Analysis of taVNS Effects on Baroreflex Sensitivity and Autonomic Nervous System Regulation During Head-up Tilt Test

Analysis of taVNS Effects on Baroreflex Sensitivity and Autonomic Nervous System Regulation During Head-up Tilt Test | Research Square window.SnipcartSettings = { analytics: { enabled: false } }; (function() { var accessVector = localStorage.getItem('access_vector') || ''; window.dataLayer = window.dataLayer || []; if (accessVector) { window.dataLayer.push({ user: { profile: { profileInfo: { snid: accessVector } } } }); } })(); (function(w,d,s,l,i){w[l]=w[l]||[];w[l].push({'gtm.start':new Date().getTime(),event:'gtm.js'});var f=d.getElementsByTagName(s)[0],j=d.createElement(s),dl=l!='dataLayer'?'&l='+l:'';j.async=true;j.src='https://www.googletagmanager.com/gtm.js?id='+i+dl;f.parentNode.insertBefore(j,f);})(window,document,'script','dataLayer','GTM-K279D39R'); Browse Preprints In Review Journals COVID-19 Preprints AJE Video Bytes Research Tools Research Promotion AJE Professional Editing AJE Rubriq About Preprint Platform In Review Editorial Policies Our Team Advisory Board Help Center Sign In Submit a Preprint Cite Share Download PDF Article Analysis of taVNS Effects on Baroreflex Sensitivity and Autonomic Nervous System Regulation During Head-up Tilt Test Geonhee Lee, Donghun Kang, Jiseok Lee, Jongshill Lee, Jeyeon Lee, and 1 more This is a preprint; it has not been peer reviewed by a journal. https://doi.org/ 10.21203/rs.3.rs-8923528/v1 This work is licensed under a CC BY 4.0 License Status: Under Review Version 1 posted 10 You are reading this latest preprint version Abstract Baroreflex dysfunction and autonomic imbalance are key pathophysiological features of hypertension, but current pharmacological approaches often fail to address these neural mechanisms. This study investigated whether transcutaneous auricular vagus nerve stimulation (taVNS) enhances autonomic regulation during blood pressure perturbation. In a randomized, single-blind, sham-controlled, crossover design experiment, 32 normotensive adults received 60-min taVNS or sham condition. Blood pressure perturbation was induced with the head-up tilt test (supine–tilt–supine). Heart rate variability (HRV) was analyzed across all four phases (S-baseline, early-tilt, late-tilt, recovery), whereas baroreflex sensitivity (BRS) was analyzed only during the 10-minute tilt phase. taVNS significantly increased parasympathetic HRV parameters (SDNN, RMSSD, pNN30, pNN50, HF) across all phases. During tilt, BRS up- and down-slope values increased significantly, indicating enhanced inter-beat interval responsiveness to systolic pressure fluctuations. In contrast, the sham procedure yielded no consistent changes in HRV or significant BRS alterations during tilt. These findings suggest that taVNS augments vagal modulation and baroreflex responsiveness, not only at rest but also during orthostatic stress, supporting a physiological mechanism that is likely mediated by auricular branch of the vagus nerve– nucleus tractus solitarius pathways. Consequently, taVNS shows potential to modulate conditions involving autonomic dysregulation, such as hypertension, and further research involving patient cohorts and longitudinal study protocols is needed. Clinical Trial: The clinical trial described in this paper was registered at https://cris.nih.go.kr/cris/index/index.do under the registration number KCT0011752 (first trial registered 20/03/2026, retrospective registration). Health sciences/Medical research Health sciences/Neurology Biological sciences/Neuroscience Biological sciences/Physiology transcutaneous auricular vagus nerve stimulation (taVNS) head-up tilt test heart rate variability (HRV) baroreflex sensitivity (BRS) Figures Figure 1 Figure 2 Figure 3 Figure 4 Figure 5 Figure 6 Figure 7 1. Introduction Hypertension is one of the most prevalent risk factors for cardiovascular disease and affects more than 1.4 billion individuals worldwide [ 1 ]. Despite its high prevalence, only about 44% of hypertension patients receive a diagnosis and treatment, and among those undergoing therapy, only 23% achieve adequate blood pressure control [ 2 ]. The current standard of care relies primarily on pharmacological therapy; however, several limitations persist, including low medication adherence due to combination drugs, interindividual variability in drug responsiveness, and adverse side effects associated with antihypertensive agents [ 3 ]. Consequently, interest in developing alternative therapeutic strategies that are both effective and minimally invasive has been growing. Hypertension is a multifactorial disorder, and autonomic nervous system (ANS) dysfunction has been recognized as a key pathophysiological contributor [ 4 – 6 ]. Among cardiovascular regulatory mechanisms, the baroreflex plays a crucial role in maintaining autonomic balance and blood pressure homeostasis [ 7 – 9 ]. When blood pressure rises, baroreceptors detect the blood pressure change and transmit afferent signals to the nucleus tractus solitarius (NTS) via the vagus nerve (VN) [ 10 , 11 ]. As a result, reductions in heart rate and myocardial contractility, accompanied by an increase in heart rate variability (HRV), contribute to the maintenance of cardiovascular homeostasis [ 12 ]. In hypertensive patients, however, impaired baroreflex function leads to sympathetic overactivation and parasympathetic withdrawal, resulting in diminished reflex modulation capacity against blood pressure fluctuations [ 13 – 16 ]. Those abnormalities lead to sustained elevation of blood pressure and impaired blood pressure control [ 17 , 18 ]. Thus, restoring vagal function or enhancing baroreflex sensitivity could have promising therapeutic potential for autonomic dysfunction–related hypertension. The VN is a major component of the ANS and plays a crucial role in parasympathetic regulation. The VN is a mixed nerve composed of both afferent (sensory) and efferent (motor) fibers, with approximately 80% being afferent and 20% efferent [ 10 , 19 , 20 ]. The afferent fibers transmit sensory information about blood pressure changes from peripheral organs such as the heart, lungs, and viscera to the NTS in the medulla [ 8 , 21 ]. The NTS integrates that information and modulates parasympathetic output via the nucleus ambiguous (NA) and the dorsal motor nucleus of the vagus (DMV), while simultaneously inhibiting sympathetic tone by activating the caudal ventrolateral medulla (CVLM) and suppressing the rostral ventrolateral medulla (RVLM). Efferent vagal fibers transmit those output signals to the sinoatrial node, atrioventricular node, and ventricular myocardium, thereby reducing the heart rate and contractility to maintain cardiovascular stability [ 7 , 22 ]. Because of those physiological properties, modulation of vagal activity has therapeutic potential for restoring autonomic balance and mitigating cardiovascular risks such as hypertension. Vagus nerve stimulation (VNS) is a neuromodulation approach involving the application of electrical impulses to the VN to modulate ANS function [ 19 , 20 , 23 , 24 ]. Invasive VNS is performed by surgically implanting electrodes around the VN and connecting them to a pulse generator. This approach is approved by the US Food and Drug Administration for the treatment of epilepsy and depression [ 25 ]. In animal studies, invasive VNS has been shown to reduce blood pressure and improve autonomic regulation [ 26 ]. However, the surgical procedure is associated with risks of complications such as infection, coughing, and voice alteration [ 27 ]. To prevent those risks, transcutaneous auricular vagus nerve stimulation (taVNS) has been proposed as a noninvasive, low-cost alternative [ 28 , 29 ]. taVNS stimulates the auricular branch of the vagus nerve (ABVN), which is located in the cymba concha and tragus of the ear [ 30 ]. Recent studies have reported that taVNS increases parasympathetic activity and improves HRV, and it has gained attention as a safe and effective method for autonomic modulation. Clancy et al. (2014) demonstrated that taVNS increased HRV and decreased muscle sympathetic nerve activity in healthy adults, promoting a shift toward parasympathetic predominance [ 31 ]. De Couck et al. (2017) reported that short (10 min) and long (1 h) taVNS sessions produced moderate increases in HRV parameters, such as the standard deviation of normal-to-normal intervals (SDNN), with more pronounced effects in females than males [ 32 ]. Moreover Antonino et al. (2017) showed that taVNS significantly enhanced cardiac baroreflex sensitivity (BRS) and reduced the low frequency/high frequency (LF/HF) ratio within a short period, confirming its parasympathetic activation effect [ 33 ]. Most previous taVNS studies have compared pre- and post-stimulation changes in resting conditions. Although that approach is useful for observing the effects of taVNS on baseline parasympathetic activity, it provides little information about reflex autonomic responsiveness during physiological stress such as blood pressure perturbation. Because the baroreflex is not fully activated in resting conditions, it is difficult to clearly determine the regulatory effects of taVNS on baroreflex function. Therefore, evaluating the effects of taVNS during conditions that induce blood pressure perturbation will provide more physiologically meaningful information for understanding its influence on baroreflex-mediated autonomic control. The head-up tilt test (HUTT) is a standard method used to induce blood pressure perturbation. During the HUTT, the transition from the supine to the tilt position causes blood to pool in the lower extremities under the influence of gravity, leading to transient reductions in central venous return, stroke volume, and arterial pressure. As a result, a transient hypotensive state occurs, activating the baroreflex, which increases sympathetic activity and suppresses parasympathetic tone to restore and maintain blood pressure. During this process, the heart rate increases and vascular tone is adjusted, allowing the ANS to compensate for the instability caused by postural change [ 34 , 35 ]. Therefore, the HUTT is a useful method for eliciting the autonomic responses associated with postural transitions and evaluating baroreflex-mediated autonomic regulation and the dynamic adaptability of the cardiovascular system, making it suitable for investigating how taVNS affects blood pressure control and autonomic responsiveness. In this study, we used the HUTT protocol to identify the effects of taVNS on baroreflex-mediated autonomic responses during induced blood pressure perturbation. This approach allowed us to examine the physiological influence of taVNS in healthy subjects, thereby establishing a foundation for future applications in clinical populations with autonomic dysfunctions such as hypertension. First, we compared changes in HRV and BRS pre- and post-stimulation within the perturbation phases to evaluate the acute effects of taVNS on cardiovascular regulation. Second, we compared those physiological responses between taVNS and a sham condition to verify that specific autonomic effects were attributable to taVNS. 2. Methods 2.1. Participants This study enrolled healthy participants with normal blood pressure. None of the participants had a history of cardiovascular disease, epilepsy, or recurrent syncope. Participants were instructed to abstain from caffeine, alcohol, and nicotine for at least 12 hours before the experiment. This study was approved by the Institutional Review Board of Hanyang University, and all experimental processes were conducted in accordance with the guidelines of the Declaration of Helsinki (HYUIRB-202501-005-2). This trial was registered on (03/20/2026) at https://cris.nih.go.kr/cris/index/index.do (KCT0011752). The experiment was conducted in Room 204 of College of Medicine Ⅱ at Hanyang University. Written informed consent was obtained from all participants before their enrollment. Sample size was estimated using G*Power based on the effect size reported in a previous study[ 36 ]. Using η² = 0.082, corresponding to an effect size of f = 0.2988722, with α = 0.05, power = 0.95, two groups, three measurements, a correlation among repeated measures of 0.5, and a nonsphericity correction of 1, the required sample size was calculated to be 32 participants. 2.2. Measurement systems Electrocardiogram (ECG) and blood pressure data were collected using a Task Force® Monitor 3040i (CNSystems, Graz, Austria). Continuous and noninvasive blood pressure monitoring was performed by placing finger cuffs on the right index and middle fingers. The right arm was supported with a sling to ensure that the finger cuffs were maintained at heart level. RR interval (RRI) values were extracted from the ECG signals, and simultaneously recorded systolic blood pressure (SBP) values were obtained. The blood pressure data were calibrated to oscillometric blood pressure values obtained in the left arm. In addition, respiratory activity was recorded using a physiological recording system (MP160, Biopac Inc., USA) to monitor potential drowsiness during the experiment. 2.3. Study protocol This study was conducted using a randomized, single-blind, sham-controlled, crossover design. Participants were assigned to one of two intervention sequences (taVNS → rest → sham or sham → rest → taVNS) using a pre-specified allocation list designed to achieve an approximately equal (1:1) distribution between the two sequences. Assignments were made sequentially according to the order of enrollment. Participants were blinded to the intervention condition (taVNS vs. sham). All participants completed two laboratory visits. In each visit, they experienced one of the two conditions: taVNS or sham condition. For the first visit, participants underwent anthropometric measurements (height and weight), followed by a sufficient resting period. After resting, heart rate (HR), SBP, and diastolic blood pressure (DBP) were measured using an oscillometric method with the participant in a seated position. Participants were then randomly assigned and received either taVNS or the sham condition. A washout period of at least two days was implemented before the second visit to minimize any potential carryover effects from the previous stimulation. The alternate stimulation condition was applied during the second visit. Throughout the entire experiment, all participants were positioned supine on a tilt table. The HUTT procedure was performed twice in each condition, encompassing two distinct phases: pre-stimulation and post-stimulation. 2.3.1. taVNS The taVNS system consisted of a medical stimulator (ELEXIR, NuEyne, Korea) and ear electrodes (tVNS Technologies, Germany) specifically designed for attachment to the cymba concha—an area exclusively innervated by the ABVN. Electrodes were positioned on the left ear, and taVNS was administered with a pulse width of 250 µs and a frequency of 25 Hz [ 37 , 38 ]. The stimulation intensity was gradually increased from 0 mA in 0.1 mA increments up to each participant’s individual sensory threshold. In the sham condition, the same electrodes were attached, and participants were informed that stimulation would be applied at a very weak intensity; however, no electrical current was actually delivered. The stimulation was applied for 60 minutes after the first HUTT and continued during the post-stimulation HUTT, resulting in a total stimulation duration of 90 minutes. 2.3.2. HUTT Before the HUTT, participants rested in the supine position for at least 10 minutes. The HUTT was conducted for a total duration of 30 minutes and consisted of three phases. The first phase was a 10-minute supine period to assess baseline autonomic activity. The second phase involved a 10-minute tilt period at 60° to evaluate autonomic responses during orthostatic stress. The third phase consisted of a 10-minute supine recovery period to observe autonomic restoration after tilting. Harms included dizziness, nausea, headache, and burn-related skin irritation. If any harm occurred, the experiment was immediately terminated. An overview of the HUTT protocol is summarized in Fig. 1 . 2.4. Feature extraction We used MATLAB R2025a software (The MathWorks, Inc., Natick, MA, USA) to extract the HRV and BRS parameters from the RRI and SBP values acquired by the Task Force® Monitor. The HRV analysis was performed across all three phases of the HUTT. In each phase, consecutive 5-minute segments without overlap were used to calculate the HRV parameters. Among them, four specific segments were selected for analysis: the last 5-minute segment before the tilt phase, while supine, was used to assess baseline autonomic activity (Supine-baseline, S-baseline), reflecting resting parasympathetic tone in the absence of orthostatic stress; the first 5 minutes immediately after tilting (early-tilt) was used to evaluate the initial autonomic response to orthostatic stress, marked by vagal withdrawal and sympathetic activation; the last 5 minutes before the end of the tilt phase (late-tilt) was selected to assess the adaptive response to sustained orthostatic load and capture the persistence or modulation of sympathetic predominance over time; and the last 5 minutes of the recovery phase (recovery), following the return to the supine position, was used to examine the reactivation of parasympathetic activity and overall autonomic recovery after stress exposure. BRS was calculated using only the 10 minutes of data obtained from the tilt phase, when blood pressure perturbations were most pronounced. 2.4.1. Heart rate variability The HRV parameters were extracted in both the time and frequency domains. The time-domain analysis provides information on how specific parameters vary over time, and the frequency-domain analysis indicates which frequency components contribute to those parameters [ 39 ]. In the time domain, the SDNN, the percentage of adjacent NN intervals differing by more than 50 ms (pNN50), and the root mean square of successive differences between adjacent NN intervals (RMSSD) were calculated. In the frequency domain, power spectral density was analyzed within the low-frequency (0.04–0.15 Hz) and high-frequency (0.15–0.40 Hz) bands, and the LF/HF ratio was computed to represent the relative balance between sympathetic and parasympathetic modulation. Definitions of the parameters included in the time- and frequency-domain parameter sets are summarized in Table 1 . Table 1 Definitions of the HRV Parameters Domain Parameter Definition Time domain MeanHR Mean heart rate SDNN Standard deviation of NN intervals RMSSD Root mean square of successive differences between adjacent NN intervals pNNx Percentage of consecutive NN intervals that differ by more than x ms Frequency domain LF Low frequency power calculated by Lomb–Scargle periodogram (0.04–0.15 Hz) HF High frequency power calculated by Lomb–Scargle periodogram (0.15–0.4 Hz) LF/HF ratio Ratio of LF to HF spectral power 2.4.2. Baroreflex sensitivity BRS was used as an index to evaluate baroreflex-mediated autonomic regulation of the cardiovascular system. BRS was estimated by quantifying beat-to-beat changes in inter-beat intervals (IBIs) in response to spontaneous fluctuations in SBP. Inter-beat intervals (IBIs) used for BRS analysis were derived from ECG R–R intervals and are therefore equivalent to the RR intervals used in HRV analysis. In this study, BRS was calculated using the sequence method [ 40 , 41 ], which is based on the beat-to-beat correlation between SBP and IBI. In the sequence method, sequences in which SBP and IBI simultaneously increased or decreased for three or more consecutive beats were identified as up sequences and down sequences, respectively. For each sequence, the linear regression slope between SBP and IBI was calculated. The mean slope of all up sequences was defined as the up-slope BRS, and the mean slope of all down sequences was defined as the down-slope BRS. The overall mean slope of all valid sequences was defined as the all-slope BRS. A sequence was considered valid only when the beat-to-beat changes in SBP and IBI exceeded threshold values of 1 mmHg and 4 ms, respectively [ 42 , 43 ]. In addition, only sequences with a correlation coefficient greater than 0.85 were included in the analysis. 2.5. Statistical analysis All statistical analyses were performed using IBM SPSS version 27 (IBM Corp., Armonk, NY, USA). The normality of each dataset was assessed using the Shapiro-Wilk test. For comparisons within the same session (pre- vs. post-stimulation), between S-baseline values obtained on different days, and within the sham session, either paired t-tests or Wilcoxon signed-rank tests were applied, as appropriate. To correct for multiple comparisons and reduce the risk of type I errors, the false discovery rate adjustment was applied using the Benjamini-Hochberg procedure. All data are expressed the mean \(\:\pm\:\) standard error of the mean (SEM), and statistical significance was set at \(\:\alpha\:=0.05\) 3. Results 3.1. Data acquisition and participant exclusion We initially enrolled 36 participants in this study. Four participants were excluded from the analysis due to poor signal quality or suspected drowsiness based on respiratory monitoring, resulting in a final dataset of 32 participants. The mean age was 25.19 \(\:\pm\:\) 3.3 years, and the sample included 15 males and 17 females. No experimental sessions were stopped due to harms. The mean HR, SBP, and DBP values measured before the experiment are presented in Table 2 . Table 2 Demographic and Psychological Characteristics Characteristic Value Participants 32 (male: 15) Age, years 25.28 ± 3.3 Weight, kg 64.78 ± 14.8 Height, cm 167.43 ± 7.6 SBP, mmHg 109.43 ± 8.8 DBP, mmHg 70.53 ± 8.8 HR, bpm 79.53 ± 11.2 3.2. Baseline HRV equivalence between the taVNS and sham conditions Before comparing the pre- and post-stimulation responses, we compared the HRV parameters between the pre-taVNS S-baseline and the pre-sham S-baseline. No significant differences were observed between the two conditions for any parameter (Table 3 ). Table 3 Comparison of Pre-stimulation S-baseline HRV Between the taVNS and Sham Conditions Parameters Pre-taVNS S-baseline Pre-sham S-baseline p-value Mean SEM Mean SEM SDNN 49.85 3.22 55.77 4 0.3282 Mean HR 70.72 1.4 69.34 1.58 0.3774 RMSSD 37.07 3.13 44.38 3.69 0.101 pNN30 36.14 3.52 42.06 3.79 0.1121 pNN50 16.77 2.81 22.39 3.27 0.1429 LF 3525.04 419.82 4761.75 871.71 0.4698 HF 2469.57 456.67 3289.28 511.69 0.1629 LF/HF ratio 2.02 0.33 1.61 0.18 0.3053 3.3. Differences in autonomic responses from pre- to post-stimulation 3.3.1. Changes in HRV following taVNS stimulation For the active stimulation group, changes in HRV from pre- to post-taVNS at each phase were compared across the four experimental phases (Table 4 and Fig. 2 ). We found that, in the active stimulation condition, taVNS significantly enhanced parasympathetic-related parameters across all phases. In the time domain, SDNN, RMSSD, pNN30, pNN50 increased after stimulation at every phase (SDNN: S-baseline p = 0.0023, early-tilt p = 0.0001, late-tilt p = 0. 0185, recovery p = 0. 0008; RMSSD: S-baseline p = 0. 0009, early-tilt p = 0. 0001, late-tilt p = 0.0005, recovery p = 0. 0016; pNN30: S-baseline p = 0. 0016, early-tilt p = 0. 0022, late-tilt p = 0. 002, recovery p = 0. 002; pNN50: S-baseline p = 0. 0007, early-tilt p = 0. 0048, late-tilt p = 0.0050, recovery p = 0.0094). Mean HR decreased consistently across phases (S-baseline p = 0.0001, early-tilt p = 0.0002, late-tilt p = 0. 0068, recovery p = 0. 0047). In the frequency domain, LF showed no difference at S-baseline ( p = 0. 2540) but increased during early-tilt and recovery (early-tilt p < 0.0001, recovery p = 0. 0084). The LF/HF ratio decreased at S-baseline and late-tilt (S-baseline p = 0. 0056, late-tilt p = 0. 0040) but was not significantly different during early-tilt or recovery (early-tilt p = 0. 8811, recovery p = 0. 3498). In contrast, HF increased significantly at all phases (S-baseline p = 0. 0007, early-tilt p = 0. 0006, late-tilt p = 0. 0023, recovery p = 0. 0002). Table 4 Comparisons of HRV from Pre- to Post-taVNS Across the Four Experimental Phases Phase Parameters Pre-taVNS Post-taVNS p-value Mean SEM Mean SEM S-baseline SDNN 49.85 3.22 65.45 5.08 0.0072 Mean HR 70.72 1.4 65.23 1 0.0007 RMSSD 37.07 3.13 51.33 3.65 0.0038 pNN30 36.14 3.52 51.13 3.35 0.0064 pNN50 16.77 2.81 29.88 3.12 0.0035 LF 3525.04 419.82 5009.67 712.65 0.3416 HF 2469.57 456.67 4647.38 616.33 0.0035 LF/HF ratio 2.02 0.33 1.31 0.16 0.0142 Early-tilt SDNN 52.84 2.12 65.61 2.97 0.0007 Mean HR 83.51 1.69 78.39 1.37 0.0007 RMSSD 21.38 1.38 26.72 1.55 0.0007 pNN30 14.03 2.01 21.25 2.16 0.0072 pNN50 4.23 0.87 7.11 1.07 0.0124 LF 2883.04 261.02 5027.09 629.8 0.0007 HF 761.54 106.18 1392.08 329.39 0.0032 LF/HF ratio 4.92 0.53 5.1 0.55 0.8811 Late-tilt SDNN 42.06 1.89 48.05 2.24 0.0412 Mean HR 83.64 1.73 78.71 1.42 0.0007 RMSSD 20.36 1.25 24.54 1.32 0.0032 pNN30 13.99 1.95 20.88 2.29 0.0072 pNN50 3.33 0.76 5.71 0.94 0.0167 LF 2869.54 293.46 3393.09 279.98 0.101 HF 726.74 93.44 1065.63 111.52 0.0072 LF/HF ratio 5.22 0.54 4.06 0.45 0.0111 Recovery SDNN 53.48 3.66 66.66 4.15 0.0038 Mean HR 68.78 1.37 65.83 1.31 0.0025 RMSSD 40.63 3.1 51.06 3.9 0.0064 pNN30 41.19 3.66 49.38 3.31 0.0072 pNN50 20.73 2.96 28.4 3.04 0.0124 LF 4261.65 762.68 5278.04 616.51 0.0198 HF 2654.83 366.1 4448.16 677.01 0.002 LF/HF ratio 1.81 0.24 1.61 0.25 0.4401 3.3.2. Changes in HRV following sham stimulation Using the same method as in the taVNS HRV analysis, we compared pre-sham and post-sham HRV across all phases. Phase-specific differences in HRV from pre- to post-sham are detailed in Table 5 and Fig. 3 . Although several parameters reached statistical significance, there was no consistent pattern across parameters. Mean HR increased significantly at S-baseline, early-tilt, and late-tilt (S-baseline p = 0.0051, early-tilt p = 0.0010, late-tilt p = 0.0115), and SDNN showed a modest increase at late-tilt ( p = 0.0179). In contrast, key parasympathetic-related parameters—RMSSD, HF power, and LF/HF ratio—did not exhibit consistent changes across phases. Table 5 Comparisons of HRV from Pre- to Post-sham Across the Four Experimental Phases Phase Parameters Pre-sham Post-sham p-value Mean SEM Mean SEM S-baseline SDNN 55.77 4 62.41 4.1 0.1601 Mean HR 69.34 1.58 66.4 1.47 0.0078 RMSSD 44.38 3.69 52.16 4.72 0.2339 pNN30 42.06 3.79 48.09 3.37 0.1657 pNN50 22.39 3.27 27.38 3.3 0.1686 LF 4761.75 871.71 5363.6 790.59 0.2067 HF 3289.28 511.69 4953.67 928.84 0.2459 LF/HF ratio 1.61 0.18 1.51 0.16 0.8811 Early-tilt SDNN 60.09 3.38 64.68 2.89 0.1601 Mean HR 81.77 1.75 77.45 1.64 0.0024 RMSSD 25.65 1.55 30.4 2.52 0.0589 pNN30 19.88 2.11 23.05 2.73 0.0513 pNN50 6.21 1.1 9.58 1.99 0.3137 LF 3194.4 360.78 4799.26 614.97 0.0078 HF 1125.69 147.06 1910.46 428.87 0.3371 LF/HF ratio 3.49 0.42 3.61 0.35 0.4401 Late-tilt SDNN 47.68 2.69 53.89 4.22 0.0524 Mean HR 81.81 1.84 78.1 1.85 0.028 RMSSD 24.65 1.43 28.6 3 0.3137 pNN30 20.36 2.23 23.03 3.3 0.33 pNN50 5.81 1.06 9.35 2.43 0.5505 LF 3710.91 544.17 4551.95 947.51 0.7894 HF 1154.42 149.05 1723.43 415.47 0.3568 LF/HF ratio 3.95 0.47 3.53 0.39 0.475 Recovery SDNN 65.53 3.29 67.97 4.66 0.5454 Mean HR 67.18 1.53 65.06 1.46 0.1223 RMSSD 54.97 4.04 59.91 8.26 0.8669 pNN30 52.11 3.5 50.24 3.95 0.8478 pNN50 31.49 3.25 30.8 3.9 0.719 LF 5449.6 609.15 5661.29 1201.64 0.7696 HF 4901.47 733.79 5166.3 1018.93 0.8478 LF/HF ratio 1.7 0.3 1.64 0.26 0.8811 3.4. Differences in baroreflex-mediated autonomic control from pre- to post-stimulation 3.4.1. Changes in BRS during taVNS stimulation BRS was used to assess the effect of taVNS on baroreflex control during induced blood pressure perturbation (tilt). The up-slope BRS increased from 9.59 ± 0.52 to 12.1 ± 0.66 ms/mmHg (p = 0.0004), and the down-slope BRS increased from 9.28 ± 0.63 to 12.16 ± 0.61 ms/mmHg (p = 0.0001) (Table 6 and Fig. 4 ). Table 6 Comparison of BRS from Pre- to Post-taVNS Across Tilt Sessions Parameters Tilt (10 min) Pre-taVNS Post-taVNS p-value Mean SEM Mean SEM Up-slope 9.59 0.52 12.1 0.66 0.0025 Down-slope 9.28 0.63 12.16 0.61 0.0007 All-slope 9.43 0.55 12.13 0.59 0.0008 3.4.2. Changes in BRS during sham stimulation As in the taVNS analysis, BRS was evaluated pre- and post-sham during the tilt phase (Table 7 and Fig. 5 ). No significant differences were observed for either the up-slope or down-slope values (up-slope: 12.18 \(\:\pm\:\) 0.83 to 13.23 \(\:\pm\:\) 1.36, p = 0. 8664; down-slope: 12.16 \(\:\pm\:\) 0.73 to 13.03 \(\:\pm\:\) 1.15 p = 0. 5249). Table 7 Comparison of BRS from Pre- to Post-sham Across Tilt Sessions Parameters Tilt (10 min) Pre-sham Post-sham p-value Mean SEM Mean SEM Up-slope 12.18 0.83 13.23 1.36 0.8811 Down-slope 12.16 0.73 13.03 1.15 0.6111 All-slope 12.17 0.74 13.13 1.2 0.8478 3.5. Response to taVNS was predicted by baseline autonomic tone To evaluate whether baseline autonomic tone predicts responsiveness to taVNS, we conducted linear regression analyses between the pre-taVNS S-baseline autonomic parameters and taVNS-induced changes. Among the frequency-domain parameters, a strong negative correlation was found between the pre-taVNS LF/HF ratio and its post-taVNS change (R² = 0.78, p < 0.0001), indicating that individuals with higher sympathetic predominance at baseline experienced greater reductions following taVNS. The mean pre-taVNS HR also showed a significant negative correlation with its change (R² = 0.50, p < 0.0001). In the time domain, moderate negative correlations were observed between the baseline parasympathetic markers—RMSSD (R² = 0.17, p = 0.0204), pNN30 (R² = 0.35, p = 0.0003), and pNN50 (R² = 0.20, p = 0.0096)—and their respective changes. These findings suggest that individuals with reduced baseline parasympathetic activity demonstrated greater improvements following taVNS (Fig. 6 ). In our analysis of BRS, we observed changes during the tilt sessions. The changes in BRS down-slope (R² = 0.22, p = 0.0062) and all-slope (R² = 0.14, p = 0.0385) showed significant negative correlations with the baseline values, implying enhanced baroreflex responsiveness, particularly in individuals with lower pre-taVNS BRS (Fig. 7 ). 4. Discussion In this study, we investigated the effects of taVNS on autonomic function by using the HUTT both pre- and post- stimulation. HRV was compared across the S-baseline, tilt, and recovery phases, whereas BRS was specifically analyzed during the tilt phase to evaluate autonomic responsiveness during induced blood pressure perturbation. In our normotensive participants, these analyses quantified the effects of taVNS during hemodynamic stress, demonstrating its capacity to enhance autonomic regulation, particularly baroreflex-mediated control. Collectively, our findings underscore the therapeutic potential of taVNS in restoring and strengthening autonomic responsiveness, which has significant implications for conditions characterized by autonomic dysfunction, such as hypertension. 4.1. Autonomic regulation reflected in HRV responses to taVNS In the S-baseline phase, most of the parasympathetic HRV parameters, particularly RMSSD, pNN50, and HF power, increased significantly, though the LF/HF ratio did not. This pattern suggests that taVNS facilitates parasympathetic activation at baseline, consistent with enhanced vagal control of the heart rate. For example, Geng et al. (2022) reported significant increases in parasympathetic HRV parameters following short taVNS sessions in young adults [ 36 ]. Also, Clancy et al. (2014) reported a reduction in the LF/HF ratio, indicating sympathetic inhibition and parasympathetic enhancement [ 31 ]. The LF/HF ratio did not change significantly in this study, which could reflect differences in stimulation duration and protocol. Nonetheless, taken together with the consistent increases in multiple parasympathetic parameters, our results support the view that taVNS attenuates relative sympathetic predominance while augmenting parasympathetic modulation [ 44 ]. By contrast, in the sham condition, some parameters reached statistical significance, but no consistent pattern was observed across parameters or phases. In particular, key parasympathetic markers (RMSSD, HF, LF/HF ratio) did not show consistent changes. These observations indicate that the HRV changes identified here are unlikely to be attributable to the mere passage of time or nonspecific factors but rather reflect physiological effects of taVNS. During the tilt phase, gravitational pooling typically elicits an increase in sympathetic activity and a suppression of vagal activity, thereby reducing parasympathetic HRV parameters and elevating the LF/HF ratio [ 45 , 46 ]. Nevertheless, in this study, the HRV parameters improved during tilt following taVNS, suggesting that taVNS might partially attenuate tilt-induced vagal withdrawal and enhance overall autonomic responsiveness. These effects can be interpreted as the afferent activation of the ABVN converging on the NTS, which in turn augments vagal efferent output via the NA/DMV and concurrently suppresses the sympathetic drive through the CVLM–RVLM pathway [ 47 – 49 ]. The HRV changes observed in this study are also consistent with afferent activation of the ABVN converging on the NTS and thereby enhancing vagal (parasympathetic) efferent output. Moreover, the improvement in HRV during the tilt phase suggests that taVNS might preserve vagal tone and enhance autonomic responsiveness during orthostatic stress. In contrast, in the sham condition, some parameters reached statistical significance, but no consistent pattern emerged across parameters or phases. Taken together, our results support the interpretation that the HRV effects reflect physiological mechanisms of taVNS, rather than the placebo effect or passage of time. 4.2. Baroreflex sensitivity enhancement during orthostatic stress Beyond HRV, we assessed BRS to quantify reflex control of the heart rate in response to blood pressure changes–a physiologically critical mechanism for short-term cardiovascular stability [ 50 , 51 ]. Importantly, compared with HRV, which provides indirect insights into autonomic modulation, BRS offers a more mechanistically specific index of baroreflex-mediated autonomic control because it directly reflects the dynamic interplay between SBP and IBI. In this study, we examined BRS during the tilt phase, a condition of orthostatic stress that physiologically induces gravitational pooling, lowering arterial pressure and typically eliciting increased sympathetic activation and vagal withdrawal [ 52 , 53 ]. That process often leads to a blunted baroreflex response in healthy individuals. However, our findings revealed that both the up-slope and down-slope BRS values increased significantly during the tilt phase after taVNS, indicating a marked enhancement of IBI responsiveness to blood pressure perturbation under stress. This suggests that taVNS can actively counteract tilt-induced autonomic imbalances by reinforcing baroreflex engagement [ 54 ]. This pattern is presumed to involve afferent activation of the ABVN, which projects to the NTS in the brainstem. This afferent input could facilitate parasympathetic outflow via the NA and DMV, while simultaneously suppressing sympathetic tone via the CVLM–RVLM inhibitory pathway. These neural interactions together strengthen baroreflex arc functionality and autonomic adaptability. In contrast, in the sham condition, BRS showed no significant change from pre- to post-stimulation, supporting the interpretation that the taVNS effect reflects physiological activation of the baroreflex pathway rather than the passage of time or expectancy. Reduced BRS is strongly associated with increased cardiovascular risk, including in patient populations with hypertension, orthostatic hypotension, and autonomic dysfunction [ 55 , 56 ]. Therefore, the findings of this study have significant translational potential. The taVNS-induced BRS enhancement observed here supports the utility of this intervention for restoring reflex autonomic balance in clinical populations. In sum, whereas the HRV analysis demonstrated enhanced parasympathetic modulation, the BRS findings provide direct, phase-specific evidence that taVNS strengthens cardiovascular reflex regulation during physiological stress, underscoring BRS modulation during tilt as the most clinically meaningful outcome of this study [ 57 ]. 4.3. Predictive role of baseline autonomic tone in taVNS responsiveness The results of the regression analysis indicate that the autonomic regulatory effects of taVNS can vary depending on an individual's baseline level of autonomic activity. The strong inverse association between the baseline LF/HF ratio and its reduction after stimulation underscores the potential of taVNS to correct autonomic imbalance, particularly in individuals with sympathetic predominance. These results align with previous findings suggesting that the effects of taVNS might be more prominent in individuals with reduced baseline autonomic balance [ 58 ]. Similarly, greater improvements in RMSSD, pNN30, and pNN50 in participants with low initial parasympathetic tone suggest that taVNS could be especially effective in restoring vagal modulation in hypoactive states [ 59 , 60 ]. Importantly, the observation that lower baseline BRS predicted greater improvements in baroreflex function highlights a key mechanistic pathway of taVNS beyond heart rate modulation. These findings support the view that baseline autonomic markers could serve as useful predictors of individualized taVNS responsiveness and inform future clinical applications, particularly in populations with autonomic dysregulation such as hypertension or orthostatic intolerance. 4.4. Novelty and contributions Most prior taVNS studies have assessed autonomic modulation at rest, used short stimulation durations, and focused on HRV. Even when BRS was assessed, measurements were typically restricted to resting conditions without sufficient blood pressure perturbation, limiting the physiological relevance and interpretability of baroreflex responsiveness. To validate the effects of taVNS in more physiologically meaningful conditions, we applied 60 minutes of taVNS at rest and subsequently induced controlled blood pressure perturbation using the HUTT. With its phased structure (S-baseline–tilt–recovery), the HUTT enables standardized observation of autonomic regulation at S-baseline, during orthostatic stress, and throughout recovery, thereby providing an excellent framework for evaluating functional resilience and stress adaptability beyond resting conditions. Our combined analysis of HRV and BRS data collected using this design demonstrates not only basal enhancement of parasympathetic activity, as evidenced by significant increases in the parasympathetic HRV parameters (e.g., HF, RMSSD) at S-baseline, but also a significant improvement in BRS during the tilt phase, confirming that taVNS can support baroreceptor reflex pathways in response to blood pressure perturbation. This enhancement of BRS during orthostatic stress is a central and novel contribution of this study. Our findings suggest that taVNS can reinforce short-term cardiovascular reflexes precisely when autonomic demand is heightened. In addition, the inclusion of a sham condition allowed us to control for potential changes in autonomic parameters due to the mere passage of time or placebo effects. In the sham sessions, BRS showed no significant changes, and although the changes in some HRV parameters reached significance, the findings did not form a consistent pattern. Collectively, these results support the interpretation that taVNS strengthens autonomic regulation via ABVN–NTS pathways, rather than reflecting nonspecific or placebo effects. 4.5. Limitations This study has several limitations. First, although our design induced blood pressure perturbation to evaluate autonomic responsiveness beyond resting conditions, our study population consisted of healthy adults, which limits the clinical generalizability of our results. In patient populations with autonomic abnormalities (e.g., hypertension, orthostatic hypotension, autonomic failure), responses to taVNS might differ. Therefore, follow-up studies with those groups are warranted. Second, because our participants were predominantly young adults, our findings might not fully capture age-related differences in autonomic responsiveness and taVNS effects. Given that autonomic flexibility and baroreflex function typically decline with age, taVNS efficacy could vary across age groups, underscoring the need for studies that include a broader age range. Third, we examined acute responses within a single session; therefore, we could not assess the cumulative effects of repeated or prolonged stimulation or potential residual effects after stimulation cessation. Future investigations using longitudinal designs are needed to determine the durability and stability of taVNS effects. In light of those limitations, future work should apply the present protocol to patients with hypertension or autonomic dysfunction and compare their responses with healthy controls to more clearly establish the therapeutic relevance of taVNS. Moreover, repeated and long-term stimulation with follow-up assessments of HRV and BRS will be important to determine whether taVNS offers sustained or cumulative benefits for blood pressure regulation and autonomic function. Such studies would provide empirical support for implementing taVNS as a noninvasive antihypertensive therapy and a strategy for autonomic reconditioning. 5. Conclusion This study quantitatively evaluated the effects of taVNS on autonomic function during blood pressure perturbation by analyzing HRV and BRS and characterizing autonomic responsiveness. We found that taVNS enhanced parasympathetic modulation and improved baroreflex responsiveness, not only at baseline but also during orthostatic stress. In comparison with the sham condition, the changes are consistent with a physiological mechanism, rather than a placebo effect. Importantly, our findings extend the evidence for taVNS beyond resting conditions to periods of rapid autonomic change, supporting its potential applicability in clinical populations with autonomic dysfunction, such as hypertension. Declarations Funding This work was supported by a National Research Foundation of Korea (NRF) grant funded by the Korean government (MSIT) (RS-2024-00333219). Author contributions G.L: Wrting – original draft, Visualization, Validation, Software, Methodology, Formal analysis, Data curation, Conceptualization. D.K: Writing – original draft, review & editing, Methodology, Formal analysis, Data curation, Conceptualization. J.L: Data curation. J.L: Writing – review & editing, Supervision. J.L: Writing – review & editing, Supervision, Project administration. I.Y.K: Writing - review & editing, Supervision, Funding acquisition. Declaration of competing interest The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper. Data Availability The datasets generated during and/or analyzed during the current study are available from the corresponding author on reasonable request. 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Effects of stimulus frequency, intensity, and sex on the autonomic response to transcutaneous vagus nerve stimulation. Brain Sci. 12 (8), 1038 (2022). Additional Declarations No competing interests reported. Cite Share Download PDF Status: Under Review Version 1 posted Reviews received at journal 28 Apr, 2026 Reviewers agreed at journal 25 Apr, 2026 Reviewers agreed at journal 23 Apr, 2026 Reviewers agreed at journal 22 Apr, 2026 Reviewers agreed at journal 20 Apr, 2026 Reviewers invited by journal 20 Apr, 2026 Editor assigned by journal 20 Apr, 2026 Editor invited by journal 27 Mar, 2026 Submission checks completed at journal 25 Mar, 2026 First submitted to journal 25 Mar, 2026 You are reading this latest preprint version Research Square lets you share your work early, gain feedback from the community, and start making changes to your manuscript prior to peer review in a journal. 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Also discoverable on Platform About Our Team In Review Editorial Policies Advisory Board Help Center Resources Author Services Accessibility API Access RSS feed Manage Cookie Preferences © Research Square 2026 | ISSN 2693-5015 (online) Privacy Policy Terms of Service Do Not Sell My Personal Information {"props":{"pageProps":{"initialData":{"identity":"rs-8923528","acceptedTermsAndConditions":true,"allowDirectSubmit":false,"archivedVersions":[],"articleType":"Article","associatedPublications":[],"authors":[{"id":629491708,"identity":"849b4649-ed17-4f1b-85e4-952c5a6d8d5a","order_by":0,"name":"Geonhee Lee","email":"","orcid":"","institution":"Hanyang University","correspondingAuthor":false,"prefix":"","firstName":"Geonhee","middleName":"","lastName":"Lee","suffix":""},{"id":629491709,"identity":"08ffc5d8-cad4-4616-8596-3a1ac00cab01","order_by":1,"name":"Donghun Kang","email":"","orcid":"","institution":"Hanyang University","correspondingAuthor":false,"prefix":"","firstName":"Donghun","middleName":"","lastName":"Kang","suffix":""},{"id":629491711,"identity":"137c8b0c-06df-45d5-8e61-c758fa1a3e67","order_by":2,"name":"Jiseok Lee","email":"","orcid":"","institution":"Hanyang University","correspondingAuthor":false,"prefix":"","firstName":"Jiseok","middleName":"","lastName":"Lee","suffix":""},{"id":629491712,"identity":"a06245a5-d3e6-4c93-91e3-372b4ca3e2c4","order_by":3,"name":"Jongshill Lee","email":"","orcid":"","institution":"Hanyang University","correspondingAuthor":false,"prefix":"","firstName":"Jongshill","middleName":"","lastName":"Lee","suffix":""},{"id":629491713,"identity":"1d20ce98-1c7b-4b7a-8697-612cb0079cbc","order_by":4,"name":"Jeyeon Lee","email":"data:image/png;base64,iVBORw0KGgoAAAANSUhEUgAAAZAAAAAyAQMAAABI0h/eAAAABlBMVEX///8AAABVwtN+AAAACXBIWXMAAA7EAAAOxAGVKw4bAAABCklEQVRIiWNgGAWjYBACxgYwZcHAwN6DLH6AoBYJBgaeM0RqgQKgFokcIrUwt/cYPvi4Q0KOX/Ltwc+FbXZ58g7MDz8wnLmH22E9Z4wNZ56RMJacnZcsPbMtudjwAJuxBMONYtxaZuSYSfO2SSRuuJ1jAGQwJ25sYDBjYPiQgFvL/Dfmv4Fa6vffPGMMZNQDtbB/w69lBo8ZM1BLgoEED8i6w4nzGXiAttzAo6UnrVhyZpuE4YwzOWbWPOeOJ25g5imWSDiDW4th++GNHz622cjzt58xvs1TVp04v71944cPx/BoaeAwQLKTjYHB4DCQgVsDA4M8A/sDJO4foEgDHuWjYBSMglEwIgEA7wNTlyaCDn4AAAAASUVORK5CYII=","orcid":"","institution":"Hanyang University","correspondingAuthor":true,"prefix":"","firstName":"Jeyeon","middleName":"","lastName":"Lee","suffix":""},{"id":629491714,"identity":"3fd29ffd-0ac0-478f-9b87-62ef94b1faad","order_by":5,"name":"In Young Kim","email":"","orcid":"","institution":"Hanyang University","correspondingAuthor":false,"prefix":"","firstName":"In","middleName":"Young","lastName":"Kim","suffix":""}],"badges":[],"createdAt":"2026-02-20 07:57:48","currentVersionCode":1,"declarations":"","doi":"10.21203/rs.3.rs-8923528/v1","doiUrl":"https://doi.org/10.21203/rs.3.rs-8923528/v1","draftVersion":[],"editorialEvents":[],"editorialNote":"","failedWorkflow":false,"files":[{"id":108072604,"identity":"be277651-5ae9-4413-a62d-a35ef56bbbe5","added_by":"auto","created_at":"2026-04-29 06:14:29","extension":"png","order_by":1,"title":"Figure 1","display":"","copyAsset":false,"role":"figure","size":171123,"visible":true,"origin":"","legend":"\u003cp\u003eExperimental protocol used in this study.\u003c/p\u003e","description":"","filename":"image1.png","url":"https://assets-eu.researchsquare.com/files/rs-8923528/v1/053f21d06543659772b09cd8.png"},{"id":108490907,"identity":"5c90eb84-7dbd-470c-a46d-c92fd5c00215","added_by":"auto","created_at":"2026-05-05 09:49:47","extension":"png","order_by":2,"title":"Figure 2","display":"","copyAsset":false,"role":"figure","size":391835,"visible":true,"origin":"","legend":"\u003cp\u003eViolin plots illustrating the distribution of HRV parameters across the four physiological phases (S-baseline, early-tilt, late-tilt, recovery), pre- and post-taVNS. Blue represents pre-taVNS and red indicates post-taVNS values. Solid horizontal lines indicate the medians; dotted lines represent quartiles. * \u003cem\u003ep\u003c/em\u003e \u0026lt;0.05, ** \u003cem\u003ep\u003c/em\u003e \u0026lt;0.01, *** \u003cem\u003ep\u003c/em\u003e \u0026lt;0.001, paired t-tests or Wilcoxon signed-rank tests.\u003c/p\u003e","description":"","filename":"image2.png","url":"https://assets-eu.researchsquare.com/files/rs-8923528/v1/1484e299e0aa2faa3c97151a.png"},{"id":108072606,"identity":"f7b204a6-f02c-4f0e-8480-2ce1361f720b","added_by":"auto","created_at":"2026-04-29 06:14:30","extension":"png","order_by":3,"title":"Figure 3","display":"","copyAsset":false,"role":"figure","size":358696,"visible":true,"origin":"","legend":"\u003cp\u003eViolin plots illustrating the distribution of HRV parameters across the four physiological phases (S-baseline, early-tilt, late-tilt, recovery), pre- and post-sham. Blue represents pre-sham, and red indicates post-sham values. 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Solid horizontal lines indicate the medians; dotted lines represent quartiles. ** \u003cem\u003ep\u003c/em\u003e \u0026lt;0.01, *** \u003cem\u003ep\u003c/em\u003e \u0026lt;0.001, paired t-tests or Wilcoxon signed-rank tests.\u003c/p\u003e","description":"","filename":"image4.png","url":"https://assets-eu.researchsquare.com/files/rs-8923528/v1/881aa76b2124f66a14898be3.png"},{"id":108181610,"identity":"f7a4e065-9425-4bea-853a-175b3d9892a5","added_by":"auto","created_at":"2026-04-30 08:58:47","extension":"png","order_by":5,"title":"Figure 5","display":"","copyAsset":false,"role":"figure","size":246329,"visible":true,"origin":"","legend":"\u003cp\u003eViolin plots illustrating the distribution of BRS parameters across tilt sessions, pre- and post-sham. Blue represents pre-sham values and red indicates post-sham values. Solid horizontal lines indicate the medians; dotted lines represent quartiles. Statistical comparisons were performed using paired t-tests or Wilcoxon signed-rank tests, as appropriate.\u003c/p\u003e","description":"","filename":"image5.png","url":"https://assets-eu.researchsquare.com/files/rs-8923528/v1/dbed0d2d106305ec6cb87ac0.png"},{"id":108072609,"identity":"881e5c90-b5cf-470e-856f-2413363eafd6","added_by":"auto","created_at":"2026-04-29 06:14:30","extension":"png","order_by":6,"title":"Figure 6","display":"","copyAsset":false,"role":"figure","size":297443,"visible":true,"origin":"","legend":"\u003cp\u003eScatterplots showing the association between pre-taVNS HRV parameters and the changes induced by taVNS. All HRV parameters are from the S-baseline phase.\u003c/p\u003e","description":"","filename":"image6.png","url":"https://assets-eu.researchsquare.com/files/rs-8923528/v1/d2f6590d5a9793ea45faeb95.png"},{"id":108072610,"identity":"91d1e439-8ce0-4813-bb82-7bdedbec533e","added_by":"auto","created_at":"2026-04-29 06:14:30","extension":"png","order_by":7,"title":"Figure 7","display":"","copyAsset":false,"role":"figure","size":111927,"visible":true,"origin":"","legend":"\u003cp\u003eScatterplots showing the association between pre-taVNS BRS parameters and the changes induced by taVNS. All BRS parameters are from the tilt sessions.\u003c/p\u003e","description":"","filename":"image7.png","url":"https://assets-eu.researchsquare.com/files/rs-8923528/v1/f9c5f390ee184c5f2d6d491a.png"},{"id":108494808,"identity":"28ec3de8-e462-4bb5-9bb1-137ac7440574","added_by":"auto","created_at":"2026-05-05 10:07:30","extension":"pdf","order_by":0,"title":"","display":"","copyAsset":false,"role":"manuscript-pdf","size":2049893,"visible":true,"origin":"","legend":"","description":"","filename":"manuscript.pdf","url":"https://assets-eu.researchsquare.com/files/rs-8923528/v1/8fec2469-edd5-4e9a-a3b9-bb374a2ba914.pdf"}],"financialInterests":"No competing interests reported.","formattedTitle":"Analysis of taVNS Effects on Baroreflex Sensitivity and Autonomic Nervous System Regulation During Head-up Tilt Test","fulltext":[{"header":"1. Introduction","content":"\u003cp\u003e \u003cdiv class=\"BlockQuote\"\u003e \u003cp\u003eHypertension is one of the most prevalent risk factors for cardiovascular disease and affects more than 1.4\u0026nbsp;billion individuals worldwide [\u003cspan citationid=\"CR1\" class=\"CitationRef\"\u003e1\u003c/span\u003e]. Despite its high prevalence, only about 44% of hypertension patients receive a diagnosis and treatment, and among those undergoing therapy, only 23% achieve adequate blood pressure control [\u003cspan citationid=\"CR2\" class=\"CitationRef\"\u003e2\u003c/span\u003e]. The current standard of care relies primarily on pharmacological therapy; however, several limitations persist, including low medication adherence due to combination drugs, interindividual variability in drug responsiveness, and adverse side effects associated with antihypertensive agents [\u003cspan citationid=\"CR3\" class=\"CitationRef\"\u003e3\u003c/span\u003e]. Consequently, interest in developing alternative therapeutic strategies that are both effective and minimally invasive has been growing.\u003c/p\u003e \u003cp\u003eHypertension is a multifactorial disorder, and autonomic nervous system (ANS) dysfunction has been recognized as a key pathophysiological contributor [\u003cspan additionalcitationids=\"CR5\" citationid=\"CR4\" class=\"CitationRef\"\u003e4\u003c/span\u003e\u0026ndash;\u003cspan citationid=\"CR6\" class=\"CitationRef\"\u003e6\u003c/span\u003e]. Among cardiovascular regulatory mechanisms, the baroreflex plays a crucial role in maintaining autonomic balance and blood pressure homeostasis [\u003cspan additionalcitationids=\"CR8\" citationid=\"CR7\" class=\"CitationRef\"\u003e7\u003c/span\u003e\u0026ndash;\u003cspan citationid=\"CR9\" class=\"CitationRef\"\u003e9\u003c/span\u003e]. When blood pressure rises, baroreceptors detect the blood pressure change and transmit afferent signals to the nucleus tractus solitarius (NTS) via the vagus nerve (VN) [\u003cspan citationid=\"CR10\" class=\"CitationRef\"\u003e10\u003c/span\u003e, \u003cspan citationid=\"CR11\" class=\"CitationRef\"\u003e11\u003c/span\u003e]. As a result, reductions in heart rate and myocardial contractility, accompanied by an increase in heart rate variability (HRV), contribute to the maintenance of cardiovascular homeostasis [\u003cspan citationid=\"CR12\" class=\"CitationRef\"\u003e12\u003c/span\u003e]. In hypertensive patients, however, impaired baroreflex function leads to sympathetic overactivation and parasympathetic withdrawal, resulting in diminished reflex modulation capacity against blood pressure fluctuations [\u003cspan additionalcitationids=\"CR14 CR15\" citationid=\"CR13\" class=\"CitationRef\"\u003e13\u003c/span\u003e\u0026ndash;\u003cspan citationid=\"CR16\" class=\"CitationRef\"\u003e16\u003c/span\u003e]. Those abnormalities lead to sustained elevation of blood pressure and impaired blood pressure control [\u003cspan citationid=\"CR17\" class=\"CitationRef\"\u003e17\u003c/span\u003e, \u003cspan citationid=\"CR18\" class=\"CitationRef\"\u003e18\u003c/span\u003e]. Thus, restoring vagal function or enhancing baroreflex sensitivity could have promising therapeutic potential for autonomic dysfunction\u0026ndash;related hypertension.\u003c/p\u003e \u003cp\u003eThe VN is a major component of the ANS and plays a crucial role in parasympathetic regulation. The VN is a mixed nerve composed of both afferent (sensory) and efferent (motor) fibers, with approximately 80% being afferent and 20% efferent [\u003cspan citationid=\"CR10\" class=\"CitationRef\"\u003e10\u003c/span\u003e, \u003cspan citationid=\"CR19\" class=\"CitationRef\"\u003e19\u003c/span\u003e, \u003cspan citationid=\"CR20\" class=\"CitationRef\"\u003e20\u003c/span\u003e]. The afferent fibers transmit sensory information about blood pressure changes from peripheral organs such as the heart, lungs, and viscera to the NTS in the medulla [\u003cspan citationid=\"CR8\" class=\"CitationRef\"\u003e8\u003c/span\u003e, \u003cspan citationid=\"CR21\" class=\"CitationRef\"\u003e21\u003c/span\u003e]. The NTS integrates that information and modulates parasympathetic output via the nucleus ambiguous (NA) and the dorsal motor nucleus of the vagus (DMV), while simultaneously inhibiting sympathetic tone by activating the caudal ventrolateral medulla (CVLM) and suppressing the rostral ventrolateral medulla (RVLM). Efferent vagal fibers transmit those output signals to the sinoatrial node, atrioventricular node, and ventricular myocardium, thereby reducing the heart rate and contractility to maintain cardiovascular stability [\u003cspan citationid=\"CR7\" class=\"CitationRef\"\u003e7\u003c/span\u003e, \u003cspan citationid=\"CR22\" class=\"CitationRef\"\u003e22\u003c/span\u003e]. Because of those physiological properties, modulation of vagal activity has therapeutic potential for restoring autonomic balance and mitigating cardiovascular risks such as hypertension.\u003c/p\u003e \u003cp\u003eVagus nerve stimulation (VNS) is a neuromodulation approach involving the application of electrical impulses to the VN to modulate ANS function [\u003cspan citationid=\"CR19\" class=\"CitationRef\"\u003e19\u003c/span\u003e, \u003cspan citationid=\"CR20\" class=\"CitationRef\"\u003e20\u003c/span\u003e, \u003cspan citationid=\"CR23\" class=\"CitationRef\"\u003e23\u003c/span\u003e, \u003cspan citationid=\"CR24\" class=\"CitationRef\"\u003e24\u003c/span\u003e]. Invasive VNS is performed by surgically implanting electrodes around the VN and connecting them to a pulse generator. This approach is approved by the US Food and Drug Administration for the treatment of epilepsy and depression [\u003cspan citationid=\"CR25\" class=\"CitationRef\"\u003e25\u003c/span\u003e]. In animal studies, invasive VNS has been shown to reduce blood pressure and improve autonomic regulation [\u003cspan citationid=\"CR26\" class=\"CitationRef\"\u003e26\u003c/span\u003e]. However, the surgical procedure is associated with risks of complications such as infection, coughing, and voice alteration [\u003cspan citationid=\"CR27\" class=\"CitationRef\"\u003e27\u003c/span\u003e]. To prevent those risks, transcutaneous auricular vagus nerve stimulation (taVNS) has been proposed as a noninvasive, low-cost alternative [\u003cspan citationid=\"CR28\" class=\"CitationRef\"\u003e28\u003c/span\u003e, \u003cspan citationid=\"CR29\" class=\"CitationRef\"\u003e29\u003c/span\u003e]. taVNS stimulates the auricular branch of the vagus nerve (ABVN), which is located in the cymba concha and tragus of the ear [\u003cspan citationid=\"CR30\" class=\"CitationRef\"\u003e30\u003c/span\u003e]. Recent studies have reported that taVNS increases parasympathetic activity and improves HRV, and it has gained attention as a safe and effective method for autonomic modulation. Clancy et al. (2014) demonstrated that taVNS increased HRV and decreased muscle sympathetic nerve activity in healthy adults, promoting a shift toward parasympathetic predominance [\u003cspan citationid=\"CR31\" class=\"CitationRef\"\u003e31\u003c/span\u003e]. De Couck et al. (2017) reported that short (10 min) and long (1 h) taVNS sessions produced moderate increases in HRV parameters, such as the standard deviation of normal-to-normal intervals (SDNN), with more pronounced effects in females than males [\u003cspan citationid=\"CR32\" class=\"CitationRef\"\u003e32\u003c/span\u003e]. Moreover Antonino et al. (2017) showed that taVNS significantly enhanced cardiac baroreflex sensitivity (BRS) and reduced the low frequency/high frequency (LF/HF) ratio within a short period, confirming its parasympathetic activation effect [\u003cspan citationid=\"CR33\" class=\"CitationRef\"\u003e33\u003c/span\u003e].\u003c/p\u003e \u003cp\u003eMost previous taVNS studies have compared pre- and post-stimulation changes in resting conditions. Although that approach is useful for observing the effects of taVNS on baseline parasympathetic activity, it provides little information about reflex autonomic responsiveness during physiological stress such as blood pressure perturbation. Because the baroreflex is not fully activated in resting conditions, it is difficult to clearly determine the regulatory effects of taVNS on baroreflex function. Therefore, evaluating the effects of taVNS during conditions that induce blood pressure perturbation will provide more physiologically meaningful information for understanding its influence on baroreflex-mediated autonomic control.\u003c/p\u003e \u003cp\u003eThe head-up tilt test (HUTT) is a standard method used to induce blood pressure perturbation. During the HUTT, the transition from the supine to the tilt position causes blood to pool in the lower extremities under the influence of gravity, leading to transient reductions in central venous return, stroke volume, and arterial pressure. As a result, a transient hypotensive state occurs, activating the baroreflex, which increases sympathetic activity and suppresses parasympathetic tone to restore and maintain blood pressure. During this process, the heart rate increases and vascular tone is adjusted, allowing the ANS to compensate for the instability caused by postural change [\u003cspan citationid=\"CR34\" class=\"CitationRef\"\u003e34\u003c/span\u003e, \u003cspan citationid=\"CR35\" class=\"CitationRef\"\u003e35\u003c/span\u003e]. Therefore, the HUTT is a useful method for eliciting the autonomic responses associated with postural transitions and evaluating baroreflex-mediated autonomic regulation and the dynamic adaptability of the cardiovascular system, making it suitable for investigating how taVNS affects blood pressure control and autonomic responsiveness.\u003c/p\u003e \u003cp\u003eIn this study, we used the HUTT protocol to identify the effects of taVNS on baroreflex-mediated autonomic responses during induced blood pressure perturbation. This approach allowed us to examine the physiological influence of taVNS in healthy subjects, thereby establishing a foundation for future applications in clinical populations with autonomic dysfunctions such as hypertension. First, we compared changes in HRV and BRS pre- and post-stimulation within the perturbation phases to evaluate the acute effects of taVNS on cardiovascular regulation. Second, we compared those physiological responses between taVNS and a sham condition to verify that specific autonomic effects were attributable to taVNS.\u003c/p\u003e \u003c/div\u003e \u003c/p\u003e"},{"header":"2. Methods","content":"\u003cdiv id=\"Sec3\" class=\"Section2\"\u003e \u003ch2\u003e2.1. Participants\u003c/h2\u003e \u003cp\u003e\u003cdiv class=\"BlockQuote\"\u003e\u003cp\u003eThis study enrolled healthy participants with normal blood pressure. None of the participants had a history of cardiovascular disease, epilepsy, or recurrent syncope. Participants were instructed to abstain from caffeine, alcohol, and nicotine for at least 12 hours before the experiment. This study was approved by the Institutional Review Board of Hanyang University, and all experimental processes were conducted in accordance with the guidelines of the Declaration of Helsinki (HYUIRB-202501-005-2). This trial was registered on (03/20/2026) at \u003cspan class=\"ExternalRef\"\u003e\u003cspan class=\"RefSource\"\u003ehttps://cris.nih.go.kr/cris/index/index.do\u003c/span\u003e\u003cspan address=\"https://cris.nih.go.kr/cris/index/index.do\" targettype=\"URL\" class=\"RefTarget\"\u003e\u003c/span\u003e\u003c/span\u003e (KCT0011752). The experiment was conducted in Room 204 of College of Medicine Ⅱ at Hanyang University. Written informed consent was obtained from all participants before their enrollment. Sample size was estimated using G*Power based on the effect size reported in a previous study[\u003cspan citationid=\"CR36\" class=\"CitationRef\"\u003e36\u003c/span\u003e]. Using η\u0026sup2; = 0.082, corresponding to an effect size of f\u0026thinsp;=\u0026thinsp;0.2988722, with α\u0026thinsp;=\u0026thinsp;0.05, power\u0026thinsp;=\u0026thinsp;0.95, two groups, three measurements, a correlation among repeated measures of 0.5, and a nonsphericity correction of 1, the required sample size was calculated to be 32 participants.\u003c/p\u003e\u003c/div\u003e\u003c/p\u003e \u003c/div\u003e \u003cdiv id=\"Sec4\" class=\"Section2\"\u003e \u003ch2\u003e2.2. Measurement systems\u003c/h2\u003e \u003cp\u003e \u003cdiv class=\"BlockQuote\"\u003e \u003cp\u003eElectrocardiogram (ECG) and blood pressure data were collected using a Task Force\u0026reg; Monitor 3040i (CNSystems, Graz, Austria). Continuous and noninvasive blood pressure monitoring was performed by placing finger cuffs on the right index and middle fingers. The right arm was supported with a sling to ensure that the finger cuffs were maintained at heart level. RR interval (RRI) values were extracted from the ECG signals, and simultaneously recorded systolic blood pressure (SBP) values were obtained. The blood pressure data were calibrated to oscillometric blood pressure values obtained in the left arm. In addition, respiratory activity was recorded using a physiological recording system (MP160, Biopac Inc., USA) to monitor potential drowsiness during the experiment.\u003c/p\u003e \u003c/div\u003e \u003c/p\u003e \u003c/div\u003e \u003cdiv id=\"Sec5\" class=\"Section2\"\u003e \u003ch2\u003e2.3. Study protocol\u003c/h2\u003e \u003cp\u003e \u003cdiv class=\"BlockQuote\"\u003e \u003cp\u003eThis study was conducted using a randomized, single-blind, sham-controlled, crossover design. Participants were assigned to one of two intervention sequences (taVNS \u003cspan fontcategory=\"NonProportional\" class=\"\" name=\"Emphasis\"\u003e\u0026rarr;\u003c/span\u003e rest \u003cspan fontcategory=\"NonProportional\" class=\"\" name=\"Emphasis\"\u003e\u0026rarr;\u003c/span\u003e sham or sham \u003cspan fontcategory=\"NonProportional\" class=\"\" name=\"Emphasis\"\u003e\u0026rarr;\u003c/span\u003e rest \u003cspan fontcategory=\"NonProportional\" class=\"\" name=\"Emphasis\"\u003e\u0026rarr;\u003c/span\u003e taVNS) using a pre-specified allocation list designed to achieve an approximately equal (1:1) distribution between the two sequences. Assignments were made sequentially according to the order of enrollment. Participants were blinded to the intervention condition (taVNS vs. sham). All participants completed two laboratory visits. In each visit, they experienced one of the two conditions: taVNS or sham condition. For the first visit, participants underwent anthropometric measurements (height and weight), followed by a sufficient resting period. After resting, heart rate (HR), SBP, and diastolic blood pressure (DBP) were measured using an oscillometric method with the participant in a seated position. Participants were then randomly assigned and received either taVNS or the sham condition. A washout period of at least two days was implemented before the second visit to minimize any potential carryover effects from the previous stimulation. The alternate stimulation condition was applied during the second visit. Throughout the entire experiment, all participants were positioned supine on a tilt table. The HUTT procedure was performed twice in each condition, encompassing two distinct phases: pre-stimulation and post-stimulation.\u003c/p\u003e \u003c/div\u003e \u003c/p\u003e \u003cdiv id=\"Sec6\" class=\"Section3\"\u003e \u003ch2\u003e2.3.1. taVNS\u003c/h2\u003e \u003cp\u003e\u003cdiv class=\"BlockQuote\"\u003e\u003cp\u003eThe taVNS system consisted of a medical stimulator (ELEXIR, NuEyne, Korea) and ear electrodes (tVNS Technologies, Germany) specifically designed for attachment to the cymba concha\u0026mdash;an area exclusively innervated by the ABVN. Electrodes were positioned on the left ear, and taVNS was administered with a pulse width of 250 \u0026micro;s and a frequency of 25 Hz [\u003cspan citationid=\"CR37\" class=\"CitationRef\"\u003e37\u003c/span\u003e, \u003cspan citationid=\"CR38\" class=\"CitationRef\"\u003e38\u003c/span\u003e]. The stimulation intensity was gradually increased from 0 mA in 0.1 mA increments up to each participant\u0026rsquo;s individual sensory threshold. In the sham condition, the same electrodes were attached, and participants were informed that stimulation would be applied at a very weak intensity; however, no electrical current was actually delivered. The stimulation was applied for 60 minutes after the first HUTT and continued during the post-stimulation HUTT, resulting in a total stimulation duration of 90 minutes.\u003c/p\u003e\u003c/div\u003e\u003c/p\u003e \u003c/div\u003e \u003cdiv id=\"Sec7\" class=\"Section3\"\u003e \u003ch2\u003e2.3.2. HUTT\u003c/h2\u003e \u003cp\u003e\u003cdiv class=\"BlockQuote\"\u003e\u003cp\u003e Before the HUTT, participants rested in the supine position for at least 10 minutes. The HUTT was conducted for a total duration of 30 minutes and consisted of three phases. The first phase was a 10-minute supine period to assess baseline autonomic activity. The second phase involved a 10-minute tilt period at 60\u0026deg; to evaluate autonomic responses during orthostatic stress. The third phase consisted of a 10-minute supine recovery period to observe autonomic restoration after tilting. Harms included dizziness, nausea, headache, and burn-related skin irritation. If any harm occurred, the experiment was immediately terminated. An overview of the HUTT protocol is summarized in Fig.\u0026nbsp;\u003cspan refid=\"Fig1\" class=\"InternalRef\"\u003e1\u003c/span\u003e.\u003c/p\u003e\u003c/div\u003e\u003c/p\u003e \u003cp\u003e \u003c/p\u003e \u003c/div\u003e \u003c/div\u003e \u003cdiv id=\"Sec8\" class=\"Section2\"\u003e \u003ch2\u003e2.4. Feature extraction\u003c/h2\u003e \u003cp\u003e \u003cdiv class=\"BlockQuote\"\u003e \u003cp\u003eWe used MATLAB R2025a software (The MathWorks, Inc., Natick, MA, USA) to extract the HRV and BRS parameters from the RRI and SBP values acquired by the Task Force\u0026reg; Monitor. The HRV analysis was performed across all three phases of the HUTT. In each phase, consecutive 5-minute segments without overlap were used to calculate the HRV parameters. Among them, four specific segments were selected for analysis: the last 5-minute segment before the tilt phase, while supine, was used to assess baseline autonomic activity (Supine-baseline, S-baseline), reflecting resting parasympathetic tone in the absence of orthostatic stress; the first 5 minutes immediately after tilting (early-tilt) was used to evaluate the initial autonomic response to orthostatic stress, marked by vagal withdrawal and sympathetic activation; the last 5 minutes before the end of the tilt phase (late-tilt) was selected to assess the adaptive response to sustained orthostatic load and capture the persistence or modulation of sympathetic predominance over time; and the last 5 minutes of the recovery phase (recovery), following the return to the supine position, was used to examine the reactivation of parasympathetic activity and overall autonomic recovery after stress exposure. BRS was calculated using only the 10 minutes of data obtained from the tilt phase, when blood pressure perturbations were most pronounced.\u003c/p\u003e \u003c/div\u003e \u003c/p\u003e \u003cdiv id=\"Sec9\" class=\"Section3\"\u003e \u003ch2\u003e2.4.1. Heart rate variability\u003c/h2\u003e \u003cp\u003e \u003cdiv class=\"BlockQuote\"\u003e \u003cp\u003eThe HRV parameters were extracted in both the time and frequency domains. The time-domain analysis provides information on how specific parameters vary over time, and the frequency-domain analysis indicates which frequency components contribute to those parameters [\u003cspan citationid=\"CR39\" class=\"CitationRef\"\u003e39\u003c/span\u003e]. In the time domain, the SDNN, the percentage of adjacent NN intervals differing by more than 50 ms (pNN50), and the root mean square of successive differences between adjacent NN intervals (RMSSD) were calculated. In the frequency domain, power spectral density was analyzed within the low-frequency (0.04\u0026ndash;0.15 Hz) and high-frequency (0.15\u0026ndash;0.40 Hz) bands, and the LF/HF ratio was computed to represent the relative balance between sympathetic and parasympathetic modulation. Definitions of the parameters included in the time- and frequency-domain parameter sets are summarized in Table\u0026nbsp;\u003cspan refid=\"Tab1\" class=\"InternalRef\"\u003e1\u003c/span\u003e.\u003c/p\u003e \u003c/div\u003e \u003c/p\u003e \u003cp\u003e \u003cdiv class=\"gridtable\"\u003e\u003ctable float=\"Yes\" id=\"Tab1\" border=\"1\"\u003e \u003ccaption language=\"En\"\u003e \u003cdiv class=\"CaptionNumber\"\u003eTable 1\u003c/div\u003e \u003cdiv class=\"CaptionContent\"\u003e \u003cp\u003eDefinitions of the HRV Parameters\u003c/p\u003e \u003c/div\u003e \u003c/caption\u003e \u003ccolgroup cols=\"3\"\u003e \u003cdiv align=\"left\" class=\"colspec\" colname=\"c1\" colnum=\"1\"\u003e\u003c/div\u003e \u003cdiv align=\"left\" class=\"colspec\" colname=\"c2\" colnum=\"2\"\u003e\u003c/div\u003e \u003cdiv align=\"left\" class=\"colspec\" colname=\"c3\" colnum=\"3\"\u003e\u003c/div\u003e \u003cthead\u003e \u003ctr\u003e \u003cth align=\"left\" colname=\"c1\"\u003e \u003cp\u003eDomain\u003c/p\u003e \u003c/th\u003e \u003cth align=\"left\" colname=\"c2\"\u003e \u003cp\u003eParameter\u003c/p\u003e \u003c/th\u003e \u003cth align=\"left\" colname=\"c3\"\u003e \u003cp\u003eDefinition\u003c/p\u003e \u003c/th\u003e \u003c/tr\u003e \u003c/thead\u003e \u003ctbody\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\" morerows=\"3\" rowspan=\"4\"\u003e \u003cp\u003eTime domain\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e \u003cp\u003eMeanHR\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c3\"\u003e \u003cp\u003eMean heart rate\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e \u003cp\u003eSDNN\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c3\"\u003e \u003cp\u003eStandard deviation of NN intervals\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e \u003cp\u003eRMSSD\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c3\"\u003e \u003cp\u003eRoot mean square of successive differences between adjacent NN intervals\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e \u003cp\u003epNNx\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c3\"\u003e \u003cp\u003ePercentage of consecutive NN intervals that differ by more than x ms\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\" morerows=\"2\" rowspan=\"3\"\u003e \u003cp\u003eFrequency \u003c/p\u003e \u003cp\u003edomain\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e \u003cp\u003eLF\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c3\"\u003e \u003cp\u003eLow frequency power calculated by Lomb\u0026ndash;Scargle periodogram (0.04\u0026ndash;0.15 Hz)\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e \u003cp\u003eHF\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c3\"\u003e \u003cp\u003eHigh frequency power calculated by Lomb\u0026ndash;Scargle periodogram (0.15\u0026ndash;0.4 Hz)\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e \u003cp\u003eLF/HF ratio\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c3\"\u003e \u003cp\u003eRatio of LF to HF spectral power\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003c/tbody\u003e \u003c/colgroup\u003e \u003c/table\u003e\u003c/div\u003e \u003c/p\u003e \u003c/div\u003e \u003cdiv id=\"Sec10\" class=\"Section3\"\u003e \u003ch2\u003e2.4.2. Baroreflex sensitivity\u003c/h2\u003e \u003cp\u003e \u003cdiv class=\"BlockQuote\"\u003e \u003cp\u003eBRS was used as an index to evaluate baroreflex-mediated autonomic regulation of the cardiovascular system. BRS was estimated by quantifying beat-to-beat changes in inter-beat intervals (IBIs) in response to spontaneous fluctuations in SBP. Inter-beat intervals (IBIs) used for BRS analysis were derived from ECG R\u0026ndash;R intervals and are therefore equivalent to the RR intervals used in HRV analysis. In this study, BRS was calculated using the sequence method [\u003cspan citationid=\"CR40\" class=\"CitationRef\"\u003e40\u003c/span\u003e, \u003cspan citationid=\"CR41\" class=\"CitationRef\"\u003e41\u003c/span\u003e], which is based on the beat-to-beat correlation between SBP and IBI. In the sequence method, sequences in which SBP and IBI simultaneously increased or decreased for three or more consecutive beats were identified as up sequences and down sequences, respectively. For each sequence, the linear regression slope between SBP and IBI was calculated. The mean slope of all up sequences was defined as the up-slope BRS, and the mean slope of all down sequences was defined as the down-slope BRS. The overall mean slope of all valid sequences was defined as the all-slope BRS. A sequence was considered valid only when the beat-to-beat changes in SBP and IBI exceeded threshold values of 1 mmHg and 4 ms, respectively [\u003cspan citationid=\"CR42\" class=\"CitationRef\"\u003e42\u003c/span\u003e, \u003cspan citationid=\"CR43\" class=\"CitationRef\"\u003e43\u003c/span\u003e]. In addition, only sequences with a correlation coefficient greater than 0.85 were included in the analysis.\u003c/p\u003e \u003c/div\u003e \u003c/p\u003e \u003c/div\u003e \u003c/div\u003e \u003cdiv id=\"Sec11\" class=\"Section2\"\u003e \u003ch2\u003e2.5. Statistical analysis\u003c/h2\u003e \u003cp\u003e \u003cdiv class=\"BlockQuote\"\u003e \u003cp\u003eAll statistical analyses were performed using IBM SPSS version 27 (IBM Corp., Armonk, NY, USA). The normality of each dataset was assessed using the Shapiro-Wilk test. For comparisons within the same session (pre- vs. post-stimulation), between S-baseline values obtained on different days, and within the sham session, either paired t-tests or Wilcoxon signed-rank tests were applied, as appropriate. To correct for multiple comparisons and reduce the risk of type I errors, the false discovery rate adjustment was applied using the Benjamini-Hochberg procedure. All data are expressed the mean \u003cspan class=\"InlineEquation\"\u003e\u003cspan class=\"mathinline\"\u003e\\(\\:\\pm\\:\\)\u003c/span\u003e\u003c/span\u003e standard error of the mean (SEM), and statistical significance was set at \u003cspan class=\"InlineEquation\"\u003e\u003cspan class=\"mathinline\"\u003e\\(\\:\\alpha\\:=0.05\\)\u003c/span\u003e\u003c/span\u003e\u003c/p\u003e \u003c/div\u003e \u003c/p\u003e \u003c/div\u003e"},{"header":"3. Results","content":"\u003cdiv id=\"Sec13\" class=\"Section2\"\u003e \u003ch2\u003e3.1. Data acquisition and participant exclusion\u003c/h2\u003e \u003cp\u003e \u003cdiv class=\"BlockQuote\"\u003e \u003cp\u003eWe initially enrolled 36 participants in this study. Four participants were excluded from the analysis due to poor signal quality or suspected drowsiness based on respiratory monitoring, resulting in a final dataset of 32 participants. The mean age was 25.19 \u003cspan class=\"InlineEquation\"\u003e\u003cspan class=\"mathinline\"\u003e\\(\\:\\pm\\:\\)\u003c/span\u003e\u003c/span\u003e 3.3 years, and the sample included 15 males and 17 females. No experimental sessions were stopped due to harms. The mean HR, SBP, and DBP values measured before the experiment are presented in Table\u0026nbsp;\u003cspan refid=\"Tab2\" class=\"InternalRef\"\u003e2\u003c/span\u003e.\u003c/p\u003e \u003c/div\u003e \u003c/p\u003e \u003cp\u003e \u003cdiv class=\"gridtable\"\u003e\u003ctable float=\"Yes\" id=\"Tab2\" border=\"1\"\u003e \u003ccaption language=\"En\"\u003e \u003cdiv class=\"CaptionNumber\"\u003eTable 2\u003c/div\u003e \u003cdiv class=\"CaptionContent\"\u003e \u003cp\u003eDemographic and Psychological Characteristics\u003c/p\u003e \u003c/div\u003e \u003c/caption\u003e \u003ccolgroup cols=\"2\"\u003e \u003cdiv align=\"left\" class=\"colspec\" colname=\"c1\" colnum=\"1\"\u003e\u003c/div\u003e \u003cdiv align=\"left\" class=\"colspec\" colname=\"c2\" colnum=\"2\"\u003e\u003c/div\u003e \u003cthead\u003e \u003ctr\u003e \u003cth align=\"left\" colname=\"c1\"\u003e \u003cp\u003eCharacteristic\u003c/p\u003e \u003c/th\u003e \u003cth align=\"left\" colname=\"c2\"\u003e \u003cp\u003eValue\u003c/p\u003e \u003c/th\u003e \u003c/tr\u003e \u003c/thead\u003e \u003ctbody\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003eParticipants\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e \u003cp\u003e32 (male: 15)\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003eAge, years\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e \u003cp\u003e25.28\u0026thinsp;\u0026plusmn;\u0026thinsp;3.3\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003eWeight, kg\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e \u003cp\u003e64.78\u0026thinsp;\u0026plusmn;\u0026thinsp;14.8\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003eHeight, cm\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e \u003cp\u003e167.43\u0026thinsp;\u0026plusmn;\u0026thinsp;7.6\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003eSBP, mmHg\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e \u003cp\u003e109.43\u0026thinsp;\u0026plusmn;\u0026thinsp;8.8\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003eDBP, mmHg\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e \u003cp\u003e70.53\u0026thinsp;\u0026plusmn;\u0026thinsp;8.8\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003eHR, bpm\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e \u003cp\u003e79.53\u0026thinsp;\u0026plusmn;\u0026thinsp;11.2\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003c/tbody\u003e \u003c/colgroup\u003e \u003c/table\u003e\u003c/div\u003e \u003c/p\u003e \u003c/div\u003e \u003cdiv id=\"Sec14\" class=\"Section2\"\u003e \u003ch2\u003e3.2. Baseline HRV equivalence between the taVNS and sham conditions\u003c/h2\u003e \u003cp\u003e \u003cdiv class=\"BlockQuote\"\u003e \u003cp\u003eBefore comparing the pre- and post-stimulation responses, we compared the HRV parameters between the pre-taVNS S-baseline and the pre-sham S-baseline. No significant differences were observed between the two conditions for any parameter (Table\u0026nbsp;\u003cspan refid=\"Tab3\" class=\"InternalRef\"\u003e3\u003c/span\u003e).\u003c/p\u003e \u003c/div\u003e \u003c/p\u003e \u003cp\u003e \u003cdiv class=\"gridtable\"\u003e\u003ctable float=\"Yes\" id=\"Tab3\" border=\"1\"\u003e \u003ccaption language=\"En\"\u003e \u003cdiv class=\"CaptionNumber\"\u003eTable 3\u003c/div\u003e \u003cdiv class=\"CaptionContent\"\u003e \u003cp\u003eComparison of Pre-stimulation S-baseline HRV Between the taVNS and Sham Conditions\u003c/p\u003e \u003c/div\u003e \u003c/caption\u003e \u003ccolgroup cols=\"6\"\u003e \u003cdiv align=\"left\" class=\"colspec\" colname=\"c1\" colnum=\"1\"\u003e\u003c/div\u003e \u003cdiv align=\"char\" char=\".\" class=\"colspec\" colname=\"c2\" colnum=\"2\"\u003e\u003c/div\u003e \u003cdiv align=\"char\" char=\".\" class=\"colspec\" colname=\"c3\" colnum=\"3\"\u003e\u003c/div\u003e \u003cdiv align=\"char\" char=\".\" class=\"colspec\" colname=\"c4\" colnum=\"4\"\u003e\u003c/div\u003e \u003cdiv align=\"left\" class=\"colspec\" colname=\"c5\" colnum=\"5\"\u003e\u003c/div\u003e \u003cdiv align=\"char\" char=\".\" class=\"colspec\" colname=\"c6\" colnum=\"6\"\u003e\u003c/div\u003e \u003cthead\u003e \u003ctr\u003e \u003cth align=\"left\" colname=\"c1\" morerows=\"1\" rowspan=\"2\"\u003e \u003cp\u003eParameters\u003c/p\u003e \u003c/th\u003e \u003cth align=\"left\" colspan=\"2\" nameend=\"c3\" namest=\"c2\"\u003e \u003cp\u003ePre-taVNS S-baseline\u003c/p\u003e \u003c/th\u003e \u003cth align=\"left\" colspan=\"2\" nameend=\"c5\" namest=\"c4\"\u003e \u003cp\u003ePre-sham S-baseline\u003c/p\u003e \u003c/th\u003e \u003cth align=\"left\" colname=\"c6\" morerows=\"1\" rowspan=\"2\"\u003e \u003cp\u003ep-value\u003c/p\u003e \u003c/th\u003e \u003c/tr\u003e \u003ctr\u003e \u003cth align=\"left\" colname=\"c2\"\u003e \u003cp\u003eMean\u003c/p\u003e \u003c/th\u003e \u003cth align=\"left\" colname=\"c3\"\u003e \u003cp\u003eSEM\u003c/p\u003e \u003c/th\u003e \u003cth align=\"left\" colname=\"c4\"\u003e \u003cp\u003eMean\u003c/p\u003e \u003c/th\u003e \u003cth align=\"left\" colname=\"c5\"\u003e \u003cp\u003eSEM\u003c/p\u003e \u003c/th\u003e \u003c/tr\u003e \u003c/thead\u003e \u003ctbody\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003eSDNN\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c2\"\u003e \u003cp\u003e49.85\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c3\"\u003e \u003cp\u003e3.22\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c4\"\u003e \u003cp\u003e55.77\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c5\"\u003e \u003cp\u003e4\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c6\"\u003e \u003cp\u003e0.3282\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003eMean HR\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c2\"\u003e \u003cp\u003e70.72\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c3\"\u003e \u003cp\u003e1.4\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c4\"\u003e \u003cp\u003e69.34\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c5\"\u003e \u003cp\u003e1.58\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c6\"\u003e \u003cp\u003e0.3774\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003eRMSSD\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c2\"\u003e \u003cp\u003e37.07\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c3\"\u003e \u003cp\u003e3.13\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c4\"\u003e \u003cp\u003e44.38\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c5\"\u003e \u003cp\u003e3.69\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c6\"\u003e \u003cp\u003e0.101\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003epNN30\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c2\"\u003e \u003cp\u003e36.14\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c3\"\u003e \u003cp\u003e3.52\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c4\"\u003e \u003cp\u003e42.06\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c5\"\u003e \u003cp\u003e3.79\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c6\"\u003e \u003cp\u003e0.1121\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003epNN50\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c2\"\u003e \u003cp\u003e16.77\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c3\"\u003e \u003cp\u003e2.81\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c4\"\u003e \u003cp\u003e22.39\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c5\"\u003e \u003cp\u003e3.27\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c6\"\u003e \u003cp\u003e0.1429\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003eLF\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c2\"\u003e \u003cp\u003e3525.04\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c3\"\u003e \u003cp\u003e419.82\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c4\"\u003e \u003cp\u003e4761.75\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c5\"\u003e \u003cp\u003e871.71\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c6\"\u003e \u003cp\u003e0.4698\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003eHF\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c2\"\u003e \u003cp\u003e2469.57\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c3\"\u003e \u003cp\u003e456.67\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c4\"\u003e \u003cp\u003e3289.28\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c5\"\u003e \u003cp\u003e511.69\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c6\"\u003e \u003cp\u003e0.1629\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003eLF/HF ratio\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c2\"\u003e \u003cp\u003e2.02\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c3\"\u003e \u003cp\u003e0.33\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c4\"\u003e \u003cp\u003e1.61\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c5\"\u003e \u003cp\u003e0.18\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c6\"\u003e \u003cp\u003e0.3053\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003c/tbody\u003e \u003c/colgroup\u003e \u003c/table\u003e\u003c/div\u003e \u003c/p\u003e \u003c/div\u003e \u003cdiv id=\"Sec15\" class=\"Section2\"\u003e \u003ch2\u003e3.3. Differences in autonomic responses from pre- to post-stimulation\u003c/h2\u003e \u003cdiv id=\"Sec16\" class=\"Section3\"\u003e \u003ch2\u003e3.3.1. Changes in HRV following taVNS stimulation\u003c/h2\u003e \u003cp\u003e \u003cdiv class=\"BlockQuote\"\u003e \u003cp\u003eFor the active stimulation group, changes in HRV from pre- to post-taVNS at each phase were compared across the four experimental phases (Table\u0026nbsp;\u003cspan refid=\"Tab4\" class=\"InternalRef\"\u003e4\u003c/span\u003e and Fig.\u0026nbsp;\u003cspan refid=\"Fig2\" class=\"InternalRef\"\u003e2\u003c/span\u003e). We found that, in the active stimulation condition, taVNS significantly enhanced parasympathetic-related parameters across all phases. In the time domain, SDNN, RMSSD, pNN30, pNN50 increased after stimulation at every phase (SDNN: S-baseline \u003cem\u003ep\u003c/em\u003e\u0026thinsp;=\u0026thinsp;0.0023, early-tilt \u003cem\u003ep\u003c/em\u003e\u0026thinsp;=\u0026thinsp;0.0001, late-tilt \u003cem\u003ep\u003c/em\u003e\u0026thinsp;=\u0026thinsp;0. 0185, recovery \u003cem\u003ep\u003c/em\u003e\u0026thinsp;=\u0026thinsp;0. 0008; RMSSD: S-baseline \u003cem\u003ep\u003c/em\u003e\u0026thinsp;=\u0026thinsp;0. 0009, early-tilt \u003cem\u003ep\u003c/em\u003e\u0026thinsp;=\u0026thinsp;0. 0001, late-tilt \u003cem\u003ep\u003c/em\u003e\u0026thinsp;=\u0026thinsp;0.0005, recovery \u003cem\u003ep\u003c/em\u003e\u0026thinsp;=\u0026thinsp;0. 0016; pNN30: S-baseline \u003cem\u003ep\u003c/em\u003e\u0026thinsp;=\u0026thinsp;0. 0016, early-tilt \u003cem\u003ep\u003c/em\u003e\u0026thinsp;=\u0026thinsp;0. 0022, late-tilt \u003cem\u003ep\u003c/em\u003e\u0026thinsp;=\u0026thinsp;0. 002, recovery \u003cem\u003ep\u003c/em\u003e\u0026thinsp;=\u0026thinsp;0. 002; pNN50: S-baseline \u003cem\u003ep\u003c/em\u003e\u0026thinsp;=\u0026thinsp;0. 0007, early-tilt \u003cem\u003ep\u003c/em\u003e\u0026thinsp;=\u0026thinsp;0. 0048, late-tilt \u003cem\u003ep\u003c/em\u003e\u0026thinsp;=\u0026thinsp;0.0050, recovery \u003cem\u003ep\u003c/em\u003e\u0026thinsp;=\u0026thinsp;0.0094). Mean HR decreased consistently across phases (S-baseline \u003cem\u003ep\u003c/em\u003e\u0026thinsp;=\u0026thinsp;0.0001, early-tilt \u003cem\u003ep\u003c/em\u003e\u0026thinsp;=\u0026thinsp;0.0002, late-tilt \u003cem\u003ep\u003c/em\u003e\u0026thinsp;=\u0026thinsp;0. 0068, recovery \u003cem\u003ep\u003c/em\u003e\u0026thinsp;=\u0026thinsp;0. 0047). In the frequency domain, LF showed no difference at S-baseline (\u003cem\u003ep\u003c/em\u003e\u0026thinsp;=\u0026thinsp;0. 2540) but increased during early-tilt and recovery (early-tilt \u003cem\u003ep\u003c/em\u003e\u0026thinsp;\u0026lt;\u0026thinsp;0.0001, recovery \u003cem\u003ep\u003c/em\u003e\u0026thinsp;=\u0026thinsp;0. 0084). The LF/HF ratio decreased at S-baseline and late-tilt (S-baseline \u003cem\u003ep\u003c/em\u003e\u0026thinsp;=\u0026thinsp;0. 0056, late-tilt \u003cem\u003ep\u003c/em\u003e\u0026thinsp;=\u0026thinsp;0. 0040) but was not significantly different during early-tilt or recovery (early-tilt \u003cem\u003ep\u003c/em\u003e\u0026thinsp;=\u0026thinsp;0. 8811, recovery \u003cem\u003ep\u003c/em\u003e\u0026thinsp;=\u0026thinsp;0. 3498). In contrast, HF increased significantly at all phases (S-baseline \u003cem\u003ep\u003c/em\u003e\u0026thinsp;=\u0026thinsp;0. 0007, early-tilt \u003cem\u003ep\u003c/em\u003e\u0026thinsp;=\u0026thinsp;0. 0006, late-tilt \u003cem\u003ep\u003c/em\u003e\u0026thinsp;=\u0026thinsp;0. 0023, recovery \u003cem\u003ep\u003c/em\u003e\u0026thinsp;=\u0026thinsp;0. 0002).\u003c/p\u003e \u003c/div\u003e \u003c/p\u003e \u003cp\u003e \u003cdiv class=\"gridtable\"\u003e\u003ctable float=\"Yes\" id=\"Tab4\" border=\"1\"\u003e \u003ccaption language=\"En\"\u003e \u003cdiv class=\"CaptionNumber\"\u003eTable 4\u003c/div\u003e \u003cdiv class=\"CaptionContent\"\u003e \u003cp\u003eComparisons of HRV from Pre- to Post-taVNS Across the Four Experimental Phases\u003c/p\u003e \u003c/div\u003e \u003c/caption\u003e \u003ccolgroup cols=\"7\"\u003e \u003cdiv align=\"left\" class=\"colspec\" colname=\"c1\" colnum=\"1\"\u003e\u003c/div\u003e \u003cdiv align=\"left\" class=\"colspec\" colname=\"c2\" colnum=\"2\"\u003e\u003c/div\u003e \u003cdiv align=\"left\" class=\"colspec\" colname=\"c3\" colnum=\"3\"\u003e\u003c/div\u003e \u003cdiv align=\"left\" class=\"colspec\" colname=\"c4\" colnum=\"4\"\u003e\u003c/div\u003e \u003cdiv align=\"left\" class=\"colspec\" colname=\"c5\" colnum=\"5\"\u003e\u003c/div\u003e \u003cdiv align=\"left\" class=\"colspec\" colname=\"c6\" colnum=\"6\"\u003e\u003c/div\u003e \u003cdiv align=\"left\" class=\"colspec\" colname=\"c7\" colnum=\"7\"\u003e\u003c/div\u003e \u003ctbody\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003ePhase\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\" morerows=\"1\" rowspan=\"2\"\u003e \u003cp\u003eParameters\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colspan=\"2\" nameend=\"c4\" namest=\"c3\"\u003e \u003cp\u003ePre-taVNS\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colspan=\"2\" nameend=\"c6\" namest=\"c5\"\u003e \u003cp\u003ePost-taVNS\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c7\" morerows=\"1\" rowspan=\"2\"\u003e \u003cp\u003ep-value\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e\u0026nbsp;\u003c/td\u003e \u003ctd align=\"left\" colname=\"c3\"\u003e \u003cp\u003eMean\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c4\"\u003e \u003cp\u003eSEM\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c5\"\u003e \u003cp\u003eMean\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c6\"\u003e \u003cp\u003eSEM\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\" morerows=\"7\" rowspan=\"8\"\u003e \u003cp\u003e\u003cb\u003eS-baseline\u003c/b\u003e\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e \u003cp\u003eSDNN\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c3\"\u003e \u003cp\u003e49.85\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c4\"\u003e \u003cp\u003e3.22\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c5\"\u003e \u003cp\u003e65.45\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c6\"\u003e \u003cp\u003e5.08\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c7\"\u003e \u003cp\u003e0.0072\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e \u003cp\u003eMean HR\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c3\"\u003e \u003cp\u003e70.72\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c4\"\u003e \u003cp\u003e1.4\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c5\"\u003e \u003cp\u003e65.23\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c6\"\u003e \u003cp\u003e1\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c7\"\u003e \u003cp\u003e0.0007\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e \u003cp\u003eRMSSD\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c3\"\u003e \u003cp\u003e37.07\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c4\"\u003e \u003cp\u003e3.13\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c5\"\u003e \u003cp\u003e51.33\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c6\"\u003e \u003cp\u003e3.65\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c7\"\u003e \u003cp\u003e0.0038\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e \u003cp\u003epNN30\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c3\"\u003e \u003cp\u003e36.14\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c4\"\u003e \u003cp\u003e3.52\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c5\"\u003e \u003cp\u003e51.13\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c6\"\u003e \u003cp\u003e3.35\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c7\"\u003e \u003cp\u003e0.0064\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e \u003cp\u003epNN50\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c3\"\u003e \u003cp\u003e16.77\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c4\"\u003e \u003cp\u003e2.81\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c5\"\u003e \u003cp\u003e29.88\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c6\"\u003e \u003cp\u003e3.12\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c7\"\u003e \u003cp\u003e0.0035\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e \u003cp\u003eLF\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c3\"\u003e \u003cp\u003e3525.04\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c4\"\u003e \u003cp\u003e419.82\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c5\"\u003e \u003cp\u003e5009.67\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c6\"\u003e \u003cp\u003e712.65\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c7\"\u003e \u003cp\u003e0.3416\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e \u003cp\u003eHF\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c3\"\u003e \u003cp\u003e2469.57\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c4\"\u003e \u003cp\u003e456.67\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c5\"\u003e \u003cp\u003e4647.38\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c6\"\u003e \u003cp\u003e616.33\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c7\"\u003e \u003cp\u003e0.0035\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e \u003cp\u003eLF/HF ratio\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c3\"\u003e \u003cp\u003e2.02\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c4\"\u003e \u003cp\u003e0.33\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c5\"\u003e \u003cp\u003e1.31\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c6\"\u003e \u003cp\u003e0.16\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c7\"\u003e \u003cp\u003e0.0142\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\" morerows=\"7\" rowspan=\"8\"\u003e \u003cp\u003e\u003cb\u003eEarly-tilt\u003c/b\u003e\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e \u003cp\u003eSDNN\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c3\"\u003e \u003cp\u003e52.84\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c4\"\u003e \u003cp\u003e2.12\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c5\"\u003e \u003cp\u003e65.61\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c6\"\u003e \u003cp\u003e2.97\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c7\"\u003e \u003cp\u003e0.0007\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e \u003cp\u003eMean HR\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c3\"\u003e \u003cp\u003e83.51\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c4\"\u003e \u003cp\u003e1.69\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c5\"\u003e \u003cp\u003e78.39\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c6\"\u003e \u003cp\u003e1.37\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c7\"\u003e \u003cp\u003e0.0007\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e \u003cp\u003eRMSSD\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c3\"\u003e \u003cp\u003e21.38\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c4\"\u003e \u003cp\u003e1.38\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c5\"\u003e \u003cp\u003e26.72\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c6\"\u003e \u003cp\u003e1.55\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c7\"\u003e \u003cp\u003e0.0007\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e \u003cp\u003epNN30\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c3\"\u003e \u003cp\u003e14.03\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c4\"\u003e \u003cp\u003e2.01\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c5\"\u003e \u003cp\u003e21.25\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c6\"\u003e \u003cp\u003e2.16\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c7\"\u003e \u003cp\u003e0.0072\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e \u003cp\u003epNN50\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c3\"\u003e \u003cp\u003e4.23\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c4\"\u003e \u003cp\u003e0.87\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c5\"\u003e \u003cp\u003e7.11\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c6\"\u003e \u003cp\u003e1.07\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c7\"\u003e \u003cp\u003e0.0124\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e \u003cp\u003eLF\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c3\"\u003e \u003cp\u003e2883.04\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c4\"\u003e \u003cp\u003e261.02\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c5\"\u003e \u003cp\u003e5027.09\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c6\"\u003e \u003cp\u003e629.8\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c7\"\u003e \u003cp\u003e0.0007\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e \u003cp\u003eHF\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c3\"\u003e \u003cp\u003e761.54\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c4\"\u003e \u003cp\u003e106.18\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c5\"\u003e \u003cp\u003e1392.08\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c6\"\u003e \u003cp\u003e329.39\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c7\"\u003e \u003cp\u003e0.0032\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e \u003cp\u003eLF/HF ratio\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c3\"\u003e \u003cp\u003e4.92\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c4\"\u003e \u003cp\u003e0.53\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c5\"\u003e \u003cp\u003e5.1\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c6\"\u003e \u003cp\u003e0.55\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c7\"\u003e \u003cp\u003e0.8811\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\" morerows=\"7\" rowspan=\"8\"\u003e \u003cp\u003e\u003cb\u003eLate-tilt\u003c/b\u003e\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e \u003cp\u003eSDNN\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c3\"\u003e \u003cp\u003e42.06\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c4\"\u003e \u003cp\u003e1.89\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c5\"\u003e \u003cp\u003e48.05\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c6\"\u003e \u003cp\u003e2.24\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c7\"\u003e \u003cp\u003e0.0412\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e \u003cp\u003eMean HR\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c3\"\u003e \u003cp\u003e83.64\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c4\"\u003e \u003cp\u003e1.73\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c5\"\u003e \u003cp\u003e78.71\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c6\"\u003e \u003cp\u003e1.42\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c7\"\u003e \u003cp\u003e0.0007\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e \u003cp\u003eRMSSD\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c3\"\u003e \u003cp\u003e20.36\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c4\"\u003e \u003cp\u003e1.25\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c5\"\u003e \u003cp\u003e24.54\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c6\"\u003e \u003cp\u003e1.32\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c7\"\u003e \u003cp\u003e0.0032\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e \u003cp\u003epNN30\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c3\"\u003e \u003cp\u003e13.99\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c4\"\u003e \u003cp\u003e1.95\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c5\"\u003e \u003cp\u003e20.88\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c6\"\u003e \u003cp\u003e2.29\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c7\"\u003e \u003cp\u003e0.0072\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e \u003cp\u003epNN50\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c3\"\u003e \u003cp\u003e3.33\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c4\"\u003e \u003cp\u003e0.76\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c5\"\u003e \u003cp\u003e5.71\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c6\"\u003e \u003cp\u003e0.94\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c7\"\u003e \u003cp\u003e0.0167\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e \u003cp\u003eLF\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c3\"\u003e \u003cp\u003e2869.54\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c4\"\u003e \u003cp\u003e293.46\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c5\"\u003e \u003cp\u003e3393.09\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c6\"\u003e \u003cp\u003e279.98\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c7\"\u003e \u003cp\u003e0.101\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e \u003cp\u003eHF\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c3\"\u003e \u003cp\u003e726.74\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c4\"\u003e \u003cp\u003e93.44\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c5\"\u003e \u003cp\u003e1065.63\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c6\"\u003e \u003cp\u003e111.52\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c7\"\u003e \u003cp\u003e0.0072\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e \u003cp\u003eLF/HF ratio\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c3\"\u003e \u003cp\u003e5.22\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c4\"\u003e \u003cp\u003e0.54\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c5\"\u003e \u003cp\u003e4.06\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c6\"\u003e \u003cp\u003e0.45\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c7\"\u003e \u003cp\u003e0.0111\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\" morerows=\"7\" rowspan=\"8\"\u003e \u003cp\u003e\u003cb\u003eRecovery\u003c/b\u003e\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e \u003cp\u003eSDNN\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c3\"\u003e \u003cp\u003e53.48\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c4\"\u003e \u003cp\u003e3.66\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c5\"\u003e \u003cp\u003e66.66\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c6\"\u003e \u003cp\u003e4.15\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c7\"\u003e \u003cp\u003e0.0038\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e \u003cp\u003eMean HR\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c3\"\u003e \u003cp\u003e68.78\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c4\"\u003e \u003cp\u003e1.37\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c5\"\u003e \u003cp\u003e65.83\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c6\"\u003e \u003cp\u003e1.31\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c7\"\u003e \u003cp\u003e0.0025\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e \u003cp\u003eRMSSD\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c3\"\u003e \u003cp\u003e40.63\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c4\"\u003e \u003cp\u003e3.1\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c5\"\u003e \u003cp\u003e51.06\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c6\"\u003e \u003cp\u003e3.9\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c7\"\u003e \u003cp\u003e0.0064\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e \u003cp\u003epNN30\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c3\"\u003e \u003cp\u003e41.19\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c4\"\u003e \u003cp\u003e3.66\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c5\"\u003e \u003cp\u003e49.38\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c6\"\u003e \u003cp\u003e3.31\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c7\"\u003e \u003cp\u003e0.0072\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e \u003cp\u003epNN50\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c3\"\u003e \u003cp\u003e20.73\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c4\"\u003e \u003cp\u003e2.96\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c5\"\u003e \u003cp\u003e28.4\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c6\"\u003e \u003cp\u003e3.04\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c7\"\u003e \u003cp\u003e0.0124\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e \u003cp\u003eLF\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c3\"\u003e \u003cp\u003e4261.65\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c4\"\u003e \u003cp\u003e762.68\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c5\"\u003e \u003cp\u003e5278.04\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c6\"\u003e \u003cp\u003e616.51\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c7\"\u003e \u003cp\u003e0.0198\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e \u003cp\u003eHF\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c3\"\u003e \u003cp\u003e2654.83\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c4\"\u003e \u003cp\u003e366.1\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c5\"\u003e \u003cp\u003e4448.16\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c6\"\u003e \u003cp\u003e677.01\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c7\"\u003e \u003cp\u003e0.002\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e \u003cp\u003eLF/HF ratio\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c3\"\u003e \u003cp\u003e1.81\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c4\"\u003e \u003cp\u003e0.24\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c5\"\u003e \u003cp\u003e1.61\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c6\"\u003e \u003cp\u003e0.25\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c7\"\u003e \u003cp\u003e0.4401\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003c/tbody\u003e \u003c/colgroup\u003e \u003c/table\u003e\u003c/div\u003e \u003c/p\u003e \u003cp\u003e \u003c/p\u003e \u003c/div\u003e \u003cdiv id=\"Sec17\" class=\"Section3\"\u003e \u003ch2\u003e3.3.2. Changes in HRV following sham stimulation\u003c/h2\u003e \u003cp\u003e \u003cdiv class=\"BlockQuote\"\u003e \u003cp\u003eUsing the same method as in the taVNS HRV analysis, we compared pre-sham and post-sham HRV across all phases. Phase-specific differences in HRV from pre- to post-sham are detailed in Table\u0026nbsp;\u003cspan refid=\"Tab5\" class=\"InternalRef\"\u003e5\u003c/span\u003e and Fig.\u0026nbsp;\u003cspan refid=\"Fig3\" class=\"InternalRef\"\u003e3\u003c/span\u003e. Although several parameters reached statistical significance, there was no consistent pattern across parameters. Mean HR increased significantly at S-baseline, early-tilt, and late-tilt (S-baseline \u003cem\u003ep\u003c/em\u003e\u0026thinsp;=\u0026thinsp;0.0051, early-tilt \u003cem\u003ep\u003c/em\u003e\u0026thinsp;=\u0026thinsp;0.0010, late-tilt p\u0026thinsp;=\u0026thinsp;0.0115), and SDNN showed a modest increase at late-tilt (\u003cem\u003ep\u003c/em\u003e\u0026thinsp;=\u0026thinsp;0.0179). In contrast, key parasympathetic-related parameters\u0026mdash;RMSSD, HF power, and LF/HF ratio\u0026mdash;did not exhibit consistent changes across phases.\u003c/p\u003e \u003c/div\u003e \u003c/p\u003e \u003cp\u003e \u003cdiv class=\"gridtable\"\u003e\u003ctable float=\"Yes\" id=\"Tab5\" border=\"1\"\u003e \u003ccaption language=\"En\"\u003e \u003cdiv class=\"CaptionNumber\"\u003eTable 5\u003c/div\u003e \u003cdiv class=\"CaptionContent\"\u003e \u003cp\u003eComparisons of HRV from Pre- to Post-sham Across the Four Experimental Phases\u003c/p\u003e \u003c/div\u003e \u003c/caption\u003e \u003ccolgroup cols=\"7\"\u003e \u003cdiv align=\"left\" class=\"colspec\" colname=\"c1\" colnum=\"1\"\u003e\u003c/div\u003e \u003cdiv align=\"left\" class=\"colspec\" colname=\"c2\" colnum=\"2\"\u003e\u003c/div\u003e \u003cdiv align=\"left\" class=\"colspec\" colname=\"c3\" colnum=\"3\"\u003e\u003c/div\u003e \u003cdiv align=\"left\" class=\"colspec\" colname=\"c4\" colnum=\"4\"\u003e\u003c/div\u003e \u003cdiv align=\"left\" class=\"colspec\" colname=\"c5\" colnum=\"5\"\u003e\u003c/div\u003e \u003cdiv align=\"left\" class=\"colspec\" colname=\"c6\" colnum=\"6\"\u003e\u003c/div\u003e \u003cdiv align=\"left\" class=\"colspec\" colname=\"c7\" colnum=\"7\"\u003e\u003c/div\u003e \u003ctbody\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003ePhase\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\" morerows=\"1\" rowspan=\"2\"\u003e \u003cp\u003eParameters\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colspan=\"2\" nameend=\"c4\" namest=\"c3\"\u003e \u003cp\u003ePre-sham\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colspan=\"2\" nameend=\"c6\" namest=\"c5\"\u003e \u003cp\u003ePost-sham\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c7\" morerows=\"1\" rowspan=\"2\"\u003e \u003cp\u003ep-value\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e\u0026nbsp;\u003c/td\u003e \u003ctd align=\"left\" colname=\"c3\"\u003e \u003cp\u003eMean\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c4\"\u003e \u003cp\u003eSEM\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c5\"\u003e \u003cp\u003eMean\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c6\"\u003e \u003cp\u003eSEM\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\" morerows=\"7\" rowspan=\"8\"\u003e \u003cp\u003e\u003cb\u003eS-baseline\u003c/b\u003e\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e \u003cp\u003eSDNN\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c3\"\u003e \u003cp\u003e55.77\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c4\"\u003e \u003cp\u003e4\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c5\"\u003e \u003cp\u003e62.41\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c6\"\u003e \u003cp\u003e4.1\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c7\"\u003e \u003cp\u003e0.1601\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e \u003cp\u003eMean HR\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c3\"\u003e \u003cp\u003e69.34\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c4\"\u003e \u003cp\u003e1.58\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c5\"\u003e \u003cp\u003e66.4\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c6\"\u003e \u003cp\u003e1.47\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c7\"\u003e \u003cp\u003e0.0078\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e \u003cp\u003eRMSSD\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c3\"\u003e \u003cp\u003e44.38\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c4\"\u003e \u003cp\u003e3.69\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c5\"\u003e \u003cp\u003e52.16\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c6\"\u003e \u003cp\u003e4.72\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c7\"\u003e \u003cp\u003e0.2339\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e \u003cp\u003epNN30\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c3\"\u003e \u003cp\u003e42.06\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c4\"\u003e \u003cp\u003e3.79\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c5\"\u003e \u003cp\u003e48.09\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c6\"\u003e \u003cp\u003e3.37\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c7\"\u003e \u003cp\u003e0.1657\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e \u003cp\u003epNN50\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c3\"\u003e \u003cp\u003e22.39\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c4\"\u003e \u003cp\u003e3.27\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c5\"\u003e \u003cp\u003e27.38\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c6\"\u003e \u003cp\u003e3.3\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c7\"\u003e \u003cp\u003e0.1686\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e \u003cp\u003eLF\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c3\"\u003e \u003cp\u003e4761.75\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c4\"\u003e \u003cp\u003e871.71\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c5\"\u003e \u003cp\u003e5363.6\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c6\"\u003e \u003cp\u003e790.59\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c7\"\u003e \u003cp\u003e0.2067\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e \u003cp\u003eHF\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c3\"\u003e \u003cp\u003e3289.28\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c4\"\u003e \u003cp\u003e511.69\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c5\"\u003e \u003cp\u003e4953.67\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c6\"\u003e \u003cp\u003e928.84\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c7\"\u003e \u003cp\u003e0.2459\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e \u003cp\u003eLF/HF ratio\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c3\"\u003e \u003cp\u003e1.61\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c4\"\u003e \u003cp\u003e0.18\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c5\"\u003e \u003cp\u003e1.51\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c6\"\u003e \u003cp\u003e0.16\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c7\"\u003e \u003cp\u003e0.8811\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\" morerows=\"7\" rowspan=\"8\"\u003e \u003cp\u003e\u003cb\u003eEarly-tilt\u003c/b\u003e\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e \u003cp\u003eSDNN\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c3\"\u003e \u003cp\u003e60.09\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c4\"\u003e \u003cp\u003e3.38\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c5\"\u003e \u003cp\u003e64.68\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c6\"\u003e \u003cp\u003e2.89\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c7\"\u003e \u003cp\u003e0.1601\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e \u003cp\u003eMean HR\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c3\"\u003e \u003cp\u003e81.77\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c4\"\u003e \u003cp\u003e1.75\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c5\"\u003e \u003cp\u003e77.45\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c6\"\u003e \u003cp\u003e1.64\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c7\"\u003e \u003cp\u003e0.0024\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e \u003cp\u003eRMSSD\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c3\"\u003e \u003cp\u003e25.65\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c4\"\u003e \u003cp\u003e1.55\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c5\"\u003e \u003cp\u003e30.4\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c6\"\u003e \u003cp\u003e2.52\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c7\"\u003e \u003cp\u003e0.0589\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e \u003cp\u003epNN30\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c3\"\u003e \u003cp\u003e19.88\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c4\"\u003e \u003cp\u003e2.11\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c5\"\u003e \u003cp\u003e23.05\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c6\"\u003e \u003cp\u003e2.73\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c7\"\u003e \u003cp\u003e0.0513\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e \u003cp\u003epNN50\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c3\"\u003e \u003cp\u003e6.21\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c4\"\u003e \u003cp\u003e1.1\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c5\"\u003e \u003cp\u003e9.58\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c6\"\u003e \u003cp\u003e1.99\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c7\"\u003e \u003cp\u003e0.3137\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e \u003cp\u003eLF\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c3\"\u003e \u003cp\u003e3194.4\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c4\"\u003e \u003cp\u003e360.78\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c5\"\u003e \u003cp\u003e4799.26\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c6\"\u003e \u003cp\u003e614.97\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c7\"\u003e \u003cp\u003e0.0078\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e \u003cp\u003eHF\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c3\"\u003e \u003cp\u003e1125.69\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c4\"\u003e \u003cp\u003e147.06\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c5\"\u003e \u003cp\u003e1910.46\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c6\"\u003e \u003cp\u003e428.87\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c7\"\u003e \u003cp\u003e0.3371\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e \u003cp\u003eLF/HF ratio\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c3\"\u003e \u003cp\u003e3.49\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c4\"\u003e \u003cp\u003e0.42\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c5\"\u003e \u003cp\u003e3.61\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c6\"\u003e \u003cp\u003e0.35\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c7\"\u003e \u003cp\u003e0.4401\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\" morerows=\"7\" rowspan=\"8\"\u003e \u003cp\u003e\u003cb\u003eLate-tilt\u003c/b\u003e\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e \u003cp\u003eSDNN\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c3\"\u003e \u003cp\u003e47.68\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c4\"\u003e \u003cp\u003e2.69\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c5\"\u003e \u003cp\u003e53.89\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c6\"\u003e \u003cp\u003e4.22\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c7\"\u003e \u003cp\u003e0.0524\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e \u003cp\u003eMean HR\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c3\"\u003e \u003cp\u003e81.81\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c4\"\u003e \u003cp\u003e1.84\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c5\"\u003e \u003cp\u003e78.1\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c6\"\u003e \u003cp\u003e1.85\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c7\"\u003e \u003cp\u003e0.028\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e \u003cp\u003eRMSSD\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c3\"\u003e \u003cp\u003e24.65\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c4\"\u003e \u003cp\u003e1.43\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c5\"\u003e \u003cp\u003e28.6\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c6\"\u003e \u003cp\u003e3\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c7\"\u003e \u003cp\u003e0.3137\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e \u003cp\u003epNN30\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c3\"\u003e \u003cp\u003e20.36\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c4\"\u003e \u003cp\u003e2.23\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c5\"\u003e \u003cp\u003e23.03\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c6\"\u003e \u003cp\u003e3.3\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c7\"\u003e \u003cp\u003e0.33\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e \u003cp\u003epNN50\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c3\"\u003e \u003cp\u003e5.81\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c4\"\u003e \u003cp\u003e1.06\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c5\"\u003e \u003cp\u003e9.35\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c6\"\u003e \u003cp\u003e2.43\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c7\"\u003e \u003cp\u003e0.5505\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e \u003cp\u003eLF\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c3\"\u003e \u003cp\u003e3710.91\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c4\"\u003e \u003cp\u003e544.17\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c5\"\u003e \u003cp\u003e4551.95\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c6\"\u003e \u003cp\u003e947.51\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c7\"\u003e \u003cp\u003e0.7894\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e \u003cp\u003eHF\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c3\"\u003e \u003cp\u003e1154.42\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c4\"\u003e \u003cp\u003e149.05\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c5\"\u003e \u003cp\u003e1723.43\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c6\"\u003e \u003cp\u003e415.47\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c7\"\u003e \u003cp\u003e0.3568\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e \u003cp\u003eLF/HF ratio\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c3\"\u003e \u003cp\u003e3.95\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c4\"\u003e \u003cp\u003e0.47\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c5\"\u003e \u003cp\u003e3.53\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c6\"\u003e \u003cp\u003e0.39\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c7\"\u003e \u003cp\u003e0.475\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\" morerows=\"7\" rowspan=\"8\"\u003e \u003cp\u003e\u003cb\u003eRecovery\u003c/b\u003e\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e \u003cp\u003eSDNN\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c3\"\u003e \u003cp\u003e65.53\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c4\"\u003e \u003cp\u003e3.29\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c5\"\u003e \u003cp\u003e67.97\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c6\"\u003e \u003cp\u003e4.66\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c7\"\u003e \u003cp\u003e0.5454\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e \u003cp\u003eMean HR\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c3\"\u003e \u003cp\u003e67.18\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c4\"\u003e \u003cp\u003e1.53\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c5\"\u003e \u003cp\u003e65.06\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c6\"\u003e \u003cp\u003e1.46\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c7\"\u003e \u003cp\u003e0.1223\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e \u003cp\u003eRMSSD\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c3\"\u003e \u003cp\u003e54.97\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c4\"\u003e \u003cp\u003e4.04\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c5\"\u003e \u003cp\u003e59.91\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c6\"\u003e \u003cp\u003e8.26\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c7\"\u003e \u003cp\u003e0.8669\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e \u003cp\u003epNN30\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c3\"\u003e \u003cp\u003e52.11\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c4\"\u003e \u003cp\u003e3.5\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c5\"\u003e \u003cp\u003e50.24\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c6\"\u003e \u003cp\u003e3.95\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c7\"\u003e \u003cp\u003e0.8478\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e \u003cp\u003epNN50\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c3\"\u003e \u003cp\u003e31.49\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c4\"\u003e \u003cp\u003e3.25\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c5\"\u003e \u003cp\u003e30.8\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c6\"\u003e \u003cp\u003e3.9\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c7\"\u003e \u003cp\u003e0.719\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e \u003cp\u003eLF\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c3\"\u003e \u003cp\u003e5449.6\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c4\"\u003e \u003cp\u003e609.15\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c5\"\u003e \u003cp\u003e5661.29\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c6\"\u003e \u003cp\u003e1201.64\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c7\"\u003e \u003cp\u003e0.7696\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e \u003cp\u003eHF\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c3\"\u003e \u003cp\u003e4901.47\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c4\"\u003e \u003cp\u003e733.79\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c5\"\u003e \u003cp\u003e5166.3\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c6\"\u003e \u003cp\u003e1018.93\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c7\"\u003e \u003cp\u003e0.8478\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e \u003cp\u003eLF/HF ratio\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c3\"\u003e \u003cp\u003e1.7\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c4\"\u003e \u003cp\u003e0.3\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c5\"\u003e \u003cp\u003e1.64\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c6\"\u003e \u003cp\u003e0.26\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c7\"\u003e \u003cp\u003e0.8811\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003c/tbody\u003e \u003c/colgroup\u003e \u003c/table\u003e\u003c/div\u003e \u003c/p\u003e \u003cp\u003e \u003c/p\u003e \u003c/div\u003e \u003c/div\u003e \u003cdiv id=\"Sec18\" class=\"Section2\"\u003e \u003ch2\u003e3.4. Differences in baroreflex-mediated autonomic control from pre- to post-stimulation\u003c/h2\u003e \u003cdiv id=\"Sec19\" class=\"Section3\"\u003e \u003ch2\u003e3.4.1. Changes in BRS during taVNS stimulation\u003c/h2\u003e \u003cp\u003e \u003cdiv class=\"BlockQuote\"\u003e \u003cp\u003eBRS was used to assess the effect of taVNS on baroreflex control during induced blood pressure perturbation (tilt). The up-slope BRS increased from 9.59\u0026thinsp;\u0026plusmn;\u0026thinsp;0.52 to 12.1\u0026thinsp;\u0026plusmn;\u0026thinsp;0.66 ms/mmHg (p\u0026thinsp;=\u0026thinsp;0.0004), and the down-slope BRS increased from 9.28\u0026thinsp;\u0026plusmn;\u0026thinsp;0.63 to 12.16\u0026thinsp;\u0026plusmn;\u0026thinsp;0.61 ms/mmHg (p\u0026thinsp;=\u0026thinsp;0.0001) (Table\u0026nbsp;\u003cspan refid=\"Tab6\" class=\"InternalRef\"\u003e6\u003c/span\u003e and Fig.\u0026nbsp;\u003cspan refid=\"Fig4\" class=\"InternalRef\"\u003e4\u003c/span\u003e).\u003c/p\u003e \u003c/div\u003e \u003c/p\u003e \u003cp\u003e \u003cdiv class=\"gridtable\"\u003e\u003ctable float=\"Yes\" id=\"Tab6\" border=\"1\"\u003e \u003ccaption language=\"En\"\u003e \u003cdiv class=\"CaptionNumber\"\u003eTable 6\u003c/div\u003e \u003cdiv class=\"CaptionContent\"\u003e \u003cp\u003eComparison of BRS from Pre- to Post-taVNS Across Tilt Sessions\u003c/p\u003e \u003c/div\u003e \u003c/caption\u003e \u003ccolgroup cols=\"6\"\u003e \u003cdiv align=\"left\" class=\"colspec\" colname=\"c1\" colnum=\"1\"\u003e\u003c/div\u003e \u003cdiv align=\"char\" char=\".\" class=\"colspec\" colname=\"c2\" colnum=\"2\"\u003e\u003c/div\u003e \u003cdiv align=\"char\" char=\".\" class=\"colspec\" colname=\"c3\" colnum=\"3\"\u003e\u003c/div\u003e \u003cdiv align=\"char\" char=\".\" class=\"colspec\" colname=\"c4\" colnum=\"4\"\u003e\u003c/div\u003e \u003cdiv align=\"char\" char=\".\" class=\"colspec\" colname=\"c5\" colnum=\"5\"\u003e\u003c/div\u003e \u003cdiv align=\"char\" char=\".\" class=\"colspec\" colname=\"c6\" colnum=\"6\"\u003e\u003c/div\u003e \u003cthead\u003e \u003ctr\u003e \u003cth align=\"left\" colname=\"c1\" morerows=\"1\" rowspan=\"2\"\u003e \u003cp\u003eParameters\u003c/p\u003e \u003c/th\u003e \u003cth align=\"left\" colspan=\"5\" nameend=\"c6\" namest=\"c2\"\u003e \u003cp\u003eTilt (10 min)\u003c/p\u003e \u003c/th\u003e \u003c/tr\u003e \u003ctr\u003e \u003cth align=\"left\" colspan=\"2\" nameend=\"c3\" namest=\"c2\"\u003e \u003cp\u003ePre-taVNS\u003c/p\u003e \u003c/th\u003e \u003cth align=\"left\" colspan=\"2\" nameend=\"c5\" namest=\"c4\"\u003e \u003cp\u003ePost-taVNS\u003c/p\u003e \u003c/th\u003e \u003cth align=\"left\" colname=\"c6\" morerows=\"1\" rowspan=\"2\"\u003e \u003cp\u003ep-value\u003c/p\u003e \u003c/th\u003e \u003c/tr\u003e \u003ctr\u003e \u003cth align=\"left\" colname=\"c2\"\u003e \u003cp\u003eMean\u003c/p\u003e \u003c/th\u003e \u003cth align=\"left\" colname=\"c3\"\u003e \u003cp\u003eSEM\u003c/p\u003e \u003c/th\u003e \u003cth align=\"left\" colname=\"c4\"\u003e \u003cp\u003eMean\u003c/p\u003e \u003c/th\u003e \u003cth align=\"left\" colname=\"c5\"\u003e \u003cp\u003eSEM\u003c/p\u003e \u003c/th\u003e \u003c/tr\u003e \u003c/thead\u003e \u003ctbody\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003eUp-slope\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c2\"\u003e \u003cp\u003e9.59\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c3\"\u003e \u003cp\u003e0.52\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c4\"\u003e \u003cp\u003e12.1\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c5\"\u003e \u003cp\u003e0.66\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c6\"\u003e \u003cp\u003e0.0025\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003eDown-slope\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c2\"\u003e \u003cp\u003e9.28\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c3\"\u003e \u003cp\u003e0.63\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c4\"\u003e \u003cp\u003e12.16\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c5\"\u003e \u003cp\u003e0.61\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c6\"\u003e \u003cp\u003e0.0007\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003eAll-slope\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c2\"\u003e \u003cp\u003e9.43\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c3\"\u003e \u003cp\u003e0.55\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c4\"\u003e \u003cp\u003e12.13\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c5\"\u003e \u003cp\u003e0.59\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c6\"\u003e \u003cp\u003e0.0008\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003c/tbody\u003e \u003c/colgroup\u003e \u003c/table\u003e\u003c/div\u003e \u003c/p\u003e \u003cp\u003e \u003c/p\u003e \u003c/div\u003e \u003cdiv id=\"Sec20\" class=\"Section3\"\u003e \u003ch2\u003e3.4.2. Changes in BRS during sham stimulation\u003c/h2\u003e \u003cp\u003e \u003cdiv class=\"BlockQuote\"\u003e \u003cp\u003eAs in the taVNS analysis, BRS was evaluated pre- and post-sham during the tilt phase (Table\u0026nbsp;\u003cspan refid=\"Tab7\" class=\"InternalRef\"\u003e7\u003c/span\u003e and Fig.\u0026nbsp;\u003cspan refid=\"Fig5\" class=\"InternalRef\"\u003e5\u003c/span\u003e). No significant differences were observed for either the up-slope or down-slope values (up-slope: 12.18 \u003cspan class=\"InlineEquation\"\u003e\u003cspan class=\"mathinline\"\u003e\\(\\:\\pm\\:\\)\u003c/span\u003e\u003c/span\u003e 0.83 to 13.23 \u003cspan class=\"InlineEquation\"\u003e\u003cspan class=\"mathinline\"\u003e\\(\\:\\pm\\:\\)\u003c/span\u003e\u003c/span\u003e 1.36, p\u0026thinsp;=\u0026thinsp;0. 8664; down-slope: 12.16 \u003cspan class=\"InlineEquation\"\u003e\u003cspan class=\"mathinline\"\u003e\\(\\:\\pm\\:\\)\u003c/span\u003e\u003c/span\u003e 0.73 to 13.03 \u003cspan class=\"InlineEquation\"\u003e\u003cspan class=\"mathinline\"\u003e\\(\\:\\pm\\:\\)\u003c/span\u003e\u003c/span\u003e 1.15 p\u0026thinsp;=\u0026thinsp;0. 5249).\u003c/p\u003e \u003c/div\u003e \u003c/p\u003e \u003cp\u003e \u003cdiv class=\"gridtable\"\u003e\u003ctable float=\"Yes\" id=\"Tab7\" border=\"1\"\u003e \u003ccaption language=\"En\"\u003e \u003cdiv class=\"CaptionNumber\"\u003eTable 7\u003c/div\u003e \u003cdiv class=\"CaptionContent\"\u003e \u003cp\u003eComparison of BRS from Pre- to Post-sham Across Tilt Sessions\u003c/p\u003e \u003c/div\u003e \u003c/caption\u003e \u003ccolgroup cols=\"6\"\u003e \u003cdiv align=\"left\" class=\"colspec\" colname=\"c1\" colnum=\"1\"\u003e\u003c/div\u003e \u003cdiv align=\"char\" char=\".\" class=\"colspec\" colname=\"c2\" colnum=\"2\"\u003e\u003c/div\u003e \u003cdiv align=\"char\" char=\".\" class=\"colspec\" colname=\"c3\" colnum=\"3\"\u003e\u003c/div\u003e \u003cdiv align=\"char\" char=\".\" class=\"colspec\" colname=\"c4\" colnum=\"4\"\u003e\u003c/div\u003e \u003cdiv align=\"char\" char=\".\" class=\"colspec\" colname=\"c5\" colnum=\"5\"\u003e\u003c/div\u003e \u003cdiv align=\"char\" char=\".\" class=\"colspec\" colname=\"c6\" colnum=\"6\"\u003e\u003c/div\u003e \u003cthead\u003e \u003ctr\u003e \u003cth align=\"left\" colname=\"c1\" morerows=\"1\" rowspan=\"2\"\u003e \u003cp\u003eParameters\u003c/p\u003e \u003c/th\u003e \u003cth align=\"left\" colspan=\"5\" nameend=\"c6\" namest=\"c2\"\u003e \u003cp\u003eTilt (10 min)\u003c/p\u003e \u003c/th\u003e \u003c/tr\u003e \u003ctr\u003e \u003cth align=\"left\" colspan=\"2\" nameend=\"c3\" namest=\"c2\"\u003e \u003cp\u003ePre-sham\u003c/p\u003e \u003c/th\u003e \u003cth align=\"left\" colspan=\"2\" nameend=\"c5\" namest=\"c4\"\u003e \u003cp\u003ePost-sham\u003c/p\u003e \u003c/th\u003e \u003cth align=\"left\" colname=\"c6\" morerows=\"1\" rowspan=\"2\"\u003e \u003cp\u003ep-value\u003c/p\u003e \u003c/th\u003e \u003c/tr\u003e \u003ctr\u003e \u003cth align=\"left\" colname=\"c2\"\u003e \u003cp\u003eMean\u003c/p\u003e \u003c/th\u003e \u003cth align=\"left\" colname=\"c3\"\u003e \u003cp\u003eSEM\u003c/p\u003e \u003c/th\u003e \u003cth align=\"left\" colname=\"c4\"\u003e \u003cp\u003eMean\u003c/p\u003e \u003c/th\u003e \u003cth align=\"left\" colname=\"c5\"\u003e \u003cp\u003eSEM\u003c/p\u003e \u003c/th\u003e \u003c/tr\u003e \u003c/thead\u003e \u003ctbody\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003eUp-slope\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c2\"\u003e \u003cp\u003e12.18\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c3\"\u003e \u003cp\u003e0.83\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c4\"\u003e \u003cp\u003e13.23\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c5\"\u003e \u003cp\u003e1.36\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c6\"\u003e \u003cp\u003e0.8811\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003eDown-slope\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c2\"\u003e \u003cp\u003e12.16\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c3\"\u003e \u003cp\u003e0.73\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c4\"\u003e \u003cp\u003e13.03\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c5\"\u003e \u003cp\u003e1.15\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c6\"\u003e \u003cp\u003e0.6111\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003eAll-slope\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c2\"\u003e \u003cp\u003e12.17\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c3\"\u003e \u003cp\u003e0.74\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c4\"\u003e \u003cp\u003e13.13\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c5\"\u003e \u003cp\u003e1.2\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c6\"\u003e \u003cp\u003e0.8478\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003c/tbody\u003e \u003c/colgroup\u003e \u003c/table\u003e\u003c/div\u003e \u003c/p\u003e \u003cp\u003e \u003c/p\u003e \u003c/div\u003e \u003c/div\u003e \u003cdiv id=\"Sec21\" class=\"Section2\"\u003e \u003ch2\u003e3.5. Response to taVNS was predicted by baseline autonomic tone\u003c/h2\u003e \u003cp\u003e \u003cdiv class=\"BlockQuote\"\u003e \u003cp\u003eTo evaluate whether baseline autonomic tone predicts responsiveness to taVNS, we conducted linear regression analyses between the pre-taVNS S-baseline autonomic parameters and taVNS-induced changes. Among the frequency-domain parameters, a strong negative correlation was found between the pre-taVNS LF/HF ratio and its post-taVNS change (R\u0026sup2; = 0.78, p\u0026thinsp;\u0026lt;\u0026thinsp;0.0001), indicating that individuals with higher sympathetic predominance at baseline experienced greater reductions following taVNS. The mean pre-taVNS HR also showed a significant negative correlation with its change (R\u0026sup2; = 0.50, p\u0026thinsp;\u0026lt;\u0026thinsp;0.0001). In the time domain, moderate negative correlations were observed between the baseline parasympathetic markers\u0026mdash;RMSSD (R\u0026sup2; = 0.17, p\u0026thinsp;=\u0026thinsp;0.0204), pNN30 (R\u0026sup2; = 0.35, p\u0026thinsp;=\u0026thinsp;0.0003), and pNN50 (R\u0026sup2; = 0.20, p\u0026thinsp;=\u0026thinsp;0.0096)\u0026mdash;and their respective changes. These findings suggest that individuals with reduced baseline parasympathetic activity demonstrated greater improvements following taVNS (Fig.\u0026nbsp;\u003cspan refid=\"Fig6\" class=\"InternalRef\"\u003e6\u003c/span\u003e). In our analysis of BRS, we observed changes during the tilt sessions. The changes in BRS down-slope (R\u0026sup2; = 0.22, p\u0026thinsp;=\u0026thinsp;0.0062) and all-slope (R\u0026sup2; = 0.14, p\u0026thinsp;=\u0026thinsp;0.0385) showed significant negative correlations with the baseline values, implying enhanced baroreflex responsiveness, particularly in individuals with lower pre-taVNS BRS (Fig.\u0026nbsp;\u003cspan refid=\"Fig7\" class=\"InternalRef\"\u003e7\u003c/span\u003e).\u003c/p\u003e \u003c/div\u003e \u003c/p\u003e \u003cp\u003e \u003c/p\u003e \u003cp\u003e \u003c/p\u003e \u003c/div\u003e"},{"header":"4. Discussion","content":"\u003cp\u003e \u003cdiv class=\"BlockQuote\"\u003e \u003cp\u003eIn this study, we investigated the effects of taVNS on autonomic function by using the HUTT both pre- and post- stimulation. HRV was compared across the S-baseline, tilt, and recovery phases, whereas BRS was specifically analyzed during the tilt phase to evaluate autonomic responsiveness during induced blood pressure perturbation. In our normotensive participants, these analyses quantified the effects of taVNS during hemodynamic stress, demonstrating its capacity to enhance autonomic regulation, particularly baroreflex-mediated control. Collectively, our findings underscore the therapeutic potential of taVNS in restoring and strengthening autonomic responsiveness, which has significant implications for conditions characterized by autonomic dysfunction, such as hypertension.\u003c/p\u003e \u003c/div\u003e \u003c/p\u003e \u003cdiv id=\"Sec23\" class=\"Section2\"\u003e \u003ch2\u003e4.1. Autonomic regulation reflected in HRV responses to taVNS\u003c/h2\u003e \u003cp\u003e\u003cdiv class=\"BlockQuote\"\u003e\u003cp\u003eIn the S-baseline phase, most of the parasympathetic HRV parameters, particularly RMSSD, pNN50, and HF power, increased significantly, though the LF/HF ratio did not. This pattern suggests that taVNS facilitates parasympathetic activation at baseline, consistent with enhanced vagal control of the heart rate. For example, Geng et al. (2022) reported significant increases in parasympathetic HRV parameters following short taVNS sessions in young adults [\u003cspan citationid=\"CR36\" class=\"CitationRef\"\u003e36\u003c/span\u003e]. Also, Clancy et al. (2014) reported a reduction in the LF/HF ratio, indicating sympathetic inhibition and parasympathetic enhancement [\u003cspan citationid=\"CR31\" class=\"CitationRef\"\u003e31\u003c/span\u003e]. The LF/HF ratio did not change significantly in this study, which could reflect differences in stimulation duration and protocol. Nonetheless, taken together with the consistent increases in multiple parasympathetic parameters, our results support the view that taVNS attenuates relative sympathetic predominance while augmenting parasympathetic modulation [\u003cspan citationid=\"CR44\" class=\"CitationRef\"\u003e44\u003c/span\u003e]. By contrast, in the sham condition, some parameters reached statistical significance, but no consistent pattern was observed across parameters or phases. In particular, key parasympathetic markers (RMSSD, HF, LF/HF ratio) did not show consistent changes. These observations indicate that the HRV changes identified here are unlikely to be attributable to the mere passage of time or nonspecific factors but rather reflect physiological effects of taVNS.\u003c/p\u003e\u003cp\u003eDuring the tilt phase, gravitational pooling typically elicits an increase in sympathetic activity and a suppression of vagal activity, thereby reducing parasympathetic HRV parameters and elevating the LF/HF ratio [\u003cspan citationid=\"CR45\" class=\"CitationRef\"\u003e45\u003c/span\u003e, \u003cspan citationid=\"CR46\" class=\"CitationRef\"\u003e46\u003c/span\u003e]. Nevertheless, in this study, the HRV parameters improved during tilt following taVNS, suggesting that taVNS might partially attenuate tilt-induced vagal withdrawal and enhance overall autonomic responsiveness. These effects can be interpreted as the afferent activation of the ABVN converging on the NTS, which in turn augments vagal efferent output via the NA/DMV and concurrently suppresses the sympathetic drive through the CVLM\u0026ndash;RVLM pathway [\u003cspan additionalcitationids=\"CR48\" citationid=\"CR47\" class=\"CitationRef\"\u003e47\u003c/span\u003e\u0026ndash;\u003cspan citationid=\"CR49\" class=\"CitationRef\"\u003e49\u003c/span\u003e].\u003c/p\u003e\u003cp\u003eThe HRV changes observed in this study are also consistent with afferent activation of the ABVN converging on the NTS and thereby enhancing vagal (parasympathetic) efferent output. Moreover, the improvement in HRV during the tilt phase suggests that taVNS might preserve vagal tone and enhance autonomic responsiveness during orthostatic stress. In contrast, in the sham condition, some parameters reached statistical significance, but no consistent pattern emerged across parameters or phases. Taken together, our results support the interpretation that the HRV effects reflect physiological mechanisms of taVNS, rather than the placebo effect or passage of time.\u003c/p\u003e\u003c/div\u003e\u003c/p\u003e \u003c/div\u003e \u003cdiv id=\"Sec24\" class=\"Section2\"\u003e \u003ch2\u003e4.2. Baroreflex sensitivity enhancement during orthostatic stress\u003c/h2\u003e \u003cp\u003e \u003cdiv class=\"BlockQuote\"\u003e \u003cp\u003eBeyond HRV, we assessed BRS to quantify reflex control of the heart rate in response to blood pressure changes\u0026ndash;a physiologically critical mechanism for short-term cardiovascular stability [\u003cspan citationid=\"CR50\" class=\"CitationRef\"\u003e50\u003c/span\u003e, \u003cspan citationid=\"CR51\" class=\"CitationRef\"\u003e51\u003c/span\u003e]. Importantly, compared with HRV, which provides indirect insights into autonomic modulation, BRS offers a more mechanistically specific index of baroreflex-mediated autonomic control because it directly reflects the dynamic interplay between SBP and IBI.\u003c/p\u003e \u003cp\u003eIn this study, we examined BRS during the tilt phase, a condition of orthostatic stress that physiologically induces gravitational pooling, lowering arterial pressure and typically eliciting increased sympathetic activation and vagal withdrawal [\u003cspan citationid=\"CR52\" class=\"CitationRef\"\u003e52\u003c/span\u003e, \u003cspan citationid=\"CR53\" class=\"CitationRef\"\u003e53\u003c/span\u003e]. That process often leads to a blunted baroreflex response in healthy individuals. However, our findings revealed that both the up-slope and down-slope BRS values increased significantly during the tilt phase after taVNS, indicating a marked enhancement of IBI responsiveness to blood pressure perturbation under stress. This suggests that taVNS can actively counteract tilt-induced autonomic imbalances by reinforcing baroreflex engagement [\u003cspan citationid=\"CR54\" class=\"CitationRef\"\u003e54\u003c/span\u003e]. This pattern is presumed to involve afferent activation of the ABVN, which projects to the NTS in the brainstem. This afferent input could facilitate parasympathetic outflow via the NA and DMV, while simultaneously suppressing sympathetic tone via the CVLM\u0026ndash;RVLM inhibitory pathway. These neural interactions together strengthen baroreflex arc functionality and autonomic adaptability.\u003c/p\u003e \u003cp\u003eIn contrast, in the sham condition, BRS showed no significant change from pre- to post-stimulation, supporting the interpretation that the taVNS effect reflects physiological activation of the baroreflex pathway rather than the passage of time or expectancy.\u003c/p\u003e \u003cp\u003eReduced BRS is strongly associated with increased cardiovascular risk, including in patient populations with hypertension, orthostatic hypotension, and autonomic dysfunction [\u003cspan citationid=\"CR55\" class=\"CitationRef\"\u003e55\u003c/span\u003e, \u003cspan citationid=\"CR56\" class=\"CitationRef\"\u003e56\u003c/span\u003e]. Therefore, the findings of this study have significant translational potential. The taVNS-induced BRS enhancement observed here supports the utility of this intervention for restoring reflex autonomic balance in clinical populations.\u003c/p\u003e \u003cp\u003eIn sum, whereas the HRV analysis demonstrated enhanced parasympathetic modulation, the BRS findings provide direct, phase-specific evidence that taVNS strengthens cardiovascular reflex regulation during physiological stress, underscoring BRS modulation during tilt as the most clinically meaningful outcome of this study [\u003cspan citationid=\"CR57\" class=\"CitationRef\"\u003e57\u003c/span\u003e].\u003c/p\u003e \u003c/div\u003e \u003c/p\u003e \u003c/div\u003e \u003cdiv id=\"Sec25\" class=\"Section2\"\u003e \u003ch2\u003e4.3. Predictive role of baseline autonomic tone in taVNS responsiveness\u003c/h2\u003e \u003cp\u003e\u003cdiv class=\"BlockQuote\"\u003e\u003cp\u003eThe results of the regression analysis indicate that the autonomic regulatory effects of taVNS can vary depending on an individual's baseline level of autonomic activity. The strong inverse association between the baseline LF/HF ratio and its reduction after stimulation underscores the potential of taVNS to correct autonomic imbalance, particularly in individuals with sympathetic predominance. These results align with previous findings suggesting that the effects of taVNS might be more prominent in individuals with reduced baseline autonomic balance [\u003cspan citationid=\"CR58\" class=\"CitationRef\"\u003e58\u003c/span\u003e]. Similarly, greater improvements in RMSSD, pNN30, and pNN50 in participants with low initial parasympathetic tone suggest that taVNS could be especially effective in restoring vagal modulation in hypoactive states [\u003cspan citationid=\"CR59\" class=\"CitationRef\"\u003e59\u003c/span\u003e, \u003cspan citationid=\"CR60\" class=\"CitationRef\"\u003e60\u003c/span\u003e]. Importantly, the observation that lower baseline BRS predicted greater improvements in baroreflex function highlights a key mechanistic pathway of taVNS beyond heart rate modulation. These findings support the view that baseline autonomic markers could serve as useful predictors of individualized taVNS responsiveness and inform future clinical applications, particularly in populations with autonomic dysregulation such as hypertension or orthostatic intolerance.\u003c/p\u003e\u003c/div\u003e\u003c/p\u003e \u003c/div\u003e \u003cdiv id=\"Sec26\" class=\"Section2\"\u003e \u003ch2\u003e4.4. Novelty and contributions\u003c/h2\u003e \u003cp\u003e \u003cdiv class=\"BlockQuote\"\u003e \u003cp\u003eMost prior taVNS studies have assessed autonomic modulation at rest, used short stimulation durations, and focused on HRV. Even when BRS was assessed, measurements were typically restricted to resting conditions without sufficient blood pressure perturbation, limiting the physiological relevance and interpretability of baroreflex responsiveness. To validate the effects of taVNS in more physiologically meaningful conditions, we applied 60 minutes of taVNS at rest and subsequently induced controlled blood pressure perturbation using the HUTT. With its phased structure (S-baseline\u0026ndash;tilt\u0026ndash;recovery), the HUTT enables standardized observation of autonomic regulation at S-baseline, during orthostatic stress, and throughout recovery, thereby providing an excellent framework for evaluating functional resilience and stress adaptability beyond resting conditions.\u003c/p\u003e \u003cp\u003eOur combined analysis of HRV and BRS data collected using this design demonstrates not only basal enhancement of parasympathetic activity, as evidenced by significant increases in the parasympathetic HRV parameters (e.g., HF, RMSSD) at S-baseline, but also a significant improvement in BRS during the tilt phase, confirming that taVNS can support baroreceptor reflex pathways in response to blood pressure perturbation. This enhancement of BRS during orthostatic stress is a central and novel contribution of this study. Our findings suggest that taVNS can reinforce short-term cardiovascular reflexes precisely when autonomic demand is heightened.\u003c/p\u003e \u003cp\u003eIn addition, the inclusion of a sham condition allowed us to control for potential changes in autonomic parameters due to the mere passage of time or placebo effects. In the sham sessions, BRS showed no significant changes, and although the changes in some HRV parameters reached significance, the findings did not form a consistent pattern. Collectively, these results support the interpretation that taVNS strengthens autonomic regulation via ABVN\u0026ndash;NTS pathways, rather than reflecting nonspecific or placebo effects.\u003c/p\u003e \u003c/div\u003e \u003c/p\u003e \u003c/div\u003e \u003cdiv id=\"Sec27\" class=\"Section2\"\u003e \u003ch2\u003e4.5. Limitations\u003c/h2\u003e \u003cp\u003e \u003cdiv class=\"BlockQuote\"\u003e \u003cp\u003eThis study has several limitations. First, although our design induced blood pressure perturbation to evaluate autonomic responsiveness beyond resting conditions, our study population consisted of healthy adults, which limits the clinical generalizability of our results. In patient populations with autonomic abnormalities (e.g., hypertension, orthostatic hypotension, autonomic failure), responses to taVNS might differ. Therefore, follow-up studies with those groups are warranted. Second, because our participants were predominantly young adults, our findings might not fully capture age-related differences in autonomic responsiveness and taVNS effects. Given that autonomic flexibility and baroreflex function typically decline with age, taVNS efficacy could vary across age groups, underscoring the need for studies that include a broader age range. Third, we examined acute responses within a single session; therefore, we could not assess the cumulative effects of repeated or prolonged stimulation or potential residual effects after stimulation cessation. Future investigations using longitudinal designs are needed to determine the durability and stability of taVNS effects.\u003c/p\u003e \u003cp\u003eIn light of those limitations, future work should apply the present protocol to patients with hypertension or autonomic dysfunction and compare their responses with healthy controls to more clearly establish the therapeutic relevance of taVNS. Moreover, repeated and long-term stimulation with follow-up assessments of HRV and BRS will be important to determine whether taVNS offers sustained or cumulative benefits for blood pressure regulation and autonomic function. Such studies would provide empirical support for implementing taVNS as a noninvasive antihypertensive therapy and a strategy for autonomic reconditioning.\u003c/p\u003e \u003c/div\u003e \u003c/p\u003e \u003c/div\u003e"},{"header":"5. Conclusion","content":"\u003cp\u003e \u003cdiv class=\"BlockQuote\"\u003e \u003cp\u003eThis study quantitatively evaluated the effects of taVNS on autonomic function during blood pressure perturbation by analyzing HRV and BRS and characterizing autonomic responsiveness. We found that taVNS enhanced parasympathetic modulation and improved baroreflex responsiveness, not only at baseline but also during orthostatic stress. In comparison with the sham condition, the changes are consistent with a physiological mechanism, rather than a placebo effect. Importantly, our findings extend the evidence for taVNS beyond resting conditions to periods of rapid autonomic change, supporting its potential applicability in clinical populations with autonomic dysfunction, such as hypertension.\u003c/p\u003e \u003c/div\u003e \u003c/p\u003e"},{"header":"Declarations","content":"\u003cp\u003eFunding\u003c/p\u003e\n\u003cp\u003eThis work was supported by a National Research Foundation of Korea (NRF) grant funded by the Korean government (MSIT) (RS-2024-00333219).\u003c/p\u003e\n\u003cp\u003eAuthor contributions\u003c/p\u003e\n\u003cp\u003e\u003cstrong\u003eG.L:\u0026nbsp;\u003c/strong\u003eWrting \u0026ndash; original draft, Visualization, Validation, Software, Methodology, Formal analysis, Data curation, Conceptualization.\u003cstrong\u003e\u0026nbsp;D.K:\u0026nbsp;\u003c/strong\u003eWriting \u0026ndash; original draft, review \u0026amp;amp; editing, Methodology, Formal analysis, Data curation, Conceptualization.\u003cstrong\u003e\u0026nbsp;J.L:\u0026nbsp;\u003c/strong\u003eData curation.\u003cstrong\u003e\u0026nbsp;J.L:\u0026nbsp;\u003c/strong\u003eWriting \u0026ndash; review \u0026amp;amp; editing, Supervision.\u003cstrong\u003e\u0026nbsp;J.L:\u0026nbsp;\u003c/strong\u003eWriting \u0026ndash; review \u0026amp;amp; editing, Supervision, Project administration.\u003cstrong\u003e\u0026nbsp;I.Y.K:\u0026nbsp;\u003c/strong\u003eWriting - review \u0026amp;amp; editing, Supervision, Funding acquisition.\u003c/p\u003e\n\u003cp\u003eDeclaration of competing interest\u003c/p\u003e\n\u003cp\u003eThe authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper.\u003c/p\u003e\n\u003cp\u003eData Availability\u003c/p\u003e\n\u003cp\u003eThe datasets generated during and/or analyzed during the current study are available from the corresponding author on reasonable request.\u003c/p\u003e"},{"header":"References","content":"\u003col\u003e\u003cli\u003e\u003cspan\u003eMills, K. 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Effects of stimulus frequency, intensity, and sex on the autonomic response to transcutaneous vagus nerve stimulation. \u003cem\u003eBrain Sci.\u003c/em\u003e \u003cb\u003e12\u003c/b\u003e (8), 1038 (2022).\u003c/span\u003e\u003c/li\u003e\u003c/ol\u003e"}],"fulltextSource":"","fullText":"","funders":[],"hasAdminPriorityOnWorkflow":false,"hasManuscriptDocX":true,"hasOptedInToPreprint":true,"hasPassedJournalQc":"","hasAnyPriority":false,"hideJournal":false,"highlight":"","institution":"","isAcceptedByJournal":false,"isAuthorSuppliedPdf":false,"isDeskRejected":"","isHiddenFromSearch":false,"isInQc":false,"isInWorkflow":false,"isPdf":false,"isPdfUpToDate":true,"isWithdrawnOrRetracted":false,"journal":{"display":true,"email":"[email protected]","identity":"scientific-reports","isNatureJournal":false,"hasQc":true,"allowDirectSubmit":false,"externalIdentity":"scirep","sideBox":"Learn more about [Scientific Reports](http://www.nature.com/srep/)","snPcode":"","submissionUrl":"","title":"Scientific Reports","twitterHandle":"","acdcEnabled":true,"dfaEnabled":true,"editorialSystem":"stoa","reportingPortfolio":"Scientific Reports","inReviewEnabled":true,"inReviewRevisionsEnabled":true},"keywords":"transcutaneous auricular vagus nerve stimulation (taVNS), head-up tilt test, heart rate variability (HRV), baroreflex sensitivity (BRS)","lastPublishedDoi":"10.21203/rs.3.rs-8923528/v1","lastPublishedDoiUrl":"https://doi.org/10.21203/rs.3.rs-8923528/v1","license":{"name":"CC BY 4.0","url":"https://creativecommons.org/licenses/by/4.0/"},"manuscriptAbstract":"\u003cp\u003eBaroreflex dysfunction and autonomic imbalance are key pathophysiological features of hypertension, but current pharmacological approaches often fail to address these neural mechanisms. This study investigated whether transcutaneous auricular vagus nerve stimulation (taVNS) enhances autonomic regulation during blood pressure perturbation. In a randomized, single-blind, sham-controlled, crossover design experiment, 32 normotensive adults received 60-min taVNS or sham condition. Blood pressure perturbation was induced with the head-up tilt test (supine\u0026ndash;tilt\u0026ndash;supine). Heart rate variability (HRV) was analyzed across all four phases (S-baseline, early-tilt, late-tilt, recovery), whereas baroreflex sensitivity (BRS) was analyzed only during the 10-minute tilt phase. taVNS significantly increased parasympathetic HRV parameters (SDNN, RMSSD, pNN30, pNN50, HF) across all phases. During tilt, BRS up- and down-slope values increased significantly, indicating enhanced inter-beat interval responsiveness to systolic pressure fluctuations. In contrast, the sham procedure yielded no consistent changes in HRV or significant BRS alterations during tilt. These findings suggest that taVNS augments vagal modulation and baroreflex responsiveness, not only at rest but also during orthostatic stress, supporting a physiological mechanism that is likely mediated by auricular branch of the vagus nerve\u0026ndash; nucleus tractus solitarius pathways. Consequently, taVNS shows potential to modulate conditions involving autonomic dysregulation, such as hypertension, and further research involving patient cohorts and longitudinal study protocols is needed.\u003c/p\u003e \u003cp\u003eClinical Trial: The clinical trial described in this paper was registered at \u003cspan class=\"ExternalRef\"\u003e\u003cspan class=\"RefSource\"\u003ehttps://cris.nih.go.kr/cris/index/index.do\u003c/span\u003e\u003cspan address=\"https://cris.nih.go.kr/cris/index/index.do\" targettype=\"URL\" class=\"RefTarget\"\u003e\u003c/span\u003e\u003c/span\u003e under the registration number KCT0011752 (first trial registered 20/03/2026, retrospective registration).\u003c/p\u003e","manuscriptTitle":"Analysis of taVNS Effects on Baroreflex Sensitivity and Autonomic Nervous System Regulation During Head-up Tilt Test","msid":"","msnumber":"","nonDraftVersions":[{"code":1,"date":"2026-04-29 06:14:25","doi":"10.21203/rs.3.rs-8923528/v1","editorialEvents":[{"type":"communityComments","content":0},{"type":"editorInvitedReview","content":"","date":"2026-04-29T02:06:22+00:00","index":"hide","fulltext":""},{"type":"reviewerAgreed","content":"100900004394384958084537671489305444020","date":"2026-04-25T13:54:52+00:00","index":"hide","fulltext":""},{"type":"reviewerAgreed","content":"179259544008297033548712071214918509549","date":"2026-04-23T06:51:36+00:00","index":"hide","fulltext":""},{"type":"reviewerAgreed","content":"324817091470106080253814465330585905735","date":"2026-04-22T21:34:26+00:00","index":"hide","fulltext":""},{"type":"reviewerAgreed","content":"209552951701662567266566774277674868611","date":"2026-04-21T02:49:54+00:00","index":"hide","fulltext":""},{"type":"reviewersInvited","content":"","date":"2026-04-20T13:28:18+00:00","index":"","fulltext":""},{"type":"editorAssigned","content":"","date":"2026-04-20T13:21:48+00:00","index":"","fulltext":""},{"type":"editorInvited","content":"","date":"2026-03-27T15:50:47+00:00","index":"","fulltext":""},{"type":"checksComplete","content":"","date":"2026-03-26T01:19:20+00:00","index":"","fulltext":""},{"type":"submitted","content":"Scientific Reports","date":"2026-03-26T01:11:45+00:00","index":"","fulltext":""}],"status":"published","journal":{"display":true,"email":"[email protected]","identity":"scientific-reports","isNatureJournal":false,"hasQc":true,"allowDirectSubmit":false,"externalIdentity":"scirep","sideBox":"Learn more about [Scientific Reports](http://www.nature.com/srep/)","snPcode":"","submissionUrl":"","title":"Scientific Reports","twitterHandle":"","acdcEnabled":true,"dfaEnabled":true,"editorialSystem":"stoa","reportingPortfolio":"Scientific Reports","inReviewEnabled":true,"inReviewRevisionsEnabled":true}}],"origin":"","ownerIdentity":"c52c4462-eee1-4ae2-bda9-cb4be6e900c6","owner":[],"postedDate":"April 29th, 2026","published":true,"recentEditorialEvents":[],"rejectedJournal":[],"revision":"","amendment":"","status":"under-review","subjectAreas":[{"id":67004555,"name":"Health sciences/Medical research"},{"id":67004556,"name":"Health sciences/Neurology"},{"id":67004557,"name":"Biological sciences/Neuroscience"},{"id":67004558,"name":"Biological sciences/Physiology"}],"tags":[],"updatedAt":"2026-04-29T06:14:25+00:00","versionOfRecord":[],"versionCreatedAt":"2026-04-29 06:14:25","video":"","vorDoi":"","vorDoiUrl":"","workflowStages":[]},"version":"v1","identity":"rs-8923528","journalConfig":"researchsquare"},"__N_SSP":true},"page":"/article/[identity]/[[...version]]","query":{"redirect":"/article/rs-8923528","identity":"rs-8923528","version":["v1"]},"buildId":"XKTyCvWXoU3ODBz1xrDgd","isFallback":false,"isExperimentalCompile":false,"dynamicIds":[84888],"gssp":true,"scriptLoader":[]}