domain: shs chim

text:
Marie-Anne Loeper-Attia
email: maloeperattia@cite-musique.fr

Physical and Chemical Interactions between Metallic Instruments and Plastic Threads

Keywords: brass, exhibition, plastic thread, polypropylene

Introduction

In a museum setting, objects are subjected to a number of factors, such as climate, lighting and display method. The items in question, instruments, can be placed directly on a surface with a screen material that avoids any contamination with the support. The presentation can be more constrained if the instrument is mounted. The display method must be adapted to the materials the item is made of, taking into account any observed degradation or fragility. A material's corrosion resistance, especially in the case of a metallic material, is not merely an intrinsic property. The amount of corrosion depends greatly on the environment. It is therefore essential to set up sound storage and display protocols that correspond to an item's specific needs. This paper discusses the support and display of musical instruments in a museum setting, specifically at the Musée de la musique -Philharmonie de Paris at its opening in 1997 and during the various stages of work in the exhibition areas, taking into account the constraints inherent to the materials, the location and the museographical approach.

Description of the museum and the particularity of the collections

The Institut national de musique was created by decree on 8 November 1793 to '[train] the artists needed to perform on national holidays' and included an 'instrument room' containing pieces confiscated from 'emigrants' . Under the terms of the Convention of 17 August 1795, the Institut became the Conservatoire de musique de Paris and included a collection of 'antique or foreign instruments, and those of our own customs, that can in their perfection serve as models' . Of the 316 items transferred to the Conservatoire in 1795, only a dozen remain today. In 1861,

Abstract

The collections at the Musée de la musique in Paris include several hundred brass, silver and silver-plated wind instruments that are often exhibited, loaned or played. For the museum's opening in 1997, special mountings were proposed and designed by Franck Hammoutène and various types of thread were used to hold the instruments by their cylindrical parts. These threads were regularly untied and re-tied, for instance, for loans to temporary exhibitions, studies and when the galleries were refurbished in 2009. They were also used for temporary reinforcement (instead of adhesives), mounting (sometimes in combination with foams) and for attaching labels. Various types of thread were used -rope, fishing line and sewing thread -composed of nylon, polyester, polyamide or polyethylene. The choice between these four materials depended on criteria such as the weight and nature of the instrument, colour of the surface it is attached to and the friction or tractive forces involved in the instrument's use. Over the years, various types of surface damage to the metallic instruments have been noticed, including mechanical damage, such as scratches, and chemical damage, such as localised corrosion. After a short description of the collection of instruments and the degradation observed, this paper discusses the solutions now being applied at the Musée de la musique. The research addresses four points: 1) identification of the mechanical and chemical damage observed using visual and microscopic observations and XRF in situ; 2) the required specifications for choosing a new type of thread; 3) the types of plastic thread chosen and their various chemical and physical characteristics; and 4) corrosion tests in a humid chamber and Oddy tests with metallic sheets in contact with various types of plastic thread. The new solutions found will be introduced into the framework of the museum's global preventive conservation protocol.

COMPOSITE OBJECTS

the French government purchased for the Conservatoire the instrument collection of Louis Clapisson, a composer and member of the Institut. Two rooms were officially opened and, for the first time, a collection of instruments was made accessible to the public in Paris, marking the birth of the instrument museum. Clapisson was the first curator, followed by the composer Hector Berlioz and then Gustave Chouquet, who significantly developed the collections. The third major milestone occurred around 1960, thanks to the Countess Geneviève de Chambure (Getreau 1996). During this period, the role and purpose of a future Musée de la musique were defined in terms of conservation, restoration, inventory and documentation (Figure 1). In 1978, with the founding of the Cité de la musique, the decision was made to hand the Conservatoire's national collections over to the state, leading to the creation of the Musée de la musique in 1995. An acquisition and restoration campaign was launched and plans were made for a new museum, which officially opened at this new site in 1997. A redesign in 2009 introduced the latest museographical changes.

The major themes covered are the 17th century and opera, the music salon of the 18th century, the great inventions of the 19th century, the new sounds of the 20th century and, finally, the musical traditions of other continents (Figure 2).

Instrument mounting and display at the Musée de la musique -Philharmonie de Paris

The mounts created for the museum when it opened in 1997 were designed by architect Frank Hammoutène. Today, the museum is still required and obliged to use the same type of mount, based on the principle that the instruments are (generally) presented vertically or in playing position. A metal armature holds them up with half-rings covered in high-density polyethylene foam and threads encircling the instrument. These museographical constraints were included in the convention signed between Frank Hammoutène and the Musée de la musique. It explains why this display method is imperative and why it must continue to be used even today. Securing the instrument in a vertical position requires adjusted grips and a mounting perfectly adapted to the instrument. This often requires fastidious adjustments (Figures 3 and4). There were, however, several exceptions to this rule when an instrument's configuration was particularly unusual and could not be made to fit the mounts designed by Frank Hammoutène.

Materials used and types of damage observed

To secure each instrument to its attachment ring, special threads were chosen, i.e. woven fishing line in two colours (grey and brown). The colour was selected to match the object. The brands used were either Caperlan thread (by Decathlon) or Nacrylan thread (by Tortue). Both types of fishing line are woven and made of Dyneema, the main component of which is high-density polyethylene (HDPE). The other types of fishing line are polyamide-based (nylon) or fluorocarbon. In addition to the main component, the threads also contain micro-pigments or abrasives that make the thread visible in water and ensure good grip in the reel during fishing. Unfortunately, the exact nature and concentration of these components were not provided by the manufacturers. Non-woven threads such as nylon (polyamide) or hemp (for the labels) were also sometimes used on the instruments. Table 1 indicates the type of fibres and their most common commercial names.

These threads, especially the woven ones, were chosen essentially for their strength. All of the data came from the supplier Kanirope (Table 2). Even though the values for Dyneema are given for 12-strand weaves rather than the 8-strand weaves of the others, it is clear that this fibre is much stronger. Given the low values of hemp and cotton, it is suitable that they be used only to attach labels.

These threads were regularly cut and removed when an instrument was taken out of its display to be loaned, restored, consulted by researchers or played by musicians. Musical instruments are at once technical objects (products of science: acoustics, mechanics, etc.), objects of use (producers of sound) and art objects [START_REF] Barclay | The preservation and use of historic musical instruments: Display case and concert hall[END_REF]. During remodelling work at the museum, all of the brass instruments (which are in fact instruments made of brass or silver-or gold-plated brass such as trumpets, saxophones and trombones) were removed from their mounts to be cleaned (Loeper-Attia 2007). It was then realised that a large number of the instruments were scratched and/or corroded where they touched the supporting threads. This damage was only visible on the metal objects; other instruments made from organic materials showed no sign of oxidation. Instruments with labels attached by old thread, as could be seen, also presented surface corrosion (Figures 567). These traces were stubborn and often impossible to remove completely with chemical processes or mechanical cleaning with abrasive powders. It was decided not to attempt to remove the scratches observed because it would have required abrading a significant amount of material. Moreover, the intervention would have been clearly visible on these larger, polished areas and it would have been necessary to clean the entire surface. The Museum's team was therefore faced with the need to find an alternative to these threads to ensure the metal instruments were properly preserved.

Looking for other materials

Surveying other museums confirmed the regular use of nylon threads, fishing line and cotton threads to secure objects to mounts.

In order to choose the threads best suited to the conservation/restoration of cultural heritage objects, particularly those made of metal, the team first established appropriate specifications and then sought suitable products on the market and examined their composition. The threads selected had to meet the following specifications:

• product traceability The threads are made from crystalline polymer fibres. These polymers are elongated macromolecules arranged in straight, parallel filaments. Their hydrogen bonds hold the chains together and partly explain their high tensile strength. The particular positioning of the macromolecular chains occurs after the thread drawing phase following extrusion [START_REF] Massardier | Etat de l' art concernant la compatibilité des matières plastiques[END_REF]).

It should be noted that a polymer in its raw form generally lacks the properties required for the application in question. Additives need to be added to the plastic [START_REF] Cavalier | Adjuvant des plastiques, carbonate de calcium additif multifonctionnel[END_REF]) and these primarily affect the aesthetics, chemical stability, UV resistance, heat resistance, cost and plasticity. One function of additives is also to slow the polymers' oxidation, which causes yellowing, potential loss of transparency, the appearance of crazing and affects the mechanical properties by reducing potential flexibility and tensile strength. This oxidation is accelerated by temperature and UV rays. Additives trap formed radicals by reacting with them and/or absorbing UV energy. Common additives employed are inert composites, generally mineral-based, such as natural or precipitated calcium carbonate, talc and china clay, graphite, molybdenum disulfide and polytetrafluoroethylene. Phosphate-, phthalate-or benzoate-based plasticisers may also be present [START_REF] Verrier | Adjuvant des plastiques, plastifiants. Techniques de l'ingénieur[END_REF]. Table 3 sets out the data collected on the primary fibres selected during the first phase of the investigation. All the values given and protocols of measurement are taken from the Techniques de l'ingénieur or mentioned reviews (see References).

It was decided to take into account only certain physical characteristics of these polymers, those that struck the team as most important to the specifications being drafted [START_REF] Dossogne | Polyéthylène. Techniques de l'ingénieur. Plastiques et composites[END_REF]).

• Modulus of elasticity: the tensile stress required to obtain a given elongation. This is a value intrinsic to the material, defined as the ratio of stress to the elastic deformation caused by this stress. It is often called Young's modulus and its unit is the Mpa (megapascal). • Breaking strength: also called stiffness or tensile strength. It is the resistance to deformation under the action of continuous stress and therefore corresponds to the tensile force under which a material reaches its breaking point. It must not be confused with stretch resistance: a material or fibre can be highly elastic yet have very high tensile strength (late rupture). • Loss of flexion or resistance to flexural stress: loss of stiffness after 60 cycles of 180° folds.

• UV resistance: this is the resistance of the fibre to breaking under natural light, measured in months [START_REF] Bohé | Comportement des matériaux à voiles de bateau[END_REF]). • Elongation at break or percent elongation: this is a non-quantified characteristic of materials and defines a material's ability to stretch to its breaking point when under tensile stress. • Melting temperature.

The results clearly show the significant differences in these fibres' behaviour. For example, polyethylene (PEN or HDPE) has a very high breaking strength, displays no loss of strength due to bending and has good UV resistance. Nylon is one of the most elastic fibres (it has high elongation at break), which allows it to absorb load peaks. Indeed, the higher a material's modulus of elasticity, the stiffer the material is; in other words, under equal stresses, a material with a high modulus of elasticity will stretch less than a material with a low modulus of elasticity.

For instrument-mounting purposes, it is therefore preferable to use a material with a high modulus of elasticity to ensure a support that is always adapted and adjusted. The loss of flexion must be low so that it can withstand bending and folding. The melting temperature must be high, as must be the breaking strength. It must also have good UV resistance. In the tests carried out, focus was therefore placed on polyethylene fibres -both with and without additives (Nacrylan, Dynema).

Comparative tests

Ageing tests

The goal was to demonstrate proper conservation of the threads chosen in a harsh environment in contact with metal. Rather than conducting an Oddy test which evaluates the gaseous effect of a composite on a metal plate, conditions closer to those in the museum setting were created, i.e. thread and metal in direct contact, since the damage observed was only the result of direct contact and not a gaseous effect. The metal support chosen was a form of brass, similar to the alloys found in brass instruments, i.e. with a mass percentage of around 30% zinc. This content is close to that of alloys now referred to as 'cartridge brass' , characterised by better ductility and higher corrosion resistance. Indeed, brasses containing up to 35% zinc are single-phase and reputed for their ductility and malleability when cold. Above 35%, hardness increases and ductility when cold is not as good, although malleability when hot is excellent. The maximum threshold for zinc content in brass is 42%, beyond which the alloys become too fragile. Two tubes and a rectangular-section rod were cleaned with abrasive powder (calcium carbonate), then rinsed and degreased with demineralised water, ethanol, acetone and cyclohexane. Various threads were then knotted to this assembly as shown on one of the tubes (Figure 8). Each thread was previously weighed to evaluate whether there was any weight loss or gain after the experiment, to help quantify any potential transfer or loss of material. Each thread was weighed four times using a Mettler Toledo precision scale (0.0001 g accuracy) before and after placing in the chamber. The tubes were placed in a climatic chamber for 30 days. The thermal cycles lasted 12 hours with a temperature variation of 18°C-22°C and relative humidity (RH) of 50%-80%.

These values corresponded to the possible variations inside the museum (one of the stores had suffered a climatic incident due to a failure in its air conditioning system and the RH had risen to 80%). After removal from the chamber, the tubes were examined and each wire was weighed. The weight variations were all consistent with the values indicated in the literature and, on average, were below 0.05%, except for the Nylon which was slightly more hygroscopic. Observation with the naked eye and a binocular magnifier revealed that every thread tested caused surface corrosion on the metal, except the polypropylene-based thread.

In phase two, tests were repeated with a thread made of polypropylene (the main component of Prolene). This material can be procured from textile manufacturers who produce these threads in large quantities. They come in various sizes, but those with diameters of less than 1 mm have ample strength. The thread tested here had a diameter of 0.25 mm and can withstand a load of 3 kg. The threads are naturally transparent up to a diameter of 1 mm and slightly opaque in larger diameters. Tests were also conducted with a monofilament thread compared to a woven or stranded thread to see if the presence of multiple strands might retain enough humidity to cause corrosion in the metal. Two polyethylene threads were tested: a monofilament thread and a thread woven from two filaments. The same protocol in the climatic chamber was applied and the same weight measurements were taken before and after the test. Other threads were knotted onto the brass plate to help characterise the corrosion products that formed on the surface of the metal. Their distribution is shown in Figure 9. After spending time in the chamber, it was again evident that only the propylene threads (monofilament and woven) did not interact with the metal plate in any way. Table 4 sums up the results of these tests.

X-ray fluorescence spectroscopy of corrosion products in ageing tests

In an effort to better understand the corrosion these threads were causing on the alloys, analysis by x-ray fluorescence spectroscopy (XRF) was done on three corroded areas on one of the tubes after time in the oven and on a non-corroded area of the same tube. The corroded areas corresponded exactly to the position of the polyester 1100/2/3 Vectran and Spectra threads. Three shots were taken of the same area in order to obtain the most accurate possible results. The measurements were taken using an ArtTAX prototype II spectrofluorometer (Intax GmbH).

The ArtTAX acquisition software connected to the spectrofluorometer allowed the spectra obtained to be processed.

ArtTAX has an application that automatically identifies the elements present in each sample. This can be useful when analysing unknown samples, but it is important to maintain a critical eye with regard to the elements identified [START_REF] Gomes | Vers l'analyse quantitative des alliages de laiton et bronze de la collection du Musée de la musique par spectrométrie de fluorescence X[END_REF]. Our analysis of the results did not provide any information on the nature of the corrosion products formed, given that the markings measured by the spectrometer and the respective spectra of the non-corroded tube and the corrosion products generated by the three threads are similar, and in fact identical to the naked eye. There are several possible explanations for this: the very small quantity of corrosion products formed and the limited range of use of the spectrofluorometer -it cannot determine elements below boron (Z=5) and above uranium (Z=92). In this case, a Coolidge tube with a molybdenum anode was used, furtherer limiting the range of use (Z=13 to Z=92). To determine the degradation product formed accurately, other analysis methods were needed.

What protocols must be adopted for metal instruments?

The conducted tests showed that most threads corrode metal sooner or later. It is highly probable that this is mainly related to the adjuvants and additives put into the fibre during manufacturing, given that Dyneema, Spectran and Nacrylan threads are made primarily of polyethylene, a material known to have no direct effect on metal [START_REF] Lavédrine | Preservation of plastic artefacts in museum collections[END_REF]). The scratches observed on the metal sheets may be due to the abrasive effect of materials added to the threads, such as calcium carbonate, china clay and talc. It is therefore recommended that a thread containing no additives be used. Pure polypropylene thread also meets the other requirements stipulated in the specifications. Since 2006, we have been using two types of pure polyethylene thread, with a diameter of 0.25 mm or 0.53 mm. They are transparent or slightly opalescent (in the case of the thicker thread) and are used to secure adjusted mountings without risk of damage to the object. Thus far, no contact corrosion or scratching as previously observed has been noticed. Some of the other threads tested in this study are now being assessed for possible partial integration with woven threads or cords on musical instruments from outside Europe.

Conclusion

In developing an adapted protocol for the mounting and display of musical instruments at the museum, it was possible to select a fibre -polypropylene without additives -that is stable over time, has adequate mechanical properties and does not react with the metal in the instruments. A sound mounting protocol was therefore successfully established. We have since expanded the use of these types of thread, whose thinness and transparency make them ideal for use as supports and for seams in fabrics, or for reinforcement or partial integration with weakened woven fibres. Better understanding of the interactions of the other types of thread with metal is still needed.

Figure

  Figure 1. Musée instrumental in 1884. Engraving by Eugène Tradoné for the second edition of Chouquet's catalogue

Figure 2 .

 2 Figure 2. Display case for 19th-century instruments

Figures 3

 3 Figures3 and 4. Instrument mounting in a display case

Figure 5 .

 5 Figure 5. Silver corrosion due to a Nacrylan thread

Figure 8 .

 8 Figure 8. Brass tube with different threads

Figure 9 .

 9 Figure 9. Brass plate with different threads

Table 2 . Flexural strength of different threads Composition Type of fibre Flexural strength daN (kg) nylon

 2

(polyamide) 8-strand, 1 mm diameter 30 hemp 8-strand, 1 mm diameter 10 cotton 8-strand, 1 mm diameter 15 Dyneema (HDPE) 12-strand, 1 mm diameter 195

Table 1 .

 1 Composition of different fibres and threads

	Woven fibres and threads		Non-woven fibres and threads
	Composition	Commercial name	Composition	commercial name
	cotton		aromatic polyamide or aramid (PAA)	Kevlar, Technora, Twaron
	non-aromatic polyamide (PA)	Rilsan, Technyl Nylon	aromatic polyester	Vectran
	non-aromatic saturated polyester (PET)	Dacron, Tergal, Tetoron	carbon
	non-aromatic saturated polyester (PEN)	Pentex
	polypropylene	Prolene
	high-density polyethylene (HDPE)	Spectra, Dyneema, Nacrylan

Figure 7. Stripe on a brass instrument due to a Caperlan thread

Table 3 .

 3 Mechanical characteristics of different fibres

	Fibres	Elasticity modulus (MPa)	Flexural strength (g/denier)	Flexion resistance (60 cycles)	Resistance to UV (months)	Elongation %	T fusion (°C)
	nylon	45	9.5	0	3 to 4	13	220
	PEN	250	10.2	0	6	6	250
	HDPE	1250	33	0	6 to 7	5	150
	aramid	550 to 950	24 to 29	7 to 25%	2 to 3	1.5 to 4	NR
	Vectran	510	23	15%	1 to 2	2	330
	carbon	1350	60	22%	without effect	1.5	NR
	polypropylene	1200 to 1700	31 to 42	0	6	1 to 6	160 to 170

Table 4 .

 4 Weight variations and effects of different threads on brass after oven testing

			Weight	Effect
	Commercial name Chemical family	variation	on
			(%)	metal
	cotton	cellulose		X
	nylon	polyamide	2	X
	Prolene	polypropylene	0.02
	Spectra	high-density polyethylene	0.01	X
	Spectra 148	high-density polyethylene	0.03	X
	Nacrylan	high-density polyethylene	0.03	X
	Dyneema	high-density polyethylene	0.03	X
	Vectran	aromatic polyester	0.03	X
	polypropylene	polypropylene	0.02
	polyester 1100/2/3 polyester	0.02	X

Acknowledgements

The author would like to thank the entire team at the Cité de la musique -Philharmonie de Paris for making themselves available and providing assistance during this research.

Materials list

Dyneema: Gremco Sarl, 1955


Michael Teders

Sabrina Bernard

Karin Gottschalk

J Luca Schwarz

Eric A Standley

Elodie Decuypere

Constantin G Daniliuc

Davide Audisio

Frédéric Taran

Frank Glorius

Accelerated Discovery in Photocatalysis by a Combined Screening Approach Involving MS-Tags

Keywords: photocatalysis, sydnones, energy transfer, hydrazides, mechanism-based screening, mesoionics

Herein, we report on the development of a MS-tag screening strategy that accelerates the discovery of photocatalytic reactions. By efficiently combining mechanism-and reaction-based screening dimensions, the respective advantages of each strategy were retained, while the drawbacks inherent to each screening approach could be eliminated. The covalent installation of a suitable MS-tag in discovered quenchers facilitated both the identification of formed products and enabled a significant reduction in the amount of reagents, catalysts and solvents required. Applying this approach led to the discovery of a mild photosensitized decarboxylative hydrazide synthesis from mesoionic sydnones and carboxylic acids as starting materials.

The development of new transformations and the improvement of existing methodologies towards "greener" alternatives are central tasks of many research programs throughout organic chemistry. 1 In this regard, catalysis has revolutionized the way valuable molecular scaffolds are constructed under mild conditions and even enabled the identification of numerous breakthroughs and unknown reactivity modes.

2 Many discoveries derive from in-depth understanding of well-established reactions and their underlying mechanisms, consecutively enabling the transfer of this gained knowledge to new classes of suitable catalysts and substrates. While this "rational-design" approach has led to many beautiful transformations, [START_REF]The Logic of Chemical Synthesis[END_REF] the breakthrough discovery potential is limited. The exploration of new reactivity modes is often enabled by utilizing discovery-oriented screening approaches, [START_REF]Handbook of Combinatorial Chemistry: Drugs, Catalysts, Materials[END_REF] as they allow a broader and systematic evaluation of chemical space.

5

These discovery-oriented screening methodologies contribute to a deep understanding of the underlying reactivity principles, that can ultimately be used in "comprehensionguided" rational-design approaches. 6 A prominent strategy for the discovery of new transformations are reaction-based screening approaches, where the formation of a new reaction product is usually identified by GC-or LC-MS analysis (Scheme 1a).

7 Hereby, pre-selected substrates, catalysts and / or reaction conditions are screened in a systematic fashion. While the setup required for such a screening approach is readily available and automatization is possible, 8 this concept has one inherent drawback with respect to catalytic reactions: detectable amounts of product have to be formed, requiring the matching of diverse reaction parameters. For this purpose, a large number of parameters must be varied, which leads to time-consuming and in the end costly protocols with an overall limited hit rate. In mechanism-based discovery-oriented screening approaches, one single step out of the whole catalytic cycle is evaluated by means of a suitable analytical tool, e.g. mass spectrometry, 9 cyclic voltammetry 10 or luminescence spectroscopy.

6,11

Such approaches therefore identify classes of substrates that interact with a catalyst and provide useful mechanistic insights (Scheme 1b). However, as this approach only covers one step of what is often a complex catalytic cycle, the development of a transformation requires either significant postscreening or rational reaction design.

Recently, we reported on a two-dimensional screening strategy in the research field of visible-light photocatalysis which merges mechanism-and reaction-based screening approaches. 12,[START_REF] Strieth-Kalthoff | Discovery of Unforeseen Energy-Transfer-Based Transformations Using a Combined Screening Approach[END_REF] The appropriate combination of these two onedimensional screening approaches retains their respective advantages in terms of breakthrough discovery potential while eliminating the drawbacks inherent to each approachwell demonstrated by our discovery of two unexpected uphill energy transfer reactions.

Although this concept bears enormous potential for the discovery of reactions and reactivity modes, it still suffers from three major limitations:

(1) The GC-MS analysis of each reaction mixture is timeconsuming.

(2) The identification of polar reaction products by GC-MS is not possible.

(3) Overall high quantities of reagents, catalysts and solvents are required due to the analytical limit-of-detection.

We envisioned that the covalent installation of a suitable MS-tag onto a lead substrate previously identified by luminescence quenching might eliminate the above-mentioned disadvantages (Scheme 1c). [START_REF] Cabrera-Pardo | Label-Assisted Mass Spectrometry for the Acceleration of Reaction Discovery and Optimization[END_REF] The installed MS-tag would allow intuitive and quick analysis of the reaction outcome using electrospray-ionization mass spectrometric analysis. Further, due to the extremely low detection limits that this analytical technique possesses, the required quantities of reagents, catalysts and solvents would be decreased significantly. A significant drawback of such a technique, however, is the need for the covalent installation of a suitable MS-tag and the need to investigate the properties of the tagged compound. In this context, also the full automatization of such a screening approach is hardly possible.

We started our conceptual study by investigating the interaction of 25 randomly selected potential quenchers -featuring diverse functional groups -using [Ir(dF(CF 3 )ppy) 2 ( dtbbpy + and E(M III */M IV ) = -1.16 V vs. Fc/Fc + ) [START_REF] Lowry | Single-Layer Electroluminescent Devices and Photoinduced Hydrogen Production from an Ionic Iridium(III) Complex[END_REF] and its high triplet excited state energy (E T = 61.82 ± 0.30 kcal/mol -1 ), 13 thus covering both electron transfer (ET) and energy transfer (EnT) domains of chemical space. Among the 25 screened substrates, we identified 6 new quenchers (Q3, Q10, Q14, Q22, Q23 and 1(Q20)) characterized by a significant quenching fraction. Among them, phenylsydnone 1 was identified to strongly interact with photoexcited best of our knowledge, visible-light photocatalysed reactions involving mesoionic compounds have not been reported. Consequently, the high degree of quenching of phenylsydnone 1 prompted us to select it as lead compound for the second MS-tag reaction-based screening dimension. Due to its high chemical robustness, low reactivity and excellent ionization properties, a phosphorous-based MS-Tag was covalently installed into the phenylsydnone scaffold in two straightforward steps, yielding MS-tagged phenylsydnone 1 tag . [START_REF]Luminescence quenching analysis revealed a quenching fraction of the phosphorous-based MS-tag of F = 24%[END_REF] We then selected 96 diverse reactants covering chemical space to discover new reactions by applying the second MS-tag reaction-based screening dimension. Using a 96 well plate with the [Ir-F] photocatalyst, tagged 1 tag and the respective reactant R1-R96 in each vial dissolved in a total reaction volume of 200 µL of acetonitrile, we irradiated the reaction mixtures using blue LEDs (λ max = 455 nm). After 24 h of irradiation, the outcome of the reactions was investigated by ESI-MS. 20 By simply comparing the obtained spectra with two reference spectra ((I) only 1 tag and hν in MeCN; (II) [Ir-F], 1 tag and hν in MeCN), additional peaks may indicate the formation of a reaction product. In total, 17 out of 96 combinations gave rise to new ESI-MS peaks. Some of the masses could directly be transformed into possible product motifs using only the mass spectra. 20 During the analysis of the reaction-based screening results, we noticed a recurring pattern of the formation of a new MS peak when a carboxylic acid functionality was present within the reactant's structure. To verify and reproduce our screening results, we decided to run this reaction on a 0.3 mmol scale using un-tagged 4fluorophenyl sydnone 1 in the presence of cyclohexanecarboxylic acid 2a and [Ir-F] under otherwise unchanged screening conditions. After the reaction and the subsequent purification process, we identified diacylhydrazide 3a as the formed reaction product, verified by NMR spectroscopy and by X-ray crystallography (see Figure 1). Next, we started optimizing the reaction parameters, such as the nature of the photocatalyst, the irradiation wavelength or the solvent using 4-fluorophenyl sydnone 1a and cyclohexanecarboxylic acid 2a as benchmark reagents. Gratifyingly, the yield of 3a could be increased from 13% to 67% by switching to [Ru(bpz) 3 ](PF 6 ) 2 ([Ru], bpz = 2,2′-bipyrazine) as photocatalyst, employing a catalyst loading of 2.5 mol% and increasing the equivalents of the carboxylic acid 2a

)](PF 6 ) ([Ir-F], dF(CF 3 )ppy = 2-(2,4- difluorophenyl)-3-trifluoromethylpyridine, dtbbpy = 4,4ʹ-di- tert-butyl-2,2ʹ-bipyridine)
22 while using acetonitrile (0.1 M) as solvent.

23 With the optimized reaction conditions in hand, we next investigated the scope and synthetic limitations of this decarboxylative hydrazide synthesis (Scheme 3a). Performing the reaction at a ten-fold higher scale worked well, delivering the product in 61% isolated yield. The utilization of cyclic secondary carboxylic acids with 5-or 3-membered ring systems was successful, delivering the products in 49% or 46% yield, respectively (3b, 3c). 24 When acetic acid was used as coupling partner, the desired product 3d could be obtained in a moderate yield of 51%. Benzoic or phenylacetic acid could also be converted, however the yield decreased to 36% and 43% (3e and 3f). The incorporation of fluorine substituents or alkyne moieties into the carboxylic acid functionality was tolerated and provided the corresponding products 3g and 3h in good yield (77-81%). Tertiary carboxylic acids could also be employed, as shown by the use of pivalic acid delivering hydrazide 3i in 45% yield. Gratifyingly, the use of unsaturated fatty acids was also possible, resulting in the formation of hydrazide 3j in 63%. The up-scaling of this reaction resulted in a slightly diminished yield of 55% (3.0 mmol scale). We next investigated the scope with respect to modifications of the sydnone's aryl moiety. Diverse functional groups, such as methoxy (3l), iodo (3m), acetyl (3n) or hydroxyl (3o) substituents, were tolerated, delivering the hydrazide products in good to excellent yields (67-85%, 3k-3o). The replacement of the phenyl group by a methyl group had no influence on the reaction -methyl hydrazide 3p could be isolated in 85% yield. The reaction further tolerates the presence of alkyl or aryl substituents at the C-4-position of the phenyl sydnone. The hydrazide products 3q-3s could be obtained in good yields (78-82%). Besides, an inversion of regioselectivity is observed for those latest examples. To further investigate the functional group tolerance and preservation of this photocatalytic hydrazide synthesis, an additive-based robustness screen was performed. 25 The results are summarized in histograms (Scheme 3b). We were delighted to see that in most cases the yield of the product was not affected by the presence of an additional additive, indicating an overall high robustness of the transformation. With an average recovered additive yield of 76%, the reaction is furthermore characterized by an extremely high functional group preservation. The obtained N,N-diacylhydrazide product scaffold 3 is of huge importance for many diverse applications in pesticide, 26 materials, [START_REF] Zhao | Hydrazide-Based Quadruply Hydrogen-Bonded Heterodimers. Structure, Assembling Selectivity, and Supramolecular Substitution[END_REF] or pharmaceutical chemistry. 28 Further, the products are important key intermediates for the synthesis of numerous heterocycles. [START_REF] Liu | Ligand-Free Cu(II)-Mediated Aerobic Oxidations of Aldehyde Hydrazones Leading to N,N′-Diacylhydrazines and 1,3,4-Oxadiazoles[END_REF] As shown in Scheme 4a, the products can be easily transformed to chiral 1,2,4-triazolium salt NHC precursors 4, which can be used for enantioselective catalysis.

30

The proposed mechanism of this transformation, which is in accordance with diverse performed mechanistic experiments (see SI for further information), is depicted in Scheme 4b and is in agreement to literature reports on the direct sensitization of mesoionic sydnones (λ < 300 nm).

18 The [Ru II ] photocatalyst is excited by visible light to its triplet excited state (E T = 48.4 kcal/mol). 11a Triplet-triplet energy transfer from 3* [Ru II ] to sydnone 1 (E T = 48.5 kcal/mol) 18b recycles the [Ru II ] ground state photocatalyst. Sensitization of 1 promotes the formation of Earl's bicyclic lactone intermediate 5, which yields diazirene 6 after decarboxylation. For unsubstituted sydnones (R=H), IM1 is formed after addition of the carboxylic acid. The corresponding products 3a-p are obtained after consecutive rearrangement. In the case of sydnone substitution (R = aryl or alkyl), nitrilimine IM2 is formed which yields the corresponding products 3q-s after carboxylic acid addition and rearrangement. A reaction quantum yield of Φ = 0.59, UV/Vis and Stern-Volmer analysis, TEMPO-trapping experiments, as well as diverse deuterium and [START_REF] Strieth-Kalthoff | Discovery of Unforeseen Energy-Transfer-Based Transformations Using a Combined Screening Approach[END_REF] C labelling experiments support this mechanistic hypothesis. 31 Transient absorption studies to prove the energy transfer activation nature of 3 are currently being investigated in our laboratories.

In conclusion, we have successfully developed a screening methodology involving MS-tags that allowed the accelerated discovery of a photocatalytic reaction. By combining mechanism-and reaction-based screening, the limitations of each individual screening approach are eliminated while establishing a highly efficient strategy potentially allowing the discovery of ground-breaking photocatalytic reactions. Indeed, the covalent installation of a suitable MS-tag both facilitates the identification of newly formed bond (dis)connections and allows significant reduction of the required amount of reagents, catalysts and solvents. Applying this approach resulted in the discovery of a highly functional group tolerant photosensitized decarboxylative hydrazide synthesis from mesoionic sydnones and carboxylic acids as starting materials. We are convinced that the application of combined screening approaches will accelerate diverse ground-breaking discoveries, ultimately expanding the toolbox of organic chemistry for highly efficient and straightforward catalytic protocols.

ASSOCIATED CONTENT

Supporting Information. Experimental details, characterization data, mechanistic experiments and copies of NMR spectra of new compounds. This material is available free of charge via the Internet at http://pubs.acs.org.

Scheme 1 .

 1 Scheme 1. Principles of a) reaction-and b) mechanism-based discovery-oriented screening approaches. c) This work: Conceptual sketch of the combined mechanism-and MS-tag reaction-based screening approach for accelerated and highly efficient discovery in photocatalysis. Cat = catalyst; Sub = substrate; Q = quencher; PC = photocatalyst.

  as photocatalyst in the first mechanism-based luminescence quenching screening dimension (Scheme 2). The photocatalyst [Ir-F] was selected due to its high excited state redox potentials (E(M III */M II ) = +1.15 V vs. Fc/Fc

  Scheme 2. Workflow-diagram illustrating the conceptual approach of the combined mechanism-and reaction-based screening strategy that lead to the discovery of a photosensitized decarboxylative hydrazide synthesis. The installation of a phosphorous-based MS-tag into a previously discovered sydnone quencher renders the second screening step highly efficient with respect to required catalyst, reagent and solvent quantities. Values in yellow or green circles represent quenching fractions of the respective substrate with [Ir-F] as photocatalyst. PC = photocatalyst; Q = quencher; R = reagent; MeCN = acetonitrile.

21

 21

Figure 1 .

 1 Figure 1. Crystal structure of N,N-diacylhydrazide 3a. Thermal ellipsoids are shown with 30% probability.

Scheme 3 .

 3 Scheme 3. a) Substrate scope and b) additive-based robustness screen results for the photosensitized decarboxylative hydazide synthesis. [a] General conditions: 1a-s (0.3 mmol), 2a-s (6.0 mmol, 20.0 equiv), [Ru] (2.5 mol%), MeCN (0.1 M), 455 nm, rt, 24 h. All stated yields are isolated. [b] HPLC purification required. [c] Product structure confirmed by X-Ray analysis, see

We thank the Deutsche Forschungsgemeinschaft (Leibniz Award), the Alexander von Humboldt Foundation (E.A.S) and SusChemSys 2.0 (M.T.) for generous financial support. We are also grateful to T. Wagner, F. Strieth-Kalthoff and L. Anhäuser (all WWU Münster) for experimental support and helpful discussions.

AUTHOR INFORMATION

Corresponding Author * E-mail: frederic.taran@cea.fr * E-mail: glorius@uni-muenster.de

Notes

The authors declare no competing financial interest.

ACKNOWLEDGMENTS


Hesham A Elshafei
email: hesham.elshafei@inserm.fr

Lesly Fornoni

Rémy Masson

Olivier Bertrand

Aurélie Bidet-Caulet

What's in Your Gamma? Activation of The Ventral Fronto-Parietal Attentional Network in Response to Distracting Sounds RUNNING TITLE: Gamma activation during bottom-up attentional capture NAMES AND AFFILIATIONS OF EACH AUTHOR

Keywords: auditory attention, attentional capture, gamma oscillations, phase synchrony, prefrontal cortex

Auditory attention operates through top-down (TD) and bottom-up (BU) mechanisms that are supported by dorsal and ventral brain networks, respectively, with the main overlap in the lateral prefrontal cortex (lPFC). A good TD/BU balance is essential to be both task-efficient and aware of our environment, yet it is rarely investigated. Oscillatory activity is a novel method to probe the attentional dynamics with evidence that gamma activity (>30Hz) could signal BU processing and thus would be a good candidate to support the activation of the ventral BU network. MEG data were collected from 21 young adults performing the Competitive Attention Task which enables simultaneous investigation of BU and TD attentional mechanisms. Distracting sounds elicited an increase in gamma activity in regions of the BU ventral network. TD attention modulated these gamma responses in regions of the inhibitory cognitive control system: the medial prefrontal and anterior cingulate cortices. Finally, distracting-sound-induced gamma activity was synchronous between the auditory cortices and several distant brain regions, notably the lPFC. We provide novel insight into the role of gamma activity (1) in supporting the activation of the BU ventral network, and (2) in subtending the TD/BU attention balance in the prefrontal cortex.

INTRODUCTION

In an environment that contains far more information than we can process at a time, we rely on our attention to prioritize the processing of only a fragment of these incoming stimuli [START_REF] Desimone | Neural mechanisms of selective visual attention[END_REF]. Attention can be oriented endogenously (top-down), in anticipation of an upcoming stimulus for example, or it can be captured exogenously (bottomup) by a salient irrelevant stimulus such as a telephone ringing [START_REF] Posner | The attention system of the human brain[END_REF][START_REF] Petersen | The attention system of the human brain: 20 years after[END_REF]. A dynamic balance between top-down (TD) and bottom-up (BU) mechanisms of attention is essential to be task-efficient while being aware, yet not fully distracted, of our surroundings.

Two major neural networks support TD (endogenous) and BU (exogenous) mechanisms of attention: a dorsal frontoparietal network comprising the posterior frontal and intraparietal cortices; and a ventral frontoparietal network, largely lateralized to the right hemisphere, comprising the temporo-parietal junction (TPJ) and the ventral prefrontal cortex (vPFC); with the two networks overlapping mainly in the lateral prefrontal cortex (lPFC) [START_REF] Kim | The large-scale neural network for spatial attention displays multifunctional overlap but differential asymmetry[END_REF][START_REF] Miller | An integrative theory of prefrontal cortex function[END_REF][START_REF] Corbetta | Control of goal-directed and stimulus-driven attention in the brain[END_REF][START_REF] Fox | Spontaneous neuronal activity distinguishes human dorsal and ventral attention systems[END_REF][START_REF] He | Breakdown of Functional Connectivity in Frontoparietal Networks Underlies Behavioral Deficits in Spatial Neglect[END_REF][START_REF] Corbetta | The reorineting system of the human brain: From environment to theory of mind[END_REF][START_REF] Asplund | A central role for the lateral prefrontal cortex in goal-directed and stimulus-driven attention[END_REF].

A promising way of addressing the dynamics of TD and BU attentional systems is to explore brain rhythms. On one hand, TD anticipatory attention is indexed by (de)synchronisation of oscillatory activity in the alpha band (review in [START_REF] Klimesch | EEG alpha oscillations: The inhibition-timing hypothesis[END_REF][START_REF] Jensen | Shaping Functional Architecture by Oscillatory Alpha Activity: Gating by Inhibition[END_REF][START_REF] Frey | Selective Modulation of Auditory Cortical Alpha Activity in an Audiovisual Spatial Attention Task[END_REF]e.g. ElShafei et al. 2018). On the other hand, BU attentional capture is signalled by an increased activity in the gamma band in the primate brain [START_REF] Buschman | Top-Down Versus Bottom-Up Control of Attention in the Prefrontal and Posterior Parietal Cortices[END_REF].

Activation in the gamma band (>30 Hz) has been associated to attention, with enhanced gamma activity in the visual (e.g. [START_REF] Fries | Modulation of oscillatory neuronal synchronization by selective visual attention[END_REF] or auditory (e.g. [START_REF] Ray | High-frequency gamma activity (80-150 Hz) is increased in human cortex during selective attention[END_REF] cortices, in response to attended visual or auditory stimuli, respectively. Gamma activity has also been observed in regions other than sensory regions (e.g. dorsolateral prefrontal cortex, intraparietal sulcus and temporo-parietal junction) in several working memory [START_REF] Michels | Simultaneous EEG-fMRI during a working memory task: Modulations in low and high frequency bands[END_REF][START_REF] Albouy | Impaired pitch perception and memory in congenital amusia: The deficit starts in the auditory cortex[END_REF], and visual [START_REF] Akimoto | Spatiotemporal Dynamics of High-Gamma Activities during a 3-Stimulus Visual Oddball Task[END_REF][START_REF] Akimoto | High-gamma activity in an attention network predicts individual differences in elderly adults' behavioral performance[END_REF] or auditory [START_REF] Lee | Generators of the gamma-band activities in response to rare and novel stimuli during the auditory oddball paradigm[END_REF][START_REF] Ahveninen | Dynamic oscillatory processes governing cued orienting and allocation of auditory attention[END_REF]) oddball tasks. Thus, gamma activity seems to promote the activation of relevant processes across the brain and not only in sensory cortices. Finally, it has been demonstrated that attention increases the coupling between frontal and relevant sensory regions via gamma synchrony [START_REF] Buschman | Top-Down Versus Bottom-Up Control of Attention in the Prefrontal and Posterior Parietal Cortices[END_REF][START_REF] Gregoriou | High-Frequency, long-range coupling between prefrontal and visual cortex during attention[END_REF][START_REF] Baldauf | Neural Mechanisms of object-based attention[END_REF]. Therefore, gamma activity would be a good candidate to support activation of the ventral network of attention. However, to our knowledge, no study has investigated the role of gamma activity in the balance between BU and TD mechanisms of attention in the human brain.

Distraction by unexpected sounds has been mostly investigated using variations of the reaction-time based oddball paradigm. In this paradigm, the response time to a target stimulus is compared in the presence (vs. absence) of a rare deviation (oddball) within a sequence of irrelevant stimuli that could be in the same [START_REF] Schröger | A Neural Mechanism for Involuntary Attention Shifts to Changes in Auditory Stimulation[END_REF] or a different [START_REF] Escera | Neural mechanisms of involuntary attention to acoustic novelty and change[END_REF]) modality than the attended target. However, the adequacy of such paradigm to provide a reliable measure of attentional capture has been recently criticized (review in [START_REF] Parmentier | The Involuntary Capture of Attention by Sound[END_REF][START_REF] Bidet-Caulet | Brain Dynamics of Distractibility: Interaction Between Top-Down and Bottom-Up Mechanisms of Auditory Attention[END_REF][START_REF] Dalton | Auditory attentional capture: Implicit and explicit approaches[END_REF][START_REF] Masson | Fronto-central P3a to distracting sounds: An index of their arousing properties[END_REF].

In 2014, Bidet-Caulet and colleagues proposed a novel paradigm, the Competitive Attention Task (CAT), an adaptation of the Posner cueing paradigm using visual cues and monaural auditory targets. In this task, TD anticipatory attention is measured by comparing trials with informative cues to trials with uninformative cues. BU attentional capture is triggered by a binaural distracting sound played during the delay between the cue and the target in only 25 % of the trials. Distraction is assessed as the impact of distracting sounds on task performance and the balance between TD and BU mechanisms can be measured by comparing responses to distracting sounds following informative vs. uninformative cues.

We have recorded MEG activity from young healthy adults performing the CAT to test the following hypotheses. (1) BU attentional capture by an isolated unexpected stimulus would be indexed by gamma activity in the ventral attentional network including the TPJ and vPFC. (2) The lPFC would support the balance between BU and TD attention by demonstrating modulations of gamma activity to distracting sounds by cue information, since the lPFC is part of both the ventral and dorsal networks of attention. Finally, we sought to investigate the connectivity, subtended by gamma activity, between the auditory cortices and other brain regions during the presentation of a distracting sound, with a prediction that the mains hubs of this connectivity would lie within the lPFC.

MATERIAL & METHODS

Participants

Twenty-one healthy participants (9 females) took part in this study. The mean age was 24.7 years ± 0.62 Standard Error of Mean (SEM). All participants were right handed, and reported normal hearing, and normal or corrected-to-normal vision. All participants were free from any neurological or psychiatric disorders. The study was approved by the local ethical committee, and subjects gave written informed consent, according to the Declaration of Helsinki, and they were paid for their participation.

Stimuli and tasks

Competitive Attention Task (CAT)

In 75 % of the trials, a target sound (100 ms duration) followed a central visual cue (200 ms duration) with a fixed delay of 1000 ms (see Figure 1). The cue was a green arrow, presented on a grey-background screen, pointing either to the left, right, or both sides. Target sounds were monaural pure tones (carrier frequency between 512 and 575 Hz; 5 ms rise-time, 5 ms fall-time). In the other 25 %, the same structure was retained, however, a binaural distracting sound (300 ms duration) was played during the cue-target delay (50-650 ms range after cue offset). Trials with a distracting sound played from 50 ms to 350 ms after the cue offset were classified as DIS1, those with a distracting sound played from 350 ms to 650 ms after the cue offset were classified as DIS2, those with no distracting sound were classified as NoDIS. A total of 40 different ringing sounds were used as distracting sounds (clock-alarm, door-bell, phone ring, etc.) for each participant.

The cue and target categories were manipulated in the same proportion for trials with and without distracting sound. In 25% of the trials, the cue was pointing left, and the target sound was played in the left ear, and in 25% of the trials, the cue was pointing right, and the target sound was played in the right ear, leading to a total of 50% of informative trials. In the other 50% of the trials, the cue was uninformative, pointing in both directions, and the target sound was played in the left (25%) or right (25%) ear. To compare brain responses to acoustically matched sounds, the same distracting sounds were played in each combination of cue category (informative, uninformative) and distractor condition (DIS1 or DIS2). Each distracting sound was thus played 4 times during the whole experiment, but no more than once during each single block to limit habituation. Participants were instructed to categorize two target sounds as either high-or low-pitched sound, by either pulling or pushing a joystick.

The target type (high or low) was manipulated in the same proportion in all conditions.

The mapping between the targets (low or high) and the responses (pull or push) was counterbalanced across participants but did not change across the blocks for each participant.

In order to account for the participants' pitch-discrimination capacities, the pitch difference between the two target sounds was defined in a Discrimination Task (see below). Participants were informed that informative cues were 100 % predictive and that a distracting sound could be sometimes played. They were asked to allocate their attention to the cued side in the case of informative cue, to ignore the distractors and to respond as quickly and correctly as possible. Participants had a 3.4 second (3400 ms) response window. In the absence of the visual cue, a blue fixation cross was presented at the center of the screen. Subjects were instructed to keep their eyes fixated on the cross.

Discrimination Task

Participants were randomly presented with one of two target sounds: a low-pitched sound (512 Hz) and a high-pitched sound (575 Hz; two semitones higher), equiprobably in each ear (four trials per ear and per pitch). As described above, participants were asked to categorize the target sounds as either high-or low-pitched sound within 3 seconds.

Procedure

Participants were seated in a sound-attenuated, magnetically shielded recording room, at a 50 cm distance from the screen. The response device was an index-operated joystick that participants moved either towards them (when instructed to pull) or away from them (when instructed to push). All stimuli were delivered using Presentation software (Neurobehavioral Systems, Albany, CA, USA). All sounds were presented through air-conducting tubes using Etymotic ER-3A foam earplugs (Etymotic Research, Inc., USA).

First, the auditory threshold was determined for the two target sounds differing by 2 semitones (512 and 575 Hz), for each ear, for each participant using the Bekesy tracking method (Von [START_REF] Békésy | Experiments in hearing[END_REF]. The target sounds were then monaurally presented at 25 dB sensation level (between 37.5 and 52.1 dB A across subjects) while the distracting sounds were binaurally played at 55 dB sensation level (between 47.5 and 62.1 dB A across subjects), above the target sound thresholds. Second, participants performed the Discrimination task. Afterwards, participants were trained with a short sequence of the Competitive Attention Task. Finally, MEG and EEG were recorded while subjects performed 10 blocks (64 trials each) leading to 240 trials in the NoDIS and 80 in the DIS conditions, for informative and uninformative cues, separately. The whole recording session lasted around 80 minutes. After the MEG/EEG session, participants' subjective reports regarding their strategies were collected.

Behavioral Data Analysis

For behavioral data analysis, a button press before target onset was considered as a false alarm (FA). A trial with no button-press after target onset and before the next cue onset was considered as a miss trial. A trial with no FA and with a button-press after target onset was counted as correct if the pressed button matched the response mapped to the target sound, and as incorrect if otherwise. Reaction-times (RTs) to targets were analysed in the correct trials only.

The influence of (1) cue condition (2 levels: informative and uninformative) and (2) distractor condition (3 levels: NoDis, DIS1 and DIS2) on median reaction times (RTs) of correct responses and on percentage of incorrect responses was tested using a linear mixed-effects models using the lme4 package [START_REF] Bates | Fitting linear mixed-effects models using lme4[END_REF] for R [START_REF] Team | R: A Language and Environment for Statistical Computing[END_REF]. For post-hoc analysis we used the Lsmean package [START_REF] Searle | Population marginal means in the linear model: an alternative to least squares means[END_REF] where p-values were considered as significant at p<0.05 and adjusted for the number of comparisons performed (Tukey method).

Brain Signal Recordings

Simultaneous EEG and MEG data were recorded, although the EEG data will not be presented here. The MEG data were acquired with a 275-sensor axial gradiometer system (CTF Systems Inc., Port Coquitlam, Canada) with continuous sampling at a rate of 600Hz, a 0-150Hz filter bandwidth, and first-order spatial gradient noise cancellation. Moreover, eye-related movements were measured using vertical and horizontal EOG electrodes. Head position relative to the gradiometer array was acquired continuously using coils positioned at three fiducial points; nasion, left and right pre-auricular points. Head position was checked at the beginning of each block to control head movements.

In addition to the MEG/EEG recordings, T1-weighted three-dimensional anatomical images were acquired for each participant using a 3T Siemens Magnetom whole-body scanner (Erlangen, Germany). These images were used for reconstruction of individual head shapes to create forward models for the source reconstruction procedures. The processing of these images was carried out using CTF's software (CTF Systems Inc., Port Coquitlam, Canada).

Data Pre-processing

Only correct trials were considered for electrophysiological analyses. Data segments for which the head position differed for more than 10 mm from the median position during the 10 blocks were excluded. In addition, data segments contaminated with muscular activity or sensor jumps were excluded semi-manually using a threshold of 2200 and 10000 femtoTesla respectively. For all participants, more than 75 % of trials remained after rejection for further analyses.

Independent component analysis was applied on the band-pass filtered (0.1-40Hz) data in order to remove eye-related (blink and saccades) and heart-related artefacts. Subsequently, components (four on average) were removed from the non-filtered data via the inverse ICA transformation. Data were further notch filtered at 50, 100 and 150Hz and high-pass filtered at 0.2Hz.

1.6 Distractor-related Gamma Activity 1.6.1 Gamma Band (Sensor level): Definition

The goal of this step was to define the time-frequency range of gamma activity of interest.

First, for each distractor onset time-range, surrogate distractors were created in the NoDIS trials with similar distribution over time than the real distractors. Afterwards, the timefrequency power, of distractor (and of surrogate distractor) trials was calculated using Morlet Wavelet decomposition with a width of four cycles per wavelet (m=7; Tallon-Baudry and Bertrand 1999) at center frequencies between 40 and 150 Hz, in steps of 1 Hz and 10 ms.

Activity between 0 and 0.35s post-distractor onset and 50-110Hz was contrasted between distractor and surrogate trials using a nonparametric cluster-based permutation analysis [START_REF] Maris | Nonparametric statistical testing of EEG-and MEG-data[END_REF]. This contrast extracts distractor-related activity clear of cuerelated activity (see Figure 2).

Gamma Band (Source level): Computation

The goal of this step was to estimate the brain regions driving gamma activity in response to distracting sounds in the time-frequency window of interest (0.1-0.3 s post-distractor onset, 60 to 100Hz) defined from the sensor-level analysis (part 1.6.1). We utilized the frequencydomain adaptive spatial technique of dynamical imaging of coherent sources (DICS; [START_REF] Gross | Dynamic imaging of coherent sources: studying neural interactions in the human brain[END_REF]. Data from both surrogate and real distractors were concatenated, and crossspectral density (CSD) matrix (-0.2 to 0.6 s, relative to real/surrogate distractor onset) were calculated using the multitaper method with a target frequency of 80 (±30) Hz. For each participant, an anatomically realistic single-shell headmodel based on the cortical surface was generated from individual head shapes [START_REF] Nolte | The magnetic lead field theorem in the quasi-static approximation and its use for magnetoencephalography forward calculation in realistic volume conductors[END_REF]. A grid with 0.5 cm resolution was normalized on an MNI template, and then morphed into the brain volume of each participant.

Leadfields for all grid points along with the CSD matrix were used to compute a common spatial filter that was used to estimate the spatial distribution of power for time-frequency window of interest (0.1-0.3 s post-distractor onset, 60 to 100Hz).

Gamma Band (Source Level): Analysis

For each participant, we estimated source-level activity (0.1-0.3 s post-distractor onset, 60 to 100Hz) for each cue category (informative and uninformative) and for both cue categories concatenated. We performed two analyses:

(1) In order to characterize the brain areas activated in the gamma band during the distracting sound presentation, distractor-related gamma activity was contrasted to surrogate distractor-related gamma activity

(2) In order to investigate the interaction between distractor response and cue information, surrogate-corrected gamma activity in the informative cue condition was contrasted to surrogate-corrected gamma activity in the uninformative cue condition.

Both tests have been carried out using non-parametric cluster-based permutation analysis [START_REF] Maris | Nonparametric statistical testing of EEG-and MEG-data[END_REF]. Please note, that for these tests, cluster permutations control for multiple comparisons in the source space dimension.

Gamma Band (Source Level): Connectivity Analysis

The aim of this analysis was to identify the brain regions that could be functionally connected in the gamma band to the auditory cortices during the presentation of the distracting sound.

We have extracted the complex values containing phase information into source space using partial canonical coherence (PCC) beamformer, a computationally efficient alternative to the DICS that provides the possibility of extracting both power and phase information on the source level. For each participant:

(1) Similarly, to the DICS beamformer, data from both surrogate and real distractors were concatenated, and cross-spectral density (CSD) matrix (-0.2 to 0.6 s, relative to real/surrogate distractor onset) were calculated using the multitaper method with a target frequency of 80 (±30) Hz. Leadfields for all grid points along with the CSD matrix were used to compute a common spatial filter that was used to estimate the spatial distribution of power and phase for the time-frequency window of interest (0.1-0.3s post-distractor onset, 60 to 100Hz).

(2) One auditory region of interest (ROI) was defined as including, in both hemispheres, the Broadmann areas 22, 41 and 42, according to the Talairach Tournoux atlas [START_REF] Talairach | Co-planar stereotaxic atlas of the human brain: 3-dimensional proportional system: an approach to cerebral imaging[END_REF][START_REF] Lancaster | Automated labeling of the human brain: a preliminary report on the development and evaluation of a forward-transform method[END_REF]).

(3) Phase synchrony [START_REF] Lachaux | Measuring phase synchrony in brain signals[END_REF] between each voxel in the auditory ROIs and all other voxels was calculated, averaged across voxels of the auditory ROI, and then Fisher Z transformed. Thus, for each extra-auditory brain voxel, a single phase synchrony value with the entirety of the auditory ROI was obtained.

Finally, distractor-related gamma phase synchrony was contrasted to surrogate distractorrelated gamma phase synchrony using non-parametric cluster-based permutation analysis [START_REF] Maris | Nonparametric statistical testing of EEG-and MEG-data[END_REF]. Please note, that for this test, cluster permutations control for multiple comparisons in the source space dimension.

Results

Behavioral Analysis

Participants correctly performed the CAT in 96.04 ± 0.29 SEM % of the trials. The remaining trials were either incorrect trials (3.95 ± 0.29 SEM %), missed trials (0.27 ± 0.06 %) or trials with FAs (0.02 ± 0.01 %).

Median Reaction Times

We found a significant main effect of cue category (F(1, 20) = 4.9, p = 0.02, η 2 = 0.36) on median reaction times in correct trials. Participants were faster when the cue was informative in comparison to the uninformative cue. In addition, we found a significant main effect of the distractor condition (F(2, 42) = 34.2, p < 0.01, η 2 = 0.49). Post-hoc tests indicated that, in comparison to the NoDIS condition, participants were faster in the early DIS1 condition (p < 0.001) but slower in the late DIS2 condition (p < 0.001). Participants were also faster in the early DIS1 than in the late DIS2 condition (p < 0.001). No interaction effect was found significant.

Percentage of Incorrect Responses

Only a main effect of the distractor condition (F(2, 42) = 3.8, p = 0.02, η 2 = 0.17) was found significant on the percentage of incorrect responses. Post-hoc tests indicated that participants, committed more errors in the late DIS2 condition in comparison to the NoDIS (p = 0.02) and early DIS1 (p = 0.07) conditions.

Gamma Activity Analysis

Gamma Sensor Level Activation

Real-distractor high-frequency activity was contrasted to that of surrogate-distractor using non-parametric cluster-based permutation testing. As shown in Figure 4

Gamma Source Level Activation

The aim of this test was to highlight the regions driving gamma activity observed at the sensor level. Based upon the sensor level results, we have computed DICS beamformer sources for each participant between 60-100Hz and 0.1-0.3s post-distractor. Real-distractor gamma activity was contrasted to that of surrogate distractors using non-parametric cluster-based permutation testing. A significant positive cluster (p < 0.01) indicating an increase in gamma activity notably in ( 1

Gamma Source Level Cue Effect Comparison

To investigate the effect of top-down attention on bottom-up processing, we analysed the effect of cue information on the gamma response to distracting sounds. For each participant, real distractor source-level data (60-100 Hz, 0.1-0.3s) were baseline corrected by subtracting surrogate-distractor activity. Corrected distractor gamma activity was contrasted between the two cue categories (informative vs. uninformative) using non-parametric cluster-based permutation testing. A significant cluster (p = 0.014) extended notably to (1) the left dorsomedial and ventromedial prefrontal cortices, and (2) the left anterior cingulate gyrus.

Other regions included the left pre-and post-central gyri, the left supplementary motor area, the left superior parietal lobule. All these regions displayed a significantly higher activation when the distracting sound was preceded by an informative cue rather than an uninformative cue. between informative and uninformative cue conditions. dmPFC: dorsomedial prefrontal cortex. vmPFC: ventromedial prefrontal cortex. ACC: anterior cingulate cortex.

Gamma Source Level Connectivity Analysis

Real-distractor phase synchrony (both auditory ROIs averaged being the reference) in the gamma band (60-100 Hz, 0.1-0.3s) was contrasted to that of surrogate distractors using nonparametric cluster-based permutation testing. A significant cluster (p < 0.01) indicated an increase in gamma synchrony (during the presentation of distracting sounds) between the auditory cortices and the ventrolateral and dorsolateral prefrontal cortex in both hemispheres. Other regions included the pre-and post-central gyri, the supplementary motor areas, the frontal eye fields and the paracentral lobule, in the left hemisphere.

DISCUSSION

In the present study, we have demonstrated that in response to salient unexpected distracting sounds, the auditory cortices and the temporo-parietal junctions in both hemispheres, and the right ventrolateral PFC were activated in the gamma band. In addition, modulation by topdown attention of gamma activity to distracting sounds was found in the left dorsomedial and ventromedial prefrontal cortices. Finally, we have evidenced synchrony in the gamma band between regions in the dorsolateral and ventrolateral prefrontal cortices and the auditory cortices during distracting sound processing.

Behavioral measures of TD and BU attentional mechanisms

Behaviorally, participants discriminated the target pitch faster in trials with an informative cue in comparison to trials with an uninformative cue. This effect is in agreement with several previous studies [START_REF] Posner | Chronometric Explorations of Mind[END_REF][START_REF] Elshafei | Two Sides of the Same Coin: Distinct Sub-Bands in the Alpha Rhythm Reflect Facilitation and Suppression Mechanisms during Auditory Anticipatory Attention[END_REF]. It is most likely related to differences in TD anticipatory attention since the informative cue provided additional information solely about the location of the target and not about its category neither its mapped response, leading to equivalent motor preparation across conditions.

In trials with distracting sounds, participants responded faster to the following target in trials with early distracting sounds rather than with late distracting sounds. This pattern can be explained in light of the phenomena triggered by a distracting sound (review in Näätänen 1992; [START_REF] Bidet-Caulet | Brain Dynamics of Distractibility: Interaction Between Top-Down and Bottom-Up Mechanisms of Auditory Attention[END_REF][START_REF] Masson | Fronto-central P3a to distracting sounds: An index of their arousing properties[END_REF]: (1) a persistent increase in arousal resulting in RT reduction (behavioral benefit) and (2) a strong transient attentional capture (exogenous orienting) leading to RT augmentation (behavioral cost); with the behavioral net effect of distracting sound varying according to the time interval between the distracting and the target sounds. Importantly, we also found that participants were less accurate to discriminate the auditory targets when preceded by late distracting sounds in comparison to the no distractor condition. This result provides further evidence of a detrimental behavioral effect of distracting sounds which orient attention away from the task at hand. Therefore, these behavioral results demonstrate that, in the CAT paradigm, TD attention is enhanced in trials with informative cue, and that a strong transient bottom-up attentional capture is triggered by distracting sounds.

Activation of the Ventral Bottom-Up Attentional Network in the Gamma band

In line with our hypothesis, in response to an unexpected salient distracting sound, we observed an increase in gamma activity in the left and right auditory cortices, the bilateral temporo-parietal junctions, and the right ventrolateral prefrontal cortex. This present result is highly consistent with the proposal by [START_REF] Corbetta | Control of goal-directed and stimulus-driven attention in the brain[END_REF]2008), based on functional magnetic resonance imaging (fMRI) studies of visual attention, that the ventral attention system, involved in bottom-up attention, includes the temporo-parietal junction and the ventral prefrontal cortex. This present finding is also in agreement with fMRI (e.g. [START_REF] Salmi | Brain networks of bottom-up triggered and top-down controlled shifting of auditory attention[END_REF][START_REF] Alho | Top-down controlled and bottom-up triggered orienting of auditory attention to pitch activate overlapping brain networks[END_REF][START_REF] Salo | Brain activity associated with selective attention, divided attention and distraction[END_REF] and MEG/EEG (e.g. [START_REF] Ahveninen | Dynamic oscillatory processes governing cued orienting and allocation of auditory attention[END_REF]) studies in the auditory modality. In addition, the right lateralization of the frontal activation is consistent with fMRI findings of a ventral network predominantly localized to the right hemisphere in the visual modality [START_REF] Corbetta | Control of goal-directed and stimulus-driven attention in the brain[END_REF][START_REF] Corbetta | The reorineting system of the human brain: From environment to theory of mind[END_REF]. Also, the bilateral activation of the TPJ is in line with a stronger activation of the left TPJ to auditory than to visual irrelevant oddball stimuli as shown in a meta-analysis of fMRI studies [START_REF] Kim | Involvement of the dorsal and ventral attention networks in oddball stimulus processing: A meta-analysis[END_REF].

Importantly, we found that the gamma activation in the ventral network in response to distracting sounds lasted from 100 to 300ms after distracting sound onset. This result confirms that BU attentional capture is a rapid and transient phenomenon, in agreement with behavioral costs observed only for late distracting sounds offsetting between 50 and 350 ms before target onset. Such activation in high frequency gamma oscillations is also consistent with the fast nature of the attentional capture phenomenon. Finally, it is worth noting that the activation of the ventral attentional network was found in response to entirely taskirrelevant distracting sounds, contrary to earlier studies which suggested that task-relevance rather than saliency is critical to the engagement of the ventral network [START_REF] Serences | Coordination of Voluntary and Stimulus-Driven Attentional Control in Human Cortex[END_REF][START_REF] Indovina | Dissociation of stimulus relevance and saliency factors during shifts of visuospatial attention[END_REF][START_REF] Corbetta | The reorineting system of the human brain: From environment to theory of mind[END_REF]. The short duration of the ventral network activation might have precluded its observation using techniques with low temporal resolution (fMRI) as previously proposed by Chica and colleagues (2013).

The PFC and the balance between TD and BU attentional mechanisms

We did not find any significant effect of cue information on gamma activity within the regions of the ventral attentional network in the first 300 ms. However, in several regions of the left prefrontal cortex, notably (and contrary to our original hypothesis) in the dorso-and ventro-medial prefrontal cortices and the anterior cingulate cortex (ACC), gamma activity was more pronounced in response to distracting sounds preceded by an informative cue rather than an uninformative cue.

These medial prefrontal regions have been hypothesized to play a role in the inhibition of irrelevant stimuli. Indeed, in humans, an increased BOLD activation of these regions is observed during presentation of irrelevant salient stimuli [START_REF] Salmi | Brain networks of bottom-up triggered and top-down controlled shifting of auditory attention[END_REF]; and an enhanced P3 response to such stimuli is found after damage of the medial PFC [START_REF] Rule | Orbitofrontal cortex and dynamic filtering of emotional stimuli[END_REF]. In the non-human primate auditory system, such role is supported by cortico-cortical connections between these regions (the medial PFC and the ACC) and inhibitory neurons in auditory association regions in order to suppress irrelevant signals [START_REF] Matsumoto | The role of the medial prefrontal cortex in achieving goals[END_REF][START_REF] Barbas | Relationship of prefrontal connections to inhibitory systems in superior temporal areas in the rhesus monkey[END_REF][START_REF] Barbas | Prefrontal pathways that control attention[END_REF][START_REF] Medalla | Specificity in Inhibitory Systems Associated with Prefrontal Pathways to Temporal Cortex in Primates[END_REF]. Importantly, electrical stimulation of the ACC has been shown to reduce auditory evoked activity in non-human primate superior temporal cortices [START_REF] Müller-Preuss | Anatomical and physiological evidence for a relationship between the "cingular" vocalization area and the auditory cortex in the squirrel monkey[END_REF][START_REF] Müller-Preuss | Inhibition of auditory cortical neurons during phonation[END_REF], providing direct evidence of an inhibitory role of these medial prefrontal regions. Therefore, in the present study, the larger gamma activation of the medial PFC regions and the ACC, during distracting sounds preceded by an informative cue, could reflect a strong and fast inhibitory signal to regions involved in the processing of task-irrelevant information. This stronger inhibition could result from an increased top-down attention load with informative cue, in line with shorter reaction times, compared to trials with uninformative cue.

The medial prefrontal localization of such regions contradicts our original hypothesis that more lateral prefrontal regions would play a prominent role in orchestrating the interplay between TD and BU attentional mechanisms, as suggested by previous studies using fMRI in human subjects [START_REF] Fox | Spontaneous neuronal activity distinguishes human dorsal and ventral attention systems[END_REF][START_REF] Corbetta | The reorineting system of the human brain: From environment to theory of mind[END_REF][START_REF] Alho | Top-down controlled and bottom-up triggered orienting of auditory attention to pitch activate overlapping brain networks[END_REF][START_REF] Katsuki | Bottom-up and top-down attention: Different processes and overlapping neural systems[END_REF][START_REF] Vossel | Dorsal and ventral attention systems: Distinct neural circuits but collaborative roles[END_REF]). However, we believe that such role for the lateral PFC cannot be ruled out. As evidenced in the non-human primate brain, the ACC has excitatory and inhibitory connections to the anterior and posterior parts of the lateral PFC, respectively [START_REF] Medalla | Anterior cingulate synapses in prefrontal areas 10 and 46 suggest differential influence in cognitive control[END_REF], with the former momentarily suspending current tasks and the latter facilitating attentional switch to a novel task (review in [START_REF] Barbas | Prefrontal pathways that control attention[END_REF]). In the context of the present paradigm, a stronger ACC to lateral PFC signal could facilitate switching from the TD task to the BU distracting sound processing, and vice versa. The opposite effects on the anterior and posterior parts of the lateral PFC combined to the insufficient spatial resolution of MEG could preclude the observation of a significant increase in gamma activation in the lateral PFC. Therefore, the medial PFC could support the interplay between top-down and bottom-up attention by (1) exercising a TD inhibitory attentional control via direct projection to the auditory cortices, and (2) by controlling task-switching between TD and BU brain operations via projections to the lateral PFC. Importantly, in the present study an increase in gamma synchrony was found, during the presentation of a distracting sound, between the auditory cortices and several distant brain regions, notably the dorso-and ventro-lateral prefrontal cortices, but not the medial prefrontal regions. This result argues for a strong implication of the lateral PFC.

Activation of the lateral PFC has also been associated with distractor suppression [START_REF] Dolcos | Regional brain differences in the effect of distraction during the delay interval of a working memory task[END_REF][START_REF] Suzuki | Distinct neural mechanisms of distractor suppression in the frontal and parietal lobe[END_REF]. It has been demonstrated that reversible inactivation of the lateral PFC (specifically the dorsolateral prefrontal cortex) results in increased distractibility in monkeys [START_REF] Suzuki | Distinct neural mechanisms of distractor suppression in the frontal and parietal lobe[END_REF], and its stimulation with tDCS decreases susceptibility to attentional capture in humans [START_REF] Cosman | Transient reduction of visual distraction following electrical stimulation of the prefrontal cortex[END_REF]. Thus, the lateral PFC could be attributed a role in cognitive inhibitory control. We posit that the lateral PFC, through gamma phase synchrony, could play a role in the propagation of the top-down inhibitory signal from the medial PFC and ACC to the auditory cortices, in order to filter out task-irrelevant distracting sounds in anticipation of the upcoming relevant target sound. This interpretation is in line with the Communication-Through-Coherence (CTC) hypothesis which proposes that anatomical connections are dynamically rendered effective or ineffective through the presence or absence of rhythmic synchronization, particularly in the gamma band [START_REF] Fries | A mechanism for cognitive dynamics: neuronal communication through neuronal coherence[END_REF]. Moreover, this suggested link between the lateral and medial subdivisions of the prefrontal cortex is in line with previous studies highlighting high interconnectivity between the lateral and medial PFC [START_REF] Miller | An integrative theory of prefrontal cortex function[END_REF][START_REF] Cole | Multi-task connectivity reveals flexible hubs for adaptive task control[END_REF]. In their study, Cole and colleagues (2013) demonstrated that the lateral PFC along with the posterior parietal cortex, constitute a highly flexible connectivity hub that could be involved in implementing task demands by biasing information flow across multiple largescale functional networks. Thus, the lateral PFC could act as an inhibitory (control) signal relay hub between nodes of the ventral bottom-up attentional network (e.g. the auditory cortex) and the medial PFC and ACC. Consequently, the lateral PFC could orchestrate the interplay between dorsal and ventral attentional networks, by relaying inhibitory signal from the medial PFC, leading to switching between TD attention towards the upcoming target and BU attention to the distracting sound.

Conclusion

Using the high temporal and spatial resolution of magnetoencephalography, we demonstrate for the first time, in the human brain, how gamma activity would support activation and communication within the ventral BU attentional network, as well as the interaction between BU and TD attention. This corroborates the proposed role for gamma oscillations as a promoter of rapid transfer of information through the cortical hierarchy [START_REF] Sedley | Do cortical gamma oscillations promote or suppress perception? An under-asked question with an over-assumed answer[END_REF]. Moreover, this finding fits in a wider framework proposing that activity in different attentional networks would be supported by different frequency bands. More precisely, slow oscillations (namely alpha) would support more top-down attentional mechanisms, while faster activities (namely gamma) would support more bottom-up attentional mechanisms [START_REF] Buschman | Top-Down Versus Bottom-Up Control of Attention in the Prefrontal and Posterior Parietal Cortices[END_REF]. Importantly, the present results strongly suggest that the medial prefrontal cortex would control the balance between topdown and bottom-up mechanisms of attention, while the lateral prefrontal cortex would orchestrate the interaction between top-down, bottom-up, and inhibition attentional networks.

ACKNOWLODGEMENTS

We would like to thank Sebastien DALIGAULT and Claude DELPUECH for technical assistance with the acquisition of electrophysiological data. This work was supported by the French National Research Agency ANR-14-CE30-0001-01 (ABC), by the Rhone-Alpes Region (HE) and by the LABEX CORTEX (ANR-11-LABX-0042). This work was performed within the framework of the LABEX CELYA (ANR-10-LABX-0060) of Université de Lyon, within the program ''Investissements d'Avenir'' (ANR-11-IDEX-0007) operated by the French ANR.

Figure 1 .

 1 Figure 1. Protocol. Top row. Example of an informative trial with no distracting sound: a onesided visual cue (200 ms duration) indicated in which ear (left or right) the target sound would be played (100 ms duration) after a fixed 1000-ms delay. Bottom row. Example of an uninformative trial with a distracting sound: a two-sided visual cue (200 ms duration) did not provide any indication in which ear (left or right) the target sound will be played. In 25 % of the trials, a binaural distracting sound (300 ms duration), such as a clock ring, was played during the delay between cue and target. The distracting sound could equiprobably onset in two different time periods after the cue offset: in the 50-350 ms range, or in the 350-650 ms range.

Figure 2 .

 2 Figure 2. Schematic depiction for baseline correction of trials with a distracting sound.

Figure 3 .

 3 Figure 3. A. Median Reaction Times (RTs) according to cue and distractor conditions. B. Percentage of Incorrect Responses according to cue and distractor conditions. * P < 0.05, ** P < 0.01, *** P < 0.001. Error bars represent SEM.

  , this contrast revealed one significant positive cluster (p = 0.002) indicating an increase in gamma activity centered spatially around left and right temporal sensors (Fig 4A), temporally between 0.1 and 0.3s post-distractor onset (Fig 4B & C), and frequency-wise, between 60 and 100 Hz (Fig 4B & D).

Figure 4 .

 4 Figure 4. Gamma activity to distractor at the sensor level. A. Topographical maps averaged between 50-110 Hz and 0-0.35 seconds post-distractor onset, of the t-values, masked at p < 0.05 of the contrast between distractor and surrogate distractor gamma activity. B. Timefrequency representations of the t-values (of the aforementioned test) of the sensors highlighted by red boxes in A. C. Frequency distribution of t-values of the aforementioned sensors averaged across the time dimension. D. Time distribution of t-values of the aforementioned sensors averaged across the frequency dimension.

  ) the left and right auditory cortices, (2) the left and right tempo-parietal junctions, and (3) the right ventrolateral prefrontal cortex (vlPFC). Other regions included the calcarine, the anterior, middle and posterior cingulate gyri, the inferior temporal gyri and the Precuneus.

Figure 5 .

 5 Figure 5. Gamma activity to distractor at the source level. Distributions of T-values, masked at p<0.05, from Cluster Based Permutation tests contrasting real and surrogate distractor gamma activity (60-100Hz and 0.1-0.3 post-distractor) at the source level. AcX: Auditory Cortex. TPJ: temporo-parietal junction. vlPFC: ventrolateral prefrontal cortex.

Figure 6 .

 6 Figure 6. Top-down modulation of gamma activity to distractor at the source level. Distributions of T-values, masked at p<0.05, from Cluster Based Permutation tests contrasting surrogate-corrected distractor gamma activity (60-100Hz and 0.1-0.3 post-distractor)

Figure 7 .

 7 Figure 7. Gamma connectivity to distractor at the source level. Distributions of T-values, masked at p<0.05, from Cluster Based Permutation tests contrasting real and surrogate distractor gamma phase synchrony (60-100Hz and 0.1-0.3 post-distractor) at the source level between the auditory ROI (bilateral auditory cortices, see image in the right top corner) and all other cortical voxels. dlPFC: dorsolateral prefrontal cortex. vlFPC: ventrolateral prefrontal cortex.