Background: Altered pattern of respiration has been shown to affect both the cardiac as well as cortical activity, which is the basis of central–autonomic dual interaction concept. On the other hand, effect of this association between altered breathing with slow cortical activity, that is, electroencephalography (EEG) theta waves (associated with learning and relaxed alertness) on the cardiac autonomic balance is largely unclear. Objective: The study aims to understand this interaction in response to altered respiratory patterns, for example, voluntary apnea, bradypnea, and tachypnea in terms of EEG and heart rate variability (HRV) correlates in normal healthy subjects. Methods: This study was conducted on 32 adult male subjects. EEG from F3, F4, P3, P4, O1 and O2 cortical areas and Lead II electrocardiography for HRV analysis was continuously recorded during aforesaid respiratory interventions. Power spectral analysis of EEG for theta waves and HRV measures, that is, RMSSD, pNN50, HF, LF, and LF/HF was calculated as % change taking resting value as 100%. Results: Apnea caused decrease in theta power, whereas an increase in LF/HF was observed in HRV. Bradypnea on the other hand, did not elicit any significant change in power of theta waves. However, decreased RMSSD and pNN50 were observed in HRV. Tachypnea led to increase in theta power with HRV depicting significantly decreased RMSSD and pNN50. Besides, significant correlation between EEG and HRV measures was found during tachypnea, which shifted toward posterior cortical sites as compared to resting condition. Conclusion: Various altered respiratory patterns caused either depressed parasympathetic or increased sympathetic output, whereas increased theta power along with posterior shift of correlation between theta power and HRV measures observed during post tachypnea might be due to involvement of global brain areas due to respiration-coupled neuronal activity. Thus, a definite link between cortical activity and autonomic output in relation to altered respiratory patterns may be suggested. Keywords Theta wave, HRV, apnea, hyperventilation, slow deep breathing Abbreviations ANS: autonomic nervous system CAN: central autonomic network CNS: central nervous system EEG: electroencephalography ECG: electrocardiography FFT: fast Fourier transformation HF: high frequency HRV: heart rate variability LF: low frequency pNN50: percent of pairs of adjacent RR interval with a difference of more than 50 msec RMSSD: square root of mean square differences of consecutive RR intervals RSA: respiratory sinus arrhythmia Introduction Department of Physiology, All India Institute of Medical Sciences, Raipur, Chhattisgarh, India Department of Medicine, JIPMER, Puducherry, India Various neuroimaging studies establishing functional Corresponding author: interaction between autonomic nervous system (ANS) and Meenakshi Sinha, Department of Physiology, All India Institute of Medical cortical processes involved in consciousness and attention Sciences, G. E. Road, Raipur, Chhattisgarh 492099, India. has supported the central autonomic network model for E-mail: email@example.com Creative Commons CC BY: This article is distributed under the terms of the Creative Commons Attribution 4.0 License (http://www. creativecommons.org/licenses/by/4.0/) which permits any use, reproduction and distribution of the work without further permission provided the original work is attributed as specified on the SAGE and Open Access pages (https://us.sagepub.com/en-us/nam/open-access-at-sage). 68 Annals of Neurosciences 27(2) 1–4 explaining ANS–CNS (central nervous system) interaction. 24 years, after obtaining Institutional Ethics Committee This interaction forms the basis for the dynamic nature clearance. Subsequently, written informed consent followed of homeostatic processes against the physiological or by detailed medical history was taken from each subject for pathological challenges to the body. In this context, heart rate selection of subjects as per criteria of exclusion and inclusion. variability (HRV), reflecting the alteration in RR intervals Individuals with medical history affecting autonomic function, over time, is being used widely for studying the functional presence of any psychological or neurological disorder, 6,7 link between cardiovascular system and CNS. smoking habit, alcohol consumption/respiratory illnesses/ On lines of the above concept, output of one such hypertension/diabetes mellitus, etc., were not included. autonomically regulated system, that is, respiratory system Recording of EEG: International electrode placement has been extensively studied to assess the ANS–CNS link. It is (10–20 system) was used to record EEG from frontal, parietal, quite obvious that altered respiratory pattern due to voluntary and occipital regions (F3, P1, O1 as left and F4, P2, O2 as control or presence of some disease conditions (e.g., chronic right leads) bilaterally with reference electrodes placed on the obstructive pulmonary disease (COPD), asthma, or fibrosis, left and right earlobes (A1 and A2). The impedance of each etc.) leads to significant alteration in the autonomic states electrode was kept at <5 kΩ. Digital EEG machine (Recorder 8–10 in terms of sympathetic and parasympathetic responses. & Medicare System, India) was connected with these Also, hypoxemia, hypercapnia, or hypocapnia induced by the electrodes for EEG acquisition. The recorded raw signals altered respiratory patterns have been shown to elicit several were digitized and then put for fast Fourier transformation hemodynamic changes, which are also reflected in altered cortical (FFT) with the help of inbuilt software for power spectral 11,12 functions. There is widespread presence of respiration- analysis to calculate power of frequency spectrum of EEG coupled neuronal activity, which reverberate to the whole brain waves. and has been linked to inter-regional communication. Besides Recording of ECG for HRV analysis: Lead II various other activities, production of slow theta waves at the electrocardiography (ECG) was recorded using the standard cortex is responsible for synchronization of neuronal activity. limb electrode placement. Recording and acquisition of ECG In this context, recent studies have documented direct link signals was done with the help of inbuilt software followed between slow nasal respiration and slow brain rhythms leading by short-term HRV analysis for the artifact free record 11,13 to increased delta-theta EEG activity. Such slow deep before and after each intervention, using Labchart software breathing induced slow EEG activities have been associated (ADInstruments, USA). with functional state of alert relaxation, enhanced cognitive Study design: All the recordings were done at the 17,18 13 processing, and meditative practices. Deep breathing, laboratory temperature of 26 ± 2 °C in the afternoon, 2–3 besides producing central-largest cortical topography, also hours post prandial. Immediately after arrival to the lab and leads to increased activation of the parasympathetic nervous then after 10–15 minutes, resting blood pressure and heart rate system. Increased correlation has been reported between HRV were measured. Then, with instruction to remain completely measures and alpha/theta rhythm of EEG during event related relaxed, ECG and EEG were simultaneously recorded on the attention exercises. On the other hand, hyperventilation, subject with eyes closed in supine position. The recording was which is classically used as an activation method during EEG done till >50% of alpha activity was observed at the occipital recording, has been found to provoke physiological slowing of electrode site. This was followed by the subjects carrying brain rhythms in the range of delta and theta activity. out the simulations of apnea, bradypnea, and tachypnea, as However, interaction of various signals to regulate the per protocol described later. Following each intervention, at cortical activity remains to be explored. Scant literature is least 15 minutes of resting record were taken so that heart available to correlate the autonomic changes with the slow rate and EEG returned to the preintervention condition. waves of cortex, mainly theta activity simultaneously during Continuous recording of ECG and EEG was done during the altered respiratory patterns in normal healthy subjects. whole study period. Therefore, present work aim to assess influence of altered respiratory patterns, that is, voluntary breath-holding (apnea), deep and slow breathing (bradypnea), and hyperventilation Protocol for Eliciting Altered Breathing Patterns (tachypnea) on the slow theta activity (by EEG analysis) with Apnea: Subjects were asked to perform voluntary breath- the parallel cardiac autonomic features (in terms of HRV) holding at the end of inspiration phase till he reaches his in the same platform, which might have important role in breaking point as confirmed by the diaphragmatic flutter. entraining central autonomic networks in healthy individuals. Bradypnea: Deep breathing was performed for a period of 3 minutes following a cycle of 6 breaths/minute to produce bradypnea. Methods Tachypnea: Deep and rapid breathing for 3 minutes at In this self-controlled prospective study, we recruited 32 a cycle of 30 breaths/minute was performed to produce healthy adult male volunteers of age group between 18 and tachypnea. Sinha et al. 69 EEG waveform reduction: Random selection of five Whitney U test. Correlation between EEG and HRV measures artifact free epochs of 6 seconds duration each was done by was estimated using Pearson’s correlation test. All statistical visually inspecting EEG records during (a) preintervention analyses were carried out at the significance level ≤.05. sessions and then (b) 0–2 minutes immediately after intervention with an interepoch interval of 20 seconds. With Results the help of FFT, EEG waveforms were decomposed into their sine wave components in terms of respective frequency bands, The present study was conducted on 32 normal adult male that is, alpha (8–12 Hz), beta (15–30 Hz), and theta (4–8 Hz) subjects with a mean BMI of 21.49 ± 2.36. All preintervention and absolute power (in uv ). However, for the present study, resting EEG and HRV values have been expressed as standard we analyzed the theta power activity only. The recorded units, whereas postintervention data are expressed as % change, powers following each postintervention session for each of resting values being taken as 100%. All postintervention the above frequency bands were calculated as percentage measures of theta power (obtained from EEG) and HRV are (%) change in relation to their respective resting absolute calculated in the first 2 minutes of intervention to see the EEG power, so that large variation among the interindividual immediate effect of the various respiratory patterns. Part of our waves can be addressed. The results have been reported as EEG findings of alpha and beta waves for these interventions mean of % change ± standard error (M ± SE). has already been published elsewhere. Computation of HRV : As our aim was to look for immediate changes (first 2 minutes) in the EEG and HRV 1. Resting/basal condition: During resting state, measures as an outcome of altered respiration, we performed significantly (p < .001) higher absolute theta power short-term HRV analysis of obtained RR intervals. For this, was recorded at parietal (P3 and P4) and occipital 5 minutes artifact free resting ECG record and 2 minutes (O1 and O2) areas than frontal site (9.7 ± 4.7 uv at postintervention ECG record (as that of EEG record) F3 and 8.87 ± 3.18 uv at F4) with maximum value 2 2 were selected with the help of software Labchart 6 PRO, at O1 and O2 (25.13 ± 10.6 uv and 23.66 ± 10.4 uv , ADInstruments, USA, and FFT was used to determine the respectively) (Figure 1). These cortical activities power spectral density. Thereafter, calculation for time domain were found to be bilaterally symmetrical, that is, indices, that is, pNN50 (percent of pairs of adjacent RR there was no significant difference between absolute interval with a difference of >50 msec), RMSSD (square root theta power at left (F3, P3, and O1) and right (F4, P4, of mean square differences of consecutive RR intervals) and and O2) sided leads. In terms of HRV, the mean time frequency domain indices, that is, LF (low frequency) power, domain measures, RMSSD and pNN50, in the resting HF (high frequency) power, and total power were done. As the state were 50.89 ± 24.01 msec and 27.04 ± 20.97%, “normalized unit” (nu) of LF and HF expresses the sympathetic respectively. HF (56.38 ± 15.3 nu) was higher and parasympathetic branches of the ANS in a balanced and (p < .001) than the LF (40.42 ± 17.47 nu) with LF/ regulated manner, we have represented these indices in “nu.” HF ratio being 1.04 ± 0.32 for the frequency domain Statistical analysis: Pre- and post-intervention absolute indices of HRV. Also, positive correlation (p < .05) power of alpha, beta, and delta waves at F3, F4, P3, P4, O1, between theta power and RMSSD and pNN50 was and O2 electrodes were compared by the two-tailed Mann– observed only at F3 during the resting state (Table 1). Table 1. Correlation Between Theta Power and HRV Indices Across Different Interventions Theta wave HRV Indices RMSSD pNN50 LF HF LF/HF * * Resting 0.40 (F3) 0.38 (F3) NS NS NS Post apnea NS NS NS NS NS Post bradypnea 0.5 (F3) NS NS NS NS * * * Post tachypnea NS 0.47 (P4) –0.46 (O1) 0.45 (P4) –0.45 (O1)* * * *** 0.41(O1) –0.44 (O2) 0.6 (O1) –0.43 (O2)* * ** 0.44 (O2) 0.54 (O2) Abbreviations: NS, no significant correlation; RMSSD, root mean square of successive differences between adjacent normal RR intervals; pNN50, percentage of number of pairs of adjacent RR interval differing by more than 50 msec; HF, high-frequency component; LF, low-frequency component. Source: Authors. Note: “r” represents values for Pearson’s correlation between theta power and HRV indices. Electrode sites depicting left (F3, O1) and right (P4, O2) sides are given in parenthesis. Significance of ‘r’ has been marked as *. *p < .05; **p < .01; ***p < .001. 70 Annals of Neurosciences 27(2) 2. Post apnea (after voluntary breath-holding): Post Figure 2. Postintervention Theta Power breath holding/apnea revealed decreased power of theta waves at all the recorded sites (Figure 2), when compared to basal state. However, this decrease was not significant, whereas all the HRV indices (except HF) increased from their resting level within 2 minutes of post apnea, which was maximum for LF/ HF, though statistically not significant (Figure 3). No significant correlation was observed between theta waves with any of the time and frequency domain indices (Table 1). 3. Post bradypnea (after slow deep-breathing): Theta power at all the recorded cortical sites did not elicit any marked or significant change following Legend: Spatial distribution of absolute power of theta activity in bradypnea (Figure 2). But the time domain measure, terms of % change from resting state following voluntary apnea, that is, RMSSD and pNN50 of HRV showed very bradypnea, and tachypnea. Significantly increased theta activity was seen at all sites as compared to resting state following voluntary significant (p < .001) decrease from its resting tachypnea. However, no significant change was observed after apnea level after 3 minutes of slow deep breathing, and bradypnea. whereas marked increase in LF/HF and LF (though Source: Authors. statistically nonsignificant) was observed (Figure 3). Note: Values are represented as mean ± SE (***p < .001). The correlation pattern showed significant (p < .05) positive correlation between theta activity and Figure 3. Postintervention HRV Indices RMSSD only at F3 cortical site (Table 1). 4. Post tachypnea (after hyperventilation): Theta activities significantly (p < .001) increased at all the frontal, parietal, and occipital electrode sites within 2 minutes of voluntary hyperventilation (Figure 2). Also, a significant decrease in RMSSD and pNN50 values were observed from their resting level, while LF/HF ratio and LF showed marked increase, though statistically nonsignificant (Figure 3). At this time, significant correlation was present between the theta waves and HRV measures (pNN50, HF, LF, and LF/HF) at P4, O1, and O2. pNN50 and HF had a Legend: Percentage change in various HRV indices following volun- tary apnea, bradypnea, and tachypnea. Significant decrease in RMSSD positive correlation, whereas LF and LF/HF always and pNN50 and marked increase in LF/HF and LF after 3 minutes showed negative correlation (Table 1). of bradypnea and tachypnea was seen. Apnea did not cause any sig- nificant change. Figure 1. Resting Theta Power Source: Authors. Note: Values are represented as mean ± SE (***p < .001). Discussion The concept of ANS–CNS two-way interaction has paved the path for several studies trying to understand the basis of this link. In this context, many reports have attempted to show how the altered respiratory pattern in different respiratory diseases or during stressful challenging situations influence the cortical activity by linking MRI/EEG findings with cardiac Legend: Figure depicts absolute power of theta activity in frontal 5,17,19 changes and thereby, HRV. However, these studies fail to (F3 and F4), parietal (P3 and P4), and occipital (O1 and O2) leads explain adequately the basic link between these two limbs due under resting conditions. Parietal and occipital areas showed signif- icantly increased theta power as compared to their frontal power. to the presence of disease/other confounding variables, which are bound to overshadow the normal physiological responses. Source: Authors. Therefore, the current report aims to study the physiological Note: Values are represented as mean ± SE (***p < .001). Sinha et al. 71 responses to altered breathing pattern and also to assess the However, no correlation was evident between HRV link between these two systems (cortical and cardiac) in the measures and theta waves following voluntary apnea. This normal healthy subjects under a common study platform. may be due to depressed cortical activity at all cortical areas EEG and HRV in resting state: During resting state, theta due to apnea induced hypercapnia and hypoxia. power was found to be significantly high posteriorly (Figure Post bradypnea (after slow-deep breathing): There was 1) with high parasympathetic tone (high HF). In our earlier no marked change observed in theta activity following 3 published report, we have already reported predominant alpha minutes of bradypnea. In our earlier paper, we had reported activity mainly posteriorly in the same group of subjects. decreased alpha activity at the posterior cortical sites in the These findings are definitely indicative of a true resting state of same recording setup. In this context, a study on pranayamic 21 33 the subjects as per synchrony of the waves. Also, the presence breathing simulating the bradypnea state in an individual of bilateral symmetry of EEG activities is in accordance with had shown that stretch induced by voluntary deep breathing the standard protocol of resting EEG recording. generate inhibitory signals, which synchronizes neural control Values of all the indices of frequency domain in our study of cardiorespiratory as well as limbic and cortical areas by were found to be similar when compared to Task Force Group resetting the autonomic functions. Report. The result indicated a higher parasympathetic/vagal Also, significantly reduced RMSSD and pNN50 and influence (Table 1) because of significantly higher HF (0.15– marked increase in LF and LF/HF signify a decreased 0.40 Hz) value, which is expected in the resting condition of parasympathetic and increased sympathetic activity due to 3 individuals. Vagosympathetic modulations are associated minutes of voluntary bradypnea. This is in accordance with 31,32 with the vagally mediated modulation of heart rate (increasing the earlier studies showing increased sympathetic activity during inspiration and decreasing during expiration), known following controlled breathing pattern. Studies on slow as the respiratory sinus arrhythmia (RSA). However, deep breathing techniques have suggested dominance of the controversy exist with regard to interpretation of the LF (0.04– parasympathetic tone by increasing HRV and RSA. Bhastrika 0.15 Hz) component, which is now believed to represent both pranayama, which is done as a slow rate exercise (respiratory sympathetic and vagal modulation and not only indicate rate 6/min), have been shown to cause strong improvement sympathetic tone. of autonomic functions by increasing the parasympathetic Positive correlation of left frontal (F3) theta waves with tone. However, contradictory reports in terms of increased 17,36,37 38,39 time domain measure (RMSSD and pNN50 indicating cardiac HF power vs no changes or even decreased HF parasympathetic control) was evident. It is known that theta power are available as an effect of such slow paced pattern activity (4–8 Hz) is seen in the waking adult EEG during of breathing. It could be emphasized in this context that all relaxed wakefulness maximally in the frontocentral regions, the reports indicating increased parasympathetic response which tends to be somewhat more evident in the midline and due to slow controlled breathing were recorded during the 30 40 temporal derivations. Therefore, the presence of significant slow breathing except the study of Lehrer et al., which has correlation between theta and RMSSD at the left frontal area reported the response immediately after the session. Therefore, in our present study corroborates with the fact. High alpha and it suggests for altered HRV power in postintervention period, less beta power were reported by us earlier also in the resting during which respiratory frequency returns to normal. Slow state. This definitely indicates that increased theta in resting breathing techniques at 9–10 breaths/minute has been seen state has relaxing effect (indicated by high parasympathetic to cause increase in HF power, whereas slower breathing 39-41 activity). at 6 breaths/minute leads to increase in LF power and is Post apnea (after breath holding): We observed decrease usually associated with sympathetic activation. Our subjects in the theta waves at all the cortical sites starting from frontal performed 6 breaths/minute to simulate voluntary bradypnea to occipital areas following voluntary apnea, which may and therefore the findings are confirmed to be in accordance be explained on the basis that the hypercapnia and hypoxia with these literatures. induced by the apnea may have caused general depressed Post tachypnea (after mild hyperventilation): Voluntary cortical activity. Marked increase in the LF and LF/HF ratio tachypnea led to increased theta power globally and bilaterally was observed in our subjects following voluntary apnea, (Figure 2). Theta power has been reported to increase which is an indication of increased sympathetic control over whenever individual perform mental tasks/meditation/ the cardiac system. exposed to external stimuli with decrease in alpha activity. Breath holding have been reported to cause activation Such increased theta activity related to phasic event was also of both sympathetic and parasympathetic system (i.e., observed in our study. activation of sympathetic limb during holding of breath and In our present study, the subjects were asked to breath parasympathetic activation during late stage of recovery) at a rate of 30/minute to simulate tachypnea, which was suggesting a pathophysiological basis of apnea-induced different from classical hyperventilation where the subject arrhythmias. Our result is in consonance with these reports required to respire as deep and fast as possible like maximum thereby suggesting increased sympathetic activity after voluntary ventilation, used as an activation technique during 31,32 voluntary apnea. EEG recording. We find that the mild hyperventilation 72 Annals of Neurosciences 27(2) in our study simulated states of yoga or meditation and required on behalf of the subject to maintain the same rate caused relaxation of cortical activity, which was reflected in of respiration (30/minute), might be responsible for a stable significant increase in the theta power, more so at posterior theta power in parietal and occipital areas. cortical sites (Figure 2) with simultaneous increase in frontal Therefore, it may be emphasized that our study is corroborating the functional association between brain alpha power (reported earlier, ). Hyperventilation induced and cardiac autonomic activity. Higher level cortical physiological slowing of brain rhythms (in delta and theta structures are known to have reciprocal connections with activity) could be a result of reduced cerebral blood flow due the subcortical structures, which in turn regulate autonomic to cerebral hypoxia associated with vasoconstriction in this input to the heart, leading thereby to its modulation in case. terms of physiological rhythm of heart rate, that is, HRV. A significantly decreased RMSSD and pNN50 and Therefore, HRV has been qualified as independent indicator marked increased LF/HF as a result of mild hyperventilation 50,3 of CNS–ANS interaction. It may be reiterated here that are indicative of reduced parasympathetic and increased all our data represent postintervention responses. Therefore, sympathetic tone. Kox et al. reported decreased appearance of positive correlation between theta waves parasympathetic drive to myocardium both during isocapnic with parasympathetic indices and negative correlation and hypercapnic hyperventilation with increased sympathetic with sympathetic indices, which is opposite to that of activation. Alexopoulos et al. have also reported exaggerated resting state, may be indicative of body’s response to the hemodynamic response due to heightened sympathetic interventions toward homeostatic balance, that is, cortical stimulation during hyperventilation. Even kapalbhati (a type stimulatory interventions leading to compensatory activation of rapid abdominal breathing yogic exercise) has been shown of parasympathetic responses and vice versa. to cause increased LF power and enhanced sympathovagal balance toward sympathetic side with decreased vagal tone that is, HF. Besides, our study also demanded a high level of Conclusion concentration while doing HV to maintain the breath rate of 30/minute. Earlier studies have shown that emotional arousal It is apparent from the discussion that the induced hypoxemia is linked to HRV with decreased HF activity due to increased or hypo/hypercapnia due to various altered respiratory 47,48 mental strain, time pressure, and state anxiety, which could patterns (e.g., voluntary apnea, bradypnea, and tachypnea) be outcome of focusing of attention and associated inhibition in normal healthy individuals caused either depressed of motor activities. Increased incidences of worrisome parasympathetic outflow or increased sympathetic output. events in daily life has been shown to cause reduction in Besides, increased theta activity with altered correlation HRV. Our findings on post-HV HRV changes corroborate pattern between EEG and HRV measures, which shifted these studies. from anterior to the posterior cortex during voluntary Theta activities were found to be significantly and hyperventilation, was prominently observed in the present positively correlated with measures of parasympathetic study. Therefore, the impact of altered respiratory pattern (pNN50, HF) and negatively with sympathetic (LF/HF and induced changes shows definite links between cortical LF) activity both at parietal and occipital areas bilaterally, post activity and autonomic outflow. The correlation between tachypnea. Besides, decreased parasympathetic and increased HRV and EEG findings may also be translated to sensitive sympathetic tone correlating with EEG wave patterns were cardiac risk markers and also to concurrent hypoxic observed mainly at parietal and occipital areas. This was again encephalopathy with predictive potential in related illnesses, in contrast to the resting state where correlation existed only for example, COPD, emphysema, etc. However, the present at the frontal site, thereby suggesting an altered link between study needs to be conducted with larger sample size cortical activity and cardiac outflow due to expected changes including assessment of blood and respiratory gas analysis in pO , pCO , and pH caused by hyperventilation induced 2 2 to conclusively comment on the functional alterations in tachypnea. The reported reverberation of the respiration- neural substrates. 13–15 coupled neuronal activity to the widespread areas of brain might be the reason for the involvement of posterior cortical Acknowledgments areas (parietal and occipital) in the present study, in terms of bringing synchronization between neuronal activity and We would like to gratefully acknowledge the contribution of all the volunteers for their willingness to participate. cardiac output due to hyperventilation. Earlier studies have reported that alpha and theta rhythms of EEG respond Author Contributions differently and in opposite ways with increasing theta power and decreasing alpha power during phasic event related M.S. Conception of the study, manuscript preparation and editing. changes. Another study shows that with increasing task R. S. Manuscript preparation and editing. demand, alpha power may desynchronize while theta power J. G. Preparation of manuscript, collection of data. synchronize. In our study also, an increased concentration G. S. Preparation of manuscript, collection and analysis of data. Sinha et al. 73 Declaration of Conflicting Interests drive and cardiovascular variability. Am J Physiol Heart Circ Physiol 2001; 280(2): H722–H729. The authors declared no potential conflicts of interest with respect to 10. Kox M, Pompe JC, van der Hoeven JG, et al. Influence of the research, authorship, and/or publication of this article. different breathing patterns on heart rate variability indices and reproducibility during experimental endotoxaemia in human Ethical Statement subjects. Clin Sci 2011; 121: 215–222. The study has complied with the guidelines for human studies 11. Herrero JL, Khuvis S, Yeagle E, et al. Breathing above the and includes evidence that the research was conducted ethically brainstem: volitional control and attentional modulation in in accordance with the World Medical Association Declaration of Helsinki. 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Annals of Neurosciences – SAGE
Published: Apr 1, 2020