J Gaspar

Y Corre

N Fedorczak

J P Gunn

C Bourdelle

S Brezinsek

J Bucalossi

N Chanet

R Dejarnac

M Firdaouss

J-L Gardarein

G Laffont

T Loarer

C Pocheau

E Tsitrone

West Team

DIVERTOR POWER LOADS AND SCRAPE OFF LAYER WIDTH IN THE LARGE ASPECT RATIO FULL TUNGSTEN TOKAMAK WEST

WEST is a full W tokamak with an extensive set of diagnostics for heat load measurements especially in the lower divertor. It is composed by infrared thermography, thermal measurement with thermocouples and fiber Bragg grating embedded few mm below the surface and flush mounted Langmuir probes. A large database including different magnetic equilibrium and input power is investigated to compare the heat load pattern (location, amplitude of the peak and heat flux decay length) on the inner and outer strike point regions : from the first ohmic diverted plasma (obtained during the second experimental campaign C2 in 2018) up to the high power (8 MW total injected) and high energy (up to 90 MJ injected energy in lower single null configuration) experiments performed in the last experimental campaign (C4 in 2019). Concerning the peak location, a good agreement (<1cm) is obtained between thermal inversions and flush-mounted LP measurements. The peak heat flux from the whole set of diagnostics is in good agreement and mainly in the ± 20% range, while the heat flux decay length reported on the target shows significant discrepancy between diagnostics and location in the machine (± 40% range). Despite such discrepancy, heat flux decay length at target is found to scale mainly with the magnetic flux expansion through the variation of the X-point height, as expected. The improved plasma performances achieved during C4 enabled to reach significant heat load in the divertor, up to 6 MW/m² with 4 MW of additional heating power showing the capability to reach the ITER relevant heat load (10 MW/m² steady state) with about 7 MW of additional power in Lmode discharge. The heat load distribution is clearly asymmetric with a 3/4 and 1/4 distribution on the outer and inner strike point region respectively for the parallel heat flux.

INTRODUCTION

One of the main goals of WEST is the assessment of power handling capabilities and lifetime of tungsten divertor components under high heat flux and high fluence operation in a full W tokamak environment [START_REF] Bourdelle | WEST Physics Basis[END_REF]. During the first four experimental campaigns (named C1 to C4), WEST operated with a mix of actively cooled ITER like tungsten plasma facing units and inertial tungsten coated graphite components [START_REF] Bucalossi | OVERVIEW OF WEST FIRST PHASE OF OPERATION[END_REF]. The preliminary step towards testing the tungsten ITER like components under ITER relevant heat flux (10 MW/m² in steady state), is to characterize the heat flux deposition pattern in terms of intensity and decay length. For this purpose, a set of complementary diagnostics allowed characterizing properties of the heat loads on the lower divertor: arrays of embedded thermocouples (TC) and Fiber Bragg Gratings (FBG) sensors [START_REF] Corre | [END_REF], infra-red thermography (IR) [START_REF] Courtois | Full coverage infrared thermography diagnostic for WEST machine protection[END_REF] and arrays of flush-mounted Langmuir probes (LP) [START_REF] Dejarnac | Flush-mounted Langmuir probes in the WEST tokamak divertor[END_REF]. First heat flux calculations were performed during early diverted ohmic plasma experiments as depicted in [START_REF] Gaspar | First heat flux estimation in the lower divertor of WEST with embedded thermal measurements[END_REF]. First comparison between FBG and IR calculations only is reported in [START_REF] Fedorczak | Cross diagnostics measurements of heat load profiles on the lower tungsten divertor of WEST in Lmode experiments[END_REF]. On this basis, the study has been extended with TC and LP measurements available during each campaign. The heat flux database is built as a function of the continuous progress achieved in WEST : from the first ohmic diverted plasma (obtained during the second experimental campaign C2 in 2018) up to the high power (up to 8 MW total injected power during 4 s) and high energy (up to 90 MJ total injected energy in lower single null configuration) steady state L-mode plasma experiments performed in the last experimental campaign (C4 in 2019) [START_REF] Bucalossi | OVERVIEW OF WEST FIRST PHASE OF OPERATION[END_REF]. We report on the heat load pattern, position of the strike point, peak heat flux and heat flux decay length, on both the outer and inner strike point regions, as a function of the plasma parameters, heating power (P tot ), divertor power (P div =P tot -P rad ), plasma current (I p ) and divertor magnetic equilibrium (far and close X-point) for deuterium and helium plasmas. It includes heat flux calculation for 228 L-mode plasma experiments achieving at least four seconds of steady state plasma to get significant heating and accurate heat flux calculation from all heat load diagnostics.

The heat load diagnostics set-up as well as the processing methodology are presented in section 2. Section 3 focus on selected discharges from the campaign C4 where all diagnostics were simultaneously available allowing crosscheck between them on estimated peak heat flux and heat flux distribution properties (peak location and decay length) on the outer strike point region. Finally, the last section extends the database from the first diverted deuterium plasma during campaign C2 up to the last helium discharge of the campaign C4, the evolution of the peak heat flux over the campaigns as well of the heat load asymmetry are discussed on both strike point regions (outer/inner).

HEAT LOAD DIAGNOSTICS SET-UP AND HEAT FLUX DATABASE

The WEST divertor consists of 12 independent toroidal sectors of 30° each composed of 38 plasma facing units. During the WEST phase 1, a mix of ITER-like actively cooled components (bulk W) [8] and non-actively cooled W-coated graphite components is used [9]. The W-coated graphite is divided in two separate components, one in the low field side (LFS/outer) and one in the high field side (HFS/inner). The WEST lower divertor is monitored by a set of complementary diagnostics allowed characterizing properties of heat loads on the lower divertor: 20 embedded TCs located at 7.5mm below the surface [10], 4 FBGs [START_REF] Corre | [END_REF] embedded at 3.5 and 7mm below the surface, IR thermography [START_REF] Courtois | Full coverage infrared thermography diagnostic for WEST machine protection[END_REF] and two arrays of 29 flush-mounted LPs [START_REF] Dejarnac | Flush-mounted Langmuir probes in the WEST tokamak divertor[END_REF].The diagnostic are spread over the 12 divertor sectors keeping symmetric toroidal location of the sensors regarding the magnetic field toroidal modulation (ripple effect). A poloidal cross section of the WEST device with two magnetic configurations with a separatix located at R ext = 2.93m and 3m is shown in fig 1 a. The WEST IR system used in this analysis consists of several different actively cooled endoscope located at the top of the chamber monitoring the lower divertor. The IR cameras are equipped with a filter at the wavelength 3.9 ± 0.1µm, a frame size of 640x512 pixels. The projected pixel size is about 2.5 mm/pixel for the reported PFC studies of this paper. One IR camera is monitoring a sector also equipped with 16 TCs including 2 PFCs with 4 TCs and the flush-mounted LPs as illustrated in fig 1 b). The IR system is calibrated and translate the collected radiance into blackbody surface temperature. The deposited heat flux is estimated from these data using the TEDDY code [START_REF] Fedorczak | Infra-red thermography estimate of deposited heat load dynamics on the lower tungsten divertor of WEST[END_REF]. The main limitations in this inversion can result from both the reflected radiance at low surface temperature [START_REF] Aumeunier | Infrared thermography in metallic environments of WEST and ASDEX Upgrade[END_REF] and the non-uniform emissivity observed on the PFCs [START_REF] Gaspar | In-situ assessment of the emissivity of tungsten plasma facing components of the WEST tokamak[END_REF]. To overcome these difficulties a procedure has been implemented in the TEDDY code to determine the effective emissivity and background reflections (supposed constant during the discharge) using the IR measurements just prior the plasma and the TC measurements [START_REF] Fedorczak | Infra-red thermography estimate of deposited heat load dynamics on the lower tungsten divertor of WEST[END_REF]. The main improvement (remaining to be done) for the IR processing in TEDDY is to implement the variation of the emissivity with the PFC temperature, for this purpose post-mortem measurement is foreseen to investigate the emissivity dependency in area presenting higher emissivity than W to complement the previous measurement performed on virgin sample [START_REF] Gaspar | Emissivity measurement of tungsten plasma facing components of the WEST tokamak[END_REF].

The embedded measurements are used to solve an inverse heat conduction problem. This problem consists in the determination of the surface heat flux (ϕ) minimizing the discrepancy between the output of a heat conduction problem giving the PFC bulk temperature and the temperature measurements provided by the PFCs with 4 TCs or with the 11 FBGs. The conjugate gradient method combined with the adjoint state is the optimization process used to solve the inverse problem [START_REF] Gaspar | First heat flux estimation in the lower divertor of WEST with embedded thermal measurements[END_REF]. As the inverse problem is ill-posed the inversion algorithm is constrained by imposing a shape function to the deposited heat flux given by Eq. 1 [START_REF] Eich | Empiricial scaling of inter-ELM power widths in ASDEX Upgrade and JET[END_REF][START_REF] Scarabosio | Outer target heat fluxes and power decay length scaling in L-mode plasmas at JET and AUG[END_REF].

(1)

From this shape, five parameters can be estimated: the background and the amplitude of the heat flux evolving in time and three parameters supposed constant during pulses with steady state plasma (fixed magnetic equilibrium, plasma density, plasma current, injected power), the heat flux decay length at the target ( , the strike point location ( , the Gaussian spreading factor and is the curvilinear length along the PFU. In this study the spreading factor is supposed to be equal to 5 mm which is the usually measured value from the IR inversion. Here we will focus on three arrays of 4 TCs embedded in two PFCs on the outer side (low field side) called TC Q6A and TC Q1A (subscript corresponding to the divertor sector) and one PFC on the inner side (high field side) also installed in the sector Q6A. The 2 PFCs (outer/inner) with 4 TCs from the sector Q6A stand next to the two arrays of 29 flush mounted LPs [START_REF] Dejarnac | Flush-mounted Langmuir probes in the WEST tokamak divertor[END_REF] and these tiles are located at the toroidal positions where the ripple modulation of the incidence angle of magnetic field lines provides the maximum deposited heat flux in each region. Each array starts from the inner side and go to the outer side with a probe spacing of 12.5 mm. During the discharges the probes voltages are swept during 1 ms every 4 ms, then the collected I-V characteristics are processed to provide the local parallel ion current density (J //i ) and T e . Local density and parallel heat flux are then estimated assuming T e =T i ( with γ=7).

FIG. 1. a) Poloidal magnetic field configuration with R ext = 2.93m and 3m. b) Top view of the lower divertor instrumented with 16 TCs (blue squares) and the 12 LPs (cyan circle) used in this study. c) Top view of the machine with typical heat load pattern on the lower divertor due to the ripple modulation (20°), the sector distribution, the antennas and the heat load diagnostics investigated here. d) 2D sketches of the PFC with 4TCs and FBG (the surface exposed to the plasma is on the top).

HEAT LOAD DIAGNOSTICS COMPARISON

The comparison of the estimated heat fluxes by the heat load diagnostics focus on the discharges from the campaign C4 (2019). The discharge database of the first cross-check analysis [START_REF] Fedorczak | Cross diagnostics measurements of heat load profiles on the lower tungsten divertor of WEST in Lmode experiments[END_REF] has been extended from 114 discharges to 165, most importantly the TC inversions from the 2 tiles instrumented with 4 TCs (Q6A and Q1A) have been added as well as the LP measurements (Q6A) for 63 discharges corresponding to the last part of the campaign. To compare the shape of the heat profiles obtained from the different diagnostics, the estimated heat fluxes from the IR and LP measurements are averaged over 1s during the stationary phase of the discharges and the profiles are fitted with the same shape function (Eq 1) used for the TCs and FBG inversions with also the spreading factor as fitted parameter. As 2 sets of TCs will be used for more clarity and we will refer to the TC

a) b) c) d)
located on the sector Q6A and Q1A with the name TC Q6A and TC Q1A , respectively. This database includes attached (T e >20 eV) L-mode Lower Single Null (LSN) discharges with heating powers from 1 to 8 MW (combining up to 4.8 MW of lower hybrid current drive and up to 3.1 MW of ion cyclotron resonance heating) with magnetic fields B T from 3.5 to 3.7 T and plasma current I p from 300 to 700 kA (corresponding to edge safety factor q 95 from 7.8 to 3.2 respectively). Here we focus on the outer strike point region as the inner region shows features on the IR and LP measurement that are not fully understood yet and already depicted in [START_REF] Fedorczak | Cross diagnostics measurements of heat load profiles on the lower tungsten divertor of WEST in Lmode experiments[END_REF].

Heat load intensity and decay length at the target

Fig 2a

) compares the peak heat fluxes estimated from the TCs/FBG and LP measurements to the heat fluxes derived from IR thermography. An overall agreement is found with a main dispersion of 20% up to 30% for a part of the database, as depicted in [START_REF] Fedorczak | Cross diagnostics measurements of heat load profiles on the lower tungsten divertor of WEST in Lmode experiments[END_REF]. This comparison shows that at the maximal heat flux location, where the surface temperature is maximal and the IR reflection influence minimal, a very good agreement is observed between the IR inversion, the embedded TCs/FBG and the LP measurements. Fig 2b ) shows the estimated strike point position s 0 with the edge diagnostics using the equation 1 describing the heat flux distribution and the magnetic reconstruction performed by the code NICE [17] using magnetic measurements and interferopolarimetry constrains. All the diagnostics agree with a dispersion of few mm which is lower than the sensors spacing (12.5 mm for FBGs and LPs and 37.5mm for TCs) and equivalent to the IR spatial resolution (about 2.5mm) The main shift is between the estimated s 0 and the reconstructed s 0 from the code NICE with a shift between 10 and 20mm and seems higher for the He discharges. Only LP measurements seem to exhibit a dependency with the magnetic configuration with some points in agreement with NICE. as function of the one the TC Q6A inversion. For the deuterium discharges (cross) 3 groups can be identified. A good agreement between TC Q6A and the LP measurements is found which is installed in the PFC next to the TC Q6A (see Fig 1 b)). Then the FBG and the TC Q1A are well in line together but 40 % higher than the first group, these diagnostics are located 180° away in the toroidal location and 60° away from the first group (see Fig 1 c)), respectively. Finally, the from the IR estimation is 40% lower compare to the values from TC Q6A which are on the same PFC. For the He discharges the LP and TC Q6A remains well in line, but the FBG estimation comes 30% lower and the IR estimation exhibit also higher discrepancy from 50 to 60% lower than the LP and TC Q6A estimations. Fig 4 shows estimated heat flux distribution estimated for the whole set of diagnostics for a particular deuterium pulse (#55070). To understand these discrepancies several studies are on-going. For the embedded measurement, as the WEST phase 2 will start in summer 2021 all the instrumented PFCs of the WEST phase 1 have been removed from the machine. An extensive post-mortem analysis will be performed to check the validity of the thermal measurement (time response, calibration etc.) as extensive numerical tests have been done to compare the inversion from TEDDY [START_REF] Fedorczak | Infra-red thermography estimate of deposited heat load dynamics on the lower tungsten divertor of WEST[END_REF] and the embedded measurement in regard to the assumptions. For the IR, a post-mortem activity is also on-going to measure the PFC emissivity and confirm the observations made in the a) b)

machine for the emissivity spatial distribution [START_REF] Gaspar | In-situ assessment of the emissivity of tungsten plasma facing components of the WEST tokamak[END_REF] due to impurities redeposition. Measurements of the emissivity evolution with the temperature is foreseen on the different areas (low and high emissivity) to take into account this variation in the IR processing performed in the TEDDY. This upgrade could contribute to the comparison especially for He discharges where long discharges have been performed with high surface temperatures reaching up to 1000 °C. Then other approach is under development for the IR processing based on inverse method to have a better evaluation of the reflected light which could perturbate the IR inversion in the cold area [START_REF] Talatizi | Inverse radiation problem with infrared images to monitor plasma-facing components temperature in metallic fusion devices[END_REF]. This upgrade will improve the background heat flux estimated with the IR inversion (overestimated with at least factor two in comparison to the TC, FBG and bolometry measurements) and could modify the estimated from the IR data. IAEA-EX/P5-10

SOL width versus L-mode scaling laws

The heat flux decay length at the target is remapped to the outer midplane using the magnetic flux expansion with , varying from 2 to 9 in the database. Fig 5 shows the heat flux decay length measured by the diagnostics and the experimental scaling laws for L-mode discharges [START_REF] Scarabosio | Outer target heat fluxes and power decay length scaling in L-mode plasmas at JET and AUG[END_REF]. The blue area corresponds to the whole set of scaling laws from L-mode discharges determined with IR thermography on the outer target of JET and ASDEX-U with carbon PFC. The red area corresponds to the scaling law with the highest correlations of the JET and ASDEX-U database defined by . The areas are determined with PSOL variation from 0.5 to 3 MW and magnetic field from 3.5 to 3.7 T corresponding to the WEST database. The comparison is performed as function of the safety factor as it is the main parameter scanned in the WEST database.

The IR values are mainly in the range of the L-mode scaling laws especially for deuterium discharges with q 95 = 4.3 (Ip= 500kA) and helium discharges with q 95 = 6.2 and 7.7 (Ip = 350 and 300 kA, respectively). The deuterium discharges performed at other q 95 seems to be slightly higher than the scaling and exhibit low dependence with q 95 especially the few discharges performed with q 95 = 3.2 (Ip = 700 kA). The from TC Q6A and LP also mainly increase with q 95 with values about 2 times higher than the set of scaling laws. As seen previously the from FBG and TC Q1A are higher and in the range of 3 times the scaling laws at the exception of the helium discharges for the FBG values (no data for TC Q1A ). The discharges with q 95 = 3.2 exhibit a surprisingly high value which do not follow the global trend. To confirm these observations and performed parametric analysis more discharges are needed, once the differences between the heat load diagnostics is fully understood. Finally, a scan of the magnetic field should be envisaged to address the impact of the magnetic field and perform a multi-machine scaling with the other machine and possibly investigate the impact of the high aspect ratio of WEST (about 5.5).

FIG. 5. Heat flux decay length at the midplane

from FBG (red), TC Q6A (blue), TC Q1A (green), LP (magenta) and IR (black) function safety factor q 95 for deuterium (+) and helium (o) discharges with prediction from L-mode scaling laws from [START_REF] Scarabosio | Outer target heat fluxes and power decay length scaling in L-mode plasmas at JET and AUG[END_REF] (blue area) the whole set of laws (red area) main scaling law.

HEAT LOADS OBSERVATIONS BASED ON EMBEDDED MEASUREMENTS

In this section we extend the database to a total of 228 discharges with discharges from the two previous campaigns called C2 and C3 with 7 and 56 discharges, respectively. We focus on the peak heat flux evolution on the divertor through the campaigns as well as the inner/outer asymmetry based on observations made with FBG and TCs inversion as all the heat load diagnostics give equivalent value for the peak heat flux and absorbed energy by the PFC [START_REF] Fedorczak | Cross diagnostics measurements of heat load profiles on the lower tungsten divertor of WEST in Lmode experiments[END_REF]. shown for 500 kA discharges, excluding a potential reduction of the SOL width over the campaigns to explain the heat flux increase. One can note that the maximal deposited heat flux observed is about 6 MW/m² for discharges with 4 MW of LH power, radiated fraction of 45% and X-point height of 120 mm showing that the 10 MW/m² could be achieved with about 7 MW of additional power in this configuration in L-mode.

Heat flux evolution over the campaigns

FIG. 6. a) Peak heat flux from embedded measurement (TC/FBG) as function of P div at the outer strike point (OSP) and Inner strike point (ISP) for C4 OSP (red), C3 OSP (blue), C2 OSP (black), C4 ISP (magenta) and C3 ISP (cyan) for deuterium (Δ) and helium (o) discharges. b) Heat flux decay length at the target as function of the X-point height for C4 OSP (red), C3 OSP (blue) and C2 OSP (black).

The TC acquisition is performed in a continuous way throughout all days and nights. As the instrumented tiles are inertial graphite tiles without active cooling, the TC measurements in between discharges can be used to perform calorimetry study and determine the absorbed energy during a discharge. To do so, the method developed at JET for the energy balance study with TC has been applied for the WEST divertor PFC instrumented with TC [START_REF] Matthews | Energy balance in JET[END_REF]. After 500s the tiles instrumented with 4 TC show uniform temperature from this time the TC measurements are averaged up to 2000s (or less depending to the time between two discharges) and fit with the cooling law:

(2)

Where

is the thermocouple temperature, the temperature of the thermal surrounding and is a constant. The parameters and are estimated from a non-linear least squares algorithm to fit the averaged thermocouple data during the cooling. Then the fitted cooling law is back extrapolated to the end of the heating discharge giving an equivalent uniform temperature allowing to calculate the corresponding absorbed energy using the specific heat of the PFC function of the tile temperature. First, the method has been validated on numerical data showing moderate errors of 5% and up to 10% when small time slice (about 200s for the highest repetition rate at WEST) is considered for the analysis. Then the method has been applied on the 228 discharges previously analysed. The absorbed energy from the cooling phase has been compared to the absorbed energy a) b)

determined from the inversion of the measurements during the discharge. The comparison has shown a good agreement between the two estimated energies with a discrepancy from 4 to 15% depending on the time slice available for the cooling phase study. Then the procedure has been applied to the whole WEST database for discharges with at least 4 MJ of injected power, representing 1272 discharges over the campaigns C2, C3 and C4. Thanks to the 1.5 mm gap between the inner and outer PFCs the energy estimated by this method will only take into account the energy deposited on each side of the divertor. But the outer PFC is partially shadowed by the baffle intercepting the radiated power and a part of the SOL heat load depending on the distance between the last closed magnetics surface and the baffle (see Fig 1 a)). The last feature from the E inner evolution is the discharges outlined with the elliptical black dashed line. Some discharges with low radiated fraction are related to have been performed soon after a boronization and other exhibit strong MHD activity with crashes on the lower divertor inducing higher deposited energy. Finally, some discharges have a magnetic configuration with Rext = 2.93 m and a low X-point height inducing that the outer strike point is close to the gap and a part of the power of the outer leg is interacting with the inner side.

Outer/Inner Asymmetries

For both LSN and USN plasmas performed so far, WEST operates with forward toroidal field direction as in ITER ( drift direction towards the lower divertor). In this configuration the outer-inner heat load a) b)

distribution is expected to be clearly asymmetric with higher heat load on the outer side [START_REF] Pitts | Edge and divertor physics with reversed toroidal field in JET[END_REF][START_REF] Maurizio | Divertor power load studies for attached L-mode Single-Null plasmas in TCV[END_REF]. This asymmetry can be expressed in terms of absorbed energy by the PFCs or heat fluxes (deposited on the PFC or parallel considering the optical projection assumption). Fig 8 a) compares the outer and inner peak parallel heat flux obtained from the projection of the deposited heat flux estimated with embedded measurement with the incident angle, varying from 2.2 to 4.2°, for the 228 discharges of the inversion database. Fig 8 a) shows an important asymmetry with outer heat flux 3 times higher than the inner leading to a ratio 3/4 and 1/4 for the heat load distribution for the outer and inner sides, respectively. As seen in the previous section this asymmetry is equivalent over the campaigns independently of the increase of the heat load reaching the divertor. No clear dependency has been found on this database with the edge safety factor q 95 , the density or the injected power, but the database is mainly composed by deuterium plasmas at 500 kA and helium plasmas at 300 kA with central density in the range of 3 -4.10 19 m -3 . This asymmetry is 15% higher when we consider the deposited heat flux corresponding to the 15% higher incident angle on the outer side. ) compares the absorbed energies on the outer and inner side using the cooling phase method [START_REF] Matthews | Energy balance in JET[END_REF] to increase the database to 1272 discharges. Three slopes emerge corresponding mainly to the different magnetic configurations with different distance between the baffle and the last closed magnetic surface. The 2/3 slope corresponds to the USN plasmas where only the radiated and neutral loads are deposited on the PFCs. One can note the 2/3 slope is different to the surface ratio S outer /S inner of the PFCs which is about 0.9, this difference is explained by the baffle shadowing a part of the radiated and neutral loads as a part of the outer PFC is under the baffle. The two other slopes correspond to LSN plasmas performed with different radial location of the plasma, the 1.5 slope corresponds to the plasmas performed at R ext =3m and the slope 1.9 to the plasma performed at R ext =2.93m. The energy asymmetry is also constant over the campaigns with equivalent slope for C3 and C4 showing no strong variation of the heat load asymmetry.

FIG. 8. a) Outer versus inner peak parallel heat flux for C4 (red), C3 (blue) and C2 (black) for deuterium (+) and helium (o) discharges. b) Outer versus inner absorbed energy C4 (red), C3 (blue) and C2 (black) for deuterium (+) and helium (o) discharges (based on TC measurements).

CONCLUSION

The discharge database of the first crosscheck analysis between IR and FBG heat flux estimation [START_REF] Courtois | Full coverage infrared thermography diagnostic for WEST machine protection[END_REF] has been extended from 114 discharges to 165 whilst three additional diagnostics has been introduced to the crosscheck analysis. The TC inversions from the 2 tiles instrumented with 4 TCs (Q6A and Q1A) have been added as well as the LP measurements (Q6A) for 63 discharges corresponding to the last part of the C4 campaign. This database includes attached discharges in L-mode, in Lower Single Null (LSN) plasma configuration with heating powers ranging from 1 to 8 MW (with up to 4.8 MW of lower hybrid current drive and up to 3.1 MW of ion cyclotron resonance heating) with magnetic field B T from 3.5 to 3.7 T and plasma current I p from 300 to 700 kA (corresponding to edge safety factor q 95 from 7.8 to 3.2 respectively). The first observation is the good agreement of the peak heat flux (± 20%) from the IR, the set of 3 embedded sensors and the LPs over a large variety of plasma scenario. This agreement remains during X-point height scan varying the magnetic flux expansion from about 2 to 6 at the target and moved radially the peak heat flux location over 6 cm. However as depicted in [START_REF] Fedorczak | Cross diagnostics measurements of heat load profiles on the lower tungsten divertor of WEST in Lmode experiments[END_REF] discrepancy is observed for the heat flux decay length from the different diagnostics. The addition of the 3 new diagnostics shows 3 groups values, the TC Q6A and LP, installed in neighboring PFC,

a) b)

exhibit equivalent values, the IR (looking at the same tile as TC Q6A ) has the lowest values (-40%) and the FBG and TC Q1A have the highest values (+ 40%). Strikingly the TC inversions performed with equivalent PFC versus ripple modulation (toroidally spaced by 60°) exhibit 40% variation on the values.

Thanks to the availability of the embedded measurements since the WEST start, the heat flux evolution over the campaigns shows clear increase with a factor about 1.7 between the campaign C3 and C4 on both strike point regions. The C2 campaign exhibit also very low heat flux lower than 0.2 MW/m² despite 2.3 MW of LHCD power. These increases cannot be attributed to a SOL width reduction as the heat flux decay length at the target remains equivalent through all the campaigns and scale mainly with the magnetic flux expansion through the variation of the X-point height as expected. The maximum heat flux observed on the outer strike point region is about 6 MW/m² with a total injected power of 4 MW of LHCD power with a radiated fraction in a range of 50%. These results are very encouraging and they exhibit the capability to reach 10 MW/m² with about 7MW of additional power in L-mode plasma. The heat load distribution is clearly asymmetric with a factor 3/4 1/4 distribution for the parallel heat flux higher on the outer region as commonly observed in forward-B divertor configuration.

FIG. 2

 2 FIG. 2. a) Peak heat flux from FBG (red), TC Q6A (blue), TC Q1A (green) and LP (magenta) compared to peak heatl flux from IR for (+) deuterium and (o) helium discharges. b) Strike point location s0 estimated from FBG (red), TC Q6A (blue), TC Q1A (green), LP (magenta) and IR (black) compared to the reconstructed strike point location from NICE for deuterium (+) and helium (o) discharges.

FIG. 3 .

 3 FIG. 3. Heat flux decay length at the targetfrom FBG (red), TC Q1A (green), LP (magenta) and IR (black) compared from TC Q6A for deuterium (+) and helium (o) discharges.

Fig 6 a

 6 Fig 6 a) shows the deposited peak heat flux as function of the divertor power (P div =P tot -P rad ) for the outer and inner side of the WEST divertor and the three consecutive campaigns. The values have been averaged over 1s during the stationary phase of each discharge. An important increase of the deposited peak heat flux versus P div over the campaigns is observed. The increase is about 1.7 between the campaigns C3 and C4 on both side of the divertor and it is higher than the dispersion during a campaign due to the different magnetic configurations performed (mainly X-point height variation leading to a modification of the magnetic flux expansion on the target). The analysed C3 database is equivalent to the C4 database in terms of magnetic configuration, plasma current (mainly 500 kA), density, and LHCD power (up to 4.7 MW during C3 and 4.8 MW for C4). The target heat flux decay length is also equivalent during the two campaigns and roughly linearly depends on the Xpoint height as illustrated in Fig6 b) with only outer shown for 500 kA discharges, excluding a potential reduction of the SOL width over the campaigns to explain the heat flux increase. One can note that the maximal deposited heat flux observed is about 6 MW/m² for discharges with 4 MW of LH power, radiated fraction of 45% and X-point height of 120 mm showing that the 10 MW/m² could be achieved with about 7 MW of additional power in this configuration in L-mode.

Fig 7 a

 7 Fig 7 a) and b) show the absorbed energy for the inner and outer PFCs of the sector Q6A instrumented with 4TCs. For the inner side the campaigns C3 and C4 exhibit two slopes with a factor 0.38 kJ/MJ and 0.57 kJ/MJ, respectively, showing an absorbed energy 1.5 times higher in C4 comparing to C3. This factor is slightly lower than the factor of 1.75 obtained in the Fig6 a), this is due to the fact that the absorbed energy E inner is the sum of the energy from the SOL deposition on the PFC, the radiated energy and the neutral loads. While the deposited heat flux in the Fig6a) is only due to the SOL deposition. TheFig 7 a) shows also the equivalent behaviour of the radiated power during C3 and C4 deduced from the absorbed energy by the lower divertor during Upper Single Null (USN) discharges. The last feature from the E inner evolution is the discharges outlined with the elliptical black dashed line. Some discharges with low radiated fraction are related to have been performed soon after a boronization and other exhibit strong MHD activity with crashes on the lower divertor inducing higher deposited energy. Finally, some discharges have a magnetic configuration with Rext = 2.93 m and a low X-point height inducing that the outer strike point is close to the gap and a part of the power of the outer leg is interacting with the inner side. Fig7 b) shows also clearly the increase of the deposited energy on the outer side between C3 and C4 with a factor of 1.6 or 2.2 depending on the magnetic configuration. These two factors can be explained by the reduction of the SOL falling on the baffle when the R ext is lower due to the increase of the distance between the last closed magnetic surface and the baffle. Once again, the USN discharges show equivalent deposited energy for C3 and C4. Finally, the energy from the C2 campaign show the very low deposited heat load on the divertor during the campaign as already shown in Fig 6a).

FIG. 7 .

 7 Fig 7 a) and b) show the absorbed energy for the inner and outer PFCs of the sector Q6A instrumented with 4TCs. For the inner side the campaigns C3 and C4 exhibit two slopes with a factor 0.38 kJ/MJ and 0.57 kJ/MJ, respectively, showing an absorbed energy 1.5 times higher in C4 comparing to C3. This factor is slightly lower than the factor of 1.75 obtained in the Fig6 a), this is due to the fact that the absorbed energy E inner is the sum of the energy from the SOL deposition on the PFC, the radiated energy and the neutral loads. While the deposited heat flux in the Fig6a) is only due to the SOL deposition. TheFig 7 a) shows also the equivalent behaviour of the radiated power during C3 and C4 deduced from the absorbed energy by the lower divertor during Upper Single Null (USN) discharges. The last feature from the E inner evolution is the discharges outlined with the elliptical black dashed line. Some discharges with low radiated fraction are related to have been performed soon after a boronization and other exhibit strong MHD activity with crashes on the lower divertor inducing higher deposited energy. Finally, some discharges have a magnetic configuration with Rext = 2.93 m and a low X-point height inducing that the outer strike point is close to the gap and a part of the power of the outer leg is interacting with the inner side. Fig7 b) shows also clearly the increase of the deposited energy on the outer side between C3 and C4 with a factor of 1.6 or 2.2 depending on the magnetic configuration. These two factors can be explained by the reduction of the SOL falling on the baffle when the R ext is lower due to the increase of the distance between the last closed magnetic surface and the baffle. Once again, the USN discharges show equivalent deposited energy for C3 and C4. Finally, the energy from the C2 campaign show the very low deposited heat load on the divertor during the campaign as already shown in Fig 6a).

Fig 8 b

  Fig 8 b) compares the absorbed energies on the outer and inner side using the cooling phase method[START_REF] Matthews | Energy balance in JET[END_REF] to increase the database to 1272 discharges. Three slopes emerge corresponding mainly to the different magnetic configurations with different distance between the baffle and the last closed magnetic surface. The 2/3 slope corresponds to the USN plasmas where only the radiated and neutral loads are deposited on the PFCs. One can note the 2/3 slope is different to the surface ratio S outer /S inner of the PFCs which is about 0.9, this difference is explained by the baffle shadowing a part of the radiated and neutral loads as a part of the outer PFC is under the baffle. The two other slopes correspond to LSN plasmas performed with different radial location of the plasma, the 1.5 slope corresponds to the plasmas performed at R ext =3m and the slope 1.9 to the plasma performed at R ext =2.93m. The energy asymmetry is also constant over the campaigns with equivalent slope for C3 and C4 showing no strong variation of the heat load asymmetry.

ACKNOWLEDGEMENTS

This work has been carried out thanks to the support of the A*MIDEX project (n°ANR-11-IDEX-0001-02) funded by the "Investissements d'Avenir" French Government program, managed by the French National Research Agency (ANR). This work has been carried out within the framework of the EUROfusion Consortium and has received funding from the Euratom research and training programme 2014-2018 and 2019-2020 under grant agreement No 633053. The views and opinions expressed herein do not necessarily reflect those of the European Commission.


Giuseppe Daniele

Claudia Lunghi

Angela Dardano

Paola Binda

Giovanni Ceccarini

Ferruccio Santini

Laura Giusti

Annamaria Ciccarone

Rosario Bellini

Carlo Moretto

Maria Concetta Morrone

Stefano Del Prato
email: stefano.delprato@unipi.it

Bariatric surgery restores visual cortical plasticity in nondiabetic subjects with obesity

à la diffusion de documents scientifiques de niveau recherche, publiés ou non, émanant des établissements d'enseignement et de recherche français ou étrangers, des laboratoires publics ou privés.

Introduction

The worldwide dramatic increase of the prevalence of obesity is generating major health concerns because of the severe comorbidities accompanying this condition [START_REF] Hruby | The Epidemiology of Obesity: A Big Picture[END_REF]. Among them, cognitive dysfunction and neurodegenerative diseases have been recently drawn growing attention [START_REF] Geijselaers | Glucose regulation, cognition, and brain MRI in type 2 diabetes: a systematic review[END_REF]. The negative impact of obesity on the central nervous system is supported by studies of magnetic resonance imaging (MRI) that have identified lacunar infarcts, white matter hyperintensities, and brain atrophy [START_REF] Karlsson | Obesity is associated with white matter atrophy: a combined diffusion tensor imaging and voxel-based morphometric study[END_REF]. These anatomic alterations are suggested to be a consequence of the metabolic disturbances, insulin resistance, abnormalities in the signaling of gut hormones and adipokines on the brain [START_REF] Balistreri | The role of adipose tissue and adipokines in obesity-related inflammatory diseases[END_REF]. Peripheral insulin resistance is a common feature in obesity and recent studies have suggested that impaired insulin action may occur in the brain as well [START_REF] Heni | Impaired insulin action in the human brain: causes and metabolic consequences[END_REF]. Insulin receptors are widespread in the hippocampal and cortical brain structures, and brain insulin resistance may contribute to the cognitive impairment and neurodegeneration observed in obesity [START_REF] Sripetchwandee | Links Between Obesity-Induced Brain Insulin Resistance, Brain Mitochondrial Dysfunction, and Dementia[END_REF]. Insulin can regulate neuronal survival and metabolism through modulation of gamma-aminobutyric acid (GABA) and glutamate receptors in the hippocampus and motor cortex, structures involved in learning and memory functions [START_REF] Stagg | The role of GABA in human motor learning[END_REF].

Weight loss, as it can be obtained with bariatric surgery, has been shown to exert beneficial effects on both brain structure and function [START_REF] Tuulari | Bariatric surgery induces white and grey matter density recovery in the morbidly obese[END_REF]. Body weight reduction has been associated with enhanced activity in neural circuits in areas involved in executive control, such as the dorsolateral prefrontal cortex [START_REF] Goldman | Executive control circuitry differentiates degree of success in weight loss following gastric-bypass surgery[END_REF], the superior frontal gyri and the posterior cingulate cortex [START_REF] Ness | Pre-surgical cortical activation to food pictures is associated with weight loss following bariatric surgery[END_REF]. Bariatric surgery does not simply lead to significant body weight reduction, but it is also associated with changes in incretins and adipokines [START_REF] Karra | Mechanisms Facilitating Weight Loss and Resolution of Type 2 Diabetes Following Bariatric Surgery[END_REF]. They are key elements of the gut-brain axis, a multidirectional communication system linking the enteric nervous system and the central nervous system via endocrine signals, such as Glucagon-Like Peptide 1 (GLP-1), Glucose-dependent insulinotropic polypeptide (GIP) and Vasoactive Intestinal Peptide (VIP), and the activation of the enteric nervous system and vagal signaling [START_REF] Carabotti | The gut-brain axis: interactions between enteric microbiota, central and enteric nervous systems[END_REF]. In keeping with an effect of GLP-1 on brain function, we have recently shown that exenatide administration can modulate cerebral glucose metabolic rate in several cortical and sub-cortical areas [START_REF] Daniele | Exenatide Regulates Cerebral Glucose Metabolism in Brain Areas Associated With Glucose Homeostasis and Reward System[END_REF] along with modulation of visual responses to food and non-food images in non-diabetic subjects with obesity undergoing functional MRI (fMRI) [START_REF] Binda | Exenatide modulates visual cortex responses[END_REF]. White adipose tissue, the body's energy depot, is also connected with the central nervous system through leptin signaling. Leptin receptors are widespread in the brain (e.g., throughout the cortex and the hippocampus) and their activation is implicated in memory processes [START_REF] Farr | Leptin and the brain: influences on brain development, cognitive functioning and psychiatric disorders[END_REF]. Leptin has also been shown to exert neuroprotective functions by inhibiting apoptosis and improving cell survival through regulation of apoptotic enzymes and activation of neurotrophic factors such as the brain-derived neurotrophic factor (BDNF) [START_REF] Teryaeva | Leptin as a neuroprotector and a central nervous system functional stability factor[END_REF]. However, it is still unknown whether bariatric surgery can impact on one of the fundamental properties of the brain: the ability to modify its connection or rewire in response to experience, a phenomenon known as neural plasticity [START_REF] Castaldi | Neuroplasticity in adult human visual cortex[END_REF].

We have recently reported (18) that a particular form of neural plasticity (visual homeostatic plasticity of ocular dominance) is severely blunted in subjects with BMI >40 Kg/m 2 . In normal weight adult subjects, a short period of monocular deprivation transiently shifts ocular dominance in favor of the deprived eye both at the perceptual [START_REF] Lunghi | Brief periods of monocular deprivation disrupt ocular balance in human adult visual cortex[END_REF][START_REF] Lunghi | Long-term effects of monocular deprivation revealed with binocular rivalry gratings modulated in luminance and in color[END_REF][START_REF] Lunghi | A cycling lane for brain rewiring[END_REF][START_REF] Zhou | Short-term monocular deprivation strengthens the patched eye's contribution to binocular combination[END_REF] and at the neural level [START_REF] Lunghi | Short-term monocular deprivation alters early components of visual evoked potentials[END_REF][START_REF] Lunghi | Short-term monocular deprivation alters GABA in the adult human visual cortex[END_REF] reflecting a compensatory regulation of ocular dominance in response to deprivation consistent with homeostatic plasticity [START_REF] Turrigiano | Homeostatic synaptic plasticity: local and global mechanisms for stabilizing neuronal function[END_REF] We have shown that a strong correlation exists between body mass index (BMI) and this form of visual plasticity [START_REF] Lunghi | Altered Visual Plasticity in Morbidly Obese Subjects[END_REF]: the effect of short-term monocular deprivation declines with increasing BMI and is completely absent in subjects with morbidly obesity. Here, we investigate the impact of bariatric surgery on early sensory plasticity and the role of main circulating gut hormones and adipokines in patients with obesity by measuring the effect of short-term monocular deprivation on ocular dominance before and after bariatric surgery.

Subjects and Methods

Participants and Recruitment

Subjects with obesity candidate for Roux-en-Y gastric bypass (RYGB) were screened for enrollment at the Obesity Centre of the Azienda-Ospedaliero Universitaria Pisana, Pisa, Italy. Subjects with age 18-60 years, BMI >35 kg/m 2 , HbA1c <6.5% and eGFR >60 ml/min/1.73m 2 were considered eligible. Individuals with the following conditions were excluded from the study:

• psychiatric disorders • mental retardation • severe cognitive impairment • neurodegenerative diseases • epilepsy • steroid treatment
• traumatic brain injury over the preceding six months

• liver function enzymes higher than twice the upper limit

• heart failure (NYHA III-IV)
• overt Type 2 and Type 1 diabetes

• pregnant or breastfeeding women

• history or current evidence of any condition, therapy, laboratory abnormality or other circumstances which, in the opinion of the investigators, were deemed to expose the patient to an unacceptable risk or could interfere with trial procedures

The study has been registered at ClinicalTrials.gov (NCT03414333) and the study protocol was approved by the local Ethics Committee and conducted in accordance with the Declaration of Helsinki (2008). Each participant provided written informed consent before entering the study.

A total of 15 subjects (Age: 42.3 ± 9.8 years, BMI: 46.1±4.9 Kg/m 2 ) were included in the study. All had normal or corrected to normal visual acuity and no visual deficits. Two participants chose not to complete the oral glucose level test; for these participants, only the neural plasticity results are available.

Study Design

At baseline, participants underwent two visits (V1 and V2) at 5-14-day interval. In V1 brain plasticity of the visual cortex was measured in fasting condition through a psychophysical technique based on the binocular rivalry evaluation before and after 2-hr monocular deprivation (MD) according to the standard protocol [START_REF] Lunghi | Brief periods of monocular deprivation disrupt ocular balance in human adult visual cortex[END_REF].

On V2, participants were admitted to our Research Unit in the morning after an overnight fast to undergo an oral glucose load (75 g OGTT). Blood samples were obtained at -120, 0, 15, 30, 45, 60, 75, 90, 105 and 120 min for determination of plasma substrate and hormone concentrations. All participants underwent RYGB within 2 weeks upon completion of baseline evaluation. Brain plasticity evaluation was then repeated 1 (V3), 3 (V4) and 6 months (V5) after surgical intervention whereas the OGTT was repeated only after 6 months (V6).

Visual Plasticity Assessment

Experimental procedures took place in a dark, quiet room after an overnight fast. Visual stimuli were generated by a VSG 2/5 stimulus generator (CRS, Cambridge Research Systems) housed in a laptop (Dell, Round Rock, TX, USA) controlled by Matlab programs (MathWorks, Natick, MA, USA). The stimuli consisted in 2 sinusoidal gratings, oriented either 45° clockwise or counterclockwise (size: 2σ = 2°, spatial frequency: 2 cpd), presented on a uniform background (luminance: 9cd/m2 CIE x=.311, y=.341) with a central black fixation point and a common squared frame to facilitate dichoptic fusion.

Visual stimuli were displayed on a 17-inch CRT monitor (FD Trinitron CRT multiscan G200) monitor, driven at a resolution of 1024x600 pixels, with a refresh rate of 120 Hz. Observers viewed the display at a distance of 57 cm through CRS Ferro-Magnetic shutter goggles that occluded alternately one of the two eyes each frame. Responses were recorded through the computer keyboard.

For binocular rivalry assessment, experimental blocks of 125 seconds were used. After an acoustic signal (beep), the binocular rivalry stimuli appeared. Subjects reported their perception (clockwise, counterclockwise or mixed) by continuously pressing with the right hand one of three keys (left, right and down arrows) of the computer keyboard. At each experimental block, the orientation associated to each eye was randomly varied so that neither subject nor the investigators knew which stimulus was associated with which eye until the end of the session. Two binocular rivalry experimental blocks were acquired before monocular deprivation and four blocks after eye-patch removal.

Monocular deprivation was performed using an eye-patch of a translucent plastic material that allowed light to reach the retina (luminance attenuation 0.07 logUnits) but completely prevented pattern vision, as assessed by the Fourier transform of a natural world image seen through the eye-patch. The dominant eye (the eye showing longer perceptual predominance in binocular rivalry) was patched for 120-min.

During the 2h of monocular occlusion patients were free to perform normal quiet activities (walking, reading, using a computer).

Laboratory assays

Plasma glucose concentration was measured using the glucose oxidase method (Beckman, Fullerton, CA, USA). Samples for GIP and GLP-1 were drawn in tube containing protease inhibitors, specifically optimized for stabilization of metabolic markers (BD P800, BD Biosciences, USA). Total GLP-1, active GLP-1 and GIP were measured by ELISA (EDM Millipore, St. Charles, Missouri, USA). Insulin and C-peptide were assessed by radioimmunoassay (IRMA, PANTEC srl Turin, Italy). VIP was measured using an Enzyme Immunoassay (RayBiotech, Norcross, GA, USA). Brain-derived neurotrophic factor (BNDF) and leptin were measured using a Sandwich Enzyme-Linked Immunosorbent Assay (RayBiotech, Norcross, GA, USA).

Insulin sensitivity was calculated as ISIcomp according to the formula: 10.000/sqrt [fasting plasma glucose (mg/dl) x fasting plasma insulin (μUI/ml) x glucose at 120 min (mg/dl) x insulin at 120 min (μUI/ml)] The oral disposition index was calculated as ISSI-2 equal to ISIcomp x AUCins/AUCgluc as previously described [START_REF] Retnakaran | Evaluation of proposed oral disposition index measures in relation to the actual disposition index[END_REF]. The area under the curve of hormones and plasma glucose were computed using the trapezoidal rule.

Analyses of visual plasticity

Perceptual reports during binocular rivalry were analyzed using Matlab. We computed the total time (T) during which the observer reported each of the three percepts: the oriented grating presented to either eye (deprived and non-deprived) and a mixture of the two (mixed percepts). To quantify ocular dominance, we defined an index (Ocular Dominance Index, ODI) ranging from 0 (complete dominance of the non-deprived eye) to 1 (complete dominance of the deprived eye), given by: ODI = T_DepEye/(T_DepEye+T_NonDep Eye) Eq.1

The Ocular Dominance Index does not consider the mixed percepts that do not change after deprivation. The effect of monocular deprivation (Neural Plasticity index, NP) was computed as the difference between the ODI measured after and before the 2h of monocular deprivation.

Statistical Analysis

Statistical analyses were performed using SPSS-2.0 (Statistical Package for Social Sciences, Chicago, IL, USA) and Matlab software. Values are presented as mean±SEM or as median (interquartile range) for variables with a skewed distribution; categorical data are expressed as percentages. Variables that were not normally distributed were log-transformed before analysis. Treatment-induced changes were examined by Wilcoxon's signed rank test and a p<0.05 (two-tailed analysis) was considered to be statistically significant.

Correlations were assessed by using a robust correlation method [START_REF] Pernet | Robust correlation analyses: false positive and power validation using a new open source matlab toolbox[END_REF], the skipped Pearson's correlation coefficient (r) and statistical significance determined by a bootstrap t-test and p-values were corrected for multiple comparisons using the Bonferroni method.

To assess the effect of bariatric surgery on visual plasticity, the change in the visual plasticity index (NP) measured before and after surgery was tested with a linear mixed model analysis performed using the fitlme function in Matlab in which time (baseline, 1 month, 3 months and 6 months after surgery) was used as fixed effect with random slope and intercept, with the model: "y ~ time + (1 + time | ID).

Post-hoc tests between the visual plasticity index measured before and after surgery were performed using a Wilcoxon signed rank test, p-values were corrected for multiple comparisons using the Bonferroni method. To determine whether, before surgery, participants with obesity showed a response to monocular deprivation, the plasticity index measured at baseline was compared against the value 0 using a Wilcoxon signed rank test.

Results

Participants and Metabolic Parameters

15 subjects with severe obesity completed the neural plasticity assessment, 13 of which also completed the metabolic assessment. Two patients withdrew the consent to repeat post RYGB assessment. The characteristics of the 13 participants who completed the whole study are summarized in Table 1.

Participants were relatively young with a baseline BMI of 46.1±4.9 Kg/m 2 . Four subjects had impaired fasting glucose and all the remaining had normal glucose tolerance and HbA1c levels (Table 1). No patient was on any medication known to affect glucose metabolism and brain function.

RYGB was followed by a significant reduction in body weight (-30.5±0.2 Kg) with a BMI at month 6 of 35.3±5.0 Kg/m 2 (p=0.001 vs. baseline). Figure 1 shows the plasma concentrations of glucose, insulin and gut hormones during OGTT. Overall, 6 months after RYGB, plasma glucose and insulin levels showed an earlier peak but lower 2-hour concentration as compared to baseline. Accordingly, ISIcomp (from 2.4±0.5 to 8.2±1.9; p=0.004) and the Disposition Index (from 1.1±0.2 to 2.9±1.1 ISSI2; p=0.02) improved in a significant manner. Total and active GLP1 release in response to glucose ingestion increased after bariatric surgery, while no changes occurred with GIP, VIP, and BDNF. Fasting plasma leptin concentration was significantly lower after RYGB as compared to baseline (Table 1).

Effect of Bariatric Surgery on Visual Cortical Plasticity

Consistently with our previous observations [START_REF] Lunghi | Altered Visual Plasticity in Morbidly Obese Subjects[END_REF], at baseline the neural plasticity index obtained by monocular deprivation was 0.03±0.03, p = 0.45, implying impaired visual cortical plasticity [START_REF] Lunghi | Long-term effects of monocular deprivation revealed with binocular rivalry gratings modulated in luminance and in color[END_REF].

Following RYGB, a progressive increase of the neural plasticity index (Linear Mixed Model Analysis: t(57)=3.35, p=0.0014) was observed, with ocular dominance shifting in favour of the deprived eye following deprivation, consistently with previous studies on normal-weight subjects [START_REF] Lunghi | Brief periods of monocular deprivation disrupt ocular balance in human adult visual cortex[END_REF][START_REF] Lunghi | Long-term effects of monocular deprivation revealed with binocular rivalry gratings modulated in luminance and in color[END_REF][START_REF] Lunghi | A cycling lane for brain rewiring[END_REF]. This increase was already statistically significant 3 months after surgery (p=0.008) (Figure 2A-B) when an average 25% weight loss was achieved (BMI from 46.1±4.9 to 35.3±5.0; p<0.01). Thereafter, the improvement of visual plasticity was constant at 6 months after surgery (p=0.0036).

Visual Cortical Plasticity and Glucose Tolerance

Baseline BMI was not correlated with plasticity index (Figure 2C). An inverse correlation was apparent between fasting plasma glucose and the plasticity index (r= -0.71; p=0.02) (Figure 2D) but not with plasma glucose and insulin concentrations during OGTT before surgery. The plasticity index strongly correlated also with the Disposition Index (and r=0.75, p=0.01; Figure 2E). No correlation was found between change of BMI, of fasting plasma glucose, of HbA1c and change of plasticity index after surgery.

Brain Plasticity, Gut Peptides, Leptin and BDNF

At baseline plasticity index showed a trend for a negative correlation with total and active GLP1 as well as with GIP, VIP, leptin and BDNF (data not shown). After surgery we found a positive correlation between changes of incremental AUC active GLP-1 and change of plasticity index (r=0.70, p=0.008; Figure 3A). Moreover, six months after surgery leptin was inversely and significantly correlated with plasticity index (r= -0.63; p=0.02)(Figure 3B). GIP, VIP and BDNF did not correlate with the plasticity index (data not shown).

A multiple linear regression analysis was performed using the change in the different hormones tested as predictors of the change in NP observed 6 months after surgery. The analysis revealed that only the change in active GLP1 was a significant predictor of the plasticity effect (t=2.6, p=0.04), while the other hormones had no significant predictive value (all ps>0.25).

Discussion

This study explored the impact of weight loss obtained by bariatric surgery on brain plasticity and its relationship with circulating gut peptides, leptin, and BDNF. To the best of our knowledge this is the first study exploring visual cortex plasticity [START_REF] Castaldi | Neuroplasticity in adult human visual cortex[END_REF] during massive weight loss following RYGB and contemporary changes in gut hormones and glucose handling in non-diabetic subjects. The results of our study confirm our earlier finding that morbid obesity is associated with a marked reduction of brain plasticity [START_REF] Lunghi | Altered Visual Plasticity in Morbidly Obese Subjects[END_REF] and reveal for the first time, that this abnormal accommodation of the brain to external stimuli can be progressively reversed by body weight reduction. In fact, the plasticity index improved 1 month after surgery to approach values commonly found in healthy subjects after 6 months with a 200% increase above the plasticity levels assessed before surgery. The response to monocular deprivation is thought to reflect transient changes in neuronal circuitry in primary visual cortex providing a marker of neural plasticity: changes in visual cortex activity consistent with the deprived eye dominance boost observed at the perceptual level have been observed with different techniques [START_REF] Lunghi | Short-term monocular deprivation alters early components of visual evoked potentials[END_REF][START_REF] Lunghi | Short-term monocular deprivation alters GABA in the adult human visual cortex[END_REF][START_REF] Binda | Response to short-term deprivation of the human adult visual cortex measured with 7T BOLD[END_REF][START_REF] Zhou | Short-term monocular patching boosts the patched eye's response in visual cortex[END_REF]. Importantly, it has been shown that the effect of monocular deprivation is also accompanied by a decrease of gamma-aminobutyric acid (GABA) concentration in the primary visual cortex of adult humans [START_REF] Lunghi | Short-term monocular deprivation alters GABA in the adult human visual cortex[END_REF]. GABA is the main inhibitory neurotransmitter in mammalian brain and has been implicated in the control of excitability, information processing, synchronization of neuronal activity and, ultimately, neuroplasticity [START_REF] Owens | Is there more to GABA than synaptic inhibition?[END_REF]. GABA is also involved in eating behaviour as suggested by experiments in rodents using GABA receptor agonists and antagonists [START_REF] Avena | Effects of baclofen and naltrexone, alone and in combination, on the consumption of palatable food in male rats[END_REF]. In the animal model, high-fat diet was associated with decreased GABA concentration in the frontal cortex and hippocampus [START_REF] Sandoval-Salazar | A high-fat diet decreases GABA concentration in the frontal cortex and hippocampus of rats[END_REF]. We therefore speculate that changes occurring with body weight reduction can interfere with the GABAergic modulation in the visual cortex and, possibly, in other areas of the brain.

The mechanisms responsible for this improvement are not completely clear. However, it is of interest that a number of changes occurring after bariatric surgery showed a relationship with changes in the plasticity index. Thus, plasticity was strongly associated to the metabolic status as indicated by the correlation with plasma glucose and beta-cell function (Disposition Index). Therefore, the worse the metabolic status, the worse the neuronal plasticity although we cannot exclude that similar association may occur with other conditions associated with insulin resistance. In all case, this association is not surprising since it has been shown that insulin signaling can enhance synaptic plasticity by increasing synapsis density in brain regions involved in the processing of visual inputs [START_REF] Chiu | Insulin receptor signaling regulates synapse number, dendritic plasticity, and circuit function in vivo[END_REF]. The well-known peripheral insulin resistance characterizing obesity may well reflect insulin resistance in the central nervous system as previously suggested [START_REF] Kullmann | Brain Insulin Resistance at the Crossroads of Metabolic and Cognitive Disorders in Humans[END_REF]. Therefore, it is tempting to postulate that brain insulin resistance may contribute to impaired activation of synaptic plasticity in the visual cortex of our subjects with obesity. In keeping with this hypothesis, the improvement of insulin sensitivity brought up by body weight reduction was strongly associated with the improvement of the brain plasticity index. These findings also are in keeping with previous studies demonstrating a partial reversibility of impaired insulin-stimulated hypothalamic response [START_REF] Matsuda | Altered hypothalamic function in response to glucose ingestion in obese humans[END_REF] after massive reduction of body weight in subjects with obesity [START_REF] Van De Sande-Lee | Partial reversibility of hypothalamic dysfunction and changes in brain activity after body mass reduction in obese subjects[END_REF]. The improvement of the plasticity index may be supported not only by amelioration of insulin action but also by changes of other hormones known to exert an effect in the brain. Bariatric surgery is associated with increased GLP-1 response to meal ingestion [START_REF] Salehi | Gastric Bypass Surgery Enhances Glucagon-Like Peptide 1-Stimulated Postprandial Insulin Secretion in Humans[END_REF], a finding confirmed in our subjects as well in response to oral glucose load. Much literature supports the central effect of GLP1, so it was not surprising to find an association between changes in GLP-1 levels ensuing RYGB and concomitant changes in the plasticity index. These results can be taken as an additional support to the proposed neuroprotective and synaptic plasticity promoting effects of GLP-1 [START_REF] Mcclean | Glucagon-like peptide-1 analogues enhance synaptic plasticity in the brain: a link between diabetes and Alzheimer's disease[END_REF]. This relationship is also of interest because of the potential implication of the effect of this hormone in the modulation of satiety and appetite. We have previously shown that the administration of exenatide, a GLP-1 analogue, to subjects with obesity can modify brain responses to food images as monitored by fMRI [START_REF] Binda | Exenatide modulates visual cortex responses[END_REF]. GLP-1 receptors are expressed in many areas of the human brain [START_REF] Alvarez | The Expression of GLP-1 Receptor mRNA and Protein Allows the Effect of GLP-1 on Glucose Metabolism in the Human Hypothalamus and Brainstem[END_REF] where they can participate in high brain functions related to food responses. An effect of GIP is not apparent in our study. Similarly, no association between VIP levels and plasticity index was found. Finally, we have also explored whether signals that are generated by the adipose tissue, the main energy depot in the body, could be linked to changes in brain plasticity that occurred with body weight reduction (i.e. loss of fat mass). To this aim we have measured baseline concentration of leptin, which dropped dramatically after surgery. Leptin is a cytokine and a satiety hormone involved in appetite regulation and energy expenditure modulation. It can cross the blood brain barrier and bind to presynaptic GABAergic neurons to produce its effects and its concentrations are typically increased in human obesity [START_REF] Lehr | Adipokines: a treasure trove for the discovery of biomarkers for metabolic disorders[END_REF]. We now report a strong and inverse correlation between reduction in leptin concentration after RYGB and the increase in the plasticity index pointing to another pathway of signal integration between the central nervous system (here probed by the plasticity index) and the energy balance through signals generated in the gut (GLP-1) and adipocytes (leptin). BDNF is widely expressed in the central nervous system, gut and other tissues but was not affected by body weight reduction and showed no association with changes of the plasticity index.

The main limitations of our work are the size of the study population and the lack of a control group.

However, this was an exploratory study and our results set the basis for future investigation on the relationship between brain plasticity and disturbances of energy metabolism. Similarly, we are totally aware that correlations between metabolic parameters and plasticity index change after surgery do not imply causality, yet they are hypothesis generating and as such our findings can help designing future studies to unravel the complexity of the brain-gut axis.

In summary, we have shown that severe impairment of visual brain plasticity occurring in subjects with morbidly obesity can be recovered by reduction in body weight. These improvements may be mediated by amelioration of (brain) insulin sensitivity, increased availability of GLP-1 and strong reduction of leptin resistance, thus supporting the fine integration between the CNS and the periphery.

Figures and Table Legend

Figure 1 -

 1 Figure 1-Plasma concentrations of gut hormones during OGTT. A: Plasma Glucose, B: Plasma Insulin, C: Total GLP-1, D: Active GLP-1, E: GIP, F: VIP. White circle: before RYGB, Black circle: after RYGB. *:p<0.05.

Figure 2 -

 2 Figure 2-A: Effect of monocular deprivation (plasticity index) at baseline and 1, 3 and 6 months after surgery. Error bars represent 1±SEM B: Scatter plot reporting the effect of monocular deprivation measured for each participant before and at two different time points after surgery: 1 month (light grey symbols) and 6 months (dark grey symbols). The dashed lines on the 0 value indicate the absence of plasticity (no effect of monocular deprivation). C: Correlations before surgery of Neural Plasticity Index and baseline BMI D: Correlations before surgery of Neural Plasticity Index and baseline fasting plasma glucose E: Correlations before surgery of Neural Plasticity Index Baseline and Disposition Index. All robust correlations are computed by a skipped Pearson correlation (27).

Figure 3 -

 3 Figure 3-A: Correlation between 6 months post-pre surgery change in incremental AUC active GLP-1 (iAUC active GLP-1 ) and plasticity index. B: Correlation between leptin and plasticity index 6 months after surgery. All robust correlations are computed by a skipped Pearson correlation (27).

  0.15, n.s. r = -0.71, p = 0.02 C B Fasting Plasma Glucose (mg/dl) r = 0.75, p = 0.01 /dl)

Table 1 -

 1 Anthropometric and metabolic characteristics of study participants at baseline and 6 months after RYGB.

	520	Table 1

Acknowledgments.

Funding support. This work was supported by grant from the University of Pisa (Project Code: PRA_2016_44), by ERC (H2020) Pupiltraits and PRIN MIUR 2017.


Armelle Decaulne

Fabienne Joliet

Laine Chanteloup

Thora Herrmann

Najat Bhiry

Jean Der Gazerian

Orsane Rousset

Taku-

teaching and research institutions in France or abroad, or from public or private research centers.

TAKUJUQ -Contribu�on of Arts for communica�ng Science

1 CNRS, LETG-Nantes, France -2 Agrocampus ouest, Ins�tut Agro, Angers, France -3 Université Lausanne, Switzerland -4 Helmholtz Centre for Environmental Research-UFZ and German Centre for Integra�ve Biodiversity Research (iDiv)

Halle-Jena-Leipzig, Leipzig, Germany -5 Laval University and Centre for Nordic studies, Québec, Canada -6 Aix-Marseille Université, Marseille, France -7 Université de Bretagne Occidentale, Brest, France Armelle Decaulne 1* , Fabienne Joliet 2 , Laine Chanteloup 3 , Thora Herrmann 4 , Najat Bhiry 5 , Jean Der Gazerian 6 , Orsane Rousset 7

RATIONALE

Geography, either social, cultural or physical, is a spa�al science; maps are therefore massively used to represent geographical results. However, maps and other scien�fic results can be complicated to read and understand as the outcomes are not easily accessible to a public beyond academia.

Within the TAKUJUQ project (He/she sees), we explore alterna�ve techniques that involve Arts for scien�fic media�on. The aim is to enhance the understanding of scien�fic results and the appropria�on of the results by those living in areas where research is taking place. OHMi NUNAVIK works in and with Indigenous commu-ni�es; we wish that the results of our research are understood by all genera�ons of Inuit/Cree who welcome the presence of researchers. The examples presented here are based on MOVE (slope mouvement) and NUNA (our land) projects. Working together with ar�sts and scien�fic mediators, we a�empt to share scien�fic facts through art and producing simplified (not simplis�c) models.

ONE LAND, SEVERAL ARCTIC REALITIES

The emic perspec�ve of young Inuit and Cree pupils is expressed in collec�vely realized short films, which showcase a lively and contemporary portrait of the ways of life connected to the land in four northern villages, sustaining thereby Inuit and Cree iconographic sovereignty. Ar�s�c and media techniques -video, drawing and interac�ve maps -allow for the encounter of different images of the Arc�c.

Interactive Map, which gives access to videos realized in the Nuna project allowing to experience by everyone the different cultural views of Nunavik (Der Gazerian et al., 2021).

Drawings illustrating the different phases of the video-making process during a workshop in Nunavik's school (watercolor pencil painting done by Orsane Rousset, 2021). This artistic mediation helps to motivate new schools to participate in workshops, which in turn enables researchers to enrich the data on local environmental perceptions.

ALTERNATIVE WAYS FOR COMMUNICATING SCIENCE

Scien�fic media�on materials are essen�al for the transmission of knowledge, in order to foster intercultural dialogues and to mutually enrich the combined results of academic research and Indigenous knowledge. A be�er communica�on of scien�fic results is key to sustaining meaningful research with applied results in Indigenous communi�es. Diachronic maps of the building of Kangiqsualujjuaq, together with the location of known snow avalanches; the 1999 event caused the death of nine and injured 25 (Decaulne et al., 2021). This is a formal academic presentation, one way of highlighting the obtained results of the research.

A journey through space and time, illustrated by the moving character; one notices the superposition between the landscape and its topographic representation. During the first decades, the life of the village is turned towards the cove; at the end of the 1990s, it is the avalanche slope that is represented as well as the building/people at stake located at its foot; then the most recent years show rather an expansion towards the valley (watercolor-colored pencil painting based on the authors' fieldwork, done by Orsane Rousset, 2021).

VILLAGE EXPANSION UNDER SNOW-AVALANCHE HAZARD

Many of the villages in Nunavik are built near slopes on which snow avalanches are likely to occur, yet this phenomenon has only been studied in recent years and deserves much more a�en�on.

In Kangiqsualujjuaq, where a drama�c avalanche occurred in 1999, its spa�al influence on the extension of the village is clearly visible: first built by the cove, the village then gathered by the slope; a�er the 1999 snow avalanche, the village development occupied the valley bo�om.

The consequences of the snow avalanche were so striking that today few people talk about this event, and that for Nunavimiut an avalanche can only be devasta�ng.