Immersion in a virtual tilted environment strongly modulates perception and action with respect to gravity: a within-person randomized trial of healthy individuals

Immersion in a virtual tilted environment strongly modulates perception and action with respect to gravity: a within-person randomized trial of healthy individuals | 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 Research Article Immersion in a virtual tilted environment strongly modulates perception and action with respect to gravity: a within-person randomized trial of healthy individuals Stéphanie Dehem, Aurélien Hugues, Ophélie Folmer, Shenhao Dai, and 3 more This is a preprint; it has not been peer reviewed by a journal. https://doi.org/ 10.21203/rs.3.rs-7472074/v1 This work is licensed under a CC BY 4.0 License Status: Posted Version 1 posted You are reading this latest preprint version Abstract Background – Immersing individuals in a virtual tilted environment (VTE) could be a way to modulate verticality representation and its consequences on action with respect to gravity. The VIRGIL study involves a basic study of healthy individuals and a clinical trial of individuals showing post-stroke lateropulsion due to a biased internal model of verticality. Here we present the preclinical experimental findings for the basic study of healthy individuals. Methods - Twenty healthy individuals received 2 sessions of 45 min of VTE immersion (18° tilt), performed 1 to 2 days apart: one session of sitting tested the VTE on verticality representation (postural vertical [PV; primary outcome] and visual vertical [VV]), and one session of standing tested the VTE effect on the active body orientation with respect to gravity (measured with inertial captors) and asymmetry of weight-bearing on lower limbs (WB; measured by posturography). Session allocation was randomized, and the VTE side (left or right) was balanced between individuals. We assessed the discomfort associated with the VTE immersion. In this exploratory study, investigators and participants could not be masked to treatment. Results - VTE modulated verticality representation, with a transmodal tilt of PV and VV toward the side that the VTE was tilted: mean (SD) magnitude 3.8° (3.8°) for PV and median (Q1:Q3) magnitude 14.0° (12.0; 14.9) for VV (both p<10 -3 and large effect size). VTE also modulated WB on the ground, increasing the load on the lower limb toward the side that the VTE was tilted (mean +2.5% [0.7], p0.05). The VTE discomfort was minimal in 75% of participants and null in 15%. Conclusion - In healthy individuals, VTE immersion strongly modulated perception and action with respect to gravity. In standing, the modulation of the WB is likely a response to the VTE to keep the body vertical. These findings open an avenue for the rehabilitation of lateropulsion after stroke. virtual reality verticality perception postural vertical visual vertical upright standing posture weight-bearing. Figures Figure 1 Figure 2 Figure 3 Figure 4 Background The sense of verticality (sense of upright) is a terminology proposed in the 2000s [ 1 – 5 ] to describe an important brain function constructed by combining gravity sensing and visual clues of verticality [ 3 , 6 , 7 ] through internal models, the existence of which has been demonstrated in animals [ 8 – 10 ], including humans [ 3 , 4 , 8 , 11 – 14 ]. The sense of upright serves to perceive the vertical orientation of the body [ 15 , 16 ] and the environment [ 6 , 15 , 17 – 19 ], and to predict the stability of objects in space [ 20 ]. and trajectories related to gravity [ 21 , 22 ]. It also serves to control actions with respect to gravity, especially balance and gait [ 23 – 30 ], and actions of upper limbs referred to top and bottom [ 31 , 32 ]. Regarding postural control, individuals with a biased internal model of verticality align their body on this wrong verticality representation, which causes a lateral whole body tilt [ 25 , 26 , 33 ], called lateropulsion [ 33 – 35 ], or a posterior whole body tilt [ 27 , 28 ], called retropulsion. Lateropulsion is the primary detrimental factor explaining balance and gait disorders in the subacute post-stroke phase [ 26 , 33 , 36 , 37 ]. A better understanding of how internal models of verticality work would improve our basic knowledge of their functioning and would help to enhance balance rehabilitation with appropriate techniques. Techniques that are supposed to modulate the internal model of verticality may be divided into 3 categories: 1) those modulating gravity sensing on Earth [ 3 , 12 , 23 , 27 , 38 – 49 ]; 2) those directly stimulating the brain by magnetic or electrical techniques [ 50 – 53 ], the effect of vestibular stimulation being more controversial with non-congruent effects on the visual vertical (VV) and on the postural vertical (PV) [ 49 , 54 , 55 ]; and 3) those using visual clues tilting the environment in a given direction [ 6 , 41 , 44 , 56 – 62 ]. Manipulating static [ 57 , 61 ] or dynamic [ 6 , 56 ] vision is long known to have a powerful effect on perception of the vertical. As galvanic vestibular [ 63 , 64 ] or somaesthetic stimulations [ 3 , 4 , 23 , 38 , 40 , 65 ], dynamic visual stimulations [ 6 , 56 ] interact with postural stabilization. Static visual manipulation can strongly modulate the internal model of verticality without interfering with postural stabilization [ 58 ]. A static tilt of the environment attracts the VV to the side with maximal effect for a frame tilted 15° to 20° away from the vertical [ 58 , 59 ]. The effect is stronger with cognitive and structural 3D enrichment [ 59 , 66 ] or by immersion in a real tilted environment [ 56 , 57 , 60 ], which is difficult to implement in a rehabilitation context. Virtual reality (VR) allows for complete immersion in a tilted environment. Two exploratory studies of healthy individuals [ 41 , 67 ] and a single case study of post-stroke lateropulsion [ 68 ] suggested that immersion in a virtual tilted environment (VTE) could be interesting for recalibrating a biased internal model of verticality and attenuating lateropulsion. The effect on the VV was powerful, the visual line being perceived as vertical when tilted about 11° toward the side that the scene was tilted downward [ 41 ]. These premises led us to set up the VIRGIL stud, which explores the effect of a VTE on the interface of perception–action with respect to gravity. As explained in the study protocol [ 69 ], the VIRGIL study associates a basic study of healthy individuals and a pilot clinical trial of individuals exhibiting post-stroke lateropulsion. This study analyses VTE effects both on verticality perception (PV and VV), and uprightness in standing (instrumental measurements of segmental body orientation and weight-bearing [WB] asymmetry). The recruitment of individuals showing lateropulsion after stroke is still ongoing. The current article reports the results of the basic study involving healthy individuals. We addressed 3 main novel and important questions: 1) Is the VTE effect on verticality perception transmodal? This implies that in addition to the modulation of VV [ 41 , 68 ], which mainly tests the vestibular contribution to gravity sensing [ 7 , 70 , 71 ], VTE also induces a modulation of the PV, which corresponds to the perception of the vertical by the body and mainly tests the somaesthetic contribution to gravity sensing [ 25 , 38 , 72 – 74 ]. If indeed VTE induces a transmodal tilt in verticality perception, then VTE acts at a high order level on verticality representation. 2) Is there any post-effect? 3) Does this VTE-induced modulation of verticality representation extend to the active body orientation in standing? This situation would provide experimental confirmation of the close relationship between verticality representation and action referred to gravity as observed in clinical neurosciences [ 4 ], and would pave the way for a clinical application of VTE immersion. We cannot exclude transitory cybersickness symptoms, which will be analysed. No benefit is expected for healthy individuals in this basic part of the study. Methods Study design This exploratory monocentric within-person randomized trial is called VIrtual Reality Glasses Use to Improve Lateropulsion and the Post-stroke Postural Vertical (VIRGIL) fulfills ethics requirements (see declarations section). The protocol has been published [69]. The study took place in Grenoble University Hospital, France. Here we report the results of the basic research performed in healthy individuals who were recruited via a public notice board. In this experimental exploratory study, investigators and participants could not be masked to the order of session presentation nor the condition with or without VTE. No interim analysis of data was performed; this article presents most data for all healthy individuals. The reporting of the study follows the 2025 Consort statement (check list in Appendix). Neither patients nor the public were involved in the design, conduct and reporting of the study. Participants On the basis of previous experimental studies performed in healthy individuals with comparable tools [3, 4, 38, 41], a sample size of 20 healthy individuals was considered sufficient to evidence changes in verticality perception (primary outcome). Inclusion criteria were 1) age 18 to 85 years, 2) social health insurance coverage, 3) giving signed, informed and free consent, 3) no stroke or neurological disease history and 4) no previous disability interfering with balance or vestibular disorders. Exclusion criteria were 1) nyctophobia and claustrophobia, 2) history of severe psychiatric disorders, 3) advanced heart failure documented in the medical record, 4) severe trunk deformation with C7 lateral deviation >30 mm due to any disease ( i.e. scoliosis, leg length inequality, etc.) or postural disorder history, 5) pregnant or breast feeding, 6) being in an exclusion period for another study, 7) under judicial or administrative supervision, 8) under guardianship or a tutelage measure, 9) receiving more than 4500 euros’ compensation for participation in previous research involving humans in the 12 months before the study. Procedure Participants were tested in 2 sessions each lasting half a day. One session was devoted to the effect of VTE on verticality perception, comprising both PV and VV, and the other to the effect on standing posture, comprising both the body orientation with respect to gravity and the WB distribution on lower limbs. The running order of sessions was pseudo-randomised: plan A for half of the individuals, with day 1 involving verticality perception and day 2 standing posture; plan B in a reverse order. Details are reported in the study protocol [69]. For sessions devoted to verticality perception, participants were installed in a sitting position in the wheel-like device that measures PV in the roll plane (Figure 1). Measuring PV with this device has been well validated by usage [13, 25, 31, 32]. Participants remained in this wheel-like device during the whole session, wearing the VR helmet. The session started first with an assessment of PV and VV (baseline), then individuals were immersed in VTE for 15 min before starting the second PV and VV assessments, performed with VTE immersion. The VTE immersion lasted about 45 min. Participants in whom the VTE induced a modulation ≥2° (53) of PV or VV remained 10 min more in the device after the VTE was stopped (they still wore the helmet displaying darkness), and new assessments were performed to search for a post-effect (darkness). The evolution of this post-effect, if any, was monitored by performing some additional measurements of PV or VV every 10 min until it disappeared. For the standing posture assessment (active body orientation and WB), measurements were performed under 2 different visual conditions: in the natural environment (baseline) then in VTE immersion (preceded by 15 min immersion in sitting). No post-effect was searched. To simultaneously assess the body orientation with respect to gravity and the WB, participants were equipped with an inertial measurement unit (IMU) system and stood on a dual force-plate form (Figure 2). All during the experiment, we asked participants about any possible discomfort experienced in relation with VR. Intervention As shown in Figures 1 and 2, participants wore the HTC Vive helmet (HTC, Taiwan), which delivered the virtual environments generated by the software RelaxationVR 1.0.6 (Virtualis, France) and the VV evaluation module generated by the software RVR-SC 2.3.5 (Virtualis, France). They wore their usual glasses within the device to correct vision if needed. Intervention was provided by trained investigators (StD, AH, CP, ShD). To avoid effects related to boredom or fatigue, 4 different immersive, static, tilted environments were presented in a fixed order: a beach, a forest, a logging road and a child's bedroom (Figure 3). Seated participants were instructed to look at the scene, the orientation of which was tilted 18° rightward or leftward to induce a maximal effect [41, 59], in a pseudorandomised order to verify that the VTE effect was symmetrical. No information about this tilt was communicated to participants, who could freely move their head during the VTE immersion. Tasks Three tasks were assessed in the frontal plane: PV, VV and the active standing posture (more details are given in the study protocol[69]). Assessments of verticality perception were performed before VTE, during VTE (15-min immersion), and 10 min after the VTE arrest. For practical reasons related to the duration of the experiment and its difficulty in individuals tested at a subacute phase after a stroke (healthy individuals of the current article were also controls in that study and had to perform the same experiment), only 2 conditions were compared for the active standing: before and during VTE. PV was measured with the device and paradigm specifically designed for this purpose [25] and that has been well validated by usage since, especially in the roll plane in healthy individuals [25] as well as in individuals with stroke [13, 25, 31] or Parkinson’s disease [33] who may exhibit a contralesional PV bias causing lateropulsion. In the current study, individuals were seated in our wheel-like framework, in complete darkness (Figure 1). During PV assessments, they were laterally maintained by adjustable lateral wedges, so that their whole-body orientation was passively moved in unison with the wheel (Figure 1B). The wheel was slowly and manually turned, in the frontal plane, and participants were asked to estimate their PV by signaling when they felt that their whole-body orientation was upright. Small adjustments were allowed if needed. During PV assessment with VTE, the tilted orientation of the scene was stabilized on the Earth’s vertical regardless of body orientation. After 2 practice trials, 10 trials were performed. PV orientation was calculated as the algebraic mean. Positive values of trials corresponded to a PV oriented to the right at baseline and in the direction of the VTE otherwise and vice versa for negative values. We calculated the 2 main indicators used in spatial perception [75] when a directional effect is expected [76]: the accuracy (orientation, mean of trials) and the precision (within-individual variability). VV test consisted of binocular visual adjustments of a bright line to the direction perceived as vertical [76]. Participants remained seated in the PV device but with trunk lateral wedges loosened. They wore the VR helmet softly maintained upright by lateral wedges to preclude any head tilt induced by the VTE [41], which might affect VV [77, 78]. They were asked to verbally set the line to the vertical [41] by telling the examinator to move the line in a certain direction. Small adjustments were allowed if needed (0.1° step). After 2 practice trials, 10 trials were performed. VV orientation was calculated as the algebraic mean [79]. A positive value corresponded to a VV oriented to the direction of the VTE tilt and a negative value to a VV oriented in the opposite direction to the VTE tilt. Ranges of normality remain to be determined for VV tested with a virtual reality device. For the active standing posture, participants were instructed to maintain the standing position comfortably, with arms hanging by sides, without talking. Feet were placed parallel and 14 cm apart. Before VTE (baseline), participants were instructed to look straight ahead to a clue placed in front of them while not wearing the VR helmet. During VTE, participants received the same instructions to look straight ahead but while wearing the VR helmet. Three trials of 20 sec were recorded for each condition. The segmental body orientation (head, upper trunk, and pelvis) was assessed in the frontal plane by placing the IMU over the occipital apex, the spinous process of the 7 th vertebra (C7) and the first sacral spinous process (S1). Results from the 3 trials were averaged and expressed in degrees with 0.1° accuracy. Posturography involved using the commercial dual force platform Feetest6 (Techno Concept) fixed to the ground in a quiet room dedicated to this [80]. The main result was the mass placed on the lower limb to the side of the VTE tilt, expressed in percentage body weight with 0.1% accuracy (3 trials averaged). The dispersion (standard deviation) of the mediolateral position of the centre of pressure (in millimeters) was also extracted from each trial, then averaged. This criterion is considered an index of postural instability [80]. Outcomes VTE effects on verticality perception Three conditions were compared for PV and VV: before, during and after VTE immersion. The main criteria analysed were PV and VV orientations. We also calculated the magnitude of the VTE modulation for PV and VV. A positive value indicated a modulation in the direction of the VR tilt and a negative value a modulation in the opposite direction. For each estimate, PV and VV, we also calculated the proportion of responders (modulation ≥2° in the direction of the VR tilt) [81]. VTE effects on active standing posture We compared two conditions, before and during VTE, for each criterion: the vertical orientation of each key body segment in the frontal plane (head, trunk and pelvis) and the WB on the ground. We also compared the postural instability before and during VTE immersion. Discomfort associated with the VTE immersion The discomfort in the VTE was quantified at the end of each session with a semi-structured interview comprising a scoring of the discomfort from 0 (no discomfort) to 10 (intolerable discomfort). We also planned to record any other eventual harm (details in supplemental material). Statistical analysis All individuals and available data were included in the analyses. Continuous data are presented with means (SD) or medians (Q1;Q3) and categorical data with numbers (%). The normality and equality of variances were checked with the Shapiro-Wilk and Brown-Forsythe statistical tests, respectively. PV and VV orientations were compared to the veridical vertical with a t-test to zero. The VTE effect on PV and VV was analysed with one-factor repeated ANOVA, comparing the 3 conditions (baseline, during and after VTE), then if significant with parametric paired t-tests (p-value adjusted). Magnitudes of the modulation induced on PV and VV were compared with a parametric paired t-test. The symmetry of VTE effect on verticality perception was analysed with a two-factor repeated measure ANOVA (2 VTE sides, 2 verticality estimates), then if significant with parametric paired t-tests (p-value adjusted). The VTE effect on outcome of the active standing was analysed with a Wilcoxon test comparing the 2 conditions (baseline, during VTE). Correlations between changes induced by VTE on VV, VP and WB were analysed by Pearson correlation if possible or Spearman correlation otherwise. Discomfort scores of the 2 sessions were compared with a Wilcoxon test. Bilateral statistics were used and the significance level was fixed at 0.05. Effect sizes were calculated according to Tomczak et al [82] and interpreted according to Cohen’s guidelines, either on t-tests (small, d>0.19; medium, d>0.49; and large, d>0.79); or on Wilcoxon tests (small, r>0.09; medium, r>0.29; and large, r>0.49) [83]. Results Participants We recruited the 20 healthy individuals, tested from July 2021 to July 2022: 12 were assigned to plan A and 8 to B. The side of the VTE was rightward for 11/20 individuals and leftward for 9/20. The mean age was 60.4 (8.0) years, and most were males (12/20; 60%). The mean BMI was 23.2 (2.42) kg/m 2 and the mean time between the 2 experimental sessions was 1.6 (0.68) days. Missing data Two individuals (10%) were not able to perform PV and VV twice. Both felt dizzy when tested for PV wearing the VTE device at baseline, in darkness, and the session had to be stopped. Therefore, their discomfort in the VTE immersion could not be assessed. Their active standing could be assessed the day after (plan A). Body orientation was not assessed in 4 individuals (20%) because of technical problems. No other data were missing. Effect of VTE immersion on verticality perception Individual data are presented in Figure 4 (A and B) and conditions are compared in Table 1. Table 1. Verticality perception in 3 conditions: at baseline and during and after virtual tilted environment (VTE) immersion. Baseline During VTE After VTE VTE effect (Baseline vs during) p-value; effect size VTE post-effect (Baseline vs after) p-value Orientation PV° (n=18) VV° (n=18) 0 (0.8) 0.5 (-0.5 ;1.3) 3.8 (3.8) 14 (12 ;14.9) 0 (1.3) 0.9 (-0.3 ;1.5) <10 -3 ; d=1.32 <10 -3 ; d=3.3 0.61 0.64 Uncertainty PV° (n=18) VV° (n=18) 1.7 (0.7) 0.7 (0.6 ;1.2) 2 (0.8) 0.7 (0.6 ;0.8) 1.9 (0.7) 1.2 (0.9 ;1.5) 0.17; - 0.24; - 0.45 0.29 Data are mean (SD) or median (Q1; Q3). Abbreviations: PV = postural vertical; VV = visual vertical. For PV orientation , data at baseline did not differ from the true vertical (t=0.13; p=0.38) and was always within the ranges of normality. In the experimental condition, PV was tilted in the same orientation as the VTE, toward the side that the environment was tilted, with a mean magnitude of 3.8° (3.8°) and a large effect size (Table 1). Most participants were responders (13/18, 72%). Among the 5 (28%) non-responders, 1 showed a surprising PV modulation oriented in the non-expected direction (i.e., the side opposite the VTE) (Figure 4A). Ten minutes after VTE, PV modulation decreased in all participants, and PV no longer differed from baseline (Table 1). Thus, there was no VTE post-effect on PV in healthy individuals. For VV orientation , data at baseline did not differ from the true vertical (t=1.64; p=0.38). In the experimental condition, VV was tilted in the same orientation as the VTE, toward the side that the environment was tilted, with a median magnitude of 14° (12;14.9) and a large effect size (Table 1). The magnitude of the modulation was much larger for VV than PV (p<10 -3 , d=1.70), but these modulation magnitudes were correlated (r=0.51; p=0.03). Most participants were responders (16/18, 89%), with a VV systematically tilted in the direction of the VTE, including the individual with a PV modulation oriented in the opposite direction. The only 2 individuals (11%) who were not responders for VV nevertheless showed a small tilt (1°) in the same orientation as the VTE. At 10 min after VTE arrest, VV modulation decreased and VV no longer differed from baseline (Table 1). Thus, there was no VTE post-effect on VV in healthy individuals. Side of the modulation . On two-factor ANOVA (2 VTE sides, 2 verticality estimates), PV and VV modulations were greater when the VTE was tilted leftward (p=0.02), with a small effect size (d=0.1). The mean PV modulation was 5.4° (3.7) for leftward VTE and 2.1° (3.8) for rightward VTE. For VV, the mean modulation was 13.5° (2.5) for leftward VTE and 9.5° (6.2) for rightward VTE. We then analysed PV and VV uncertainties (Table 1). Uncertainties were low, which attested to the robustness of the measurements, despite the experimental conditions and repeated measurements of the study. Of note, they were not affected by the VTE immersion, so judgements of verticality directions remained precise even when the internal model of verticality was experimentally biased by the VTE Effect of VTE immersion on active standing Data are presented in Table 2 and Figure 4C. Table 2. Participants’ active standing posture at baseline and during virtual tilted environment (VTE) immersion. Baseline During VTE VTE effect p-value; effect size Body orientation Mean ° O1 C7 S1 -1.1 (1.7) -0.1 (1.7) -1.0 (2.1) -1.3 (3.7) -0.8 (3.7) -1.4 (2.0) 0.82; - 0.49; - 0.28; - Posturography WB, % 49.4 (3.1) 51.9 (3.8) <10 -3 ; r=0.71 Postural instability (mm) 1.1 (0.4) 1.3 (0.4) 0.07; - Data are mean (SD). Abbreviations: COP = center of pressure; WB = % of body weight supported by the lower limb at the side of the VTR; O1 = occipital apex; C7 = the spinous process of the 7 th vertebra; S1 = first sacral spinous process Body orientation . The segmental body orientation in the frontal plane did not differ before and during VTE, but the inter-individual data dispersion was twice higher with VTE, at occiput and C7 level (Table 2). Mass distribution . The VTE induced a strong WB change, loading the lower limb on side of the VTE more than the other limb (Figure 4C), with a large effect size: 49.4% (3.1) before VTE versus 51.9% (3.8) during VTE (p <10 -3 ; r=0.71). WB modulation was comparable for rightward and leftward VTE tilt (p=0.13). Most participants behaved this way (17/20, 85%) (Figure 4C), with a mean WB modulation of 3.1% (1.8). This VTE modulation of WB was not correlated with the VTE modulation of verticality perception, PV (r=0.13, p=0.60) or VV (r=0.02, p=0.91). The VTE immersion did not significantly affect the amount of body sway (Table 2), so the postural stability in standing was comparable at baseline and during VTE, during the short duration of the recording (20 sec). Discomfort associated with the VTE immersion Scores for discomfort associated with the VTE immersion varied from 0 to 3. Discomfort scores did not differ between sessions (median 1 [0 to 2] vs 1 [0 to 1]; p=0.10). We averaged these scores to analyse the global discomfort associated with the VTE during the whole experiment. Only 5/20 (25%) individuals experienced no discomfort (score of 0). Others (15/20, 75%) experienced minimal discomfort (score > 0 and < 3). VV data obtained for healthy individuals tested with a VR device VV data obtained before VTE in 19 participants may help give an estimate of the ranges of normality expected for VV performed with a VTE device, head maintained upright as recommended [76, 78]. Data distribution was not Gaussian, ranging from -1.9° to +2.7°, with 5th and 95th percentiles at -1.9° and +2.6°. If we add a possible measurement error (adjustment of the helmet, line step), round values, and to stay symmetrical with respect to zero, the estimated range of normality was from -3° to +3°. The within-individual variability was also low, with the 90 th percentile at 1.6° (threshold of normality 2°). Discussion Our study tested 3 main hypotheses in 20 healthy individuals: the VTE effect on verticality perception is transmodal, followed by a post-effect, and with an impact on the active body orientation in standing. The study partially confirmed these hypotheses. A 45-min VTE immersion induced a transmodal modulation in verticality representation toward the side of the tilted environment, with a magnitude much greater for VV (13.5°) than PV (3.8°), the modulation on both estimates being correlated. Most participants were responders: 16/18 (89%) for VV and 13/18 (72%) for PV. This VTE-induced modulation extended to the active body orientation in standing, eliciting a complex postural behaviour. Participants remained vertical and stable, but in response to the VTE tilt, loaded their lower limb more to that side. No post-effect was found 10 min after the VTE arrest. The VTE discomfort was minimal in 75% of participants and null in 15%. Effect of VTE immersion on verticality representation Our study is one of the first to investigate the VTE effect on verticality perception in healthy individuals, VV [41] or PV [67], and the first to investigate both modalities. It revealed that the VTE has a transmodal effect on VV and PV, their modulations being correlated. This finding indicates the existence of a high-order modulation of verticality representation. Because of the powerful VTE modulation on PV and VV orientations, without imprecision, the VTE had a specific directional effect on the internal model of verticality, which remained robust although experimentally biased. This is an important finding advocating for the use of the VTE in a clinical context, to recalibrate a biased verticality representation. Effect of VTE immersion on active standing The VTE-induced modulation was extended to the active body orientation in standing, which was predicted by the concept of an internal model of verticality [3, 4, 25], thus supporting a close link between perception an action with respect to gravity [3, 4, 11, 13, 14, 21, 25, 31, 41, 84]. This VTE elicited a complex postural behaviour. Participants remained vertical, as observed in a previous study [68], and stable. However, the present study reveals that they responded to the VTE by loading their lower limb to the side of the tilt. This WB change translated a directional effect of the VTE on body posture in standing, the projection of the centre of mass on the ground being shifted toward the VTE tilt side. This behaviour may be considered a way to counteract the expectation effect of the VTE predicted by the theory of destabilizing body tilt in healthy individuals and may mean that remaining vertical is a priority of the postural control to avoid imbalance. The increase in inter-individual variability in the segmental body orientation with respect to gravity is an indicator of the complexity of this postural adaptation in response to the VTE, all individuals not behaving similarly. Finally, from a behavioural point of view, these experimental results demonstrate the existence of a dissociated regulation for the 2 domains of the postural control, organized as postulated by Massion [85], from a control of the body orientation with respect to gravity and a control of the postural stabilisation with respect to the base of support. This postural control organisation in 2 independent components is supported by the demonstration in animals that each component relies on specific neural circuits [86, 87]. Clearly, this is now the way to conceive, assess and treat postural disorders [26, 88]. The results of the present study also allow for better understanding the WB asymmetry after stroke, in a context of a clinical bias of verticality representation. Greater VTE effect on VV than PV The greater effect on VV than PV is likely due to the specific information involved for each modality. VV mainly tests the visuo-vestibular contribution to the internal model of verticality [3, 7, 74, 89], whereas PV mainly tests the contribution of the somaesthetic gravity sensing [25, 38, 54, 72, 73]. Beyond somatosensory information, and considered from the prism of spatial frames of reference, VV is viewed as a way to test how an individual experiences the upright of the environment, whereas PV is viewed as a way to test how an individual experiences the upright of her/his own body [13]. On VV , we found a VTE effect comparable to that previously reported in healthy individuals with the same equipment but a unique VTE pattern displaying a child bedroom [41]. Pooled data from both studies show that the VV modulation toward the VTE tilt side was constant, with 33/35 (94%) individuals being responders (modulation ≥ 2°), mostly with an enormous magnitude, > 10°. An important difference between the 2 studies was the head orientation, free and tilted toward the VTE tilt in the first study and maintained approximately upright in the current study. This difference excludes the possibility that the VTE effect on VV would have been magnified by a head tilt, indeed impossible over some degrees in the current study (lateral wedges at distance of the head). Neither of the 2 studies monitored eye torsion, so one cannot exclude that the VV tilt would have been magnified by an eye torsion induced by the VTE, especially in the present study, in which the head was maintained upright. Indeed, eye torsion is a sufficient mechanism to induce an enormous VV tilt [74, 90], other modalities of verticality perception being normal [74]. In the current study, the VTE also modulated PV, so a false positive result caused by eye torsion is implausible. In the present study, the magnitude of modulation was much greater for VV than PV. This magnitude of VV modulation induced by the VTE is similar to that obtained when participants are inside an actual tilted room [60] and twice stronger than that obtained with other types of devices eliciting non-immersive 3D environments [58, 66]. These strong effects supported by a large effect size were predicted by optimizing several factors well known to enhance modulation of the VV when presented in a tilted environment: the richness and meaningfulness of the indices of the environment supposedly indicating the direction of the vertical but presented tilted [56, 59, 91], the angular size of the material displayed [91, 92] and a tilt of the environment about 18° for maximal effect [58, 59]. One may even wonder whether the characteristics of the visual line displayed within the VR helmet might have contributed to the powerful VV modulation. It is an unusually large visual line in terms of angular size, which is a factor known to affect VV results [93]. On PV , we found that the body was perceived vertical when tilted toward the tilt of environment, a result congruent with that of another study in individuals of same age [67]. During the VTE, verticality representation partly follows the visual clues supposedly indicating the direction of the vertical but presented tilted. In our study, the VTE effect was twice higher than that reported in the other study [67], with a much lower inter-individual variability, most participants being responders (modulation ≥ 2°). The effect size was large in our study and not reported in the other study. Our better results seem related to the quality of our PV testing, well validated by usage [2, 13, 25, 27, 28, 31, 32, 94]. This device and procedure are unique, progressively implemented during several months before starting assessment for studies [25] and regularly improved since. However, individuals who feel uncomfortable in darkness (> 10 min) wearing the VR helmet (baseline measurements in darkness) cannot complete this session. This was the case for 2/20 (10%) of our healthy individuals at baseline. No post-effect on verticality representation The only study investigating the VTE effect on verticality found clues of a post-effect, with the persistence at 6 min of head tilt [41]. In the present study, we found no post-effect at 10 min after the VTE arrest, for PV or VV. During this short time, individuals remained seated in complete darkness, still installed in the device used for PV, set horizontal. This device, which maintains them upright, give clues of uprightness (the seat itself as well as adjustable lateral wedges for the head, the trunk with the arms, and the pelvis). This experimental setup might explain in part why the VTE effect on verticality representation does not last when visual cues of a wrong verticality disappear. The current study tested healthy individuals with normal gravity sensing and normal functioning of their internal model of verticality. The return to baseline might be slower in individuals with altered gravity sensing (somaesthetic and vestibular graviception) and abnormal functioning of their internal model of verticality. This hypothesis will be tested in the second part of the VIRGIL study dedicated to individuals with lateropulsion caused by a wrong verticality representation after a hemisphere stroke. Discomfort with the VTE No important cybersickness was reported by participants of our study, in which they did not have to move within a surrounding. In contrast, the global discomfort seemed high in healthy individuals deambulating in hospital corridors virtually displayed with a 20° tilt[95], many stopping the experiment before the end. This discomfort in tasks involving postural control may have several reasons. In addition to non-congruent information on verticality given by vision and that given by gravity sensing, which may induce dizziness, the lack of optic flow when moving around might create another conflict between visual information of movement on one hand and vestibular and proprioceptive information of movement on the other [96]. Ranges of normality for VV tested with a VR device Since the first publication in 2018 [41], VV is increasingly being tested with a VR device and regularly presented as a new test. Testing VV with this method is reliable [97, 98]. In testing head maintained upright as recommended [76, 78, 98], we found narrow estimated ranges of normality (baseline) in individuals aged about 60 years. Therefore, our setting allowed participants to be accurate and precise when adjusting the visual line displayed within the helmet to the direction they perceived as vertical. This good result may be explained by a perfect darkness within the helmet, without any visual information inducing noise in the data. For orientation (accuracy), the normality ranged from -3° to +3°, which is better than that is sometimes reported for virtual VV [97] but slightly greater than what is obtained with standard mechanical or digital methods, also with head maintained upright [25, 70]. Several reasons might explain that the range of normality of VV with a virtual device is less narrow than that with standard methods. The weight and the bulk of the helmet could play a role as well as the cybersickness even if whether it affects VV is unclear [41, 99]. The unusually large size of the visual line (large angular size) might also play a role. Further investigations are needed to comparatively analyse these methods. Clinical implication This study opens interesting perspectives for individuals with lateropulsion after hemisphere stroke, a condition characterized by a biased perception of verticality and postural asymmetry [3, 25, 100]. This is the second part of the VIRGIL study, the recruitment of which is ongoing. The post-effect question should be central. In the Virgil study, the immersion in the virtual environment is passive, individuals being simply instructed to explore the 4 VTE scenes successively presented (Figure 3). An active set-up could be interesting, with individuals interacting with the virtual environment, for example by playing with falling objects. This will allow them to realize they make errors and lead them to progressively rectify their action. This active process involving the timing component of the internal model of gravity [22] might strengthen its plasticity and prolong its modulation after the VTE arrest. Future research might consider this track to favour the persistence of a post-effect. Study limitations The principal limitation of the study was that we did not monitor eye orientation. Eye torsion may be induced by the virtual tilt of the environment, especially when the head is maintained, as in our study. VV covaries with eye torsion [74, 101], so the magnitude of the VV tilt may have been due in part to eye torsion. This situation might explain in part why the effect was much greater on VV than PV. A second limitation was a global quantification of the discomfort experienced by participants after each session, with an analogous scale. This approach does not analyse the nature of symptoms, as do cybersickness questionnaires. However analogic scorings allow a quick and satisfactory estimation of the discomfort intensity, feasible even in dizzy individuals. The interpretation of the WB change might be refined by assessments of lateral forces and moments, not measured in our study. Conclusion In healthy individuals, we show that a 45-min immersion in VTE induced a modulation of verticality representation associated with a modulation of active standing. The clinical interest of this approach may now be investigated in individuals showing post-stroke lateropulsion due to a wrong sense of verticality. The lack of a post-effect in healthy individuals does not predict whether or not the effect will persist in individuals with a biased internal model of verticality. Declarations Ethics approval and consent to participate VIRGIL protocol was approved by an Institutional Review Board (Comité de Protection des Personnes Ile de France X; 2020-A02941-38) which was randomly selected from a national panel, and registered at ClinicalTrials.gov in May 2021 (https://clinicaltrials.gov/study/NCT04911738). All healthy individuals recruited gave written informed consent to participate in the study. Consent for publication All authors approved the submitted version, and agreed both to be personally accountable for the author's own contributions and to ensure that questions related to the accuracy or integrity of any part of the work, even ones in which the author was not personally involved, are appropriately investigated, resolved, and the resolution documented in the literature. Availability of data and materials Details on the prototype used to test PV may be requested from the corresponding author. Data are available on reasonable request under conditions detailed in the study protocol [69]. Competing interests None Funding This work was supported by the Fondation Paul Bennetot (grant no. AP-FPB-18-004) and also the VIRTUALIS company (providing the VRE device and program). The funders did not interfere in any step of the research (design, conduct, analysis or reporting). Authors' contributions S. De. - P reparation of documents for the ethics committee and trial registration, d ata collection, d ata curation, statistical analyses, preparation of tables and figures, writing original draft. A. H. - P reparation of documents for the ethics committee and trial registration, data collection, d ata curation , statistical analyses , data analysis, intellectual content, editing O. F. - Data collection, intellectual content. S. Da. - Study conception , p reparation of documents for the ethics committee and trial registration, data collection. C. P. - Study conception, p reparation of documents for the ethics committee and trial registration, data collection, intellectual content , editing. E. L. - D ata curation , data analysis, i ntellectual content, editing, submission of the article. D. P. - F unding acquisition, study conception, study supervision, data curation, data analyses, writing original draft. 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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-7472074","acceptedTermsAndConditions":true,"allowDirectSubmit":true,"archivedVersions":[],"articleType":"Research Article","associatedPublications":[],"authors":[{"id":510996380,"identity":"1f1d68ca-e77a-49d7-9564-345f93ef6c83","order_by":0,"name":"Stéphanie Dehem","email":"","orcid":"","institution":"Centre Hospitalier Universitaire de Grenoble","correspondingAuthor":false,"prefix":"","firstName":"Stéphanie","middleName":"","lastName":"Dehem","suffix":""},{"id":510996381,"identity":"0c363984-e517-4e3b-925b-bff56f52d307","order_by":1,"name":"Aurélien Hugues","email":"","orcid":"","institution":"Centre Hospitalier Universitaire de Grenoble","correspondingAuthor":false,"prefix":"","firstName":"Aurélien","middleName":"","lastName":"Hugues","suffix":""},{"id":510996382,"identity":"280e698b-a834-4cdc-8578-a084146c2f19","order_by":2,"name":"Ophélie Folmer","email":"","orcid":"","institution":"Centre Hospitalier Universitaire de Grenoble","correspondingAuthor":false,"prefix":"","firstName":"Ophélie","middleName":"","lastName":"Folmer","suffix":""},{"id":510996383,"identity":"78b53a5e-87d5-41b6-b448-e7288b473d54","order_by":3,"name":"Shenhao Dai","email":"","orcid":"","institution":"Centre Hospitalier Universitaire de Grenoble","correspondingAuthor":false,"prefix":"","firstName":"Shenhao","middleName":"","lastName":"Dai","suffix":""},{"id":510996384,"identity":"f92fb61f-6809-441a-b195-674d0648693b","order_by":4,"name":"Céline Piscicelli","email":"","orcid":"","institution":"Centre Hospitalier Universitaire de Grenoble","correspondingAuthor":false,"prefix":"","firstName":"Céline","middleName":"","lastName":"Piscicelli","suffix":""},{"id":510996385,"identity":"7396ad25-67eb-4674-8184-c5781d1893ae","order_by":5,"name":"Eugénie Lhommée","email":"","orcid":"","institution":"Centre Hospitalier Universitaire de Grenoble","correspondingAuthor":false,"prefix":"","firstName":"Eugénie","middleName":"","lastName":"Lhommée","suffix":""},{"id":510996386,"identity":"02cf572f-cc1e-40d2-819a-86eaad7bcf89","order_by":6,"name":"Dominic Pérennou","email":"data:image/png;base64,iVBORw0KGgoAAAANSUhEUgAAAZAAAAAyAQMAAABI0h/eAAAABlBMVEX///8AAABVwtN+AAAACXBIWXMAAA7EAAAOxAGVKw4bAAABBklEQVRIie3QsUrDQBzH8V8JxOXarP8Q6TP84aBFEHyVlEJcAl0daggUsrkb6EM4OgYC1yUPkJIOgUAmh4qTg8VEKIh41lHwvtNxdx+4/wEm018sOy7OYvu4tFEDzmkisk/EB9z4JCH/l2RUrdT++XE35m3TNgK3C8dbqdq/AU01xt2peZoWreQqmEqBzUW6VtfsF6Dz7HvCZSitYZLPHqrQ9oYHxd3OhGYJItI8jMvFi/XWk21hewKKrz7IAaQnoWUNelKKniyZqSexnnSzyMFdkku3CCbuGhlTGXSzKNKS7scavCb5eLTJW3pCxM79XNX75aWW4MtBrtn/gUT6myaTyfRvewe2OVn++FJ7mwAAAABJRU5ErkJggg==","orcid":"","institution":"Centre Hospitalier Universitaire de Grenoble","correspondingAuthor":true,"prefix":"","firstName":"Dominic","middleName":"","lastName":"Pérennou","suffix":""}],"badges":[],"createdAt":"2025-08-27 13:23:19","currentVersionCode":1,"declarations":"","doi":"10.21203/rs.3.rs-7472074/v1","doiUrl":"https://doi.org/10.21203/rs.3.rs-7472074/v1","draftVersion":[],"editorialEvents":[],"editorialNote":"","failedWorkflow":false,"files":[{"id":90929090,"identity":"684c9cd1-7199-4b35-b8a9-90943f10ae67","added_by":"auto","created_at":"2025-09-09 16:03:29","extension":"png","order_by":1,"title":"Figure 1","display":"","copyAsset":false,"role":"figure","size":310646,"visible":true,"origin":"","legend":"\u003cp\u003eSet-up for the session devoted to verticality perception: A) upright; B) postural vertical testing.\u003c/p\u003e","description":"","filename":"Fig1.png","url":"https://assets-eu.researchsquare.com/files/rs-7472074/v1/64d19377df6790226a5af27e.png"},{"id":90929092,"identity":"5aff466a-e7ba-42f4-8811-1dc56cb82121","added_by":"auto","created_at":"2025-09-09 16:03:29","extension":"png","order_by":2,"title":"Figure 2","display":"","copyAsset":false,"role":"figure","size":94377,"visible":true,"origin":"","legend":"\u003cp\u003eSet-up for the session devoted to active standing posture.\u003c/p\u003e","description":"","filename":"Fig2.png","url":"https://assets-eu.researchsquare.com/files/rs-7472074/v1/5bea5a604d0fae77c53202ed.png"},{"id":90929094,"identity":"74f42b4d-a0a6-4a03-8c8a-91f18c2354f0","added_by":"auto","created_at":"2025-09-09 16:03:29","extension":"png","order_by":3,"title":"Figure 3","display":"","copyAsset":false,"role":"figure","size":329384,"visible":true,"origin":"","legend":"\u003cp\u003eFour static immersive tilted environments.\u003c/p\u003e","description":"","filename":"Fig3.png","url":"https://assets-eu.researchsquare.com/files/rs-7472074/v1/5174bc4fe13b6dfb4ec9fa7c.png"},{"id":90929093,"identity":"6f2449a8-0be8-475e-bc61-389887dacb04","added_by":"auto","created_at":"2025-09-09 16:03:29","extension":"png","order_by":4,"title":"Figure 4","display":"","copyAsset":false,"role":"figure","size":67652,"visible":true,"origin":"","legend":"\u003cp\u003eIndividual data at baseline and during and after virtual tilted environment immersion. Results for A) postural vertical (PV) orientation; B) visual vertical (VV) orientation; C) weight-bearing (WB) asymmetry. Abbreviations: VTR = virtual tilted reality; WB = % of body weight supported by the lower limb on the side of the VTR.\u003c/p\u003e","description":"","filename":"Fig4.png","url":"https://assets-eu.researchsquare.com/files/rs-7472074/v1/66774c96dc4e221a6e4109e6.png"},{"id":98426663,"identity":"7e952ec2-acde-4039-9f12-911a529c0b6b","added_by":"auto","created_at":"2025-12-17 16:38:09","extension":"pdf","order_by":0,"title":"","display":"","copyAsset":false,"role":"manuscript-pdf","size":1896088,"visible":true,"origin":"","legend":"","description":"","filename":"manuscript.pdf","url":"https://assets-eu.researchsquare.com/files/rs-7472074/v1/6cfd22de-b3bd-4a4d-a9b9-b39cfa31c768.pdf"},{"id":90930557,"identity":"b10802ba-c995-435d-8f42-7757cbf94d4f","added_by":"auto","created_at":"2025-09-09 16:11:29","extension":"docx","order_by":0,"title":"","display":"","copyAsset":false,"role":"supplement","size":32876,"visible":true,"origin":"","legend":"","description":"","filename":"VIRGILHealthyCONSORTchecklist.docx","url":"https://assets-eu.researchsquare.com/files/rs-7472074/v1/d0f2b167087469c5e3111f0a.docx"}],"financialInterests":"No competing interests reported.","formattedTitle":"Immersion in a virtual tilted environment strongly modulates perception and action with respect to gravity: a within-person randomized trial of healthy individuals","fulltext":[{"header":"Background","content":"\u003cp\u003eThe sense of verticality (sense of upright) is a terminology proposed in the 2000s [\u003cspan additionalcitationids=\"CR2 CR3 CR4\" citationid=\"CR1\" class=\"CitationRef\"\u003e1\u003c/span\u003e\u0026ndash;\u003cspan citationid=\"CR5\" class=\"CitationRef\"\u003e5\u003c/span\u003e] to describe an important brain function constructed by combining gravity sensing and visual clues of verticality [\u003cspan citationid=\"CR3\" class=\"CitationRef\"\u003e3\u003c/span\u003e, \u003cspan citationid=\"CR6\" class=\"CitationRef\"\u003e6\u003c/span\u003e, \u003cspan citationid=\"CR7\" class=\"CitationRef\"\u003e7\u003c/span\u003e] through internal models, the existence of which has been demonstrated in animals [\u003cspan additionalcitationids=\"CR9\" citationid=\"CR8\" class=\"CitationRef\"\u003e8\u003c/span\u003e\u0026ndash;\u003cspan citationid=\"CR10\" class=\"CitationRef\"\u003e10\u003c/span\u003e], including humans [\u003cspan citationid=\"CR3\" class=\"CitationRef\"\u003e3\u003c/span\u003e, \u003cspan citationid=\"CR4\" class=\"CitationRef\"\u003e4\u003c/span\u003e, \u003cspan citationid=\"CR8\" class=\"CitationRef\"\u003e8\u003c/span\u003e, \u003cspan additionalcitationids=\"CR12 CR13\" citationid=\"CR11\" class=\"CitationRef\"\u003e11\u003c/span\u003e\u0026ndash;\u003cspan citationid=\"CR14\" class=\"CitationRef\"\u003e14\u003c/span\u003e]. The sense of upright serves to perceive the vertical orientation of the body [\u003cspan citationid=\"CR15\" class=\"CitationRef\"\u003e15\u003c/span\u003e, \u003cspan citationid=\"CR16\" class=\"CitationRef\"\u003e16\u003c/span\u003e] and the environment [\u003cspan citationid=\"CR6\" class=\"CitationRef\"\u003e6\u003c/span\u003e, \u003cspan citationid=\"CR15\" class=\"CitationRef\"\u003e15\u003c/span\u003e, \u003cspan additionalcitationids=\"CR18\" citationid=\"CR17\" class=\"CitationRef\"\u003e17\u003c/span\u003e\u0026ndash;\u003cspan citationid=\"CR19\" class=\"CitationRef\"\u003e19\u003c/span\u003e], and to predict the stability of objects in space [\u003cspan citationid=\"CR20\" class=\"CitationRef\"\u003e20\u003c/span\u003e]. and trajectories related to gravity [\u003cspan citationid=\"CR21\" class=\"CitationRef\"\u003e21\u003c/span\u003e, \u003cspan citationid=\"CR22\" class=\"CitationRef\"\u003e22\u003c/span\u003e]. It also serves to control actions with respect to gravity, especially balance and gait [\u003cspan additionalcitationids=\"CR24 CR25 CR26 CR27 CR28 CR29\" citationid=\"CR23\" class=\"CitationRef\"\u003e23\u003c/span\u003e\u0026ndash;\u003cspan citationid=\"CR30\" class=\"CitationRef\"\u003e30\u003c/span\u003e], and actions of upper limbs referred to top and bottom [\u003cspan citationid=\"CR31\" class=\"CitationRef\"\u003e31\u003c/span\u003e, \u003cspan citationid=\"CR32\" class=\"CitationRef\"\u003e32\u003c/span\u003e]. Regarding postural control, individuals with a biased internal model of verticality align their body on this wrong verticality representation, which causes a lateral whole body tilt [\u003cspan citationid=\"CR25\" class=\"CitationRef\"\u003e25\u003c/span\u003e, \u003cspan citationid=\"CR26\" class=\"CitationRef\"\u003e26\u003c/span\u003e, \u003cspan citationid=\"CR33\" class=\"CitationRef\"\u003e33\u003c/span\u003e], called lateropulsion [\u003cspan additionalcitationids=\"CR34\" citationid=\"CR33\" class=\"CitationRef\"\u003e33\u003c/span\u003e\u0026ndash;\u003cspan citationid=\"CR35\" class=\"CitationRef\"\u003e35\u003c/span\u003e], or a posterior whole body tilt [\u003cspan citationid=\"CR27\" class=\"CitationRef\"\u003e27\u003c/span\u003e, \u003cspan citationid=\"CR28\" class=\"CitationRef\"\u003e28\u003c/span\u003e], called retropulsion. Lateropulsion is the primary detrimental factor explaining balance and gait disorders in the subacute post-stroke phase [\u003cspan citationid=\"CR26\" class=\"CitationRef\"\u003e26\u003c/span\u003e, \u003cspan citationid=\"CR33\" class=\"CitationRef\"\u003e33\u003c/span\u003e, \u003cspan citationid=\"CR36\" class=\"CitationRef\"\u003e36\u003c/span\u003e, \u003cspan citationid=\"CR37\" class=\"CitationRef\"\u003e37\u003c/span\u003e].\u003c/p\u003e\u003cp\u003eA better understanding of how internal models of verticality work would improve our basic knowledge of their functioning and would help to enhance balance rehabilitation with appropriate techniques. Techniques that are supposed to modulate the internal model of verticality may be divided into 3 categories: 1) those modulating gravity sensing on Earth [\u003cspan citationid=\"CR3\" class=\"CitationRef\"\u003e3\u003c/span\u003e, \u003cspan citationid=\"CR12\" class=\"CitationRef\"\u003e12\u003c/span\u003e, \u003cspan citationid=\"CR23\" class=\"CitationRef\"\u003e23\u003c/span\u003e, \u003cspan citationid=\"CR27\" class=\"CitationRef\"\u003e27\u003c/span\u003e, \u003cspan additionalcitationids=\"CR39 CR40 CR41 CR42 CR43 CR44 CR45 CR46 CR47 CR48\" citationid=\"CR38\" class=\"CitationRef\"\u003e38\u003c/span\u003e\u0026ndash;\u003cspan citationid=\"CR49\" class=\"CitationRef\"\u003e49\u003c/span\u003e]; 2) those directly stimulating the brain by magnetic or electrical techniques [\u003cspan additionalcitationids=\"CR51 CR52\" citationid=\"CR50\" class=\"CitationRef\"\u003e50\u003c/span\u003e\u0026ndash;\u003cspan citationid=\"CR53\" class=\"CitationRef\"\u003e53\u003c/span\u003e], the effect of vestibular stimulation being more controversial with non-congruent effects on the visual vertical (VV) and on the postural vertical (PV) [\u003cspan citationid=\"CR49\" class=\"CitationRef\"\u003e49\u003c/span\u003e, \u003cspan citationid=\"CR54\" class=\"CitationRef\"\u003e54\u003c/span\u003e, \u003cspan citationid=\"CR55\" class=\"CitationRef\"\u003e55\u003c/span\u003e]; and 3) those using visual clues tilting the environment in a given direction [\u003cspan citationid=\"CR6\" class=\"CitationRef\"\u003e6\u003c/span\u003e, \u003cspan citationid=\"CR41\" class=\"CitationRef\"\u003e41\u003c/span\u003e, \u003cspan citationid=\"CR44\" class=\"CitationRef\"\u003e44\u003c/span\u003e, \u003cspan additionalcitationids=\"CR57 CR58 CR59 CR60 CR61\" citationid=\"CR56\" class=\"CitationRef\"\u003e56\u003c/span\u003e\u0026ndash;\u003cspan citationid=\"CR62\" class=\"CitationRef\"\u003e62\u003c/span\u003e].\u003c/p\u003e\u003cp\u003eManipulating static [\u003cspan citationid=\"CR57\" class=\"CitationRef\"\u003e57\u003c/span\u003e, \u003cspan citationid=\"CR61\" class=\"CitationRef\"\u003e61\u003c/span\u003e] or dynamic [\u003cspan citationid=\"CR6\" class=\"CitationRef\"\u003e6\u003c/span\u003e, \u003cspan citationid=\"CR56\" class=\"CitationRef\"\u003e56\u003c/span\u003e] vision is long known to have a powerful effect on perception of the vertical. As galvanic vestibular [\u003cspan citationid=\"CR63\" class=\"CitationRef\"\u003e63\u003c/span\u003e, \u003cspan citationid=\"CR64\" class=\"CitationRef\"\u003e64\u003c/span\u003e] or somaesthetic stimulations [\u003cspan citationid=\"CR3\" class=\"CitationRef\"\u003e3\u003c/span\u003e, \u003cspan citationid=\"CR4\" class=\"CitationRef\"\u003e4\u003c/span\u003e, \u003cspan citationid=\"CR23\" class=\"CitationRef\"\u003e23\u003c/span\u003e, \u003cspan citationid=\"CR38\" class=\"CitationRef\"\u003e38\u003c/span\u003e, \u003cspan citationid=\"CR40\" class=\"CitationRef\"\u003e40\u003c/span\u003e, \u003cspan citationid=\"CR65\" class=\"CitationRef\"\u003e65\u003c/span\u003e], dynamic visual stimulations [\u003cspan citationid=\"CR6\" class=\"CitationRef\"\u003e6\u003c/span\u003e, \u003cspan citationid=\"CR56\" class=\"CitationRef\"\u003e56\u003c/span\u003e] interact with postural stabilization. Static visual manipulation can strongly modulate the internal model of verticality without interfering with postural stabilization [\u003cspan citationid=\"CR58\" class=\"CitationRef\"\u003e58\u003c/span\u003e]. A static tilt of the environment attracts the VV to the side with maximal effect for a frame tilted 15\u0026deg; to 20\u0026deg; away from the vertical [\u003cspan citationid=\"CR58\" class=\"CitationRef\"\u003e58\u003c/span\u003e, \u003cspan citationid=\"CR59\" class=\"CitationRef\"\u003e59\u003c/span\u003e]. The effect is stronger with cognitive and structural 3D enrichment [\u003cspan citationid=\"CR59\" class=\"CitationRef\"\u003e59\u003c/span\u003e, \u003cspan citationid=\"CR66\" class=\"CitationRef\"\u003e66\u003c/span\u003e] or by immersion in a real tilted environment [\u003cspan citationid=\"CR56\" class=\"CitationRef\"\u003e56\u003c/span\u003e, \u003cspan citationid=\"CR57\" class=\"CitationRef\"\u003e57\u003c/span\u003e, \u003cspan citationid=\"CR60\" class=\"CitationRef\"\u003e60\u003c/span\u003e], which is difficult to implement in a rehabilitation context.\u003c/p\u003e\u003cp\u003eVirtual reality (VR) allows for complete immersion in a tilted environment. Two exploratory studies of healthy individuals [\u003cspan citationid=\"CR41\" class=\"CitationRef\"\u003e41\u003c/span\u003e, \u003cspan citationid=\"CR67\" class=\"CitationRef\"\u003e67\u003c/span\u003e] and a single case study of post-stroke lateropulsion [\u003cspan citationid=\"CR68\" class=\"CitationRef\"\u003e68\u003c/span\u003e] suggested that immersion in a virtual tilted environment (VTE) could be interesting for recalibrating a biased internal model of verticality and attenuating lateropulsion. The effect on the VV was powerful, the visual line being perceived as vertical when tilted about 11\u0026deg; toward the side that the scene was tilted downward [\u003cspan citationid=\"CR41\" class=\"CitationRef\"\u003e41\u003c/span\u003e].\u003c/p\u003e\u003cp\u003eThese premises led us to set up the VIRGIL stud, which explores the effect of a VTE on the interface of perception\u0026ndash;action with respect to gravity. As explained in the study protocol [\u003cspan citationid=\"CR69\" class=\"CitationRef\"\u003e69\u003c/span\u003e], the VIRGIL study associates a basic study of healthy individuals and a pilot clinical trial of individuals exhibiting post-stroke lateropulsion. This study analyses VTE effects both on verticality perception (PV and VV), and uprightness in standing (instrumental measurements of segmental body orientation and weight-bearing [WB] asymmetry).\u003c/p\u003e\u003cp\u003eThe recruitment of individuals showing lateropulsion after stroke is still ongoing. The current article reports the results of the basic study involving healthy individuals. We addressed 3 main novel and important questions: 1) Is the VTE effect on verticality perception transmodal? This implies that in addition to the modulation of VV [\u003cspan citationid=\"CR41\" class=\"CitationRef\"\u003e41\u003c/span\u003e, \u003cspan citationid=\"CR68\" class=\"CitationRef\"\u003e68\u003c/span\u003e], which mainly tests the vestibular contribution to gravity sensing [\u003cspan citationid=\"CR7\" class=\"CitationRef\"\u003e7\u003c/span\u003e, \u003cspan citationid=\"CR70\" class=\"CitationRef\"\u003e70\u003c/span\u003e, \u003cspan citationid=\"CR71\" class=\"CitationRef\"\u003e71\u003c/span\u003e], VTE also induces a modulation of the PV, which corresponds to the perception of the vertical by the body and mainly tests the somaesthetic contribution to gravity sensing [\u003cspan citationid=\"CR25\" class=\"CitationRef\"\u003e25\u003c/span\u003e, \u003cspan citationid=\"CR38\" class=\"CitationRef\"\u003e38\u003c/span\u003e, \u003cspan additionalcitationids=\"CR73\" citationid=\"CR72\" class=\"CitationRef\"\u003e72\u003c/span\u003e\u0026ndash;\u003cspan citationid=\"CR74\" class=\"CitationRef\"\u003e74\u003c/span\u003e]. If indeed VTE induces a transmodal tilt in verticality perception, then VTE acts at a high order level on verticality representation. 2) Is there any post-effect? 3) Does this VTE-induced modulation of verticality representation extend to the active body orientation in standing? This situation would provide experimental confirmation of the close relationship between verticality representation and action referred to gravity as observed in clinical neurosciences [\u003cspan citationid=\"CR4\" class=\"CitationRef\"\u003e4\u003c/span\u003e], and would pave the way for a clinical application of VTE immersion. We cannot exclude transitory cybersickness symptoms, which will be analysed. No benefit is expected for healthy individuals in this basic part of the study.\u003c/p\u003e"},{"header":"Methods","content":"\u003cp\u003e\u003cstrong\u003eStudy design\u003c/strong\u003e\u003c/p\u003e\n\u003cp\u003eThis exploratory monocentric within-person randomized trial is called VIrtual Reality Glasses Use to Improve Lateropulsion and the Post-stroke Postural Vertical (VIRGIL) fulfills ethics requirements (see declarations section). The protocol has been published [69]. The study took place in Grenoble University Hospital, France. Here we report the results of the basic research performed in healthy individuals who were recruited via a public notice board.\u003c/p\u003e\n\u003cp\u003eIn this experimental exploratory study, investigators and participants could not be masked to the order of session presentation nor the condition with or without VTE.\u003c/p\u003e\n\u003cp\u003eNo interim analysis of data was performed; this article presents most data for all healthy individuals. The reporting of the study follows the 2025 Consort statement (check list in Appendix). Neither patients nor the public were involved in the design, conduct and reporting of the study.\u003c/p\u003e\n\u003cp\u003e\u003cstrong\u003eParticipants\u003c/strong\u003e\u003c/p\u003e\n\u003cp\u003eOn the basis of previous experimental studies performed in healthy individuals with comparable tools [3, 4, 38, 41], a sample size of 20 healthy individuals was considered sufficient to evidence changes in verticality perception (primary outcome). Inclusion criteria were 1) age 18 to 85 years, 2) social health insurance coverage, 3) giving signed, informed and free consent, 3) no stroke or neurological disease history and 4) no previous disability interfering with balance or vestibular disorders. Exclusion criteria were 1) nyctophobia and claustrophobia, 2) history of severe psychiatric disorders, 3) advanced heart failure documented in the medical record, 4) severe trunk deformation with C7 lateral deviation\u0026nbsp;\u0026gt;30 mm due to any disease (\u003cem\u003ei.e.\u003c/em\u003e scoliosis, leg length inequality, etc.) or postural disorder history, 5) pregnant or breast feeding, 6) being in an exclusion period for another study, 7) under judicial or administrative supervision, 8) under guardianship or a tutelage measure, 9) receiving more than 4500 euros\u0026rsquo; compensation for participation in previous research involving humans in the 12 months before the study.\u003c/p\u003e\n\u003cp\u003e\u003cstrong\u003eProcedure\u003c/strong\u003e\u003c/p\u003e\n\u003cp\u003eParticipants were tested in 2 sessions each lasting half a day. One session was devoted to the effect of VTE on verticality perception, comprising both PV and VV, and the other to the effect on standing posture, comprising both the body orientation with respect to gravity and the WB distribution on lower limbs. The running order of sessions was pseudo-randomised: plan A for half of the individuals, with day 1 involving verticality perception and day 2 standing posture; plan B in a reverse order. Details are reported in the study protocol [69].\u003c/p\u003e\n\u003cp\u003eFor sessions devoted to verticality perception, participants were installed in a sitting position in the wheel-like device that measures PV in the roll plane (Figure 1). Measuring PV with this device has been well validated by usage [13, 25, 31, 32]. Participants remained in this wheel-like device during the whole session, wearing the VR helmet. The session started first with an assessment of PV and VV (baseline), then individuals were immersed in VTE for 15 min before starting the second PV and VV assessments, performed with VTE immersion. The VTE immersion lasted about 45 min. Participants in whom the VTE induced a modulation \u0026ge;2\u0026deg; (53) of PV or VV remained 10 min more in the device after the VTE was stopped (they still wore the helmet displaying darkness), and new assessments were performed to search for a post-effect (darkness). The evolution of this post-effect, if any, was monitored by performing some additional measurements of PV or VV every 10 min until it disappeared.\u003c/p\u003e\n\u003cp\u003eFor the standing posture assessment (active body orientation and WB), measurements were performed under 2 different visual conditions: in the natural environment (baseline) then in VTE immersion (preceded by 15 min immersion in sitting). No post-effect was searched. To simultaneously assess the body orientation with respect to gravity and the WB, participants were equipped with an inertial measurement unit (IMU) system and stood on a dual force-plate form (Figure 2).\u003c/p\u003e\n\u003cp\u003eAll during the experiment, we asked participants about any possible discomfort experienced in relation with VR.\u003c/p\u003e\n\u003cp\u003e\u003cstrong\u003eIntervention\u003c/strong\u003e\u003c/p\u003e\n\u003cp\u003eAs shown in Figures 1 and 2, participants wore the HTC Vive helmet (HTC, Taiwan), which delivered the virtual environments generated by the software RelaxationVR 1.0.6 (Virtualis, France) and the VV evaluation module generated by the software RVR-SC 2.3.5 (Virtualis, France). They wore their usual glasses within the device to correct vision if needed. Intervention was provided by trained investigators (StD, AH, CP, ShD).\u003c/p\u003e\n\u003cp\u003eTo avoid effects related to boredom or fatigue, 4 different immersive, static, tilted environments were presented in a fixed order: a beach, a forest, a logging road and a child\u0026apos;s bedroom (Figure 3). Seated participants were instructed to look at the scene, the orientation of which was tilted 18\u0026deg; rightward or leftward to induce a maximal effect [41, 59], in a pseudorandomised order to verify that the VTE effect was symmetrical. No information about this tilt was communicated to participants, who could freely move their head during the VTE immersion.\u003c/p\u003e\n\u003cp\u003e\u003cstrong\u003eTasks\u003c/strong\u003e\u003c/p\u003e\n\u003cp\u003e\u003cem\u003eThree tasks were assessed in the frontal plane: PV, VV and the active standing posture\u003c/em\u003e (more details are given in the study protocol[69]). Assessments of verticality perception were performed before VTE, during VTE (15-min immersion), and 10 min after the VTE arrest. For practical reasons related to the duration of the experiment and its difficulty in individuals tested at a subacute phase after a stroke (healthy individuals of the current article were also controls in that study and had to perform the same experiment), only 2 conditions were compared for the active standing: before and during VTE.\u003c/p\u003e\n\u003cp\u003e\u003cem\u003ePV was measured\u0026nbsp;\u003c/em\u003ewith the device and paradigm specifically designed for this purpose [25] and that has been well validated by usage since, especially in the roll plane in healthy individuals [25] as well as in individuals with stroke [13, 25, 31] or Parkinson\u0026rsquo;s disease [33] who may exhibit a contralesional PV bias causing lateropulsion. In the current study, individuals were seated in our wheel-like framework, in complete darkness\u0026nbsp;(Figure 1). During PV assessments, they were laterally maintained by adjustable lateral wedges, so that their whole-body orientation was passively moved in unison with the wheel (Figure 1B). The wheel was slowly and manually turned, in the frontal plane, and participants were asked to estimate their PV by signaling when they felt that their whole-body orientation was upright. Small adjustments were allowed if needed.\u0026nbsp;During PV assessment with VTE, the tilted orientation of the scene was stabilized on the Earth\u0026rsquo;s vertical regardless of body orientation.\u0026nbsp;After 2 practice trials, 10 trials were performed. PV orientation was calculated as the algebraic mean.\u0026nbsp;Positive values of trials corresponded to a PV oriented to the right at baseline and in the direction of the VTE otherwise and vice versa for negative values. We calculated the 2 main indicators used in spatial perception\u0026nbsp;[75]\u0026nbsp;when a directional effect is expected\u0026nbsp;[76]: the accuracy (orientation, mean of trials) and the precision (within-individual variability).\u003c/p\u003e\n\u003cp\u003e\u003cem\u003eVV test\u003c/em\u003e consisted of binocular visual adjustments of a bright line to the direction perceived as vertical [76]. Participants remained seated in the PV device but with trunk lateral wedges loosened. They wore the VR helmet softly maintained upright by lateral wedges to preclude any head tilt induced by the VTE [41], which might affect VV [77, 78]. They were asked to verbally set the line to the vertical [41] by telling the examinator to move the line in a certain direction. Small adjustments were allowed if needed (0.1\u0026deg; step). After 2 practice trials, 10 trials were performed. VV orientation was calculated as the algebraic mean [79]. A positive value corresponded to a VV oriented to the direction of the VTE tilt and a negative value to a VV oriented in the opposite direction to the VTE tilt. Ranges of normality remain to be determined for VV tested with a virtual reality device.\u003c/p\u003e\n\u003cp\u003e\u003cspan id=\"_Toc43243434\"\u003eFor the active standing posture, participants were instructed to maintain the standing position comfortably, with arms hanging by sides, without talking. Feet were placed parallel and 14 cm apart. Before VTE (baseline), participants were instructed to look straight ahead to a clue placed in front of them while not wearing the VR helmet. During VTE, participants received the same instructions to look straight ahead but while wearing the VR helmet. Three trials of 20 sec were recorded for each condition. The segmental body orientation (head, upper trunk, and pelvis) was assessed in the frontal plane by placing the IMU over the occipital apex, the spinous process of the 7\u003csup\u003eth\u003c/sup\u003e vertebra (C7) and the first sacral spinous process (S1). Results from the 3 trials were averaged and expressed in degrees with 0.1\u0026deg; accuracy. Posturography involved using the commercial dual force platform Feetest6 (Techno Concept) fixed to the ground in a quiet room dedicated to this\u0026nbsp;\u003c/span\u003e[80]. The main result was the mass placed on the lower limb to the side of the VTE tilt, expressed in percentage body weight with 0.1% accuracy (3 trials averaged). The dispersion (standard deviation) of the mediolateral position of the centre of pressure (in millimeters) was also extracted from each trial, then averaged. This criterion is considered an index of postural instability [80].\u003c/p\u003e\n\u003cp\u003e\u003cstrong\u003eOutcomes\u003c/strong\u003e\u003c/p\u003e\n\u003cp\u003e\u003cem\u003eVTE effects on verticality perception\u003c/em\u003e\u003c/p\u003e\n\u003cp\u003eThree conditions were compared for PV and VV: before, during and after VTE immersion. The main criteria analysed were PV and VV orientations. We also calculated the magnitude of the VTE modulation for PV and VV. A positive value indicated a modulation in the direction of the VR tilt and a negative value a modulation in the opposite direction. For each estimate, PV and VV, we also calculated the proportion of responders (modulation \u0026ge;2\u0026deg; in the direction of the VR tilt) [81].\u003c/p\u003e\n\u003cp\u003e\u003cem\u003eVTE effects on active standing posture\u003c/em\u003e\u003c/p\u003e\n\u003cp\u003eWe compared two conditions, before and during VTE, for each criterion: the vertical orientation of each key body segment in the frontal plane (head, trunk and pelvis) and the WB on the ground. We also compared the postural instability before and during VTE immersion.\u003c/p\u003e\n\u003cp\u003e\u003cem\u003eDiscomfort associated with the VTE immersion\u003c/em\u003e\u003c/p\u003e\n\u003cp\u003eThe discomfort in the VTE was quantified at the end of each session with a semi-structured interview comprising a scoring of the discomfort from 0 (no discomfort) to 10 (intolerable discomfort). We also planned to record any other eventual harm (details in supplemental material).\u003c/p\u003e\n\u003cp\u003e\u003cstrong\u003eStatistical analysis\u003c/strong\u003e\u003c/p\u003e\n\u003cp\u003eAll individuals and available data were included in the analyses. Continuous data are presented with means (SD) or medians (Q1;Q3) and categorical data with numbers (%). The normality and equality of variances were checked with the Shapiro-Wilk and Brown-Forsythe statistical tests, respectively.\u003c/p\u003e\n\u003cp\u003ePV and VV orientations were compared to the veridical vertical with a t-test to zero. The VTE effect on PV and VV was analysed with one-factor repeated ANOVA, comparing the 3 conditions (baseline, during and after VTE), then if significant with parametric paired t-tests (p-value adjusted). Magnitudes of the modulation induced on PV and VV were compared with a parametric paired t-test. The symmetry of VTE effect on verticality perception was analysed with a two-factor repeated measure ANOVA (2 VTE sides, 2 verticality estimates), then if significant with parametric paired t-tests (p-value adjusted). The VTE effect on outcome of the active standing was analysed with a Wilcoxon test comparing the 2 conditions (baseline, during VTE). Correlations between changes induced by VTE on VV, VP and WB were analysed by Pearson correlation if possible or Spearman correlation otherwise. Discomfort scores of the 2 sessions were compared with a Wilcoxon test.\u003c/p\u003e\n\u003cp\u003eBilateral statistics were used and the significance level was fixed at 0.05. Effect sizes were calculated according to Tomczak \u003cem\u003eet al\u003c/em\u003e [82] and interpreted according to Cohen\u0026rsquo;s guidelines, either on t-tests (small, d\u0026gt;0.19; medium, d\u0026gt;0.49; and large, d\u0026gt;0.79); or on Wilcoxon tests (small, r\u0026gt;0.09; medium, r\u0026gt;0.29; and large, r\u0026gt;0.49) [83].\u003c/p\u003e"},{"header":"Results","content":"\u003cp\u003e\u003cstrong\u003eParticipants\u003c/strong\u003e\u003c/p\u003e\n\u003cp\u003eWe recruited the 20 healthy individuals, tested from July 2021 to July 2022: 12 were assigned to plan A and 8 to B. The side of the VTE was rightward for 11/20 individuals and leftward for 9/20. The mean age was 60.4 (8.0) years, and most were males (12/20; 60%). The mean BMI was 23.2 (2.42) kg/m\u003csup\u003e2\u0026nbsp;\u003c/sup\u003eand the mean time between the 2 experimental sessions was 1.6 (0.68) days.\u003c/p\u003e\n\u003cp\u003e\u003cstrong\u003eMissing data\u003c/strong\u003e\u003c/p\u003e\n\u003cp\u003eTwo individuals (10%) were not able to perform PV and VV twice. Both felt dizzy when tested for PV wearing the VTE device at baseline, in darkness, and the session had to be stopped. Therefore, their discomfort in the VTE immersion could not be assessed. Their active standing could be assessed the day after (plan A). Body orientation was not assessed in 4 individuals (20%) because of technical problems. No other data were missing.\u003c/p\u003e\n\u003cp\u003e\u003cstrong\u003eEffect of VTE immersion on verticality perception\u003c/strong\u003e\u003c/p\u003e\n\u003cp\u003eIndividual data are presented in Figure 4 (A and B) and conditions are compared in Table 1.\u003c/p\u003e\n\u003cp\u003e\u003cstrong\u003eTable 1.\u003c/strong\u003e Verticality perception in 3 conditions: at baseline and during and after virtual tilted environment (VTE) immersion.\u0026nbsp;\u003c/p\u003e\n\u003ctable border=\"0\" cellspacing=\"0\" cellpadding=\"0\" width=\"701\"\u003e\n \u003ctbody\u003e\n \u003ctr\u003e\n \u003ctd valign=\"top\" style=\"width: 90px;\"\u003e\n \u003cp\u003e\u0026nbsp;\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 109px;\"\u003e\n \u003cp\u003eBaseline\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 128px;\"\u003e\n \u003cp\u003eDuring VTE\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 110px;\"\u003e\n \u003cp\u003eAfter VTE\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 142px;\"\u003e\n \u003cp\u003eVTE effect\u003c/p\u003e\n \u003cp\u003e(Baseline vs during)\u003c/p\u003e\n \u003cp\u003ep-value; effect size\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 123px;\"\u003e\n \u003cp\u003eVTE post-effect\u003c/p\u003e\n \u003cp\u003e(Baseline vs after)\u003c/p\u003e\n \u003cp\u003ep-value\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd valign=\"top\" style=\"width: 90px;\"\u003e\n \u003cp\u003e\u003cem\u003eOrientation\u003c/em\u003e\u003c/p\u003e\n \u003cp\u003ePV\u0026deg; (n=18)\u003c/p\u003e\n \u003cp\u003e\u0026nbsp;\u003c/p\u003e\n \u003cp\u003eVV\u0026deg; (n=18)\u003c/p\u003e\n \u003cp\u003e\u0026nbsp;\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 109px;\"\u003e\n \u003cp\u003e\u0026nbsp;\u003c/p\u003e\n \u003cp\u003e0 (0.8)\u003c/p\u003e\n \u003cp\u003e\u0026nbsp;\u003c/p\u003e\n \u003cp\u003e0.5 (-0.5\u0026nbsp;;1.3)\u003c/p\u003e\n \u003cp\u003e\u0026nbsp;\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 128px;\"\u003e\n \u003cp\u003e\u0026nbsp;\u003c/p\u003e\n \u003cp\u003e3.8 (3.8)\u003c/p\u003e\n \u003cp\u003e\u0026nbsp;\u003c/p\u003e\n \u003cp\u003e14 (12\u0026nbsp;;14.9)\u003c/p\u003e\n \u003cp\u003e\u003csup\u003e\u0026nbsp;\u003c/sup\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 110px;\"\u003e\n \u003cp\u003e\u0026nbsp;\u003c/p\u003e\n \u003cp\u003e0 (1.3)\u003c/p\u003e\n \u003cp\u003e\u0026nbsp;\u003c/p\u003e\n \u003cp\u003e0.9 (-0.3\u0026nbsp;;1.5)\u003c/p\u003e\n \u003cp\u003e\u0026nbsp;\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 142px;\"\u003e\n \u003cp\u003e\u0026nbsp;\u003c/p\u003e\n \u003cp\u003e\u0026lt;10\u003csup\u003e-3\u003c/sup\u003e; d=1.32\u003c/p\u003e\n \u003cp\u003e\u0026nbsp;\u003c/p\u003e\n \u003cp\u003e\u0026lt;10\u003csup\u003e-3\u003c/sup\u003e; d=3.3\u003c/p\u003e\n \u003cp\u003e\u0026nbsp;\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 123px;\"\u003e\n \u003cp\u003e\u0026nbsp;\u003c/p\u003e\n \u003cp\u003e0.61\u003c/p\u003e\n \u003cp\u003e\u0026nbsp;\u003c/p\u003e\n \u003cp\u003e0.64\u003c/p\u003e\n \u003cp\u003e\u0026nbsp;\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd valign=\"top\" style=\"width: 90px;\"\u003e\n \u003cp\u003e\u003cem\u003eUncertainty\u003c/em\u003e\u003c/p\u003e\n \u003cp\u003ePV\u0026deg; (n=18)\u003c/p\u003e\n \u003cp\u003e\u0026nbsp;\u003c/p\u003e\n \u003cp\u003eVV\u0026deg; (n=18)\u003c/p\u003e\n \u003cp\u003e\u0026nbsp;\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 109px;\"\u003e\n \u003cp\u003e\u0026nbsp;\u003c/p\u003e\n \u003cp\u003e1.7 (0.7)\u003c/p\u003e\n \u003cp\u003e\u0026nbsp;\u003c/p\u003e\n \u003cp\u003e0.7 (0.6\u0026nbsp;;1.2)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 128px;\"\u003e\n \u003cp\u003e\u0026nbsp;\u003c/p\u003e\n \u003cp\u003e2 (0.8)\u003c/p\u003e\n \u003cp\u003e\u0026nbsp;\u003c/p\u003e\n \u003cp\u003e0.7 (0.6\u0026nbsp;;0.8)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 110px;\"\u003e\n \u003cp\u003e\u0026nbsp;\u003c/p\u003e\n \u003cp\u003e1.9 (0.7)\u003c/p\u003e\n \u003cp\u003e\u0026nbsp;\u003c/p\u003e\n \u003cp\u003e1.2 (0.9\u0026nbsp;;1.5)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 142px;\"\u003e\n \u003cp\u003e\u0026nbsp;\u003c/p\u003e\n \u003cp\u003e0.17; -\u003c/p\u003e\n \u003cp\u003e\u0026nbsp;\u003c/p\u003e\n \u003cp\u003e0.24; -\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 123px;\"\u003e\n \u003cp\u003e\u0026nbsp;\u003c/p\u003e\n \u003cp\u003e0.45\u003c/p\u003e\n \u003cp\u003e\u0026nbsp;\u003c/p\u003e\n \u003cp\u003e0.29\u003c/p\u003e\n \u003cp\u003e\u0026nbsp;\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003c/tbody\u003e\n\u003c/table\u003e\n\u003cp\u003eData are mean (SD) or median (Q1; Q3). Abbreviations: PV = postural vertical; VV = visual vertical.\u003c/p\u003e\n\u003cp\u003e\u003cem\u003eFor PV orientation\u003c/em\u003e, data at baseline did not differ from the true vertical (t=0.13; p=0.38) and was always within the ranges of normality. In the experimental condition, PV was tilted in the same orientation as the VTE, toward the side that the environment was tilted, with a mean magnitude of 3.8\u0026deg; (3.8\u0026deg;) and a large effect size (Table 1). Most participants were responders (13/18, 72%). Among the 5 (28%) non-responders, 1 showed a surprising PV modulation oriented in the non-expected direction (i.e., the side opposite the VTE) (Figure 4A). Ten minutes after VTE, PV modulation decreased in all participants, and PV no longer differed from baseline (Table 1). Thus, there was no VTE post-effect on PV in healthy individuals.\u003c/p\u003e\n\u003cp\u003e\u003cem\u003eFor VV orientation\u003c/em\u003e, data at baseline did not differ from the true vertical (t=1.64; p=0.38). In the experimental condition, VV was tilted in the same orientation as the VTE, toward the side that the environment was tilted, with a median magnitude of 14\u0026deg; (12;14.9) and a large effect size (Table 1). The magnitude of the modulation was much larger for VV than PV (p\u0026lt;10\u003csup\u003e-3\u003c/sup\u003e, d=1.70), but these modulation magnitudes were correlated (r=0.51; p=0.03). Most participants were responders (16/18, 89%), with a VV systematically tilted in the direction of the VTE, including the individual with a PV modulation oriented in the opposite direction. The only 2 individuals (11%) who were not responders for VV nevertheless showed a small tilt (1\u0026deg;) in the same orientation as the VTE. At 10 min after VTE arrest, VV modulation decreased and VV no longer differed from baseline (Table 1). Thus, there was no VTE post-effect on VV in healthy individuals.\u003c/p\u003e\n\u003cp\u003e\u003cem\u003eSide of the modulation\u003c/em\u003e. On two-factor ANOVA (2 VTE sides, 2 verticality estimates), PV and VV modulations were greater when the VTE was tilted leftward (p=0.02), with a small effect size (d=0.1). The mean PV modulation was 5.4\u0026deg; (3.7) for leftward VTE and 2.1\u0026deg; (3.8) for rightward VTE. For VV, the mean modulation was 13.5\u0026deg; (2.5) for leftward VTE and 9.5\u0026deg; (6.2) for rightward VTE.\u003c/p\u003e\n\u003cp\u003e\u003cem\u003eWe then analysed PV and VV uncertainties\u003c/em\u003e (Table 1). Uncertainties were low, which attested to the robustness of the measurements, despite the experimental conditions and repeated measurements of the study. Of note, they were not affected by the VTE immersion, so judgements of verticality directions remained precise even when the internal model of verticality was experimentally biased by the VTE\u003c/p\u003e\n\u003cp\u003e\u003cstrong\u003eEffect of VTE immersion on active standing\u003c/strong\u003e\u003c/p\u003e\n\u003cp\u003eData are presented in Table 2 and Figure 4C.\u003c/p\u003e\n\u003cp\u003e\u003cstrong\u003eTable 2.\u003c/strong\u003e Participants\u0026rsquo; active standing posture at baseline and during virtual tilted environment (VTE) immersion.\u003c/p\u003e\n\u003ctable border=\"0\" cellspacing=\"0\" cellpadding=\"0\" width=\"528\"\u003e\n \u003ctbody\u003e\n \u003ctr\u003e\n \u003ctd valign=\"top\" style=\"width: 129px;\"\u003e\n \u003cp\u003e\u0026nbsp;\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 119px;\"\u003e\n \u003cp\u003eBaseline\u003c/p\u003e\n \u003cp\u003e\u0026nbsp;\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 118px;\"\u003e\n \u003cp\u003eDuring VTE\u003c/p\u003e\n \u003cp\u003e\u0026nbsp;\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 162px;\"\u003e\n \u003cp\u003eVTE effect\u003c/p\u003e\n \u003cp\u003ep-value; effect size\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd valign=\"top\" style=\"width: 129px;\"\u003e\n \u003cp\u003e\u003cem\u003eBody orientation\u003c/em\u003e\u003c/p\u003e\n \u003cp\u003eMean\u003cem\u003e\u0026deg;\u003c/em\u003e\u003c/p\u003e\n \u003cp\u003e\u0026nbsp; \u0026nbsp; \u0026nbsp; \u0026nbsp; \u0026nbsp; \u0026nbsp;O1\u003c/p\u003e\n \u003cp\u003e\u0026nbsp;\u003c/p\u003e\n \u003cp\u003e\u0026nbsp; \u0026nbsp; \u0026nbsp; \u0026nbsp; \u0026nbsp; \u0026nbsp;C7\u003c/p\u003e\n \u003cp\u003e\u0026nbsp;\u003c/p\u003e\n \u003cp\u003e\u0026nbsp; \u0026nbsp; \u0026nbsp; \u0026nbsp; \u0026nbsp; \u0026nbsp;S1\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 119px;\"\u003e\n \u003cp\u003e\u0026nbsp;\u003c/p\u003e\n \u003cp\u003e\u0026nbsp;\u003c/p\u003e\n \u003cp\u003e-1.1 (1.7)\u003c/p\u003e\n \u003cp\u003e\u0026nbsp;\u003c/p\u003e\n \u003cp\u003e-0.1 (1.7)\u003c/p\u003e\n \u003cp\u003e\u0026nbsp;\u003c/p\u003e\n \u003cp\u003e-1.0 (2.1)\u003c/p\u003e\n \u003cp\u003e\u0026nbsp;\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 118px;\"\u003e\n \u003cp\u003e\u0026nbsp;\u003c/p\u003e\n \u003cp\u003e\u0026nbsp;\u003c/p\u003e\n \u003cp\u003e-1.3 (3.7)\u003c/p\u003e\n \u003cp\u003e\u0026nbsp;\u003c/p\u003e\n \u003cp\u003e-0.8 (3.7)\u003c/p\u003e\n \u003cp\u003e\u0026nbsp;\u003c/p\u003e\n \u003cp\u003e-1.4 (2.0)\u003c/p\u003e\n \u003cp\u003e\u0026nbsp;\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 162px;\"\u003e\n \u003cp\u003e\u0026nbsp;\u003c/p\u003e\n \u003cp\u003e\u0026nbsp;\u003c/p\u003e\n \u003cp\u003e0.82; -\u003c/p\u003e\n \u003cp\u003e\u0026nbsp;\u003c/p\u003e\n \u003cp\u003e0.49; -\u003c/p\u003e\n \u003cp\u003e\u0026nbsp;\u003c/p\u003e\n \u003cp\u003e0.28; -\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd valign=\"top\" style=\"width: 129px;\"\u003e\n \u003cp\u003e\u003cem\u003ePosturography\u003c/em\u003e\u003c/p\u003e\n \u003cp\u003eWB, \u003cem\u003e%\u003c/em\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 119px;\"\u003e\n \u003cp\u003e\u0026nbsp;\u003c/p\u003e\n \u003cp\u003e49.4 (3.1)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 118px;\"\u003e\n \u003cp\u003e\u0026nbsp;\u003c/p\u003e\n \u003cp\u003e51.9 (3.8)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 162px;\"\u003e\n \u003cp\u003e\u0026nbsp;\u003c/p\u003e\n \u003cp\u003e\u0026lt;10\u003csup\u003e-3\u003c/sup\u003e; r=0.71\u003c/p\u003e\n \u003cp\u003e\u003csup\u003e\u0026nbsp;\u003c/sup\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd valign=\"top\" style=\"width: 129px;\"\u003e\n \u003cp\u003e\u003cem\u003ePostural instability (mm)\u003c/em\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 119px;\"\u003e\n \u003cp\u003e1.1 (0.4)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 118px;\"\u003e\n \u003cp\u003e1.3 (0.4)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 162px;\"\u003e\n \u003cp\u003e0.07; -\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003c/tbody\u003e\n\u003c/table\u003e\n\u003cp\u003eData are mean (SD). Abbreviations: COP = center of pressure; WB = % of body weight supported by the lower limb at the side of the VTR; O1 = occipital apex; C7 = the spinous process of the 7\u003csup\u003eth\u003c/sup\u003e vertebra; S1 = first sacral spinous process\u003c/p\u003e\n\u003cp\u003e\u003cem\u003eBody orientation\u003c/em\u003e. The segmental body orientation in the frontal plane did not differ before and during VTE, but the inter-individual data dispersion was twice higher with VTE, at occiput and C7 level (Table 2).\u003c/p\u003e\n\u003cp\u003e\u003cem\u003eMass distribution\u003c/em\u003e. The VTE induced a strong WB change, loading the lower limb on side of the VTE more than the other limb (Figure 4C), with a large effect size: 49.4% (3.1) before VTE versus 51.9% (3.8) during VTE (p \u0026lt;10\u003csup\u003e-3\u003c/sup\u003e; r=0.71). WB modulation was comparable for rightward and leftward VTE tilt (p=0.13). Most participants behaved this way (17/20, 85%) (Figure 4C), with a mean WB modulation of 3.1% (1.8). This VTE modulation of WB was not correlated with the VTE modulation of verticality perception, PV (r=0.13, p=0.60) or VV (r=0.02, p=0.91). The VTE immersion did not significantly affect the amount of body sway (Table 2), so the postural stability in standing was comparable at baseline and during VTE, during the short duration of the recording (20 sec).\u003c/p\u003e\n\u003cp\u003e\u003cstrong\u003eDiscomfort associated with the VTE immersion\u003c/strong\u003e\u003c/p\u003e\n\u003cp\u003eScores for discomfort associated with the VTE immersion varied from 0 to 3. Discomfort scores did not differ between sessions (median 1 [0 to 2] vs 1 [0 to 1]; p=0.10). \u0026nbsp;We averaged these scores to analyse the global discomfort associated with the VTE during the whole experiment. Only 5/20 (25%) individuals experienced no discomfort (score of 0). Others (15/20, 75%) experienced minimal discomfort (score \u0026gt; 0 and \u0026lt; 3).\u003c/p\u003e\n\u003cp\u003e\u003cstrong\u003eVV data obtained for healthy individuals tested with a VR device\u003c/strong\u003e\u003c/p\u003e\n\u003cp\u003eVV data obtained before VTE in 19 participants may help give an estimate of the ranges of normality expected for VV performed with a VTE device, head maintained upright as recommended [76, 78]. Data distribution was not Gaussian, ranging from -1.9\u0026deg; to +2.7\u0026deg;, with 5th and 95th percentiles at -1.9\u0026deg; and +2.6\u0026deg;. If we add a possible measurement error (adjustment of the helmet, line step), round values, and to stay symmetrical with respect to zero, the estimated range of normality was from -3\u0026deg; to +3\u0026deg;. The within-individual variability was also low, with the 90\u003csup\u003eth\u003c/sup\u003e percentile at 1.6\u0026deg; (threshold of normality 2\u0026deg;).\u003c/p\u003e"},{"header":"Discussion","content":"\u003cp\u003eOur study tested 3 main hypotheses in 20 healthy individuals:\u0026nbsp;the VTE effect on verticality perception is transmodal,\u0026nbsp;followed by a post-effect, and with an impact on the active body orientation in standing. The study partially confirmed these hypotheses. A 45-min VTE immersion induced a transmodal modulation in verticality representation toward the side of the tilted environment, with a magnitude much greater for VV (13.5°) than PV (3.8°), the modulation on both estimates being correlated. Most participants were responders: 16/18 (89%) for VV and 13/18 (72%) for PV. This VTE-induced modulation extended to the active body orientation in standing, eliciting a complex postural behaviour. Participants remained vertical and stable, but in response to the VTE tilt, loaded their lower limb more to that side. No post-effect was found 10 min after the VTE arrest. The VTE discomfort was minimal in 75% of participants and null in 15%.\u003c/p\u003e\n\u003cp\u003e\u003cstrong\u003eEffect of VTE immersion on verticality\u003c/strong\u003e\u003cstrong\u003erepresentation\u003c/strong\u003e\u003c/p\u003e\n\u003cp\u003eOur study is one of the first to investigate the VTE effect on verticality perception in healthy individuals, VV [41] or PV [67], and the first to investigate both modalities. It revealed that the VTE has a transmodal effect on VV and PV, their modulations being correlated. This finding\u0026nbsp;indicates the existence of a high-order modulation of verticality representation. Because of the powerful VTE modulation on PV and VV orientations, without imprecision, the VTE had a specific directional effect on the internal model of verticality, which remained robust although experimentally biased. This is an important finding advocating for the use of the VTE in a clinical context, to recalibrate a biased verticality representation.\u003c/p\u003e\n\u003cp\u003e\u003cstrong\u003eEffect of VTE immersion on active standing\u003c/strong\u003e\u003c/p\u003e\n\u003cp\u003eThe VTE-induced modulation was extended to the active body orientation in standing, which was predicted by the concept of an internal model of verticality [3, 4, 25], thus supporting a close link between perception an action with respect to gravity [3, 4, 11, 13, 14, 21, 25, 31, 41, 84]. This VTE elicited a complex postural behaviour. Participants remained vertical, as observed in a previous study [68], and stable. However, the present study reveals that they responded to the VTE by loading their lower limb to the side of the tilt. This WB change translated a directional effect of the VTE on body posture in standing, the projection of the centre of mass on the ground being shifted toward the VTE tilt side. This behaviour may be considered a way to counteract the expectation effect of the VTE predicted by the theory of destabilizing body tilt in healthy individuals and may mean that remaining vertical is a priority of the postural control to avoid imbalance. The increase in inter-individual variability in the segmental body orientation with respect to gravity is an indicator of the complexity of this postural adaptation in response to the VTE, all individuals not behaving similarly.\u003c/p\u003e\n\u003cp\u003eFinally, from a behavioural point of view, these experimental results demonstrate the existence of a dissociated regulation for the 2 domains of the postural control, organized as postulated by Massion [85], from a control of the body orientation with respect to gravity and a control of the postural stabilisation with respect to the base of support. This postural control organisation in 2 independent components is supported by the demonstration in animals that each component relies on specific neural circuits [86, 87]. Clearly, this is now the way to conceive, assess and treat postural disorders [26, 88]. The results of the present study also allow for better understanding the WB asymmetry after stroke, in a context of a clinical bias of verticality representation.\u003c/p\u003e\n\u003cp\u003e\u003cstrong\u003eGreater VTE effect on VV than PV\u003c/strong\u003e\u003c/p\u003e\n\u003cp\u003e\u003cem\u003eThe greater effect on VV than PV\u003c/em\u003e is likely due to the specific information involved for each modality. VV mainly tests the visuo-vestibular contribution to the internal model of verticality [3, 7, 74, 89], whereas PV mainly tests the contribution of the somaesthetic gravity sensing [25, 38, 54, 72, 73]. Beyond somatosensory information, and considered from the prism of spatial frames of reference, VV is viewed as a way to test how an individual experiences the upright of the environment, whereas PV is viewed as a way to test how an individual experiences the upright of her/his own body [13].\u003c/p\u003e\n\u003cp\u003e\u003cem\u003eOn VV\u003c/em\u003e, we found a VTE effect comparable to that previously reported in healthy individuals with the same equipment but a unique VTE pattern displaying a child bedroom [41]. Pooled data from both studies show that the VV modulation toward the VTE tilt side was constant, with 33/35 (94%) individuals being responders (modulation ≥ 2°), mostly with an enormous magnitude, \u0026gt; 10°. An important difference between the 2 studies was the head orientation, free and tilted toward the VTE tilt in the first study and maintained approximately upright in the current study. This difference excludes the possibility that the VTE effect on VV would have been magnified by a head tilt, indeed impossible over some degrees in the current study (lateral wedges at distance of the head). Neither of the 2 studies monitored eye torsion, so one cannot exclude that the VV tilt would have been magnified by an eye torsion induced by the VTE, especially in the present study, in which the head was maintained upright. Indeed, eye torsion is a sufficient mechanism to induce an enormous VV tilt [74, 90], other modalities of verticality perception being normal [74]. In the current study, the VTE also modulated PV, so a false positive result caused by eye torsion is implausible. In the present study, the magnitude of modulation was much greater for VV than PV. This magnitude of VV modulation induced by the VTE is similar to that obtained when participants are inside an actual tilted room [60] and twice stronger than that obtained with other types of devices eliciting non-immersive 3D environments [58, 66]. These strong effects supported by a large effect size were predicted by optimizing several factors well known to enhance modulation of the VV when presented in a tilted environment: the richness and meaningfulness of the indices of the environment supposedly indicating the direction of the vertical but presented tilted [56, 59, 91], the angular size of the material displayed [91, 92] and a tilt of the environment about 18° for maximal effect [58, 59]. One may even wonder whether the characteristics of the visual line displayed within the VR helmet might have contributed to the powerful VV modulation. It is an unusually large visual line in terms of angular size, which is a factor known to affect VV results [93].\u003c/p\u003e\n\u003cp\u003e\u003cem\u003eOn PV\u003c/em\u003e, we found that the body was perceived vertical when tilted toward the tilt of environment, a result congruent with that of another study in individuals of same age [67]. During the VTE, verticality representation partly follows the visual clues supposedly indicating the direction of the vertical but presented tilted. In our study, the VTE effect was twice higher than that reported \u0026nbsp;in the other study [67], with a much lower inter-individual variability, most participants being responders (modulation ≥ 2°). The effect size was large in our study and not reported in the other study. Our better results seem related to the quality of our PV testing, well validated by usage [2, 13, 25, 27, 28, 31, 32, 94]. This device and procedure are unique, progressively implemented during several months before starting assessment for studies [25] and regularly improved since. However, individuals who feel uncomfortable in darkness (\u0026gt; 10 min) wearing the VR helmet (baseline measurements in darkness) cannot complete this session. This was the case for 2/20 (10%) of our healthy individuals at baseline.\u003c/p\u003e\n\u003cp\u003e\u003cstrong\u003eNo post-effect on verticality\u003c/strong\u003e\u003cstrong\u003erepresentation\u003c/strong\u003e\u003c/p\u003e\n\u003cp\u003eThe only study investigating the VTE effect on verticality found clues of a post-effect, with the persistence at 6 min of head tilt [41]. In the present study, we found no post-effect at 10 min after the VTE arrest, for PV or VV. During this short time, individuals remained seated in complete darkness, still installed in the device used for PV, set horizontal. This device, which maintains them upright, give clues of uprightness (the seat itself as well as adjustable lateral wedges for the head, the trunk with the arms, and the pelvis). This experimental setup might explain in part why the VTE effect on verticality representation does not last when visual cues of a wrong verticality disappear. The current study tested healthy individuals with normal gravity sensing and normal functioning of their internal model of verticality. The return to baseline might be slower in individuals with altered gravity sensing (somaesthetic and vestibular graviception) and abnormal functioning of their internal model of verticality. This hypothesis will be tested in the second part of the VIRGIL study dedicated to individuals with lateropulsion caused by a wrong verticality representation after a hemisphere stroke.\u003c/p\u003e\n\u003cp\u003e\u003cstrong\u003eDiscomfort with the VTE\u003c/strong\u003e\u003c/p\u003e\n\u003cp\u003eNo important cybersickness was reported by participants of our study, in which they did not have to move within a surrounding. In contrast, the global discomfort seemed high in healthy individuals deambulating in hospital corridors virtually displayed with a 20° tilt[95], many stopping the experiment before the end. This discomfort in tasks involving postural control may have several reasons. In addition to non-congruent information on verticality given by vision and that given by gravity sensing, which may induce dizziness, the lack of optic flow when moving around might create another conflict between visual information of movement on one hand and vestibular and proprioceptive information of movement on the other [96].\u003c/p\u003e\n\u003cp\u003e\u003cstrong\u003eRanges of normality for VV tested with a VR device\u003c/strong\u003e\u003c/p\u003e\n\u003cp\u003eSince the first publication in 2018 [41], VV is increasingly being tested with a VR device and regularly presented as a new test. Testing VV with this method is reliable [97, 98]. In testing head maintained upright as recommended [76, 78, 98], we found narrow estimated ranges of normality (baseline) in individuals aged about 60 years. Therefore, our setting allowed participants to be accurate and precise when adjusting the visual line displayed within the helmet to the direction they perceived as vertical. This good result may be explained by a perfect darkness within the helmet, without any visual information inducing noise in the data. For orientation (accuracy), the normality ranged from -3° to +3°, which is better than that is sometimes reported for virtual VV [97] but slightly greater than what is obtained with standard mechanical or digital methods, also with head maintained upright [25, 70]. Several reasons might explain that the range of normality of VV with a virtual device is less narrow than that with standard methods. The weight and the bulk of the helmet could play a role as well as the cybersickness even if whether it affects VV is unclear [41, 99]. The unusually large size of the visual line (large angular size) might also play a role. Further investigations are needed to comparatively analyse these methods.\u003c/p\u003e\n\u003cp\u003e\u003cstrong\u003eClinical implication\u003c/strong\u003e\u003c/p\u003e\n\u003cp\u003eThis study opens interesting perspectives for individuals with lateropulsion after hemisphere stroke, a condition characterized by a biased perception of verticality and postural asymmetry [3, 25, 100]. This is the second part of the VIRGIL study, the recruitment of which is ongoing. The post-effect question should be central. In the Virgil study, the immersion in the virtual environment is passive, individuals being simply instructed to explore the 4 VTE scenes successively presented (Figure 3). An active set-up could be interesting, with individuals interacting with the virtual environment, for example by playing with falling objects. This will allow them to realize they make errors and lead them to progressively rectify their action. This active process involving the timing component of the internal model of gravity [22] might strengthen its plasticity and prolong its modulation after the VTE arrest. Future research might consider this track to favour the persistence of a post-effect.\u003c/p\u003e\n\u003cp\u003e\u003cstrong\u003eStudy limitations\u003c/strong\u003e\u003c/p\u003e\n\u003cp\u003eThe principal limitation of the study was that we did not monitor eye orientation. Eye torsion may be induced by the virtual tilt of the environment, especially when the head is maintained, as in our study. VV covaries with eye torsion [74, 101], so the magnitude of the VV tilt may have been due in part to eye torsion. This situation might explain in part why the effect was much greater on VV than PV. A second limitation was a global quantification of the discomfort experienced by participants after each session, with an analogous scale. This approach does not analyse the nature of symptoms, as do cybersickness questionnaires. However analogic scorings allow a quick and satisfactory estimation of the discomfort intensity, feasible even in dizzy individuals. The interpretation of the WB change might be refined by assessments of lateral forces and moments, not measured in our study.\u003c/p\u003e"},{"header":"Conclusion","content":"\u003cp\u003eIn healthy individuals, we show that a 45-min immersion in VTE induced a modulation of verticality representation associated with a modulation of active standing. The clinical interest of this approach may now be investigated in individuals showing post-stroke lateropulsion due to a wrong sense of verticality. The lack of a post-effect in healthy individuals does not predict whether or not the effect will persist in individuals with a biased internal model of verticality.\u003c/p\u003e"},{"header":"Declarations","content":"\u003cp\u003e\u003cstrong\u003eEthics approval and consent to participate\u003c/strong\u003e\u003c/p\u003e\n\u003cp\u003eVIRGIL protocol was approved by an Institutional Review Board (Comit\u0026eacute; de Protection des Personnes Ile de France X; 2020-A02941-38) which was randomly selected from a national panel, and registered at ClinicalTrials.gov in May 2021 (https://clinicaltrials.gov/study/NCT04911738). All healthy individuals recruited gave written informed consent to participate in the study.\u003c/p\u003e\n\u003cp\u003e\u003cstrong\u003eConsent for publication\u003c/strong\u003e\u003c/p\u003e\n\u003cp\u003eAll authors approved the submitted version, and agreed both to be personally accountable for the author\u0026apos;s own contributions and to ensure that questions related to the accuracy or integrity of any part of the work, even ones in which the author was not personally involved, are appropriately investigated, resolved, and the resolution documented in the literature.\u003c/p\u003e\n\u003cp\u003e\u003cstrong\u003eAvailability of data and materials\u003c/strong\u003e\u003c/p\u003e\n\u003cp\u003eDetails on the prototype used to test PV may be requested from the corresponding author. Data are available on reasonable request under conditions detailed in the study protocol [69].\u003c/p\u003e\n\u003cp\u003e\u003cstrong\u003eCompeting interests\u003c/strong\u003e\u003c/p\u003e\n\u003cp\u003eNone\u003c/p\u003e\n\u003cp\u003e\u003cstrong\u003eFunding\u003c/strong\u003e\u003c/p\u003e\n\u003cp\u003eThis work was supported by the Fondation Paul Bennetot (grant no. AP-FPB-18-004) and also the VIRTUALIS company (providing the VRE device and program). The funders did not interfere in any step of the research (design, conduct, analysis or reporting).\u003c/p\u003e\n\u003cp\u003e\u003cstrong\u003eAuthors\u0026apos; contributions\u003c/strong\u003e\u003c/p\u003e\n\u003cp\u003e\u003cstrong\u003eS. De. - P\u003c/strong\u003ereparation of documents for the ethics committee and trial registration, d\u003cstrong\u003eata collection, d\u003c/strong\u003eata curation, statistical analyses, preparation of tables and figures, writing original draft.\u003c/p\u003e\n\u003cp\u003e\u003cstrong\u003eA. H. - P\u003c/strong\u003ereparation of documents for the ethics committee and trial registration,\u003cstrong\u003e\u0026nbsp;data collection, d\u003c/strong\u003eata curation\u003cstrong\u003e,\u0026nbsp;\u003c/strong\u003estatistical analyses\u003cstrong\u003e, data analysis,\u0026nbsp;\u003c/strong\u003eintellectual content, editing\u003c/p\u003e\n\u003cp\u003e\u003cstrong\u003eO. F.\u0026nbsp;\u003c/strong\u003e\u003cstrong\u003e-\u0026nbsp;\u003c/strong\u003e\u003cstrong\u003eData collection,\u0026nbsp;\u003c/strong\u003eintellectual content.\u003c/p\u003e\n\u003cp\u003e\u003cstrong\u003eS. Da. -\u0026nbsp;\u003c/strong\u003eStudy conception\u003cstrong\u003e, p\u003c/strong\u003ereparation of documents for the ethics committee and trial registration, \u003cstrong\u003edata collection.\u003c/strong\u003e\u003c/p\u003e\n\u003cp\u003e\u003cstrong\u003eC. P. - Study conception, p\u003c/strong\u003ereparation of documents for the ethics committee and trial registration, \u003cstrong\u003edata collection,\u0026nbsp;\u003c/strong\u003eintellectual content\u003cstrong\u003e, editing.\u003c/strong\u003e\u003c/p\u003e\n\u003cp\u003e\u003cstrong\u003eE. L. - D\u003c/strong\u003eata curation\u003cstrong\u003e, data analysis, i\u003c/strong\u003entellectual content, editing, submission of the article.\u003c/p\u003e\n\u003cp\u003e\u003cstrong\u003eD. P. - F\u003c/strong\u003eunding acquisition, study conception, study supervision, data curation, data analyses, writing original draft.\u003c/p\u003e\n\u003cp\u003e\u003cstrong\u003eAcknowledgments\u003c/strong\u003e\u003c/p\u003e\n\u003cp\u003eWe gratefully thank the participants who gave their time for this exploratory basic research.\u003c/p\u003e"},{"header":"References","content":"\u003col\u003e\n \u003cli\u003eKaptein RG, Van Gisbergen JAM. Interpretation of a discontinuity in the sense of verticality at large body tilt. J Neurophysiol 2004;91.\u003c/li\u003e\n \u003cli\u003eBarbieri G, Gissot AS, P\u0026eacute;rennou D. Ageing of the postural vertical. Age 2010;32:51-60.\u003c/li\u003e\n \u003cli\u003eBarra J, Marquer A, Joassin R, Reymond C, Metge L, Chauvineau V, et al. Humans use internal models to construct and update a sense of verticality. Brain 2010;133:3552-63.\u003c/li\u003e\n \u003cli\u003eBarra J, P\u0026eacute;rennou D, Thilo KV, Gresty MA, Bronstein AM. 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Test-Retest Reliability of Dynamic Subjective Visual Vertical and Visual Dependency in Older Adults Using Virtual Reality Methods. Percept Mot Skills 2024;131:2069-84.\u003c/li\u003e\n \u003cli\u003eMichelson PL, McCaslin DL, Jacobson GP, Petrak M, English L, Hatton K. Assessment of Subjective Visual Vertical (SVV) Using the \u0026quot;Bucket Test\u0026quot; and the Virtual SVV System. Am J Audiol 2018;27:249-59.\u003c/li\u003e\n \u003cli\u003eArdic FN, Metin U, Gokcan BE. Subjective Visual Vertical test with the 3D virtual reality system: effective factors and cybersickness. Acta Otolaryngol 2023;143:570-5.\u003c/li\u003e\n \u003cli\u003eDai S, Piscicelli C, Clarac E, Baciu M, Hommel M, Perennou D. Lateropulsion After Hemispheric Stroke: A Form of Spatial Neglect Involving Graviception. Neurology 2021;96:e2160-e71.\u003c/li\u003e\n \u003cli\u003eLorincz EN, Hess BJ. Dynamic effects on the subjective visual vertical after roll rotation. J Neurophysiol 2008;100:657-69.\u003c/li\u003e\n\u003c/ol\u003e"}],"fulltextSource":"","fullText":"","funders":[],"hasAdminPriorityOnWorkflow":false,"hasManuscriptDocX":true,"hasOptedInToPreprint":true,"hasPassedJournalQc":"","hasAnyPriority":false,"hideJournal":true,"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":"researchsquare","isNatureJournal":false,"hasQc":true,"allowDirectSubmit":true,"externalIdentity":"","sideBox":"","snPcode":"","submissionUrl":"/submission","title":"Research Square","twitterHandle":"researchsquare","acdcEnabled":true,"dfaEnabled":false,"editorialSystem":"","reportingPortfolio":"","inReviewEnabled":false,"inReviewRevisionsEnabled":true},"keywords":"virtual reality, verticality perception, postural vertical, visual vertical, upright, standing posture, weight-bearing.","lastPublishedDoi":"10.21203/rs.3.rs-7472074/v1","lastPublishedDoiUrl":"https://doi.org/10.21203/rs.3.rs-7472074/v1","license":{"name":"CC BY 4.0","url":"https://creativecommons.org/licenses/by/4.0/"},"manuscriptAbstract":"\u003cp\u003e\u003cstrong\u003eBackground – \u003c/strong\u003eImmersing individuals in a virtual tilted environment (VTE) could be a way to modulate verticality representation and its consequences on action with respect to gravity. The VIRGIL study involves a basic study of healthy individuals and a clinical trial of individuals showing post-stroke lateropulsion due to a biased internal model of verticality. Here we present the preclinical experimental findings for the basic study of healthy individuals.\u003c/p\u003e\n\u003cp\u003e\u003cstrong\u003eMethods - \u003c/strong\u003eTwenty healthy individuals received 2 sessions of 45 min of VTE immersion (18° tilt), performed 1 to 2 days apart: one session of sitting tested the VTE on verticality representation (postural vertical [PV; primary outcome] and visual vertical [VV]), and one session of standing tested the VTE effect on the active body orientation with respect to gravity (measured with inertial captors) and asymmetry of weight-bearing on lower limbs (WB; measured by posturography). Session allocation was randomized, and the VTE side (left or right) was balanced between individuals. We assessed the discomfort associated with the VTE immersion. In this exploratory study, investigators and participants could not be masked to treatment.\u003c/p\u003e\n\u003cp\u003e\u003cstrong\u003eResults - \u003c/strong\u003eVTE modulated verticality representation, with a transmodal tilt of PV and VV toward the side that the VTE was tilted: mean (SD) magnitude 3.8° (3.8°) for PV and median (Q1:Q3) magnitude 14.0° (12.0; 14.9) for VV (both p\u0026lt;10\u003csup\u003e-3 \u003c/sup\u003eand large effect size). VTE also modulated WB on the ground, increasing the load on the lower limb toward the side that the VTE was tilted (mean +2.5% [0.7], p\u0026lt;10\u003csup\u003e-3\u003c/sup\u003e, large effect size). The active body orientation remained vertical during VTE immersion (p\u0026gt;0.05). The VTE discomfort was minimal in 75% of participants and null in 15%.\u003c/p\u003e\n\u003cp\u003e\u003cstrong\u003eConclusion - \u003c/strong\u003eIn healthy individuals, VTE immersion strongly modulated perception and action with respect to gravity. In standing, the modulation of the WB is likely a response to the VTE to keep the body vertical. These findings open an avenue for the rehabilitation of lateropulsion after stroke.\u003c/p\u003e","manuscriptTitle":"Immersion in a virtual tilted environment strongly modulates perception and action with respect to gravity: a within-person randomized trial of healthy individuals","msid":"","msnumber":"","nonDraftVersions":[{"code":1,"date":"2025-09-09 16:03:24","doi":"10.21203/rs.3.rs-7472074/v1","editorialEvents":[{"type":"communityComments","content":0}],"status":"published","journal":{"display":true,"email":"[email protected]","identity":"researchsquare","isNatureJournal":false,"hasQc":true,"allowDirectSubmit":true,"externalIdentity":"","sideBox":"","snPcode":"","submissionUrl":"/submission","title":"Research Square","twitterHandle":"researchsquare","acdcEnabled":true,"dfaEnabled":false,"editorialSystem":"","reportingPortfolio":"","inReviewEnabled":false,"inReviewRevisionsEnabled":true}}],"origin":"","ownerIdentity":"a0ffe82f-5658-4709-9231-48d8326a2d5d","owner":[],"postedDate":"September 9th, 2025","published":true,"recentEditorialEvents":[],"rejectedJournal":[],"revision":"","amendment":"","status":"posted","subjectAreas":[],"tags":[],"updatedAt":"2025-12-12T07:24:32+00:00","versionOfRecord":[],"versionCreatedAt":"2025-09-09 16:03:24","video":"","vorDoi":"","vorDoiUrl":"","workflowStages":[]},"version":"v1","identity":"rs-7472074","journalConfig":"researchsquare"},"__N_SSP":true},"page":"/article/[identity]/[[...version]]","query":{"redirect":"/article/rs-7472074","identity":"rs-7472074","version":["v1"]},"buildId":"8U1c8b4HqxoKbykW_rLl7","isFallback":false,"isExperimentalCompile":false,"dynamicIds":[84888],"gssp":true,"scriptLoader":[]}