Gaëlle Keromnes
email: g.keromnes@ch-guillaumeregnier.fr

Sylvie Chokron

Macarena-Paz Celume

Alain Berthoz

Michel Botbol

Roberto Canitano

Foucaud Du Boisgueheneuc

Nemat Jaafari

Nathalie Lavenne-Collot

Brice Martin

Tom Motillon

Bérangère Thirioux

Valeria Scandurra

Moritz Wehrmann

Ahmad Ghanizadeh

Sylvie Tordjman
email: s.tordjman@ch-guillaumeregnier.fr

Dr Gaelle Keromnes

Prof Sylvie Tordjman

Exploring self-consciousness from self-and other-image recognition in the mirror: concepts and evaluation

Keywords: Self, Self-consciousness, Self-awareness, Body, Body-self, Body image, Self-image recognition, Body perception, Intermodal sensory perception, Body action, Development

A review of the concepts of self-consciousness is presented, highlighting the important role of the body (particularly, body perception but also body action) and the social other in the construction of self-consciousness. More precisely, body perception, especially intermodal sensory perception including kinesthetic perception, is involved in the construction of a sense of self allowing self-nonself differentiation. Furthermore, the social other, through very early social and emotional interactions, provides meaning to the infant's perception and contributes to the development of his/her symbolization capacities. This is a necessary condition for body image representation and awareness of a permanent self in a time-space continuum (invariant over time and space). Self-image recognition impairments in the mirror are also discussed regarding a comprehensive developmental theory of self-consciousness. Then, a neuropsychological and neurophysiological approach to self-consciousness reviews the role of complex brain activation/integration pathways and the mirror neuron system in self-consciousness. Finally, this article offers new perspectives on self-consciousness evaluation using the mirror as an experimental paradigm to study self-and other-image and body recognition.

INTRODUCTION

Self-consciousness can be defined for an individual as the awareness of his/her own body in a time-space continuum and its interactions with the environment -including others. It also encompasses the awareness that the individual has of his/her own identity, built over time in interaction with others. It is at the root of higher level processes, such as the theory of mind or empathy, processes that allow us not only to be aware of others but also to differentiate ourselves from them, from their image and from their perceptive and emotional experiences [START_REF] Rochat | Five levels of self-awareness as they unfold early in life[END_REF][START_REF] Decety | Shared representations between self and other: a social cognitive neuroscience view[END_REF].

Self-consciousness is at the intersection of different disciplines, such as neurophysiology, psychiatry, psychology/neuropsychology, psychoanalysis and philosophy, which puts it at the center of many research topics. Many authors have highlighted the crucial role of the body in the development of self-consciousness, both as an interface with the environment and as an actual part of the self (body-self) [START_REF] Damasio | Subcortical and cortical brain activity during the feeling of self-generated emotions[END_REF][START_REF] Ionta | Multi-sensory and sensorimotor foundation of bodily selfconsciousness -an interdisciplinary approach[END_REF]. In addition, the importance of the mirror in psychoanalytic and psycho-developmental models of self-consciousness strengthens the place of body-self in the construction of self-image recognition that implies selfconsciousness [START_REF] Wallon | Les Origines du caractère chez l'enfant[END_REF].

We propose, in this article, first to review research on the concepts of self-consciousness, including the development of self-consciousness and the role of the body (in particular, body perception but also body action) and the social other in the construction of self-consciousness, and second to offer new perspectives on the evaluation of self-consciousness using the experimental paradigm of the mirror.

CONCEPTS OF SELF-CONSIOUSNESS AND SELF-IMAGE Theoretical bases: conceptualizing the self

For centuries, theorists have sought to understand and define self-consciousness. One of the theoretical models that lasted until the early twentieth century is that of an innate selfconsciousness, at least in its bodily dimension. In this model, the subject is born subject and knows himself as a subject. His/her subsequent psychic development concerns how he/she will build and shape the world around him/her. According to [START_REF] Piaget | La naissance de l'intelligence chez l'enfant[END_REF], the interactions between the child and the environment around him/her are governed by the rhythm at which the maturation of his/her central nervous system takes place. His fundamental work in developmental psychology has influenced many of his successors, including Merleau-Ponty (1964) whose philosophical work has partly focused on the phenomenology of perception. Some of the notions he developed joined Piaget's ideas. Notably, he insisted on the importance of the other for the individual, while involving a certain degree of innate self-consciousness, especially with a body schema already present in the child at a very young age and thanks to which he/she will be able to interact with others.

At the beginning of the twentieth century new currents of thought appeared, principally with the publication of Vygtosky's (1933). Vygotsky's ideas were far from Piagetian theories, by questioning the Piagetian egocentric stage that places the child at the center of the development of the self and the surrounding world representations. For Vygotsky, the child is not the main worker of this construction; he/she is a learner and it is the presence of the other and of the external environment which will allow him/her to be able to build him/herself as an individual [START_REF] Vygotsky | Mind in Society: The Development of Higher Psychological Processes[END_REF]. These ideas will be taken up by many contemporaries. In France, the influence of Wallon's work (1959a) was particularly important. Through his work, he questions a possible coconstruction of self-consciousness and consciousness of the other based on the individual's interactions with the external environment. Wallon focuses on the importance of the presence of the other to be with the child in his/her self-construction. The child learns attitudes from others, first by simple mimicry, then by a kind of reciprocal emotional contagion. According to Wallon, this emotional reciprocity comes to sign the initial impossibility for the child to dissociate him/herself from others during the first months of life. He/she would not be aware of being a separate individual from his/her parents. It is through a game of reciprocal stimulation and alternation that the child finally would become aware of the boundary that separates him/her from the other, from his/her own ego. For Wallon, this development of self-consciousness ends at the age of 3, age of crisis in which he/she can affirm him/herself and oppose to others his/her own desires and ideas. This approach dominated currents of thought during the following decades. [START_REF] Neisser | Two perceptually given aspects of the self and their development[END_REF] describes two distinct ways of building the self: a) Through body perceptions and interactions with the environment, and b) Through the relationship with others.

Furthermore, other authors such as [START_REF] Prinz | Self in the mirror[END_REF] discussed the notion of social mirroring and proposed that social mirroring is a prerequisite for the constitution of mental selves. Finally, [START_REF] Webb | The attention schema theory: a mechanistic account of subjective awareness[END_REF] highlighted the important role of attention processing in the development of self-consciousness, with regard to external and internal environmental stimuli.

A summary of the conceptualizations of the self is presented in Table 1.

+++ Insert Here Table 1 +++

More global approaches to the concept of self-consciousness have been proposed more recently, notably by [START_REF] Damasio | Le Sentiment même de soi : Corps, émotion, conscience[END_REF], whose work focuses on the study of the neural basis of cognition and behavior. He has been one of the most active researchers in the field of awareness/consciousness exploring the mechanisms that underlie it. In his work, he provides a summary of ideas developed over his various studies by offering three distinct levels of awareness/consciousness that ultimately lead to self-consciousness: a) Primary consciousness, b) Reflexive consciousness, and c) Self-consciousness. Primary consciousness is a kind of vigilant core consciousness which develops between the age of six months to one year old and allows the child to evolve in his/her environment even when he/she is not able to differentiate between him/herself and the rest of the world. Primary consciousness is shared by other animal species with sensory organs and a complex brain. Reflexive consciousness allows the individual to understand that he/she is the one who directs his/her own actions and thoughts, and that he/she controls his/her reasoning and behavior. It corresponds to the consciousness of not being the other and would be common to humans and big primates. Self-consciousness, the higher level of consciousness, refers to the ability to appropriate one's own history, to be aware of a unity of the self that persists despite the passage of time and the environmental changes. According to Damasio, this does not appear before the age of two in human beings. It is this selfconsciousness that will allow the individual to exist as such throughout his/her life.

The notion of primary consciousness developed by [START_REF] Damasio | Le Sentiment même de soi : Corps, émotion, conscience[END_REF] can be compared to the concept of "minimal self". The minimal self represents the most basic level of the self. It refers to self-consciousness as a subject of an immediate experience and pre-reflexive origin of action, experience and thought [START_REF] Gallagher | Philosophical conceptions of the self: implications for cognitive science[END_REF]. The pre-reflexive "it is mine" (or feeling of belonging; of "mineness") of a conscious experience, is a central characteristic of the minimal self. Therefore, the minimal self can be differentiated from more elaborate aspects of the self, such as the reflexive self (explicit consciousness of an "I") and the narrative self (experience of a self with specific characteristics and one's personal history).

More recently, [START_REF] Decety | Shared representations between self and other: a social cognitive neuroscience view[END_REF] presented their conceptualization of self in a literature review. This conceptualization reflects in some ways the stratification model described by Damasio. Accordingly, the construction of the self is a multidimensional and evolving process that takes place from infancy and develops throughout the first years of life. The different levels, types, contents and alterations of self-consciousness are summarized in Table 2.

+++ Insert Here Table 2 +++

In light of these different approaches, two primordial concepts can be highlighted. The first is that the acquisition of self-consciousness comes mainly by the differentiation between oneself and the other, with the recognition of each other's identities. The second concept is that the body, an interface between oneself and the other, is one of the essential keys in the course of this process. This concept is developed in the next section.

Concerning the first concept, self-consciousness would be built in relation to the other (relational dyad), through relational and emotional synchronization, and through the other's eyes.

The mother looks at the baby and the baby looks at the mother, but he/she sees also his/her reflection in the eyes of the mother. Self-consciousness, with the integration of body image, also passes by the imitation of the other, going for example from simple imitation in the new born of sticking out the tongue to more complex development including the child's verbal language.

Here we could hypothesize that self-consciousness is built up as an imitation of the other, with the representation of what is identical through synchronization, but also with the representation of what is different. Later on, the appearance of a gendered body refers to sexual differentiation and is probably in adolescence a new mobilizing lever of this process.

The role of the body in self-consciousness

Body perception and self-consciousness

Today, links between body and mind seem to be well established. Clinical practice recalls it every day, judging by the frequency of the psychosomatic manifestations observed in patients with psychiatric disorders [START_REF] Testa | Psychiatric emergencies (part I): psychiatric disorders causing organic symptoms[END_REF]. The body appears here as reflecting psychological problems and at the center of the psychological process of self-consciousness [START_REF] Gernet | Corps et subjectivité[END_REF].

For Wallon (1959b), when the child is born, he/she sees him/herself as dislocated, with distinct parts and members, and gradually, he/she sees them unified in a coherent body. The consciousness of a body self would therefore be an indispensable prerequisite for the construction of the child's personality. This concept was first introduced in 1794 under the name of cenesthesia; which Hübner defined as a general sensibility that represents to the soul the state of its body whereas the sensibility informs it on the external world and that the internal sense gives representations, judgments, ideas and concepts [START_REF] Starobinski | Le concept de cénesthésie et les idées neuropsychologiques de Moritz Schiff[END_REF]. Wallon will later describe it in a simpler way by designating under this term two types of sensibilities: an internal and visceral sensibility, and a proprioceptive and postural sensibility whose joint action will be responsible for kinesthetic sensations. This concept of cenesthesia evolved towards the concept of body schema at the end of the nineteenth century, following [START_REF] Bonnier | Le Sens des attitudes[END_REF] clinical observations on impairments in the perception of the own body resulting from certain neurological lesions or benign disorders such as vertigo. The existence of a normal perceptive system to which these anomalies would be related is then hypothesized. This perceptual system would correspond to what [START_REF] Head | Sensory disturbances from cerebral lesions[END_REF]Holmes (1911-1912) conceptualized shortly thereafter under the term of body schema. This corporeal pattern would gradually form in the first months of life, when the child seems to have a keen interest in exploring his/her own body through touch, but also to explore his/her immediate environment. Through this exploration, the child gradually learns the boundaries between his/her body and his/her surroundings. Although several studies have underlined the risk of body schema deficits in children with severe visual deficits (for a review, see [START_REF] Lueck | Vision and the Brain[END_REF], Head and Holmes rejected any participation of the optical pathways in the acquisition of this body schema which reflects an overall intuition concerning the present situation of the body in space.

This last remark emphasizes the fundamental difference between this body schema concept and the self-image concept introduced by Paul Schilder (1968). The first one is based on postural elements whereas the other refers to the symbolic and affective experience based above all on a visual perception of oneself. The two, however, are not dissociated given that they contribute together to the constitution of the body-self.

As body schema, self-image is not innate but is acquired gradually. The concept of selfimage is affectively and symbolically charged. Self-image is not just an observed image. It includes also how individuals represent their own body in their mind and the others' representations on their own body. This representation is initially performed as part of the interactions between the child and the other, as if the child could see him/herself first through the eyes of the other before being able to imagine his/her own body. Various authors have described the important role of the mirror in the construction of self-image and, more broadly, the self. This aspect will be detailed later. This overview of ideas which developed for over a hundred years shows the importance of the body in major theories of developmental psychology. Indeed, more recent authors, such as [START_REF] Damasio | Le Sentiment même de soi : Corps, émotion, conscience[END_REF], have highlighted the central place occupied by the body in the phenomenon of consciousness. They support the idea that conscious thinking is primarily based on our visceral perceptions. In their model, they developed different possible levels of selfconsciousness, placing bodily perception before any level of consciousness. The perception of the external world described in primary consciousness becomes possible only if this fundamental bodily perception is operational.

In recent years, many authors have also participated in improving our understanding of the pathways involved in self-consciousness, with a very specific focus on "body selfconsciousness" [START_REF] Pasqualini | Seeing" and "feeling" architecture: how bodily self-consciousness alters architectonic experience and affects the perception of interiors[END_REF][START_REF] Aspell | Keeping in touch with one's self: multisensory mechanisms of self-consciousness[END_REF]. This concept is divided into three dimensions: self-localization, first-person perspective and self-identification.

Different experimental studies have shown that bodily self-consciousness is malleable. Sforza et al. (2010), for example, studied facial recognition in healthy individuals, through a simple experimental paradigm. An examiner touched the subject's face while the subject observed the same action being applied simultaneously to another person's face. The results of this study showed frequent errors in identifying the image of the other as his own. Similarly, by manipulating visual-tactile inputs, an illusory feeling of ownership can be induced by an artificial hand (rubber hand illusion; [START_REF] Botvinick | Rubber hands "feel" touch that eyes see[END_REF]. As a matter of fact, viewing another person's hand or face being stroked in synchrony with strokes applied to our own corresponding non-visible hand or face can induce illusory self-attribution of the visible hand or face.

Moreover, participants perceive their hand to be at a position that is displaced toward the fake hand's position (proprioceptive drift) or judge another person's face as similar to their own face.

Many experimental paradigms have shown similar results, suggesting that bodily selfconsciousness may waiver with contradictory sensory stimulation. In addition, as discussed below, our motor actions may also contribute to self-consciousness.

Body action and self-consciousness

As recently underlined, the motor control system in the brain not only controls complex actions but is also concerned by body representation (Murata et al., 2016). More precisely, Murata et al. (2016) showed that the motor control system contributes to perception of the hands as part of one's own body. According to Gallagher (2005), the perception of one's own body is the fundamental process of self-recognition. In this way, the hands are not only effectors in movement, but could be considered as a link between the mind and motor control. Along those lines, what is called now the sense of agency can be viewed as a subjective awareness that one's generated action is attributed to one's self. The sense of agency occurs when an executed action is recognized as being generated by one's own body. The sense of agency is thus expected to occur exclusively during voluntary movement. According to Blakemore et al.' model (1999), a copy of the motor command, that is the efference copy, can pass into the forward model to predict feedback in response to a given motor command. In this way, the comparison between sensory feedback and the corollary discharge contributes both to the precision of the movement and to recognition of who generated the observed action. In turn, the sense of agency participates to the construction of self-consciousness through the production and the control of motor actions.

Several neuropsychological and neuroimaging experiments have revealed that the inferior parietal cortex is involved in the sense of agency (for a review, see Murata et al. 2016). Indeed, as demonstrated by Sirigu et al. (1999), patients with lesions of the inferior parietal cortex present deficits in agency recognition. Moreover, in the same way, a few human brain imaging studies have reported that the inferior parietal cortex is involved in the detection of agency of action in healthy participants [START_REF] Farrer | Modulating the experience of agency: a positron emission tomography study[END_REF](Farrer et al., , 2008;;Decety and Grezes, 2006;[START_REF] Chambon | An online neural substrate for sense of agency[END_REF]. Interestingly as we will discuss below, parietal lesions are also responsible for spatial neglect as well as somatoparaphrenia, two neuropsychological deficits that can also affect selfconsciousness.

Neuropsychological approach to self-consciousness

Disturbed sense of agency and disturbed body ownership

As discussed above, the sense of body ownership, as well as the awareness of being causally involved in an action, the sense of agency, have been mostly investigated in healthy participants by using experimental as well as functional neuroimaging methods [START_REF] Farrer | Modulating the experience of agency: a positron emission tomography study[END_REF]Tsakiris et al., 2007a). A complementary approach is the study of neurological patients showing specific neuropsychological disturbances of these senses after brain damage.

As discussed below, brain-damaged patients, especially after a stroke, may present anosognosia for hemiplegia (AHP) affecting the sense of ownership and therefore selfconsciousness. Brain-damaged patients with AHP deny typically the weakness of their paretic or plegic contralestional limb and are convinced that they move properly. These patients may also show a disturbed sense of ownership, with respect to paretic/plegic limb. They experience their contralesional limb as not belonging to them and may even attribute them to other people. This deficit is often called 'somatoparaphrenia'. Anosognosia for hemiplegia is thus characterized by their false belief that they are not paralyzed. Their feeling of being or not being causally involved in an actiontheir sense of agencyis thus dramatically disturbed. As incredible as it may appear, despite the obvious fact that the contralesional limb is severely paralyzed, these patients behave as if the disorder does not exist. When they are asked to move the paretic/plegic arm or leg, they may do nothing or may move the limb of the opposite side. However, in both situations, they are either convinced that they have successfully executed the task or may argue that they can move in a generic manner. Interestingly, although they are unable to move their contralesional limb when asked to do so, they may explain their impossibility either by confabulations (I could move it yesterday, but my arm is now tired) or by external causes (The ground is slippery, and I cannot walk on it), [START_REF] Nathanson | Denial of illness; its occurrence in one hundred consecutive cases of hemiplegia[END_REF]. Regarding the neuroanatomical correlates of the AHP, several studies have suggested that the right insular cortex might be a crucial anatomical region in integrating input signals related to self-awareness about the functioning of body parts (see Karnath and Baier for a review). In addition, confirming this hypothesis, converging evidence has been reported that the anterior insular cortex is also a central structure for pain mechanisms and temperature regulation [START_REF] Craig | Functional imaging of an illusion of pain[END_REF][START_REF] Kong | Using fMRI to dissociate sensory encoding from cognitive evaluation of heat pain intensity[END_REF]. In this way, the anterior insular cortex could well represent an important correlate of human "interoception" as well as a crucial cortical area for body ownership, for the sense of agency and more generally for self-consciousness [START_REF] Craig | How do you feel? Interoception: the sense of the physiological condition of the body[END_REF][START_REF] Craig | How do you feel--now? The anterior insula and human awareness[END_REF]. Moreover, the anterior insular cortex was suggested to be involved in other cognitive and emotional processes that could well contribute to self-consciousness such as the feelings of anger or anxiety (Phillips et al, 1997;[START_REF] Damasio | Subcortical and cortical brain activity during the feeling of self-generated emotions[END_REF], craving [START_REF] Contreras | Inactivation of the interoceptive insula disrupts drug craving and malaise induced by lithium[END_REF][START_REF] Naqvi | Damage to the insula disrupts addiction to cigarette smoking[END_REF], and visual selfrecognition [START_REF] Devue | Here I am: the cortical correlates of visual self-recognition[END_REF].

Finally, anosognosia and disturbed sense of body ownership are often associated with another neuropsychological deficit consecutive to a right parietal lesion and affecting spatial representation: unilateral spatial neglect.

Personal neglect

Unilateral spatial neglect (USN) is a fascinating disorder in which patients are unaware of the hemispace contralateral to the lesion. Usually a left USN is observed after a right parietal lesion.

As [START_REF] Schilder | L'image du corps. Paris : Gallimard. self-generated movement following left parietal lesion[END_REF] has proposed, space can be divided in extrapersonal space, peripersonal space and personal space. Along those lines, patients suffering from USN may ignore either the extrapersonal space (either near or far) or the personal space contralateral to the lesion. In this latter case, when suffering from personal neglect, patients ignore their own contralesional body parts. Indeed, patients may not use their contralesional hemibody although not being paralyzed.

In some cases, patients may exhibit somatophrenia and can explain that their contralesional arm or leg is behind the closet, or that their husband or wife took it with them. Importantly, many patients are unaware they have these problems (anosognosia).

A neuropsychological approach can indeed be of interest to assess the role of the different cortical and subcortical structures involved in self-consciousness to decipher the neurophysiological basis of self-consciousness as presented below.

Neurophysiological approach to self-consciousness

Evolutionary psychology postulates that self-consciousness, as well as other higher cognitive faculties, would be unique to the human being and thus, would distinguish us from animal species, even from the most evolved ones. This self-consciousness would have appeared gradually during evolution, in parallel with societal changes. These theories are now challenged by neurobiological advances, highlighting the involvement of certain brain structures in the process of self-consciousness reported in some primates. This observation requires a better understanding of the neurophysiological mechanisms involved.

Complex activation and integration pathways

Schilder, psychiatrist and psychoanalyst, departed from psycho-developmental theories of selfconsciousness in 1935 to question the neurophysiological mechanisms allowing an individual to be situated in a given space-time [START_REF] Schilder | L'image du corps. Paris : Gallimard. self-generated movement following left parietal lesion[END_REF]. His ideas opened new perspectives on various research projects. Since that time and still today, many experimental paradigms have been designed and developed to understand better the neurological pathways of self-consciousness. [START_REF] Lhermitte | L'image de notre corps[END_REF] was one of the first to publish his research on the neurophysiological mechanisms of self-consciousness. He described a probable activation of right parietal cerebral structures related to the process of acquisition of the self-image. Numerous studies supported later this hypothesis and it appears nowadays well established that right brain structure, particularly parietal ones, are involved in global self-consciousness (Taylor, 2000).

More specifically, besides the involvement of the inferior parietal cortex in the sense of agency described above in the "Body action and self-consciousness" section, the primordial role of the temporoparietal junction has been also reported [START_REF] Graziano | The temporoparietal junction and awareness[END_REF][START_REF] Ionta | Multi-sensory and sensorimotor foundation of bodily selfconsciousness -an interdisciplinary approach[END_REF]. It corresponds to a zone of integration of multimodal sensory information that may play a key role in the first-person perspective, and the distinction between oneself and the other, as well as in some more complex mechanisms of the theory of mind, which includes the ability to understand the intentions, desires and beliefs of the other. Aspell, Leggenhagger and Blanke (2012) studied more particularly its activation during the phenomenon of out-of-body experiences both by continuous electroencephalographic monitoring during such phenomena, but also by observing that such experiments could be triggered in healthy individuals by transcranial magnetic stimulation (TMS) of the temporoparietal junction (Blanke et al.,2005).

The role of frontal cortical structures was also discussed concerning more specifically an activation of the pre-frontal cortex which would intervene in the process of differentiation between self and others (Van Veluw and Chance, 2014). It is noteworthy that several fRMI studies on the theory of mind have highlighted the key role of the median prefrontal cortex (Van Veluw and Chance, 2014).

Finally, the role of the vestibular system was also described in the development of spatial bodily self-consciousness [START_REF] Pfeiffer | The vestibular system: a spatial reference for bodily self-consciousness[END_REF]). One of its functions is to provide information on the position of the body taking into account the variations of the Earth's gravitational system, essential for the brain's encoding of the body's spatial orientation in the environment. Some studies have hypothesized that the vestibular system could be part of a larger network involved in spatial exploration including the parietal lobes and the anterior insular cortex already mentioned in the section on "Disturbed sense of agency and disturbed body ownership" [START_REF] Brandt | Vestibular cortex lesions affect the perception of verticality[END_REF][START_REF] Karnath | The anatomy of spatial neglect based on voxelwise statistical analysis: a study of 140 patients[END_REF]. This could well explain how caloric vestibular stimulation may reduce somatophrenia. Indeed, it was demonstrated that such stimulation applied in right braindamaged patients can induce transitory remission of anosognosia for hemiparesis as well as permanent disparition of somatophrenia [START_REF] Cappa | Remission of hemineglect and anosognosia during vestibular stimulation[END_REF][START_REF] Bisiach | Remission of somatoparaphrenic delusion through vestibular stimulation[END_REF][START_REF] Rode | Partial remission of hemiplegia and somatoparaphrenia through vestibular stimulation in a case of unilateral neglect[END_REF][START_REF] Vallar | Anosognosia for left-sided motor and sensory deficits, motor neglect, and sensory hemiinattention: is there a relationship?[END_REF]. Also, caloric vestibular stimulation can reduce anosognosia for hemiplegia (AHP) and unilateral spatial neglect (USN) [START_REF] Cappa | Remission of hemineglect and anosognosia during vestibular stimulation[END_REF][START_REF] Bisiach | Remission of somatoparaphrenic delusion through vestibular stimulation[END_REF][START_REF] Rode | Partial remission of hemiplegia and somatoparaphrenia through vestibular stimulation in a case of unilateral neglect[END_REF][START_REF] Vallar | Anosognosia for left-sided motor and sensory deficits, motor neglect, and sensory hemiinattention: is there a relationship?[END_REF], confirming the role of the vestibular-parietal network in body awareness and self-consciousness.

It is noteworthy that integrated models of self-consciousness, involving sensory and motor multimodal integration, are related to ideas already developed by Sherrington almost one century ago. Sir C.S. Sherrington (1857Sherrington ( -1952) ) was an English neurologist who received the Nobel prize in medicine with E.D. Adrian in 1932 for their work on the neural system.

According to their work, the self-consciousness in the here and now is based on visuo-musculolabyrinthic or tactile-muscular-labyrinthic perceptions (Wallon, 1959). This model echoes also some of Piaget's ideas, as he described within his developmental stages a first sensorimotor stage during which the child exists only through movement and sensation [START_REF] Piaget | Les stades du développement intellectuel de l'enfant et de l'adolescent. Le problème des stades en psychologie de l'enfant[END_REF]. This description shows even today the importance of sensory stimulation and how it can be integrated in the brain towards the construction of self-consciousness, especially in very young children.

Within this process of integration and complex activation, the role of a particular neuron systemthe mirror neurons -is subject of much debate.

The mirror neuron system

Mirror neurons were first described by [START_REF] Rizzolatti | Neurones miroirs (Les)[END_REF]. They are a system of motor neurons whose particularity is to activate themselves both when we perform a given action but also when we see someone else performing the same action, or even when we think of or speak about its realization without however initiating it. They were first detected in monkeys after it was observed that they could frequently perform an action immediately after seeing it in one of their congeners, as if mirroring the other.

These descriptions might suggest that the neurons involved in such reactions are at the level of the optical pathways and are activated by visual stimulation. However, Rizzolatti's studies in functional brain imaging suggest that this "mirrored" reaction would correspond to a brain activation at the level of the premotor frontal cortex, the superior temporal sulcus and certain parietal areas (Rizzolati and Sinigaglia, 2008). Other recent functional MRI studies confirm these data, without showing any activation in the occipital visual areas [START_REF] Calvo-Merino | Action observation and acquired motor skills: an FMRI study with expert dancers[END_REF]. Studies of mirror neurons system in primates showed an activation of the F5 brain area that corresponds in humans to the Broca area (i.e. the inferior part of F3 corresponding to Brodmann's areas 44 and 45). It could be hypothesized that these mirror neurons also have a role in the production of verbal language and in the ability to communicate with others.

It is recognized that these neurons underlie partly our ability to connect with each other. This finding placed them at the center of social cognition. Their role was particularly discussed in the ability to differentiate oneself from the other, but also in the interactions with others, at bodily, affective and cognitive levels (as in the phenomenon of empathy, for example).

A parallel can be made here between the mirror neurons functioning and the gestual and emotional reciprocity described by Wallon. In Wallon's theory (1959b), the infant reproduces many actions that he/she sees in adults (a smile, for example) as if he/she was facing a mirror.

And it is through these experiences, more precisely through identification and differentiation processes, that self-consciousness can develop.

At present, the mirror neuron system suffers from some criticism. The mirror neurons are criticized for their lack of specificity, and more recent research suggests that they have been granted quickly with too much credit [START_REF] Hickok | The myth of mirror neurons: the real neuroscience of communication and cognition[END_REF]. Their discovery nevertheless created an emulation that has brought a lot to scientific research.

Despite constant efforts to understand better the specific paths involved in selfconsciousness, these are not yet well established. Limits appear given the complexity of the information to be processed. For some authors such as Seth et al. (2006), [START_REF] Tononi | Schizophrenia and the mechanisms of conscious integration[END_REF] or [START_REF] Damasio | Le Sentiment même de soi : Corps, émotion, conscience[END_REF], there is no fixed structure responsible for the existence of selfconsciousness at its different levels. For these authors, self-consciousness responds in fact to a much more comprehensive brain activation that allows an individual to locate him/herself in the here and now, and to take into consideration his/her personal history with associated affects.

SELF-IMAGE AND THE MIRROR A brief history of the mirror

Today, omnipresent in our homes, the mirror is an ancient object whose form or use has changed over the centuries. The appearance of first mirrors is difficult to date. Descriptions can be found in ancient times when they were already known for their reflective capacity. The first mirrors were made of glass and lead. Their preparation from these materials involve some work and so made the object scarce and expensive. It remained the richest privilege for centuries. In the manufacture mirrors (Melchior-Bonnet, 2011).

It was not until the end of the seventeenth century that mirrors were more affordable, spread in homes, and became a need for everyone. The introduction of mirrors in our lives has probably much changed the way people perceive their own image [START_REF] Melchior-Bonnet | L'invention du reflet[END_REF].

Alongside these historical and societal considerations, it is interesting to note that the mirror has long been seen as a fascinating object. In the study of the Inca civilization, we find mirror descriptions used as "fire lighter" [START_REF] Nordenskiôld | Miroirs convexes et concaves en Amérique[END_REF]. This very special ability, yet based on simple optical properties, was then an almost magical object and, in fact, a luxury item.

In the Middle Ages, the most beautiful and expensive mirrors were installed in castles of noble or royal people, and poets or storytellers of the time were celebrating their magical power of reflection. It is precisely this power of fascinating reflection that is found in many ancient myths.

Since ancient times, self-reflection is the subject of many productions. The most common is the myth of Narcissus or Perseus. In both cases, the mirror or the reflect finishes in a tragic death.

Narcissus pays the price for his vanity and love for his reflection he sees in the water. Perseus is using the reflectivity of a mirror to defeat and kill his enemy Medusa. It might be seen here as the beginning of a reflection on self-consciousness.

The importance of the other in the construction of self-consciousness: the theories of the mirror

In his work on building self-consciousness, [START_REF] Wallon | Les Origines du caractère chez l'enfant[END_REF] explains how young children, interacting with their environment, gradually become aware of their own body. One of the major parts of his work is the description of the reaction of the child in the mirror. Wallon observed that between six months and two years old, the child develops a fascination with his/her reflection in the mirror, even after having understood that is fictional. The child can contemplate this reflection a long time, enjoying looking at this "other" who is not "a real self". Starting with the first reflections, looking at the mirror with his/her parents, he/she turns to them in search of reassurance, as a validation that the image he/she is seeing is actually him/herself.

As we mentioned earlier, it is through this game of alternation and sharing between him/herself and the other that the child becomes aware of his/her individuality. The mirror is, for Wallon, one of the major mediators in this process, because it is through it that the child can interact with others. [START_REF] Zazzo | Images du corps et conscience de soi[END_REF] followed some of Wallon's ideas. He published his observations from the reactions of an infant confronted with his/her images via his/her reflection in a mirror, but also photographs and films. He states that when the child is facing the mirror as well as other visual aids, the recognition of the other is far above self-recognition. He establishes also that for the three types of images (mirror, photo, film) there is a first period during which we observe that the subject appears not to recognize or even watch his/her own image. Besides, he explains that the recognition of the other through the mirror begins well before in an image or movie.

However, if the self-image in the mirror is recognized much earlier, it remains a long time affected by uncertainty and anxiety unlike still images such as photographs.

The finding showed that between two and three years old, the child become increasingly aware of his/her body image and would be able to understand that he/she is alone facing his/her own image and that his/her reflection is not somebody else or a double. According to Zazzo, this development occurs in parallel with the explosion of language, an additional tool that helps the child to understand the distinction between him/herself and the other and between him/her and his/her reflection.

Yet the essential work of Wallon and Zazzo appear neglected when, some years later, Lacan grabbed the topic and brought it to psychoanalysis by publishing "The mirror stage as formative of the function of the I as it is revealed in psychoanalytic experience". In a replay of the theories developed by Wallon, Lacan describes how the mirror stage helps the child to give up his/her fragmented body to become aware of its identity through the mirror image [START_REF] Lacan | Le stade du miroir[END_REF].

The description of the "Stage of the mirror" by Lacan is now a cornerstone of the psychoanalytic approach to the construction of the self. Lacan himself referred the origin of his theory to the work of the American psychologist James Mark Baldwin who also influenced Piaget and Vygtosky. Baldwin's theories focused on the progressive distinction between self and other through social interactions. It was one of the first to see the way the child behaves in front his/her reflection as an indicator of the construction of the self (Müller and Runions, 2003).

Many other authors were concerned about this topic in the aftermath of Lacan, notably Françoise Dolto, who published in 1987 with Nasio "The child of the mirror". If she adhered partially to Lacan's theories, her approach differs on an essential point. Unlike Lacan (and Wallon before him) who described the infant as a fragmented being, with no containment in the months preceding the identification with reflection, Dolto highlights a primary narcissism that makes the child a cohesive whole, maintained through basic external and visceral sensations.

Therefore, the infant cannot be fully satisfied with this image as it is incomplete, reflecting only one side of his/her body, whereas he/she even "feels as a whole in his/her being " [START_REF] Dolto | L'enfant du miroir[END_REF].

The weight given to the mirror in psychoanalytic and psycho-developmental theories stresses the importance of body-self and self-image, but also the importance of the other in the construction of self-consciousness.

Impairments in self-image recognition in the mirror

Disorders of self-consciousness are related to various disturbances of the pathways involved in self-consciousness. Different components of self-consciousness can be impaired and produce various clinical syndromes. Impairments in bodily self-consciousness lead to somatognosic disorders among which are found the out-of-body experiences, the heautoscopy and the autoscopic hallucinations. These phenomena have been widely studied in the case of disorders of neurological origin, particularly in certain dementia syndromes [START_REF] Blanke | I and me: self-portraiture in brain damage[END_REF]. Their mechanisms are still poorly understood, although Blanke has been able to demonstrate a dysfunction of the temporoparietal areas previously described, with the additional involvement of certain occipital areas in the case of autoscopic hallucinations (Blanke and Mohr, 2005).

Heautoscopy was described by [START_REF] Lhermitte | L'image de notre corps[END_REF] in his work «The image of our body» like an almost hallucinatory experience during which the patient suddenly sees his image appearing in front of him. He explains it schematically by two essential components: a visual hallucination and a disturbance of bodily self-consciousness. The latter causes the individual a feeling of partial depersonalization that makes it difficult for him/her to locate him/herselfeither in his/her own body or projected in the autoscopic image. One of the variations of this heautoscopy (or illusion of the double) is the phenomenon of negative heautoscopy that Maupassant has described so well, when sinking into madness: Indeed, he described this phenomenon in which the individual no longer sees his/her image in a reflective surface. This illustration highlights an example of a situation in which the relationship to the mirror is disturbed. It shows also that such disruptions in the recognition of self-image are not confined to neurological disorders. They are also common in psychiatric disorders and especially psychotic disorders.

It is currently accepted that early disturbances of the child's psychological development can be associated with various psychiatric disorders which may eventually become fixed in adulthood (Jones, 1997;[START_REF] Tackett | A unifying perspective on personality pathology across the lifespan: Developmental considerations for the fifth edition of the Diagnostic and Statistical Manual of Mental Disorders[END_REF]. Given the important role of the mirror during psychological development, we can suppose that the relation to the mirror, and therefore to the reflection, is disturbed in children with atypical psychological development. Salem Shentoub was one of the first to study self-recognition in children with developmental disabilities, including intellectual disability. He described the reaction of "mentally retarded » children in front of the mirror and observed differences in their behaviors compared to typically developing children [START_REF] Rustin | Comportement de l'enfant arriéré devant le miroir[END_REF]. The reported reactions are varied, ranging from an apparent absence of self-image recognition to complex affective manifestations, including preliminary interactions with the reflection or various stereotyped behaviors. However, the children's reactions in front of the mirror appear to be an extension of their usual behavior and the confrontation with their image does not trigger in these children more specific reactions, even in the most severe cases. The most alarming observation was the apparent absence of selfrecognition, which questions a possible absence of recognition of the other as well as selfconsciousness impairments. Nevertheless, Shentoub observed that the repetition of mirror experiences in the same child allowed him/her to become acquainted with the other and with his/her image, and this was associated with an overall positive behavioral evolution. He was already raising here a possible remediation that could be accomplished through the mirror image. These intellectually disabled children observed by Shentoub did not show a psychotic disorder marked by an internal disorganization or a rupture with reality. However, it cannot be ruled out that young patients with schizophrenia might also exhibit some atypical behaviors when facing mirrors due to their own perceptual and/or cognitive developmental disturbances.

The psychoanalytic theories presented briefly in this article allow us to consider these disturbances of self-image recognition as an indicator or even a possible marker of a disturbance of psychological development occurring upstream of the mirror stage. Lacan, himself, mentions in his work the absence of reaching the mirror stage in psychotic patients, thus preventing their symbolic identification with their own image.

On this topic, Paul Abely described in the early 1930s "a need for certain individuals to examine themselves at length and frequently in front of a reflective surface" (quoted in [START_REF] Meaulle | Le signe du miroir : reflets cliniques et théoriques[END_REF]. He reported here a phenomenon he observed at the dawn of the appearance of early dementia in some of his patients. In his descriptions, this fixation on the mirror can be accompanied by a search for dialogue with the reflection which is considered as a distinct other.

Shortly after him, François Achille-Delmas published similar observations. We note today with regret that their respective work remains little recognized [START_REF] Meaulle | Le signe du miroir : reflets cliniques et théoriques[END_REF].

The observations they developed, almost simultaneously but separately, now refer to the same concept, the "mirror sign". This sign would be for them a simple clinical marker of psychotic disorganization. Indeed, they observed in patients with neurotic disorders very different reactions from those described above. The mirror sign, for these authors, more than a fascination for the patient's reflection, corresponds in fact to a search for the patient's own image in the mirror -an image that disintegrates more and more permanently with the onset of psychotic disorders. It is noteworthy that in the interpretation they make of this mirror sign, this sign would be part of the prodromal phase and would disappear once the disorder developed.

It is noteworthy that the mirror can be used to study impairments in self-image recognition. A new paradigm for the study of self-other differentiation, self-identity and selfimage recognition, and manipulation of spatial reference frames in social interactions, was proposed by Alain Berthoz (Collège de France, Paris), using the "Double Mirror" designed by Moritz Werhmann (Alter Ego System©), and studied by Berengère Thirioux and collaborators (2016). This paradigm of the double mirror was used recently to study self-other differentiation in individuals with schizophrenia compared to typically developing controls (TDC) [START_REF] Keromnes | Self-other rcognition impairments in individuals with schizophrenia: a new experimental paradigm using a double mirror[END_REF]. The results showed that individuals with schizophrenia, independently of age and schizophrenia severity, were centered on their own image compared to TDC, with both significant earlier self-recognition and delayed other-recognition during the visual recognition task. In addition, there was no significant effect of intermodal sensory stimulation on self-other recognition in individuals with schizophrenia, whereas self-centered functioning was significantly increased by visual-tactile stimulation and decreased by visual-kinesthetic stimulation in TDC. The findings suggest that self-other recognition impairments might be a possible endophenotypic trait of schizophrenia..

CONCLUSIONS

The literature review presented in this article emphasizes the role of body perception, body actions and of the self-image in the construction of self-consciousness. Of importance, we demonstrated here that a multidisciplinary approach is mandatory to address such a complex concept. We aimed also to highlight the interest of self-image recognition in the mirror to assess The subject is a learner from the others and external environment allowing him/her to build For each experience there is a neural representational system constituting the minimal supervenience basis for specific experiences

  This process involves physical, psychological and social factors and allows the development of different types of consciousness with different levels. Decety and Sommerville highlighted the cognitive dimension of self-development involving shared self-other representations, ultimately leading to self-other differentiation.

  of building the self: (a) through body perceptions and interactions with environmental objects, and (b) through relationships with others Kiverstein (2007)

TABLE 1 . Conceptualizing the Self.

 1 The subject is born subject and knows himself as a subject. Psychological development concerns how children build and shape the world around, governed by the maturation of the The subject learns behaviors through imitation and emotional contagion and cannot be therefore dissociated from others during the first months of life. Through reciprocal stimulation and alternation, the child becomes aware of limits between him/herself and the other, and develops his/her own ego

	Authors	Conceptualization
	Piaget
	(1936)
		Central Nervous System
	Wallon
	(1959)
	Merleau-	Importance of the other. A certain degree of innate self-consciousness exists (body schema)
	Ponty	allowing social interactions
	(1964)
	Vygostki
	(1978)

self-consciousness but also the role of the other in self-image recognition. Self-image development might be a good indicator of the evolution of the self-consciousness process, especially through self-and other-image recognition in the mirror (Tordjman and Mailhes, 2009).

Self-consciousness can be impaired in one or several of its components (identity, body, etc.).

Self-recognition, and notably self-image recognition, can be disturbed in various disorders, especially neurodevelopmental disorders (dementia, psychiatric disorders, etc.) [START_REF] Blanke | I and me: self-portraiture in brain damage[END_REF].

Considering impairments in self-consciousness and self-image recognition may open important perspectives, especially for early diagnosis and therapeutic strategies in neurodevelopmental disorders. However, a limit of such phenomenological inquiry remains the detection of these disturbances that relies on patients' verbal reports [START_REF] Martin | Temporal structure of consciousness and minimal self in schizophrenia[END_REF]. These patients' reports should indeed be interpreted with caution, especially because body-self is related to non-verbal aspects of consciousness. Thus, a challenge consists in finding a way to objectify such selfdisturbances in individuals with a non-verbal approach [START_REF] Mishara | Self-disturbances in schizophrenia: history, phenomenology, and relevant findings from research on metacognition[END_REF]. The double mirror, mentioned previously in this article might be a useful instrument to investigate further self-other recognition impairments in self-consciousness disorders in general and neurodevelopmental disorders such as schizophrenia or Autism Spectrum Disorder. Self-other face identification in the mirror may improve bodily self-consciousness and sustain self-other differentiation in these disorders. Future studies are required to explore this perspective. In particular, the double mirror system could be useful for early diagnosis, follow-up, and therapeutic perspectives based on cognitive remediation helping individuals with self-consciousness disorders to improve selfother differentiation.

AUTHORS CONTRIBUTIONS

GK and ST wrote the first draft of the article. SC contributed in a significant way to this article by adding notably the part on the neuropsychological approach to self-consciousness. MPC revised the first draft of the article. AB, MB, RC, FDB, NJ, NLC, BM, TM, BT, VS, MW and AG reviewed and approved the final version of the article.

CONFLICT OF INTEREST STATEMENT:

The authors declare that this article is not relevant of any commercial or financial relationships that could be construed as a potential conflict of interest. =

Solipsism and existential reorientation

The sense of personal experience becomes affected

Striking tendency to experience one' s body predominantly as an object: an increasing experiential distance between subjectivity and corporeality ("disembodiment").

Mental contents become quasi-autonomous ("automatic" thoughts), without ipseity and with a rupture of the stream of thoughts (thoughts may appear as if from nowhere)

Inferential reflection arises as a consequence of a deficient sense of myness

To be excessively preoccupied with philosophical, supernatural, or metaphysical themes *Five levels [START_REF] Rochat | Five levels of self-awareness as they unfold early in life[END_REF] in contrast to a level zero corresponding to a level of confusion with absence of self-consciousness


Izadora Mayumi

Fujinami Tanimoto

Benjamin Cressiot

Jean Roman

Nathalie Jarroux

Gilles Patriarche

Bruno Le Pioufle

Juan Pelta

Laurent Bacri

NANOPARTICLE DETECTION BY SOLID-STATE NANOPORE INTEGRATED INTO A REUSABLE MICROFLUIDIC DEVICE

Keywords: Solid-state nanopore, microfluidics, protein detection, polymer functionalization

Solid-state nanopores can be used as electrical biosensors at the single molecule resolution. Such high resolution sensors provide a promising approach to address societal challenges in health and biotechnology. Nevertheless, the analytes detection is still limited by non-specific interactions between these molecules and the membrane supporting the nanopore. Therefore, we performed a polymer functionalization of the nanopore surface that allows to passivate the membrane and to control the pore size. Moreover, we integrated the solid-state nanopore in a reusable microfluidic device, thereby reducing the sample volume needed to perform the detection. The combination of these two approaches is applied to the sensing of single thyroglobulin protein.

INTRODUCTION

Solid-state nanopores have been used to characterize the biomolecular interactions in a controlled environment. [START_REF] Malekian | Detecting Selective Protein Binding Inside Plasmonic Nanopores: Toward a Mimic of the Nuclear Pore Complex[END_REF] One can tune their diameter to better fit the analyte size and they present better stability than the biological ones. [START_REF] Niedzwiecki | Single-Molecule Observation of Protein Adsorption onto an Inorganic Surface[END_REF][START_REF] Roman | Solid-State Nanopore Easy Chip Integration in a Cheap and Reusable Microfluidic Device for Ion Transport and Polymer Conformation Sensing[END_REF] Nanopore sensing is performed from an electric detection. Whenever the analyte transiently resides inside the nanopore there is an ionic current drop. However, the interactions between nanoparticles and the nanopore are not well established. A high surface energy of the membrane, 2 missing events due to high translocation speed and the pore-to-pore variability limit the experiments reproducibility. Another challenge is that in classical microfluidic devices the nanopore chip needs to be irreversibly sealed into it, whereas the analytes chamber are not hermetically sealed leading to potential cross contamination during the solution exchange process. Hence, this work will focus on improving the membrane chemical and physical surface properties, by functionalizing its surface to avoid nonspecific interactions and to control the nanopore size, and on the integration of solid-state nanopores into a microfluidic device (Fig. 1a-b). The efficiency of such set-up was confirmed by the detection of single thyroglobulin transport.

EXPERIMENTAL

Si3N4 membranes are pierced with a TEM. Polyethylene glycol (PEG) 7 kDa chains are grafted over the nanopore surface. [START_REF] Roman | Solid-State Nanopore Easy Chip Integration in a Cheap and Reusable Microfluidic Device for Ion Transport and Polymer Conformation Sensing[END_REF] This nanopore is inserted in between two identical subunits that formed the microfluidic device. [START_REF] Roman | Solid-State Nanopore Easy Chip Integration in a Cheap and Reusable Microfluidic Device for Ion Transport and Polymer Conformation Sensing[END_REF] Part of the surfaces of those subunits are not covalently bonded, in order to achieve the reversible packaging (Fig. 1a). [START_REF] Roman | Solid-State Nanopore Easy Chip Integration in a Cheap and Reusable Microfluidic Device for Ion Transport and Polymer Conformation Sensing[END_REF] The polydimethylsiloxane (PDMS) microfluidic circuit device is casted on a 3D-printed polyethylene terephthalate (PET) mold on a silicon wafer. The ionic current is measured using Ag/AgCl electrodes.

RESULTS AND DISCUSSION

The fabrication of PDMS based devices needs a master mold, usually obtained by photolithography techniques, which are time consuming and require a clean room. Here, we show that a 3D-printer can make molds in laboratory and usable for fast conception of microfluidic devices (Fig. 1a). This approach allows us to work with a hermetic system, avoiding possible contamination and fluid evaporation (Fig. 1b) and to reduce the analyte volume to 100 µL, which is important for biologic fluids. Besides, this device facilitates the changes in fluids. The final set-up confirms the capacity to detect protein at single molecule level, from variation of ionic current trace after addition of thyroglobulin (Ø = 18 nm) (Fig. 1c). The current blockades show the presence of thyroglobulin. The high signal to noise ratio -98% -shows a high confinement controlled by the PEG chain grafting .

CONCLUSION

Here, we stated the feasibility of the nanopore integration in reusable microfluidic device without permanent sealing between the nanopore and the device, which makes possible changes of small amount of electrolyte solutions and on nanopore manipulation. We demonstrate the control on PEG chain conformation along the nanopore surface. The system allows the detection of thyroglobulin transport through the nanopores with a high signal-to-noise ratio.

Figure 1 :

 1 Figure 1: a) Microfluidic device protocol. b) 3D sketch of microfluidic device with the nanopore inserted on it (left) and a picture of the device with the nanopore chip (right). c) Current trace measured after the addition of thyroglobulin by one nanopore (Ø = 28 nm, length 20 nm) grafted by PEG 7 kDa chain. ΔV = 1 V, 50 mM LiCl, 0.1 M Tris, pH 7.4.

ACKNOWLEDGEMENTS

This work is supported by DIM Respore, DEFI Instrumentation aux limites 2016/2017, ANR Epsilomics.