R Charlot

F Martin

L Roussel-Dherbey

D Maniguet

F Pellerin

C Volpi

G Boujrouf

M Parry

Braccini

S Comby-Dassonneville

F Volpi

C Boujrouf

G Parry

M Braccini

S Iruela

A Antoni-Zdziobeka

Y Champion

M Verdier

F Charlot

R Martin

F Roussel-Dherbey

L Maniguet

D Pellerin
email: d.pellerin@scientec.fr

Development and application of a multifunctional nanoindenter: coupling to electrical measurements and integration in-situ in a scanning electron microscope

Keywords: Electrical contact, nanoindentation, scanning electron microscope, area monitoring, oxide cracking, breakdown

HAL is

I. INTRODUCTION

The understanding and the quantitative analysis of the electro-mechanical processes involved at the interface between two solids are of crucial interest for both academic and applied purposes [START_REF] Holm | Electrics Contacts, Theory and Applications[END_REF][START_REF] Braunovic | Electrical Contacts, Fundamental, Applications and Technology[END_REF]: electric connectors for electrotechnics and automotive applications, intermittent contacts in mechanical switches (at both macro-and micro-scales), microelectronics,... The development of scanning probe microscopy (SPM) triggered the experimental study of these phenomena at small-scale [START_REF] Binnig | Atomic Force Microscope[END_REF]4,[START_REF] Eyben | Probing Semiconducteurs Technology and Devices with Scanning Spreading Resistance Microscopy[END_REF], but only the coupling of electrical measurements with instrumented indentation (independent load and displacement measurements) provided the precise control and monitoring of both contact mechanics and electrical conduction [START_REF] Nili | In situ nanoindentation: Probing nanoscale multifunctionality[END_REF]. Initiated by the monitoring of phase transformation under pressure [START_REF] Clarke | Amorphization and Conductivity of Silicon and Germanium Induced by Indentation[END_REF][START_REF] Pharr | Electrical resistance of metallic contacts on silicon and germanium during indentation[END_REF][START_REF] Ruffell | An in situ electrical measurement technique via a conducting diamond tip for nanoindentation in silicon[END_REF], resistive-indentation has then been extended to the study of other phenomena: native oxide fracture [START_REF] Pethica | Contact of characterised metal surfaces at very low loads: Deformation and adhesion[END_REF][START_REF] Stauffer | Plastic response of the native oxide on Cr and Al thin films from in situ conductive nanoindentation[END_REF][START_REF] Nguyen | Electric contact resistance for monitoring nanoindentation-induced delamination[END_REF][START_REF] Shimizu | The investigation of electrical contacts using newly designed nano-indentation manipulator in scanning electron microscope[END_REF], MEMS operation at small scales [START_REF] Duvivier | Investigation of the Electrical Resistance of Au / Au Thin Film Micro Contacts[END_REF][START_REF] Arrazat | Discrete Analysis of Gold Surface Asperities Deformation under Spherical Nano-Indentation Towards Electrical Contact Resistance Calculation[END_REF] and contact area computation during nanoindentation tests [START_REF] Fang | Continuous electrical in situ contact area measurement during instrumented indentation[END_REF][START_REF] Sprouster | Quantitative electromechanical characterization of materials using conductive ceramic tips[END_REF]. In the past decades, numerous efforts have been made to further expand the capabilities of nanoindentation [START_REF] Nili | In situ nanoindentation: Probing nanoscale multifunctionality[END_REF]: real-time imaging [START_REF] Rabe | Observation of fracture and plastic deformation during indentation and scratching inside the scanning electron microscope[END_REF][START_REF] Wall | Development on an in situ nanoindentation specimen holder for the high voltage electron microscope[END_REF], coupling with multifunctional characterisation tools [START_REF] Sridhar | Electrical response during indentation of piezoelectric materials: a new method for material characterization[END_REF][START_REF] Rar | Piezoelectric nanoindentation[END_REF], high temperature measurements [START_REF] Schuh | Nanoindentation and contactmode imaging at high temperatures[END_REF],... The present article reports the development and the application of a home-made multifunctional characterisation device based on a commercial nanoindentation head. This device combines mechanical and electrical characterisations, and can be integrated insitu in a Scanning Electron Microscope (SEM). Quantitative electrical characterisations cover resistive and capacitive measurements (focus is made on resistive measurements in this paper). In-situ SEM integration allows precise positioning of local nanoindentation tests (with a precision better than 100nm) as well as the positioning of electrically-coupled nanoindentation maps.

II. EXPERIMENTAL DETAILS

The experimental set-up combines different commercial instruments, with customized adapter systems. Fig. 1 presents the Infra-Red view of the set-up once integrated within the SEM chamber. The nanoindentation head is a commercial actuator (InForce 50 actuator from Nanomechanics Inc / KLA-Tencor), displaying a maximum load of 50mN and a static load resolution below 0.1 µN. This force-controlled actuator enables continuous stiffness measurement (CSM) through locked-in detection of displacements induced by oscillatory loads superimposed to the main load signal. This CSM mode gives access to the continuous extraction of both hardness and elastic modulus during indentation [START_REF] Oliver | Measurement of hardness and elastic modulus by instrumented indentation: Advances in understanding and refinements to methodology[END_REF]. A fast mapping technique is also available, allowing high-speed nanoindentation tests (~1 indent per second). The indentation tip is screwed on a 1.5 cm-long extension. All the experiments presented in this paper have been performed with boron-doped diamond (BDD) tips with resistivity in the range of [0.2-2] Ω.cm (with either Berkovich, cube-corner or flat-punch shapes). Electrical contacts to the tip are made with thin copper wires connected to fixed sockets. Actuator and sample displacements are performed with linear positioners from SmarAct GmbH. Typical travel ranges are at the cm-scale with a ~1 nm resolution. An overall stiffness larger than 10 6 N/m has been extracted, thus validating the overall mechanical behavior. The SEM apparatus used was a Field Emission Gun (FEG) GEMINI SEM 500 from Zeiss [START_REF] Maniguet | Fuel cells and ceramic-characterizing real-worlds sample with a fesem ready for challenges[END_REF]. The arrangement of the analytical tools within the SEM chamber has been optimized to improve the observation angle during indentations. In standard conditions, the specimen surface was scanned under a 60° tilt angle, that was softwarecorrected during experiments. The SEM-integration allows positioning of indents with a precision better than 100nm. As an illustration, Fig. 2(a) presents a 1µm-large gold island (obtained by dewetting of a gold film on sapphire substrate) after a 'smiley pattern' obtained from three indents. Resistance measurements are conducted with a ResiScope apparatus from CSI/Scientec. Originally developed for conductive-atomic force microscopy [START_REF] Houzé | Imaging the local electrical properties of metal surfaces by atomic force microscopy with conducting probes[END_REF], this device is optimised for real-time and self-compliant resistance measurements. It ranges from 100  to 1 T, with acquisition rates up to 1kHz. The high resistance sensitivity is illustrated in Fig. 2(b) with a typical 1 kHz monitoring of contact resistance during indentation: the figure inset zooms in on the resistance oscillations induced by the CSM mode at 100Hz. These resistance oscillations correspond to contact area variations of 0.3%, confirming the high sensitivity of the apparatus.

III. RESISTIVE-NANOINDENTATION ON METALS

A. Contact area monitoring

The real-time monitoring of resistance during nanoindentation is of particular interest for the quantitative analysis of nanoindentation tests. Indeed, the simultaneous computation of sample Young's modulus and hardness relies on a precise knowledge of the contact area Ac. However even for the simplest cases of homogeneous semi-infinite specimens, the determination of Ac is strongly affected by pile-up or sink-in phenomena that occur at the contact periphery (Fig. 3). The actual contact area may then be misinterpreted by 20-30%. The standard methods widely used to extract contact area require analytical models based on material rheology assumptions [START_REF] Oliver | An improved technique for determining hardness and elastic modulus using load and displacement sensing indentation experiments[END_REF][START_REF] Loubet | Mechanical Properties and Deformation Behavior of Materials Having Ultra-Fine Microstructures : Nanoexperiments with a surface force apparatus[END_REF]. On the contrary, the direct monitoring of contact area by resistive-nanoindentation should bring supplementary inputs for the quantitative analysis of indentation tests. Some attempts to combine micro-or nano-indentation to resistive measurements to quantitatively analyze the indentation process have been reported [START_REF] Fang | Continuous electrical in situ contact area measurement during instrumented indentation[END_REF][START_REF] Sprouster | Quantitative electromechanical characterization of materials using conductive ceramic tips[END_REF] but the monitoring of contact area was not processed. Typical resistance-versus-depth curves obtained on a gold bulk specimen are shown in Fig. 4. As expected, resistance continuously decreases as the mechanical contact area increases [START_REF] Sprouster | Quantitative electromechanical characterization of materials using conductive ceramic tips[END_REF]. It can be seen that the resistance does not depend on the applied voltage, thus evidencing an Ohmiclike electrical contact. One of the bottleneck steps for the quantitative analysis of resistive-nanoindentation tests is the appropriate analytical description of the electrical measurement chain. In the case where the indenting tip is much more resistive than the specimen (typical case of a metal being indented with a doped-diamond tip), the measured resistance is essentially due to the tip contribution. Under this condition (and if the specimen is oxide-free), the resistance of the overall set-up can be simply given by (1) (for more details, see [START_REF] Comby-Dassonneville | Resistive-nanoindentation: contact area monitoring by real-time electrical contact resistance measurement[END_REF]):

Rmeasured = A + B/(hc+h0)
(1) A and B are two constants that depend only on the experimental set-up (tip geometry and resistivity, series resistance,…) but not on the specimen (A and B have to be determined experimentally during the calibration step, see below). h0 is the length of the tip defect (unavoidable rounded apex of the tip). This description being established, the experimental extraction of the contact area can be processed through a 3-step procedure:  Step 1: The tip geometry is determined from direct AFM characterisation. This step generates the tip "shape function" that relates the projected contact area to the contact depth hc.  Step 2: An electrical calibration is carried out (on a gold bulk single crystal for instance), aiming at the determination of the A and B constants (see ( 1)). As A and B depend only on the experimental set-up, a one-toone analytical correspondence is then established between the electrical resistance and the contact depth (independently of the specimen).  Step 3: The contact area monitoring of any oxide-free specimen can then be performed. Using the shape function (step 1), the contact area is finally determined from the contact depth values (step 2) for this specimen to be characterized. This procedure has been applied and validated on a 200 nm-thick polycrystalline gold film deposited on a sapphire substrate. Such a composite geometry is a model case of complex rheology which is depth-dependent and where no analytical model exists. To do so, resistivenanoindentation tests with various final penetration depths have been performed. For each test, post-mortem AFM measurements have been conducted to compare the contact area to the one monitored by our procedure. Fig. 5 compares those data, and shows an excellent agreement between our predictions and the effective areas. For comparison, the contact area computed from the standard Oliver-Pharr method [START_REF] Oliver | An improved technique for determining hardness and elastic modulus using load and displacement sensing indentation experiments[END_REF] (based on sink-in assumption) is also reported showing a ~50% discrepancy. Such a precise monitoring of the tip-to-sample contact area has been reported for the first time in literature in [START_REF] Comby-Dassonneville | Resistive-nanoindentation: contact area monitoring by real-time electrical contact resistance measurement[END_REF].

B. Ballistic and diffusive conductive regimes

It is also interesting to note that the high sensitivity of both the indentation column and the ResiScope module allows the direct observation of the transition from ballistic to diffusive conductive regimes at the very first steps of nanoindentation. In order to highlight this point, a set of nanoindentation tests is shown in Fig. 6 (only 5 tests are plotted for clarity). Two trends are clearly observed, with a transition circa 3.5 nm. Beyond this point, the resistance evolves as the reciprocal of the penetration depth (see (1)), which is the signature of a diffusive regime. Below this transition depth, a slope discontinuity is observed, toward a power-law dependence. This nm-scale transition depth may be attributed to the combination of several mechanisms:  Sharvin condition: When the contact radius is comparable to the electron mean free path, the lateral restriction imposed to the electrical current leads to a ballistic transport regime. In that case, the electrical contact conductance evolves as a power-law of contact radius [START_REF] Sharvin | A possible method for studying fermi surfaces[END_REF][START_REF] Holm | Electrics Contacts, Theory and Applications[END_REF]. In the present case, the mean free path of electrons in this highly-doped diamond tip is estimated to be circa 2 nm [START_REF] Barjon | Resistivity of boron doped diamond[END_REF][START_REF] Kapilashrami | Boron Doped diamond films as electron donors in photovoltaics: An X-ray absorption and hard X-ray photoemission study[END_REF][START_REF] Kardakova | Relaxation of the resistive superconducting state in boron-doped diamond films[END_REF], which is in good agreement with the present transition depth.  Multi--spots model: Based on Holm's approach [START_REF] Holm | Electrics Contacts, Theory and Applications[END_REF], it has been shown that if a macroscopic contact is the combination of a large number of local spots (because of roughness, surface contamination, native oxide,…), the total contact conductance is the sum of the individual conductances with an additional term accounting for the spot interaction. It has been shown that this approach also deviates from the simple diffusive model [START_REF] Greenwood | Constriction resistance and the real area of contact[END_REF].

 Intermittent contact: Before the mechanical contact is continuously established, the intrinsic nanoindenter vibrations (1.7 nm standard deviation in our system) may also lead to intermittent local contacts.

C. Electrical and mechanical properties: local characterisation and mapping

As already mentioned, the integration of this resistivenanoindentation set-up within the SEM allows precise positioning of the spot to analyze as well as the electromechanical mapping of a specimen surface. These two advantages are illustrated through the study of an AgPdCu alloy designed to combine high conductivity and large yield strength. The composition was chosen within the miscibility gap of this ternary alloy [START_REF] Khera | Phase Equilibrium Studies in Solid Copper-Silver-Palladium Alloys at Elevated Temperatures[END_REF][START_REF] Kubaschewski | Ag-Cu-Pd[END_REF] and annealed for 890 h. Three phases were identified by X-Ray diffraction (Fig. 7): one phase is Ag-rich while two are Curich (B2 and A1 crystal lattice structures). The Ag-and Cu-rich phases can be distinguished clearly by SEM (Fig. 8): the Ag-rich phase appears as the lightest domains while the two Cu-rich phases appear as a unique continuous dark domain (the B2 and A1 crystal structures cannot be discriminated). Fig. 8 presents an SEM view of the sample after a local indent performed on the Ag-rich phase (lightest domain). Fig. 9 (a)-(b) collect the resistance and hardness measures obtained over 28 indents on the two domains. The Cu-rich domain appears as more conductive than the Ag-rich one, but it also appears as harder. The higher resistance of the Ag-rich domain can be attributed either to a larger intrinsic resistivity, to a more resistive native-oxide or to different material rheologies. However the data dispersion (on hardness and resistance) requires a more statistical approach, which can be fulfilled by a large-scale mapping applied to a region of interest. Fig. 10 reports such a combined mapping of contact resistance, elastic modulus and hardness measured simultaneously over a 120×120 µm 2 area. This map first confirms the trend observed from the individual local characterisations, but also allows a clear correlation between harder and more conductive domains.

IV. RESISTIVE-NANOINDENTATION ON NATIVE OXIDE LAYER

The electro-mechanical behavior of two metals in contact often faces the presence of an oxide layer at their interface. Thus, the control of the electrical degradation of this oxide under a mechanical stress is critical [START_REF] Stauffer | Plastic response of the native oxide on Cr and Al thin films from in situ conductive nanoindentation[END_REF][START_REF] Shimizu | The investigation of electrical contacts using newly designed nano-indentation manipulator in scanning electron microscope[END_REF]. The present set-up opens to the quantitative analysis of current leakage and/or breakdown phenomena. To do so, different materials have been studied: aluminum, copper and silicon (either natively-oxidized or capped by chemically-deposited oxides). In the present paper, for sake of clarity, focus is made on natively-oxidized aluminum [001] single crystal. The tests reported in the present paper were performed at room atmosphere. The alumina thickness was estimated to be 6-9 nm by X-Ray reflectometry. Representative resistance-vs-depth curves for different polarizations are shown in Fig. 11. First it can be seen that the contact resistance depends strongly on the applied voltage. This non-linearity of the electrical contact is confirmed by the current-voltage characteristics monitored at different penetration depths (Fig. 12). In terms of depth-dependence, the trends are drastically different for large or small applied voltages. Under large voltages (5 and 10 V), the resistance decreases the same way as for gold indentation (Fig. 4): at first order, contact resistance decreases as the reciprocal of the penetration depth. In contrast, at low voltages (0.5 and 2 V), large instabilities (up and down) are observed. This low/large voltage discrepancy can be first explained by the electrical breakdown of the oxide. According to the approach proposed by Gloos et al. [START_REF] Gloos | Properties of native ultra thin aluminium oxide tunnel barriers[END_REF], the breakdown voltage of this alumina layer can be estimated to be 2.2 V (+/-0.6 V). This value is in agreement with our experimental transition voltage (between 2 and 5V): beyond this polarization threshold, the oxide conductivity is large enough to make it transparent to electronic transport. It is to be noted that the mechanical failure of the oxide (detected by steep depth rises during indentation) is not sufficient to explain resistance drops: for the same test conditions (voltage, environment,…), an oxide crack can go along with a resistance drop (Fig. 13) or can occur without any resistance change (Fig. 14). This observation is in agreement with [START_REF] Stauffer | Plastic response of the native oxide on Cr and Al thin films from in situ conductive nanoindentation[END_REF] and [START_REF] Shimizu | The investigation of electrical contacts using newly designed nano-indentation manipulator in scanning electron microscope[END_REF] on the Al2O3/Al and SnO2/Sn systems, respectively. However the behavior observed at low voltages (i.e. before dielectric breakdown) is not straightforward. The random resistance rises (highlighted by black arrows in Fig. 11) and drops are unexpected while the contact area continuously increases. Comparable behaviors have already been reported for instance by Bouchoucha et al [START_REF] Bouchoucha | Influence of electric eldson tribological behaviour of electrodynamical copper/steel contacts[END_REF] on copper-steel contacts at constant force. The resistance rises were attributed to oxide growth. However some characteristic magnitudes were drastically different from our experiments: (1) while their resistances were multiplied by a factor of 4, our resistance changes covered several orders of magnitude and (2) the time constant of their resistance variations were two orders of magnitude slower than in our case. We propose to explain these up and down instabilities from electrochemical processes occurring within the oxide. As a solid electrolyte, alumina ensures electrical conduction through ionic processes only, meaning that conduction is essentially due to oxygen vacancy transport [START_REF] Desportes | Electrochimie des solides[END_REF]. In the present experiment, oxygen vacancy mobility is highly promoted by local electromigration [START_REF] Braunovic | Electrical Contacts, Fundamental, Applications and Technology[END_REF] and mechanical deformation. The electrochemical reactions involved at the diamond-tip/alumina and the alumina/aluminum interfaces are given by equations (2) (oxygen vacancy reduction) and (3) (oxygen production), respectively.

(2)

(3) These two reactions describe two competing trends in terms of resistance evolution. As the experiments are performed at room atmosphere, oxygen supply is fast enough to promote the first reaction at the diamond/alumina interface, thus pumping oxygen vacancies through the oxide and finally reducing the overall resistance. On the contrary, the second reaction describes the oxide growth at the second alumina/aluminum interface, thus increasing the overall resistance. These antagonistic trends can clearly explain the observed resistance instabilities at low voltages. This explanation is in agreement with the experiments performed under different relative humidity environment (not shown here [39]). V. CONCLUSION An experimental set-up dedicated to the coupling of local electrical and mechanical characterisations is presented. This set-up combines a nanoindentation head to fine electrical measurements in-situ in a scanning electron microscope. The experimental performances of the set-up (precision and sensitivity) are illustrated on both oxide-free and oxidized metals. First the ability to monitor quantitatively the contact area all along a nanoindentation test is demonstrated. Then a two-domain metallic system is characterized through either individual indents on each domain or large-scale mapping. Finally the electrical behavior of a native oxide is analyzed and described on the basis of dielectric breakdown and electrochemical processes. The prospects for further experiments are wide. For instance, this set-up can be applied to the characterisation of small-scale piezoelectric structures, or to the monitoring of permittivity transients induced by mechanical loads.

Fig. 1 .

 1 Fig. 1. Infra-Red view of the set-up once integrated within the SEM. (1 = Nanoindenter head, 2 = Extender + tip, 3 = Specimen, 4 = SEM column)

Fig. 2 .

 2 Fig. 2. Illustrations of the set-up performances. (a) Gold island after three individual indents (without tilt-correction). (b) Typical resistancevs-time curve during nanoindentation

Fig. 3 .

 3 Fig.3. Effect of material rheology on contact area and contact depth. The penetration depth h is the depth reached by the tip from the initial specimen surface, while the contact depth hc describes the length of the tip in contact with the specimen.

Fig. 4 .

 4 Fig. 4. Resistance-vs-depth curves for bulk Au nanoindentation with a doped-diamond Berkovich tip under different polarizations.

Fig. 5 .

 5 Fig. 5. Contact area against penetration depth on the Au thin film. Comparison of the computed data (open markers) with the corresponding post-mortem AFM measurements (solid markers). Predicted contact area from Oliver and Pharr model in dotted line.

Fig. 7 .

 7 Fig. 7. -2 X-Ray diffractogram of the AgPdCu alloy. Performed with Kα Cu source.

Fig. 8 .

 8 Fig. 8. SEM view of an indent left after local testing of the Ag-rich phase. The white triangle at the bottom of the image is the indenter tip.

Fig. 9 .

 9 Fig. 9. Electrical and mechanical data from 28 indents performed in both Ag-and Cu-rich phases. (a) Resistance and (b) Hardness evolutions with indentation depth. Hardness data were extracted from Oliver-Pharr model [26].

Fig. 6 .

 6 Fig. 6. Resistance-vs-depth curves for bulk Au nanoindentation with a doped-diamond Berkovich tip, in log-log scale.

Fig. 10 .

 10 Fig. 10. Typical mapping of resistive and mechanical properties. (a) SEM micrograph of the domain after indentation (each dark dot is an indentation imprint). (b)-(c)-(d) Mapping of the electrical resistance (in log-scale), the elastic modulus and hardness, respectively. Mechanical magnitudes were extracted from Oliver-Pharr model [26].

Fig. 11 .

 11 Fig. 11. Resistance-vs-depth curves for natively-oxidized Al nanoindentation under different polarizations.

Fig. 12 .

 12 Fig. 12. Current-voltage curves extracted at different depth during Al nanoindentation. Depths range from 100 to 1400 nm.

Fig. 13 .

 13 Fig. 13. Resistance and depth evolution during natively-oxidized Al indentation: the oxide cracking observed on the depth curve (black arrow) is accompanied by a resistance drop. Same test conditions as Fig. 14 (Applied voltage: 5V).

Fig. 14 .

 14 Fig. 14. Resistance and depth evolution during natively-oxidized Al indentation: the oxide cracking observed on the depth curve (black arrow) is not accompanied by a resistance drop. Same test conditions as Fig. 13 (Applied voltage: 5V).

ACKNOWLEDGMENT This work has been performed with the financial support of the Centre of Excellence of Multifunctional Architectured Materials "CEMAM" n° ANR-10-LABX-44-01. The CEMAM program is funded by the French Agence Nationale de la Recherche (ANR). The authors thank the technical team of SIMaP lab (B. Mallery, S. Massucci, N. Vidal) for its support, the CMTC platform (physico-chemical characterization platform of Grenoble INP), as well as members of CSI/Scientec company (Les Ulis, France) for their support for the functionalization of the nanoindentation head: L. Pacheco, A. Lecoguiec and S. Poulet.


Aurely Ameller

Aline Picard

Fabien D'hondt

Guillaume Vaiva

Pierre Thomas

Delphine Pins

implicit recognition of Familiar and Unfamiliar Faces in schizophrenia: a study of the skin conductance response in Familiarity Disorders

Keywords: schizophrenia, skin conductance response, familiarity disorders, capgras, Fregoli

Objective: Familiarity is a subjective sensation that contributes to person recognition. This process is described as an emotion-based memory-trace of previous meetings and could be disrupted in schizophrenia. Consequently, familiarity disorders could be involved in the impaired social interactions observed in patients with schizophrenia. Previous studies have primarily focused on famous people recognition. Our aim was to identify underlying features, such as emotional disturbances, that may contribute to familiarity disorders in schizophrenia. We hypothesize that patients with familiarity disorders will exhibit a lack of familiarity that could be detected by a flattened skin conductance response (SCR).

Method:

The SCR was recorded to test the hypothesis that emotional reactivity disturbances occur in patients with schizophrenia during the categorization of specific familiar, famous and unknown faces as male or female. Forty-eight subjects were divided into the following 3 matched groups with 16 subjects per group: control subjects, schizophrenic people with familiarity disorder, and schizophrenic people without familiarity disorders.

results: Emotional arousal is reflected by the skin conductance measures. The control subjects and the patients without familiarity disorders experienced a differential emotional response to the specific familiar faces compared with that to the unknown faces. Nevertheless, overall, the schizophrenic patients without familiarity disorders showed a weaker response across conditions compared with the control subjects. In contrast, the patients with familiarity disorders did not show any significant differences in their emotional response to the faces, regardless of the condition. conclusion: Only patients with familiarity disorders fail to exhibit a difference in emotional response between familiar and non-familiar faces. These patients likely emotionally process familiar faces similarly to unknown faces. Hence, the lower feelings of familiarity in schizophrenia may be a premise enabling the emergence of familiarity disorders.

inTrODUcTiOn Misidentification disorders refer to disorders in a patient's sense of personal relatedness to other people; patients deny the identity of other people who are either close to them or are strangers [START_REF] Hirstein | The misidentification syndromes as mindreading disorders[END_REF]. Experiences in which patients do not recognize someone they know or believe that someone they know has been replaced by another person to persecute them are core features of misidentification disorders. In Fregoli syndrome [START_REF] Courbon | Syndrome d'illusion de Fregoli schizophrenie[END_REF], patients recognize unknown people and believe that they are friends or relatives who have assumed the faces of strangers. These patients often have persecutory delusions centered upon these relatives or friends.

The most commonly described misidentification disorder is Capgras syndrome [START_REF] Capgras | L'illusion des sosies dans un délire systématisé chronique[END_REF][START_REF] Luauté | Capgras syndrome: agnosia of identification and delusion of reduplication[END_REF]. Patients with Capgras syndrome recognize specific familiar faces but have the delusional belief that the familiar person is an impostor or a clone appearing as whom they claim to be. Patients with CS argue that there is something "weird" in the personality of the person and/or that minor physical features (e.g., iris color) have changed.

The following two independent but cooperative processes are beneficial for accessing information regarding an individual person: identification and recognition [START_REF] Yonelinas | Recollection and familiarity: examining controversial assumptions and new directions[END_REF]. Identification is defined as the retrieval of the identity of an object or individual. Recognition is the knowledge that an object or an individual has been previously encountered. Recognition is a cognitive process is that associated with memory. Recognition can be further divided into the following two different processes [START_REF] Yonelinas | Recollection and familiarity: examining controversial assumptions and new directions[END_REF]: recollection and familiarity. Recollection refers to the conscious remembrance of a prior experience, which provides access to the contextual details of this prior event (e.g., where when). Familiarity is a subjective sensation that occurs during stimulus processing and is unconsciously attributed to past experiences. Hence, familiarity is a preconscious process that contributes to the recognition of an individual without the need to consciously remember the context in which the person has been previously met. Familiarity has been described as an emotion-based memory-trace of previous meetings and acts as a facilitator [START_REF] Young | Capgras delusion: an interactionist model[END_REF]. The more frequently a person encounters another, the easier it is to recognize him or her. Hence, misidentification disorder may, in fact, be a core defect in familiarity. Therefore, the ambiguous name "misidentification" should be reconsidered. In this article, we use the term "familiarity disorders, " which is a more accurate term than "misidentification disorders, " based on the neurocognitive processes described above.

Familiarity disorders can be features of many psychiatric and neurological disorders (such as Alzheimer's or Lewy dementia, ischemic stroke, and Parkinson's disease). In particular, familiarity disorders are widely described in patients in schizophrenia, and these disorders may be the cause of the core defects in social interactions. Therefore, a better understanding of familiarity disorders in schizophrenia is critical. Familiarity disorders encompass two polarities. Hypofamiliarity refers to a lack of familiarity of individuals close to the person (such as in Capgras syndrome), whereas hyperfamiliarity refers to an increased sense of familiarity of unknown people (such as in Fregoli syndrome). Nevertheless, the distinction between hypo-and hyperfamiliarity appears to be weak because the co-occurrence of Capgras syndrome and Fregoli syndrome has been described in some schizophrenic patients [START_REF] Feinberg | Delusional misidentification[END_REF][START_REF] Silva | A case of "subjective" Frégoli syndrome[END_REF]. Indeed, patients may first present with Capgras syndrome and then develop Fregoli syndrome in the course of their disease [START_REF] Sno | A continuum of misidentification symptoms[END_REF]. Both syndromes might represent different disturbances in the same system that can oscillate and, therefore, allow both syndromes to be present in the same patient. Indeed, patients may show certain symptoms of familiarity disorders regardless of their polarity (hyper-or hypofamiliarity), which further supports the hypotheses that these syndromes are on a continuum.

The familiarity evoked by a particular stimulus elicits an overt emotional response that is mediated by autonomic arousal [START_REF] Ellis | Accounting for delusional misidentifications[END_REF][START_REF] Tranel | Knowledge without awareness: an autonomic index of facial recognition by prosopagnosics[END_REF]. An easily measurable index of this autonomic arousal is the skin conductance response (SCR). Indeed, the SCR is a reliable autonomic marker of central activation that is indicative of emotional arousal and its somatovisceral impact [START_REF] Hondt | Early brain-body impact of emotional arousal[END_REF]. SCRs have been recorded in control subjects and patients with schizophrenia with and without familiarity disorders, who were passively looking at pictures of famous and unknown faces [START_REF] Ellis | Reduced autonomic responses to faces in Capgras delusion[END_REF]. While the control subjects and the patients without familiarity disorders displayed larger SCRs in response to the famous faces than that to the unknown faces, the patients with Capgras syndrome did not show a difference in the SCR to both types of faces. Patients with familiarity disorders appear to consider the famous faces unfamiliar. However, the sample size was too small for a definitive conclusion; only five patients with Capgras syndrome were tested. Moreover, Capgras syndrome is described as affecting the recognition of close people who are affectively related to the patient [START_REF] Courbon | Syndrome d'illusion de Fregoli schizophrenie[END_REF][START_REF] Capgras | L'illusion des sosies dans un délire systématisé chronique[END_REF][START_REF] Luauté | Capgras syndrome: agnosia of identification and delusion of reduplication[END_REF]. Furthermore, famous people are not always associated with a strong emotional investment [START_REF] Gobbini | Social and emotional attachment in the neural representation of faces[END_REF].

A model proposed by Hirstein (1) in the field of theory-ofmind posits that familiar people are represented by both allocentric and egocentric representations. Allocentric representations are established during each encounter with a person and stored in semantic memory in the third-person perspective. In contrast, egocentric representations are simulated representations of a person in the first-person perspective. General representations, which are established by the aggregation of autobiographical memory information into concepts about people or objects, are activated for strangers, allowing interactions with unknown people by simulating their mental state. According to Hirstein, prior to affective failure, patients with Capgras syndrome are unable to access the egocentric representation of a relative. This inability may create a feeling of ambiguity regarding the person's familiarity because the two representations do not match, and the activation of a generic representation is elicited as it would be in the presence of strangers.

In the present study, we characterized the affective processing involved in familiarity disorders in patients with schizophrenia. We hypothesized that the familiarity disorders in schizophrenia are caused by emotional disturbances. Therefore, the SCR was recorded during a face categorization task using a set of specific highly familiar and homogeneous faces selected from the subjects' set of specific familiar individuals. Indeed, the subjects' degree of familiarity with these faces was both quantitatively and qualitatively more important and controlled than that with famous faces or recently learned faces of unfamiliar people. As previously suggested, hypo-and hyperfamiliarity might result from failures in a single system. Consequently, we hypothesized that in contrast to the controls and patients without familiarity disorders (FD-), the amplitude of the affective response in patients with familiarity disorders (FD+) would not be different regardless of the polarity of their disorder and the familiarity of the faces.

MaTerials anD MeThODs

Participants

Thirty-eight outpatients with schizophrenia (nine women) but without any psychiatric comorbidity (DSM-IV criteria) were recruited at the Lille University Hospital. The patients were assessed and assigned to one of two different groups based on their clinical relevance. FD+ patients showed at least one symptom of familiarity disorders. FD-patients had no history of such symptoms. The familiarity disorders were assessed using eight questions regarding hypo-and hyperfamiliarity experiences. The following four questions were used to assess hypofamiliarity: have you ever not recognized a familiar person? Have you ever experienced a feeling of strangeness or oddity in the presence of a familiar person? Had this familiar person changed? Was it a double? The following four questions were used to assess hyperfamiliarity: Have you ever been fooled into believing a stranger was a familiar person? Have you ever experienced a sense of familiarity to a stranger? Have you ever been convinced that you recognize a familiar person in someone unknown? Did that person appear to be a double? The FD+ group included eight patients with hypofamiliarity symptoms, five patients with hyperfamiliarity symptoms and three patients with both hyper-and hypofamiliarity symptoms. The FD+ patients showed at least one symptom of FD. All patients in the FD+ group reported that they experienced an FD at the time of the experiment. No patient in the FD-group had ever experienced such symptoms.

Eighteen healthy controls who matched the patients were recruited via local advertising. The control subjects had no psychiatric disorders as assessed by the MINI [START_REF] Sheehan | The mini-international neuropsychiatric interview (MINI): the development and validation of a structured diagnostic psychiatric interview for DSM-IV and ICD-10[END_REF]. There was no clinical evidence of prosopagnosia in any participant. No participant had an active substance use disorder based on a clinical interview. Due to the lack of SCR recordings of 6 patients and 2 controls, 32 patients with schizophrenia (9 left-handed) and sixteen healthy controls (3 left-handed) completed the entire study. Such an absence of recording has been previously described in the SCR literature [for review, see Ref. [START_REF] Dawson | The electrodermal system. 2nd ed[END_REF]]. The patients were divided into the following two groups: people with schizophrenia without FD [FD-(N = 16)] and people with schizophrenia with FDs [FD+ (N = 16)].

The participants' characteristics are summarized in Table 1. This study was approved by the local ethics committee (CPP, Nord-Ouest IV, France), and written informed consent was obtained from each participant or guardian. All participants had normal or corrected-to-normal vision.

Procedures

The experimental procedures included two phases. The entire task required approximately 15 min to complete. During the first phase (see Figure 1), the SCR data were collected during the presentation of 30 different black and white photographs of faces (10 specific familiar, 10 famous, and 10 unknown), which were presented in a random order using E-Prime 2.0 software (Psychology Software Tools, Pittsburgh, PA, USA). The famous faces were selected from the Internet, and the unknown faces were selected from the neutral faces in the Karolinska Directed Emotional Faces [START_REF] Goeleven | The Karolinska directed emotional faces: a validation study[END_REF][START_REF] Lundqvist | The Karolinska Directed Emotional Faces -KDEF[END_REF]. All faces had neutral expressions (mouth closed) and a direct gaze direction and were presented once on a uniform gray background (800 × 600 pixels). The external features of the faces were removed, and the faces were equalized in size (300 × 462 pixels-11 × 9.5° degree of visual angle), brightness and contrast using Adobe Photoshop ® . The participants placed their heads on a chin rest with their eyes positioned centrally 60 cm from the monitor (Intel computer, Sony screen, resolution 1,280 × 1,024 pixels, refresh rate 60 Hz). The participants were asked to categorize the face displayed as a male or female by pressing one of two keys on a keyboard as quickly as possible. An implicit recognition task was preferred to avoid having patients focus on face recognition while ensuring that their attention was directed toward the faces.

Because the frequency of encounters may influence familiarity processing, strict temporal criteria were applied in selecting the familiar persons for each participant. The familiar persons were colleagues or friends who were encountered several days a week for at least 6 months. For the patients, the familiar persons could have been selected (if needed) from among the medical staff using the same temporal criteria.

The homogeneity of the stimuli was assessed in the three familiarity conditions. Twenty healthy controls (10 males) were asked to rate the attractiveness and approachability of the specific familiar, famous and unknown faces from 1 to 10. As expected [START_REF] Mcdonald | Covert detection of attractiveness among the neurologically intact: evidence from skin-conductance responses[END_REF], the famous faces were rated higher in attractiveness than the specific familiar faces (Z = -3.84; P = 0.0001) and unknown faces (Z = -3.75; P = 0.0001), but there was no significant difference between the specific familiar and unknown faces (Z = -0.38; P = 0.70). Furthermore, there were no differences in approachability among the conditions (between famous and specific familiar faces: Z = -0.67; P = 0.49; between unknown and specific familiar faces: Z = -0.30; P = 0.76 and between unknown and famous faces: Z = -0.69; P = 0.48). During the second phase, we ensured that all participants recognized the specific familiar and famous faces and did not recognize the unknown people. The participants were presented with the same pictures as those presented during phase one. The participants were asked to state the name of each person they recognized. No SCR data were recorded during phase 2.

Data recording and analyses

Behavioral Data

During both tasks, the response accuracy and response time were recorded for each stimulus. The percentage of correct responses was calculated for each condition.

scr Data

The SCR data were recorded using the constant-voltage method (0.5 V) at a sampling rate of 600 Hz using a commercial skin conductance sampling device (BiopacMP35, Biopac Systems Inc., Goleta, Canada). Ag-AgCl electrodes (8 mm diameter active area) filled with 0.05 M NaCl electrolytes were attached to the palm side of the middle phalanges of the second and third fingers of the participants' left hands. To avoid movement that could impair the SCR recording, the right fingers pressing the keys were comfortably positioned on the keyboard to limit the movement amplitude. To minimize the number of non-responders, prior to the experiment, we ensure that the SCR was elicited by mental calculation and deep breathing. The amplitude and latency of the SCR were measured.

The SCR data were then extracted using BSL-pro software©. The SCRs were determined using the standard latency criterion of 1-4 s [START_REF] Tranel | Knowledge without awareness: an autonomic index of facial recognition by prosopagnosics[END_REF][START_REF] Dawson | The electrodermal system. 2nd ed[END_REF][START_REF] Boucsein | Publication recommendations for electrodermal measurements[END_REF][START_REF] Critchley | Electrodermal responses: what happens in the brain[END_REF]. The first peak in amplitude within this latency window was recorded. All SCR data were low-pass filtered at 50 Hz. Trials during which the stimulation did not produce an SCR were included in the mean data for each participant as a zero value. The amplitude of the SCR was defined as the difference in the SCR measurement between the peak and inflection curve after a stimulus presentation. To normalize the data, the amplitude of the SCR was logarithmically transformed [log(1 + amplitude)] [START_REF] Dawson | The electrodermal system. 2nd ed[END_REF][START_REF] Boucsein | Publication recommendations for electrodermal measurements[END_REF].

statistical analyses

Using a repeated-measures ANCOVA to accommodate nonsphericity, a Greenhouse-Geisser correction was applied to the average SCR amplitude [log(1 + amplitude)] or behavioral data (reaction times and correct responses) using the three participant groups as the between-subject factor and the familiarity conditions as the within-subject factor. We used sex and age as cofactors. The polarity of the FD in the FD+ group was not examined due to a potential lack of statistical power. If the ANCOVA was significant, we conducted intragroup and intergroup comparisons using Student's t-tests. The normality of the data (Levene's test) was confirmed prior to performing a parametric test. Spearman's correlations were performed in the patients to determine the correlations between the SCR amplitude in each condition and age, treatment (both chlorpromazine-and diazepam-equivalents) and symptom severity (PANSS subscores: positive or negative). All statistical analyses were performed using SPSS ® 15.0, and the level of significance was set at P < 0.05. Because multiple comparisons were performed, we corrected the level of significance to P < 0.01 in the post hoc analyses [START_REF] Lord | Multiple analyses in clinical trials: sound science or data dredging?[END_REF].

Demographic Data

The age, sex, positive and negative PANSS subscores, illness duration, and both chlorpromazine-equivalent and diazepamequivalent doses were recorded for all participants or patients only according to their relevance (cf. Table 1). The three groups did not differ in age, while sex showed a trend toward significance. The negative symptom severity and illness duration did not differ between the patient groups; nevertheless, a trend toward significance was observed for the positive symptoms between both patient groups. All patients received second-generation antipsychotic medication with similar mean chlorpromazineequivalent doses between the patient groups. Some patients received benzodiazepines (N = 4 in FD-; N = 7 in FD+) with similar mean diazepam-equivalent doses.

Behavioral Data

During the first phase of the study, the categorization performance (male or female) was not different between the groups (see Table 2 for more details). There was no significant group effect on accuracy scr Data

Main Results

The results of the ANCOVA showed significant effects of familiarity conditions [F(2,90) = 4.82; P = 0.003; η 2 = 0.28] and group [F(2,45) = 6.09; P = 0.005; η 2 = 0.21] on the SCR amplitude, and a significant group × condition interaction was observed [F(4,90) = 4.82; P = 0.003; η 2 = 0.28]. The results are presented in Figures 2345.

A significant effect of familiarity conditions on the SCR amplitude was found in the control group [F(2,30) = 30.99; P < 0.0001; η 2 = 0.67]. The results showed higher SCRs in response to specific familiar faces (0.144 ± 0.062 μS) than those in response to famous faces (0.101 ± 0.063 μS), which, in turn, were higher than those in response to unknown faces [0.088 ± 0.070 μS; specific familiar vs. famous: t(15) = 5.70; P < 0.0001, specific familiar vs. unknown: t(15) = 6.80; P < 0.0001, famous vs. unknown: t(15) = 2.01; P = 0.06]. The more familiar the faces, the higher the SCR.

In the FD-patient group, there was a trend toward an effect of familiarity condition on the SCR amplitude [F(2,30) = 20.96; P = 0.07; η 2 = 0.16]. The same amplitude profile as that in the controls was found in this subject group with decreasing SCRs from specific familiar faces (0.067 ± 0.083 μS) to unknown faces (0.04 ± 0.049 μS) and famous faces in an intermediate position (0.053 ± 0.071 μS). Nevertheless, the only significant effect was found between the specific familiar and unknown faces [t(15) = 2.82; P = 0.01]. Thus, for the FD-patients, similarly to the controls, the more familiar the faces, the higher the SCR.

In the FD ± patient group, the global effect of familiarity on the SCR amplitude was not significant [F(2,30) = 1.12; P = 0.33; η 2 = 0.01], and no significant effect was found among the conditions. The SCR amplitude did not differ among the specific familiar faces (0.037 ± 0.049 μS), famous faces (0.045 ± 0.072 μS), and unknown faces (0.034 ± 0.053 μS). For the FD+ patients, the SCR amplitude did not differ regardless of the degree of the familiarity of the faces.

Groups of Interest

The SCR amplitude in the FD-patients was generally weaker in all conditions compared with the SCR in the control subjects, resulting in a significant group effect [F(1,30) = 6.47; P = 0.01; η 2 = 0.178]. Moreover, the comparison of the controls and FDgroups showed a trend toward a significant group × familiarity condition interaction [F(2,60) = 3.45; P = 0.03; η 2 = 0.10].

Regarding the FD-patients, the SCR amplitude in the FD+ patients was globally weaker than the SCR in the control subjects, resulting in a significant group effect [F(1,30) = 11.44; P = 0.002; η 2 = 0.27]. Moreover, the comparison of the control and FD+ groups showed a significant group × familiarity condition interaction [F(2,60) = 16.18; P < 0.0001; η 2 = 0.35]. Finally, the FD+ patients differed from the FD-patients only in the specific familiar faces condition [t(30) = 6.72; P = 0.01].

Correlations

No significant correlations were found between the SCR amplitudes in response to the three familiarity conditions and age, treatment (both chlorpromazine-equivalents and diazepamequivalents), and symptom severity (PANSS subscores).

Anticholinergic Power

Subsequently, to ensure that the anticholinergic effects of the medications did not affect the SCR data, all patient medications were classified as one of four degrees of potential anticholinergic power (three for "high potential" to zero for "no anticholinergic effect scientifically proven") in accordance with a review initially conducted for geriatric use of anticholinergic properties [START_REF] Boily | Comment évaluer la charge anticholinergique?[END_REF]. Then, we ensured that both patient groups did not differ in the repartition of the anticholinergic power (Chi2(1) = 1.59; P = 0.29).

DiscUssiOn

In the current study, we explored FDs in patients with schizophrenia using a three-condition task that enabled us to discriminate the SCRs to specific familiar, famous, and unknown faces. Our results demonstrated that in healthy subjects, the more familiar the person, the stronger the emotional response linked to the feeling of familiarity. The same process occurs in the FD-patients, although these patients display a weaker emotional response across all conditions as indicated by the lower SCR amplitudes. However, the FD+ patients experienced an absence of emotional responses linked to the feeling of familiarity regardless of the familiarity of the faces that were presented (known or unknown). The feeling of familiarity elicited by emotional processes is not modulated by the degree of familiarity of the perceived faces. This result cannot be attributed to a lack of face recognition, which could be specific to the FD+ patients, because our results suggest that schizophrenic patients do correctly recognize faces, at least based on the visual features of the pictures. The gradient of the SCR does not, in fact, reflect cognitive or perceptual processes but only emotional responses to faces. Our results are consistent with those found in previous studies in healthy individuals [START_REF] Ellis | Reduced autonomic responses to faces in Capgras delusion[END_REF][START_REF] Mcdonald | Covert detection of attractiveness among the neurologically intact: evidence from skin-conductance responses[END_REF][START_REF] Herzmann | What's special about personally familiar faces? A multimodal approach[END_REF]. These previous studies using SCR measurements have shown that control subjects have a greater emotional response to familiar people than that to strangers.

Famous Faces are not Familiar Faces

Our study addressed the crucial question of whether FDs in patients with schizophrenia are more apparent with individuals close to the person considering the well-documented clinical description of this delusion (2-4). To the best of our knowledge, the present study is the first to investigate the SCR properties of FDs in patients with schizophrenia with respect to familiarity status using personally specific familiar faces and, therefore, ecologically valid face stimuli. It has been suggested that recognizing pictures of famous faces does not engage the normal face recognition processes that are engaged in the recognition of personally familiar faces [START_REF] Carbon | Famous faces as icons. The illusion of being an expert in the recognition of famous faces[END_REF][START_REF] Knappmeyer | The use of facial motion and facial form during the processing of identity[END_REF][START_REF] Liccione | Familiarity is not notoriety: phenomenological accounts of face recognition[END_REF][START_REF] Tong | Robust representations for faces: evidence from visual search[END_REF]. A specific familiar face indicates that the individual to whom the face belongs is encountered regularly, thereby the specific representation may be more flexible and more closely related to the feelings generated by the person. Indeed, our study shows that the feeling of familiarity in response to specific familiar faces is associated with a stronger emotional response than that in response to famous faces. The more homogeneous stimuli, the lack of an iconic image, or the more flexible representations may be responsible for this stronger emotional response [START_REF] Herzmann | What's special about personally familiar faces? A multimodal approach[END_REF]. In previous studies [START_REF] Gobbini | Social and emotional attachment in the neural representation of faces[END_REF][START_REF] Herzmann | What's special about personally familiar faces? A multimodal approach[END_REF] involving healthy subjects, a decrease in SCRs and emotional neural activation, as measured in the paracingulate cortex, from unknown to famous and specific familiar faces was found with no difference between the famous and unknown faces. However, in a study by Ellis et al. (13), similarly to our study, the control subjects exhibited higher SCRs in response to the famous faces than those in response to the unknown faces, but our study showed that this effect was lower in response to the specific familiar faces. Hence, these results show that the response to famous faces is variable according to each study. Altogether, these results validate the hypothesis that famous materials are not adapted in familiarity studies. Finally, these findings shed light on the importance of emotion in specific familiar face processing compared to the processing of other types of faces (famous or unknown people).

The processing of famous faces may be primarily based on basic or general representations, which would elicit more cognitive processes than emotional processes that are linked to the feeling of familiarity [START_REF] Qin | How is our self related to midline regions and the default-mode network?[END_REF]. If representations of famous people cannot be used by people with FD, these faces will activate generic representations that are, in fact, related to the people with FDs' knowledge about the famous people. Therefore, the SCR level in response to famous faces is between that of unknown and familiar faces.

a continuum between normal and Pathological; Familiarity

To the best of our knowledge, our study was the first controlled study to explore two groups of people with schizophrenia. Our results fit particularly well with the hypothesis of a continuum from normal to pathological functioning in FDs [START_REF] Sno | A continuum of misidentification symptoms[END_REF]. Indeed, all people with schizophrenia exhibited lower SCRs, which has already been documented in the literature [START_REF] Dawson | The electrodermal system. 2nd ed[END_REF]. Nevertheless, the patients with and without FDs exhibited different profiles of emotional responses to the faces, showing that their SCRs can still be modulated. The first stage of the disorder was captured by the FD-patients, who showed a global decrease in the feeling of familiarity as measured by their lower SCR amplitudes than those of the controls; however, the FD-patients still maintained differences in emotional feeling depending on the familiarity status. Thus, during this stage, the patients may have emotional disturbances, such as emotional flattering [START_REF] Ameller | What is more familiar than I? Self, other and familiarity in schizophrenia[END_REF], as shown by the decreased SCR in people with schizophrenia without FDs, which may lead to a "weird" feeling in the presence others. Based on our results, we hypothesize that the lower feeling of familiarity in patients with schizophrenia may be a premise enabling the emergence of FDs as proposed by Coltheart et al. [START_REF] Coltheart | Abductive inference and delusional belief[END_REF] in his two-step delusional models that explain the emergence of delusion. Therefore, it could be a necessary, albeit insufficient condition, for an FD to develop. During the second stage, the FD may be expressed in the FD+ patients, which, in turn, leads to an extinction of the feeling of familiarity. According to Hirstein's model [START_REF] Hirstein | The misidentification syndromes as mindreading disorders[END_REF], the absence of the simultaneous activation of egocentric and allocentric representations of someone close to the patient may cause the feeling of a lack of familiarity and the subsequent decrease in the SCR observed in the patients with FDs. This model may also explain why the delusion of CS does not affect the response to famous people despite the absence of a feeling of familiarity. Notably, our results, which were based on the SCR, appear to be specific to the FD and independent of the medication doses or schizophrenia symptom severity.

Having a lower sense of familiarity implies a lower impression of the continuity of the world, which could then disrupt the sense of reality. Face-to-face encounters require responding and entering a relationship (which does not occur with famous people). Relationships with relatives involve the self, and familiar faces are embodied stimuli with meaning that include the self [START_REF] Liccione | Familiarity is not notoriety: phenomenological accounts of face recognition[END_REF]. The anomalies of "self-experience" are known to be specific to schizophrenia [START_REF] Parnas | Anomalous subjective experience among first-admitted schizophrenia spectrum patients: empirical investigation[END_REF][START_REF] Parnas | Anomalies of subjective experience in schizophrenia and psychotic bipolar illness[END_REF]. The sense of reality and the subsequent continuity of the world are obtained according to self-experiences. Hence, disturbances in the self-experience in schizophrenia could lead to a distorted sense of reality. Thus, from the phenomenological perspective, these disturbances could result in the emergence of schizophrenia [START_REF] Parnas | A disappearing heritage: the clinical core of schizophrenia[END_REF]. In a previous SCR study involving schizophrenic patients that did not consider FD [START_REF] Ameller | What is more familiar than I? Self, other and familiarity in schizophrenia[END_REF], we used an equivalent paradigm with specific familiar, self and unknown faces. The people with schizophrenia exhibited the same familiarity in response to the self-face as that in response to the specific familiar faces. Therefore, a lower sense of familiarity in response to faces may involve a lower sense of self-face experience (as a part of face familiarity). From a phenomenological perspective, the disrupted sense of familiarity could, therefore, be a core feature of schizophrenia.

limitations of the study

One limitation of this study is the absence of a standardized clinical evaluation of familiarity disorders. Nevertheless, to the best of our knowledge, no psychometric instrument has been validated to date. As an illustration of the need for a psychometric scale, the reported prevalence of Capgras syndrome in schizophrenic patients in the literature is very heterogeneous, ranging from 4.1% [START_REF] Kirov | Prevalence of delusional misidentification syndromes[END_REF] to 28% [START_REF] Odom-White | Misidentification syndromes in schizophrenia: case reviews with implications for classification and prevalence[END_REF] and up to 40% [START_REF] Cutting | Delusional misidentification and the role of the right hemisphere in the appreciation of identity[END_REF] in the same population (schizophrenia). A better categorization of FDs is a critical issue to be addressed by future studies.

Our control experiment using healthy subjects demonstrated a difference in attractiveness between famous faces and both specific familiar and unknown faces, while approachability was similar among the conditions. Moreover, a previous study showed that familiarity preference, which was evaluated by higher attractiveness, was preserved in schizophrenia [START_REF] Antonius | Familiarity preference in schizophrenia is associated with ambivalent attitudes towards others[END_REF]. This difference is present only in famous faces. Thus, an effect of attractiveness on our primary results could lead to a greater SCR in response to famous faces [START_REF] Mcdonald | Covert detection of attractiveness among the neurologically intact: evidence from skin-conductance responses[END_REF]. The control subjects exhibited higher SCRs in response to specific familiar faces than in response to famous faces. These data confirm that our study examined familiarity rather than attractiveness. In fact, the increased SCR in response to attractiveness appears to occur only in subliminal conditions [START_REF] Mcdonald | Covert detection of attractiveness among the neurologically intact: evidence from skin-conductance responses[END_REF].

Furthermore, a trend toward significance was observed for the difference between the patient groups in the positive PANSS subscores. This result is not surprising because FD+ patients have a delusion of familiarity that is rated in the positive PANSS subscore in items dedicated to delusion assessment. Nevertheless, the absence of a correlation between the positive PANSS subscore and the SCR amplitude excludes a direct relationship between this positive symptom and the observed SCR difference between the patient groups.

Finally, an individual's mood has been shown to impact skin conductance [START_REF] De Vries | Enhanced method for robust mood extraction from skin conductance[END_REF]. Nevertheless, mood is a tonic process that varies during the day by the minute and is more linked to tonic than phasic skin conductance, such as the SCR [START_REF] De Vries | Enhanced method for robust mood extraction from skin conductance[END_REF]. Moreover, it has been shown that higher levels of both tonic and phasic SCRs are more linked to the negative symptoms [START_REF] Holt | Failure of neural responses to safety cues in schizophrenia[END_REF][START_REF] Williams | Fronto-limbic and autonomic disjunctions to negative emotion distinguish schizophrenia subtypes[END_REF] because the negative symptoms could lead to the implementation of coping strategies in states of over arousal due to schizophrenia [START_REF] Schell | Electrodermal predictors of functional outcome and negative symptoms in schizophrenia[END_REF]. In our study, the patients' moods were not directly assessed; nevertheless, some items on the PANSS (such as the negative and general subscores) allow such an assessment, and no difference was observed between the groups; in addition, there was no correlation between the negative symptoms and the SCR results. Moreover, the absence of a difference in the SCRs among the three groups in response to the unknown faces suggests that the SCR could be the same in the control subjects and patients.

conclusion

To the best of our knowledge, this study is the first to compare patients with and without familiarity disorders using material that is specific to each participant to evaluate familiarity in schizophrenia. In the control subjects, the more familiar the person, the stronger the emotional response linked to the feeling of familiarity. The same process occurs in the FD-patients, although these patients display a weaker emotional response across all conditions as indicated by the lower SCR amplitudes. However, the FD+ patients experienced an absence of emotional responses linked to the feeling of familiarity regardless of the familiarity of the faces that were presented (known or unknown). The feeling of familiarity elicited by emotional processes is not modulated by the degree of familiarity of the perceived faces.

eThics sTaTeMenT

The study was approved by the local ethics committee (CPP, Nord-Ouest IV, France), and written informed consent was obtained from each participant or guardian. aUThOr cOnTriBUTiOns AA, AP, FD, GV, PT, and DP contributed to the conception or design of the work; AA and AP have made the acquisition of the data; AA, FD, and DP have analyzed and interpreted the data; AA drafted the work; AP, FD, GV, PT, and DP revising it critically for important intellectual content; and all authors have given their final approval of the version to be published and their agreement to be accountable for all aspects of the work in ensuring that questions related to the accuracy or integrity of any part of the work are appropriately investigated and resolved.

acKnOWleDgMenTs

We would like to thank Laetitia Delbos and Anne-Laure Cote, who helped in recruiting the participants and conducting the study. We would also like to thank Renaud Jardri for reading a previous version of the manuscript.

Frontiers

  in Psychiatry | www.frontiersin.org September 2017 | Volume 8 | Article 181

FigUre 1 |

 1 FigUre1| Schematic representation of the task. Time is presented in decreasing order from right to left. After the presentation of a fixation cross for 2 s, a face (randomly unknown, famous, or familiar) was presented to the participant until he/she responded. Then, a blank screen appeared for 8 to 18 s to allow time for the skin conductance response (SCR) recording. The random duration of the blank screen was to avoid SCR habituation effects.

  [F(2,45) = 0.03; P = 0.96] or a familiarity condition effect [F(2,90) = 2.16; P = 0.12]. No group × familiarity condition interaction was observed [F(4,90) = 0.41; P = 0.80]. The response times were not significantly different between the groups [F(2,45) = 3.45; P = 0.53] or among the familiarity conditions [F(2,90) = 0.08; P = 0.91], and there was no group × familiarity condition interaction [F(4,90) = 0.73; P = 0.57]. During the second phase of the study, the recognition performance did not show a significant group effect on accuracy [F(2,45) = 2.90; P = 0.65] or a familiarity condition effect [F(2,90) = 0.95; P = 0.38]. There was no group × familiarity condition interaction [F(4,90) = 0.69; P = 0.59].

FigUre 2 |

 2 FigUre 2 | Amplitude of skin conductance response (SCR) in μS (microsiemens) in the three groups of control subjects (controls), schizophrenic patients without familiarity disorders (FD-), and schizophrenic patients with familiarity disorders (FD+) in the three conditions. Error bars represent the standard deviation.

Frontiers

  in Psychiatry | www.frontiersin.org September 2017 | Volume 8 | Article 181

FigUre 4 |

 4 FigUre 4 | Scatter Plot of the amplitude of skin conductance response (SCR) in μS (microsiemens) in the three groups of control subjects (controls), schizophrenic patients without familiarity disorders (FD-), and schizophrenic patients with familiarity disorders (FD+) in the famous conditions.

FigUre 5 |

 5 FigUre 5 | Scatter Plot of the amplitude of skin conductance response (SCR) in μS (microsiemens) in the three groups of control subjects (controls), schizophrenic patients without familiarity disorders (FD-), and schizophrenic patients with familiarity disorders (FD+) in the unknown conditions.

Frontiers

  in Psychiatry | www.frontiersin.org September 2017 | Volume 8 | Article 181

TaBle 1 |

 1 Demographic data of the three groups of control subjects (controls), schizophrenic patients without familiarity disorders (FD-) and schizophrenic patients with familiarity disorders (FD+).

		controls (N = 16)	FD-(N = 16)	FD+ (N = 16)	P
	Age (years)	37.2 ± 10.7	37.2 ± 10.7	33.3 ± 9.6	0.66
	Sex	9♂ 7♀	15♂ 1♀	12♂ 4♀	0.058
	PANSS+		18.3 ± 3.3	22.2 ± 3.9	0.059
	PANSS-		18.17 ± 2.9	21.18 ± 4.1	0.14
	Diazepam		4.5 ± 3.1	5.7 ± 6.2	1.0
	equivalent
	Chlorpromazine		1033.4 ± 1117.5 857.3 ± 526.5 0.69
	Equivalent (mg)
	The three groups described in the table are the control subjects (controls),
	schizophrenic patients without familiarity disorders (FD-), and schizophrenic patients
	with familiarity disorders (FD+).
	PANSS, Positive And Negative Symptoms Scale.

TaBle 2 |

 2 Categorization of percentage of correct responses and response time in ms during phase 1 and phase 2 in the 3 groups of control subjects (controls), schizophrenic patients without familiarity disorders (FD-) and schizophrenic patients with familiarity disorders (FD+).

		controls (N = 16) FD-(N = 16) FD+ (N = 16)
	Phase 1
	Familiar categorization	92 ± 8	92 ± 10	91 ± 7
	Familiar response time	1,051 ± 338	1,517 ± 536	1,423 ± 454
	Famous categorization	96 ± 7	95 ± 7	94 ± 9
	Famous response time	915 ± 327	1,517 ± 571	1,520 ± 703
	Unknown categorization	95 ± 5	94 ± 12	97 ± 6
	Unknown response time	1,004 ± 334	1,517 ± 833	1,496 ± 455
	Phase 2
	Familiar categorization	92 ± 8	92 ± 10	91 ± 7
	Famous categorization	96 ± 7	95 ± 7	94 ± 9
	Unknown categorization	95 ± 5	94 ± 12	97 ± 6
				5

Frontiers in Psychiatry | www.frontiersin.org September 2017 | Volume 8 | Article 181 resUlTs

Frontiers in Psychiatry | www.frontiersin.org September 2017 | Volume 8 | Article 181

Conflict of Interest Statement:

The authors declare that the research was conducted in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest.

The reviewer YC and handling editor declared their shared affiliation.

Copyright © 2017 Ameller, Picard, D'Hondt, Vaiva, Thomas and Pins. This is an open-access article distributed under the terms of the Creative Commons Attribution License (CC BY). The use, distribution or reproduction in other forums is permitted,

provided the original author(s) or licensor are credited and that the original publication in this journal is cited, in accordance with accepted academic practice. No use, distribution or reproduction is permitted which does not comply these terms.