Both whole-body rotation and visual flow induce cardiovascular autonomic response in Human, but visual response is overridden by vestibular stimulation

doi:10.21203/rs.3.rs-2495834/v1

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Both whole-body rotation and visual flow induce cardiovascular autonomic response in Human, but visual response is overridden by vestibular stimulation

https://doi.org/10.21203/rs.3.rs-2495834/v1

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published 14 Mar, 2023

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While the influence of the vestibular and extra-vestibular gravity signals on the cardiovascular system has been demonstrated, there is little evidence that visual stimuli can trigger cardiovascular responses. Furthermore, there is no evidence of interaction between visual and vestibular signals in autonomic control, as would be expected since they are highly integrated. The present study explored the cardiovascular responses to vestibular and visual stimuli in normal subjects. We hypothesized that the visual stimuli would modify the cardiovascular response to vestibular stimulation, especially when the latter is ambiguous with respect to gravity. Off-Vertical-Axis-Rotation (OVAR) was used to stimulate vestibular and extra-vestibular receptors of gravity in 48 healthy young adults while virtual reality was used for visual stimulation. Arterial pressure (AP), respiratory rate and ECG were measured. The analysis accounted for the respiratory modulation of AP and heart rate (HR). Vestibular stimulation by OVAR was shown to modulate both mean arterial pressure (MAP) and HR, while the visual stimulation was significantly affecting HR modulation, but not MAP. Moreover, the specific visual effect was present only when the subjects were not in rotation. Therefore, visual stimulation is able to modulate the heart rate, but is overridden by vestibular stimulation due to real movement.

Biological sciences/Neuroscience/Sensory processing

Biological sciences/Physiology/Circulation/Blood flow

Biological sciences/Physiology/Respiration

arterial pressure

heart rate

breathing rate

synchronization

OVAR

vection

otolith system

vestibular system

vision

The present study has confirmed the existence of a visually-induced cardio-respiratory response in human subjects. However, this response is overridden by vestibular stimulation.

A large amount of evidence from animal and human studies suggest that vestibular input participates in autonomic response to postural change through vestibulo-autonomic reflexes ^1–5. While it has been shown that the semicircular canals, the vestibular end organs specialized in detecting head rotations, may contribute to these vestibulo-autonomic reflexes, most studies have focused on the role of the otolith organs, the vestibular end organs specialized in detecting head linear acceleration (gravity and inertial acceleration). Indeed, among the movements of the body, it is those that reorient it in relation to gravity (thus detected by the otolith organs) that mostly affect the physiological systems and it has been shown that vestibular otolith organs contribute to the control of arterial pressure (AP) during changes in posture ⁵. For example, vestibular loss impairs cardiovascular tonic response to changes in the body orientation with respect to gravity ^6,7 or to changes in the level of gravity ⁸.

Even in the absence of vestibular stimulation, visual input alone can induce a sense of self-motion, which is called vection. The role of vision in autonomous postural regulation has been much less studied than that of the vestibular system. This was first appreciated in vestibulo-lesioned cats, who were able to recover their postural AP control when visual cues for their orientation in space were present ⁹. Only two studies addressed this question in human subjects, both demonstrating highly heterogeneous results. Aoki and collaborators ¹⁰ have reported two different mean arterial pressure (MAP) adjustment reactions to illusory tilt motion induced by visual stimulus in human subjects. Six of ten subjects had their MAP significantly increased in response to vection, while four of ten decreased their MAP. Interestingly, the MAP response to real tilt was also minimal in the latter 4 subjects. Wood and colleagues ¹¹ also had visually induced tilt sensation in human subjects and found an increase in heart rate (HR) and a decrease in MAP in a subset of subjects. These data suggest that autonomic regulation related to gravity reorientation can be triggered by purely visual input in human subjects, albeit with high interindividual variability. In sum, the change of body orientation with respect to gravity provokes cardio-vascular adjustments, which can also be induced by purely visual tilt in some subjects.

Peripheral otolith system, as well as other extra-vestibular graviceptors, cannot differentiate between gravity and inertial linear acceleration ¹², the phenomenon known as the tilt/translation ambiguity. Convergence of visual and vestibular inputs plays a significant role in our perceptions of spatial orientation and motion ¹³ and ambiguous vestibular signals ^14,15 could be disambiguated by visual input ^11,16. This raises the question of whether the vestibular and visual systems act directly on the cardiovascular system (via vestibulo- and visuo-autonomic "reflexes") or indirectly after disambiguation of the otolith input to consider only its gravitational component (i.e. the inclination relative to the vertical).

To investigate whether a different visual reinterpretation of the same vestibular input could alter the autonomic response to changes in orientation with respect to gravity, we employed a protocol using combined visual and vestibular stimuli. For this purpose, we chose a perceptually ambiguous vestibular stimulus, off-axis vertical rotation (OVAR). OVAR in the dark can evoke different perceptions of self-movement (Fig. 1), most often along a conical or cylindrical pattern ¹⁵, sometimes variations of these, like a flower-shaped pattern or inversed conical pattern ¹⁷. The difference between the two major types of the OVAR perception (cone and cylinder) can be driven by the way the vestibular information is interpreted: as inertial acceleration (cylinder) or as gravity (cone) ¹⁸. Our hypothesis is that during OVAR, visual input would disambiguate motion perception from the vestibular system and that the visual stimulations leading to different perceptions of self-motion, would differently affect the modulation of physiological parameters. This difference in modulation is suggested because only tilt with respect to gravity (i.e. cone perception), and not movements in the horizontal plane (i.e. cylinder perception), requires postural adjustment of the AP ⁵.

According to this hypothesis our predictions were that (1) the vestibular stimulation would modulate AP and HR; (2) the visual stimulation would lead to a partial reinterpretation of the same vestibular information (OVAR): combined to OVAR, the visual stimulation that would partly be interpreted as tilt (“Cone”) would provoke a greater modulation than the one that is entirely interpreted as translation (“Cylinder”).

Participants

48 healthy adult volunteers were recruited for this study. Any vestibular and neurologic diseases were criteria of exclusion. Subjects who have not finished the protocol on the rotatory chair due to motion sickness (9 subjects) or technical issues (3 subjects) were excluded from the final analysis. Therefore, data from 36 subjects (15 female, 21 male; 24 ± 5 years old) were reported. Informed consent was obtained from all participants. The study was approved by an Ethics Committee (CPP Ouest I n° IDRCB 2022-A01513-40). All methods were carried out in accordance with relevant guidelines and regulations.

Stimulation

OVAR was performed using an automated rotatory chair driven by a MicroFlex E150 servo drive (ABB, Zurich, Switzerland) operated with Mint WorkBench software (ABB, Zurich, Switzerland), with an axis inclined at 10° with respect to gravity. The direction of rotation was counterclockwise. The velocity of rotation was 60°/s (0,167 Hz), which is perceptually the most ambiguous frequency for vestibular cues interpretation, according to previous studies ^19,20. This frequency was chosen to facilitate the switching, by visual stimulation, between cone and cylinder movement perception.

Visual stimulation was presented with virtual reality (VR) googles (HTC Vive, angle 110°, 90 Hz, 1080 x 1200 pixels per eye). The virtual environment represented a virtual room with furniture to give reliable visual cues for verticals. The rotation of the virtual visual environment was synchronized with the rotation of the chair with the help of an integrated accelerometer, so the visual motion velocity was also 60°/s. Two visual motion patterns were created: moving along a “Cylinder” with a radius about 1 meter or a “Cone” with a radius about 0,6 meters, an apex below the body and a 10° inclination with respect to the gravitational vertical. The cylindrical motion pattern was created as a sum of harmonic oscillations along the interaural and naso-occipital axes. The conical path was composed of the same oscillations, but of lower amplitude, with the addition of periodic tilt around the same axes. Thus, the “Cylinder” is a translation-only movement in a plane parallel to the floor, while the “Cone” is the combination of the translation and tilt with respect to vertical (Fig. 1). We consider that the presence of tilt is decisive in AP adjustment during postural changes, so we expect a different vascular reaction to the “Cone”, than for the “Cylinder”.

Measurements

Continuous arterial pressure, as well as systolic – SAP, diastolic – DAP and MAP, were measured with an automatic continuous noninvasive arterial pressure monitor (Finometer Pro, FMS, Amsterdam, The Netherlands) placed on the middle finger of the left hand held at the heart level. The correction of hydrostatic levels was applied with the help of a Finometer integrated system. Pressure values provided by this system do not significantly differ from those taken directly from the radial artery in subjects in various physiological conditions ²¹, and there is a good agreement in the evaluation of beat-to-beat variations ²². Electrocardiogram (ECG) was measured with a 3-leads ECG (Contact Precision Instruments, Cambridge, USA). Breathing frequency (BF) was measured with the help of a commercial monitor and nasal prongs (Oridion, Microcap monitor CO2, Jerusalem, Israel). The parameters analyzed were the RR-interval (RRI, ms), MAP, SAP, DAP (Torr), and BF (min^− 1). A one-axis accelerometer (FA101, FGP Sensors & Instrumentation, France) was used to record the phases of the chair rotation.

All signals were acquired with the help of the acquisition system Notocord-hem (Notocord Hem 4.2, Notocord Systems, Croissy-sur-Seine, France).

The level of MS evoked by the rotatory chair stimulation was assessed before and after the experimental session with a diagnostic criteria proposed by Graybiel and colleagues ²³. The symptoms were divided in categories with varying symptom intensities. The subject could underline only one level of intensity per category. The score of 1–2 points was interpreted as Slight Malaise, 3–7 points as Moderate Malaise, 8–15 as Severe Malaise and ≥ 16 points were regarded as Frank Sickness.

Procedure / Experimental Design

Subjects sat on a rotatory chair in darkness. The subjects were secured with a harness and a head support restrained the movements of their heads while rotating on the chair to prevent the cross-coupling stimulation. During all the experimental trials, they wore VR goggles, except for the pauses. Every subject performed 6 trials combining 3 visual conditions:(1) self-rotation along a cylindrical path, i.e. “cylinder”, (2) self-rotation along a conical path, i.e. “cone” and no visual stimulus, i.e. “darkness” with 2 vestibular conditions: (1) OVAR and (2) motionless). During motionless condition, subjects sat on the rotatory chair without any physical motion applied. During OVAR condition, the rotation started with the axis of rotation inclined at 10 degrees, in the dark. The duration of every rotation trial was 114 seconds, pauses were made between each trial. The first minute of rotation was not included in the analysis to avoid the influence of the semicircular canals, so the visual stimulation was also turned on after 1 minute of OVAR, in order to minimize the time the subjects experienced the combination of visual stimulations with actual rotation which was relatively nauseogenic. The OVAR and Motionless conditions were interchanging in trials, in order to diminish the possibility of motion sickness provoked by the OVAR. The order of the visual and visual-vestibular trial pairs was counterbalanced. The MS diagnostic criteria were applied twice: before and after the experimental session and the difference between the scores after and before was taken as the final MS score.

Analysis

The first 60 seconds of the recording were discarded to assure that the vestibular stimulation is purely otolithic, without the semicircular canals’ component. The recordings were cut cycle by cycle, based on the accelerometer data, and 9 cycles were averaged for every condition and for every subject. The grand mean – the cycle averaged across all cycles and all subjects for the three visual conditions during OVAR is shown in Fig. 2. An example of individual mean cycles for the three conditions is shown in Fig. 3. A cosinor model was fitted to these averaged cycles, and offset and modulation (amplitudes and phase) were estimated. As breathing is known to modulate the HR through a mechanism called respiratory sinus arrythmia, we have calculated the frequency at which the spectral peak of the BF occurred, in order to control for this modulation predictor. The operations were effectuated in Matlab R2017a.

Statistics

Average values of the MAP, SAP, DAP, RRI and breathing rate were compared with RM ANOVA with a condition factor (6 conditions). In order to test the influence of rotatory and visual conditions on the modulation of MAP and RRI and their synchronization by breathing, we ran a linear mixed model analysis in R (R Core Team, 2021, Boston, MA, USA) using the linear mixed-effects models fit by maximum likelihood from the lme4 package ²⁴. The p-values were provided with lmerTest package ²⁵. Pairwise comparisons were made with multcomp package ²⁶ between the sessions with the Dunnett method and FDR method p-value adjustment. To assure the normality of residuals, the amplitude of modulation of RRI (RRI_A) was transformed to the natural logarithm of RRI_A. To model the effect of stimuli and respiration on the modulation of RRI and MAP we included natural logarithm of the RRI_A and the amplitude of modulation of MAP (MAP_A) as dependent variables and added fixed effects of mean breathing frequency, rotatory condition (OVAR/Motionless), visual condition (Darkness/Cylinder/Cone), as well as the interactions between rotation and visual stimulation. We included Subject as a random effect. The model specification for MAP modulation was as follows: MAP_A ~ Breathing_Fr + Rotation + Visual + Rotation * Visual + (1|Subject), the same for the natural logarithm of RRI_A.

The MAP, SAP and DAP, the RR interval, and the breathing rate averaged through 54 seconds of measurements across all the subjects for each condition are presented in the Table 1. RM ANOVA with a condition factor (6 conditions) has shown no statistically significant differences for mean, systolic and diastolic arterial pressure and the RR-interval between conditions. Breathing rate was found significantly different with RM ANOVA (p = 0.045 with a Huynh-Feldt sphericity correction), however the Bonferroni-adjusted post-hoc test has shown no significant difference between any of the conditions.

Table 1

– the mean values for the arterial pressure, RR interval and breathing rate
	MAP, Torr	SAP, Torr	DAP, Torr	RRI, ms	BR, rpm
All conditions pooled	91.0 ± 11.4	117.8 ± 13.5	73.1 ± 10.8	808.5 ± 146.7	15.6 ± 3.4
Darkness Motionless	90.0 ± 10.4	118.2 ± 13.2	74.4 ± 9.9	825.9 ± 149.9	14.6 ± 2.7
Cylinder Motionless	90.2 ± 11.1	116.8 ± 13.0	72.8 ± 10.9	812.6 ± 137.9	15.4 ± 4.0
Cone Motionless	90.5 ± 12.0	116.7 ± 13.5	73.0 ± 11.2	798.9 ± 136.3	14.9 ± 3.1
Darkness OVAR	92.5 ± 11.4	120.2 ± 13.5	74.0 ± 11.1	815.7 ± 164.8	15.7 ± 3.5
Cylinder OVAR	91.2 ± 11.4	118.9 ± 13.9	72.9 ± 10.6	789.1 ± 149.8	16.2 ± 3.7
Cone OVAR	89.8 ± 12.3	116.1 ± 14.2	71.8 ± 11.7	808.9 ± 147.5	16.4 ± 3.4

Figure 2 shows the grand mean of the modulation cycle of the MAP and RRI at the stimulus frequency, averaged across all the participants for the three OVAR conditions. On average, there seems to be no difference in the amplitude or phase of the modulation neither for MAP, nor for RRI between conditions. A subject-by-subject visual inspection suggests that the phase of the modulation is quite stable for every subject in the three rotational conditions. However, this phase differs from subject to subject, which is quite visible for the MAP (Fig. 3).

Modulations of the MAP and RRI at the frequency of the body rotation induced by visual and/or vestibular stimulation are evaluated with the mixed models.

For MAP_A (Table 2) there were significant main effects of respiratory rate and rotation, indicating that the MAP_A modulation is affected by the breathing frequency and by rotation. For RRI_A (Table 2) there were significant main effects of the breathing frequency and rotation, and also of the visual Cone effect, that seems to be different depending on the rotation.

Table 2 shows the summary of the models for the modulation amplitudes of MAP and RRI. The estimate is an estimate of the coefficient beta of the predictor or the interaction of predictors in the linear model. The significant p-value of the predictor indicates that the predictor explains well some part of the variance in the model. Breathing frequency has a negative coefficient for both MAP and RRI, therefore with other factors controlled, the higher the frequency of breathing, the lower the amplitude of modulation. On the contrary, the addition of rotation (positive coefficient), increases the amplitude of modulation with respect to motionless conditions. For the RRI_A, the Cone visual condition with no rotation also increases modulation.

Table 2

– Summary of the LMM model evaluating the effect of the Breathing frequency, rotation and visual stimulation, and the interaction between rotation and visual stimulation on the amplitudes if modulation of MAP and RRI (in the logarithmic scale). Signif. codes: ‘***’ – p < 0.001, ‘**’ – p < 0.01, ‘*’ – p < 0.05, ‘.’ – p < 0.1
	MAP_A						RRI_A
	Estimate	SE	DF	t-value	p-value		Estimate	SE	DF	t-value	p-value
(Intercept)	0.27	0.25	174	1.08	0.2811		3.33	0.31	174	10.63	< .0001	***
Breathing frequency	-3.83	0.92	174	-4.14	0.0001	***	-5.43	1.15	174	-4.72	< .0001	***
OVAR	1.99	0.13	174	15.36	< .0001	***	0.76	0.15	174	4.98	< .0001	***
Cylinder	0.03	0.13	174	0.24	0.8124		0.20	0.15	174	1.28	0.2013
Cone	0.08	0.13	174	0.61	0.5453		0.44	0.15	174	2.87	0.0047	**
OVAR : Cylinder	0.02	0.18	174	0.13	0.8991		-0.27	0.22	174	-1.24	0.2159
OVAR : Cone	-0.17	0.18	174	-0.93	0.3517		-0.47	0.22	174	-2.19	0.0300	*

Table 3 shows the pairwise comparison contrasts for all conditions. The amplitudes of modulation of MAP are all significantly different between OVAR and Motionless conditions regardless of the visual stimulation. The amplitudes of modulation of RRI are all significantly different between OVAR conditions and Motionless Darkness and Cylinder conditions, but not between OVAR and Motionless Cone condition. Moreover, the Motionless Cone condition is significantly different from the baseline Motionless Darkness condition.

Table 3

– Pairwise contrasts for the LMM models for MAP_A and RRI_A (in the logarithmic scale) between all the conditions. P-value fdr -adjusted. Signif. codes: ‘***’ – p < 0.001, ‘**’ – p < 0.01, ‘*’ – p < 0.05, ‘.’ – p < 0.1
					MAP_A					RRI_A
					Estimate	df	t-value	p-value		Estimate	df	t-value	p-value
Darkness	Motionless	-	Cylinder	Motionless	-0.1069	186	-0.535	0.6355		-0.2183	186	-1.405	0.2177
Darkness	Motionless	-	Cone	Motionless	-0.1218	186	-0.612	0.6249		-0.4297	186	-2.775	0.0130	*
Darkness	Motionless	-	Darkness	OVAR	-3.1933	187	-15.944	< .0001	*******	-0.7497	187	-4.815	< .0001	*******
Darkness	Motionless	-	Cylinder	OVAR	-3.3483	188	-16.587	< .0001	*******	-0.6687	188	-4.260	0.0002	**
Darkness	Motionless	-	Cone	OVAR	-2.9906	189	-14.758	< .0001	*******	-0.7201	188	-4.570	0.0001	**
Cylinder	Motionless	-	Cone	Motionless	-0.0149	186	-0.075	0.9406		-0.2114	186	-1.364	0.2177
Cylinder	Motionless	-	Darkness	OVAR	-3.0863	186	-15.499	< .0001	*******	-0.5314	186	-3.433	0.0028	**
Cylinder	Motionless	-	Cylinder	OVAR	-3.2414	186	-16.228	< .0001	*******	-0.4505	186	-2.901	0.0104	*
Cylinder	Motionless	-	Cone	OVAR	-2.8836	187	-14.408	< .0001	*******	-0.5018	187	-3.225	0.0045	**
Cone	Motionless	-	Darkness	OVAR	-3.0715	186	-15.381	< .0001	*******	-0.3200	186	-2.062	0.0762
Cone	Motionless	-	Cylinder	OVAR	-3.2265	187	-16.058	< .0001	*******	-0.2391	187	-1.530	0.1914
Cone	Motionless	-	Cone	OVAR	-2.8688	188	-14.233	< .0001	*******	-0.2904	188	-1.853	0.1090
Darkness	OVAR	-	Cylinder	OVAR	-0.1551	186	-0.778	0.5472		0.0810	186	0.522	0.6947
Darkness	OVAR	-	Cone	OVAR	0.2027	186	1.015	0.4246		0.0296	186	0.191	0.8491
Cylinder	OVAR	-	Cone	OVAR	0.3578	186	1.797	0.1110		-0.0514	186	-0.332	0.7931

Motion sickness evaluation with the Graybiel’s diagnostic criteria has shown an average score of 4.5 ± 4.1 which corresponds to a moderate malaise ²³ in 36 subjects. Including the individual Graybiel score into LMM has shown no significant effect of the MS score on the amplitudes of modulation of MAP (p = 0.95) or RRI (p = 0.29), so the factor was excluded from the final models.

This study evaluated the effects of OVAR and visual stimulation on the modulation of the AP and HR. We found that OVAR induces significant modulations of MAP and HR, whereas for the visual stimulus, only the cone induces significant modulations, but only of HR and differently if the subjects are rotating or not.

The higher peak of the MAP modulation cycle appears slightly before the nose-down position (Fig. 2) while the RR-interval is on the contrary lowest slightly before the nose-down position. This finding is coherent with the previous findings by Kaufmann et al. ² who demonstrated that AP and HR, as well as the muscle sympathetic nerve activity were entrained by OVAR, with the higher peak of AP and lower peak of RR-interval around the nose-down position. The modulation of the MAP by the OVAR could come from the difference in hydrostatic levels of the hand and heart in the nose-up and nose-down positions. However, these hydrostatic level differences were accounted for and cancelled with the help of the dedicated system of Finometer Pro. In addition, the MAP modulation was in phase advance with the actual rotation of the body, and this phase shift was different between subjects, but quite persistent under different conditions for the same subject (Fig. 3). This observation suggests that the modulation is the result of neural regulation, as the hydrostatic phase would be the same for all subjects. Therefore, this study confirms previous findings that the vestibular stimulation by OVAR can modulate the AP and HR in healthy subjects ².

To analyze the effect of OVAR on modulation of HR and AP, we needed to take into account another strong modulator affecting these parameters, which is the respiratory cycle. Breathing causes oscillations of the AP at the breathing frequency, as well as tachycardia during inspiration and bradycardia during expiration, the phenomenon called the respiratory sinus arrhythmia. Breathing frequency in our data indeed is correlated to the modulation, and the closer the breathing frequency is to the stimulus frequency, the higher the modulation. Therefore, if respiration is not taken into account, the stimulus-related modulation would be blurred and its source could be misinterpreted, especially when the respiratory frequency is close to the stimulus frequency or its harmonics. Indeed, a previous study has demonstrated that OVAR is able to synchronize the respiration in a subgroup of subjects ³. To separate the respiratory effect on the modulation of physiological parameters, we have used the mixed model in the analysis of the data, where we correlated the individual amplitude of modulation of the MAP to the individual frequency of respiration. Having this parameter controlled, the visual and vestibular factors can therefore be assessed. The amplitude of modulation of the MAP is significantly correlated with the individual frequency of respiration, especially for the non-OVAR conditions, that reflects the respiratory-driven part of the modulation. Body rotation by OVAR decreases this dependency, while augmenting the amplitude of modulation, therefore introducing another factor of modulation of the MAP at the stimulus frequency.

Like for the MAP, modulation of the HR also presented individually varying phase shifts. The HR modulation amplitude was also strongly correlated with the breathing frequency, reflecting the respiratory sinus arrhythmia ²⁷. The HR was also modulated by the vestibular part of the stimulation.

Concerning the hypothesis that different visual reinterpretation of the same vestibular input would alter the autonomic response, the results are less clear. The MAP modulation was unaffected by the visual input. The HR modulation was affected by Cone condition, but not by the Cylinder. This was expected, as long as it is the inclination part of the stimulus, which is absent in the Cylinder, that is supposed to provoke the adjustment of the AP. The effect of Cone visual stimulus was different whether the subject was in rotation or not. The HR was modulated differently from the control condition (Darkness/Immobile) when the Cone visual stimulus was projected while the subjects were immobile; however, when the OVAR stimulation was applied, no visual effect was discernible. It seems that the vestibular and visual effects on the HR do not add up independently, but that the vestibular effect overrides the visual one. In sum, the HR can be modulated by visual cues, when only those are available to sense the motion. Moreover, only the motion that includes inclination with respect to gravitational vertical can modulate the HR. When cues from the vestibular system and the body are present, the visual input does not add any additional impact on the modulation. As all of those signals presumably are weighted and combined to form an integrated estimate of tilt, the weight of one signal might be greater than the others for certain types of regulations. The visual impact could also be diminished by the use of virtual reality goggles, which despite its immersiveness stays only an approximation of the natural visual environment. It has been shown that a sensory mismatch in such an internal representation of movement can lead to the rearrangement of the sensory modalities, by calibrating the modality which receives the lowest weight ²⁸.

OVAR is a relatively nauseogenic type of vestibular stimulation ^29,30. Therefore, the demonstration of a visual-autonomic effect may be limited by motion sickness which may interfere with the results. The procedure was designed to maximally avoid symptoms of MS but it was not possible to eliminate them completely. MS can be associated with changes in the AP or HR; however, the average values of AP or HR were stable across different conditions. Moreover, when including MS factor in the statistical model for modulation amplitudes, we found that it did not significantly affect the mean or modulation of AP and HR.

It needs to be noted that OVAR stimulates not only the vestibular sensors of gravity, the otolith system, but also the extra-vestibular graviceptors, located in the trunk by Mittelstaedt ³¹. These sensors add to posture-related autonomic adaptations ³ and perception of vertical ³². Several studies have been dedicated to deduce the proportional effect of vestibular and trunk graviceptors in some functions: it has been found that eye-movement is almost entirely controlled by the vestibular system ³³, while the autonomic functions and the perception of the vertical are affected by both gravity sensors ^3,32. However, vestibular graviceptors predominate for vertical perception ³² while extra-vestibular graviceptors predominate for autonomic regulations ³.

Finally, the fact that visual stimulus was able to modulate only the cardiac response, but not the arterial pressure, may indicate that the autonomic response is driven by the parasympathetic system. Accordingly, recent data demonstrates parasympathetic activation by visual rotation in healthy male subjects ³⁴.

Overall, we conclude that the graviceptors stimulation by OVAR modulates AP and HR. We also conclude that the visual stimulation that includes illusory body tilt can also modulate the HR, but not the AP, when only the visual stimulation is present. The hypothesis of the visual reinterpretation of the vestibular effect was not confirmed, as the visual effect disappears in presence of the real body rotation. Finally, we conclude that the vestibular and somatosensory effects on the HR modulation override the visual effects.

Acknowledgments: This study if funded by the Région Normandie (00115524-21E06581). Authors sincerely thank all participants for their implication in the present study. We thank the lab engineer Daniel Zuba for all the help he provided for this experiment.

Author contributions: P.D. and H.N. conceived the project and designed the experiment, O.K. performed the experiment, O.K. and O.E. analyzed the data, O.K. wrote the draft of the manuscript; All authors reviewed and commented on the manuscript.

Data availability statement: The datasets used and/or analyzed during the current study available from the corresponding author on reasonable request.

Competing interests: The authors declare that the research was conducted in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest.

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No competing interests reported.

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Both whole-body rotation and visual flow induce cardiovascular autonomic response in Human, but visual response is overridden by vestibular stimulation

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