effect for up to 2 h, 24 h after CFA injection. pVNS for 30 min prolonged the antihyperalgesic effect for up to 7 h, 96 h after CFA injection. However, it did not alter the edema or temperature at both analyzed times (24 and 96 h). Furthermore, the combination of pVNS plus swimming exercise, but not swimming exercise alone, reduced IL-6 levels in the paw and spinal cord, as well as IL-10 levels in the spinal cord. Conclusion: pVNS potentiates the analgesic effect induced by swimming, which may be, at least in part, mediated by the modulation of inflammatory cytokines in the periphery (paw) and central nervous system (spinal cord). Therefore, the combination of these therapies may serve as an important adjunctive treatment for persistent inflammatory pain. [ABSTRACT FROM AUTHOR]

ObjectiveThis study evaluated the antihyperalgesic and anti-inflammatory effects of percutaneous vagus nerve electrical stimulation (pVNS) associated with physical exercise, i.e., swimming, in mice with peripheral inflammation.MethodsThe pain model was induced by intraplantar (i.pl.) injection of Freund’s complete adjuvant (CFA). Sixty-four male Swiss mice (35–40 g) received an i.pl. of CFA and underwent behavioral tests, i.e., mechanical hyperalgesia, edema, and paw temperature tests. Additionally, cytokine levels, specifically interleukin-6 (IL-6) and interleukin-10 (IL-10), were determined by enzyme-linked immunosorbent assay. Mice were treated with swimming exercise for 30 min alone or associated with different time protocols (10, 20, or 30 min) of stimulation in the left ear with random frequency during four consecutive days.ResultspVNS for 20 min prolonged the antihyperalgesic effect for up to 2 h, 24 h after CFA injection. pVNS for 30 min prolonged the antihyperalgesic effect for up to 7 h, 96 h after CFA injection. However, it did not alter the edema or temperature at both analyzed times (24 and 96 h). Furthermore, the combination of pVNS plus swimming exercise, but not swimming exercise alone, reduced IL-6 levels in the paw and spinal cord, as well as IL-10 levels in the spinal cord.ConclusionpVNS potentiates the analgesic effect induced by swimming, which may be, at least in part, mediated by the modulation of inflammatory cytokines in the periphery (paw) and central nervous system (spinal cord). Therefore, the combination of these therapies may serve as an important adjunctive treatment for persistent inflammatory pain.

Amyotrophic lateral sclerosis (ALS) is a neurodegenerative disease with variable phenotypic expressions which has been associated with autonomic dysfunction. The cardiovascular system seems to be affected especially in the context of bulbar involvement. We describe four new cases of Tako-Tsubo syndrome (TTS) in ALS patients with an appraisal of the literature. We present a late-stage ALS patient with prominent bulbar involvement that presented TTS during hospitalization. We then retrospectively identify three additional ALS–TTS cases reporting relevant clinical findings. TTS cardiomyopathy has been observed in different acute neurological conditions, and the co-occurrence of ALS and TTS has already been reported. Cardiovascular autonomic dysfunctions have been described in ALS, especially in the context of an advanced diseases and with bulbar involvement. Noradrenergic hyperfunction linked to sympathetic denervation and ventilatory deficits coupled in different instances with a trigger event could play a synergistic role in the development of TTS in ALS. Sympathetic hyperfunctioning and ventilatory deficits in conjunction with cardiac autonomic nerves impairment may play a role in the development of TTS in a context of ALS. [ABSTRACT FROM AUTHOR]

The current study examined the effects of Alpha-Glycerylphosphorylcholine (A-GPC) on heart rate variability (HRV) and hemodynamic responses following a sprint interval exercise (SIE) in women who were overweight or obese. Participants (n = 12, 31.0 ± 4.6 years; 29.4 ± 2.1 kg/m2) consumed 1000 mg of A-GPC or a placebo after eating breakfast in a randomized, double-blind cross-over design. After 60 min, participants performed two bouts of the SIE (30 s Wingate) interspersed with 4 min of active recovery (40 rpm). Hemodynamic variables and HRV domains were measured before and 60 min after the A-GPC consumption, immediately after SIE, and every 15 min up to 120 min during recovery. A-GPC consumption increased resting levels of both the time domain (Standard Deviation of RR wave intervals [SDNN] and percentage of interval differences of adjacent RR intervals greater than 50 ms [pNN50%]) and frequency domain (high frequency [HF] and low frequency [LF]) variables of HRV (p < 0.05). Moreover, HRV variables (except for LF/HF) decreased (p < 0.05) immediately after SIE in the A-GPC and placebo sessions. Systolic and diastolic blood pressure increased (p < 0.05) immediately after SIE in both trials. Both HRV and hemodynamic variables recovered (p < 0.05) faster in the A-GPC compared to the placebo session. We concluded that A-GPC consumption recovers HRV and blood pressure faster following strenuous exercise in overweight and obese women, and that it might favorably modify cardiac autonomic function. [ABSTRACT FROM AUTHOR]

Background/Aim: Misophonia is a disorder characterized by reduced tolerance to specific sounds or stimuli known as "triggers," which tend to evoke negative emotional, physiological, and behavioral responses. In this study, we aimed to better characterize participants with misophonia through the evaluation of the response of the autonomic nervous system to "trigger sounds," a psychometric assessment, and the analysis of the neurological pathways. Materials and methods: Participants included 11 adults presenting with misophonic disturbance and 44 sex-matched healthy controls (HCs). Following recently proposed diagnostic criteria, the participants listened to six "trigger sounds" and a "general annoyance" sound (baby crying) during a series of physiological tests. The effects were examined through functional magnetic resonance imaging (fMRI), the analysis of heart rate variability (HRV), and of galvanic skin conductance (GSC). The fMRI was performed on a 3T Scanner. The HRV was obtained through the analysis of electrocardiogram, whereas the GSC was examined through the positioning of silver-chloride electrodes on fingers. Furthermore, the psychometric assessment included questionnaires focused on misophonia, psychopathology, resilience, anger, and motivation. Results: Participants with misophonia showed patterns of increased sympathetic activation in response to trigger sounds and a general annoyance sound, the low frequency (LF) component of HRV, the sympathetic index, and the number of significant GSC over the threshold, where the amplitude/phasic response of GSC was higher. The fMRI analysis provided evidence for the activation of the temporal cortex, the limbic area, the ventromedial prefrontal/premotor/cingulate cortex, and the cerebellum in participants with misophonia. In addition, the psychometric assessment seemed to differentiate misophonia as a construct independent from general psychopathology. Conclusion: These results suggest the activation of a specific auditoryinsulalimbic pathway at the basis of the sympathetic activation observed in participants with misophonia in response to "trigger and general annoyance sounds." Further studies should disentangle the complex issue of whether misophonia represents a new clinical disorder or a non-pathological condition. These results could help to build diagnostic tests to recognize and better classify this disorder. The relevance of this question goes beyond purely theoretical issues, as in the first case, participants with misophonia should receive a diagnosis and a targeted treatment, while in the second case, they should not. [ABSTRACT FROM AUTHOR]

Autonomic system plays a pivotal role in the pathogenesis of paroxysmal atrial fibrillation (AF). Skin sympathetic nerve activity (SKNA) is a noninvasive tool for assessing sympathetic tone. However, data on changes in SKNA after ablation are limited. Here, we retrospectively enrolled 37 patients with symptomatic drug-refractory paroxysmal AF who underwent pulmonary vein isolation (PVI) with radiofrequency ablation (RFA) or cryoablation (CBA). SKNA was measured from the chest and right arm 1 day prior to ablation, as well as 1 day and 3 months after ablation. One day after ablation, the SKNA-Arm increased from 517.1 µV (first and third quartiles, 396.0 and 728.0, respectively) to 1226.2 µV (first and third quartiles, 555.2 and 2281.0), with an increase of 179.8% (125% and 376.0%) (p < 0.001); the SKNA-Chest increased from 538.2 µV (first and third quartiles, 432.9 and 663.9) to 640.0 µV (first and third quartiles, 474.2 and 925.6), with an increase of 108.3% (95.6% and 167.9%) (p = 0.004), respectively. In those without recurrence, there was a significant increase in SKNA 1 day after ablation as compared with those before ablation. Twelve patients received SKNA measurement 3 months after ablation; both SKNA-Arm (p = 0.31) and SKNA-Chest (p = 0.27) were similar to those before ablation, respectively. Among patients with symptomatic drug-refractory paroxysmal AF receiving PVI, increased SKNA was observed 1 day after ablation and returned to the baseline 3 months after ablation. Elevation of SKNA was associated with lower early and late recurrences following ablation. [ABSTRACT FROM AUTHOR]

Background/AimMisophonia is a disorder characterized by reduced tolerance to specific sounds or stimuli known as “triggers,” which tend to evoke negative emotional, physiological, and behavioral responses. In this study, we aimed to better characterize participants with misophonia through the evaluation of the response of the autonomic nervous system to “trigger sounds,” a psychometric assessment, and the analysis of the neurological pathways.Materials and methodsParticipants included 11 adults presenting with misophonic disturbance and 44 sex-matched healthy controls (HCs). Following recently proposed diagnostic criteria, the participants listened to six “trigger sounds” and a “general annoyance” sound (baby crying) during a series of physiological tests. The effects were examined through functional magnetic resonance imaging (fMRI), the analysis of heart rate variability (HRV), and of galvanic skin conductance (GSC). The fMRI was performed on a 3T Scanner. The HRV was obtained through the analysis of electrocardiogram, whereas the GSC was examined through the positioning of silver-chloride electrodes on fingers. Furthermore, the psychometric assessment included questionnaires focused on misophonia, psychopathology, resilience, anger, and motivation.ResultsParticipants with misophonia showed patterns of increased sympathetic activation in response to trigger sounds and a general annoyance sound, the low frequency (LF) component of HRV, the sympathetic index, and the number of significant GSC over the threshold, where the amplitude/phasic response of GSC was higher. The fMRI analysis provided evidence for the activation of the temporal cortex, the limbic area, the ventromedial prefrontal/premotor/cingulate cortex, and the cerebellum in participants with misophonia. In addition, the psychometric assessment seemed to differentiate misophonia as a construct independent from general psychopathology.ConclusionThese results suggest the activation of a specific auditory-insula-limbic pathway at the basis of the sympathetic activation observed in participants with misophonia in response to “trigger and general annoyance sounds.” Further studies should disentangle the complex issue of whether misophonia represents a new clinical disorder or a non-pathological condition. These results could help to build diagnostic tests to recognize and better classify this disorder. The relevance of this question goes beyond purely theoretical issues, as in the first case, participants with misophonia should receive a diagnosis and a targeted treatment, while in the second case, they should not.

Post-traumatic epilepsy (PTE) is a formidable and frequent consequence of traumatic brain injury (TBI) in the long term. 41 patients with PTE were examined, mostly men of working age. The time of formation of PTE after was 14.3 ± 1.4 months, which decreased depending on the severity of brain injury, the average frequency of seizures was 2.93 ± 0.8 per month.Focal seizures were mainly registered (63.4%, p Typical comorbid symptoms in people with PTE were cognitive deficits, which correlated with the severity of TBI, as well as depressive and anxiety symptoms. Depressive layers were more often observed in the presence of the focal component of seizures (94.7%, p

In this study, the extent to which different emotions of pregnant women can be predicted based on heart rate-relevant information as indicators of autonomic nervous system functioning was explored using various machine learning algorithms. Nine heart rate-relevant autonomic system indicators, including the coefficient of variation R-R interval (CVRR), standard deviation of all NN intervals (SDNN), and square root of the mean squared differences of successive NN intervals (RMSSD), were measured using a heart rate monitor (MyBeat) and four different emotions including "happy," as a positive emotion and "anxiety," "sad," "frustrated," as negative emotions were self-recorded on a smartphone application, during 1 week starting from 23rd to 32nd weeks of pregnancy from 85 pregnant women. The k-nearest neighbor (k-NN), support vector machine (SVM), logistic regression (LR), random forest (RF), naïve bayes (NB), decision tree (DT), gradient boosting trees (GBT), stochastic gradient descent (SGD), extreme gradient boosting (XGBoost), and artificial neural network (ANN) machine learning methods were applied to predict the four different emotions based on the heart rate-relevant information. To predict four different emotions, RF also showed a modest area under the receiver operating characteristic curve (AUC-ROC) of 0.70. CVRR, RMSSD, SDNN, high frequency (HF), and low frequency (LF) mostly contributed to the predictions. GBT displayed the second highest AUC (0.69). Comprehensive analyses revealed the benefits of the prediction accuracy of the RF and GBT methods and were beneficial to establish models to predict emotions based on autonomic nervous system indicators. The results implicated SDNN, RMSSD, CVRR, LF, and HF as important parameters for the predictions. [ABSTRACT FROM AUTHOR]

Pupil diameter fluctuates in association with changes in brain states induced by the neuromodulator systems. However, it remains unclear how the neuromodulator systems control the activity of the iris sphincter (constrictor) and dilator muscles to change the pupil size. The present study compared temporal patterns of pupil dilation during movement when each muscle was pharmacologically manipulated in the human eye. When the iris sphincter muscle was blocked with tropicamide, the latency of pupil dilation was delayed and the magnitude of pupil dilation was reduced during movement. In contrast, when the iris dilator muscle was continuously stimulated with phenylephrine, the latency and magnitude of rapid pupil dilation did not differ from the untreated control eye, but sustained pupil dilation was reduced until the end of movement. These results suggest that the iris sphincter muscle, which is under the control of the parasympathetic pathway, is quickly modulated by the neuromodulator system and plays a major role in rapid pupil dilation. However, the iris dilator muscle receives signals from the neuromodulator system with a slow latency and is involved in maintaining sustained pupil dilation. NEW & NOTEWORTHY By pharmacologically manipulating the pupil dilator and constrictor muscles of human eye separately, we found that the pupil constrictor muscle is a primary controller of rapid pupil dilation upon brain arousal. However, the pupil dilator muscle, which is innervated by the sympathetic nervous system and is generally considered as a major regulator of pupil dilation, is not involved in rapid pupil dilation, but was involved in long-lasting pupil dilation. [ABSTRACT FROM AUTHOR]

In this study, the extent to which different emotions of pregnant women can be predicted based on heart rate-relevant information as indicators of autonomic nervous system functioning was explored using various machine learning algorithms. Nine heart rate-relevant autonomic system indicators, including the coefficient of variation R-R interval (CVRR), standard deviation of all NN intervals (SDNN), and square root of the mean squared differences of successive NN intervals (RMSSD), were measured using a heart rate monitor (MyBeat) and four different emotions including “happy,” as a positive emotion and “anxiety,” “sad,” “frustrated,” as negative emotions were self-recorded on a smartphone application, during 1 week starting from 23rd to 32nd weeks of pregnancy from 85 pregnant women. The k-nearest neighbor (k-NN), support vector machine (SVM), logistic regression (LR), random forest (RF), naïve bayes (NB), decision tree (DT), gradient boosting trees (GBT), stochastic gradient descent (SGD), extreme gradient boosting (XGBoost), and artificial neural network (ANN) machine learning methods were applied to predict the four different emotions based on the heart rate-relevant information. To predict four different emotions, RF also showed a modest area under the receiver operating characteristic curve (AUC-ROC) of 0.70. CVRR, RMSSD, SDNN, high frequency (HF), and low frequency (LF) mostly contributed to the predictions. GBT displayed the second highest AUC (0.69). Comprehensive analyses revealed the benefits of the prediction accuracy of the RF and GBT methods and were beneficial to establish models to predict emotions based on autonomic nervous system indicators. The results implicated SDNN, RMSSD, CVRR, LF, and HF as important parameters for the predictions.

Purpose: In this study, we aimed to reveal the detailed anatomy of mental nerve branches to the inferior labial glands. Methods: Embalmed cadaveric heads were used in this study and the mental nerve branches to the inferior labial glands were dissected. Branches to the glands were then excised for histological observation. Results: On all sides, the inferior labial glands were innervated by small branches arising from mental nerve branches that innervated the lower lip. No nerve branches to the inferior labial gland crossed the midline. Histological observation found that the tissue to the inferior labial gland were composed primarily of nerve fibers with a small number of surrounding vessels. Histological findings in examined specimens were consistent. Conclusion: The inferior labial glands were innervated by small branches of the mental nerve to the lower lip. [ABSTRACT FROM AUTHOR]

Posterior circulation involves the vertebrobasilar arteries, which supply oxygen and glucose to vital human brainstem structures and other areas. This complex circulatory- perfusion system is not homogenous throughout the day; rather, its hemodynamic changes rely on physiological demands, ensuring brainstem perfusion. This dynamic autoregulatory pattern maintains cerebral perfusion during blood pressure changes. Accumulative evidence suggests that activity within the autonomic nervous system is involved in the regulation of cerebral blood flow. Neither the sympathetic nor parasympathetic nervous systems work independently. Functional studies have shown a tight and complicated cross talk between these systems. In pathological processes where sympathetic stimulation is present, systemic vasoconstriction is followed, representing the most important CNS parasympathetic trigger that will promote local vasodilation. Stroke is a clear example of this process. The posterior circulation is affected in 30% of strokes, causing high morbidity and mortality outcomes. Currently, the management of ischemic stroke is focused on thrombolytic treatment and endovascular thrombectomy within an overall tight 4.5 to 6 h ischemic time window. Therefore, the autonomic nervous system could represent a potential therapeutic target to modulate reperfusion after cerebral ischemia through vasodilation, which could potentially decrease infarct size and increase the thrombolytic therapeutic ischemic window. In addition, shifting the autonomic nervous system balance toward its parasympathetic branch has shown to enhance neurogenesis and decrease local inflammation. Regretfully, the vast majority of animal models and human research on neuromodulation during brain ischemia have been focused on anterior circulation with disappointing results. In addition, the source of parasympathetic inputs in the vertebrobasilar system in humans is poorly understood, substantiating a gap and controversy in this area. Here, we reviewed current available literature regarding the parasympathetic vascular function and challenges of its stimulation in the vertebrobasilar system. [ABSTRACT FROM AUTHOR]

Posterior circulation involves the vertebrobasilar arteries, which supply oxygen and glucose to vital human brainstem structures and other areas. This complex circulatory- perfusion system is not homogenous throughout the day; rather, its hemodynamic changes rely on physiological demands, ensuring brainstem perfusion. This dynamic autoregulatory pattern maintains cerebral perfusion during blood pressure changes. Accumulative evidence suggests that activity within the autonomic nervous system is involved in the regulation of cerebral blood flow. Neither the sympathetic nor parasympathetic nervous systems work independently. Functional studies have shown a tight and complicated cross talk between these systems. In pathological processes where sympathetic stimulation is present, systemic vasoconstriction is followed, representing the most important CNS parasympathetic trigger that will promote local vasodilation. Stroke is a clear example of this process. The posterior circulation is affected in 30% of strokes, causing high morbidity and mortality outcomes. Currently, the management of ischemic stroke is focused on thrombolytic treatment and endovascular thrombectomy within an overall tight 4.5 to 6 h ischemic time window. Therefore, the autonomic nervous system could represent a potential therapeutic target to modulate reperfusion after cerebral ischemia through vasodilation, which could potentially decrease infarct size and increase the thrombolytic therapeutic ischemic window. In addition, shifting the autonomic nervous system balance toward its parasympathetic branch has shown to enhance neurogenesis and decrease local inflammation. Regretfully, the vast majority of animal models and human research on neuromodulation during brain ischemia have been focused on anterior circulation with disappointing results. In addition, the source of parasympathetic inputs in the vertebrobasilar system in humans is poorly understood, substantiating a gap and controversy in this area. Here, we reviewed current available literature regarding the parasympathetic vascular function and challenges of its stimulation in the vertebrobasilar system.

Repetitive transcranial magnetic stimulation (rTMS) is a safe non-invasive neuromodulation technique used for the treatment of various neuropsychiatric disorders. The effect of rTMS applied to the cortex on autonomic functions has not been studied in detail in patient cohorts, yet patients who receive rTMS may have disease-associated impairments in the autonomic system and may receive medication that may pronounce autonomic dysfunctions. Using data from the 'rTMS for the Treatment of Negative Symptoms in Schizophrenia' (RESIS) trial we evaluated the effect of rTMS applied to the left dorsolateral prefrontal cortex (DLPFC) on autonomic nervous system-related parameters such as blood pressure (BP) and heart rate (HR) in both reclining and standing postures from screening up to 105 days after intervention among patients with schizophrenia. 157 patients received either active (n = 76) or sham (n = 81) rTMS treatment. Apart from gender no significant group differences were observed. During intervention, Linear Mixed Model (LMM) analyses showed no significant time × group interactions nor time effects for any of the variables (all p > 0.055). During the whole trial beside a significant time × group interaction for diastolic BP (p = 0.017) in the standing posture, no significant time × group interactions for other variables (all p > 0.140) were found. These secondary analyses of the largest available rTMS trial on the treatment of negative symptoms in schizophrenia did not show a significant effect of active rTMS compared to sham rTMS on heart rate or blood pressure, neither during the intervention period nor during the follow-up period. [ABSTRACT FROM AUTHOR]

The carotid body (CB) is the main peripheral chemoreceptor for arterial respiratory gases O2 and CO2 and pH, eliciting reflex ventilatory, cardiovascular, and humoral responses to maintain homeostasis. This review examines the fundamental biology underlying CB chemoreceptor function, its contribution to integrated physiological responses, and its role in maintaining health and potentiating disease. Emphasis is placed on 1) transduction mechanisms in chemoreceptor (type I) cells, highlighting the role played by the hypoxic inhibition of O2-dependent K1 channels and mitochondrial oxidative metabolism, and their modification by intracellular molecules and other ion channels; 2) synaptic mechanisms linking type I cells and petrosal nerve terminals, focusing on the role played by the main proposed transmitters and modulatory gases, and the participation of glial cells in regulation of the chemosensory process; 3) integrated reflex responses to CB activation, emphasizing that the responses differ dramatically depending on the nature of the physiological, pathological, or environmental challenges, and the interactions of the chemoreceptor reflex with other reflexes in optimizing oxygen delivery to the tissues; and 4) the contribution of enhanced CB chemosensory discharge to autonomic and cardiorespiratory pathophysiology in obstructive sleep apnea, congestive heart failure, resistant hypertension, and metabolic diseases and how modulation of enhanced CB reactivity in disease conditions may attenuate pathophysiology. [ABSTRACT FROM AUTHOR]

Smoking causes sympathovagal changes and peripheral vessel injury, which can be assessed by heart rate variability (HRV) that includes endothelial nitric oxide (NO) and sLOX-1 markers, respectively. This study aimed to investigate the HRV and NO changes in acute smoking and sLOX-1 overproduction in chronic smoking. A total of 60 males were recruited. Thirty smokers and 30 non-smokers were studied. At first the HRV parameters were obtained from all subjects. Only smokers were then consecutively recorded for 5 min and 15 min after smoking a single cigarette with simultaneous blood collection at each time point for NO and sLOX-1 measurements. We found a significant lowering of HRV and a positive correlation between sLOX-1 and mean arterial pressure in smokers. After 5 min of smoking, an immediate adverse effect of autonomic function was represented by the HRV along with an immediate lowering of NO which is a vasodilator. Acute smoking influences the autonomic neural control from NO-mediated modulation which can be assessed by the noninvasive technique of HRV analysis.

The hypothalamus and Locus Coeruleus (LC) share a variety of functions, as both of them take part in the regulation of the sleep/wake cycle and in the modulation of autonomic and homeostatic activities. Such a functional interplay takes place due to the dense and complex anatomical connections linking the two brain structures. In Alzheimer's disease (AD), the occurrence of endocrine, autonomic and sleep disturbances have been associated with the disruption of the hypothalamic network; at the same time, in this disease, the occurrence of LC degeneration is receiving growing attention for the potential roles it may have both from a pathophysiological and pathogenetic point of view. In this review, we summarize the current knowledge on the anatomical and functional connections between the LC and hypothalamus, to better understand whether the impairment of the former may be responsible for the pathological involvement of the latter, and whether the disruption of their interplay may concur to the pathophysiology of AD. Although only a few papers specifically explored this topic, intriguingly, some pre-clinical and post-mortem human studies showed that aberrant protein spreading and neuroinflammation may cause hypothalamus degeneration and that these pathological features may be linked to LC impairment. Moreover, experimental studies in rodents showed that LC plays a relevant role in modulating the hypothalamic sleep/wake cycle regulation or neuroendocrine and systemic hormones; in line with this, the degeneration of LC itself may partly explain the occurrence of hypothalamic-related symptoms in AD. [ABSTRACT FROM AUTHOR]

Total sleep deprivation (TSD) is associated with endothelial dysfunction and a consequent decrease in vascular reactivity and increase in peripheral vascular resistance. These effectors compromise the body's ability to thermoregulate in hot and cold stress conditions. We investigated heat‐unacclimated young adult men (26 ± 2 years) to determine whether 36 hr of TSD compared to an 8 or 4‐hr sleep condition, would suppress the responses of the autonomic system (body rectal temperature [Tre], heart rate [HR], root mean square of successive interbeat intervals, physiological strain, blood pressure [BP], circulating blood catecholamines, sweating rate and subjective sensations) to whole‐body uncompensable passive heat stress in traditional Finnish sauna heat (Tair = 80–90°C, rh = 30%). Sauna bathing that induced whole‐body hyperthermia had a residual effect on reducing BP in the 8‐hr and 4‐hr sleep per night conditions according to BP measurements. By contrast, 36 hr of total wakefulness led to an increase in BP. These observed sleep deprivation‐dependent differences in BP modifications were not accompanied by changes in the blood plasma epinephrine and norepinephrine concentrations. However, during sauna bathing, an increase in BP following 36 hr of TSD was accompanied by significant decreases in body Tre, HR and physiological strain, together with a diminished sweating rate, enhanced vagus‐mediated autonomic control of HR variability, and improved thermal perception by the subjects. Our results suggest the impaired ability of the body to accumulate external heat in the body's core under uncompensable passive heat conditions following 36 hr of TSD, because of the TSD‐attenuated autonomic system response to acute heat stress. [ABSTRACT FROM AUTHOR]

Background: Modifying the autonomic system after catheter ablation may prevent the recurrence of atrial fibrillation (AF). Evaluation of skin sympathetic nerve activity (SKNA) is a noninvasive method for the assessment of sympathetic activity. However, there are few studies on the effects of different energy settings on SKNA., Objective: To investigate the changes in SKNA in different energy settings and their relationship to AF ablation outcomes., Methods: Seventy-two patients with paroxysmal and persistent AF were enrolled. Forty-three patients received AF ablation with the conventional (ConV) energy setting (low power for long duration), and 29 patients using a high-power, short-duration (HPSD) strategy. The SKNA was acquired from the right arm 1 day before and after the radiofrequency ablation. We analyzed the SKNA and ablation outcomes in the different energy settings., Results: Both groups had a similar baseline average SKNA (aSKNA). We found that the median aSKNA increased significantly from 446.82 μV to 805.93 μV (p = 0.003) in the ConV group but not in the HPSD group. In the ConV group, patients without AF recurrence had higher aSKNA values. However, the 1-year AF recurrence rate remained similar between both groups (35 % vs. 28 %, p = 0.52)., Conclusion: The post-ablation aSKNA levels increased significantly in the ConV group but did not change significantly in the HPSD group, which may reflect different neuromodulatory effects. However, the one-year AF recurrence rates were similar for both groups. These results demonstrate that the HPSD strategy has durable lesion creation but less lesion depth, which may reduce collateral damage., Competing Interests: Declaration of competing interest None., (Copyright © 2023 Elsevier Ltd. All rights reserved.)

New Findings: What is the central question of this study?The aim of the present study was to assess the effects of sleep restriction on self‐report and autonomic responses to neutral and sad film clips.What is the main finding and its importance?Ratings of sadness and heart rate deceleration were greater while watching the sad clip, with no effect of sleep restriction, whereas heart rate variability and skin conductance were impacted by sleep restriction and, to a lesser extent, by film clips. The results suggest that autonomic function was adaptively altered by sleep restriction, in order to maintain a 'normal' response to emotional cues, despite mounting fatigue. Habitual insufficient sleep has long‐term health consequences via its impact on autonomic nervous system (ANS) function and on regulation of emotion. To our knowledge, the effects of insufficient sleep on emotion‐induced ANS function have not been tested. The present study aimed to address this lacuna. Using an emotion induction procedure, the effects of sleep restriction on physiological responses to validated neutral and sad film clips were assessed in a two‐by‐two, pseudo‐randomized, cross‐over design. Thirty‐one participants, aged 20–33 years, were assessed after sleeping for either 5 h (sleep restricted, SR) or 8 h (well rested, WR) per night, for three consecutive nights. Physiological measures included heart rate, heart rate variability, skin conductance response (SCR) and participants' ratings of affect and fatigue. There was no effect of sleep conditions on self‐reported negative affect, but watching the sad clip reduced self‐reported fatigue in the SR condition. There was greater heart rate deceleration while watching sad relative to neutral clips, independent of the sleep condition. Sleep restriction increased heart rate variability measures, with no effect of emotion induction. There was an interaction of emotion induction with sleep condition for SCR, with more SCRs to sad relative to neutral clips in the WR condition, and the opposite effect in the SR condition. Combined, the results suggest that the ANS response to an emotional cue was altered by sleep restriction. The results suggest an adaptive ANS response to mild, chronic sleep restriction, resulting in constant heart rate response and self‐reported experience across WR and SR conditions, despite mounting fatigue. [ABSTRACT FROM AUTHOR]

To understand the mechanisms of N3 sleep interruptions in patients with sleepwalking episodes and/or sleep terrors (SW/ST), we evaluated whether autonomic reactions preceded or accompanied behavioural arousals from NREM sleep stage N3. In 20 adult patients with SW/ST and 20 matched controls without parasomnia, heart rate and pulse wave amplitude were measured beat‐to‐beat during the 10 beats preceding and during the 15 beats succeeding a motor arousal from N3 sleep. Respiratory rate and amplitude were measured during the same 25 successive beats. In patients with SW/ST, the N3 arousals were associated with a 33% increase in heart rate, a 57% decrease in pulse wave amplitude (indicating a major vasoconstriction), a 24% increase in respiratory rate and a doubling of respiratory amplitude. Notably, tachycardia and vasoconstriction started 4 s before motor arousals. A similar profile (tachycardia and vasoconstriction gradually increasing from the 4 s preceding arousal and post‐arousal increase of respiratory amplitude, but no polypnea) was also observed, with a lower amplitude, during the less frequent 38 quiet N3 arousals in control subjects. Parasomniac arousals were associated with greater tachycardia, vasoconstriction and polypnea than quiet arousals, with the same pre‐arousal gradual increases in heart rate and vasoconstriction. Autonomic arousal occurs 4 s before motor arousal from N3 sleep in patients with SW/ST (with a higher adrenergic reaction than in controls), suggesting that an alarming event during sleep (possibly a worrying sleep mentation or a local subcortical arousal) causes the motor arousal. [ABSTRACT FROM AUTHOR]

Background: Heart rate variability (HRV) is a noninvasive method for assessing autonomic function. Age, sex, and chronic conditions influence HRV. Objectives: Our aim was to evaluate HRV measures exploring differences by age, sex, and race in a sample from a rural area. Methods: Analytical sample (n = 1,287) included participants from the 2010 to 2016 evaluation period of the Baependi Heart Study, a family-based cohort in Brazil. Participants underwent 24-hour Holter-ECG (Holter) monitoring. To derive population reference values, we restricted our analysis to a ‘healthy’ subset (i.e. absence of medical comorbidities). A confirmatory analysis was conducted with a subgroup sample that also had HRV derived from a resting ECG 10’-protocol obtained during the same time period. Results: The ‘healthy’ subset included 543 participants. Mean age was 40 ± 14y, 41% were male, 74% self-referred as white and mean body-mass-index was 24 ± 3kg/m2. Time domain HRV measures showed significant differences by age-decade and by sex. Higher values were observed for males across almost all age-groups. Parasympathetic associated variables (rMSSD and pNN50) showed a U-shaped distribution and reversal increase above 60y. Sympathetic-parasympathetic balance variables (SDNN, SDANN) decreased linearly by age. Race differences were no significant. We compared time domain variables with complete data (Holter and resting ECG) between ‘healthy’ versus ‘unhealthy’ groups. Higher HRV values were shown for the ‘healthy’ subset compared with the ‘unhealthy’ group. Conclusion: HRV measures vary across age and sex. A U-shaped pattern and a reversal increase in parasympathetic variables may reflect an age-related autonomic dysfunction even in healthy individuals that could be used as a predictor of disease development.

Abstract Background Current therapies for heart failure (HF) are followed by strategies to improve quality of life and exercise tolerance, besides reducing morbidity and mortality. Some HF patients present changes in the musculoskeletal system and inspiratory muscle weakness, which may be restored by inspiratory muscle training, thus increasing respiratory muscle strength and endurance, maximal oxygen uptake (VO2), functional capacity, respiratory responses to exercise, and quality of life. Yoga therapies have been shown to improve quality of life, inflammatory markers, and peak VO2 mostly in HF patients with a reduced ejection fraction. However, the effect of different yoga breathing techniques in patients showing HF with a preserved ejection fraction (HFpEF) remain to be assessed. Methods/design A PROBE (prospective randomized open blinded end-point) parallel-group trial will be conducted at two specialized HF clinics. Adult patients previously diagnosed with HFpEF will be included. After signing informed consent and performing a pre-test intervention, patients will be randomized into three groups and provided with either (1) active yoga breathing techniques; (2) passive yoga breathing techniques (pranayama); or and (3) control (standard pharmacological treatment). Follow-up will last 8 weeks (16 sessions). The post-intervention tests will be performed at the end of the intervention period for analysis of outcomes. Interventions will occur continuously according to patients’ enrollment. The main outcome is respiratory muscular resistance. A total of 33 enrolled patients are expected. The present protocol followed the SPIRIT guidelines and fulfilled the SPIRIT checklist. Discussion This trial is probably the first to assess the effects of a non-pharmacological intervention, namely yoga and specific breathing techniques, to improve cardiorespiratory function, autonomic system, and quality of life in patients with HFpEF. Trial registration REBEC Identifier: RBR-64mbnx (August 19, 2012). Clinical Trials Register: NCT03028168. Registered on 16 January 2017).

Parkinson's disease (PD) is a relatively common neurological disorder which an anesthesiologist often encounters, especially with an increasing elderly surgical population. PD is associated with certain physiological aberrancies in the cardiovascular, respiratory, autonomic, and neurological systems that can have profound anesthetic implications. Drugs used in anesthesia may also interact with antiparkinsonian medications. There is controversy about the optimal anesthetic management of patients with PD. However, both general and regional anesthesia have been successfully used and described in these patients. We describe a case of a 65-year-old male with recently diagnosed PD posted for rectopexy. The patient underwent regional anesthesia successfully, and the perioperative period was uneventful. Hence, anesthetic management of patients with PD involves comprehensive evaluation, careful consideration, and meticulous planning to prevent and manage the complications that arise perioperatively.

Abstract: Immersive virtual reality (VR) consists of immersion in artificial environments through the use of real-time render technologies and the latest generation devices. The users feel just as immersed as they would feel in an everyday life situation, and this sense of presence seems to have therapeutic potentials. However, the VR mechanisms remain only partially known. This study is novel in that, for the first time in VR research, appropriate controls for VR contexts, immersive characteristics (ie, control VR), and multifaceted objective and subjective outcomes were included in a within-subject study design conducted on healthy participants. Participants received heat thermal stimulations to determine how VR can increase individual heat-pain tolerance limits (primary outcome) measured in degrees Celsius and seconds while recording concurrent autonomic responses. We also assessed changes in pain unpleasantness, mood, situational anxiety, and level of enjoyment (secondary outcomes). The VR induced a net gain in heat-pain tolerance limits that was paralleled by an increase of the parasympathetic responses. VR improved mood, situational anxiety, and pain unpleasantness when participants perceived the context as enjoyable, but these changes did not influence the increases in pain tolerance limits. Distraction increased pain tolerance limits but did not induce such mood and physiological changes. Immersive VR has been anecdotally applied to improve acute symptoms in contexts such as battlefield, emergency, and operating rooms. This study provides a mechanistic framework for VR as a low-risk, nonpharmacological intervention, which regulates autonomic, affective (mood and situational anxiety), and evaluative (subjective pain and enjoyment ratings) responses associated with acute pain. [ABSTRACT FROM AUTHOR]

Background: The role of deep brain stimulation (DBS) in the management of motor symptoms in patients with Parkinson's disease is well defined. However, it is becoming increasingly clear that DBS can either improve or worsen a number of non‐motor phenomena. Objectives: We examined the published literature to better understand the effects on autonomic symptoms following DBS of the subthalamic nucleus and the globus pallidus interna. Methods: We conducted a PubMed search of studies regarding the effects of DBS on the autonomic system published from January 2001. We searched for the following terms and their combinations: Parkinson's disease, deep brain stimulation, subthalamic nucleus, globus pallidus interna, autonomic dysfunction. Results: Most studies reported in the literature focus on DBS targeting the subthalamic nucleus, with particular emphasis on favorable outcomes regarding gastrointestinal function and bladder control. However, the emergence or worsening of autonomic symptoms in subgroups of patients has also been documented. More controversial is the effect of stimulation on the cardiovascular, pulmonary, and thermo‐regulatory systems as well as sexual functioning. Data regarding the influence of DBS on the autonomic system when the target is the globus pallidus interna is less forthcoming, with target selection varying according to centre and clinical indication. Conclusions: DBS appears to affect the autonomic nervous system, with varying degrees of influence, which may or may not be clinically beneficial for the patient. A better understanding of these effects could help personalize stimulation for individual patients with autonomic disorders and/or avoid autonomic symptoms in susceptible patients. [ABSTRACT FROM AUTHOR]

Background: Heart rate variability (HRV) is a noninvasive method for assessing autonomic function. Age, sex, and chronic conditions influence HRV. Objectives: Our aim was to evaluate HRV measures exploring differences by age, sex, and race in a sample from a rural area. Methods: Analytical sample (n = 1,287) included participants from the 2010 to 2016 evaluation period of the Baependi Heart Study, a family-based cohort in Brazil. Participants underwent 24-hour Holter-ECG (Holter) monitoring. To derive population reference values, we restricted our analysis to a 'healthy' subset (i.e. absence of medical comorbidities). A confirmatory analysis was conducted with a subgroup sample that also had HRV derived from a resting ECG 10'-protocol obtained during the same time period. Results: The 'healthy' subset included 543 participants. Mean age was 40 ± 14y, 41% were male, 74% self-referred as white and mean body-mass-index was 24 ± 3kg/m². Time domain HRV measures showed significant differences by age-decade and by sex. Higher values were observed for males across almost all age-groups. Parasympathetic associated variables (rMSSD and pNN50) showed a U-shaped distribution and reversal increase above 60y. Sympathetic-parasympathetic balance variables (SDNN, SDANN) decreased linearly by age. Race differences were no significant. We compared time domain variables with complete data (Holter and resting ECG) between 'healthy' versus 'unhealthy' groups. Higher HRV values were shown for the 'healthy' subset compared with the 'unhealthy' group. Conclusion: HRV measures vary across age and sex. A U-shaped pattern and a reversal increase in parasympathetic variables may reflect an age-related autonomic dysfunction even in healthy individuals that could be used as a predictor of disease development. [ABSTRACT FROM AUTHOR]

Introduction: dysautonomic dysfunction and cognitive impairment represent the most disabling non-motor features of Parkinson's Disease (PD). Recent evidences suggest the association between Orthostatic Hypotension (OH) and PD-Dementia. However, little is known on the interactions between cardiovascular dysautonomia and Mild Cognitive Impairment (MCI). We aimed to evaluate the association between cardiovascular dysautonomia and MCI in patients with PD.Methods: non-demented PD patients belonging to the PACOS cohort underwent a comprehensive instrumental neurovegetative assessment including the study of both parasympathetic and sympathetic function (30:15 ratio, Expiratory-Inspiratory ratio [E-I] and presence of Orthostatic Hypotension [OH]). Diagnosis of MCI was made according to the MDS criteria level II.Results: we enrolled 185 PD patients of whom 102 (55.1%) were men, mean age was 64.6 ± 9.7 years, mean disease duration of 5.6 ± 5.5 years with a mean UPDRS-ME score of 31.7 ± 10.9. MCI was diagnosed in 79 (42.7%) patients. OH was recorded in 52 (28.1%) patients, altered 30:15 ratio was recorded in 39 (24.1%) patients and an altered E-I ratio was found in 24 (19.1%) patients. Presence of MCI was associated with an altered 30:15 ratio (adjOR 2.83; 95%CI 1.25-6.40) but not with an altered E-I ratio, while OH was associated only with the amnestic MCI subgroup (OR 2.43; 95% CI 1.05-5.06).Conclusion: in our study sample, MCI was mainly associated with parasympathetic dysfunction in PD. [ABSTRACT FROM AUTHOR]

Rapid developments in laboratory-based research in the past decade have provided important new insight into the cellular and molecular mechanisms of nociception. However, the integration of the new understanding into clinical practice is hampered by our inability to combine discrete and often disparate bodies of knowledge and to translate new facts into a perspective of disease-specific significance and case-specific relevance. This process is also inhibited by the current classification systems, which focus heavily on the peripheral anatomy and provide little room to incorporate new understanding of the central nervous system (CNS) in the pathogenesis of disease. If central targets become the object of treatment, crude and often invalid measures of CNS, neuroendocrine, and autonomic processes are used as justification. With the widening gap between bench top-derived research data and clinical practice, an effort needs to be made to translate the basic science frontier into meaning for patients. The muscle-related conditions constitute the most enigmatic subset among the remporomandibular disorders (TMD). These conditions also represent the most prevalent presentations among the TMD, with at least 50% of cases falling into this category. Intense research in the past 10 years has resulted in (1) an improved epidemiologic and clinical description of the phenomenon; (2) new understanding of the molecular, neurophysiologic, and psychophysiologic mechanisms of nociception; and (3) the emergence of metabolic, neuroendocrinologic, and genetic findings. Rather than focusing on the dismissal of previous etiologic constructs, this paper attempts to define what the muscle-related TMD are rather than what they are not. Special consideration is given to the large spectrum of case presentations and the fact that the more severe and persistent forms occur in women more often than in men. With this perspective in mind, the intent of this project was to develop a conceptual framework of the pathogenesis and clinical phenomenology of the muscle-related TMD. [ABSTRACT FROM AUTHOR]

Purpose: To investigate the effects of an oral glucose tolerance test (OGTT) on baroreflex sensitivity (BRS) in a sample of healthy adolescents, and how acute exercise bouts of different intensities alter the effects of the OGTT on BRS.Methods: Thirteen male adolescents (14.0 ± 0.5 years) completed three conditions on separate days in a counterbalanced order: (1) high-intensity interval exercise (HIIE); (2) moderate-intensity interval exercise (MIIE); and (3) resting control (CON). At ~ 90 min following the conditions, participants performed an OGTT. Supine heart rate and blood pressure were monitored continuously at baseline, 60 min following the conditions, and 60 min following the OGTT. A cross-spectral method (LFgain) was used to determine BRS gain. Arterial compliance (AC) was assessed as the BRS vascular component. LFgain divided by AC (LFgain/AC) was used as the autonomic component.Results: Although non-significant, LFgain moderately decreased post-OGTT when no exercise was performed (pre-OGTT = 24.4 ± 8.2 ms mmHg- 1; post-OGTT = 19.9 ± 5.6 ms mmHg- 1; ES = 0.64, P > 0.05). This was attributed to the decrease in LFgain/AC (pre-OGTT = 1.19 ± 0.5 ms µm- 1; post-OGTT = 0.92 ± 0.24 ms µm- 1; ES = 0.69, P > 0.05). Compared to CON (Δ = - 4.4 ± 8.7 ms mmHg- 1), there were no differences for the pre-post-OGTT delta changes in LF/gain for HIIE (Δ = - 3.5 ± 8.2 ms mmHg- 1) and MIIE (Δ = 1.3 ± 9.9 ms mmHg- 1) had no effects on BRS following the OGTT (all ES < 0.5). Similarly, compared to CON (Δ = - 0.23 ± 0.40 ms µm- 1) there were no differences for the pre-post-OGTT delta changes in LF/gain for HIIE (Δ = - 0.22 ± 0.49 ms µm- 1) and MIIE (Δ = 0.13 ± 0.36 ms µm- 1).Conclusion: A moderate non-significant decrease in BRS was observed in adolescents following a glucose challenge with no apparent effects of exercise. [ABSTRACT FROM AUTHOR]

The vagus nerve is responsible for the parasympathetic innervation of the major thoracic and abdominal organs. It also carries sensory afferent fibres from these viscera and reaches different brain structures. These connections have proven useful in the treatment of different diseases. Afferent stimulation of the left vagus nerve is used to treat epilepsy and major depression, and stimulation of the right vagus nerve is being tried for the treatment of heart failure. The device used for the therapy delivers intermittent stimuli. It is indicated worldwide for the treatment of drug-resistant epilepsy in patients who are not appropriate candidates for respective surgery. It has also received approval for the treatment of major depression, obesity and episodic cluster headache by the Food and Drug Administration. Randomised controlled trials and prospective studies have confirmed the efficacy and safety of this therapy in epilepsy. Nevertheless, sporadic cases of ventricular asystole have been reported. To evaluate the effect of vagus nerve stimulation therapy on the autonomic nervous system, different studies that assess heart function and blood pressure changes have been conducted, although the methods employed were not homogeneous. These studies have found subtle or no significant changes in heart rate variability and blood pressure in epileptic patients. Moreover, this therapy may reduce the risk of one of the most lethal conditions in epilepsy—sudden unexpected death. [ABSTRACT FROM AUTHOR]

Although motion of the head and body has been suspected or known as the provocative cause for the production of motion sickness for centuries, it is only within the last 20 yr that the source of the signal generating motion sickness and its neural basis has been firmly established. Here, we briefly review the source of the conflicts that cause the body to generate the autonomic signs and symptoms that constitute motion sickness and provide a summary of the experimental data that have led to an understanding of how motion sickness is generated and can be controlled. Activity and structures that produce motion sickness include vestibular input through the semicircular canals, the otolith organs, and the velocity storage integrator in the vestibular nuclei. Velocity storage is produced through activity of vestibular-only (VO) neurons under control of neural structures in the nodulus of the vestibulo-cerebellum. Separate groups of nodular neurons sense orientation to gravity, roll/tilt, and translation, which provide strong inhibitory control of the VO neurons. Additionally, there are acetylcholinergic projections from the nodulus to the stomach, which along with other serotonergic inputs from the vestibular nuclei, could induce nausea and vomiting. Major inhibition is produced by the GABAB receptors, which modulate and suppress activity in the velocity storage integrator. Ingestion of the GABAB agonist baclofen causes suppression of motion sickness. Hopefully, a better understanding of the source of sensory conflict will lead to better ways to avoid and treat the autonomic signs and symptoms that constitute the syndrome. [ABSTRACT FROM AUTHOR]

Abstract Background Prior studies have shown that resting heart rate variability (HRV) is reduced in those with alcohol use disorders (AUD). However, HRV following an acute stressful stimulus (reactive HRV), and the relationship between resting or reactive HRV and drinking, craving and relapse in AUD have received less attention. Methods Studies using HRV in relationship to acute or chronic alcohol consumption were included in this review. Manuscripts that related to alcohol in the context of cardiovascular disease were excluded. Results Thirty-three articles were included and findings are presented in healthy social drinkers, moderate/heavy drinkers without AUD and individuals with AUD. Results on resting and reactive HRV were presented separately. Acute alcohol reduced resting HRV in healthy subjects but healthy controls had higher resting HRV then AUD subjects and moderate/heavy drinkers (in some studies). Resting HRV improved in AUD subjects only after at least 4 months of abstinence. AUD subjects had higher reactive HRV scores when compared to controls. In AUD subjects increased reactivity was related to more craving, faster relapse and more negative mood. Reactive HRV showed slower improvement with abstinence in AUD subjects. Conclusions Chronic, heavy alcohol has a negative effect on the autonomic nervous system and may be a sensitive biomarker of craving and relapse. Highlights • Resting HRV is reduced in those with alcohol use disorders. • AUD individuals show a stronger and increased reactive HRV following negative stimuli. • High Frequency (HF)-HRV is a sensitive biomarker of craving and relapse. [ABSTRACT FROM AUTHOR]