Pierre-Jean Bénard
email: pierre-jean.benard@math.u-bordeaux.fr

Yann Traonmilin

Jean-François Aujol

Projected Block Coordinate Descent for sparse spike estimation

Keywords: spike super-resolution, non-convex optimization, over-parametrization, block-coordinate descent

We consider the problem of recovering off-the-grid spikes from linear measurements. The state of the art Over-Parametrized Continuous Orthogonal Matching Pursuit (OP-COMP) with Projected Gradient Descent (PGD) successfully recovers those signals. In most cases, the main computational cost lies in a unique global descent on all parameters (positions and amplitudes). In this paper, we propose to improve this algorithm by accelerating this descent step. We introduce a new algorithm, based on Block Coordinate Descent, that takes advantages of the sparse structure of the problem. Based on qualitative theoretical results, this algorithm shows improvement in calculation times in realistic synthetic microscopy experiments.

I. INTRODUCTION

The off-the-grid super-resolution problem consists in recovering spikes from linear measurements in a continuous setting. It has applications in many fields. Among these applications, one can cite Single Molecule Localization Microscopy (SMLM) or Magnetic Resonance Imaging (MRI). In these fields, the signals to recover display properties of sparsity that can be exploited for a faster recovery.

Let x 0 be an off-the-grid sparse signal over R d . Such signals can be modeled as a sum of K Dirac measures:

x 0 = K i=1 a i δ ti (1)
where a = (a 1 , . . . , a K ) ∈ R K are the amplitudes and t = (t 1 , . . . , t K ) ∈ R K×d are the positions of the spikes. We observe the signal through a linear operator A from the space M of finite signed measures over R d to C m with m the number of measurements. The result of this observation is y ∈ C m which can be written as y = Ax 0 . Note that we consider the noiseless case in this article for the sake of clarity.

A way to recover the true signal x 0 from its observation is to find the minimizer of a non-convex least-square problem:

x * ∈ arg min x∈ΣK,ǫ Ax -y 2 2 (2)
where Σ K,ǫ , defined in [START_REF] Bénard | Estimation of off-the-grid sparse spikes with over-parametrized projected gradient descent: theory and application[END_REF], is a set modeling a separation constraint between spikes. We consider the set of parameters Θ K,ǫ , Θ K,ǫ = θ = (a 1 , . . . , a K , t 1 , . . . , t K ) ∈ R K(d+1) , ∀i, j ∈ {1, . . . , K}, i = j, t it j 2 > ǫ} . [START_REF] Beck | On the convergence of block coordinate descent type methods[END_REF] We can rewrite [START_REF] Allen-Zhu | Even faster accelerated coordinate descent using non-uniform sampling[END_REF] with the variable θ:

x 0 = φ(θ) := K i=1 a i δ ti ∈ Σ K,ǫ . (4)
The unknown x 0 belongs to the low dimensional model

Σ K,ǫ = φ(Θ K,ǫ ) (5)
The problem (2) can then be written as

θ * ∈ arg min θ∈ΘK,ǫ g(θ) with g(θ) := Aφ(θ) -y 2 2 . ( 6
)
Theoretical guarantees for the recovery of x 0 with (2) have been given in [START_REF] Gribonval | Compressive Statistical Learning with Random Feature Moments[END_REF]. As an example, when the linear operator A models random Fourier measurements at frequencies drawn with a Gaussian distribution and dim(y) O(K 2 dpolylog(K, d)), we have x * = x 0 . In practice, Sliding Continuous Orthogonal Matching Pursuit (SCOMP) [START_REF] Keriven | Compressive k-means[END_REF] has been successful at minimizing [START_REF] Auslender | Asymptotic properties of the fenchel dual functional and applications to decomposition problems[END_REF]. Recovery guarantees are given in [START_REF] Elvira | OMP and continuous dictionaries: Is k-step recovery possible?[END_REF], [START_REF] Elvira | When does OMP achieve exact recovery with continuous dictionaries? Applied and Comp[END_REF], [START_REF] Bénard | Estimation of off-the-grid sparse spikes with over-parametrized projected gradient descent: theory and application[END_REF]. We can also cite the Sliding Frank-Wolfe (SFW) algorithm [START_REF] Denoyelle | The Sliding Frank-Wolfe Algorithm and its Application to Super-Resolution Microscopy[END_REF], that aims to solve a regularized version of [START_REF] Auslender | Asymptotic properties of the fenchel dual functional and applications to decomposition problems[END_REF]. Although state-of-the-art methods can fully recover signals in this setting, they lack of performance in computation time. The Over-Parametrized COMP + Projected Gradient Descent (OP-COMP + PGD) algorithm has been introduced to address these performance issues [START_REF] Traonmilin | Projected gradient descent for non-convex sparse spike estimation[END_REF], [START_REF] Bénard | Fast off-the-grid sparse recovery with over-parametrized projected gradient descent[END_REF]. This method initializes an over-parametrized signal without a costly descent step (OP-COMP). Then, it performs a single descent on all parameters while performing a projection to reduce the number of spikes (PGD). It has been proven that a good initialization of the signal is possible in K steps [START_REF] Bénard | Estimation of off-the-grid sparse spikes with over-parametrized projected gradient descent: theory and application[END_REF]. This means that each initialized spike is close to a true spike, on the conditions that one has a sufficient separation ǫ and a wellbehaved operator A. However, these conditions are not always verified. In these cases, while OP-COMP + PGD is still faster than SFW and SCOMP, it lacks in efficiency during the descent on all parameters in θ. The large number of gradients to compute is the main limiting factor of OP-COMP + PGD [START_REF] Bénard | Estimation of off-the-grid sparse spikes with over-parametrized projected gradient descent: theory and application[END_REF].

For gradients descent methods, an idea to accelerate computation time is the Block Coordinate descent (BCD). It consists in only performing iterations of the descent on a subset of the coordinates of the parameters that we estimate.

The idea of an underlying structure to separate the signal in blocks is common in many applications (see e.g. [START_REF] Shi | A primer on coordinate descent algorithms[END_REF], [START_REF] Wright | Coordinate descent algorithms[END_REF]). Among many applications, there are Non-Negative Matrix Factorization [START_REF] Xu | A block coordinate descent method for regularized multiconvex optimization with applications to nonnegative tensor factorization and completion[END_REF], Sparse Logistic Regression [START_REF] Wu | Coordinate descent algorithms for lasso penalized regression[END_REF].

The LASSO problem has also been with BCD methods [START_REF] Li | Coordinate descent optimization for l1 minimization with application to compressed sensing; a greedy algorithm[END_REF], [START_REF] Wright | Coordinate descent algorithms[END_REF].

The definition of Block Coordinate Descent relies on the blocking strategy, the block selection rule and the block update rule [START_REF] Nutini | Let's make block coordinate descent converge faster: Faster greedy rules, message-passing, active-set complexity, and superlinear convergence[END_REF]. Blocking strategy. The blocks can be either fixed beforehand or variable and recomputed at each iteration. Fixed blocks permit better control and separation in sub-problems [START_REF] Sardy | Block coordinate relaxation methods for nonparametric wavelet denoising[END_REF] when the structure of the problem is known before computations [START_REF] Meier | The group lasso for logistic regression[END_REF]. Variable blocks allow more freedom, e.g. by creating blocks based on greedy methods [START_REF] Tseng | A coordinate gradient descent method for nonsmooth separable minimization[END_REF] such as Gauss-Southwell. Block selection rule. As the choice of the block to update may lead to different minima, it is a main area of focus for BCD methods [START_REF] Shi | A primer on coordinate descent algorithms[END_REF]. Basic ideas such as the cyclic variants for index choice are common as they are deterministic methods with proven convergence [START_REF] Beck | On the convergence of block coordinate descent type methods[END_REF]. Implementation-wise, they are simple and do not require computation overhead. Instead of going through all coordinates in a cyclic order, one can use randomized methods by choosing coordinates based on a uniform distribution [START_REF] Nesterov | Efficiency of coordinate descent methods on huge-scale optimization problems[END_REF], weighted distribution [START_REF] Allen-Zhu | Even faster accelerated coordinate descent using non-uniform sampling[END_REF] or just from arbitrary rules [START_REF] Richtárik | Iteration complexity of randomized blockcoordinate descent methods for minimizing a composite function[END_REF]. Greedy methods are also used in the block selection process. They choose the most suitable block at each iteration by solving an optimization problem [START_REF] Nutini | Let's make block coordinate descent converge faster: Faster greedy rules, message-passing, active-set complexity, and superlinear convergence[END_REF]. A well known greedy method, for its efficiency both theoretically and practically and its simplicity, is the Gauss-Southwell (GS) rule which select a block based on the norm of its gradient,

b k ∈ arg max b∈B ∇g(θ k ) b 2 . ( 7
)
where B is the set of all blocks. Other greedy methods such as Maximum Improvement [START_REF] Chen | Maximum block improvement and polynomial optim[END_REF] or GS-Lipschitz [START_REF] Nutini | Coordinate descent converges faster with the gauss-southwell rule than random selection[END_REF] are also valid choices for block selection rules. Greedy methods perform better than cyclic or random methods but at the cost of a more expensive computation [START_REF] Nutini | Coordinate descent converges faster with the gauss-southwell rule than random selection[END_REF]. Block update rule. The role of this rule is to make the chosen block maximally decrease the objective function (like (2)). It is important to use a block update rule suited with the problem.

Starting with the classical gradient descent, one can set the step-size in different ways (fixed, approximate line-search or optimal step-size) to improve performance [START_REF] Bertsekas | Nonlinear programming[END_REF]. Many more descent methods used in convex and non-convex optimization are used in BCD. Among the many methods introduced, one can use proximal update [START_REF] Auslender | Asymptotic properties of the fenchel dual functional and applications to decomposition problems[END_REF], stochastic gradient [START_REF] Nemirovski | Robust stochastic approximation approach to stochastic programming[END_REF] depending, for example, on the geometry of the objective function. In our case, we wish to improve upon the Projected Gradient Descent from OP-COMP + PGD using a FISTA Restart method for the block updating rule. An early use of FISTA for BCD method can be found in [START_REF] Qin | Efficient block-coordinate descent algorithms for the group lasso[END_REF]. While there are no theoretical guarantees for the convergence of FISTA in BCD methods, it works well in various cases [START_REF] Chambolle | On the convergence of the iterates of" fista[END_REF].

Contributions. In this paper, our main contribution is an accelerated method for recovering sparse signals based on OP-COMP + PGD. We propose a Projected Block Coordinate Descent method that performs the descent step on spikes that have not already converged. The main ingredient for this BCD is a block selection strategy based on the specific structure of the sparse spike model to decompose the problem in small blocks. We define the three ingredients defining BCD within the OP-COMP + PGD method and justify qualitatively our choices. We provide synthetic experiments in the context of microscopy that show an improvement up to 35% in calculation time compared to PGD.

II. THE PROJECTED BLOCK COORDINATE DESCENT ALGORITHM

In this section, we motivate the idea of using a block system to divide our problem in a sum of smaller and simpler problems. Moreover, we describe our method: the projected Block Coordinate Descent. This descent only operates on parameters of non-converged spikes of the estimated signal.

A. A result to guide block selection

The Block Coordinate Descent (BCD) is a way to fasten the computation time of descent algorithms by using the underlying structure of the problem. In our case, the more spikes there are in the signal to recover, the more parameters there are to compute in the descent process. As our model contains a separation constraint, every spike to be recovered is estimated by one or more initialized spikes independently of the other true spikes. This leads to two cases: either there is one initialized spike estimating a true spike, or a cluster of initialized spikes. For one spike estimations, the convergence to their associated true spike is fast. On the contrary for the clusters of initialized spikes, their convergence is much slower toward a true spike [START_REF] Bénard | Estimation of off-the-grid sparse spikes with over-parametrized projected gradient descent: theory and application[END_REF]. We propose to only compute the gradients of spikes that have not yet converged. Next, we show qualitatively why we can use our model to separate the recovery of each spike using our separation constraint with an idealized initialized signal.

Let x 0 = K i=1 a i δ ti ∈ Σ K,ǫ the signal to recover and x = K j=1 b j δ sj the initialized signal obtained with COMP. Suppose that x is well initialized i.e. for all i ∈ {1, . . . , K}, t is i 2 < ǫ 3 . By computing their difference, we get

x 0 -x = K i=1 (a i δ ti -b i δ si ) = K i=1 ν i (8)
where

ν i = a i δ ti -b i δ si is called a ǫ 3 -dipole. From [5], we recall the definition of a ǫ 3 -dipole, Definition 1 ((ǫ-)Dipole). An ǫ-dipole is a measure ν = aδ t - bδ s where t -s 2 ≤ ǫ.
Let us also recall the definition of ǫ 3 -separated dipoles, Definition 2 ((ǫ)-Separation of dipoles). Two dipoles

ν 1 = a 1 δ t1 -b 1 δ s1 and ν 2 = a 2 δ t2 -b 2 δ s2 are ǫ-separated if their support is strictly ǫ-separated, i.e. if t 1 -t 2 2 > ǫ and t 1 - s 2 2 > ǫ and s 1 -t 2 2 > ǫ and s 1 -s 2 2 > ǫ.
The following lemma gives us bounds to better interpret the block structure of our model with our initialization x.

Lemma 1. Let x 0 = K i=1 a i δ ti ∈ Σ K,ǫ and x = φ(θ) = K i=1 b i δ si with θ = (b 1 , . . . , b K , s 1 , . . . , s K ) such that for all ∈ {1, . . . , K}, t i -s i 2 < ǫ 3 .
Let A be a linear operator from the space of finite measures over R d to C m . Suppose that for two ǫ 3 -separated ǫ 3 dipoles ν 1 , ν 2 , there exists µ A > 0 such that A follows the assumption,

Aν 1 , Aν 2 ≤ µ A Aν 1 2 2 Aν 2 2 2 . ( 9
)
Then we obtain

y -Ax 2 2 ≤ K i=1 Aν i 2 2 + µ A K i,j=1 i =j Aν i 2 2 Aν j 2 2 . ( 10
)
Moreover, let ∂ i,r g(θ) be the partial derivative of g(θ) with respect to the r-th coordinate of s i . Then we get

∂ i,r y -Ax 2 2 -∂ i,r Aν i 2 2 ≤ 2a i (K -1)µ A ∂ i,r Aν i 2 2 max j∈{1,...,K} Aν j 2 2 . (11)
Proof. Since we suppose that for all i ∈ {1, . . . , K}, t i -

s i 2 < ǫ 3 , we can write x 0 -x = K i=1 (a i δ ti -b i δ si ) as a sum of ǫ 3 -dipoles K i=1 ν i .
To get [START_REF] Denoyelle | The Sliding Frank-Wolfe Algorithm and its Application to Super-Resolution Microscopy[END_REF], we first start by expanding y -

Ax 2 2 , y -Ax 2 2 = A(x 0 -x) 2 2 = A K i=1 ν i 2 2 (12) = K i=1 Aν i 2 2 + K i,j=1 i =j Aν i , Aν j (13)
We use our assumption (9) so we can bound Aν i , Aν j ,

y -Ax 2 2 ≤ K i=1 Aν i 2 2 + µ A K i,j=1 i =j Aν i 2 2 Aν j 2 2 . ( 14
)
Now, we prove [START_REF] Elvira | OMP and continuous dictionaries: Is k-step recovery possible?[END_REF]. Using Proposition 2.1 in [START_REF] Traonmilin | The basins of attraction of the global minimizers of the non-convex sparse spike estimation problem[END_REF], we have

∂ i,r y -Ax 2 2 = 2a i Re A∂ i,r δ si , A K j=1 ν j (15) = 2a i Re A∂ i,r δ si , Aν i + 2a i Re A∂ i,r δ si , A K j=1 j =i ν j . (16)
Using our assumption (9), we get (using the fact that this identity is also verified for Dirac derivatives that are generalized dipoles [START_REF] Traonmilin | The basins of attraction of the global minimizers of the non-convex sparse spike estimation problem[END_REF]):

∂ i,r y -Ax 2 2 ≤ 2a i Re A∂ i,r δ si , Aν i + 2a i µ A ∂ i,r Aδ si 2 2 K j=1 j =i Aν j 2
∂ i,r y -Ax 2 2 -∂ i,r Aν i 2 2 ≤ 2a i µ A (K -1) ∂ i,r Aν i 2 2 max j∈{1,...,K} Aν j 2 2 . ( 18
)
Using the result [START_REF] Denoyelle | The Sliding Frank-Wolfe Algorithm and its Application to Super-Resolution Microscopy[END_REF] from Lemma 1, we get that in order to minimize y -Ax 2 2 , a sufficient condition is to minimize individually each Aν i 2 2 , i.e. recover K distinct 1-spike signals.

To distinguish converged spikes from non-converged spikes, we will compare their gradients using the result (11) from Lemma 1. Indeed, the absolute difference between ∂ i,r y -Ax 2 2 and ∂ i,r Aν i 2 2 is small: For common observation operators (e.g. Gaussian filter), we have that the mutual coherence parameter µ A is small and the terms ∂ i,r Aν i 2 2

and sup j∈{1,...,K} Aν j 2 2 are bounded. In practice, the overparametrization of the initialized signal yields more spikes than dipoles, however the simpler case given by Lemma 1 suggests that blocks of spikes with large gradients should be considered for the selection strategy.

B. Description of the algorithm

Our new algorithm: the Projected Block Coordinate Descent (Algorithm 1) is an improvement of the Projected Gradient Descent [START_REF] Traonmilin | Projected gradient descent for non-convex sparse spike estimation[END_REF], which performs a descent on all parameters while enforcing a separation constraint on the positions of the estimated spikes. We keep this main feature and we integrate our Block Coordinate Descent acceleration. Our method is derived from the Gauss-Southwell rule. We choose our blocks from the set of all blocks B super-res , where each block represents a spike. In each iteration of the main loop, we compute the norm of the gradients ( ∇[g(θ)] i 2 for all i ∈ {1, . . . , K}) associated to each spike of the estimated signal with ∇[g(θ)] i := ∇g((a i , t i )) i.e. the gradients for the amplitude and position of the spike i. Then, we create two sets I and J. The set

I = {i, ∇[g(θ)] i 2 ≥ threshold × max j ∇[g(θ)] j 2 }
represents all spikes that have not yet converged. In practice, we set manually the value of threshold and we discuss this choice in more details in the next section. We set J = {1, . . . , K}\I. We note x I = i∈I a i δ si and x J = j∈J a j δ sj . With only the selected spikes from I, we perform a projected gradient descent on x I for a fixed number of iteration m it (or until convergence). Note that the observation in this partial projected descent y I is y -Ax J i.e. the original observation updated with the non-selected spikes from this iteration. If a projection occurs during this descent, we stop the projected gradient descent. We merge both signals x I and x J and we compute again I and J. We continue this process until convergence of our estimated signal x. To perform the descent, we choose the FISTA Restart algorithm [START_REF] Candes | Adaptive restart for accelerated gradient schemes[END_REF] as in practice it outperforms a classic Gradient Descent and it provides fast convergence.

III. EXPERIMENTS

In this section, we compare our new Projected Block Coordinate Descent with the state-of-the-art Projected Gradient Descent. The signal to recover in every experiment is composed of 50 Dirac measures for MA-TIRF in 3 dimensions [START_REF] Denoyelle | The Sliding Frank-Wolfe Algorithm and its Application to Super-Resolution Microscopy[END_REF]. As these methods aim to recover a signal from an initial estimation, we use Over-Parametrized Continuous Orthogonal

Algorithm 1 Projected Block Coordinate Descent. BCD(y, A, θ (0) , n it , m it threshold) n ← 0 k ← #spikes while n < n it do I = {i, ∇[g(θ (n) )] i 2 ≥ threshold × max j ∇[g(θ (n) )] j 2 } J = {1, . . . , k} \ I θ(n) ← θ (n) i , i ∈ I , θ(n) ← θ (n) j , j ∈ J ỹ ← y -Aφ( θ(n) ) θ(n * ) ← projected_descent(ỹ, θ(n) , m it ) θ (n * ) ← θ(n * ) i if i ∈ I else θ(n) i i=1,...,k θ (n) ← θ (n * )
k ← #spikes end while return θ (nit) end procedure Matching Pursuit (OP-COMP) for the initialization of the signal.

The linear operator used for the observations is the MA-TIRF operator [START_REF] Denoyelle | The Sliding Frank-Wolfe Algorithm and its Application to Super-Resolution Microscopy[END_REF]. It is used in microscopy for recovering cells in 3D images. The positions t are in a domain of size 6.4mm×6.4mm×0.8mm. The observation is composed of 4 planes which represent different focal angles. Each plane is composed of 64 × 64 pixel. In total, dim(y) = 64 × 64 × 4 = 16 384. The amplitudes follow a uniform distribution U ( [START_REF] Allen-Zhu | Even faster accelerated coordinate descent using non-uniform sampling[END_REF][START_REF] Auslender | Asymptotic properties of the fenchel dual functional and applications to decomposition problems[END_REF]). The code for these experiments is available for download at [START_REF] Bénard | Code of the experiments[END_REF]. In Fig. 1(a), we display a focal plane of the observation. It corresponds to an image taken at a certain angle. Though it is in 2 dimensions, the combination of multiple angles is useful to recover spikes in 3D. We see in this figure that most of the spikes are well separated. In Fig. 1(b), we have the true signal and the initialized signal by OP-COMP. Note that every spike from the ground truth has at least one initialized spike close to itself. Moreover, the over-parametrization is clearly visible as the number of initialized spikes is larger than the number of spikes to recover. In Fig. 2(a), we observe that the spikes are well recovered by PGD as expected. In Fig. 2(c) (in blue), we show the norm of the residue y -Ax 2 2 through the iterations for both PGD (in blue) and BCD (in red). Note that we stop the descent when the norm of the residue gets below 2 × 10 -8 . For PGD, the norm of the residue decreases and reaches its minimum at 2 × 10 -8 . The sudden jumps in the norm of the residue are due to the projection used.

In Fig. 2(b), we obtain an estimated signal by BCD similar to the one obtained with PGD. In Fig. 2(c) (in red), as for PGD, we observe the norm of the residue through the iterations of BCD. We note that for the same norm of the residue, BCD converges much faster with an acceleration of almost 35% in computation time. While the start of both methods takes the same time for about 2000 iterations, we observe a clear acceleration as the time passes. Indeed, as seen in Figure 3(a), the fraction of gradients computed at each iteration of BCD decreases. A good empirical value for the choice of threshold in Algorithm 1 is 10 -3 . This value is used for all of our experiments. It provides a good trade-off in terms of minimization of g (see Equation ( 6)) and computation time. Indeed, this threshold limits the number of blocks used for each projected_descent by selecting only non-converged spikes. At the start of the descent, almost all gradients are still computed at each iteration, but as the iterations passes, the fraction of computed gradients decreases, hence the computation time gained over PGD. Both Figures 3(a) and 3(b) reveal that by computing fewer gradients, we can gain time on the total computation. being tested on 10 similar signals composed of 50 spikes with a high separation between spikes, the results stay the same and we have that in general, BCD is 35% faster than PGD for MA-TIRF. Other metrics used to compare both estimations are the Jaccard, Precision and Recall. For these metrics, there is no particular difference between the two methods PGD and BCD.

We note that for other kind of linear operators (such as the Fourier Transform), performances of the BCD can vary, but it always improves the computation speed.

IV. DISCUSSION/CONCLUSION

To conclude, we observe that the block structure for the sparse spike resolution permits to improve computation time of descent algorithms. Indeed, in a realistic microscopy setting, the time gained by BCD is up to 35% when compared to previous methods. For future works, we intend to try other greedy methods for a better block selection. Moreover, one can parallelize the descent on the different blocks as it is a major benefit of Block Coordinate Descent methods.

Figure 1 .

 1 (a) Ground truth and a plane of its observation through MA-TIRF, (b) Ground truth and the initialized signal by OP-COMP.

Figure 2 .

 2 Figure 2. (a) Ground truth and the estimated signal by PGD with MA-TIRF, (b) Ground truth and the estimated signal by BCD with MA-TIRF, (c) Comparison norms of residues by PGD and BCD in function of time.

Figure 3 .

 3 Figure 3. (a) Fraction of spikes whose gradients are computed during BCD, (b) Time elapsed for PGD and BCD in function of the number of iterations

  Re A∂ i,r δ si , Aν i = ∂ i,r Aν i

	2 . (17)
	We max j∈{1,...,K} Aν j bound each 2 2 . 2a i 2 Aν j 2 2 Moreover, by 2 . Finally, we obtain their maximum we have that

V. ACKNOWLEDGMENTS

This work was supported by the French National Research Agency (ANR) under reference ANR-20-CE40-0001 (EF-FIREG project). Experiments presented in this paper were carried out using the PlaFRIM experimental testbed, supported by Inria, CNRS (LABRI and IMB), Université de Bordeaux, Bordeaux INP and Conseil Régional d'Aquitaine (see https://www.plafrim.fr).


Maelenn Guerchet
email: maelenn.guerchet@unilim.fr

MSc Nathalie Bouscaren

PhD Sophie Pilleron

MD Pascal Mbelesso

MD Bebene Ndamba-Bandzouzi

MD Jean-Francois Dartigues

PhD Jean-Pierre Clement

PhD Pierre-Marie Preux

MD, PhD Marie-Laure Darde

MD, PhD Maelenn Guerchet

Bébène Ndamba-Bandzouzi

Jean- François Dartigues

Jean-Pierre Clément

Marie-Laure Dardé

Maëlenn Guerchet

Dr Maëlenn Guerchet

PREVALENCE OF TOXOPLASMOSIS AND ITS ASSOCIATION WITH DEMENTIA IN OLDER ADULTS IN CENTRAL AFRICA: A RESULT FROM THE EPIDEMCA PROGRAMME

Keywords: Dementia, Alzheimer's Disease, Toxoplasmosis, seroprevalence, older adults, sub-Saharan Africa Dementia, Alzheimer's Disease, Toxoplasma gondii, seroprevalence, older adults, sub-Saharan Africa

Objective: This study aimed at estimating the seroprevalence of Toxoplasma gondii infection in older adults living in Central Africa and at investigating its association with dementia using data from the Epidemiology of Dementia in Central Africa programme, a population-based study. Methods: A cross-sectional multicenter population-based study was carried out among participants aged ≥65 years living in rural and urban areas of the Central African Republic and the Republic of Congo. Blood samples were collected from each consenting participant. The detection of anti-T.gondii immunoglobulin G antibodies was done in France using a commercially available ELISA kit. Participants were interviewed using a standardized questionnaire including sociodemographic characteristics. DSM-IV criteria were required for a diagnosis of dementia. Multivariate binary logistic regression models were used to estimate the association between toxoplasmosis infection and dementia. Results: Among 1,662 participants, the seroprevalence of toxoplasmosis was 63.0% (95% confidence interval (CI): 60.7-65.3) overall, 66.6% (95%CI: 63.4-69.8) in Central African Republic and 59.4% (95%CI: 56.1-62.7) in the Republic of Congo. In multivariate analyses, toxoplasmosis status was significantly associated with

increasing age (p=0.006), Republic of Congo (p=0.002), urban area (p=0.001) and previous occupation (p=0.002). No associations between dementia and toxoplasmosis status or anti-T gondii IgG titres were found. Conclusion: Being infected with T. gondii was not associated with dementia among older adults in Central Africa. Our findings are consistent with some previous studies and add to the knowledge on the relationship between T. gondii infection and neurological disorders.

INTRODUCTION (3,103 words)

Globally, 25-30% of individuals are infected with Toxoplasma gondii (T.gondii) (1;2) with disparities across regions, depending on geographical and socio-economic conditions (1;2). Previous studies estimated at around 40% the prevalence of T.gondii infection in general population in the Republic of Congo (ROC) and in the Central African Republic (CAR) (3;4;4). T.gondii infection seroprevalence is primarily studied in population at risk for developing acute toxoplasmosis such as women of childbearing age and immuno-compromised patients. Although the risk of being infected with T.gondii increases with age [START_REF] Wilking | Prevalence, incidence estimations, and risk factors of Toxoplasma gondii infection in Germany: a representative, cross-sectional, serological study[END_REF], its prevalence among older adults and the effect of age on anti-T.gondii antibody titre evolution remain largely unknown.

During a primary T.gondii infection, the invasive tachyzoite stages circulate in the blood, invade the various organs, cross the blood-brain barrier and establish themselves in the brain cells probably as soon as the end of the first week of infection. This acute toxoplasmosis phase lasts a few weeks. It is usually asymptomatic, but can also present as a benign disease with lymphadenopathies, fever and asthenia. Beyond this acute phase, the invasive tachyzoite stages are no longer present, and the chronic stage of infection is characterized by the presence of latent toxoplasmic cysts in the tissues, and more particularly the central nervous system. This chronic stage is assumed to persist throughout life without inducing any symptoms in immunocompetent patients [START_REF] Robert-Gangneux | Epidemiology of and diagnostic strategies for toxoplasmosis[END_REF].

Dementia is a neurodegenerative disease characterized by progressive decline in cognitive functions, progressive functional impairment, and behavioural and psychological symptoms (6). Alzheimer's disease, characterized by two core cerebral lesions (β amyloid plaques and neurofibrillary tangles), is the most common cause of dementia among older people. Lewy Body disease, frontotemporal lobar degeneration, and vascular disease, are other common causes of dementia, differing in pathophysiology [START_REF] Hickey | Dementia: Person-Centered Assessment and Intervention. 2018. (8) Pathological correlates of late-onset dementia in a multicentre, community-based population in England and Wales. Neuropathology Group of the Medical Research Council Cognitive Function and Ageing Study (MRC CFAS)[END_REF]. However, mixed pathologies are much more common than 'pure' forms of dementia (8). Dementia has a significant impact on those affected, their families and society, with considerable costs worldwide [START_REF]The global impact of Dementia[END_REF]. Demographic ageing worldwide is expected to lead to a dramatic increase in the number of cases, and African countries are not spared by this phenomenon [START_REF] Guerchet | Dementia in sub-Saharan Africa: challenges and opportunities[END_REF]. The prevalence of dementia in adults aged 65 years and older was recently estimated between 6.4% and 8.5% in CAR and between 5.7% and 6.7% in ROC (11;12). Literature studying the association between latent T.gondii infection and neurological or psychiatric disorders is growing [START_REF] Pearce | The relationship between Toxoplasma gondii infection and mood disorders in the third National Health and Nutrition Survey[END_REF][START_REF] Ngoungou | Toxoplasmosis and epilepsy-systematic review and meta analysis[END_REF][START_REF] Fabiani | Toxoplasmosis and neuropsychiatric diseases: can serological studies establish a clear relationship?[END_REF][START_REF] Severance | Toxoplasma gondii-A Gastrointestinal Pathogen Associated with Human Brain Diseases[END_REF][START_REF] Del | Is Toxoplasma gondii a Trigger of Bipolar Disorder?[END_REF]. Chronic infection compromised goal-directed behaviour [START_REF] Beste | Latent Toxoplasma gondii infection leads to deficits in goal-directed behavior in healthy elderly[END_REF], affected several aspects of memory (19;20), led to a decline in visual motor coordination, coding ability and short term memory [START_REF] Nimgaonkar | Temporal Cognitive Decline Associated With Exposure to Infectious Agents in a Population-based, Aging Cohort[END_REF], and to a more rapid decline in executive function and cognitive decline among older adults [START_REF] Nimgaonkar | Temporal Cognitive Decline Associated With Exposure to Infectious Agents in a Population-based, Aging Cohort[END_REF]. Cognitive dysfunctions were attributed to cysts' location in the brain (22;23), to the immune response in chronically infected patients [START_REF] Hamdani | Cognitive deterioration among bipolar disorder patients infected by Toxoplasma gondii is correlated to interleukin 6 levels[END_REF], or to a change in cerebral metabolism (23;25). A chronic infection accompanied by an increase in interferon γ (IFN-γ) production decreases the tryptophan pool affecting kynurenic acid and serotonin levels. Moreover, T.gondii infection increases the activity of the tyrosine hydrolase that in turn releases dopamine. The increase in kynurenic acid and dopamine levels along with the decrease in serotonin level were associated with cognitive dysfunctions in rodents (23;26;27) and in humans [START_REF] Xiao | MicroRNA-132 dysregulation in Toxoplasma gondii infection has implications for dopamine signaling pathway[END_REF]. T.gondii infection was however shown to decrease β-amyloid plaque deposition in the cortex and hippocampus suggesting positive effects of T.gondii infection on the pathogenesis and progression of Alzheimer's disease (AD) in mice [START_REF] Cabral | Dissecting Amyloid Beta Deposition Using Distinct Strains of the Neurotropic Parasite Toxoplasma gondii as a Novel Tool[END_REF][START_REF] Mohle | Chronic Toxoplasma gondii infection enhances beta-amyloid phagocytosis and clearance by recruited monocytes[END_REF][START_REF] Jung | Toxoplasma gondii infection in the brain inhibits neuronal degeneration and learning and memory impairments in a murine model of Alzheimer's disease[END_REF]. In humans, case-control studies dedicated to T.gondii infection and dementia reported contradictory results [START_REF] Mahami-Oskouei | Toxoplasmosis and Alzheimer: can Toxoplasma gondii really be introduced as a risk factor in etiology of Alzheimer?[END_REF][START_REF] Perry | Seroprevalence and Serointensity of Latent Toxoplasma gondii in a Sample of Elderly Adults With and Without Alzheimer Disease[END_REF][START_REF] Yahya | Impact of ApoE genotypes variations on Toxoplasma patients with dementia[END_REF][START_REF] Kusbeci | Could Toxoplasma gondii have any role in Alzheimer disease?[END_REF]. Most studies focused on the Alzheimer's subtype (32;33;35). Two studies found no association between AD and toxoplamosis infection in the USA [START_REF] Perry | Seroprevalence and Serointensity of Latent Toxoplasma gondii in a Sample of Elderly Adults With and Without Alzheimer Disease[END_REF] and in Iran [START_REF] Mahami-Oskouei | Toxoplasmosis and Alzheimer: can Toxoplasma gondii really be introduced as a risk factor in etiology of Alzheimer?[END_REF] whilst the third one in Turkey suggested that toxoplasma infection may be involved in the pathogenetic mechanisms of AD [START_REF] Kusbeci | Could Toxoplasma gondii have any role in Alzheimer disease?[END_REF]. The only study investigating dementia (all subtypes combined), in Egypt, showed that toxoplasma positive participants had an increased likelihood of having dementia, regardless of their ApoE genotype [START_REF] Yahya | Impact of ApoE genotypes variations on Toxoplasma patients with dementia[END_REF]. To our knowledge, no study has been conducted in sub-Saharan African countries yet, where both dementia and T. gondii epidemiology may present particular aspects.

We aimed first at estimating the seroprevalence of T.gondii infection among older adults in Central Africa; secondly, at investigating the association between T.gondii infection and dementia, within the Epidemiology of Dementia in Central Africa (EPIDEMCA) programme, a large population-based study.

METHODS

Participants

Our study population consisted of participants included in the EPIDEMCA programme, a multicentre cross-sectional population-based study conducted in CAR and ROC between November 2011 and December 2012. The detailed methodology is described in an open access publication [START_REF] Guerchet | Epidemiology of dementia in Central Africa (EPIDEMCA): protocol for a multicentre population-based study in rural and urban areas of the Central African Republic and the Republic of Congo[END_REF]. In essence, participants aged 65 years and older who had lived in the study area for at least six months were included. The study areas included the capitals of CAR (Bangui) and ROC (Brazzaville), and two rural areas (Nola in CAR and Gamboma in ROC). The sample size was calculated a priori with the aim of estimating dementia prevalence, and was then rounded at 500 in each study site. In absence of detailed census, the participants' selection in urban areas was carried out using a proportional random sampling (to represent Bangui and Brazzaville's diverse populations) while a door-to-door approach was preferred due to logistic and financial constraints in rural areas. Response rates varied between 93 and 97% across sites, with the only exclusion criteria being refusal or the presence of severe disease with short-term high risk of death.

Serological analysis

Each consenting participant had 20 mL of blood collected into two polypropylene EDTA tubes by a dedicated nurse. Whole fresh blood samples were centrifuged and aliquoted within few hours to avoid degradation due to high temperatures and then frozen at -20°C or -80°C in the nearest laboratory.

Plasma aliquots were stored at the Pasteur Institute of Bangui in CAR and the National Laboratory of Public Health in Brazzaville in ROC before dry-ice shipping to the University of Limoges where plasma samples were kept stored at -80°C until analysed. In 2014, the detection of anti-T.gondii immunoglobulin G (IgG) was done using the VIDAS TOXO IgG II test (Biomérieux, France), according to the manufacturer's instructions. This test is validated for detection of anti-T.gondii IgG in plasma. Results were reported in International Units per millilitre (IU/mL). Samples with anti-T.gondii IgG <4 IU/mL were considered as seronegative. A sample was considered as positive when the titre was equal or greater than 8 IU/mL. Samples with titres ≥300 UI/mL were diluted in the negative control included with the VIDAS TOXO IgG II test until titres could be determined. Titres comprised between 4 IU/mL and 8 IU/mL were considered as equivocal and further analysed by VIDAS TOXO competition (Biomérieux, France), which better correlated with low titres of the usual reference test, namely dye-test. Samples with indexes below 1.6 were considered as seropositive according to the manufacturer's instructions. The T.gondii positive group included all participants that were positive either with VIDAS Toxo IgG II or with VIDAS Toxo Competition assay.

Dementia assessment

Dementia was assessed following a two-stage process. First, cognitive screening was performed using the Community Screening Interview for Dementia (CSI-D) (37) adapted, back-translated and pretested in the local languages (Sango in CAR, Lari, Lingala, and Kituba in ROC). Every participant obtaining a poor performance on the CSI-D cognitive tests (COGSCORE ≤24.5) was suspected of having cognitive impairment and referred for neurological assessment. During the second phase which was conducted at the hospital 3-14 weeks later, further psychometric tests were conducted, including the Free and Cued Selective Reminding Test (38), Zazzo's cancellation task (39) and Isaac's Set Test of verbal fluency (40). Neurologists performed clinical examination, recorded history of stroke and presence of depressive disorders, and assessed orientation skills and daily activities. Dementia was diagnosed according to the DSM-IV criteria [START_REF]Diagnostic and statistical manual of mental disorders[END_REF]. An experienced neurologist (JFD) reviewed all medical records and cognitive test performances in order to reach a consensus.

Statistical analysis

Sociodemographic

data included age, sex, marital status (married, never married/widowed/divorced/separated), education (no education, at least primary school), occupation (farmer/breeder/fisher vs. other), country (CAR, ROC) and area (urban, rural). Age was ascertained from official documents, using historical events or from an informant if previous methods were unsuccessful. All variables were collected during the first phase in all participants.

Study population characteristics were described in terms of means with corresponding standard deviations for age, median with its inter-quartiles range (IQR) for antibody titres and cognitive scores, and percentages for all categorical variables. Prevalence of toxoplasmosis was presented with its 95% confidence interval (CI). Comparisons were carried out between countries using the Chi-square test and Kruskal-Wallis test when appropriate. The correlation between the anti-IgG titre and age was tested using the Spearman test.

Factors associated with T.gondii infection were examined using logistic regression models. All factors associated with T.gondii infection and dementia at p<0.20 in univariate analysis were included in multivariate logistic regression model. The variable selection was carried out using a backward stepwise approach in which variables considered to be a confounder (odds ratio's variation above 15%) were kept in the model. The association between toxoplasmosis and dementia was first analysed in unadjusted logistic regression model and then in a model adjusted for age, sex, country, area and education.

In a sensitivity analysis, we ran the fully-adjusted logistic regression model with quintiles of anti-IgG titres as dependent variable instead of toxoplasmosis status.

The level of significance was fixed at 0.05 for all analyses. Statistical analyses were carried-out using Stata version 10.1 for Windows (StataCorp, College Station, TX).

RESULTS

Characteristics of the EPIDEMCA participants

Among 2,002 participants included in the EPIDEMCA study, 340 participants were excluded because they did not have blood samples due to refusals (n=176), impossible blood withdrawal (n=35), poor health conditions (n=34), absence on the day of blood collections (n=9), and non-exploitable samples (n=86). A total of 1,662 participants were therefore analysed (Figure 1).

General socio-demographic characteristics are shown in Table 1. Participants were 73.1 (±6.6) years on average and ROC participants were older and less likely living as a couple than those from CAR.

Seroprevalence of Toxoplasma infection

Of the 1,662 individuals, 1,047 were found to be positive for anti-T.gondii IgG antibodies, i.e. a seroprevalence of 63.0% (95%CI: 60.7-65.3). The seroprevalence was lower in ROC than in CAR (p=0.002) and as a whole, lower in rural areas than urban areas (57.3% [95%CI: 53.9-60.7] vs. 68.5%

[95%CI:65.4-71.6]; p<0.001) (Figure 2). In both country, the seroprevalence was significantly associated with areas (p<0.001) but the urban-rural gradient was inversed.

In bivariate analyses, T.gondii infection was significantly associated with increasing age in 5-year bands, country, rural areas, no education, and previous occupation. In multivariate analysis, T.gondii infection remained significantly associated with country, area and previous occupation (Table 2).

Median anti-T.gondii IgG titre was 32 (IQR 120) IU/mL (min-max: 0-15 000), 22 (105) IU/mL in ROC and 47 (128) IU/mL in CAR (p<0.001). A total of 99 participants (6.0%) had anti-T.gondii IgG titre>300 IU/mL, 44 (5.3%) in CAR and 55 (6.0%) in ROC (p=0.28), and 48 (2.9%) had a titre above 1000 IU/mL, 21 (2.5%) in CAR and 27 (3.2%) in ROC (p=0.40). No correlation between the anti-IgG titre and age was found (r=0.044; p=0.07).

Association between T.gondii infection and dementia

A total of 379 participants were excluded because cognitive status could not be determined for 276 of them (including 174 lost of follow up or missing) and 102 participants were diagnosed with MCI, resulting in an analytical sample size of 1,386 participants (Figure 1). Among them, 100 (7.2%) had dementia. Table 3 presents the socio-economic and clinical characteristics of participants with and without dementia. The T.gondii infection seroprevalence did not differ significantly based on the cognitive status: 64.0% (95%CI: 54.6-73.4) in participants with dementia versus 63.4% (95%CI: 60.7-66.0) in those without dementia (p=0.94). In the unadjusted and adjusted models, no association was shown between T.gondii seroprevalence and dementia (respectively OR=1.0 (95%CI: 0.7-1.6) and adjusted OR=1.0 (95%CI: 0.6-1.6)).

In a sensitivity analysis, we replaced the Toxoplasma infection status by quintiles of anti-IgG titre (Figure 3). No association was observed in both unadjusted (p=0.13) or adjusted models (p=0.36).

DISCUSSION

To our knowledge, this large population-based study is the first study to investigate the prevalence of T.gondii infection in older native African adults and the first study to examine its relationship with dementia in the Central African context. We found a high prevalence of T.gondii infection in older people regardless of areas (urban or rural) and countries. However we did not find any association between T.gondii and dementia.

In African tropical countries, such as CAR and ROC, a high prevalence of toxoplasmosis is usually observed due to the low sanitary conditions, with poor or inexistent water treatment (1;2). In these conditions, soil, food and water contaminated with oocysts increase the risk of T.gondii infection.

The higher seroprevalence observed in CAR may be partly explained by the lower socioeconomic status in CAR compared to ROC (41). T.gondii infection was described as associated with poverty in different countries due to poor hygienic and sanitary conditions [START_REF] Bahia-Oliveira | Highly endemic, waterborne toxoplasmosis in north Rio de Janeiro state, Brazil[END_REF][START_REF] Frenkel | Toxoplasmosis and its prevention in cats and man[END_REF][START_REF] Hotez | Neglected parasitic infections and poverty in the United States[END_REF].

In our study, the seroprevalence was significantly higher in urban areas than in rural areas as a whole, but differences were observed at the country level. In CAR, the seroprevalence was higher in rural area than in urban area while, in ROC, an inverse rural-urban gradient was observed. In ROC, a more westernised lifestyle of Brazzaville inhabitants could lead to a more frequent meat intake than in Gamboma where meat is more expensive. Seroprevalence was also lower in people who worked or are working in farms, fisheries or with livestock. People performing better paid occupations may thus have access to a diet richer in fruits, vegetables and meat that may be contaminated with parasite.

Unfortunately, soil exposure was not collected and data about food consumption were limited.

Heterogeneity in populations (women of childbearing age vs. older people) and design (case-control vs. cross-sectional survey) limits the comparison of our findings with other studies.

Surprisingly, we found a relatively large number of older adults with high antibody titres. Although studies on the evolution of the T.gondii serology in older populations are scarce [START_REF] Engroff | Seroepidemiology of Toxoplasma gondii in elderly individuals treated under the Family Health Strategy, Porto Alegre, Rio Grande do Sul, Brazil][END_REF], it is generally accepted that antibody titre decreases with age and are maintained at a low level over lifetime after an initial primary infection [START_REF] Montoya | Toxoplasmosis[END_REF]. Lifetime persistence of anti-T.gondii IgG results from continuous immune system stimulation by long-lasting tissue cysts. The usual decrease in antibody titres in older adults is hypothesized to be linked to the development of immunosenescence [START_REF] Weiskopf | The aging of the immune system[END_REF]. Several hypotheses may explain the relatively high proportion of elevated titres in older people in our study: i) a primary infection during the sample collection. The detection of IgM antibodies could have confirmed this hypothesis, but it was not tested here due to financial constraints; ii) a reinfection by a different Toxoplasma strain that would have resulted in an increase in IgG titres. Indeed, clinical observations have shown that an immune response against a chronic infection does not prevent reinfection of immunocompetent individuals with a strain different that the one responsible for the primary infection [START_REF] Elbez-Rubinstein | Congenital toxoplasmosis and reinfection during pregnancy: case report, strain characterization, experimental model of reinfection, and review[END_REF]. This hypothesis cannot be ruled out in our study since different genotypes have been identified in Central Africa [START_REF] Ajzenberg | Genotype of 88 Toxoplasma gondii isolates associated with toxoplasmosis in immunocompromised patients and correlation with clinical findings[END_REF][START_REF] Mercier | Additional haplogroups of Toxoplasma gondii out of Africa: population structure and mouse-virulence of strains from Gabon[END_REF][START_REF] Galal | Toxoplasma and Africa: One Parasite, Two Opposite Population Structures[END_REF]. The immunosenescence or a T-cell exhaustion during a chronic infection [START_REF] Gigley | T cell exhaustion in protozoan disease[END_REF] could facilitate the process of re-infection. iii) a non-specific and chronic immune stimulation due to different infectious agents (malaria, and other parasitic and viral diseases); iv) a genetic background leading to a higher humoral immune response in African population. Indeed, a high proportion (40.8%) of high levels of anti-T.gondii IgG (>400 IU/mL) was also reported in CAR in younger people [START_REF] Morvan | Toxoplasmosis at the Pasteur Institute of Bangui, Central African Republic (1996-1998): serological data][END_REF].

Previous studies that examined the association between T.gondii chronic infection and Alzheimer's disease (AD) or dementia reported conflicting results [START_REF] Mahami-Oskouei | Toxoplasmosis and Alzheimer: can Toxoplasma gondii really be introduced as a risk factor in etiology of Alzheimer?[END_REF][START_REF] Perry | Seroprevalence and Serointensity of Latent Toxoplasma gondii in a Sample of Elderly Adults With and Without Alzheimer Disease[END_REF][START_REF] Yahya | Impact of ApoE genotypes variations on Toxoplasma patients with dementia[END_REF][START_REF] Kusbeci | Could Toxoplasma gondii have any role in Alzheimer disease?[END_REF]. Our findings are contradictory with the ones of the only study assessing T.gondii infection as a correlate of dementia, carried out in a much younger population in Egypt [START_REF] Yahya | Impact of ApoE genotypes variations on Toxoplasma patients with dementia[END_REF]. Different methodologies, including participant recruitment and statistical analyses, may explain these discrepancies. Another explanation may be the influence of the T.gondii strain on chronic brain infection in immunocompetent patients. In in-vitro cell culture systems, different immune responses or neurotransmitter expression were observed in human nervous cell infected by diverse T.gondii strains [START_REF] Mammari | In vitro infection of human nervous cells by two strains of Toxoplasma gondii: a kinetic analysis of immune mediators and parasite multiplication[END_REF][START_REF] Xiao | Differential effects of three canonical Toxoplasma strains on gene expression in human neuroepithelial cells[END_REF][START_REF] Xiao | Abnormalities of neurotransmitter and neuropeptide systems in human neuroepithelioma cells infected by three Toxoplasma strains[END_REF]. In humans, a serotyping study suggested that serological pattern consistent with Type I strain in mothers was more susceptible to be associated with psychosis in offspring [START_REF] Xiao | Serological pattern consistent with infection with type I Toxoplasma gondii in mothers and risk of psychosis among adult offspring[END_REF]. More recently, in a murine model of AD, only mice infected with a type II strain of T.gondii, a major lineage that predominates in Europe and North America, were protected against deposition of amyloid beta, a marker of AD, despite both type II and type III strains establishing a chronic CNS infection and inflammatory response [START_REF] Cabral | Dissecting Amyloid Beta Deposition Using Distinct Strains of the Neurotropic Parasite Toxoplasma gondii as a Novel Tool[END_REF]. Mice infected with an attenuated type I strain that does not persist in mouse brain were not protected against amyloid beta deposition. Transposing data from animal models to human populations is particularly delicate as not all dementia subtypes share the same pathophysiological process and knowledge of the strains circulating in different countries is still incomplete (51;58;59). We however can reasonably think that our participants were infected by African strains, which share some genetic similarities with type I strains. Our results suggest that strains circulating in sub-Saharan Africa have no association with dementia.

The main strengths of our study are the use of a large, multicentre population-based design, the high number of participants with blood sample and a rigorous methodological method for establishing dementia diagnosis. However, a few limitations must be acknowledged. We were not able to analyse dementia sub-types, notably Alzheimer's disease, due to low frequencies. Additionally, we lack data that might influence our results such as timing of initial infection, interactions with other infectious diseases, and host genetic factors, as well as wealth or income which are potential confounders. Due to the study design, we are not able to rule out that earlier deaths due to T.gondii seropositivity obscured the association with dementia.

This large multicentre population-based study showed a high prevalence of T.gondii infection in older adults in Central Africa, with disparities in two neighbouring but different countries and areas related to socioeconomic and sanitary conditions. We failed to show any association between T.gondii chronic

Declaration of interest

We declare that we have no conflict of interest.

  Approvals were obtained from the ethical committee supervised by the Ministry of Public Health in CAR, the Comité d'Éthique de la Recherche en Sciences de Santé in ROC, and an ethical review board from the Comité de Protection des Personnes du Sud-Ouest et d'Outre-Mer 4 in France. All participants and/or their families gave informed consent prior to inclusion in the study. Written consent was obtained when feasible. Consent was obtained by thumbprint for illiterate people.

  infection and dementia but future investigations should consider the association with Alzheimer's disease and Mild Cognitive Impairment. Another perspective would be to evaluate associated infectious agents as done for other neurological conditions (60). MNPS-009-01 grant -the EPIDEMCA group (Maëlenn Guerchet, Bébène Ndamba-Bandzouzi, Pascal Mbelesso, Sophie Pilleron, Iléana Désormais, Philippe Lacroix, Victor Aboyans, Jean-Claude Desport, Pierre Jésus, Achille E. Tchalla, Benoît Marin, Jean-Pierre Clément, Jean-Charles Lambert, Jean-François Dartigues and Pierre-Marie Preux) -the participants in the EPIDEMCA study -the interviewers and nurses involved in this project for their assistance -town halls, mayors, and chiefs of districts for their collaboration -the Universities of Bangui (Central African Republic) -Marien Ngouabi in Brazzaville (Republic of Congo) -the Health ministries of the Central African Republic and the Republic of Congo, for their moral support -University of Limoges.

Figure 2 :

 2 Figure 2: Seroprevalence of Toxoplasma infection based on country and area, EPIDEMCA, 2011-

Figure 3 :

 3 Figure 3: Prevalence of dementia based on quintiles of anti-Toxoplasma IgG titres (n=1,386), EPIDEMCA, 2011-2012.

Table 1 :

 1 Sociodemographic characteristics of participants based on country (n=1,662), EPIDEMCA, 472

	473	2011-2012

Table 2 :

 2 Factors associated with Toxoplasma seroprevalence (n=1662), EPIDEMCA, 2011-2012

	Univariate analysis	Initial multivariate model	Final multivariate model

80+ 96 (15.6) 204 (19.5) 1.4 (1.0-1.8) 1.5 (1.1-2.1) 1.5 (1.1-2.0)

.7 (0.6-0.9) 0.7 (0.6-0.9) 0.7 (0.6-0.9)

	Area		0.001		0.001
	Rural	348 (56.6) 467 (44.6)	1	1	1
	Urban	267 (43.4) 580 (55.4) 1.6 (1.3-2.0)	1.4 (1.1-1.8)	1.4 (1.2-1.8)
	Education		0.019	0.288
	No education	446 (72.6) 702 (67.1)	1	1

Table 3 .

 3 Characteristics of participants according to dementia diagnosis, EPIDEMCA, 2011-2012

	No dementia	Dementia
	(n=1286)	(n=100)	p

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Acknowledgments

The authors would like to thank:

-French National Research Agency (ANR) for funding this study through the ANR-09-


Franck Marc Veyrat

Franck Soudan

LES CHEMINS DE LA CULTURE, BOURG-EN-BRESSE : pour un PAYSAGE hypermédia

archive ouverte pluridisciplinaire HAL, est destinée au dépôt

hypermédia2 sur le territoire de Bourg-en-Bresse, l'idée est bien alors de créer des chemins de traverse, liés bien sûr aux désirs des habitants de s'approprier des lieux emblématiques de la culture mais également des places publiques, des points de rencontre pour se retrouver ensemble, échanger des idées, discourir. Les Chemins de la Culture sont nés de cette volonté. Comment créer un PAYSAGE hypermédia entre art et communication, intimement lié au développement d'une nouvelle politique culturelle de la Ville de Bourg-en-Bresse ? Xavier Marcon, directeur des Affaires Culturelles, écrit de ce projet qu'il consiste "à définir une matrice organisationnelle qui soit autant physique que symbolique".3 Celle-ci, "matérialisée sur le territoire, assurera une animation sectorielle continue de l'espace publique en s'appuyant sur les forces vives constitutives de la diversité culturelle de ce territoire. Elle permettra la mise en place de parcours diversifiés d'une forme culturelle à une autre, d'une pratique culturelle à une expression culturelle, le tout avec le souci constant de la diversité et de l'accessibilité physique et symbolique à l'art et à la culture, pour que le droit à la culture soit effectivement inventé et mis en oeuvre, avec, par et pour les habitants. Ce dispositif pourrait donc être vu comme une grille de programmation grandeur nature établie sur le territoire urbain lui-même. […]. Il s'agirait de pouvoir faire travailler l'université sur la démarche ellemême afin d'aider à sa théorisation d'une part (l'institution a besoin d'une appropriation théorique de ses actions afin d'éclairer ses choix et la prise de recul), et / ou de faire travailler des étudiants pour l'élaboration de projets d'aménagements des stations à matérialiser sur le territoire : travail à la croisée de la signalétique urbaine, de l'oeuvre d'art, de l'action culturelle en train de se faire, de la communication institutionnelle innovante" 4 … Grandeur nature. Car si nous sommes devant un tissu urbain et culturel, la notion de paysage reste ici fondamentale. Ce dispositif s'ancre autour d'une articulation à plusieurs niveaux d'un paysage mental lié à des habitus, une Histoire / des histoires, des manières d'appréhender le monde… des changements géopolitiques et sociaux, des flux de population. Alors comment prendre en compte effectivement à travers ce tissage culturel l'importance d'une situation fortement ancrée entre un passé révolu et simultanément un avenir associé à une agriculture qui génère toujours d'importantes richesses ? Comment intégrer et donner une place à de nouveaux arrivants sur le territoire ? Comment réconcilier le centre historique et des banlieues en plein essor, dramatiquement postées au-delà du périphérique ? Et surtout de quelle manière associer les habitants à ce nouveau dispositif mis en place ? Enfin comment faire de Bourgen-Bresse, situé historiquement au carrefour de la Bourgogne, la Savoie et de la France -et qui s'est affirmée autrefois à travers des constructions ambitieuses et monumentales à l'instar du Monastère Royal de Brou 5 -une nouvelle capitale culturelle de la Région Rhône-Alpes Auvergne ? En effet si nous connaissons tous par exemple le célèbre poulet de Bresse 6 qui bénéficie incontestablement d'une renommée internationale, peu d'entre nous vont choisir de faire de Bourg-en-Bresse une étape touristique incontournable... Un boulevard périphérique à plusieurs voies coupe la ville en deux, la transformant en lieu de passage sans nous donner l'envie nécessairement de nous arrêter ; malgré une vie culturelle foisonnante qui mixe musique actuelle, programmation théâtrale, sciences, art et patrimoine, celle-ci est partagée entre plusieurs lieux disséminés sur le territoire et ne génère plus ou peu de lien social…

2_ÉMERGENCE-i

"L'urbanisme unitaire n'est pas idéalement séparé du terrain actuel des villes. Il est formé à partir de l'expérience de ce terrain, et à partir des constructions existantes. Nous avons autant à exploiter les décors actuels, par l'affirmation d'un espace urbain ludique tel que le fait reconnaître la dérive, qu'à en construire de totalement inédits".7

Autrefois le jardin définissait une zone tampon entre la nature restée vierge et le château ou la ville fortifiée. Quelquefois même construit, pensé à l'intérieur des remparts, cette interface structurelle proposait différents points de vue pour construire des entrées et des sorties, mais aussi des errances. Le château est censé avoir disparu. Matériellement, la ville a perdu ses remparts. Et, avec les systèmes de géolocalisation, nous possédons normalement les clefs du labyrinthe. Le jardin, au sens culturel du terme, ne définit plus de chemins. Il n'y a plus de point de départ, ni d'arrivée. Car, avec le téléphone portable par exemple, il n'y a plus de zone tampon physique entre nos points de vue i-matérialisés (par anticipation transformés en données tangibles et numériques) et tous nos déplacements possibles, nos dérives nécessaires. L'expérience prospective 8 d'un corps qui serait ®-MIS en jeu SE VOIT subtilement déplacée (remplacée ?) au travers d'une expérience projective obtenue par simulation. Le citoyen ne découvre plus SA ville. Vite submergé par les flux et les réseaux lui indiquant les points d'informations où il pourrait éventuellement se rendre, il est ensuite gentiment raccompagné (littéralement ®-CONDUIT) chez lui. À contrario de ce quadrillage presque systématique, cet urbanisme unitaire utopique autrefois suggéré par les Situationnistes ne va pouvoir émerger qu'en recréant de nouveaux dispositifs de jeu. Et, dans ce contexte de ®-MISE EN FICTION, si le jardin proposait un imaginaire de paysage la carte va devenir le véritable noeud structurel du projet les Chemins de la Culture. C'est en effet de la conception même de cette carte interactive que va naître le cheminement, au travers duquel se manifestera l'ambition de revalorisation du patrimoine culturel et du tissu public communautaire offert aux habitants.

Mais qu'en pensent-ils ? Le plus simple bien sûr aurait été de mettre en place un questionnaire et de le distribuer aux habitants de Bourg-en-Bresse. Or, peu de temps auparavant, Jean-François Debat (PS) vient d'être élu comme nouveau maire : la nouvelle équipe municipale choisit un lieu emblématique -l'hôtel Marron de Meillonnas 9 -pour être associé à l'art contemporain et accueillir la direction des Affaires Culturelles. Ces changements importants dans la vie publique nous incitent alors à partir directement à la rencontre des habitants. Le dispositif imaginé, mixant anthropologie visuelle et art hypermédia, va s'inspirer d'une expérience précédente originale créée pendant la Biennale Internationale Design Saint-Étienne 2008 par Catherine Beaugrand autour de l'urban gaming SUGOROKU 10 . Il va nous permettre non seulement de comprendre le territoire mais d'engager une véritable approche systémique du dis-courir. Des étudiants en Master parcourent la ville, filment et interrogent les habitants par rapport aux lieux où ils se trouvent et qu'ils traversent, la manière dont ils les entrevoient, leurs désirs de comprendre et de mieux connaître la ville, les événements qui s'y déroulent, l'importance dans cette découverte de l'utilisation des technologies numériques… Ainsi, progressivement, une cartographie des flux -tant physiques que numériques, des chemins empruntés par les habitants -pour traverser la ville ou se rendre d'un lieu à un autre, est dessinée, commentée, répertoriée avant d'imaginer ce qui pourrait être installé pour construire cet eSPACE11 hypermédia des Chemins de la Culture. Malheureusement cette 8 http://www.millenaire3.com/fileadmin/user_upload/textes/Prospective_au_GL_JLMolin.pdf, Rédigé par Jean-Loup Molin, La prospective au défi de l'action publique. Réflexions à partir de l'expérience du Grand Lyon : "Le niveau d'exigence croissant de la population vis-à-vis de tous les aspects de la vie urbaine fait qu'il n'est plus possible d'une part d'appréhender l'habitant simplement comme un administré, et d'autre part de s'appuyer sur la fiction du comportement moyen d'un individu moyen... qui n'existe pas". p.7. Jean-Loup Molin est responsable du pôle veille et recherche du Grand Lyon, Direction de la prospective et du dialogue public. Consulté en ligne le 24 avril 2015. Consultable également à partir de la revue Futuribles, n°386, juin 2012, https://www.futuribles.com/fr/base/revue/386/ 9 "La sauvegarde d'un patrimoine. Joyau architectural édifié en 1774 par Gaspard Constant Marron, baron de Meillonnas et fondateur des fameuses faïenceries, cet élégant hôtel de style Louis XV est inscrit à l'inventaire des monuments historiques. Après plusieurs années de restauration, le bâtiment a retrouvé son lustre d'antan" : http://www.meillonnas-faience-brou.fr "L'Hôtel Marron de Meillonnas a retrouvé sa vocation culturelle née au Siècle des Lumières. Doté d'une signature moderne, H2M devient l'épicentre du dispositif des Chemins de la Culture visant à renouveler les modalités d'accès à la culture. Prenez l'air d'H2M sur les Chemins de la Culture. H2M est un pôle d'information, de découvertes et de pratiques culturelles. La cour André Malraux est un lieu de création qui met en scène diverses manifestations culturelles au croisement de l'image, de la musique et de la scène". http://www.bourgenbresse.fr/Vivre-a-Bourg/Culture/H2M-Hotel-Marron-de-Meillonnas H2M abrite en outre, le siège de la direction des affaires culturelles de la Ville de Bourg-en-Bresse.

  Ce labyrinthe contextuel va devoir être repensé et enrichi par Franck Soudan lors d'une thèse CIFRE. Placée sous la direction de Jacques Ibanez-Bueno, en co-direction avec Marc Veyrat, des hybridations entre art, communication, urbanité et numérique vont progressivement créer un maillage d'interconnections. Associé volontairement dès la genèse de ce projet ambitieux par la Direction des Affaires Culturelles, tout notre groupe de recherche G-SICA (laboratoire LLSETI : Image, Communication & Art Numérique) ainsi que des étudiants de Master 1 & 2 vont être impliqués dans cette première phase de réflexion autour des Chemins de la Culture. Construire une réflexion théorique à partir d'une étude anthropologique du territoire, étudier les usages pour comprendre comment il fonctionne et génère des flux (sociaux, économiques, politiques), tout d'abord afin de convaincre une majorité d'élus ainsi que les habitants de Bourg-en-Bresse de son importance capitale ; ensuite seulement imaginer des dispositifs innovants pour les faire fonctionner en réseau (ce sera là en grande partie le travail de Franck Soudan) ; enfin enquêter et rendre compte des impacts effectifs sur le territoire quelque temps après son installation. Ce travail va donc se dérouler en plusieurs phases. De 2008 à 2010, c'est en quelque sorte la genèse de l'oeuvre, l'étude du territoire entre errances et doutes. Nous nous déplaçons plusieurs fois à Bourg-en-Bresse. Ce sont également les premières tractations avec la mairie et la direction des Affaires Culturelles (Carole Brandon / Marc Veyrat). Puis va s'ouvrir une phase d'enquêtes filmées, réalisées par les Master 1 & 2 (Ghislaine Chabert / Jacques Ibanez-Bueno / Marc Veyrat), début 2010, pour préparer une présentation devant les élus réunis en conseil municipal. Après validation par ce dernier, le projet entrera enfin dans un calendrier. Il est en quelque sorte alors réellisé, c'est-à dire associé à une temporalité de conception et de mise en place. Après seulement va arriver le temps de la thèse CIFRE… http://www.cheminsdelaculture.fr/

  "… 10 ®-LIRE à ce propos Marc Veyrat, SUGOROKU, des petits chemins de toutes les couleurs, in HYPERURBAIN 4 / Mobilité et Parcours Hybrides, sous la direction de Patrizia Laudati, Dominique Laousse et Khaldoun Zeik, Éditions Europia,Paris, 2014, p.59-78. cartographie impose à nouveau des contingences, des choix, des décisions politiques.Toute la difficulté du projet revient alors à trouver des co-incidences entre une commande impérative et posée en amont, et le vécu du territoire, impétueux, qui n'énonce pas les mêmes enjeux et ne dis-court pas sur les mêmes chemins. La volonté politique, d'abord, peut s'énumérer en fonction des exigences suivantes : 1. Communication et médiation nécessaires : nous ne devons plus pouvoir dire qu'il ne passe rien de culturel à Bourg-en-Bresse ; 2. Dé-segmentarisation et réseautage : il faut trouver un moyen de détacher les publics habitués d'un lieu de fréquentation unique ; 3. Physibilité 12 et présence visuelle : la réponse à la commande doit être visible, l'accès au dispositif doit pouvoir se faire à partir de l'espace physique. Cette énumération ne correspond donc pas seulement à l'énoncé d'un besoin mais bien à une demande. En effet : imaginons que nous soyons vendeurs de pizzas, la demande pourrait correspondre à la commande d'une 4 fromages. Mais le besoin que nous satisferions auprès de notre client est la faim 13 elle-même. La petite étude menée par G-SICA et les étudiants du département Communication Hypermédia pointe déjà un peu mieux les problèmes de la ville : -dans quel but : pour que la valeur réelle du territoire s'accorde avec la valeur perçue, afin que l'effort remarquable mené par la DAC trouve tout son écho auprès des citoyens de Bourg-en-Bresse / en région Rhône-Alpes / en France / dans le monde ? Pour imaginer comment nous pourrions nous servir de ces études menées sur le terrain sans en rester prisonniers et les transfigurer, c'est-à-dire les interroger depuis une posture artistique, un autre projet artistique commencé dès 2010 -U-rss 14 http://u-rss.eu -va nous servir de terrain expérimental. Car l'eSPACE de SOI, l'expression offerte à un individu pluggé malgré lui sur le tissu social de Bourg-en-Bresse, passe désormais au jour du i -au jour de l'information et d'un Je "hyperréel" (Baudrillard) -par un ensemble d'interfaces / pliages. De plus les réseaux, décuplés par l'apparition du téléphone mobile -cet outil / écran qui nous permet pratiquement de communiquer en temps réel mais aussi avec des territoiresnous projettent dans des U-topics discontinus, des U><U plus ou moins fictionnels en forme de tranches d'apparitions interférant avec, sur, contre les outils de géolocalisation, de mise en visibilité et à fortiori ceux de contrôle. JARDIN-® : l'aire jardinable -monumentale et en réseau de cette nature urbaine qui va être suggérée par le projet -définit certes un dispositif cartographique mais qui doit engendrer sur le terrain ce que nous pourrions nommer une "archi-sculpture". 15 Avec "La Bicyclette ensevelie" 16 réalisée par Claes Oldenburg & Coosje Van Bruggen dans le Parc de la Villette en 1990, les enjeux sont multiples. Tout d'abord le spectateur / promeneur s'inscrit nécessairement dans une expérience physique du lieu. Bien sûr mentalement celui-ci s'inscrit dans un processus cartographique : la disposition de chacun des éléments n'est pas fortuite. La sculpture ®-AGIT à l'architecture, la provoque et construit un cheminement qui va nous écarter ou nous inciter à l'affronter, à l'aide de l'oeuvre. Ainsi, non seulement chaque fragment de la bicyclette ®-compose à la fois une distanciation au lieu par le point de vue obtenu au moment de sa découverte, mais suggère également un réseau de forces telluriques, souterraines, presque occultes par le fait d'être ensevelie, soustraite au toutes les tentatives jusqu'à présent pour impliquer nos différents partenaires dans la construction et la diffusion sur leur réseau de cartes interactives se sont plus ou moins soldées par des demi-échecs. En 2011, avec le portrait social Réseau Musées Méditerranée 18 , l'idée d'une carte nous apparaît très vite, comme évidente, ne serait-ce que pour remplacer l'existante où le choix de Google Earth est injustifié parce qu'il nécessite l'installation d'un plugin. Par ailleurs, dans sa globalité, le site de l'époque reflète très mal la volonté réticulaire du titre, mais l'architecture de l'information présente l'avantage d'être littéralement traduite à l'interface. Sans habillage, nue, transparente, nous pouvons apercevoir à travers chaque fiche 14 Marc Veyrat & Franck Soudan, U-rss in Village Pipole, in Usages de l'Internet, Éducation et Culture, sous la direction de Gilles Rouet, collection Local & Global, Éditions L'Harmattan, Paris, 2012. Au centre de l'oeuvre U-rss se pose la question du portrait social. Qu'est-ce que le portrait au jour du i ? C'est moins une question physique (normalisation, chirurgie de la retouche) qu'@-faire de liens et d'informations entretenus, déployés, commentés, partagés sur les réseaux. Le lieu du portrait est un lieu d'interférences numériques, en ligne, consultable H24 et multinodal. 15 Philippe Sabourdin, La bicyclette ensevelie / Claes Oldenburg & Coosje Van Bruggen, Éditions Canopé, Futuroscope, 2014, p.45… Quand l'errance des artistes se superpose à l'errance du projet : "Le 7 mai 1986, Coosje Van Bruggen entre par curiosité dans la librairie Gallimard du boulevard Raspail, à Paris. Là, son attention est attirée par un livre. Il s'agit du premier roman de Samuel Beckett écrit en français. Sur la couverture, se trouve un personnage sur une bicyclette. C'est Molloy. La sculpture naîtra de cette image qui réactive un ancien projet dont les deux artistes avaient fait une épure photographique en 1978. […] La Bicyclette ensevelie 'incarnera' l'errance circulaire de ce personnage handicapé qui, menacé de déséquilibre, ne fait qu'un avec sa bicyclette", p.37. 16 Claes Oldenburg & Coosje Van Bruggen, La bicyclette ensevelie (Buried Bicycle), 1990, Parc de La Villette, Paris. musée un certain nombre de liens explicites vers un autre musée du réseau. Mais il n'est nulle part fait mention de la qualité de ce lien. Ainsi l'idée de programmer une chair à ce squelette de données s'avère offrir une nouvelle vie à ce réseau. À l'issue d'une première version, nous insistons sur l'opportunité visuelle de la carte interactive, sur sa capacité à exprimer la puissance territoriale des informations : une carte permet en effet de ®-produire une connexion affective avec le territoire. Mais, face à cette tactique consistant à avoir rendu lisible le réseau sur le territoire, la réaction des conservateurs fut largement sceptique. Car faire passer le texte dans l'image, rendre perceptible l'associativité promue par les institutions ou confronter la signification des segments territoriaux à la réalité de la matière, c'est une manière effective de faire remonter les traces aux actions, de rétro-projeter les intentions. La carte est toujours l'enjeu du dis-courir. C'est le lieu du secret, du programme mis à jour -à travers sa légende, ses partis pris formels -®-plaçant sous l'oeil du lecteur tous les possibles d'un territoire. La carte simultanément chiffre er déchiffre. Ainsi, ®-agencer une cartographie, c'est individuer la technique sur des lieux temporaires, instituer des plans informatifs, un dis-courir propulsé par des machines de vision (Virilio). La cartographie de Bourg-en-Bresse ne va pas échapper à la règle. Car cet objet-lieu est le support computant du territoire ; il permet dans son maillage -le programme au regard de sa mise en forme et inversement -de mettre en relation les attributs ethno-esthétiques d'une possible controverse. Machine-territoire, la carte manifeste, intensifie l'affectivité des traces, des relations à l'altération. Elle situe véritablement -pour celui qui la crée comme pour celui qui la lit -le lieu effectif du politique, l'®-JARDINABLE. Tout l'enjeu de cette première phase du travail à Bourg-en-Bresse, va être de ®-PENSER LES CHEMINS : les chemins mnémotechniques d'un territoire de l'i-lisible mis au regard d'un corps social, un urbanisme unitaire en quelque sorte éclairé par un dispositif cartographique suffisamment ouvert -dans l'idéal d'un U-topic voire même autogéré -pour engendrer des i-LÉGOS discontinus, élastiques et exponentiels. Se faire corps (dans le corps/US public), c'est naviguer parmi un soi éclaté, mille fois réfléchi sur les écrans ; cela revient à individuer des événements mis au regard d'un dispositif réflexif (pointés au risque de LA CARTE), à exprimer un enchaînement de points de vue dans la série des images computées. Ces fragments (les i-LÉGOS), pointent des résidus de la projection virtuelle des événements phénoménologiques à venir à travers cette matière cartographiée. Les traces de cette matière (qui ne seront pas forcément d'ailleurs écrites sur la carte) articulent un réseau qui fabrique les marques de notre présence et marges de notre épaisseur ontologique, les empreintes d'un acte emporté à travers sa propre synergie du dessein et la modulation programmée d'un système syntaxique, déporté et légendé. JARDIN-® Bourg-en-Bresse imposera donc de comprendre l'altération d'un i-RÉEL (des réseaux informatifs) sur un terrain de jeu, à travers l'hybridation d'un territoire à une carte. Avec toujours un certain risque. Car révéler des liens, montrer, situer où, comment des points de vue interférent peut engendrer des luttes politiques. La manière de lire contient le pouvoir. L'accès à la légende de la carte donne la clef du territoire. Car le château n'est plus un lieu physique, il est désormais enfermé derrière des murs virtuels, translucides mais suffisamment hermétiques pour ne laisser passer que ceux déchiffrant le code. Pour accéder au château, il ne faut pas seulement savoir traverser le labyrinthe informationnel, il est désormais nécessaire de retourner le lieu, cultiver le terreau même de l'information : son programme.

nous n'y avons pas faim. Ce n'est pas que nous nous y ennuyons, c'est que le rapport entre le territoire et ses habitants est paradoxalement dévalué alors que la ville, notamment par le travail de la DAC et l'énergie qu'insuffle les opérateurs culturels, dispose d'une richesse incroyable. Cinq questions émergent et constituent un milieu autour duquel devraient se ligner ces points de coïncidence entre la volonté politique et ce que les enquêtes menées auprès des habitants nous auront permis de révéler :

-à quoi tout cela va t'il servir ? : à revaloriser la programmation culturelle de la ville ; -à qui cela sera utile : aux opérateurs partenaires et aux citoyens ; -sur quoi cela agit-il : sur la ®-PRÉSENTATION du territoire ; -comment cela marche : par un renouvellement des modalités d'accès à la culture basé sur l'usage d'un dispositif numérique en premier lieu consultable sur Internet. Celui ci doit permettre de centraliser toute action culturelle de qualité (ingrédients labellisés tels des AOC) en fonction d'un groupe de descripteurs commun et partagé (le menu). Associé à un moteur de recherche, ce dispositif doit enfin permettre de trouver un événement quelconque, mais surtout de donner envie de chercher (en quelque sorte de faire saliver). regard. Puisque cet élément est indissociable d'un terrain (le Parc) et d'un ensemble (la Bicyclette), l'idée est donc de provoquer à travers les Chemins de la Culture une distance critique. L'acte citoyen qui sera mis en place, de manière in/visible par le biais du réseau dans une cartographie, doit questionner le seuil du visible. L'archi-sculpture infirme un eSPACE séquencé, tout à la fois discontinu et disruptif. "No risk no fun". 17

Or, dans U-rss,

Marc Veyrat / Franck Soudan -2015

Roland Barthes, Fragments d'un discours amoureux, Éditions du Seuil, Paris, 1977, p.7.

Ce dispositif a été imaginé au départ lors de rencontres informelles entre Carole Brandon, Xavier Marcon et Marc Veyrat. Il va progressivement se déployer avec, autour de toutes les ressources prospectives en recherche, dont dispose dans les années 2010 le département Communication Hypermédia, : Jacques Ibanez-Bueno, Ghislaine Chabert en Sciences de l'Information Communication, Carole Brandon et Marc Veyrat en Art.

Xavier Marcon, directeur des affaires culturelles, déclaration d'intention, avril 2009.

Idem 3 .

En 2015 le Monastère Royal de Brou a été élu Monument préféré des français. http://brou.monuments-nationaux.fr.

In L'Internationale Situationniste n°3, sous la direction de Guy Debord, Paris, décembre 1959, p.13. ®-VOIR à ce propos l'intégrale des 12 numéros de la revue : http://www.larevuedesressources.org/internationale-situationniste-integrale-des-12numeros-de-la-revue-parus-entre-1958-et,2548.html

"L'oeuvre en réseau se trouve toujours confrontée à une distorsion spatiale et temporelle. Entre l'espace-temps physique des utilisateurs et l'espace-temps du programme et des réseaux, ce nouveau territoire qui se dessine est un lieu hybride -l'eSPACE -constitué désormais d'espaces virtuels ET i-réels,

Antoine Schmitt, http://www.cuberevue.com/no-risk-no-fun/1443

L'