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Hypertension affects an estimated 1.3 billion people worldwide and is considered the number one contributor to mortality via stroke, heart failure, renal failure, and dementia. Although the physiologic mechanisms leading to the development of essential hypertension are poorly understood, the regulation of cerebral perfusion has been proposed as a primary cause. This article proposes a novel etiology for essential hypertension. Our hypothesis developed from a review of nuclear medicine scans, where the authors observed a significantly abnormal increase in nasal turbinate vasodilation in hypertensive patients using quantitative region of interest analysis. The authors propose that nasal turbinate vasodilation and resultant blood pooling obstruct the flow of cerebrospinal fluid passing through nasal turbinate lymphatics, thereby increasing intracranial pressure. The authors discuss the glymphatic/lymphatic clearance system which is impaired with age, and at which time hypertension also develops. The increased intracranial pressure leads to compensatory hypertension via Cushing's mechanism, i.e., the selfish brain hypothesis. The nasal turbinate vasodilation, due to increased parasympathetic activity, occurs simultaneously along with the well-established increased sympathetic activity of the cardiovascular system. The increased parasympathetic activity is likely due to an autonomic imbalance secondary to the increase in worldwide consumption of processed food. This hypothesis explains the rapid worldwide rise in essential hypertension in the last 50 years and offers a novel mechanism and a new paradigm for the etiology of essential hypertension. This new paradigm offers compelling evidence for the modulation of parasympathetic nervous system activity as a novel treatment strategy, specifically targeting nasal turbinate regulation, to treat diseases such as hypertension, idiopathic intracranial hypertension, and degenerative brain diseases. The proposed mechanism of essential hypertension presented in this paper is a working hypothesis and confirmatory studies will be needed.

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BACKGROUND: Subtypes of atrial fibrillation (AF) can differ, and exact mechanisms in which patients benefit from the pulmonary vein isolation (PVI) remain not fully understood. During PVI, vagal innervation of the heart may also be affected. Thus, non-invasive methods of intraprocedural assessment of such PVI impact are sought. METHODS: From 1-minute ECG recordings performed before and after PVI, we investigated short-term deceleration capacity (ST-DC) and short-term heart rate variability (ST-HRV) to determine their potential as indicators of parasympathetic activity before and after ablation. RESULTS: In 24 consecutive patients with paroxysmal AF included in the study, there were a significant differences in ST-DC and ST-HRV parameters measured before and after PVI. After 3 months, patients with baseline ST-DC ≥ 7.5 ms were less likely to experience AF recurrence when compared to patients with baseline ST-DC < 7.5 ms (0% vs 31%, p = 0.0496). There were no differences in AF recurrence after 12 months of follow-up (36% vs 38%, p = 0.52). CONCLUSION: PVI leads to significant changes in ST-DC and ST-HRV, and these parameters can serve as indicators of vagal denervation after AF ablation. Patients with more prominent baseline ST-DC are less likely to experience AF recurrence during the post-PVI 3-month blanking period.

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In recent years, there has been an increasing interest in studying brain-heart interactions. Methodological advancements have been proposed to investigate how the brain and the heart communicate, leading to new insights into some neural functions. However, most frameworks look at the interaction of only one brain region with heartbeat dynamics, overlooking that the brain has functional networks that change dynamically in response to internal and external demands. We propose a new framework for assessing the functional interplay between cortical networks and cardiac dynamics from noninvasive electrophysiological recordings. We focused on fluctuating network metrics obtained from connectivity matrices of EEG data. Specifically, we quantified the coupling between cardiac sympathetic-vagal activity and brain network metrics of clustering, efficiency, assortativity, and modularity. We validate our proposal using open-source datasets: one that involves emotion elicitation in healthy individuals, and another with resting-state data from patients with Parkinson's disease. Our results suggest that the connection between cortical network segregation and cardiac dynamics may offer valuable insights into the affective state of healthy participants, and alterations in the network physiology of Parkinson's disease. By considering multiple network properties, this framework may offer a more comprehensive understanding of brain-heart interactions. Our findings hold promise in the development of biomarkers for diagnostic and cognitive/motor function evaluation.

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This study aimed to evaluate the feasibility of transcutaneous auricular vagal nerve stimulation (tAVNS) in healthy horses and its effect on heart rate variability (HRV). The study comprised three phases: the selection of mares, their acclimatization to the tAVNS, and the stimulation phase. Stimulation was performed with two electrodes positioned on the right pinna. The settings were 0.5 mA, 250 µs, and 25 Hz for pulse amplitude, pulse width, and pulse frequency, respectively. HRV was analysed before (B1), during (T), and after (B2) the tAVNS. From the 44 mares initially included, only 7 completed the three phases. In these mares, the heart rate (HR) was significantly lower, and frequency domain parameters showed an increased parasympathetic tone in B2 compared with B1. However, in 3/7 mares, the HR was significantly higher during T compared with B1 and B2, compatible with a decreased parasympathetic tone, while in 4/7 mares, the HR was significantly lower and the parasympathetic nervous system index was significantly higher during T and B2 compared with B1. The tAVNS is an economical and easy procedure to perform and has the potential to stimulate vagal activity; however, it was poorly tolerated in the mares included in this study.

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BACKGROUND: Osteoarthritis (OA) is a chronic degenerative joint disease causing limited mobility and pain, with no curative treatment available. Recent in vivo studies suggested autonomic alterations during OA progression in patients, yet clinical evidence is scarce. Therefore, autonomic tone was analyzed in OA patients via heart rate variability (HRV) measurements. METHODS: Time-domain (SDRR, RMSSD, pRR50) and frequency-domain (LF, HF, LF/HF) HRV indices were determined to quantify sympathetic and parasympathetic activities. In addition, perceived stress, WOMAC pain as well as serum catecholamines, cortisol and dehydroepiandrosterone-sulphate (DHEA-S) were analyzed. The impact of the grade of disease (GoD) was evaluated by linear regression analysis and correlations with clinical data were performed. RESULTS: GoD significantly impacted the autonomic tone in OA patients. All time-domain parameters reflected slightly decreased HRV in early OA patients and significantly reduced HRV in late OA patients. Moreover, frequency-domain analysis revealed decreased HF and LF power in all OA patients, reflecting diminished parasympathetic and sympathetic activities. However, LF/HF ratio was significantly higher in early OA patients compared to late OA patients and implied a clear sympathetic dominance. Furthermore, OA patients perceived significantly higher chronic stress and WOMAC pain levels compared to healthy controls. Serum cortisol and cortisol/DHEA-S ratio significantly increased with GoD and positively correlated with WOMAC pain. In contrast, serum catecholamines only trended to increase with GoD and pain level. CONCLUSIONS: This prospective study provides compelling evidence of an autonomic dysfunction with indirect sympathetic dominance in early and late knee OA patients for the first time based on HRV analyses and further confirmed by serum stress hormone measurements. Increased sympathetic activity and chronic low-grade inflammation in OA as well as in its major comorbidities reinforce each other and might therefore create a vicious cycle. The observed autonomic alterations coupled with increased stress and pain levels highlight the potential of HRV as a prognostic marker. In addition, modulation of autonomic activity represents an attractive future therapeutic option.

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BACKGROUND: Autonomic nervous system (ANS) testing has aided in our ability to evaluate autonomic dysfunction in migraine patients. We reviewed the literature in multiple databases which investigate ANS function in migraine patients and healthy subjects. METHODS: This systematic review and meta-analysis examined the respective deep breathing, Valsalva manoeuvre, orthostatic and isometric challenge results, using the Preferred Reporting Items for Systematic Reviews and Meta-Analyses (PRISMA) and Meta-analyses of Observational Studies in Epidemiology (MOOSE) statements. RESULTS: Seven articles met all inclusion criteria. Fixed-effects meta-analysis showed migraine patients (n = 424), collectively, had lower interictal autonomic test results compared with healthy controls (n = 268). In detail, this was true for the standardized mean difference (g) of deep breathing (g= -0.32; 95% confidence interval (CI) -0.48, -0.16), orthostatic challenge (g= -0.28; 95% CI -0.44, -0.13) and isometric challenge (g= -0.55; 95% CI -0.71, -0.39) and for the difference of means (MD) of the Valsalva ratio (MD = -0.17; 95% CI -0.23, -0.10). CONCLUSIONS: Interictal ANS dysfunction can be identified in migraine patients when compared to healthy controls. These findings indicate the importance to evaluate ANS function in migraine patients - especially, as migraine-specific prophylactic therapies (such as anti-calcitonin gene-related peptide (CGRP) antibodies) may affect the function of the ANS.

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PURPOSE: This study aimed to assess the course of changes in choroidal morphology after immersion of the foot in warm water at 40°C using enhanced depth imaging optical coherence tomography (EDI-OCT). METHODS: Forty-three right eyes of 43 healthy participants were included. Changes in choroidal morphology were determined using EDI-OCT to evaluate subfoveal choroidal thickness (SCT). Systolic, diastolic, and mean blood pressures (SBP, DBP, and MBP, respectively) were also measured to determine systemic circulatory dynamics at baseline, immediately after immersion (0 min), and 10, 20, and 30 min after immersion. RESULTS: Immediately after immersion, SBP, DBP, and MBP were significantly declined versus baseline. In contrast, the SCT was significantly increased after warm water immersion. However, all these parameters did not change significantly compared to the baseline within 30 min. CONCLUSION: In the normal eye, parasympathetic nerve activity induced by warming stimuli increases choroidal morphology in response to a decrease in systemic circulatory activity, which normalizes within 30 min. The findings of this study may provide basic data for the prevention and treatment of various choroidal diseases in which sympathetic hyperactivity is involved in the pathogenesis.

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We investigated the utility of heart rate (HR) and heart rate variability (HRV) for identifying individuals who may terminate work early due to excessive heat strain. Forty-eight men and women (median = 36 years; Q1 = 20 years; Q3 = 54 years) attempted 180 min of moderate-intensity work at a fixed metabolic rate (∼200 W/m2; ∼3.5 METs) in a hot environment (wet-bulb globe temperature: 32 °C). Receiver operating characteristics (ROC) curves were used to identify the ability of indices of HR (absolute HR, percentage of maximum HR, percentage of HR reserve) and HRV (root-mean-square of successive differences (RMSSD), high-frequency power, and detrended fluctuation analysis component alpha 1 (DFA α1)) to discriminate between participants who completed the 180 min work bout or terminated prematurely. Participants who terminated work prematurely (n = 26) exhibited higher HR and percentage of HR measures, as well as reduced RMSSD and DFA α1 after the first hour of work compared to participants who completed the bout. The discriminative utility of HR and HRV indices was strongest within the first hour of work, with percentage of HR reserve demonstrating excellent discriminative power (ROC area under curve (AUC) of 0.8). Stratifying participants by age and sex improved ROC AUC point estimates for most indices, particularly in female participants. The study provides preliminary evidence supporting the use of noninvasive cardiac monitoring for predicting work tolerance in healthy individuals exposed to occupational heat stress. HR and percentage of HR reserve were suggested to discriminate work termination most effectively. Further investigations are warranted to explore the influence of individual factors and refine the discriminative thresholds for early identification of excessive occupational heat strain.

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BACKGROUND: Reduced vagally-mediated heart rate variability (HRV) has been associated with anxiety disorders (AD). The aim of this study was to use a wearable device and remote study design to re-evaluate the association of HRV with ADs, anxiety-related traits, and confounders. METHODS: 240 individuals (AD = 120, healthy controls = 120) completed an at-home assessment of their short-term resting vagally-mediated HRV using a wristband, monitored over videoconference. Following quality control, analyses were performed investigating differences in HRV between individuals with AD (n = 119) and healthy controls (n = 116), associations of HRV with anxiety-related traits and confounders, and antidepressants effects on HRV in patients, including analyses stratified by ancestry (i.e., European, East Asian, African). RESULTS: Among the confounders investigated, only age had a significant association with HRV. Patients with an AD had significantly lower vagally-mediated HRV than healthy controls in the European subsample, with a trend of significance in the whole sample. HRV was significantly associated with the Hamilton Anxiety Rating Scale (HAM-A) but not with antidepressant use in the European subsample. LIMITATIONS: The study measures occurred in a non-standardized at-home setting, and the three ancestry group sample sizes were unequal. CONCLUSIONS: This study demonstrates reduced vagally-mediated HRV among patients with ADs compared to healthy controls. Results also point to low HRV being related to more physical anxiety symptoms (measured via HAM-A), suggesting a possible anxiety subtype. Overall, this study highlights the feasibility of using wearables for patients and encourages exploration of the biological and clinical utility of HRV as a risk factor for ADs.

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Modulation of the parasympathetic tone leads to extensive physiological reactions at several levels, including the decreased production of proinflammatory cytokines. Many studies have demonstrated that chronic inflammatory diseases are associated with reduced parasympathetic and increased sympathetic activities. Moreover, it was demonstrated that a low parasympathetic and a high sympathetic activity in patients with rheumatoid arthritis (RA) predicts a poor therapeutic response to anti-tumor necrosis factor (TNF) treatment compared to RA patients with a more balanced autonomic nervous system. The autonomic equilibrium could be restored by electrical stimulation of the vagus nerve. Considering the patients who do not sufficiently respond to the available drugs, patients for whom the effectiveness of the drugs wanes over time, or have drug-related adverse events, a nonpharmacological approach such as bioelectronics might be a useful supplement as an instrument in the successful extension of the therapeutic armamentarium for rheumatic diseases; however, there is a great need for further studies and the development of novel therapeutic strategies in the field of neuroimmunology.

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Inflammaging refers to the age-related low grade, sterile, chronic, systemic, and long-lasting subclinical, proinflammatory status, currently recognized as the main risk factor for development and progression of the most common age-related diseases (ARDs). Extensive investigations were focused on a plethora of proinflammatory stimuli that can fuel inflammaging, underestimating and partly neglecting important endogenous anti-inflammaging mechanisms that could play a crucial role in such age-related proinflammatory state. Studies on autonomic nervous system (ANS) functions during aging highlighted an imbalance toward an overactive sympathetic nervous system (SNS) tone, promoting proinflammatory conditions, and a diminished parasympathetic nervous system (PNS) activity, playing anti-inflammatory effects mediated by the so called cholinergic anti-inflammatory pathway (CAP). At the molecular level, CAP is characterized by signals communicated via the vagus nerve (with the possible involvement of the splenic nerves) through acetylcholine release to downregulate the inflammatory actions of macrophages, key players of inflammaging. Notably, decreased vagal function and increased burden of activated/senescent macrophages (macrophaging) probably precede the development of several age-related risk factors and diseases, while increased vagal function and reduced macrophaging could be associated with relevant reduction of risk profiles. Hypothalamic-pituitary-adrenal axis (HPA axis) is another pathway related to ANS promoting some anti-inflammatory response mainly through increased cortisol levels. In this perspective review, we highlighted that CAP and HPA, representing broadly "anti-inflammaging" mechanisms, have a reduced efficacy and lose effectiveness in aged people, a phenomenon that could contribute to fuel inflammaging. In this framework, strategies aimed to re-balance PNS/SNS activities could be explored to modulate systemic inflammaging especially at an early subclinical stage, thus increasing the chances to reach the extreme limit of human lifespan in healthy status.

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Cardioneuroablation (CNA) is being increasingly used to treat patients with vasovagal syncope (VVS). Bradycardia, in the cardioinhibitory subtype of VVS, results from transient parasympathetic overactivity leading to sinus bradycardia and/or atrioventricular block. By mitigating parasympathetic overactivity, CNA has been shown to improve VVS symptoms in clinical studies with relatively small sample sizes and short follow-up periods (<5 years) at selected centers. However, CNA may potentially tip the autonomic balance to a state of sympathovagal imbalance with attenuation of cardiac parasympathetic activity. A higher heart rate is associated with adverse cardiovascular events and increased mortality in healthy populations without cardiovascular diseases. Chronic sympathovagal imbalance may also affect the pathophysiology of spectra of cardiovascular disorders including atrial and ventricular arrhythmias. This review addresses potential long-term pathophysiological consequences of CNA for VVS.

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Background: Second-degree atrioventricular (AV) block at rest is very common in horses. The underlying molecular mechanisms are unexplored, but commonly attributed to high vagal tone. Aim: To assess whether AV block in horses is due to altered expression of the effectors of vagal signalling in the AV node, with specific emphasis on the muscarinic acetylcholine receptor (M2) and the G protein-gated inwardly rectifying K+ (GIRK4) channel that mediates the cardiac IK,ACh current. Method: Eighteen horses with a low burden of second-degree AV block (median 8 block per 20 h, IQR: 32 per 20 h) were assigned to the control group, while 17 horses with a high burden of second-degree AV block (median: 408 block per 20 h, IQR: 1,436 per 20 h) were assigned to the AV block group. Radiotelemetry ECG recordings were performed to assess PR interval and incidence of second-degree AV block episodes at baseline and on pharmacological blockade of the autonomic nervous system (ANS). Wenckebach cycle length was measured by intracardiac pacing (n = 16). Furthermore, the expression levels of the M2 receptor and the GIRK4 subunit of the IKACh channel were quantified in biopsies from the right atrium, the AV node and right ventricle using immunohistochemistry and machine learning-based automated segmentation analysis (n = 9 + 9). Results: The AV block group had a significantly longer PR interval (mean ± SD, 0.40 ± 0.05 s; p < 0.001) and a longer Wenckebach cycle length (mean ± SD, 995 ± 86 ms; p = 0.007) at baseline. After blocking the ANS, all second-degree AV block episodes were abolished, and the difference in PR interval disappered (p = 0.80). The AV block group had significantly higher expression of the M2 receptor (p = 0.02), but not the GIRK4 (p = 0.25) in the AV node compared to the control group. Both M2 and GIRK4 were highly expressed in the AV node and less expressed in the atria and the ventricles. Conclusion: Here, we demonstrate the involvement of the m2R-IK,ACh pathway in underlying second-degree AV block in horses. The high expression level of the M2 receptor may be responsible for the high burden of second-degree AV blocks seen in some horses.

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BACKGROUND: This study aimed to examine the changes to choroidal blood flow velocity using laser speckle flowgraphy (LSFG) in healthy eyes after warm water immersion at 40°C. METHODS: Data regarding the right eyes of 23 healthy volunteers were included. The mean blur rate (MBR) of the macula, which represents the choroidal blood flow velocity, was evaluated using LSFG. Intraocular pressure (IOP), systolic blood pressure (SBP), diastolic blood pressure (DBP), mean blood pressure (MBP), ocular perfusion pressure (OPP), and MBR were assessed at baseline, immediately after immersion (0 minutes), and 10, 20, and 30 minutes later. RESULTS: At 0 minutes, SBP, DBP, MBP, and OPP values were lower than those at baseline. The MBR significantly declined immediately after immersion to -6.0 ± 5.2%. However, there were no changes in these parameters after 10, 20, or 30 minutes. A significant positive correlation was observed between the MBR, SBP, DBP, MBP, and OPP values. In healthy individuals, the dominant parasympathetic activity induced by warm stimulation reduced the choroidal hemodynamic rate in the macula and decreased systemic circulatory dynamics, which normalized after 10 minutes. CONCLUSIONS: These findings suggest that the dominant parasympathetic activity induced by warm water immersion at 40°C may lead to a reduction in the systemic circulation rate and choroidal blood flow rate in the macula. These findings may help prevent and treat various retinal choroidal diseases, in which sympathetic hyperactivity is involved in the pathogenesis of the disease.

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Most of the studies on the effect of trait positive affect (PA) and cardiovascular activity have focused on heart rate (HR) and blood pressure (BP) rather than heart rate variability (HRV). However, trait PA might sustain homeostasis for the autonomic system (ANS) by reducing activity in the sympathetic system (SNS) and increasing the activity in the parasympathetic system (PNS). A common index for the PNS is the vagal tone measured indirectly through HRV. The present study assessed whether trait PA influences cardiovascular response to various stress tasks by monitoring participants' HRV measured by RMSSD (root mean square of successive differences) along with HR and interbeat interval (IBI). A total of 54 participants performed various cognitive tasks and Trier Social Stress Tasks while their vital signs were monitored, and trait PA was measured with PANAS. The cognitive tasks included both high- and low-stress tasks, including fatigue-inducing 20 min Stroop tasks. The results showed overall higher HRV as measured by RMSSD for participants who have higher levels of trait PA, indicating more PNS activity compared with low-trait-PA individuals, particularly at the end of the task performance during the fatigue induction. High-trait-PA individuals also had a lower HR during the fatigue-inducing task and a higher IBI. The results support previous work by further indicating a more adaptive response and consequently better emotional regulation for high-trait-PA individuals in a complex, prolonged task setting.

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Heart rate variability (HRV) is a psychophysiological measure of particular interest in esports due to its potential to monitor player self-regulation. This study aimed to systematically review the utilisation of HRV in esports. Consideration was given to the methodological and theoretical underpinnings of previous works to provide recommendations for future research. The protocol was made available on the Open Science Framework. Inclusion criteria were empirical studies, examining HRV in esports, using esports players, published in English. Exclusion criteria were non-peer-reviewed studies, populations with pre-existing clinical illness other than Internet Gaming Disorder (IGD), opinion pieces or review papers. In November 2022 a search of Web of Science, PubMed, and EBSCOHost identified seven studies using HRV in esports. Risk of bias was assessed using the Mixed Methods Appraisal Tool. Narrative review identified two primary uses of HRV in esports; stress response and IGD. A lack of theoretical and methodological underpinning was identified as a major limitation of current literature. Further investigation is necessary before making recommendations regarding the use of HRV in esports. Future research should employ sound theoretical underpinning such as the use of vagally mediated HRV and the robust application of supporting methodological guidelines when investigating HRV in esports.

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Objective: A novel protocol for paired associative stimulation (PAS), called high PAS, consists of high-intensity transcranial magnetic stimulation (TMS) and high-frequency peripheral nerve stimulation (PNS). High PAS was developed for spinal cord injury rehabilitation and targets plastic changes in stimulated pathways in the corticospinal tract, which improves motor function. As therapy interventions can last many weeks, it is important to fully understand the effects of high PAS, including its effect on the cardiovascular system. Heart rate variability (HRV) has been used to measure changes in both sympathetic and parasympathetic systems. Methods: We used short-term HRV measurements to evaluate the effects of one 20-min session of high PAS on 17 healthy individuals. HRV was recorded for 5 min before (PRE), during (STIM), immediately after (POST), 30 min after (POST30), and 60 min after (POST60) the stimulation. Five participants repeated the HRV setup with sham stimulation. Results: A significant decrease in low-frequency (LF) power (n.u.) (p = 0.002), low-frequency to high-frequency (HF) ratio (p = 0.017), in Poincaré plot [the standard deviation of RR intervals perpendicular to (SD1) and along (SD2) the line of identity SD2/SD1 ratio p < 0.001], and an increase in HF power (n.u.) (p = 0.002) were observed between PRE and STIM conditions; these changes were fully reversible immediately after stimulation. PRE to POST by 3% (p = 0.015) and continued to decline until POST60 by 5% (p = 0.011). LF power (ms2) (p = 0.017) and SD2 (p = 0.015) decreased from PRE to STIM and increased from PRE to POST (p = 0.025 and p = 0.017, respectively). The results from sham PAS exhibited a trend similar to active high-PAS stimulation. Conclusions: High PAS does not have sustained effects during 60-min follow-up on cardiovascular functions, as measured by HRV. None of the short-term results indicates activation of the sympathetic nervous system in healthy individuals. Observed changes in HRV indicate higher parasympathetic activity during stimulation, which is reversible, and is plausibly explained by the fact that the participants spend 20 min without moving, talking, or using phones while being stimulated.

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INTRODUCTION: The therapeutic structure of occupational therapy (OT) includes groups. Although the presence of others is expected to be relaxing due to the social buffering effect and the tend and befriend theory, it has not been sufficiently validated in accordance with the therapeutic structure of OT. The aim of this study was to investigate the electrophysiological evidence for the effectiveness of parallel groups and states of concentration on craft activities used in OT. METHODS: Thirty healthy young adults were used as controls to measure EEG and autonomic activity during craft activities in three conditions: alone, parallel, and nonparallel. EEG was analyzed using exact low-resolution electromagnetic tomography, and autonomic activity was analyzed using Lorenz plot analysis. RESULTS: Parasympathetic activity was significantly higher in the parallel condition than in the alone condition. A significant negative correlation was found between current source density and parasympathetic activity in the region centered on the right insular cortex in the α1 band, and functional connectivity in regions including the anterior cingulate cortex and insular cortex was associated with autonomic activity. CONCLUSION: Craft activities that occurred during frontal midline theta rhythm also increased parasympathetic activity. The results suggest that the parallel groups used in OT and the intensive state of craft activities induce a social buffering effect that increases parasympathetic activity despite the absence of physical contact or social support. This provides evidence for the effectiveness of the therapeutic structure of occupational activities and groups in OT.

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Modulation of the parasympathetic tone leads to extensive physiological reactions at several levels, including the decreased production of proinflammatory cytokines. Many studies have demonstrated that chronic inflammatory diseases are associated with reduced parasympathetic and increased sympathetic activities. Moreover, it was demonstrated that a low parasympathetic and a high sympathetic activity in patients with rheumatoid arthritis (RA) predicts a poor therapeutic response to anti-tumor necrosis factor (TNF) treatment compared to RA patients with a more balanced autonomic nervous system. The autonomic equilibrium could be restored by electrical stimulation of the vagus nerve. Considering the patients who do not sufficiently respond to the available drugs, patients for whom the effectiveness of the drugs wanes over time, or have drug-related adverse events, a nonpharmacological approach such as bioelectronics might be a useful supplement as an instrument in the successful extension of the therapeutic armamentarium for rheumatic diseases; however, there is a great need for further studies and the development of novel therapeutic strategies in the field of neuroimmunology.

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The utility of heart rate variability (HRV) for characterizing psychological stress is primarily impacted by methodological considerations such as study populations, experienced versus induced stress, and method of stress assessment. Here, we review studies on the associations between HRV and psychological stress, examining the nature of stress, ways stress was assessed, and HRV metrics used. The review was performed according to the PRISMA guidelines on select databases. Studies that examined the HRV-stress relationship via repeated measurements and validated psychometric instruments were included (n = 15). Participant numbers and ages ranged between 10 and 403 subjects and 18 and 60 years, respectively. Both experimental (n = 9) and real-life stress (n = 6) have been explored. While RMSSD was the most reported HRV metric (n = 10) significantly associated with stress, other metrics, including LF/HF (n = 7) and HF power (n = 6) were also reported. Various linear and nonlinear HRV metrics have been utilized, with nonlinear metrics used less often. The most frequently used psychometric instrument was the State-Trait Anxiety Inventory (n = 10), though various other instruments have been reported. In conclusion, HRV is a valid measure of the psychological stress response. Standard stress induction and assessment protocols combined with validated HRV measures in different domains will improve the validity of findings.

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