Mary-Ambre Carvalho

Hervé Dekkiche

Sébastien Richeter

Corinne Bailly

Lydia Karmazin

Declan Mckearney

Daniel B Leznoff

Guillaume Rogez

Bertrand Vileno

Sylvie Choua

Romain Ruppert
email: rruppert@unistra.fr.tel

Antiferromagnetic coupling in copper(II)porphyrin dimers linked by copper(II

Keywords: Porphyrinoids, copper(II)porphyrin, porphyrin dimers, magnetic interactions, antiferromagnetic coupling

INTRODUCTION

Porphyrins are aromatic compounds with exceptional electronic properties widely found in Nature. Many synthetic modifications of their structure were conducted to improve mainly their electronic properties or catalytic activities.

Porphyrins extended with conjugated systems were described in the literature and conjugated porphyrin arrays have been studied extensively [1]. Many of these studies were conducted to improve the electronic properties of the molecules, ie longer wavelength absorptions, better electron and/or energy transfer within the systems, etc. Despite the potential importance of molecular materials using magnetic interactions between metal ions [START_REF] Kahn | Molecular Magnetism[END_REF], studies concerning the long-range magnetic interactions within long linear systems build from porphyrins are limited until now [START_REF] Segawa | [END_REF]. Cofacial porphyrinoid systems were in contrary studied very early [4] and these magnetic interactions are now quite well understood [5]. Coplanar di-or oligo-porphyrinoids were much less studied. Some typical dinuclear systems synthesized from porphyrinoids are represented in Figure 1. The interaction between two copper(II) ions located in fused phthalocyanines dimers was studied by several authors [6][7][8][9]. The groups of Barrett and Hoffman studied extensively the magnetic interactions between metal ions in homo-or hetero-dinuclear porphyrazines bearing an additional external ligand [10][11][12][13]. More recently, Matano and Imahori's groups studied the magnetic coupling between two copper(II) in diazaporphyrin dimers [14][15][16]. Some studies of fused benzoporphyrin dimers, larger oligopyrrolic compounds or other porphyrinoids were also reported [START_REF]See for example : a) Chmielewski PJ[END_REF][18][19][20][21]. Porphyrins bearing enamino(thio)ketones were used as external ligands to bind metal ions. Numerous dimers linked by metal ions were prepared by our group (see Figure 3) [23]. Strong electronic interactions were present in these dimers [23c-23d]. For example, very fast energy transfers were observed between the two individual porphyrins of an unsymmetrical dimer. Magnetic interactions between metalloporphyrins were also found in porphyrin dimers linked by a simple amino group [24]. We here report on the synthesis and the magnetic properties of two copper(II)porphyrin dimers linked by a paramagnetic copper(II) ion or a diamagnetic palladium(II) ion (see Figure 3). These two dimers were also structurally characterized.

RESULTS AND DISCUSSION

Synthesis and characterization

The dimer Cu-Pd-Cu was described earlier and obtained by reaction of the monomeric copper(II)porphyrin 1 with ½ equivalent of Pd(OAc) 2 in toluene at 80 °C for 24 hours [23b]. The Cu-Cu-Cu dimer was obtained in a similar manner, by reacting copper(II)porphyrin 1 with an excess of the appropriate starting source of copper(II) (see Scheme 1). The Cu-Cu-Cu dimer was isolated in very good yield (90%) by using reaction conditions applied earlier for the palladium(II) linked dimer.

Scheme 1. Preparation of dimer Cu-Cu-Cu.

As expected and in good agreement with the data of diamagnetic dimers isolated before, the electronic spectra of the two dimers were bathochromically shifted when compared to monomer 1. In addition, and again as observed before for diamagnetic compounds [23b, 23d], this shift was dependant on the nature of the linking ion and was larger for the palladium(II) linked dimer. The electronic delocalization of the aromatic π-electrons of the two porphyrins is more efficient with participation of the 4d orbitals of the linking Pd(II) than with the 3d orbitals of the linking Cu(II). The larger bathochromic shift is not due to changes in the distances between the two copper(II)porphyrins as shown by comparing the values measured in two X-ray structures (vide infra). The lowest energy bands for the two dimers were located at 680 nm (Cu-Cu-Cu) and 696 nm (Cu-Pd-Cu) (see Figure 4). The X-ray structures were solved for the two dimers Cu-Cu-Cu (see Figure 5) and Cu-Pd-Cu (see Figure 6).

Selected representative bond lengths measured in the two structures are listed in Table 1. Both structures are centrosymmetric with the centers of symmetry located at the linking palladium(II) or copper(II) ions. Consequently, the three ions Cu-Pd-Cu and Cu-Cu-Cu are aligned in the two porphyrin dimers. In both structures, the coordination geometry around the linking ion was trans square planar. The copper(II)porphyrins were ruffled, becaue the presence of an additional fused aromtic ring introduced steric hindrance between the hydrogen atoms H2 and H24 (see Figure 5 and6). The copper(II) ions in the core of the porphyrins were almost perfectly located in the plane of the four nitrogen atoms (178° < angles N-Cu-N < 180°). In both structures, the three methyl of one or several t-butyl groups are disordered between two positions. Table 1. Selected bond lengths and distances measured in the X-ray structures of dimers Cu-Pd-Cu and Cu-Cu-Cu.

Magnetic properties

The static susceptibility measurement of dimer Cu-Pd-Cu was performed in the 1.8-300 K temperature range with an applied field of 10000 Oe (See Figure 7 and Figure S9). The χT vs. T curve is quasi constant in all the temperature range, with a Curie constant of 0.778 emu⋅K⋅mol -1 in agreement with the presence of two non-coupled Cu(II) ions with a g value of 2.04 [START_REF] Kahn | Molecular Magnetism[END_REF]. Finally the M = f(H) curve at 1.8 K fits relatively well with two Brillouin function for S = ½ with g = 2.08(2) (see SI, Figure S10).

The static susceptibility measurement of dimer Cu-Cu-Cu was performed in the 1.8-300 K temperature range with an applied field of 10000 Oe (see Figure 7). In dimer Cu-Pd-Cu the two external Cu(II) were non-coupled. If the interaction between the two external Cu(II) ions is neglected in dimer Cu-Cu-Cu, the spin Hamiltonian is thus the following :

H = -J S Cuint ⋅(S Cuext1 + S Cuext2 ) + β[g ext (S Cuext1 + S Cuext2 ) + g int S Cuint ] H
If one considers only one g value for the two different copper(II) ions, the fit was clearly not perfect. By using two g values for the two different copper(II) ions, the fit leads to the following values : J = -25.2(5) cm -1 , g = 2.12(1) (for the central Cu(II)), and g = 2.09(1) (for the two peripheral Cu(II)). Finally the M = f(H) curve at 1.8K fits well with a Brillouin function for S = ½ (which correspond to the ground state of the system, see SI Figure S12). This coupling constant value (J = -25 cm -1 ) found for this trinuclear porphyrin dimer is significantly larger than the values reported earlier for the fused Cu(II)porphyrin dimer of Osuka (J = -2.86 cm -1 ) [22b] and comparable with the value reported by Matano for a β-β linked Cu(II)azaporphyrin dimer (J = -19.3 cm -1 ). The direct β-β linkage and the almost coplanar Cu(II)azaporphyrin dimers were invoked to explain the increase in the coupling values found in Matano's dimers [15]. Full lines correspond to the best fit considering two g values (see text).

EPR studies

The EPR spectra of frozen dilute solution of Cu-Pd-Cu complex (10 -4 M) were recorded at X-band (Figure 8). From 4 K to 120 K, the spectra display a pattern in the parallel region with a set of non-equidistant lines different from those of the monomeric Cu(II)porphyrin. This result is probably due to a low magnetic exchange interaction between the two copper(II) whereas the dipolar interaction is probably close to zero considering the distance between the two coppers (14.3 Å). To simulate the spectrum (see figure S14 in SI), a spin hamiltonian (described in the SI) consisting of a sum of individual spin Hamiltonians for the isolated Cu(II) centers and an interacting Hamiltonian which accounts for the isotropic and anisotropic exchange interactions between the two Cu(II) centers was used. The EPR spectra of the trinuclear complex Cu-Cu-Cu were similarly recorded at X-band down to 4 K in frozen dilute solution in CH 2 Cl 2 (see Table 2 for selected EPR data). The temperature dependent spectra are shown in figure 9.

The spectrum below ca. 15 K was similar to a mononuclear copper complex. The spin hamiltonian parameters were close to those obtained for the monomeric copper(II)porphyrin (see Figure S15). Above 20 K two new features were observed as originating from the previous unresolved low temperature spectrum. The intensity of these two transitions increased up to 120 K, whereas the intensity of the central line decreased continuously. The EPR spectrum at 22 K was different from tthe spectrum previously observed for Cu-Pd-Cu with additional lines in the parallel component of the hyperfine tensor. The value of A z is divided by three compared to the mononuclear complex and a transition was also observed at half field. Further superhyperfine splitting was also observed at 67 K in the perpendicular part of the spectrum at ∼330 mT due to the interaction of the unpaired electron with equivalent nitrogen nuclei of the porphyrin. Table 2. EPR data for the three compounds in frozen CH 2 Cl 2 solution. Three exchange-coupled S = 1/2 ions were expected to give two doublets (S = 1/2) and one quartet (S = 3/2) with the corresponding S Z spin projections m S = ±1/2 and m S = ±1/2, ±3/2. The distribution of the relative energies of these various spin states depends on the J value. According to the SQUID measurements, the signal observed at 4 K is attributed to an S = 1/2 spin and the ground state is a doublet (see figure S15 for the simulation). By increasing the temperature, a second doublet should be populated and then a quartet. The EPR lines observed above 20 K must be consequently ascribed to the thermal population of the S = 3/2 spin multiplets with a small and unresolved zero-field splitting (see Figure S16 for the simulation). The EPR susceptibility obtained from the doubly integrated EPR line followed the same behavior than the static susceptibility (see Figure 10). It thus corroborated the magnetic behavior of this 3-spins system for the isolated molecule in dilute solution, being interpreted along the same way as a linear and symmetrical three S = 1/2 spins model [25][26]. It confirmed the low spin ground state with J = -19 ± 0.5 cm -1 . This is close to, although not identical to the value derived in the polycrystalline state. The difference in the J value is better ascribed to different average molecular conformation in the frozen dilute solution compared to the solid state. As a matter of fact orbital overlap hence magnetic exchange is very sensitive to the molecular conformation. These results were in favor of the ability of Cu(II) to operate as a relay for magnetic exchange for the two copper porphyrins via probably a spin polarization mechanism along the two conjugated porphyrins.

EXPERIMENTAL PART

General information

The HRMS ESI and MALDI were obtained on a Bruker MicrOTOF. UV-vis spectra were recorded in dichloromethane with a Cary 5000 UV-Vis-NIR double-beam instrument. Chromatographic separations were performed with silica gel (Merck, 40-63 µm). Dichloromethane was distilled over calcium hydride. All other solvents and reagents were used without further purification. The copper(II)porphyrin monomer and the palladium(II) linked dimer were prepared according to previously published procedures [23b].

Preparation of the dimer Cu-Cu-Cu.

To a solution of the copper(II)-enaminoketoporphyrin (50 mg, 0.05 mmol, 1 eq) in toluene (20 mL) was added Cu(OAc) 2 (14 mg, 0.08 mmol, 1.5 eq). The mixture was refluxed for 18h under argon.

Evaporation of the solvent and cristallization from CH 2 Cl 2 /n-hexane/methanol afforded the title compound (49 mg, 0.02 mmol, 90%) as dark green crystals. Crystals suitable for X-ray diffraction analysis were obtained by vapor diffusion of methanol into a chlorobenzene solution. Maldi-TOF (m/z) : Calcd for C 138 H 148 Cu 3 N 10 O 2 (M + •) 2165.967 ; found 2166.073. UV-visible (CH 2 Cl 2 ) : λ max = 373 nm (ε = 60900 L.cm -1 .mol -1 ), 413 (78400), 486 (292000), 624 (26900), 661 (42000), 680 (59200).

X-Ray diffraction. The crystals were placed in oil, and a single crystal was selected, mounted on a glass fibre and placed in a low-temperature N 2 stream. X-Ray diffraction data collection was carried out on a Bruker APEX II DUO Kappa-CCD diffractometer equipped with an Oxford Cryosystem liquid N 2 device, using Cu-Kα radiation (λ = 1.54178 Å) for compound Cu-Cu-Cu, and Mo-Kα radiation (λ = 0.71073 Å) for compound Cu-Pd-Cu. The crystal-detector distance was 40 mm. The cell parameters were determined (APEX2 software) [START_REF]M86-E01078 APEX2 User Manual[END_REF] from reflections taken from three sets of 20 frames, each at 10s exposure. The structures were solved by direct methods using the program SHELXS-2013 [START_REF] Sheldrick | [END_REF]. The refinement and all further calculations were carried out using SHELXL-2013 [29]. The H-atoms were included in calculated positions and treated as riding atoms using SHELXL default parameters. The non-H atoms were refined anisotropically, using weighted full-matrix least-squares on F2. A semi-empirical absorption correction was applied using SADABS in APEX2 [START_REF]M86-E01078 APEX2 User Manual[END_REF]; transmission factors: T min/ T max = 0.5863/0.7528 for compound Cu-Cu-Cu and T min/ T max = 0.6539/0.7456 for compound Cu-Pd-Cu. The SQUEEZE instruction in PLATON [30] was applied. The residual electron density was assigned to two chlorobenzene molecules for compound Cu-Cu-Cu, and to two molecules of the 1,2-dichlorobenzene solvent for compound Cu-Pd-Cu. EPR measurements. EPR spectra were recorded on an EMXplus spectrometer (Bruker Biospin GmbH), equipped with a high sensitivity resonator (4119HS-W1, Bruker) operating at X-band (ca. 9.4 GHz). An ESR900 cryostat (Oxford Instruments) was used for the low temperature measurements. Sample solutions in quartz tubes were sealed after being degassed by three freeze-pump-thaw cycles. Simulations of EPR spectra were achieved by means of lab-made scripts based on Easyspin toolbox under Matlab (Mathworks©) environment [26]. Accurate simulations for Cu-Pd-Cu and Cu-Cu-Cu were prevented by the large spectral line widths and g strain was used to adjust the fits. The temperature dependence intensity of the double integrated EPR signal (c) for the Cu-Cu-Cu complex was fitted by the the equation used for the magnetic measurements.

Crystal data

CONCLUSION

The synthesis of two porphyrin dimers linked by copper(II) or palladium(II) was described. Both compounds were structurally characterized. Strong electronic interactions between the porphyrins were found for both dimers. This was clearly shown by the large bathochromic shifts of the Q bands and the splitting of the Soret bands in the electronic spectra of the dimers. Magnetic interactions between the copper(II) ions were also observed within these two dimers.

Whereas the magnetic coupling between the two copper(II) ion was negligible for the Cu-Pd-Cu dimer, the antiferromagnetic coupling between the copper(II) ions was quite large (J = -25.2 cm -1 ) for the Cu-Cu-Cu dimer. The linking copper(II) can be described as a relay to increase the interactions between the two copper(II)porphyrins. In the near future, by building larger copper(II) linked oligoporphyrins, long-range magnetic coupling can be envisaged. The introduction of different paramagnetic ions as linking units to generate heteronuclear dimers might even lead to completely different coupling values between the paramagnetic sites. This was shown earlier by the groups of Hoffman and Barrett in the case of heterobinuclear porphyrazines [10][11][12][13].

Figure 1 .

 1 Figure 1. Examples of dinuclear molecules built from different porphyrinoids (all peripheral substituents ommitted).

Figure 2 .

 2 Figure 2. Bis-copper(II) or bis-silver(II) triply fused porphyrin dimers studied by Osuka and coll. [22b].

Figure 3 .

 3 Figure 3. Chemical structures of the porphyrin dimers Cu-Cu-Cu and Cu-Pd-Cu.

Figure 4 .

 4 Figure 4. Electronic spectra of the porphyrin dimers Cu-Cu-Cu, Cu-Pd-Cu, and of the copper(II)porphyrin monomer (dotted line).

Figure 5 .

 5 Figure 5. X-ray structure of the porphyrin dimer Cu-Cu-Cu. Top : side view showing the planar linking complex and the ruffled structure of the copper(II)porphyrin (all meso-aryl groups omitted), bottom: view showing the centrosymmetric porphyrin dimer (all hydrogen atoms omitted).

Figure 6 .

 6 Figure 6. X-ray structure of the porphyrin dimer Cu-Pd-Cu. Top : side view showing the planar linking complex and the ruffled structure of the copper(II)porphyrin (all meso-aryl groups omitted), bottom: view showing the centrosymmetric porphyrin dimer (all hydrogen atoms omitted).

Figure 7 .

 7 Figure 7. χT vs T (green squares) and χ vs T (red circles) for dimer Cu-Cu-Cu and dimer Cu-Pd-Cu (blue squares).

Figure 8 .

 8 Figure 8. X-Band EPR spectra of complex Cu-Pd-Cu (black) at 4 K and Cu(II)porphyrin (orange) at 28 K in frozen CH 2 Cl 2 solution.

Figure 9 .

 9 Figure 9. X-band EPR spectra of Cu-Cu-Cu in frozen CH 2 Cl 2 solution at 4 K (in black) and 70 K (in purple).

Figure 10 .

 10 Figure 10. Temperature dependence of the EPR intensity of Cu-Cu-Cu in frozen CH 2 Cl 2 solution.

  Cu-Cu-Cu. C 138 H 148 Cu 3 N 10 O 2 , M = 2169.28 g.mol -1 , green plate, crystal size 0.35 x 0.25 x 0.11 mm, triclinic, space group P-1, a = 9.3827(2) Å, b = 15.4981(4) Å, c = 24.8388(7) Å, α = 73.993(2)°, β = 81.347(2)°, γ = 86.276(2)°, V = 3431.30(15) Å 3 , Z = 1, ρ calc = 1.050 Mg/m 3 , T = 173(2) K, Cu-Kα = 1.54178, 1.868 < θ < 66.892, 42895 reflections measured, 11993 unique reflections, R 1 = 0.0984, wR 2 = 0.1552, GoF = 1.028. CCDC Nr 1920312. Crystal data Cu-Pd-Cu. C 150 H 156 Cl 4 Cu 2 N 10 O 2 Pd, M = 2506.12 g.mol -1 , black prism, crystal size 0.40 x 0.18 x 0.12 mm, triclinic, space group P-1, a = 15.6352(9) Å, b = 16.9970(11) Å, c = 20.0876(12) Å, α = 105.830(2)°, β = 106.0470(10)°, γ = 93.3380(10)°, V = 4883.9(5) Å 3 , Z = 1, ρ calc = 0.852 Mg/m 3 , T = 173(2) K, MoKα = 0.71073, 1.403 < θ < 28.032, transmission factors: T min /T max = 0.6539/0.7456, 87752 reflections measured, 23526 unique reflections, R 1 = 0.1012, wR 2 = 0.1883, GoF = 1.023. CCDC Nr 1920313. Magnetic measurements. Magnetic measurements were performed at the Institut de Physique et Chimie des Matériaux de Strasbourg (UMR CNRS-UdS 7504) using a Quantum Design SQUID-VSM magnetometer. Data were corrected for the sample holder and diamagnetism was estimated from Pascal constants. Dimer Cu-Cu-Cu : M = 2169.36 g/mol, m = 4.56 mg, shape correction = 1.064 Dimer Cu-Pd-Cu : M = 2212.23 g/mol, m = 5.23 mg, shape correction = 1.035

  /or M 2 = Cu and/or V=O

Figure 2 . 13 Figure 3 . 14 Scheme 1 .

 2133141 Figure 2. Bis-copper(II) or bis-silver(II) triply fused porphyrin dimers studied by Osuka and coll. [22b].

Figure 4 .

 4 Figure 4. Electronic spectra of the porphyrin dimers Cu-Cu-Cu, Cu-Pd-Cu, and of the copper(II)porphyrin monomer (dotted line).

Figure 5 .

 5 Figure 5. X-ray structure of the porphyrin dimer Cu-Cu-Cu. Top : side view showing the planar linking complex and the ruffled structure of the copper(II)porphyrin (all meso-aryl groups omitted), bottom: view showing the centrosymmetric porphyrin dimer (all hydrogen atoms omitted).

Figure 6 .

 6 Figure 6. X-ray structure of the porphyrin dimer Cu-Pd-Cu. Top : side view showing the planar linking complex and the ruffled structure of the copper(II)porphyrin (all meso-aryl groups omitted), bottom: view showing the centrosymmetric porphyrin dimer (all hydrogen atoms omitted).

Figure 7 .

 7 Figure 7. χT vs T (green squares) and χ vs T (red circles) for dimer Cu-Cu-Cu and dimer Cu-Pd-Cu (blue squares).Full lines correspond to the best fit considering two g values (see text).

Figure 8 .

 8 Figure 8. X-Band EPR spectra of complex Cu-Pd-Cu (black) at 4 K and Cu(II)porphyrin (orange) at 28 K in frozen CH 2 Cl 2 solution.

Figure 10 .

 10 Figure 10. Temperature dependence of the EPR intensity of Cu-Cu-Cu in frozen CH 2 Cl 2 solution.

Table 2 .

 2 EPR data for the three compounds in frozen CH 2 Cl 2 solution.

	Compound	g //	g⊥	A //	63 Cu	A⊥ 63 Cu	A 14 N	D (MHz)
				(MHz)	(MHz)	(MHz)
	Cu(II)porphyrin 1	2.223	2.065		540	30	50	-
	Cu-Cu-Cu (4K), S = 1/2	2.252	2.049		540	30	-	-
	Cu-Cu-Cu (70K), S = 3/2	2.262	2.045		180	10	40	450

Figure 1. Examples of dinuclear molecules built from different porphyrinoids (all peripheral substituents ommitted).

See FigureS13for the simulated spectrum.

ACKNOWLEDGEMENTS

Continuous financial support from the University of Strasbourg and the CNRS are acknowledged. MAC thanks the FRC-Labex CSC for her PhD fellowship (ANR-10-LABX-0026 CSC). HD thanks the French Ministry of Research for a PhD fellowship. We are grateful to the French EPR Federation of Research (RENARD, IR-RPE CNRS 3443). DBL is grateful to NSERC of Canada for generous research support.


Norma Gomes

Sepideh Iranfar

Slah Aridhi

Alice Guyon
email: alice.guyon@ipmc.cnrs.fr

Martine Adrian-Scotto

Gabriel Gandolfo

Sandra Perez

Physiological and psychological effects of rapid relaxation devices using sensorial immersion: a pilot study

Keywords: sensorial immersion relaxation devices, blood pressure, heart rate, attention tests, anxiety, well being

In developed societies, the number of people diagnosed with chronic stress-related illnesses has risen rapidly in recent years. To meet the increasing demand for relaxation and well-being, several companies have developed relaxation installations to be used within business premises or in public locations. The effects of such devices on physiological and psychological parameters have not been scientifically tested yet. This pilot study (N=40) evaluates the variations of 4 physiological and 11 psychological parameters on four different groups, three of them using a different rapid (15 minute) sensorial immersion relaxation devices and a control group using no device. The objective of the study was to identify the psychological and psychological parameters of interest and to study the effects of the devices on these parameters. Physiological parameters measured included heart rate, blood pressure, SpO2 and posture. Psychological parameters included an anxiety survey and four numerical scales to evaluate well-being, energy gain, and subjective muscular and nervous relaxation. We also used cognitive tests and verbatim reports.

We identified significant physiological and psychological parameters that can be of use for evaluating rapid relaxation devices (particularly mean blood pressure, posture, subjective muscular and nervous relaxation and some of the cognitive test results). Interestingly, the parameters variations differed between groups.

This study paves the way for further analysis of relaxation devices and suggests that rapid sensorial immersion relaxation devices can be of use in stressful environments. Each device could particularly help specific users, depending upon their needs.

I INTRODUCTION

Stress is a physiological response to adverse stimuli resulting in the activation of the sympathetic nervous system [START_REF] Dantzer | Stress and immunity: an integrated view of relationships between the brain and the immune system[END_REF]. Chronic stress is the repeated or prolonged activation of the stress response, and often leads to chronic diseases such as asthma, skin diseases, anxiety, depression, cardiovascular dysfunction or even cancer (Salleh 2008, Thayer and[START_REF] Thayer | Psychosomatics and psychopathology: looking up and down from the brain[END_REF]. In developed societies, the number of people diagnosed with chronic stress-related illnesses has risen rapidly in recent years. To meet the increasing demand for relaxation and well-being interventions, several companies have developed relaxation immersion installations that can be used by businesses or in other public locations (hospitals, transportation, schools, etc.) [START_REF] Culbert | Perspectives on Technology-Assisted Relaxation Approaches to Support Mind-Body Skills Practice in Children and Teens: Clinical Experience and Commentary[END_REF]). Increasing evidence is available regarding the benefits of long-term approaches, such as several weeks of yoga and meditation training on stress reduction [START_REF] Goyal | Meditation programs for psychological stress and well-being: a systematic review and meta-analysis[END_REF][START_REF] Pal | The effects of short-term relaxation therapy on indices of heart rate variability and blood pressure in young adults[END_REF][START_REF] Pascoe | Yoga, mindfulness-based stress reduction and stress-related physiological measures: A meta-analysis[END_REF][START_REF] Saeed | Depression and Anxiety Disorders: Benefits of Exercise, Yoga, and Meditation[END_REF]). However, no scientific studies exist for one-off, short duration techniques [START_REF] Culbert | Perspectives on Technology-Assisted Relaxation Approaches to Support Mind-Body Skills Practice in Children and Teens: Clinical Experience and Commentary[END_REF]. Therefore, the stress reduction efficiencies of these installations are unknown, as are the physiological and psychological consequences of the use of such devices. We chose to focus on three of these devices using sensorial immersion that proposed protocols of short duration (inferior to 15 min) and were compatible with a physiological non-invasive and accessible physiological analysis (e.g. EEG, respiratory belt and finger oximeter). The first one, Neural Up® by iCare-Science, an apparatus based on spatialized audition of sound frequencies, which are supposed to reduce stress by acting on the nervous system through the auditory pathway (https://www.neuralup-solutions.com/). Another is Be-Breathe® by Ino-Sens, which consists of a warming armchair modifying the posture with an audio respiratory exercise that prompts the respiratory rhythm of the user. This device is supposed to decrease stress mainly while improving physiological parameters (http://www.ino-sens.com/). The Cobtek laboratory in Nice, France (http://www.innovation-alzheimer.fr/relax/), has also developed a relaxation room, the "Relax room", which shows a 3D virtual movie of travel to an island, accompanied by music, where the rhythm complements the images. This device, using the visual and auditory systems, is supposed to favor a better attention after the relaxation period by reducing anxiety. We compared these three devices to a control group doing a 15-minute relaxation with no device. The term "relaxation" covers many aspects including muscular relaxation, nervous relaxation and a global sensation of well-being and state of rest [START_REF] Norelli | Relaxation Techniques[END_REF]. It can also be viewed as an emotional state (psychological and physiological) in which emotions and behaviors are interrelated and appraised within a specific context [START_REF] Scherer | What are emotions? and how can they be measured?[END_REF]. A variety of measures have been used to recognize this emotional state, including self-report, startle response, behavioral response, autonomic measurement, and neurophysiologic measurement [START_REF] Mauss | Measures of emotion: A review[END_REF]. This pilot study was conducted to establish effect sizes for appropriately powered future a priori studies and to determine the most relevant parameters to be used for analyzing rapid relaxation devices. We measured before and after the intervention physiological parameters that are known to be modulated in an opposite way by stress and relaxation, such as heart rate, blood pressure, SpO2 and posture. For instance, heart rate is increasing under stress while decreasing during relaxation [START_REF] Pal | The effects of short-term relaxation therapy on indices of heart rate variability and blood pressure in young adults[END_REF]. Mean blood pressure is a good indicator of stress levels [START_REF] Zimmerman | Stress and hypertension[END_REF] and can be decreased by relaxation [START_REF] Dickinson | Relaxation therapies for the management of primary hypertension in adults: a Cochrane review[END_REF]. Breathing deeply can increase the SpO2 [START_REF] Mengelkoch | A review of the principles of pulse oximetry and accuracy of pulse oximeter estimates during exercise[END_REF] and it has been shown that muscle relaxation and breathing interventions can have significant therapeutic effects for a variety of problems [START_REF] Lehrer | Heart rate variability biofeedback and other psychophysiological procedures as important elements in psychotherapy[END_REF]. Finally, a period of relaxation could improve the straightening of the body posture [START_REF] Drzaƚ-Grabiec | Changes of the body posture parameters in the standing versus relaxed sitting and corrected sitting position[END_REF].We excluded parameters such as skin conductance, salivary cortisol or alpha-amylase levels as they have been shown to be less reliable for short-term tests due to potential confounding effects [START_REF] Strahler | Simultaneous measurement of salivary cortisol and alphaamylase: Application and recommendations[END_REF][START_REF] Tronstad | Waveform difference between skin conductance and skin potential responses in relation to electrical and evaporative properties of skin[END_REF]). 1 We measured psychological parameters, by application of a set of stress and anxiety self-evaluation questionnaires [START_REF] Klainin-Yobas | Effects of relaxation interventions on depression and anxiety among older adults: a systematic review[END_REF]. We also used numeric rating scales to evaluate well-being, energy gain, muscular and nervous relaxation, before and after the intervention (adapted from [START_REF] Van Griensven | Pain, a textbook for health professionals[END_REF]).

Changes at the physiological level induced by psychosocial stress have been shown to be closely related to cognitive performance [START_REF] Lupien | Effects of stress throughout the lifespan on the brain, behaviour and cognition[END_REF][START_REF] Sanger | The influence of acute stress on attention mechanisms and its electrophysiological correlates[END_REF], as in attention [START_REF] Cornelisse | A randomized trial on mineralocorticoid receptor blockade in men: effects on stress responses, selective attention, and memory[END_REF]) and memory tasks [START_REF] Chamberlain | Noradrenergic modulation of working memory and emotional memory in humans[END_REF][START_REF] Kuhlmann | Effects of oral cortisol treatment in healthy young women on memory retrieval of negative and neutral words[END_REF]): a mild stress is thought to facilitate cognitive performances such as memory tasks, whereas an extreme stress may impair them. On the other hand, practices such as meditation and mindfulness have been shown to improve sustained attention [START_REF] Maclean | Intensive meditation training improves perceptual discrimination and sustained attention[END_REF], cognitive flexibility (Lutz et al. 2008, Moore and[START_REF] Moore | Meditation, mindfulness and cognitive flexibility[END_REF] and inhibition processes [START_REF] Bailey | Mindfulness meditators show altered distributions of early and late neural activity markers of attention in a response inhibition task[END_REF]. However, some types of relaxation, by decreasing vigilance, could alter the cognitive performances [START_REF] Amihai | Arousal vs. relaxation: a comparison of the neurophysiological and cognitive correlates of Vajrayana and Theravada meditative practices[END_REF]. Therefore, we hypothesized that a period of relaxation could modify memory and attentional performance and thus we included in this study six parameters evaluating sustained attention and short-term memory. We chose to use the Stroop test, which is measuring the aptitude to inhibit automatic response, and gives information on selective attention, cognitive flexibility and processing speed [START_REF] Stroop | Studies of interference in serial verbal reactions[END_REF], the Sustained Attention to Response Task (SART), a go/no-go task that requires participants to withhold behavioral response to a single, infrequent target, allowing to evaluate the impulsiveness [START_REF] Smilek | Failures of sustained attention in life, lab, and brain: ecological validity of the SART[END_REF] and the Corsi blocks which allows an rapid evaluation of the spatial working memory [START_REF] Vandierendonck | Working memory components of the Corsi blocks task[END_REF]). This pilot investigated the variation of 15 different physiological and psychological parameters, chosen because they cover different aspects of relaxation, on three different rapid relaxation approaches using devices, and a control group using no device. Our objectives were to investigate if 1) some parameters could be more relevant than others to evaluate relaxation state; 2) the use of rapid relaxation devices with sensorial immersion could improve the relaxation of the participant relative to control group with no device; 3) depending on the device employed, some of the parameters could vary differently among groups after the intervention.

II MATERIALS AND METHODS

Groups of participants

The experiment was conducted with 40 healthy volunteers (who were not paid for the study). The participants were between 24 and 68 years old, with an average of 42.7 ± 11.5 years old, including 28 women and 12 men (Table 1). They were distributed in four groups (10 participants per group) using pseudo-randomization in order to acquire comparable groups in terms of age and sex. There were seven women and three men in each group. All participants declared that there they were not dependent on drugs or alcohol, except four participants smoking occasionally (one in each group). Participants were not taking medication except 3 participants taking medicine for hyper or 1 Two companion articles will describe respectively 1) the effects induced during the relaxation period on electroencephalograms (EEG), respiratory rate and photoplethysmograms (PPG) and 2) the effect of the relaxation on voice parameters (such as prosody and vocal frequency) and facial emotions extracted from 3minute videos recorded before and after relaxation. A schema of the repartition of the data presentation in these three articles is shown in Annex 1. Further studies will analyze electroencephalogram (EEG), PhotoPlethysmoGraph (PPG) and respiration data recorded during the relaxation period, and videos acquired before and after the relaxation interval.

Relaxation devices

We named the groups as follows: G1 for the control group; G2, Neural Up® device; G3, Be-breathe® chair; and G4, Cobtek "Relax Room" (Figure 1). G1 was the control group: the participants remained seated in an armchair with their eyes closed. They were equipped with noise-cancelling headphones and asked to breathe calmly throughout the 15-minute session. G2 tested the Neural Up® device, a solution developed by iCare Sciences, and composed of a patented acoustic technology based on relaxing sound frequencies (Tibetan sounds) that alternate between right and left ears, giving a sensation of spatialized sound around the body. The participants remained seated in an armchair with their eyes closed and were equipped with noise-cancelling headphones. After 2.5-minute rest (baseline), the headphones delivered the Neural Up® sound for 10 minutes, followed by 2.5-minutes additional rest, in order to oblain a whole protocol of 15 minutes. G3 tested the Ino-Sens Be-Breathe® device, a warming armchair with a back massage and swing, which is synchronized with the respiratory rhythm and communicates audio-respiratory instructions to the participant to inhale for 5 seconds and exhale for 5 seconds. The participants were installed in the Be-Breathe® chair, instructed to breathe with their abdomen and equipped with noisecancelling headphones and a sleeping mask that covered their eyes. The Be-Breathe® chair was configured for a complex 15-minute sequence including: 1-minute rest, 1-minute audio instructions where the chair reached the horizontal position; 9 minutes of respiration movements driven by the armchair where the participant had a back massage and swing for the last 7 minutes in rhythm with respiration; then 3 minutes of rest in an inclined position and finally coming back to the seated position and resting for 1 minute. G4 tested the Cobtek laboratory "Relax Room": A relaxation cabin was employed to present a 3Dmovie containing virtual images of a realistic universe and then of a fantasy world on an island, with animals (butterfly, turtles) followed by virtual immersion in the water. The movie also presented sounds that began with a fast tempo and slowed down during the island travel phase, and came back to the initial rhythm at the end. The participants remained seated in a chair, equipped with glasses for 3D vision, in front of a large screen. After 3-minute rest, the 3-D movie was presented for a duration of 9 minutes followed by 3-minute rest.

Figure 1: Different relaxation devices used in the study.

Protocol

We developed a protocol in order to test and compare the effect of the different devices. All procedures contributing to this work comply with the ethical standards of the relevant national and institutional committees on human experimentation and with the Helsinki Declaration of 1975, as revised in 2008. The Université Côte d'Azur ethics committee for non-interventional research (CERNI, Comité d'Ethique pour les Recherches Non Interventionnelles) approved this protocol (Protocol number : CERNI-2019-5). Briefly, participants were given the information letter and consent form 15 days before the experiments. They gave us back the signed consent mentioning the authorization to be video-recorded before starting the experiment. All the experiences were videorecorded. The different parameters measured are described in Annex 1. Annex 2 presents a protocol showing the order in which we proceeded to the different measurements for each participant.

Physiological measurements

Immediately before and after each 15-minute relaxation session, we measured the systolic and diastolic blood pressure (to determine the mean arterial blood pressure = 1/3 systolic + 2/3 diastolic) and the cardiac rhythm of the participant using an armband (OMRON® M2). We measured the SpO2 (partial saturation in oxygen) using a fingertip pulse oximeter (CardioSensys® v1. 0, Sensoria Analytics). Participants were allowed to rest quietly in an armchair 5 minutes before measurement were taken. Before and after the 15-minute relaxation session, we also evaluated the standing posture of each participant by measuring the height of the eyes using a horizontal laser-pointer on a vertical scale.

Psychological parameters

The participants completed a preliminary survey on general data such as pre-existing conditions, level of physical exercise, specific diet, addictions (tobacco, alcohol, cannabis or other drugs) and sleeping habits, all of which may influence the data analyses.

Regarding the self-evaluation data collection, the participants used four numeric rating scales from 1 to 10 adapted from pain numeric rating scale [START_REF] Van Griensven | Pain, a textbook for health professionals[END_REF] to indicate their states of: 1) subjective general condition (physical, moral, and emotional), 2) subjective fatigue, 3) subjective muscular tension, and 4) subjective nervous or psychological tension.

They also completed a self-evaluation survey about their stress state and anxiety levels to permit the analysis of the self-perception of the participants, before and after the relaxation session. We used the following two forms: Perceived Stress Scale (PSS), the most widely used psychological metric for measuring the perception of stress. The 10 questions in the PSS concern feelings and thoughts over the past month.

It is a measure of the degree to which the situations in participant's life are appraised as stressful.

Items were designed quantify the level of unpredictability, uncontrollability, and overload in the lives of the respondents. The scale also includes a number of direct questions about current levels of stress experienced [START_REF] Cohen | A global measure of perceived stress[END_REF].

State-Trait Anxiety Inventory Form Y-1 (STAI-Y-1) or S-Anxiety scale: STAI has been used

extensively in research and clinical practice. It comprises separate self-report scales for measuring state and trait anxiety. The S-Anxiety scale consists of twenty statements that evaluate how respondents feel "right now, at this moment". The essential qualities evaluated by the S-Anxiety scale are feelings of apprehension, tension, nervousness, and worry. Scores on the S-Anxiety scale increase in response to physical danger and psychological stress, and decrease as a result of relaxation training [START_REF] Spielberger | Manual for the State-Trait Anxieg Inventor_y STAI (Form Y)[END_REF].

The questionnaires for the preliminary data (pathologies, physical exercise, diet, etc.) and for selfevaluation about stress (PSS Form) and anxiety (STAI-Y Form) were created using the Google Forms application (in an anonymous way) with versions in English and in French. The participants could select either English or French and responded using a tablet and we verified the registry of their answers on-line. The form responses were stored in .CSV files.

Subjective perceived duration and Verbatim

The participants were asked to comment on their experience during the relaxation session by giving three words at the end of the experiment. We compiled the words used by the participants of each group and then used a word cloud generator (https://www.jasondavies.com/wordcloud/). In the generated word cloud, word sizes are proportional to their frequency of apparition in the speeches of the 10 participants of each group. Additionally, after the session, participants were also asked to evaluate the perceived duration of the relaxation experience.

Attention tests

The participants performed a set of three attention tests, before and after the relaxation session: Stroop Task: The name of a color (e.g., "blue", "green", or "red") is printed on a computer screen, which is shown to the participant. Sometimes it is printed in the color that corresponds with its name and other times in a color that is different from the name (e.g., the word "red" printed in blue ink) [START_REF] Wright | What Stroop tasks can tell us about selective attention from childhood to adulthood[END_REF]. The so-called Stroop effect [START_REF] Stroop | Studies of interference in serial verbal reactions[END_REF] demonstrates that the reaction time to press a button corresponding to the color of the word when the ink mismatches the name of the color takes longer and is more prone to errors than when the ink color and word match. The Stroop effect is reported as the average response time in incompatible trials (for instance the word Green written in red) minus compatible trials (for instance the word Green written in green). This test In this test, a visual mask is presented in the middle of the screen, which is then replaced by a digit (1 to 9). Each digit is presented for 250 ms followed by a 900 ms mask. The digits appearing on the screen were 5 mm high and the screen was placed at 30 cm from the participants. The task requires the participant to press the space bar whenever a digit is presented, as fast as possible, except for the digit '3' (for which no response should be entered). SART is a measure of impulsive responding and sustained attention. We used the open-source application PsychoPy2 (http://www.psychopy.org/) to run a SART code available at GitHub, and we did some adaptations in the code to define the number of digits played (100 trials). For the test applied after the relaxation session, changed the digit '3' to '5' to decrease the bias effect of learning during the post-session test. All the data were stored in .CSV files.

Corsi Block-tapping test: This is a task designed to assess the visual memory span [START_REF] Kessels | The Corsi Block-Tapping Task: standardization and normative data[END_REF]. 9 blocks "light" up on a computer screen in a sequence (starting with a sequence of 2 blocks and increasing by 1 in each trial). The participant is required to use the mouse to click the same blocks and in the same sequence. If done correctly, the participant progresses to a higher number of blocks; if wrong, he or she gets once more chance; if wrong again, the final score is the number of positions retrieved (the Corsi block span). For Corsi-block test, we used PsyToolkit (https://www.psytoolkit.org/experiment-library/experiment_corsi.html).

Data analysis

We created a folder for each participant including the experiment guidelines based on the entire protocol. This was strictly followed for each participant and notes were taken of certain measurements and participant answers. The file was anonymous (no name, first name, date of birth or place of birth).

Statistics

For the statistical analysis, we used Sigmaplot-10.0, GraphPad Prism-6 and InvivoStat-3.7.0.0 software. Similar to age and sex, body mass index (BMI) can influence physiological parameters measurements such as heart rate [START_REF] Quer | Inter-and intraindividual variability in daily resting heart rate and its associations with age, sex, sleep, BMI, and time of year: Retrospective, longitudinal cohort study of 92,457 adults[END_REF]) and blood pressure [START_REF] Khoo | Blood pressure, body mass index, heart rate and levels of blood cholesterol and glucose of volunteers during National Heart Weeks, 1995-1997[END_REF]. In addition, different stress levels between groups at the beginning of the experiment could affect the relaxation process and the physiological and psychological measurements. Therefore, we checked that these parameters were equilibrated between groups at the beginning of the experiment. To compare the baseline characteristics of the participants between groups (in terms of age, body mass index (weight/ height 2 ), weight and height, and different parameters measured before the relaxation) we used one-way parametric ANOVA. The groups did not differ on these measures at p>0.3. We first evaluated the effects of the relaxation protocols on the different parameters measured using a repeated measures 2-way parametric ANOVA (time x 4 groups). Given the small sample size, this analysis did not reveal differences between groups but revealed a significant time effect for all groups (indicating an effect of the relaxation period) for most parameters (except for SpO2 and some of the attention parameters). As the four groups were independent, and because this study is exploratory in nature, we then compared the values from before and after the relaxation period for each independent group using paired t-tests. We applied a Holm correction for each independent group taking into account all the 15 parameters tested. As we didn't correct for the four groups, some of the effect revealed might be false text. Corrected p values inferior to 0.05 were considered significant. We measured effect sizes using Hedges'g formula adapted for small samples, as effect sizes are not affected by sample size:

The effect was considered as small for g < 0.2, medium for g = 0.5 and large for g > 0.7 (J. [START_REF] Cohen | The earth is round (p<0.05)[END_REF][START_REF] Schmidt | Eight common but false objections to the discontinuation of significance testing in the analysis of research data[END_REF].

We hypothesized that the magnitude of the relaxation effect would be greater if the stress or anxiety of the participant was high at the beginning of the intervention. To evaluate the possibility of a correlation between the initial stress or anxiety level of the participants and the relaxation effect, we correlated the stress and anxiety survey score before the relaxation with the different parameters that changed following the relaxation session for all participants (value post-minus value prerelaxation session). For the correlation studies, we used Heatmap built by a Python-3.7.0 script using the "corr()" method, which evaluates the Pearson's correlation between all the sets of variables. The result was graphed using "matplotlib" (Python plot utility source: https://medium.com/@sebastiannorena/finding-correlation-between-many-variablesmultidimensional-dataset-with-python-5deb3f39ffb3).

To obtain the correlation graphs, we used Sigmaplot-10.0 linear regression. In each plot, 3 points were detected as outliers by the software and were removed from the plot before the linear regression was computed. For each regression, we calculated the correlation coefficient r as well as the F and p value.

III RESULTS

Baseline characteristics of the study participants

After pseudo-randomization, we obtained a similar distribution in terms of age, body mass index (weight/ height 2 ), weight and height in each group, as illustrated in Annex 3. The stress level of the participants at the beginning of the study was comparable between all 4 groups (Annex 3).

Physiological measurements

We compared the values of physiological measurements made before and after the intervention for each independent group. The variations in heart rate from before and after intervention did not reach significance in any group (Fig 2A). Similarly, regarding SpO2, the changes in SpO2 did not reach significance for any group (Fig 2B).

The mean arterial blood pressure significantly decreased after the relaxation session in G3 (Be-Breathe® chair) (p<0.01), with an effect size of -0.32 and the decrease was close to significance in G2 (spatialized sound) (P=0.078) with a larger effect size of -0.750 (Fig 2D).

The systolic, diastolic and pulse pressure variations are shown in Figure 3. Overall, these changes did not reach significance, although the mean decreased in all groups, with the major changes observed in G3.

Regarding the posture, we measured a significant increase in the height of the eyes only in G4 (Relax room), with an effect size of 0.272 (Fig 2D). Apart from postural change, G4 showed the fewest changes in physiological parameters following the relaxation session, whereas the largest changes were observed in G3.

Self evaluations

The data obtained in evaluations using scales of well-being or energy gain did not show significant differences among groups between pre-and post-relaxation across all groups (Fig 4A andB). However, we observed a significant increase in subjective muscular relaxation in G3 (with an effect size of 0.736) and a significant increase in subjective nervous relaxation in G1 and G2 with effect sizes of respectively 1.166 and 0.778).

Self-reported anxiety

We observed no significant effect of relaxation on anxiety levels (measured by STAI-Y form) in any group. However, decrease in anxiety levels were close to significance for G1 (control group, p=0.092, effect size of -0.754) and G4 ("Relax Room", p=0.148 , effect size of -0.685).

Estimation of the relaxation duration

As illustrated Fig 5B, participants in G3 estimated the duration of the relaxation significantly much shorter than the objective duration (15 min), whereas the other groups kept a good notion of time.

Verbatim

We compiled the words used by the participants to describe their relaxation session experience. The results, presented in Figure 5C, show that expressions meaning "relaxed", "pleasant", and "nice" are frequently used by all participants, regardless of their group. However, there were some minor differences between groups, for instance the appearance of "short" for G3, in agreement with the result of Figure 5B, "packing" for G2 or "travel" for G4, corresponding to the diversity of the sensorial stimulus of each device.

Attention tests

The Stroop effect was unchanged after the relaxation session (Fig 6A). However, we did observe a significantly reduced reaction time in the Stroop test (related to processing speed) in G1, G2 and G4 with effect sizes of respectively -0.740, -0.718 and -0.480 (Fig. 7B). In addition, the Stroop test accuracy improvement after the relaxation session was close to significance in G4 (p=0.096) with an effect size of 0.735 (Fig 6C). Independent of the group, the relaxation sessions did not modify the average number of Corsi blocks memorized by the participants (Fig 6D). Finally, in the SART test, the target accuracy was significantly improved for G4 with an effect size of 0.797 (Fig 6E)

while the non-target accuracy was unchanged for all groups.

Table 2 summarizes the results obtained from Pre and Post relaxation analyses, allowing a clear comparison of the changes in variables within each group and giving an overview of the effects sizes observed for each parameter tested. Table 2 also presents the Holm-adjusted p-values for the 15 variables revealed by paired t-tests. All 4 groups showed improvements in different aspects regarding physiological and self-reported effects, including the control group (G1). We observed dominant physiological changes in G3 (with a reduction of mean blood pressure) while cognitive effects were notable for G4.

Impact of the anxiety state of the participant at the beginning of the relaxation

We hypothesized that the magnitude of the relaxation effect would be greater if the stress or anxiety of the participant was high at the beginning of the intervention. To evaluate the possibility of a correlation between the initial stress or anxiety level of the participants and the relaxation effect, we correlated the stress and anxiety survey score before the relaxation with the different parameters that changed following the relaxation session for all participants (value post-minus value prerelaxation session).

The results were then presented as a heat map (Figure 8), which revealed a good correlation between well-being, muscular and nervous relaxation subjective data with the initial anxiety level. However, it can be seen that the initial stress level did not correlate well with the subjective data. Figure 8 depicts correlations between initial anxiety levels (before relaxation) and the variation observed in well-being, subjective muscular and nervous relaxation between the values recorded pre-and post-relaxation (values post minus pre). Correlation coefficients were r= 0.43 for wellbeing, r=0.37 for muscular, and r=0.44 for nervous relaxation, meaning that there was a slight tendency for the relaxation to be more efficient for the participants who were the most anxious just before the relaxation. Although the correlations were small, they were significant.

IV CONCLUSION AND REFERENCES

Discussion

This pilot study compared the variations in physiological and psychological parameters, before and after a relaxation session using three commercial devices and a control group where participants relaxed without the use of any device. For this study, we chose to measure a series of 15 parameters that we expected to change with the relaxation state of the participants, such as blood pressure [START_REF] Dickinson | Relaxation therapies for the management of primary hypertension in adults: a Cochrane review[END_REF], heart rate [START_REF] Pal | The effects of short-term relaxation therapy on indices of heart rate variability and blood pressure in young adults[END_REF]), anxiety (Klainin-Yobas et al. 2015) and 6 cognitive parameters [START_REF] Lupien | Effects of stress throughout the lifespan on the brain, behaviour and cognition[END_REF]). These technologies are under-evaluated and protocols to estimate their efficacy are needed. Our study allowed determining a set of parameters that seems to be appropriate for measuring rapid relaxation effects and establishing effect sizes for appropriated powered future a priori studies. Among the variables that changed the most, we observed the physiological parameters mean blood pressure (particularly in G3, a group where the participants breathed deeply). Among the selfreported effects, we noted large variations on values obtained on the subjective muscular and nervous relaxation numerical scales, which showed large effect sizes and significance in most groups (Table 2). We also observed decreases on subjective measurements of anxiety after relaxation close to significance for G1 and G4 (Fig 5A). The effect of relaxation could depend on the initial anxiety level of the participants. Correlation studies showed that the perceived magnitude of subjective muscular and nervous relaxation (using scales) was proportional to the participants' level of anxiety before the relaxation intervention, independently of the group. Therefore, a rapid relaxation session is likely to be particularly efficient when people are anxious; conversely, there might be a ceiling effect in parameter improvements for rapid relaxation if the participants were initially relaxed. In our protocol, we did not purposefully stress a participant before the relaxation period. However, it is possible that the initial attention tests may have induced stress in some participants [START_REF] Mejia-Mejia | Physiological coherence in healthy volunteers during laboratory-induced stress and controlled breathing[END_REF].

Regarding the cognitive parameters, Stroop and SART attention tests parameters showed important differences in parameters that were particularly obvious in G4, a dispositive that is indeed supposed to help improving attention. The reaction time in the Stroop test improved after the relaxation session in all groups. This effect might be due to an increase in processing speed after the relaxation session. However, it could also be due to a learning effect. At the opposite, some variables did not change much. Among physiological effects, posture showed little changes (although we got significant result in G4, the effect size was low). Surprisingly, the heart rate remained quite stable although it has been described to vary with stress [START_REF] Pal | The effects of short-term relaxation therapy on indices of heart rate variability and blood pressure in young adults[END_REF]. 15 minutes might not be enough to observe significant variations on heart rate and heart rate variability parameters will probably tell us more information on relaxing effects (von [START_REF] Rosenberg | Resolving Ambiguities in the LF/HF Ratio: LF-HF Scatter Plots for the Categorization of Mental and Physical Stress from HRV[END_REF]). Among self-reported effects, well-being and energy gain numerical scales self-reports showed only small variations. This could be because after the relaxation session, the participants often felt a sensation of being asleep, which can seem opposite of energy gain and well-being. Among cognitive parameters, the number of Corsi blocks memorized also did not change after relaxation for any group, thus, short-term memory did not improve with greater relaxation in this study. Interestingly, while certain metrics in attention tests improved after relaxation, others were unchanged : the Stroop effect (the difference between the reaction time to congruent vs. incongruent stimuli) did not vary after the relaxation session for any group, suggesting that the cognitive flexibility was not affected by rapid relaxation.

In this study, we also tried to compare the different relaxation devices compared to a group using no device by studying the variations obtained on the different parameters tested. We are aware of the limitations of this study. Given the low sample size, the statistical analysis was a concern. All groups were equivalent for all parameters tested at the beginning of the relaxation as revealed by one-way ANOVA. Repeated measure two-way ANOVA did not reveal any difference between groups. However, there was a time effect for almost all the parameters tested, meaning that the relaxation period induced significant changes. As groups were independent, we used paired t-tests to compare the effects within each group over the 15 parameters tested, while using a stringent Holm/Bonferroni correction. This statistical approach has some limitations: Holm-Bonferroni correction could induce false negative due to its rigor. On the other hand, due to the lack of multiple corrections across groups, this method is also likely to induce false positive. This analysis revealed that the relaxation treatments were more efficient at modifying certain parameters in some groups compared to others. This approach has the advantage of allowing a comparison between the effects of the different devices. The use of effect size, that are supposed to be unaffected by sample size [START_REF] Huberty | Multivariate analysis versus multiple univariate analyses[END_REF] allowed us to obtain an estimation of the variation range of the parameters. Due to the sample of participants used in the study (students and teachers from the University), the generalizability of this study with larger sample size may pose problems for replication with other populations. The low sample of participants also prevented a true random allocation. However, this pilot study allows us to make some assumptions on the efficacy of each device. Interestingly, in G1 (control), where the participants were simply seated in an armchair and told to relax and breathe calmly (G1), we observed an increase in subjective muscular and nervous relaxation (Fig 4C -D) and a decrease in the Stroop test reaction time (Fig 6B). In addition, the participants used words like "relaxed, pleasant, good, etc." to describe their experience (Fig. 6C).

We can thus deduce that rapid relaxation, even without devices, can help people to achieve a sense of well-being in our "time-poor" society. In G2, where the participants were listening to spatialized Tibetan sounds, we observed a very similar profile as compared to G1.

The most significant variation we found in G3 concerned the physiological parameters, especially blood pressure (Fig 2). This result is not very surprising as the device used by G3 prompts the participants to breathe deeply and slowly, leading them to the state of "cardiac coherence", which is known to promote the activation of the parasympathetic system [START_REF] Mccraty | Cardiac coherence, self-regulation, autonomic stability, and psychosocial well-being[END_REF][START_REF] Tiller | Cardiac coherence: a new, noninvasive measure of autonomic nervous system order[END_REF]. The G3 participants were the only ones to lose the sense of time, estimating that the duration of their relaxation session to be much shorter than it actually was (Fig 5B). The participants of G3 also felt, on average, a significant increase in subjective muscular relaxation (Fig 4C). Interestingly, for G4 after relaxation, we found an improvement in participants' posture with no other physiological parameter changes. We also found an improvement in some of the assessed cognitive tasks. In the go/no-go SART (in which the participants have to press a key after every number presented on the screen except for a specific chosen number, the target), the target accuracy (non-response to a selected number) was improved for G4. Similarly, the Stroop reaction time significantly decreased (Table 2). Overall, G4 seemed to show improvement in attention. The "Relax Room" (G4) was conceived to encourage people to relax before they perform tests (specifically, tests to reveal the presence of Alzheimer's disease). The direction of the effect we observed in this pilot study is congruent with expected effect of this device on attention.

From this study, we can thus conclude that as little as 15 minutes of relaxation positively impacts physiological and psychological parameters. The use of a relaxation device may improve some aspects of relaxation. The spatialized sounds in Neural Up® (G2) improved the subjective nervous relaxation and the Stroop reaction time after relaxation. The Be-breathe® chair (G3) encouraged deeper, slower respiration, producing improved physiological changes, offering a real "disconnection" as evidenced by the participants' loss of the awareness of passing time, with no significant impact on the subsequent attention test results. The "Relax Room" (G4) enhanced the performance in attention tests and the improved participants' posture with no other physiological parameter changes.

Using a device can be particularly helpful for people who are not used to practicing relaxation. However, for people who are used to practicing relaxation or meditation regularly, the protocol followed by G1 could be sufficient to rapidly reach a state of relaxation. Even for untrained people, it has been shown that respiration in cardiac coherence could help to decrease stress (Mejia-Mejia et al. 2018).

While the majority of studies on relaxation are currently based on subjective measurements only, our study, which also includes objective criteria such as physiological measurements in the evaluations, has provided a more detailed analysis. Indeed, our study shows that for all groups, there is no clear correlation between the effects of relaxation according to subjective analyses (when a participant self-evaluates) and physiological parameters such as blood pressure (Table 2). This means that the participants may perceive themselves to be more relaxed despite the absence of a corresponding change in their physical parameters (for instance blood pressure). Furthermore, for G4, we observed an improvement in the attention test performance, but no significant changes in blood pressure parameters.

Our study illustrates that there are many different aspects of relaxation and that different relaxation devices can target one or more of these aspects.

Conclusion

In conclusion, this pilot study identified several parameters allowing the evaluation of different aspects of relaxation when using sensorial immersion rapid relaxation devices. Such technologies could be helpful in stressful environments, and could improve some aspects of relaxation compared with relaxation with no device. Future studies could help identifying the most suitable relaxation device for each user, according to its specific needs. The ability to choose the device that would maximize the relaxation for each individual would represent a great advance and would provide better health and well-being in a shorter time. The quantification of relaxation parameters used in this study may contribute to assessing in the future the degree of relaxation for each participant, in order to improve existing relaxation devices. A further study with a larger cohort will allow directing participants with a given stress profile to the device that best suits their needs.

Date and time of the end of the session :

________________________________________

  ISSN: 2430-3038, ©JIMIS, Creative Commons Revue en libre accès : j i m i s .e pi s c i e nc e s .o r g Volume : N -Année : 2020, DOI : 10.18713/JIMIS-021120-9-1 hypothyroidism (which were stabilized). The majority of participants were from Université Côte d'Azur or French research centers (students, teachers, employees, etc.). Both French and English speakers participated and participants could select either English or French language for the surveys. The whole protocol, including the relaxation phase (15 minutes) and the measurements of the parameters (pre and post relaxation), lasted 1 hour. The experiments were performed at room temperature (20-23°C) between 10 am. and 6 pm. on 4 consecutive weeks in April-May 2019.

  ISSN: 2430-3038, ©JIMIS, Creative Commons Revue en libre accès : j i m i s .e pi s c i e nc e s .o r g Volume : N -Année : 2020, DOI : 10.18713/JIMIS-021120-9-1 allows measuring the aptitude to inhibit an automatic reading response and it is used as a tool in the evaluation of executive functions. For Stroop test, we used PsyToolkit library of experiments (https://www.psytoolkit.org/experiment-library/stroop.html) and we created a French version of the test. Each test consisted in 40 trials. Sustained Attention to Response Task (SART, Smilek et al. 2010):

  positive. Only Holm corrected p values are given in the ISSN: 2430-3038, ©JIMIS, Creative Commons Revue en libre accès : j i m i s .e pi s c i e nc e s .o r g Volume : N -Année : 2020, DOI : 10.18713/JIMIS-021120-9-1

Figure 2 :Figure 3 :

 23 Figure 2: Physiological measurements before and after relaxation period for each group. A) Heart rate; B) SpO2; C) Mean arterial blood pressure (2/3 diastolic + 1/3 systolic blood pressure); D) Posture (evaluated by the height of the eyes). Dots represent the values pre-and post-intervention of a single participant, linked by a line. Bars represent the mean +/-s.e.m. (standard error of the mean) for the whole group (n=10), pre-(white bars) and post-(grey bars) intervention. One-way ANOVA revealed no significant difference between groups pre-intervention (white bars). Repeated measure 2-way ANOVA revealed no effect between groups but a significant time effect for heart rate, mean arterial blood pressure and posture. * p<0.05, ** p<0.01, paired t-test between pre-and post-values for each group adjusted for multiple comparisons by Holm/Bonferroni correction. P values close to significance are indicated on top of the bars.

Figure 4 :

 4 Figure 4: Self-evaluation before (pre) and after (post) the relaxation, measured using scales from 1 to 10 for: A) well-being, B) perception of gain of energy, C) subjective muscular relaxation state and D) subjective nervous relaxation state. Dots represent the values pre-and post-intervention of a single participant, linked by a line. Bars represent the mean +/-s.e.m. for the whole group (n=10) before (white bars) and after (grey bars) intervention. One-way ANOVA revealed no significant difference between groups pre-intervention (white bars). Repeated measure 2-way ANOVA revealed no effect between groups but a significant effect of time for all four self-evaluation parameters. * p<0.05, ** p<0.01 paired t-test between pre and post values for each group adjusted for multiple comparisons by Holm/Bonferroni correction. P values close to significance are indicated on top of the bars.

Figure 5 :

 5 Figure 5: Anxiety, duration estimation and verbatim reports. A) Anxiety evaluated using the STAI-Y state survey. Dots represent the values pre-and postintervention of a single participant, linked by a line. Bars represent the mean +/-s.e.m. for the whole group (n=10) before (white bars) and after (grey bars) intervention. One-way ANOVA revealed no significant difference between groups pre-intervention (white bars). Repeated measure 2-way

  ISSN: 2430-3038, ©JIMIS, Creative Commons Revue en libre accès : j i m i s .e pi s c i e nc e s .o r g Volume : N -Année : 2020, DOI : 10.18713/JIMIS-021120-9-1

Figure 6 :

 6 Figure 6: Attention tests. Results obtained with the attention tests before (Pre) and after (Post) relaxation for the four groups. A) Stroop effect (mean reaction time of congruent minus incongruent presentation). B) Reaction time for the Stroop test (including both congruent and non-congruent presentations). C) Stroop test accuracy (number of correct answers for 40 trials) D) Number of Corsi Bloks memorized. E) SART target accuracy (% of good responses). F) SART non-target accuracy (% of good responses).Dots represent the values pre-and post-intervention of a single participant, linked by a line. Bars represent the mean +/-s.e.m. for the whole group (n=10) before (white bars) and after (grey bars) intervention. One-way ANOVA revealed no significant difference between groups pre-intervention (white bars). Repeated measure 2-way ANOVA revealed no effect between groups but a significant

Figure 7 :

 7 Figure 7: Heat map representing the level of correlation between the parameters analyzed for all participants in the four groups. Pre Stress: Stress before the relaxation evaluated with the PSS; Pre Anx: Anxiety before the relaxation evaluated with the STAI state survey; Posture: Delta Post-Pre relaxation of height of the eyes to evaluate the posture; Heart Rate: Delta Post-Pre relaxation of heart rate; SpO2: Delta Post-Pre relaxation of SpO2; Mean BP: Delta Post-Pre relaxation of mean arterial blood pressure; Well-being: Delta Post-Pre relaxation of subjective evaluation with scales; Energy: Delta Post-Pre relaxation of subjective evaluation of energy gain with scales; Muscle: Delta Post-Pre relaxation of subjective evaluation of muscular relaxation with scales; Nervous: Delta Post-Pre relaxation of subjective evaluation of nervous relaxation with scales; Corsi: Delta Post-Pre relaxation of score obtained with the Corsi attention test; Stroop Effect: Delta Post-Pre relaxation of score obtained for the Stroop Effect; Stroop RT: Delta Post-Pre relaxation of reaction time obtained with the Stroop test; Stroop Acc: Delta Post-Pre relaxation of the Stroop test accuracy; SART Tg: Delta Post-Pre relaxation of scores obtained in the SART test for the target digit and SART NTg: Delta Post-Pre relaxation of scores obtained in the SART test for the non-target digit.

  ISSN: 2430-3038, ©JIMIS, Creative Commons Revue en libre accès : j i m i s .e pi s c i e nc e s .o r g Volume : N -Année : 2020, DOI : 10.18713/JIMIS-021120-9-1

Figure 8 :

 8 Figure 8: Linear correlation plots showing the relation between anxiety level before the relaxation (in abscissa) and A) the subjective well-being variation (Post minus Pre relaxation value); B) the subjective muscular relaxation variation (Post minus Pre relaxation value); and C) the subjective nervous relaxation variation (Post minus Pre relaxation value). Each dot represents a participant with a color code indicating the group. Correlation coefficients (r), F and p values are indicated in each box.

  ISSN: 2430-3038, ©JIMIS, Creative Commons Revue en libre accès : j i m i s .e pi s c i e nc e s .o r g Volume : N -Année : 2020, DOI : 10.18713/JIMIS-021120-9-1

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  3038, ©JIMIS, Creative Commons Revue en libre accès : j i m i s .e pi s c i e nc e s .o r g Volume : N -Année : 2020, DOI : 10.18713/JIMIS-021120-9photo at 1m from the wall and posture evaluation Height H1 of the eyes on a vertical graduate scale (in meter) Right now, please indicate at which level you estimate your condition (physical, moral, emotional as a whole, as you feel it). ISSN: 2430-3038, ©JIMIS, Creative Commons Revue en libre accès : j i m i s .e pi s c i e nc e s .o r g Volume : N -Année : 2020, DOI : 10.18713/JIMIS-021120-9-1 Investigator : Please write the A1 score below A3 = ISSN: 2430-3038, ©JIMIS, Creative Commons Revue en libre accès : j i m i s .e pi s c i e nc e s .o r g Volume : N -Année : 2020, DOI : 10.18713/JIMIS-021120-9-1 5-Subjective energy gain evaluation -By referring to your state o fatigue at this moment, can you indicate at which level you estimate it on this linear scale? Investigator : Note below the estimated level of fatigue/energy A4= 6-Muscular tension subjective evaluation -By referring to your state of muscular tension at this moment, can you indicate at which level you estimate it on this linear scale? By referring to your state of nervous tension at this moment, can you indicate at which level you estimate it on this linear scale? was used during the session ISSN: 2430-3038, ©JIMIS, Creative Commons Revue en libre accès : j i m i s .e pi s c i e nc e s .o r g Volume : N -Année : 2020, DOI : 10.18713/JIMIS-021120-9-1 Installation of the subject -Check the following points: The subject went to the restroom before the session Glass of water available to the subject Subject well installed on the armchair Ungraded shirt collar and beld (if needed) Legs uncrossed, head resting and jaws released Hands affixed to the armrests Headban and noise reduction headphones installed Installation of measurement sensors -The investigators checks the setting up of measurement sensors : Note below the SPO2 and the values of blood pressure measured at T0 (to be indicated) : photo at 1m from the wall and posture evaluations Height H'1 of the eyes on a vertical graduate scale (in meter) H'1 = 4-Please answer the following questions Did you feel your body sensation during the whole experience? Yes/No Did you keep the notion of space surrounding you during the experience Yes/No How long do you think the experience lasted? ISSN: 2430-3038, ©JIMIS, Creative Commons Revue en libre accès : j i m i s .e pi s c i e nc e s .o r g Volume : N -Année : 2020, DOI : 10.18713/JIMIS-021120-9-1 Investigator : Note below the estimated level of fatigue/energy B4= 9-Muscular tension subjective evaluation -By referring to your state of muscular tension at this moment, can you indicate at which level you estimate it on this linear scale? By referring to your state of nervous, pschological tension at this moment, can you indicate at which level you estimate it on this linear scale? ISSN: 2430-3038, ©JIMIS, Creative Commons Revue en libre accès : j i m i s .e pi s c i e nc e s .o r g Volume : N -Année : 2020, DOI : 10.18713/JIMIS-021120-9-1 Investigateur/investigator : -Please write the score B4 below : B6 = ISSN: 2430-3038, ©JIMIS, Creative Commons Revue en libre accès : j i m i s .e pi s c i e nc e s .o r g Volume : N -Année : 2020, DOI : 10.18713/JIMIS-021120-9participant the survey to give back one week after the relaxing device experience.

Table 1 :

 1 Characteristics of the participants in terms of age, weight, height and BMI. Mean ± s.e.m. N=10 per group. One-way ANOVA non-significant between groups for each parameter (p>0.5). BMI: body mass index.

		G1 -Control	G2-NeuralUp	G3-BeBreathe	G4-Relax room
	Age (years)	44.0 ± 13.1	43.2 ± 13.0	42.5 ± 10.6	41.1 ± 10.4
	Weight (kg)	65.9 ± 14.8	66.8 ± 10.6	63.4 ± 14.1	69.5 ± 15.2
	Height (cm)	167.8 ± 7.2	172.0 ± 10.7	169.1 ± 7.0	168.0 ± 7.8
	BMI (kg/cm 2 )	23.4 ± 5.2	23.0 ±2.3	22.2 ± 5.4	24.8 ± 5.5

j i m i s .e pi s c i e nc e s .o r g Volume

ISSN: 2430-3038, ©JIMIS, Creative Commons Revue en libre accès : : N -Année : 2020, DOI : 10.18713/JIMIS-021120-9-1

Table 2 :

 2 Changes in parameters for each group.Mean values ± standard deviation Pre and Post relaxation are indicated for each group as well as Hedges'g effect sizes (in blue, large effect sizes (with an absolute value > 0.7) indicated in bold) and P values of paired t test, adjusted for multiple comparisons (Holm/Bonferroni correction). P<0.15 in red, * p<0.05, ** p<0.01, *** p<0.001. N=10 per group.

F Financial support

This work was supported by the French government through the UCA-Jedi project managed by the National Research Agency (ANR-15-IDEX-01) and, in particular, by the interdisciplinary Institute for Modeling in Neuroscience and Cognition (NeuroMod) of the Université Côte d'Azur. Norma Gomes was funded by Neuromod institute of UCA. Sepideh Iranfar was funded by Sensoria Analytics startup.

Informations for Be -Breathe -Amrchair with following parameters :

Position

Zero Gravity

Swing Activated Press 50%

Respiratiry system

Inspi 5 s. / Expi 5 s. (0,10 Hz) We compared data from the four groups using one-way ANOVA. There was no significant difference between groups (P>0.3).

Informations for CobteK

Position

D Acknowledgements

The authors would like to thank all the volunteers that participated this study. We thank Christian Müller from Ino-Sens for allowing us to use the Be-Breathe® chair, Chris Hayot from Icare Science for allowing us to use the Neural Up® software, and Philippe Robert, Renault David and Auriane Gros for welcoming us in Cobtek and allowing us to use the "Relax Room". We are grateful to Francois Bremond and Srijan Das for their help in posture analysis. We thank Patricia Bouret, Fabienne Colette, Solène Granjeon-Noriot and Thomas Lorivel for their statistical advice. We thank Karina Aridhi and Abby Cuttriss (from the Office of International Scientific Visibility, Université Côte d'Azur) for English corrections.

E Data availability

The data that support the findings of this study and the repeated measures parametric analysis are available from the corresponding authors on reasonable request.

G Conflict of interest

The authors declare they have no conflict of interest. The devices used in this study were kindly loaned by the companies with their agreement to proceed to the experiments. A research collaboration contract was signed between Sensoria Analytics and the CNRS.