Stanislas Dehaene

Jean-Pierre Changeux

Experimental and theoretical approaches to conscious processing

Recent experimental studies and theoretical models have begun to address the challenge of establishing a causal link between subjective conscious experience and measurable neuronal activity.

The present review focuses on the well-delimited issue of how an external or internal piece of information goes beyond non-conscious processing and gains access to conscious processing, a transition characterized by the existence of a reportable subjective experience. Converging neuroimaging and neurophysiological data, acquired during minimal experimental contrasts between conscious and non-conscious processing point to objective neural measures of conscious access: late amplification of relevant sensory activity, long-distance cortico-cortical synchronisation at beta and gamma frequencies, and "ignition" of a large-scale prefronto-parietal network. We confront these findings to current theoretical models of conscious processing, including the Global Neuronal Workspace (GNW) model according to which conscious access occurs when incoming information is made globally available to multiple brain systems through a network of neurons with long-range axons densely distributed in prefrontal, parieto-temporal and cingulate cortices. The clinical implications of these results for general anesthesia, coma, vegetative state and schizophrenia are discussed.

Introduction

Understanding the neuronal architectures that give rise to conscious experience is one of the central unsolved problems of today's neuroscience, despite its major clinical implications for general anesthesia, coma, vegetative-state or minimally conscious patients. The difficulties are numerous.

Notably, the term "consciousness" has multiple meanings, most of which are difficult to precisely define in a manner amenable to experimentation. In this review, we outline recent advances made in understanding the delimited issue of conscious access: how does an external or internal piece of information gain access to conscious processing, defined as a reportable subjective experience?

We start by a brief overview of the relevant vocabulary and theoretical concepts. We then examine the experimental studies that have attempted to delineate the objective physiological mechanisms of conscious sensory perception by contrasting it with minimally different, yet nonconscious processing conditions, using a variety of methods: behavior, neuroimaging, time-resolved electro-and magneto-encephalography, and finally single-cell electrophysiology and pharmacology.

We critically examine how the present evidence fits or argues against existing models of conscious processing, including the Global Neuronal Workspace (GNW) model. We end by examining possible consequences of these advances for pathological brain states, including general anaesthesia, coma and vegetative states.

I. Vocabulary and major experimental paradigms

Conscious state versus conscious contents "Conscious" is an ambiguous word. In its intransitive use (e.g. "the patient was still conscious"), it refers to the state of consciousness, also called wakefulness or vigilance, which is thought to vary almost continuously from coma and slow-wave sleep to full vigilance. In its transitive use (e.g. "I was not conscious of the red light"), it refers to conscious access and/or conscious processing of a specific piece of information. The latter meaning is the primary focus of this review. At any given moment, only a limited amount of information is consciously accessed and defines the current conscious content, which is reportable verbally or by an intended gesture. At the same time, many other processing streams co-occur but remain non-conscious.

Major experimental paradigms

A broad variety of paradigms (reviewed in [START_REF] Kim | Psychophysical magic: rendering the visible 'invisible[END_REF] are now available to create a minimal contrast between conscious and non-conscious stimuli [START_REF] Baars | A cognitive theory of consciousness[END_REF], and thus isolate the moment and the physiological properties of conscious access. A basic distinction is whether the nonconscious stimulus is subliminal or preconscious [START_REF] Dehaene | Conscious, preconscious, and subliminal processing: a testable taxonomy[END_REF][START_REF] Kanai | Subjective discriminability of invisibility: A framework for distinguishing perceptual and attentional failures of awareness[END_REF]. A subliminal stimulus is one in which the bottom-up, stimulus-driven information is so reduced as to make it undetectable, even with focussed attention. A preconscious stimulus, by contrast, is one which is potentially visible (its energy and duration is such that it could be seen), but which, on a given trial, is not consciously perceived due to temporary distraction or inattention.

Subliminal presentation is often achieved by masking, a method whereby the subjective visibility of a stimulus is reduced or eliminated by the presentation, in close spatial and temporal contiguity, of other stimuli acting as "masks" [START_REF] Breitmeyer | Visual Masking: Time Slices through Conscious and Unconscious Vision[END_REF]. For instance, a word flashed for 33 ms is visible when presented in isolation, but becomes fully invisible when preceded and followed by geometrical shapes. Masked stimuli are frequently used to induce subliminal priming, the facilitation of the processing of a visible target by the prior presentation of an identical or related subliminal prime (for review, see Kouider and Dehaene, 2007). Subliminal presentation can also be achieved with threshold stimuli, where the contrast or energy of a stimulus is progressively reduced until its presence is unnoticeable. Binocular rivalry is another common paradigm whereby the image in one eye becomes subliminal by competition with a rivaling image presented in the other eye. Participants typically report temporal alternations in the image which is consciously perceived. However, a variant of binocular rivalry, the continuous flash suppression paradigm allows an image to be made permanently invisible by presenting continuously flashing shapes in the other eye [START_REF] Tsuchiya | Continuous flash suppression reduces negative afterimages[END_REF].

An equally large range of techniques allows for preconscious presentation. In inattentional blindness, a potentially visible but unexpected stimulus remains unreported when the participants' attention is focused on another task [START_REF] Mack | Inattentional blindness[END_REF][START_REF] Simons | Change blindness: theory and consequences[END_REF]. The attentional blink (AB) is a short-term variant of this effect where a brief distraction by a first stimulus T1 prevents the conscious perception of a second stimulus T2 briefly presented within a few hundreds of milliseconds of T1 [START_REF] Raymond | Temporary suppression of visual processing in an RSVP task: an attentional blink?[END_REF]. In the related psychological refractory period (PRP) effect [START_REF] Pashler | Dual-task interference in simple tasks: data and theory[END_REF][START_REF] Welford | The "psychological refractory period" and the timing of high speed performance --A review and a theory[END_REF], T2 is unmasked and is therefore eventually perceived and processed, but only after a delay during which it remains non-conscious [START_REF] Corallo | Limits on introspection: distorted subjective time during the dual-task bottleneck[END_REF][START_REF] Marti | Mapping introspection's blind spot: Reconstruction of dual-task phenomenology using quantified introspection[END_REF]. The "distracting" event T1 can be a surprise event that merely captures attention [START_REF] Asplund | A central role for the lateral prefrontal cortex in goal-directed and stimulus-driven attention[END_REF]. The minimum requirement, in order to induce AB, appears to be that T1 is consciously perceived [START_REF] Nieuwenstein | Temporal constraints on conscious vision: on the ubiquitous nature of the attentional blink[END_REF]. Thus, PRP and AB are closely related phenomena that point to a serial limit or "bottleneck" in conscous access [START_REF] Jolicoeur | Concurrent response-selection demands modulate the attentional blink[END_REF][START_REF] Marti | Mapping introspection's blind spot: Reconstruction of dual-task phenomenology using quantified introspection[END_REF][START_REF] Wong | The Relationship Between Attentional Blink and Psychological Refractory Period[END_REF] and can be used to contrast the neural fate of two identical stimuli, only one of which is consciously perceived [START_REF] Sergent | Timing of the brain events underlying access to consciousness during the attentional blink[END_REF].

Objective versus subjective criteria for conscious access

How can an experimenter decide whether his experimental subject was or was not conscious of a stimulus? According to a long psychophysical tradition, grounded in signal-detection theory, a stimulus should be accepted as non-conscious only if subjects are unable to perform above chance on some direct task of stimulus detection or classification. This strict objective criterion raises problems, however [START_REF] Persaud | Post-decision wagering objectively measures awareness[END_REF][START_REF] Schurger | Awareness, loss aversion, and post-decision wagering[END_REF]. First, it tends to overestimate conscious perception: there are many conditions in which subjects perform better than chance, yet still deny perceiving the stimulus. Second, performance can be at chance level for some tasks, but not others, raising the issue of which tasks count as evidence of conscious perception or merely of subliminal processing. Third, the approach requires accepting the null hypothesis of chance-level performance, yet performance never really falls down to zero, and whether it is significant or not often depends on arbitrary choices such as the number of trials dedicated to its measurement.

For these reasons, recent alternative approaches emphasize either pure subjective reports, such as ratings of stimulus visibility [START_REF] Sergent | Is consciousness a gradual phenomenon? Evidence for an all-ornone bifurcation during the attentional blink[END_REF] or second-order commentaries such as post-decision wagering (would you bet that your response was correct? [START_REF] Persaud | Post-decision wagering objectively measures awareness[END_REF]. The wagering method and related confidence judgements provide a high motivation to respond truthfully and in an unbiased manner [START_REF] Schurger | Awareness, loss aversion, and post-decision wagering[END_REF]. Furthemore, they can be adapted to nonhuman subjects [START_REF] Kiani | Representation of confidence associated with a decision by neurons in the parietal cortex[END_REF][START_REF] Terrace | Comparative metacognition[END_REF]. However, they can sometimes exceed chance level even when subjects deny seeing the stimulus [START_REF] Kanai | Subjective discriminability of invisibility: A framework for distinguishing perceptual and attentional failures of awareness[END_REF]. Conversely, subjective report is arguably the primary data of interest in consciousness research. Furthermore, reports of stimulus visibility can be finely quantified, leading to the discovery that conscious perception can be "all-or-none" in some paradigms [START_REF] Del Cul | Brain dynamics underlying the nonlinear threshold for access to consciousness[END_REF][START_REF] Del Cul | Preserved subliminal processing and impaired conscious access in schizophrenia[END_REF][START_REF] Sergent | Is consciousness a gradual phenomenon? Evidence for an all-ornone bifurcation during the attentional blink[END_REF]. Subjective reports also present the advantage of assessing conscious access immediately and on every trial, thus permitting post-experiment sorting of conscious versus nonconscious trials with identical stimuli (e.g. Del Cul et al., 2007;[START_REF] Lamy | Neural Correlates of Subjective Awareness and Unconscious Processing: An ERP Study[END_REF][START_REF] Pins | The neural correlates of conscious vision[END_REF][START_REF] Sergent | Timing of the brain events underlying access to consciousness during the attentional blink[END_REF][START_REF] Wyart | Neural dissociation between visual awareness and spatial attention[END_REF].

Although the debate about optimal measures of conscious perception continues, it is important to acknowledge that objective assessments, wagering indices and subjective reports are generally in excellent agreement [START_REF] Del Cul | Preserved subliminal processing and impaired conscious access in schizophrenia[END_REF][START_REF] Del Cul | Causal role of prefrontal cortex in the threshold for access to consciousness[END_REF][START_REF] Persaud | Post-decision wagering objectively measures awareness[END_REF]. For instance, in visual masking, the conscious perception thresholds derived from objective and subjective data are essentially identical across subjects (r²=0.96, slope≈1) [START_REF] Del Cul | Preserved subliminal processing and impaired conscious access in schizophrenia[END_REF]. Those data suggest that conscious access causes a major change in the global availability of information, whether queried by objective or by subjective means, whose mechanism is the focus of the present review.

Selective attention versus conscious access

Conscious access must be distinguished from the related concept of attention. William James (1890) provided a well-known definition of attention as "the taking possession by the mind, in clear and vivid form, of one out of what seem several simultaneously possible objects or trains of thought". The problem with this definition is that it conflates two processes that are now clearly separated in cognitive psychology and cognitive neuroscience (e.g. [START_REF] Huang | What is the unit of visual attention? Object for selection, but Boolean map for access[END_REF][START_REF] Posner | Attentional networks[END_REF]: selection and access. Selection, also called selective attention, refers to the separation of relevant versus irrelevant information, isolation of an object or spatial location, based on its saliency or relevance to current goals, and amplification of its sensory attributes. Access refers to its conscious "taking possession of the mind" -the subject of the present review.

Empirical evidence indicates that selection can occur without conscious processing [START_REF] Koch | Attention and consciousness: two distinct brain processes[END_REF]. For instance, selective spatial attention can be attracted to the location of a target stimulus that remains invisible [START_REF] Bressan | The attentional cost of inattentional blindness[END_REF][START_REF] Mccormick | Orienting attention without awareness[END_REF][START_REF] Robitaille | Fundamental properties of the N2pc as an index of spatial attention: effects of masking[END_REF][START_REF] Woodman | Dissociations among attention, perception, and awareness during object-substitution masking[END_REF]. Selective attention can also amplify the processing of stimuli that remain non-conscious [START_REF] Kentridge | Attended but unseen: visual attention is not sufficient for visual awareness[END_REF][START_REF] Kiefer | Attentional modulation of unconscious "automatic" processes: evidence from event-related potentials in a masked priming paradigm[END_REF][START_REF] Naccache | Unconscious masked priming depends on temporal attention[END_REF]. Finally, in simple displays with a single target, conscious access can occur independently of selection [START_REF] Wyart | Neural dissociation between visual awareness and spatial attention[END_REF]. In cluttered displays, however, selection appears to be a prerequisite of conscious access: when faced with several competing stimuli, we need attentional selection in order to gain conscious access to just one of them (Dehaene and Naccache, 2001;[START_REF] Mack | Inattentional blindness[END_REF]. These findings indicate that selective attention and conscious access are related but dissociable concepts that should be carefully separated, attention frequently serving as a "gateway" that regulates which information reaches conscious processing

II. Experimental studies of the brain mechanisms of conscious access

With this vocabulary at hand, we turn to empirical studies of conscious access. The simplest experiments consist in presenting a brief sensory stimulus which is sometimes consciously accessible, sometimes not, and using behavior, neuroimaging and neurophysiological recording to monitor the depth of its processing and how it differs as a function of conscious reportability.

Experiments contrasting visible and invisible stimuli

Behavioral evidence. A visual stimulus which is masked and remains invisible can nevertheless affect behaviour and brain activity at multiple levels (for review, see Kouider and Dehaene, 2007;Van den Bussche et al., 2009b). Subliminal priming has now been convincingly demonstrated at visual, semantic and even motor levels. For instance, when a visible target image is preceded by a subliminal presentation of the same image, simple decisions, such as judging if it refers to an object or animal, are accelerated compared to when the image is not repeated. Crucially, this repetition effect resists major changes in the physical stimulus, such as presenting the same word in upper case versus lower case (Dehaene et al., 2001) or presenting the same face in two different orientations [START_REF] Kouider | Activity in Face-Responsive Brain Regions is Modulated by Invisible, Attended Faces: Evidence from Masked Priming[END_REF], suggesting that invariant visual recognition can be achieved without awareness. At the semantic level, subliminal extraction of the meaning of words has now been demonstrated for a variety of word categories (e.g. [START_REF] Gaillard | Nonconscious semantic processing of emotional words modulates conscious access[END_REF][START_REF] Naccache | Unconscious semantic priming extends to novel unseen stimuli[END_REF]Van den Bussche et al., 2009a). At even more advanced levels, a subliminal stimulus can bias motor responses [START_REF] Dehaene | Imaging unconscious semantic priming[END_REF][START_REF] Leuthold | Mechanisms of priming by masked stimuli: inferences from eventrelated potentials[END_REF]. Subliminal monetary incentives enhance subjects' motivation in a demanding force task, indicating that motivation is modulated by non-conscious signals [START_REF] Pessiglione | How the brain translates money into force: a neuroimaging study of subliminal motivation[END_REF]. So is task setting: masked shapes can act as cues for task switching and lead to detectable changes in task set [START_REF] Lau | Unconscious activation of the cognitive control system in the human prefrontal cortex[END_REF]. Even inhibitory control can be partially launched non-consciously, as when a non-conscious "stop" signal slows down or interrupts motor responses [START_REF] Van Gaal | Frontal cortex mediates unconsciously triggered inhibitory control[END_REF] (see figure 1).

The above list suggests that entire chains of specialized processors can be subject to nonconscious influences. Nevertheless, three potential limits to subliminal processing have been identified (Dehaene and Naccache, 2001). First, subliminal priming quickly decreases with processing depth, such that only small influences are detectable at higher cognitive and decision levels [START_REF] Dehaene | Conscious and nonconscious processes: distinct forms of evidence accumulation? In Better Than Conscious? Decision Making, the Human Mind, and Implications For Institutions[END_REF][START_REF] Van Gaal | Frontal cortex mediates unconsciously triggered inhibitory control[END_REF]. For instance, a subliminal number can enter into a single numerical operation, but not a series of two arbitrary operations [START_REF] Sackur | The cognitive architecture for chaining of two mental operations[END_REF].

Second, subliminal priming decreases with elapsed time, and therefore typically ceases to be detectable after 500 ms [START_REF] Dupoux | Subliminal speech perception and auditory streaming[END_REF][START_REF] Greenwald | Three cognitive markers of unconscious semantic activation[END_REF][START_REF] Mattler | Inhibition and decay of motor and nonmotor priming[END_REF]. For instance, classical conditioning across a temporal gap only obtains when participants report being aware of the relations among the stimuli [START_REF] Clark | Classical conditioning, awareness, and brain systems[END_REF] (although see [START_REF] Bekinschtein | Classical conditioning in the vegetative and minimally conscious state[END_REF]. Third, subliminal stimuli typically fail to yield lasting and flexible modifications in executive control. Human subjects generally excel in identifying strategies that exploit virtually any statistical relation amongst stimuli, but such strategic control appears to require consciousness (Posner et al., 1975[START_REF] Posner | Attention and Cognitive Control[END_REF]) and is not deployed when the stimuli are masked or unattended and therefore are not consciously detected [START_REF] Heinemann | Context-specific prime-congruency effects: On the role of conscious stimulus representations for cognitive control[END_REF][START_REF] Kinoshita | Unconscious cognition isn't that smart: Modulation of masked repetition priming effect in the word naming task[END_REF][START_REF] Merikle | Parallels between perception without attention and perception without awareness[END_REF][START_REF] Van Den Bussche | Conscious and unconscious proportion effects in masked priming[END_REF]. For instance, under conscious conditions, subjects typically slow down after a conflict or error trial, but may not do so when the error or conflict is non-conscious [START_REF] Kunde | Sequential modulations of stimulus-response correspondence effects depend on awareness of response conflict[END_REF][START_REF] Nieuwenhuis | Error-related brain potentials are differentially related to awareness of response errors: evidence from an antisaccade task[END_REF] (for two interesting exceptions, see [START_REF] Logan | Cognitive illusions of authorship reveal hierarchical error detection in skilled typists[END_REF][START_REF] Van Gaal | Unconsciously triggered conflict adaptation[END_REF].

Brain-scale neuroimaging. Functional magnetic resonance imaging (fMRI) can provide a global image of the brain activity evoked by a visible or invisible stimulus, integrated over a few seconds. [START_REF] Grill-Spector | The dynamics of object-selective activation correlate with recognition performance in humans[END_REF] first used fMRI to measured visual activity evoked by masked pictures presented below or above the visibility threshold. Activation of the primary visual area V1 was largely unaffected by masking, but the amount of activation in more anterior regions of lateral occipital and fusiform cortex strong correlated with perceptual reports. A year later (Dehaene et al., 2001), a similar contrast between masked and unmasked words, now at the whole-brain level, again revealed a strong correlation of conscious perception with fusiform activity, but also demonstrated extended areas of activation uniquely evoked by conscious words, including inferior prefrontal, mesial frontal and parietal sites (figure 1). In more recent fMRI work, using a masking paradigm where conscious reports followed a characteristic U-shaped curve as a function of the target-mask delay, fusiform and midline prefrontal and inferior parietal regions again closely tracked conscious perception [START_REF] Haynes | Visibility reflects dynamic changes of effective connectivity between V1 and fusiform cortex[END_REF]). An important control was recently added: participants' objective performance could be equated while subjective visibility was manipulated [START_REF] Lau | Relative blindsight in normal observers and the neural correlate of visual consciousness[END_REF]. In this case, a correlate of visibility could only be detected in left dorsolateral prefrontal cortex. Some authors have found correlations of fMRI activation with visibility of masked versus unmasked stimuli exclusively in posterior visual areas (e.g. [START_REF] Tse | Visibility, visual awareness, and visual masking of simple unattended targets are confined to areas in the occipital cortex beyond human V1/V2[END_REF]. However, in their paradigm, even the unmasked stimuli were probably not seen because they were unattended and irrelevant, which can prevent conscious access [START_REF] Dehaene | Conscious, preconscious, and subliminal processing: a testable taxonomy[END_REF]Kouider et al., 2007;[START_REF] Mack | Inattentional blindness[END_REF]. Overall, fMRI evidence suggests two convergent correlates of conscious access: [START_REF]of Learning and Memory: A Comprehensive Reference[END_REF] amplification of activity in visual cortex, clearest in higher-visual areas such as the fusiform gyrus, but possibly including earlier visual areas (e.g. Haynes et al., 2005a;[START_REF] Polonsky | Neuronal activity in human primary visual cortex correlates with perception during binocular rivalry[END_REF][START_REF] Williams | Attenuation of neural responses in primary visual cortex during the attentional blink[END_REF]; (2) emergence of a correlated distributed set of areas, virtually always including bilateral parietal and prefrontal cortices (see figure 1). Time-resolved imaging methods. Event-related potentials (ERPs) and magneto-encephalography (MEG) are non-invasive methods for monitoring at a millisecond scale, respectively, the electrical and magnetic fields evoked by cortical and subcortical sources in the human brain. Both techniques have been used to track the processing of a masked stimulus in time as it crosses or does not cross the threshold for subjective report. In the 1960s already, ERP studies showed that early visual activation can be fully preserved during masking [START_REF] Schiller | Metacontrast: its relation to evoked potentials[END_REF]. This early finding has been supported by animal electrophysiology [START_REF] Bridgeman | Correlates of metacontrast in single cells of the cat visual system[END_REF][START_REF] Bridgeman | Visual evoked potentials: concomitants of metacontrast in late components[END_REF][START_REF] Kovacs | Cortical correlate of pattern backward masking[END_REF][START_REF] Lamme | Masking interrupts figure-ground signals in V1[END_REF][START_REF] Rolls | The neurophysiology of backward visual masking: information analysis[END_REF] and by essentially all recent ERP and MEG studies (Dehaene et al., 2001;[START_REF] Del Cul | Brain dynamics underlying the nonlinear threshold for access to consciousness[END_REF][START_REF] Fahrenfort | Masking disrupts reentrant processing in human visual cortex[END_REF][START_REF] Koivisto | The relationship between awareness and attention: Evidence from ERP responses[END_REF][START_REF] Koivisto | Independence of visual awareness from the scope of attention: an electrophysiological study[END_REF][START_REF] Lamy | Neural Correlates of Subjective Awareness and Unconscious Processing: An ERP Study[END_REF][START_REF] Melloni | Synchronization of neural activity across cortical areas correlates with conscious perception[END_REF][START_REF] Railo | The electrophysiological correlates of stimulus visibility and metacontrast masking[END_REF][START_REF] Van Aalderen-Smeets | Investigating neurophysiological correlates of metacontrast masking with magnetoencephalography[END_REF]. Evidence from the attentional blink also confirms that the first 200 ms of initial visual processing can be fully preserved on trials in which subjects deny seeing a stimulus [START_REF] Sergent | Timing of the brain events underlying access to consciousness during the attentional blink[END_REF][START_REF] Vogel | Electrophysiological evidence for a postperceptual locus of suppression during the attentional blink[END_REF] (see figure 2).

In ERPs, the most consistent correlate of visibility appears to be a late (~300-500 ms) and broadly distributed positive component called P3 or sometimes P3b (to distinguish it from the focal anterior P3a which is thought to reflect automatic attention attraction and can occur non-consciously (e.g. [START_REF] Muller-Gass | Evidence for the auditory P3a reflecting an automatic process: elicitation during highly-focused continuous visual attention[END_REF][START_REF] Salisbury | Auditory event-related potentials during stage 2 NREM sleep in humans[END_REF]). A similarly slow and late waveform is seen in MEG (van [START_REF] Van Aalderen-Smeets | Investigating neurophysiological correlates of metacontrast masking with magnetoencephalography[END_REF]. The generators of the P3b ERP have been shown by intracranial recordings and ERP-fMRI correlation to involve a highly distributed set of nearly-simultaneous active areas including hippocampus and temporal, parietal and frontal association cortices [START_REF] Halgren | Generators of the late cognitive potentials in auditory and visual oddball tasks[END_REF][START_REF] Mantini | Large-scale brain networks account for sustained and transient activity during target detection[END_REF]. The P3b has been reproducibly observed as strongly correlated with subjective reports, both when varying stimulus parameters (e.g. Del Cul et al., 2007) and when comparing identical trials with or without conscious perception (e.g. [START_REF] Babiloni | Visuo-spatial consciousness and parieto-occipital areas: a high-resolution EEG study[END_REF]Del Cul et al., 2007;[START_REF] Fernandez-Duque | Representation of change: separate electrophysiological markers of attention, awareness, and implicit processing[END_REF][START_REF] Koivisto | The earliest electrophysiological correlate of visual awareness?[END_REF][START_REF] Lamy | Neural Correlates of Subjective Awareness and Unconscious Processing: An ERP Study[END_REF][START_REF] Niedeggen | Change blindness and time to consciousness[END_REF][START_REF] Pins | The neural correlates of conscious vision[END_REF][START_REF] Sergent | Timing of the brain events underlying access to consciousness during the attentional blink[END_REF] (however, this effect may disappear when the subject already has a conscious working memory representation of the target: [START_REF] Melloni | Expectations change the signatures and timing of electrophysiological correlates of perceptual awareness[END_REF].

The effect is not easily imputable to increased post-perceptual processing or other task confounds, as many studies equated attention and response requirements on conscious and non-conscious trials (e.g. Del Cul et al., 2007;[START_REF] Gaillard | Converging intracranial markers of conscious access[END_REF][START_REF] Lamy | Neural Correlates of Subjective Awareness and Unconscious Processing: An ERP Study[END_REF][START_REF] Sergent | Timing of the brain events underlying access to consciousness during the attentional blink[END_REF]. For instance, [START_REF] Lamy | Neural Correlates of Subjective Awareness and Unconscious Processing: An ERP Study[END_REF] compared correct aware versus correct unaware trials in a forced-choice localization task on a masked stimulus, thus equating for stimuli and responses, and again observed a tight correlation with the P3b component.

Human ERP and MEG recordings also revealed that conscious perception is also accompanied, during a similar time window, by increases in the power of high-frequency fluctuations, primarily in the gamma band (>30 Hz), as well as their phase synchronization across distant cortical sites [START_REF] Doesburg | Rhythms of consciousness: binocular rivalry reveals large-scale oscillatory network dynamics mediating visual perception[END_REF][START_REF] Melloni | Synchronization of neural activity across cortical areas correlates with conscious perception[END_REF][START_REF] Rodriguez | Perception's shadow: long-distance synchronization of human brain activity[END_REF][START_REF] Schurger | Induced gamma-band oscillations correlate with awareness in hemianopic patient GY[END_REF][START_REF] Wyart | How ongoing fluctuations in human visual cortex predict perceptual awareness: baseline shift versus decision bias[END_REF]. In lower frequencies belonging to the alpha and low beta bands (10-20 Hz), the data is more ambiguous, as both power increases [START_REF] Gross | Modulation of long-range neural synchrony reflects temporal limitations of visual attention in humans[END_REF] and decreases [START_REF] Gaillard | Converging intracranial markers of conscious access[END_REF][START_REF] Wyart | How ongoing fluctuations in human visual cortex predict perceptual awareness: baseline shift versus decision bias[END_REF] have been reported, perhaps due to paradigm-dependent variability in the deployment of dorsal parietal attention networks associated with decreases in alpha-band power [START_REF] Sadaghiani | Intrinsic connectivity networks, alpha oscillations, and tonic alertness: a simultaneous electroencephalography/functional magnetic resonance imaging study[END_REF]. Even when power decreases in these low frequencies, however, their long-distance phase synchrony is consistently increased during conscious perception [START_REF] Gaillard | Converging intracranial markers of conscious access[END_REF][START_REF] Gross | Modulation of long-range neural synchrony reflects temporal limitations of visual attention in humans[END_REF]. The globally distributed character of these power and synchrony increases seems essential, because recent results indicate that localized increases in these parameters can be evoked by non-conscious stimuli, particularly during the first 200 ms of stimulus processing [START_REF] Fisch | Neural ''Ignition'': Enhanced Activation Linked to Perceptual Awareness in Human Ventral Stream Visual Cortex[END_REF][START_REF] Gaillard | Converging intracranial markers of conscious access[END_REF][START_REF] Melloni | Synchronization of neural activity across cortical areas correlates with conscious perception[END_REF]. Thus, short-lived focal increases in gamma-band power are not unique to conscious states,but track activation of both conscious and non-conscious local cortical circuits [START_REF] Ray | Differences in gamma frequencies across visual cortex restrict their possible use in computation[END_REF]. However, their significant enhancement on consciously perceived trials, turning into an all-or-none pattern after 200 ms, appears as a potentially more specific marker of conscious access [START_REF] Fisch | Neural ''Ignition'': Enhanced Activation Linked to Perceptual Awareness in Human Ventral Stream Visual Cortex[END_REF][START_REF] Gaillard | Converging intracranial markers of conscious access[END_REF].

The high spatial precision and signal-to-noise ratio afforded by intracranial recording in epileptic patients provides essential data on this point. [START_REF] Gaillard | Converging intracranial markers of conscious access[END_REF] contrasted the fate of masked (subliminal) versus unmasked (conscious) words while recording from a total of 176 local sites using intracortical depth electrodes in 10 epileptic patients. Four objective signatures of conscious perception were identified (figure 3): ( 1) late (>300 ms) and distributed event-related potentials contacting sites in prefrontal cortex; (2) large and late (>300 ms) increases in induced power (indexing local synchrony) in high-gamma frequencies (50-100 Hz), accompanied by a decrease in lower-frequency power (centered around 10 Hz); (3) increases in long-distance cortico-cortical synchrony in the beta frequency band 13-30 Hz; (4) increases in causal relations amongst distant cortical areas, bidirectionally but more strongly in the bottom-up direction (as assessed by Granger causality, a statistical technique that measures whether the time course of signals at one site can forecast the future evolution of signals at another distant site). [START_REF] Gaillard | Converging intracranial markers of conscious access[END_REF] noted that all four signatures coincided in the same time window (300-500 ms) and suggested that they might constitute different measures of the same state of distributed "ignition" of a large cortical network including prefrontal cortex. Indeed, seen stimuli had a global impact on late evoked activity virtually anywhere in the cortex: 68.8% of electrode sites, although selected for clinical purposes, were modulated by the presence of conscious words (as opposed to 24.4% of sites for non-conscious words).

Neuronal recordings. A pioneering research program was conducted by Logothetis and collaborators using monkeys trained to report their perception during binocular rivalry [START_REF] Leopold | Activity changes in early visual cortex reflect monkeys' percepts during binocular rivalry[END_REF][START_REF] Sheinberg | The role of temporal cortical areas in perceptual organization[END_REF][START_REF] Wilke | Local field potential reflects perceptual suppression in monkey visual cortex[END_REF]. By recording from V1, V2, V4, MT, MST, IT and STS neurons, and presenting two rivalling images, only one of which led to high neural firing, they identified a fraction of cells whose firing rate increased when their preferred stimuli was perceived, thus participating in a conscious neuronal assembly. The proportion of such cells increased from about 20% in V1/V2 to 40% in V4, MT or MST, to as high as 90% in IT and STS. This finding supports the hypothesis that subjective perception is associated with distributed cell assemblies whose neurons are denser in higher associative cortices than in primary and secondary visual cortices. Surprisingly, fMRI signals correlate quite strongly with conscious perception during rivalry in area V1 (Haynes and Rees, 2005;[START_REF] Polonsky | Neuronal activity in human primary visual cortex correlates with perception during binocular rivalry[END_REF] and even in the lateral geniculate nucleus of the thalamus (Haynes et al., 2005a;[START_REF] Wunderlich | Neural correlates of binocular rivalry in the human lateral geniculate nucleus[END_REF]. The discrepancy between fMRI and single-cell recordings was addressed in a recent electrophysiological study [START_REF] Maier | Divergence of fMRI and neural signals in V1 during perceptual suppression in the awake monkey[END_REF]; see also [START_REF] Wilke | Local field potential reflects perceptual suppression in monkey visual cortex[END_REF]: within area V1 of the same monkeys, fMRI signals and lowfrequency (5-30 Hz) local field potentials (LFPs) correlated with subjective visibility while highfrequency (30-90 Hz) LFPs and single-cell firing rate did not. One interpretation of this finding is that V1 neurons receive additional top-down synaptic signals during conscious perception compared to non-conscious perception, although these signals need not be translated into changes in average firing rate [START_REF] Maier | Divergence of fMRI and neural signals in V1 during perceptual suppression in the awake monkey[END_REF].

The masking paradigm afforded a more precise measurement of the timing of conscious information progression in the visual system. In area V1, multi-unit recordings during both threshold judgments [START_REF] Super | Two distinct modes of sensory processing observed in monkey primary visual cortex (V1)[END_REF] and masking paradigms [START_REF] Lamme | Masking interrupts figure-ground signals in V1[END_REF] identified two successive response periods. The first period was phasic, time-locked to stimulus onset, and reflected objective properties such as stimulus orientation, whether or not they were detectable by the animal. The second period was associated with a late, slow and long-lasting amplification of firing rate, called figure-ground modulation because it was specific to neurons whose receptive field fell on the foreground "figure" part of the stimulus. Crucially, only this second phase of late amplification correlated tightly with stimulus detectability in awake animals [START_REF] Lamme | Masking interrupts figure-ground signals in V1[END_REF][START_REF] Super | Two distinct modes of sensory processing observed in monkey primary visual cortex (V1)[END_REF] and vanished under anesthesia [START_REF] Lamme | Figure-ground activity in primary visual cortex is suppressed by anesthesia[END_REF]. Thus, although different forms of masking can affect both initial and late neural responses [START_REF] Macknik | Optical images of visible and invisible percepts in the primary visual cortex of primates[END_REF][START_REF] Macknik | Neuronal correlates of visibility and invisibility in the primate visual system[END_REF], the work of Lamme and colleagues suggests that it is the late sustained phase which is most systematically correlated with conscious visibility. A similar conclusion was reached from earlier recordings in infero-temporal cortex [START_REF] Kovacs | Cortical correlate of pattern backward masking[END_REF][START_REF] Rolls | The neurophysiology of backward visual masking: information analysis[END_REF] and frontal eye fields [START_REF] Thompson | The detection of visual signals by macaque frontal eye field during masking[END_REF][START_REF] Thompson | Antecedents and correlates of visual detection and awareness in macaque prefrontal cortex[END_REF].

Only a single study to date has explored single-neuron responses to seen or unseen stimuli in human cortex [START_REF] Quiroga | Human single-neuron responses at the threshold of conscious recognition[END_REF]. Pictures followed at a variable delay by a mask were presented while recording from the antero-medial temporal lobe in five patients with epilepsy. A very late response was seen, peaking around 300 ms and extending further in time. This late firing reflected tightly the person's subjective report, to such an extent that individual trials reported as seen or unseen could be categorically distinguished by the neuron's firing train (see figure 4). Such a late categorical response is consistent with the hypothesis that conscious access is "all-or-none", leading either to a high degree of reverberation in higher association cortex (conscious trial) or to a vanishing response (Dehaene et al., 2003b;[START_REF] Sergent | Timing of the brain events underlying access to consciousness during the attentional blink[END_REF][START_REF] Sergent | Is consciousness a gradual phenomenon? Evidence for an all-ornone bifurcation during the attentional blink[END_REF].

Single-cell electrophysiology has also contributed to a better description of the postulated role of synchrony in conscious perception [START_REF] Rodriguez | Perception's shadow: long-distance synchronization of human brain activity[END_REF][START_REF] Varela | The brainweb: phase synchronization and large-scale integration[END_REF]. Within a single area such as V4, the degree to which single neurons synchronize with the ongoing fluctuations in localfield potential is a predictor of stimulus detection [START_REF] Womelsdorf | Gamma-band synchronization in visual cortex predicts speed of change detection[END_REF]. Across distant areas such as FEF and V4 [START_REF] Gregoriou | High-frequency, long-range coupling between prefrontal and visual cortex during attention[END_REF] or PFC and LIP [START_REF] Buschman | Top-down versus bottom-up control of attention in the prefrontal and posterior parietal cortices[END_REF], synchrony is enhanced when the stimulus in the receptive field is attended and is thus presumably accessed consciously. Consistent with human MEG and intracranial studies (e.g. [START_REF] Gaillard | Converging intracranial markers of conscious access[END_REF][START_REF] Gross | Modulation of long-range neural synchrony reflects temporal limitations of visual attention in humans[END_REF], synchronization involves both gamma and beta bands, the latter being particularly enhanced during top-down attention [START_REF] Buschman | Top-down versus bottom-up control of attention in the prefrontal and posterior parietal cortices[END_REF]. During the late phase of attention-driven activity, causal relations between distant areas are durably enhanced in both directions, but more strongly so in the bottom-up direction from V4 to FEF [START_REF] Gregoriou | High-frequency, long-range coupling between prefrontal and visual cortex during attention[END_REF], again similar to human findings [START_REF] Gaillard | Converging intracranial markers of conscious access[END_REF] and compatible with the idea that sensory information needs to be propagated anteriorily, particularly to PFC, before becoming consciously reportable.

Experiments with perceived and unperceived stimuli outside the visual modality

Although vision remains the dominant paradigm, remarkably similar signatures of conscious access have been obtained in other sensory or motor modalities (see figure 1).

In the tactile modality, threshold-level stimuli were studied both in humans with magnetoencephalography and in awake monkeys with single-cell electrophysiology (de Lafuente andRomo, 2005, 2006;[START_REF] Jones | Neural correlates of tactile detection: a combined magnetoencephalography and biophysically based computational modeling study[END_REF]. In the monkey, the early activity of neurons in the primary somatosensory area S1 was identical on detected and undetected trials, but within 180 ms the activation expanded into parietal and medial frontal cortices (MFC) where it showed a large difference predictive of behavioral reports (high activation on detected trials and low activity on undetected trials, even for constant stimuli). In humans, a similar two-phase pattern was identified within area S1 [START_REF] Jones | Neural correlates of tactile detection: a combined magnetoencephalography and biophysically based computational modeling study[END_REF]. According to the authors, modelling of these S1 potentials required the postulation of a late top-down input from unknown distant areas to supragranular and granular layers, specific to detected stimuli. Thus, as in the visual modality [START_REF] Del Cul | Brain dynamics underlying the nonlinear threshold for access to consciousness[END_REF][START_REF] Super | Two distinct modes of sensory processing observed in monkey primary visual cortex (V1)[END_REF], tactile cortices may be mobilized into a conscious assembly only during a later phase of top-down amplification, synchronous to the activation of higher association cortices.

In the auditory modality, similarly, stimuli which are not consciously detected still trigger considerable sensory processing, including 40-Hz steady-state responses [START_REF] Gutschalk | Neural correlates of auditory perceptual awareness under informational masking[END_REF] and mismatch negativities (MMN), i.e. electrophysiological responses that arise primarily from the temporal lobe in response to rare, deviant or otherwise unpredictable auditory stimuli [START_REF] Allen | Neural representation of consciously imperceptible speech sound differences[END_REF]Bekinschtein et al., 2009a;[START_REF] Diekhof | Top-down and bottom-up modulation of brain structures involved in auditory discrimination[END_REF][START_REF] Näätänen | The role of attention in auditory information processing as revealed by eventrelated potentials and other brain measures of cognitive function[END_REF]. Once again, conscious and non-conscious stimuli differ in a late (>200 ms) and global P3 wave arising from bilateral prefrontoparietal generators, with joint enhancement of temporal auditory cortices (Bekinschtein et al., 2009a;[START_REF] Diekhof | Top-down and bottom-up modulation of brain structures involved in auditory discrimination[END_REF]. These localizations are confirmed by an fMRI study that contrasted detected versus undetected near-threshold noise bursts [START_REF] Sadaghiani | Distributed and antagonistic contributions of ongoing activity fluctuations to auditory stimulus detection[END_REF] (figure 1). Similarly, an fMRI study of speech listening at different levels of sedation showed partially preserved responses in temporal cortices, but the total disappearance of activation in the left inferior frontal gyrus during deep sedation [START_REF] Davis | Dissociating speech perception and comprehension at reduced levels of awareness[END_REF]. A study by [START_REF] Hasson | Abstract coding of audiovisual speech: beyond sensory representation[END_REF] further suggests that the content of what we consciously hear does not depend on early modality-specific responses in auditory cortex, but rather on late fronto-parietal cross-modal computations. Using the McGurk illusion (perception of a syllable "ta" when simultaneously hearing "pa" and seeing a face saying "ka"), they dissociated the objective auditory and visual stimuli from the subjective percept. Using fMRI repetition suppression, they then showed that early auditory cortices coded solely for the objective auditory stimulus, while the perceived subjective conscious content was reflected in the activation of the left posterior inferior frontal gyrus and anterior inferior parietal lobule. In this instance, at least, PFC activation could not be attributed to a generic process of attention, detection or memory, but demonstrably encoded the specific syllable perceived.

Turning to the action domain, several studies have demonstrated that the awareness of ones' action, surprisingly, is not associated with primary or premotor cortices, but arises from a higherlevel representation of intentions and their expected sensory consequences which involves prefrontal and parietal cortices, notably the angular gyrus (AG) [START_REF] Desmurget | Movement intention after parietal cortex stimulation in humans[END_REF][START_REF] Farrer | The angular gyrus computes action awareness representations[END_REF]. Using direct cortical stimulation, [START_REF] Desmurget | Movement intention after parietal cortex stimulation in humans[END_REF] observed a double dissociation: premotor stimulation often led to overt movements that the subject was not aware of performing, while angular gyrus stimulation led to a subjective perception of movement intention and performance even in the absence of any detectable muscle activation. In normal subjects, disrupted sensori-motor feedback has also been used to define a minimal contrast between subliminal versus conscious gestures. For instance, when a temporal delay or a spatial bias was introduced in the visual feedback provided to participants about their own hand movements, they continuously adjusted their behavior, but these motor adjustments were only perceived consciously when the disruption exceeded a certain threshold [START_REF] Farrer | The angular gyrus computes action awareness representations[END_REF][START_REF] Slachevsky | Preserved adjustment but impaired awareness in a sensory-motor conflict following prefrontal lesions[END_REF]. fMRI revealed that this non-linearity related to a bilateral distributed network involving AG and PFC cortices [START_REF] Farrer | The angular gyrus computes action awareness representations[END_REF].

Perhaps the clearest evidence for a two-stage process in action awareness comes from studies of error awareness [START_REF] Nieuwenhuis | Error-related brain potentials are differentially related to awareness of response errors: evidence from an antisaccade task[END_REF]. In an anti-saccade paradigm, participants were instructed to move their eyes in the direction opposite to a visual target. This instruction generated frequent errors, where the eyes first moved towards the stimulus and then away from it. Many of these erroneous eye movements remained undetected. Remarkably, immediately after such undetected errors, a strong and early (~80 ms) ERP component called the error-related negativity arose from midline frontal cortices (anterior cingulate or pre-SMA). Only when the error was consciously detected was this early waveform amplified and followed by a massive P3-like waveform, which fMRI associated with the expansion of activation into a broader network including left inferior frontal/anterior insula activity [START_REF] Klein | Neural correlates of error awareness[END_REF].

Convergence with studies of inattention and dual-tasks

The experiments reviewed so far considered primarily subliminal paradigms where access to conscious reportability was modulated by reducing the incoming sensory information. However, similar findings arise from preconscious paradigms where withdrawal of attentional selection is used to modulate conscious access [START_REF] Dehaene | Conscious, preconscious, and subliminal processing: a testable taxonomy[END_REF], resulting in either failed (attentional blink, AB) delayed conscious access (psychological refractory period or PRP). In such states, initial visual processing, indexed by P1 and N1 waves, can be largely or even entirely unaffected [START_REF] Sergent | Timing of the brain events underlying access to consciousness during the attentional blink[END_REF][START_REF] Sigman | Brain mechanisms of serial and parallel processing during dualtask performance[END_REF][START_REF] Vogel | Electrophysiological evidence for a postperceptual locus of suppression during the attentional blink[END_REF]. However, only perceived stimuli exhibit an amplification of activation in task-related sensory areas (e.g. parahippocampal place area for pictures of places) as well as the unique emergence of lateral and midline prefrontal and parietal areas (see also [START_REF] Asplund | A central role for the lateral prefrontal cortex in goal-directed and stimulus-driven attention[END_REF][START_REF] Marois | The neural fate of consciously perceived and missed events in the attentional blink[END_REF][START_REF] Slagter | Neural competition for conscious representation across time: an fMRI study[END_REF][START_REF] Williams | Attenuation of neural responses in primary visual cortex during the attentional blink[END_REF]. Temporally resolved fMRI studies indicate that, during the dual-task bottleneck, PFC activity evoked by the second task is delayed [START_REF] Dux | Isolation of a central bottleneck of information processing with time-resolved FMRI[END_REF][START_REF] Sigman | Brain mechanisms of serial and parallel processing during dualtask performance[END_REF]. With electrophysiology, the P3b waveform again appears as a major correlate of conscious processing which is both delayed during the PRP [START_REF] Dell'acqua | Central processing overlap modulates P3 latency[END_REF][START_REF] Sigman | Brain mechanisms of serial and parallel processing during dualtask performance[END_REF] and absent during AB [START_REF] Kranczioch | Temporal dynamics of access to consciousness in the attentional blink[END_REF][START_REF] Sergent | Timing of the brain events underlying access to consciousness during the attentional blink[END_REF]. Seen versus blinked trials are also distinguished by another marker, the synchronization of distant frontoparietal areas in the beta band [START_REF] Gross | Modulation of long-range neural synchrony reflects temporal limitations of visual attention in humans[END_REF].

William James (1890) noted how conscious attention and effort are required for the controlled execution of novel non-routine sequential tasks, but is no longer needed or even detrimental once routine sets in. Thus, the comparison of effortful versus automatic tasks provides another contrast which, although not quite as minimal as the previous ones, should at least provide signatures of conscious-level processing consistent with other paradigms. Indeed, a broad network including inferior and dorsolateral prefrontal, anterior cingulate and lateral parietal and intraparietal components is activated whenever human subjects perform effortful single or dual tasks [START_REF] Marois | Capacity limits of information processing in the brain[END_REF], and its activation diminishes with training in parallel to the reduction in behavioral cost [START_REF] Dux | Training improves multitasking performance by increasing the speed of information processing in human prefrontal cortex[END_REF]. Strikingly, it suddenly drops as soon as subjects move into a routine mode of task execution [START_REF] Landmann | Dynamics of Prefrontal and Cingulate Activity during a Reward-Based Logical Deduction Task[END_REF][START_REF] Procyk | Anterior cingulate activity during routine and nonroutine sequential behaviors in macaques[END_REF] (figure 5). On the contrary, focal cortical regions associated with automatized processing of the relevant sensory or motor attributes remain invariant or may even increase their activation in the course of routinization (e.g. [START_REF] Sigman | Top-down reorganization of activity in the visual pathway after learning a shape identification task[END_REF].

Broad fronto-parietal networks also figure prominently amongst the distributed networks of coactive areas that can be isolated during spontaneous brain activity in the absence of an explicit task goal [START_REF] Beckmann | Investigations into resting-state connectivity using independent component analysis[END_REF][START_REF] Fox | Spontaneous neuronal activity distinguishes human dorsal and ventral attention systems[END_REF][START_REF] Greicius | Functional connectivity in the resting brain: a network analysis of the default mode hypothesis[END_REF][START_REF] Mantini | Electrophysiological signatures of resting state networks in the human brain[END_REF][START_REF] Vincent | Evidence for a frontoparietal control system revealed by intrinsic functional connectivity[END_REF]. How this activity relates to conscious processing remains debated, since it can still be observed, to some extent, during sleep [START_REF] He | Electrophysiological correlates of the brain's intrinsic large-scale functional architecture[END_REF], vegetative state [START_REF] Boly | Functional connectivity in the default network during resting state is preserved in a vegetative but not in a brain dead patient[END_REF] or sedation in both humans [START_REF] Greicius | Persistent default-mode network connectivity during light sedation[END_REF] and monkeys [START_REF] Vincent | Intrinsic functional architecture in the anaesthetized monkey brain[END_REF]. To resolve this issue, a direct test consists in identifying participants with a given spontaneous activity pattern and asking them whether they were experiencing a particular conscious content [START_REF] Christoff | Experience sampling during fMRI reveals default network and executive system contributions to mind wandering[END_REF][START_REF] Mason | Wandering minds: the default network and stimulus-independent thought[END_REF]. Such studies reveal a tight correlation between default-mode network activity and self-reported "mind-wandering" into episodic memory and self-oriented thought. [START_REF] Smallwood | Going AWOL in the Brain: Mind Wandering Reduces Cortical Analysis of External Events[END_REF] further demonstrated that, during such mind-wandering periods, the P3 wave evoked by external events is reduced. Overall, these findings indicate that spontaneous activity, like external goal-driven activity, invades large-scale fronto-parietal networks and impose a strong limitation on the processing of external events, with the same signature as the attentional blink.

In conclusion, human neuroimaging methods and electrophysiological recordings during conscious access, under a broad variety of paradigms, consistently reveal a late amplification of relevant sensory activity, long-distance cortico-cortical synchronisation at beta and gamma frequencies, and "ignition" of a large-scale prefronto-parietal network.

III. Theoretical modeling of conscious access

The above experiments provide a convergent database of observations. In the present section, we examine which theoretical principles may account for these findings. We briefly survey the major theories of conscious processing, with the goal to try to isolate a core set of principles, common to most theories, and which begin to make sense of existing observations. We then describe in more detail a specific theory, the Global Neuronal Workspace (GNW), whose simulations coarsely capture the contrasting physiological states underlying non-conscious versus conscious processing.

Convergence towards a set of core concepts for conscious access

Although consciousness research includes wildly speculative proposals [START_REF] Eccles | How the self controls its brain[END_REF][START_REF] Jaynes | The Origin of Consciousness in the Breakdown of the Bicameral Mind[END_REF][START_REF] Penrose | The emperor's new mind[END_REF], research of the past decades has led to an increasing degree of convergence towards a set of concepts considered essential in most theories (for review, see [START_REF] Seth | Models of consciousness[END_REF]. Four such concepts can be isolated.

A supervision system. In the words of William James, "consciousness" appears as "an organ added for the sake of steering a nervous system grown too complex to regulate itself" (James, 1890, chapter 5). [START_REF] Posner | Attention, self-regulation and consciousness[END_REF]Posner and Snyder, 1975) and [START_REF] Shallice | Dual functions of consciousness[END_REF]Shallice) first proposed that information is conscious when it is represented in an 'executive attention' or 'supervisory attentional' system that controls the activities of lower-level sensory-motor routines and which is associated with prefrontal cortex (figure 6). In other words, a chain of sensory, semantic and motor processors can unfold without our awareness, as reviewed in the previous section, but conscious perception seems needed for the flexible control of their execution, such as their onset, termination, inhibition, repetition or serial chaining.

A serial processing system. Descartes (1648Descartes ( /1937) first observed that "ideas impede each other". [START_REF] Broadbent | Perception and Communication[END_REF] theorized conscious perception as involving access to a limited-capacity channel where processing is serial, one object at a time. The attentional blink and psychological refractory period effects indeed confirm that conscious processing of a first stimulus renders us temporarily unable to consciously perceive other stimuli presently shortly thereafter. Several psychological models now incorporate the idea that initial perceptual processing is parallel and nonconscious, and that conscious access is serial and occurs at the level of a later central bottleneck [START_REF] Pashler | Dual-task interference in simple tasks: data and theory[END_REF] or second processing stage of working memory consolidation [START_REF] Chun | A two-stage model for multiple target detection in rapid serial visual presentation[END_REF].

A coherent assembly formed by re-entrant or top-down loops. In the context of the maintenance of invariant representations of the body/world through reafference (von Holst and Mittelstaedt, 1950), [START_REF] Edelman | Neural Darwinism[END_REF] proposed re-entry as an essential component of the creation of a unified percept: the bidirectional exchange of signals across parallel cortical maps coding for different aspects of the same object. More recently, the dynamic core hypothesis [START_REF] Tononi | Consciousness and complexity[END_REF] proposes that information encoded by a group of neurons is conscious only if it achieves not only differentiation (i.e the isolation of one specific content out of a vast repertoire of potential internal representations), but also integration (i.e. the formation of a single, coherent and unified representation, where the whole carries more information than each part alone). A notable feature of the dynamic core hypothesis is the proposal of a quantitative mathematical measure of information integration called Φ, high values of which are achieved only through a hierarchical recurrent connectivity and would be necessary and sufficient to sustain conscious experience: "consciousness is integrated information" [START_REF] Tononi | Consciousness as integrated information: a provisional manifesto[END_REF]. This measure has been shown to be operative for some conscious/non-conscious distinctions such as anesthesia (e.g. Lee et al., 2009b), but it is computationally complicated and, as a result, has not yet been broadly applied to most of the minimal empirical contrasts reviewed above.

In related proposals, Crick andKoch (1995, 2003;[START_REF] Crick | What is the function of the claustrum?[END_REF] suggested that conscious access involves forming a stable global neural coalition. They initially introduced reverberating gamma-band oscillations around 40 Hz as a crucial component, then proposed an essential role of connections to prefrontal cortex. Lamme and colleagues [START_REF] Lamme | The distinct modes of vision offered by feedforward and recurrent processing[END_REF][START_REF] Super | Two distinct modes of sensory processing observed in monkey primary visual cortex (V1)[END_REF] produced data strongly suggesting that feedforward or bottom-up processing alone is not sufficient for conscious access, and that top-down or feedback signals forming recurrent loops are essential to conscious visual perception. Llinas and colleagues [START_REF] Llinas | The neuronal basis for consciousness[END_REF][START_REF] Llinas | Of dreaming and wakefulness[END_REF] have also argued that consciousness is fundamentally a thalamocortical closed-loop property in which the ability of cells to be intrinsically active plays a central role.

A global workspace for information sharing. The theatre metaphor [START_REF] Taine | De l'intelligence[END_REF] compares consciousness to a narrow scene that allows a single actor to diffuse his message. This view has been criticized because, at face value, it implies a conscious homunculus watching the scene, thus leading to infinite regress [START_REF] Dennett | Consciousness explained[END_REF]. However, capitalizing on the earlier concept of a blackboard system in artificial intelligence (a common data structure shared and updated by many specialized modules), [START_REF] Baars | A cognitive theory of consciousness[END_REF] proposed an homunculus-free psychological model where the current conscious content is represented within a distinct mental space called global workspace, with the capacity to broadcast this information to a set of other processors (figure 6). Anatomically, Baars speculated that the neural bases of his global workspace might comprise the « ascending reticular formation of the brain stem and midbrain, the outer shell of the thalamus and the set of neurons projecting upward diffusely from the thalamus to the cerebral cortex ».

We introduced the Global Neuronal Workspace (GNW) model as an alternative cortical mechanism capable of integrating the supervision, limited-capacity and re-entry properties [START_REF] Changeux | The Neuronal Workspace Model: Conscious Processing and Learning[END_REF][START_REF] Dehaene | Ongoing spontaneous activity controls access to consciousness: a neuronal model for inattentional blindness[END_REF][START_REF] Dehaene | Conscious, preconscious, and subliminal processing: a testable taxonomy[END_REF]Dehaene et al., 1998a;Dehaene and Naccache, 2001;Dehaene et al., 2003b). Our proposal is that a subset of cortical pyramidal cells with long-range excitatory axons, particularly dense in prefrontal, cingulate, and parietal regions, together with the relevant thalamocortical loops, form a horizontal "neuronal workspace" interconnecting the multiple specialized, automatic and non-conscious processors (figure 6). A conscious content is assumed to be encoded by the sustained activity of a fraction of GNW neurons, the rest being inhibited. Through their numerous reciprocal connections, GNW neurons amplify and maintain a specific neural representation. The long-distance axons of GNW neurons then broadcast it to many other processors brain-wide. Global broadcasting allows information to be more efficiently processed (because it it no longer confined to a subset of non-conscious circuits, but can be flexibly shared by many cortical processors) and to be verbally reported (because these processors include those involved in formulating verbal messages). While non-conscious stimuli can be quickly and efficient processed along automatized or pre-instructed processing routes before quickly decaying within a few seconds, conscious stimuli would be distinguished by their lack of "encapsulation" in specialized processes and their flexible circulation to various processes of verbal report, evaluation, memory, planning and intentional action, many seconds after their disappearance [START_REF] Baars | A cognitive theory of consciousness[END_REF]Dehaene and Naccache, 2001). Dehaene and Naccache (2001) postulate that "this global availability of information ( …) is what we subjectively experience as a conscious state".

Explicit simulations of conscious ignition

The GNW has been implemented as explicit computer simulations of neural networks [START_REF] Dehaene | Ongoing spontaneous activity controls access to consciousness: a neuronal model for inattentional blindness[END_REF]Dehaene et al., 1998a;Dehaene et al., 2003b; see also [START_REF] Zylberberg | Neurophysiological bases of exponential sensory decay and top-down memory retrieval: a model[END_REF]. These simulations incorporate spiking neurons and synapses with detailed membrane, ion channel and receptor properties, organized into distinct cortical supra-granular, granular, infragranular and thalamic sectors with reasonable connectivity and temporal delays. Although the full GNW architecture was not simulated, four areas were selected and hierarchically interconnected (figure 7). Bottom-up feed-forward connections linked each area to the next, while long-distance topdown connections projected to all preceding areas. Moreover, in a simplifying assumption, bottomup connections impinged on glutamate AMPA receptors while the top-down ones, which are slower, more numerous and more diffuse, primarily involved glutamate NMDA receptors (the plausibility of this hypothesis is discussed further below). In higher areas, inputs competed with each other through GABAergic inhibitory interneurons, and it was assumed (though not explicitly simulated) that the winning representation would be broadcasted by additional long-distance connections to yet other cortical regions.

Initial simulations explored the sequence of activity leading to conscious access. When sensory stimulation was simulated as a brief depolarizing current at the lowest thalamic level, activation propagated according to two successive phases (see figure 7): (1) initially, a brief wave of excitation progressed into the simulated hierarchy through fast AMPA-mediated feedforward connections, with an amplitude and duration directly related to the initial input; (2) in a second stage, mediated by the slower NMDA-mediated feedback connections, the advancing feed-forward wave amplified its own inputs in a cascading manner, quickly leading the whole stimulus-relevant network into a global self-sustained reverberating or "ignited" state. This ignition was characterized by an increased power of local cortico-thalamic oscillations in the gamma band (Dehaene et al., 2003b), as well as increased synchrony across distant regions (Dehaene, unpublished simulations).

This second phase of the simulation reproduces most of the empirical signatures of conscious access: late, all-or-none, cortically distributed potentials involving prefrontal cortex and other high-level associative cortices, with simultaneous increases in high-frequency power and synchrony (e.g. de [START_REF] De Lafuente | Neural correlate of subjective sensory experience gradually builds up across cortical areas[END_REF][START_REF] Del Cul | Brain dynamics underlying the nonlinear threshold for access to consciousness[END_REF][START_REF] Gaillard | Converging intracranial markers of conscious access[END_REF].

In GNW simulations, ignition manifests itself as a depolarization of layer II/III apical dendrites of pyramidal dendrites in a subset of activated GNW neurons defining the conscious contents, the rest being inhibited. In a geometrically accurate model of the pyramidal cell, the summed postsynaptic potentials evoked by long-distance signalling amongst these distributed sets of active cells would create slow intracellular currents travelling from the apical dendrites towards the cell's soma, summing up on the cortical surface as negative slow cortical potentials (SCPs) over regions coding for the conscious stimulus (see [START_REF] He | The fMRI signal, slow cortical potential and consciousness[END_REF]. Simultaneously, many other GNW neurons are strongly suppressed by lateral inhibition via GABAergic interneurons and define what the current conscious content is not. As already noted by Rockstroh et al. (1992, p. 175), assuming that many more neurons are inhibited than activated, "the surface positivity corresponding to these inhibited networks would then dominate over the relatively smaller spots of negativity caused by the reverberating excitation". Thus, the model can explain why, during conscious access, the resulting event-related potential is dominated by a positive waveform, the P3b. This view also predicts that scalp negativities should appear specifically over areas dense in neurons coding for the current conscious content. Indeed, in a spatial working memory task, all stimuli evoke a broad P3b, but when subtracting ERPs ipsilateral and controlateral to the side of the memorized items, negative potentials appeared over parietal cortex contralateral to the memorized locations [START_REF] Vogel | Neural activity predicts individual differences in visual working memory capacity[END_REF].

Further GNW simulations showed that ignition could fail to be triggered under specific conditions, thus leading to simulated non-conscious states. For very brief or low-amplitude stimuli, a feedforward wave was seen in the initial thalamic and cortical stages of the simulation, but it died out without triggering the late global activation, because it was not able to gather sufficient selfsustaining reverberant activation [START_REF] Dehaene | Ongoing spontaneous activity controls access to consciousness: a neuronal model for inattentional blindness[END_REF]. Even at higher stimulus amplitudes, the second global phase could also be disrupted if another incoming stimulus had been simultaneously accessed (Dehaene et al., 2003b). Such a disruption occurs because during ignition, the GNW is mobilized as a whole, some GNW neurons being active while the rest is actively inhibited, thus preventing multiple simultaneous ignitions. A strict seriality of conscious access and processing is therefore predicted and has been simulated [START_REF] Dehaene | Ongoing spontaneous activity controls access to consciousness: a neuronal model for inattentional blindness[END_REF]Dehaene et al., 2003b;[START_REF] Zylberberg | The brain's router: a cortical network model of serial processing in the primate brain[END_REF]. Overall, these simulations capture the two main types of experimental conditions known to lead to non-conscious processing: subliminal states due to stimulus degradation (e.g. masking), and preconscious states due to distraction by a simultaneous task (e.g. attentional blink).

The transition to the ignited state can be described, in theoretical physics terms, as a stochastic phase transition -a sudden change in neuronal dynamics whose occurrence depends in part on stimulus characteristics and in part on spontaneous fluctuations in activity [START_REF] Dehaene | Ongoing spontaneous activity controls access to consciousness: a neuronal model for inattentional blindness[END_REF]Dehaene et al., 2003b). In GNW simulations, prestimulus fluctuations in neural discharges only have a small effect on the early sensory stage, which largely reflects objective stimulus amplitude and duration, but they have a large influence on the second slower stage, which is characterized by NMDA-based reverberating integration and ultimately leads to a bimodal "all-ornone" distribution of activity, similar to empirical observations [START_REF] Quiroga | Human single-neuron responses at the threshold of conscious recognition[END_REF][START_REF] Sergent | Timing of the brain events underlying access to consciousness during the attentional blink[END_REF][START_REF] Sergent | Is consciousness a gradual phenomenon? Evidence for an all-ornone bifurcation during the attentional blink[END_REF]. Due to these fluctuations, across trials, the very same stimulus does or does not lead to global ignition, depending in part on the precise phase of the stimulus relative to ongoing spontaneous activity. This notion that pre-stimulus baseline fluctuations partially predict conscious perception is now backed up by considerable empirical data (e.g. [START_REF] Boly | Baseline brain activity fluctuations predict somatosensory perception in humans[END_REF][START_REF] Palva | Early neural correlates of conscious somatosensory perception[END_REF][START_REF] Sadaghiani | Distributed and antagonistic contributions of ongoing activity fluctuations to auditory stimulus detection[END_REF][START_REF] Super | Internal state of monkey primary visual cortex (V1) predicts figure-ground perception[END_REF][START_REF] Wyart | How ongoing fluctuations in human visual cortex predict perceptual awareness: baseline shift versus decision bias[END_REF]. More generally, these simulations provide a partial neural implementation of the psychophysical framework according to which conscious access corresponds to a "decision" based on the accumulation of stimulus-based evidence, prior knowledge and biases [START_REF] Dehaene | Conscious and nonconscious processes: distinct forms of evidence accumulation? In Better Than Conscious? Decision Making, the Human Mind, and Implications For Institutions[END_REF]and the mathematical appendix in Del Cul et al., 2009; for specific implementations, see [START_REF] Lau | A higher order Bayesian decision theory of consciousness[END_REF].

Modeling spontaneous activity and serial goal-driven processing

An original feature of the GNW model, absent from many other formal neural network models, is the occurence of highly structured spontaneous activity [START_REF] Dehaene | Ongoing spontaneous activity controls access to consciousness: a neuronal model for inattentional blindness[END_REF].

Even in the absence of external inputs, the simulated GNW neurons are assumed to fire spontaneously, in a top-down manner, starting from the highest hierarchical levels of the simulation and propagating downwards to form globally synchronized ignited states. When the ascending vigilance signal is large, several such spontaneous ignitions follow each other in a never-ending "stream", and can block ignition by incoming external stimuli [START_REF] Dehaene | Ongoing spontaneous activity controls access to consciousness: a neuronal model for inattentional blindness[END_REF]. These simulations capture some of the empirical observations on inattentional blindness [START_REF] Mack | Inattentional blindness[END_REF] and mind wandering [START_REF] Christoff | Experience sampling during fMRI reveals default network and executive system contributions to mind wandering[END_REF][START_REF] Mason | Wandering minds: the default network and stimulus-independent thought[END_REF][START_REF] Smallwood | Going AWOL in the Brain: Mind Wandering Reduces Cortical Analysis of External Events[END_REF]. More complex network architectures have also been simulated in which a goal state is set and continuously shapes the structured patterns of activity which are spontaneously generated, until the goal is ultimately attained [START_REF] Dehaene | A hierarchical neuronal network for planning behavior[END_REF][START_REF] Zylberberg | The brain's router: a cortical network model of serial processing in the primate brain[END_REF]. In these simulations, ignited states are stable only for a transient time period and can be quickly destabilized by a negative reward signal that indicates deviation from the current goal, in which case they are spontaneously and randomly replaced by another discrete combination of workspace neurons. The dynamics of such networks is thus characterized by a constant flow of individual coherent episodes of variable duration, selected by reward signals in order to achieve a defined goal state. Architectures based on these notions have been applied to a variety of tasks (delayed response: [START_REF] Dehaene | A simple model of prefrontal cortex function in delayedresponse tasks[END_REF]; Wisconsin card sorting: [START_REF] Dehaene | The Wisconsin Card Sorting Test: Theoretical analysis and modelling in a neuronal network[END_REF]Tower of London: Dehaene and Changeux, 1997;Stroop: Dehaene et al., 1998a), although a single architecture common to all tasks is not yet in sight (but see [START_REF] Rougier | Prefrontal cortex and flexible cognitive control: rules without symbols[END_REF]. As illustrated in figure 5, they provide a preliminary account of why GNW networks are spontaneously active, in a sustained manner, during effortful tasks that require series of conscious operations, including search, dual-task and error processing.

In summary, we propose that a core set of theoretical concepts lie at the confluence of the diverse theories that have been proposed to account for conscious access: high-level supervision; serial processing; coherent stability through re-entrant loops; and global information availability.

Furthermore, once implemented in the specific neuronal architecture of the GNW model, these concepts begin to provide a schematic account of the neurophysiological signatures that, empirically, distinguish conscious access from non-conscious processing. In particular, simulations of the GNW

IV. Present experimental and theoretical challenges

The existing empirical data on conscious access still presents many challenges for theorizing. Indeed, the above theoretical synthesis may still be refuted if some of its key neural components were found to be implausible or altogether absent in primate cerebral architecture, or if its predicted patterns of activity (the late "ignition") were found to be unnecessary, artifactual, non-coding or noncausally related to conscious states. We consider each of these potential challenges in turn.

Connectivity and architecture of long-distance cortical networks

Pyramidal neurons with long-distance axons. The main anatomical premise of the GNW model is that it consists of "a distributed set of cortical neurons characterized by their ability to receive from and send back to homologous neurons in other cortical areas horizontal projections through longrange excitatory axons mostly originating from the pyramidal cells of layers II and III" (Dehaene et al., 1998a) and more densely distributed in prefrontal and inferior parietal cortices. Do these units actually exist? The "special morphology" of the pyramidal cells from the cerebral cortex was already noted by [START_REF] Cajal | Cajal on the Cerebral Cortex: An Annotated Translation of the Complete Writings[END_REF][START_REF] Cajal | Cajal on the Cerebral Cortex: An Annotated Translation of the Complete Writings[END_REF], who mentioned their "long axons with multiple collaterals" and their "very numerous and complex dendrites". Von [START_REF] Economo | The cytoarchitectonics of the human cerebral cortex[END_REF] further noted that these large pyramidal cells in layers III and V are specially abundant in areas "spread over the anterior two-thirds of the frontal lobe, (…) the superior parietal lobule" and "the cingulate cortex", among other cortical areas. Recent investigations have confirmed that long-distance cortico-cortical and callosal fibers primarily (though not exclusively) arise from layer II-III pyramids. Furthermore, quantitative analyses of the dendritic field morphology of layer III pyramidal neurons revealed a continuous increase of complexity of the basal dendrites from the occipital up to the prefrontal cortex within a given species [START_REF] Defelipe | The pyramidal neuron of the cerebral cortex: morphological and chemical characteristics of the synaptic inputs[END_REF]Elston andRosa, 1997, 1998) and from lower species (owl monkey, marmoset) up to humans [START_REF] Elston | Cortex, cognition and the cell: new insights into the pyramidal neuron and prefrontal function[END_REF]. Layer PFC pyramidal neurons have as many as 16 times more spines in PFC than in V1 and, as a result, "the highly spinous cells in prefrontal areas may integrate many more inputs than cells in areas such as V1, TE, and 7a." [START_REF] Elston | Pyramidal cells of the frontal lobe: all the more spinous to think with[END_REF]. These observations confirm that PFC cells exhibit the morphological adaptations needed for massive longdistance communication, information integration and broadcasting postulated in the GNW model, and suggest that this architecture is particularly developed in the human species.

Global brain-scale white-matter networks involving PFC. The GNW model further assumes that long-distance neurons form brain-scale networks involving prefrontal cortex as a key node. PFC indeed receives the most diverse set of corticocortical inputs from areas involved in processing all sensory modalities [START_REF] Cavada | The anatomical connections of the macaque monkey orbitofrontal cortex. A review[END_REF][START_REF] Fuster | The prefrontal cortex (4th edition)[END_REF][START_REF] Kringelbach | The functional neuroanatomy of the human orbitofrontal cortex: evidence from neuroimaging and neuropsychology[END_REF][START_REF] Pandya | Prefrontal cortex in relation to other cortical areas in rhesus monkey: architecture and connections[END_REF][START_REF] Petrides | Distinct parietal and temporal pathways to the homologues of Broca's area in the monkey[END_REF]. In the monkey cerebral cortex, long-range connections link, among others, the prefrontal cortex (area 46), the superior temporal sulcus, parietal area 7a and the hippocampus together with the contralateral anterior and posterior cingulum, area 19 and the parahippocampal gyrus [START_REF] Goldman-Rakic | Topography of cognition: Parallel distributed networks in primate association cortex[END_REF]. In addition, areas within PFC are multiply interconnected [START_REF] Barbas | Architecture and intrinsic connections of the prefrontal cortex in the rhesus monkey[END_REF][START_REF] Preuss | Ipsilateral cortical connections of granular frontal cortex in the strepsirhine primate Galago, with comparative comments on anthropoid primates[END_REF], and the superficial layers in PFC are characterized by an abundance of horizontal intrinsic axon projections that arise from supragranular pyramidal cells [START_REF] Kritzer | Intrinsic circuit organization of the major layers and sublayers of the dorsolateral prefrontal cortex in the rhesus monkey[END_REF][START_REF] Melchitzky | Synaptic targets of the intrinsic axon collaterals of supragranular pyramidal neurons in monkey prefrontal cortex[END_REF][START_REF] Melchitzky | Synaptic targets of pyramidal neurons providing intrinsic horizontal connections in monkey prefrontal cortex[END_REF][START_REF] Pucak | Patterns of intrinsic and associational circuitry in monkey prefrontal cortex[END_REF], thus exhibiting the massive and recurrent interconnectivity needed to sustain GNW ignition.

In humans, the course of cortical tracts can now be confirmed by diffusion tensor imaging (DTI) and tractography algorithms (figure 8), yet with important limitations. Measurements typically average over relatively large voxels (a few millimeters aside) that contain a diversity of criss-crossing fibers. Even recent articles claiming to study the entire connectome (e.g. [START_REF] Hagmann | Mapping the Structural Core of Human Cerebral Cortex[END_REF] suffer for underestimation of the true long-distance connectivity of areas 46, 6, FEF and LIP, critical to GNW theory and known from macaque invasive tracer studies and careful human anatomical dissections dating from the end of the 19th century (Dejerine, Meynert, Fleschig). In a still up-to-date volume, Dejerine (1895) distinguished five main tracts of long association fibers running deeply in the human white matter. Consistent with the GNW hypothesis, four of them connect prefrontal cortex with other cortical areas and are confirmed by diffusion tensor tractography [START_REF] Catani | A diffusion tensor imaging tractography atlas for virtual in vivo dissections[END_REF] and by correlation of cortical thickness measures [START_REF] Bassett | Hierarchical organization of human cortical networks in health and schizophrenia[END_REF]He et al., 2009). The networks thus identified converge well with those extracted by fMRI intercorrelation patterns during the resting state or by phase synchrony in the beta band during either working memory [START_REF] Bassett | Cognitive fitness of cost-efficient brain functional networks[END_REF] or attentional blink [START_REF] Gross | Modulation of long-range neural synchrony reflects temporal limitations of visual attention in humans[END_REF].

The importance of long-distance cortical projection pathways in conscious perception was recently tested in patients at the very first clinical stage of multiple sclerosis (MS), a neurological disease characterized by extensive white matter damage leading to perturbed long-distance connectivity (He et al., 2009;[START_REF] Reuter | Intact subliminal processing and delayed conscious access in multiple sclerosis[END_REF][START_REF] Reuter | White matter damage impairs access to consciousness in multiple sclerosis[END_REF]. As predicted, MS patients showed abnormal conscious perception of masked stimuli: they needed a longer target-mask delay before conscious access occurred. Furthermore, this behavioral anomaly correlated with structural damage in the dorsolateral prefrontal white matter and the right occipito-frontal fasciculus (figure 8).

Importantly, subliminal priming was preserved.

While recent results thus support the existence of massive long-distance cortical networks involving PFC and their role in conscious perception, two points should be stressed. First, the PFC is increasingly being decomposed into multiple specialized and lateralized subnetworks (e.g. [START_REF] Koechlin | The architecture of cognitive control in the human prefrontal cortex[END_REF][START_REF] Voytek | Contingent aftereffects distinguish conscious and preconscious color processing[END_REF]. These findings need not, however, been seen as contradicting the GNW hypothesis that these subnetworks, through their tight interconnections, interact so strongly as to make any information coded in one area quickly available to all others. Second, in addition to PFC, the non-specific thalamic nuclei, the basal ganglia, and some cortical nodes are likely to contribute to global information broadcasting [START_REF] Voytek | Contingent aftereffects distinguish conscious and preconscious color processing[END_REF]. The precuneus, in particular, may also operate as a cortical "hub" with a massive degree of interconnectivity [START_REF] Hagmann | Mapping the Structural Core of Human Cerebral Cortex[END_REF][START_REF] Iturria-Medina | Studying the human brain anatomical network via diffusion-weighted MRI and Graph Theory[END_REF]. This region, plausibly homologous to the highly connected macaque posteromedial cortex (PMC) [START_REF] Parvizi | Neural connections of the posteromedial cortex in the macaque[END_REF], is an aggregate of convergencedivergence zones [START_REF] Meyer | Convergence and divergence in a neural architecture for recognition and memory[END_REF] and is tightly connected to PFC area 46 and other workspace regions [START_REF] Goldman-Rakic | The "psychic" neuron of the cerebral cortex[END_REF]. In humans, the PMC may play a critical role in humans in self-referential processing [START_REF] Cavanna | The precuneus: a review of its functional anatomy and behavioural correlates[END_REF][START_REF] Damasio | The feeling of what happens[END_REF][START_REF] Vogt | Posterior cingulate, precuneal and retrosplenial cortices: cytology and components of the neural network correlates of consciousness[END_REF], thus allowing any conscious content to be integrated into a subjective first-person perspective.

NMDA receptors and GNW simulations. GNW simulations assume that long-distance bottom-up connections primarily impinge on fast glutamate AMPA receptors while top-down ones primarily concern the slower glutamate NMDA receptor. This assumption contributes importantly to the temporal dynamics of the model, particularly the separation between a fast phasic bottom-up phase and a late sustained integration phase, mimicking experimental observations. It can be criticized as both receptor types are known to be present in variable proportions at glutamatergic synapses (Karl Zilles, personal communication). However, physiological recordings show that, in agreement with the model, NMDA antagonists do not interfere with early bottom-up sensory activity, either in auditory [START_REF] Javitt | Role of cortical N-methyl-Daspartate receptors in auditory sensory memory and mismatch negativity generation: implications for schizophrenia[END_REF] or in visual areas [START_REF] Self | Different contributions of glutamate receptors to figure-ground segregation and visually driven activity in primary visual cortex[END_REF]. Typically, they only affect later integrative events such as the mismatch negativity in auditory cortex [START_REF] Javitt | Role of cortical N-methyl-Daspartate receptors in auditory sensory memory and mismatch negativity generation: implications for schizophrenia[END_REF] or the figure-ground modulation of firing in primary visual cortex neurons [START_REF] Self | Different contributions of glutamate receptors to figure-ground segregation and visually driven activity in primary visual cortex[END_REF]. Thus, although GNW simulations adopted a highly simplified anatomical assumption of radically distinct distributions of NMDA and AMPA, which may have to be qualified in more realistic models, the notion that NMDA receptors contribute primarily to late, slow and top-down integrative processes is plausible (for a related argument, see [START_REF] Wong | The Relationship Between Attentional Blink and Psychological Refractory Period[END_REF].

Is conscious perception slow and late?

A strong statement of the proposed theoretical synthesis is that early bottom-up sensory events, prior to global ignition (<200-300 ms), contribute solely to non-conscious percept construction and do not systematically distinguish consciously seen from unseen stimuli. In apparent contradiction with this view, certain experiments, using both visual [START_REF] Pins | The neural correlates of conscious vision[END_REF] or tactile stimuli [START_REF] Palva | Early neural correlates of conscious somatosensory perception[END_REF], have observed that the early incoming wave of sensory-evoked activity (e.g. P1 component) is already enhanced on conscious compared to non-conscious trials. Lamme and collaborators [START_REF] Fahrenfort | Masking disrupts reentrant processing in human visual cortex[END_REF] found amplification in visual cortex, just posterior to the P1 wave (110-140 ms). More frequently, at around 200-300 ms, surrounding the P2 ERP component, more negative voltages are reported over posterior cortices on visible compared to invisible trials [START_REF] Del Cul | Brain dynamics underlying the nonlinear threshold for access to consciousness[END_REF][START_REF] Fahrenfort | Masking disrupts reentrant processing in human visual cortex[END_REF][START_REF] Koivisto | The relationship between awareness and attention: Evidence from ERP responses[END_REF][START_REF] Koivisto | The earliest electrophysiological correlate of visual awareness?[END_REF][START_REF] Railo | The electrophysiological correlates of stimulus visibility and metacontrast masking[END_REF][START_REF] Sergent | Timing of the brain events underlying access to consciousness during the attentional blink[END_REF]. Koivisto and collaborators have called this event the visual awareness negativity (VAN).

Several arguments, however, mitigate the possibility that these early or mid-latency differences already reflect conscious perception. First, they may not be necessary and sufficient, as they are absent from several experiments (e.g. [START_REF] Lamy | Neural Correlates of Subjective Awareness and Unconscious Processing: An ERP Study[END_REF][START_REF] Van Aalderen-Smeets | Investigating neurophysiological correlates of metacontrast masking with magnetoencephalography[END_REF] (although one cannot exclude that they failed to be detected). Second, and most crucially, their profile of variation with stimulus variables such as target-mask delay does not always track the variations in subject's conscious reports [START_REF] Del Cul | Brain dynamics underlying the nonlinear threshold for access to consciousness[END_REF][START_REF] Van Aalderen-Smeets | Investigating neurophysiological correlates of metacontrast masking with magnetoencephalography[END_REF]. Third, they typically consist only in small modulations that ride on top of early sensory activations that are still strongly present on non-conscious trials [START_REF] Del Cul | Brain dynamics underlying the nonlinear threshold for access to consciousness[END_REF][START_REF] Fahrenfort | Masking disrupts reentrant processing in human visual cortex[END_REF][START_REF] Sergent | Timing of the brain events underlying access to consciousness during the attentional blink[END_REF]. Fourth, in this respect they resemble the small electrophysiological modulations that have been found to partially predict later perception even prior to the stimulus (e.g. [START_REF] Boly | Baseline brain activity fluctuations predict somatosensory perception in humans[END_REF][START_REF] Palva | Early neural correlates of conscious somatosensory perception[END_REF][START_REF] Sadaghiani | Distributed and antagonistic contributions of ongoing activity fluctuations to auditory stimulus detection[END_REF][START_REF] Super | Internal state of monkey primary visual cortex (V1) predicts figure-ground perception[END_REF][START_REF] Wyart | How ongoing fluctuations in human visual cortex predict perceptual awareness: baseline shift versus decision bias[END_REF], where it logically impossible that they already participate in the neural mechanism of conscious access.

Thus, these early events may reflect fluctuations in prestimulus priors and in sensory evidence that contribute to subsequent conscious access, rather than be constitutive of a conscious state per se [START_REF] Dehaene | Ongoing spontaneous activity controls access to consciousness: a neuronal model for inattentional blindness[END_REF][START_REF] Wyart | How ongoing fluctuations in human visual cortex predict perceptual awareness: baseline shift versus decision bias[END_REF].

The evidence on this topic is still evolving, however, as a recent study found strong correlation of visibility with the P3b component when participants had no expectation of the stimuli, but a shift to the earlier P2 component when they already had a working memory representation of the target [START_REF] Melloni | Expectations change the signatures and timing of electrophysiological correlates of perceptual awareness[END_REF]. This study suggests that the timing of conscious access may vary with the experimental paradigm, and that a Bayesian perspective, taking into account the subject's prior knowledge at multiple hierarchical cortical levels [START_REF] Del Cul | Causal role of prefrontal cortex in the threshold for access to consciousness[END_REF][START_REF] Kiebel | A hierarchy of time-scales and the brain[END_REF], may be an essential conceptual ingredient that still needs to be integrated to the above synthesis.

Whether it takes 200 ms, 300 ms, or even more, the slow and integrative nature of conscious perception is confirmed behaviorally by observations such as the "rabbit illusion" and its variants [START_REF] Dennett | Consciousness explained[END_REF][START_REF] Geldard | The cutaneous 'rabbit': a perceptual illusion[END_REF][START_REF] Libet | Time of conscious intention to act in relation to onset of cerebral activity (readiness-potential). The unconscious initiation of a freely voluntary act[END_REF], where the way in which a stimulus is ultimately perceived is influenced by post-stimulus events arising several hundreds of milliseconds after the original stimulus. Psychophysical paradigms that rely on quickly alternating stimuli confirm that conscious perception integrates over ~100 ms or more, while non-conscious perception is comparatively much faster (e.g. [START_REF] Forget | Temporal integration in visual word recognition[END_REF]Vul and MacLeod, 2006).

Interestingly, recent research also suggests that spontaneous brain activity, as assessed by resting-state EEG recordings, may be similarly parsed into a stochastic series of slow "microstates", stable for at least 100 ms, each exclusive of the other, and separated by sharp transitions [START_REF] Lehmann | Spatio-temporal dynamics of alpha brain electric fields, and cognitive modes[END_REF][START_REF] Van De Ville | EEG microstate sequences in healthy humans at rest reveal scale-free dynamics[END_REF]. These microstates have recently been related to some of the fMRI resting-state networks [START_REF] Britz | BOLD correlates of EEG topography reveal rapid resting-state network dynamics[END_REF]. Crucially, they are predictive of the thought contents reported by participants when they are suddenly interrupted [START_REF] Lehmann | Core networks for visualconcrete and abstract thought content: a brain electric microstate analysis[END_REF][START_REF] Lehmann | Brain electric microstates and momentary conscious mind states as building blocks of spontaneous thinking: I. Visual imagery and abstract thoughts[END_REF]. Thus, whether externally induced or internally generated, the "stream of consciousness" may consist in a series of slow, global, and transiently stable cortical states [START_REF] Changeux | Mechanisms of neural integration at the brain-scale level. The neuronal workspace and microstate models[END_REF].

Can non-conscious stimuli produce a global ignition?

Another pillar of the proposed theoretical synthesis is that global ignition is unique to conscious states. This view would be challenged if some non-conscious stimuli were found to reproducibly evoked intense PFC activations, P3b waves, or late and distributed patterns of brain-scale synchronization. Taking up this challenge, some studies have indeed reported small but significant activations of prefrontal regions and a P3-like wave evoked by infrequent non-conscious stimuli [START_REF] Brazdil | Intracerebral event-related potentials to subthreshold target stimuli[END_REF][START_REF] Brazdil | Effect of subthreshold target stimuli on event-related potentials[END_REF][START_REF] Muller-Gass | Evidence for the auditory P3a reflecting an automatic process: elicitation during highly-focused continuous visual attention[END_REF][START_REF] Salisbury | Auditory event-related potentials during stage 2 NREM sleep in humans[END_REF]. However, this wave is usually a novelty P3a response, with a sharp midline anterior positivity suggesting focal anterior midline generators, rather than the global P3 or "late positive complex" response evoked by novel stimuli. Similarly, van Gaal et al. (2010a) used fMRI to examine which areas contributed to subliminal versus conscious processing of "no-go" signals -rare visual cues that instructed subjects to refrain from responding on this particular trial. Their initial observations suggested, provocatively, that subliminal no-go signals evoked prefrontal potentials corresponding to non-conscious executive processing [START_REF] Van Gaal | Frontal cortex mediates unconsciously triggered inhibitory control[END_REF]. Subsequent fMRI, however, indicated that the generators of the subliminal response inhibition effect were restricted to a small set of specialized processors in midline preSMA and the junction of the bilateral anterior insula with the inferior frontal gyrus. Only conscious no-go signals triggered a broad and more anterior activation expanding into anterior cingulate, inferior and middle frontal gyrus, dorsolateral prefrontal cortex and inferior parietal cortex -a network fully compatible with the GNW model (see figure 1).

Identifying the limits of nonconscious processing remains an active area of research, as new techniques for presentation of non-conscious stimuli are constantly appearing (e.g. [START_REF] Arnold | Binocular switch suppression: a new method for persistently rendering the visible 'invisible[END_REF][START_REF] Wilke | Generalized flash suppression of salient visual targets[END_REF]. A recent masking study observed that subliminal task-switching cues evoked detectable activations in premotor, prefrontal and temporal cortices [START_REF] Lau | Unconscious activation of the cognitive control system in the human prefrontal cortex[END_REF], but with a much reduced amplitude compared to conscious cues. Another more challenging study [START_REF] Diaz | Unconscious word processing engages a distributed network of brain regions[END_REF] reported a large network of cortical perisylvian regions (inferior frontal, inferior temporal and angular gyrus) activated by subliminal words relative to subliminal pseudowords, and surprisingly more extended than in previous reports (e.g. Dehaene et al., 2001).

Attentional blink studies also suggest that unseen words may cause surprisingly long-lasting ERP components (N400) (see also [START_REF] Gaillard | Subliminal words durably affect neuronal activity[END_REF][START_REF] Vogel | Electrophysiological evidence for a postperceptual locus of suppression during the attentional blink[END_REF]. A crucial question for future research is whether these activations remain confined to specialized subcircuits, for instance in the left temporal lobe [START_REF] Sergent | Timing of the brain events underlying access to consciousness during the attentional blink[END_REF], or whether they constitute true instances of global cortical processing without consciousness.

Do prefrontal and parietal networks play a causal role in conscious access?

Brain imaging is only correlational in nature, and leaves open the possibility that distributed ignition involving PFC is a mere epiphenomenon or a consequence of conscious access, rather than being one of its necessary causes. Causality is a demanding concept that can only be assessed by systematic lesion or interference methods, which are of very limited applicability in human subjects.

Nevertheless, one prediction of the GNW model is testable: lesioning or interfering with prefrontal or parietal cortex activity, at sites quite distant from visual areas, should disrupt conscious vision. This prediction was initially judged as so counter-intuitive as to be immediately refuted by clinical observations, because frontal lobe patients do not appear to be unconscious [START_REF] Pollen | On the neural correlates of visual perception[END_REF].

However, recent evidence actually supports the GNW account. In normal subjects, transcranial magnetic stimulation (TMS) over either parietal or prefrontal cortex can prevent conscious perception and even trigger a sudden subjective disappearance of visual stimulis during prolonged fixation [START_REF] Kanai | TMS over the intraparietal sulcus induces perceptual fading[END_REF], change blindness [START_REF] Beck | Right parietal cortex plays a critical role in change blindness[END_REF], binocularly rivalry [START_REF] Carmel | Right parietal TMS shortens dominance durations in binocular rivalry[END_REF], inattentional blindness [START_REF] Babiloni | Human ventral parietal cortex plays a functional role on visuospatial attention and primary consciousness. A repetitive transcranial magnetic stimulation study[END_REF], and attentional blink paradigms [START_REF] Kihara | Differential contributions of the intraparietal sulcus and the inferior parietal lobe to attentional blink: evidence from transcranial magnetic stimulation[END_REF]. Over prefrontal cortex, bilateral theta-burst TMS leads to a reduction of subjective visibility with preserved objective sensori-motor performance [START_REF] Rounis | Theta-burst transcranial magnetic stimulation to the prefrontal cortex impairs metacognitive visual awareness[END_REF]. We recently made similar observations in patients with focal prefrontal lesions [START_REF] Del Cul | Causal role of prefrontal cortex in the threshold for access to consciousness[END_REF]: their masking threshold was significantly elevated, in tight correlation with the degree of expansion of the lesions into left anterior prefrontal cortex, while subliminal performance on "not-seen" trials did not differ from normal. In more severe and diffuse cases, following traumatic brain injury, bilateral lesions of frontoparietal cortices or, characteristically, of the underlying white matter, can cause coma or vegetative state [START_REF] Tshibanda | Magnetic resonance spectroscopy and diffusion tensor imaging in coma survivors: promises and pitfalls[END_REF]. Frontal-lobe patients also suffer from impaired conscious processing, in such syndromes as hemineglect, abulia, akinetic mutism, anosognosia, or impaired autonoetic memory, while they frequently exhibit preserved or even heightened capacity for automatic action as indexed by utilization and imitation behaviors [START_REF] Husain | Visual neglect associated with frontal lobe infarction[END_REF][START_REF] Lhermitte | Utilization behaviour" and its relation to lesions of the frontal lobe[END_REF][START_REF] Passingham | The frontal lobes and voluntary action[END_REF]. Indeed, spatial hemineglect, in which conscious access fails for stimuli contralateral to the lesion, can arise from focal frontal lesions as well as from impairments of the long-distance fiber tracts linking posterior visual areas with the frontal lobe [START_REF] Bartolomeo | Left unilateral neglect as a disconnection syndrome[END_REF][START_REF] He | Breakdown of functional connectivity in frontoparietal networks underlies behavioral deficits in spatial neglect[END_REF][START_REF] Thiebaut De Schotten | Direct evidence for a parietal-frontal pathway subserving spatial awareness in humans[END_REF][START_REF] Urbanski | Brain networks of spatial awareness: evidence from diffusion tensor imaging tractography[END_REF] (figure 8).

While suggestive, these observations do not quite suffice to establish that a frontal contribution is causally necessary for conscious perception. Arguably, the above effects may not necessarily indicate a direct or central contribution of PFC to conscious access, but rather could be mediated by another brain structure under the influence of PFC or parietal networks, such as the thalamic nuclei. Also it is difficult to exclude a contribution of reduced top-down attention or enhanced distractibility in frontal patients or TMS subjects -although some studies have attempted to control for these factors by equalizing primary task performance [START_REF] Rounis | Theta-burst transcranial magnetic stimulation to the prefrontal cortex impairs metacognitive visual awareness[END_REF] or by demonstrating a preserved capacity for attentional modulation [START_REF] Del Cul | Causal role of prefrontal cortex in the threshold for access to consciousness[END_REF]. Ultimately, the crucial experiment would involve inducing a change in the actual conscious content, rather than a mere elevation of the reportability threshold, by stimulating PFC or other components of the GNW networks. While we know of no such experiment yet, micro-stimulation and optogenetic methods now make it feasible, at least in non-human animals.

Does the theory lead to clinical applications?

A strong test for any theory of consciousness is whether it can be clinically used. Conscious access is altered or reduced in three clinicial situations: schizophrenia, anesthesia, and loss of consciousness due to coma or vegetative state. Can the proposed theoretical synthesis shed some light on these issues?

Schizophrenia. [START_REF] Friston | Schizophrenia: a disconnection syndrome? Clinical neuroscience[END_REF] first hypothesized that schizophrenia results from a functional disconnection of long-distance prefrontal cortex projection affecting primarily the strength of N-methyl-D-aspartate receptor (NMDAR)-mediated synaptic transmission [START_REF] Niswender | Metabotropic glutamate receptors: physiology, pharmacology, and disease[END_REF]; see also [START_REF] Roopun | Region-specific changes in gamma and beta2 rhythms in NMDA receptor dysfunction models of schizophrenia[END_REF][START_REF] Stephan | Dysconnection in schizophrenia: from abnormal synaptic plasticity to failures of self-monitoring[END_REF]. [START_REF] Bullmore | The dysplastic net hypothesis: an integration of developmental and dysconnectivity theories of schizophrenia[END_REF] further suggested a disruption of anatomical connectivity possibly associated with an aberrant synaptic elimination during late adolescence and early adulthood [START_REF] Changeux | Selective stabilization of developing synapses as a mechanism for the specification of neuronal networks[END_REF][START_REF] Mcglashan | Schizophrenia as a disorder of developmentally reduced synaptic connectivity[END_REF], a possibility consistent with the fact that many potential risk genes are involved in neuronal and connectivity development [START_REF] Karlsgodt | Developmental disruptions in neural connectivity in the pathophysiology of schizophrenia[END_REF]. White matter tracks volume or density are, indeed, reduced in a number of regions, including the temporal and prefrontal lobes, the anterior limb of the internal capsule and the cingulum bundle [START_REF] Lynall | Functional connectivity and brain networks in schizophrenia[END_REF][START_REF] Oh | Thalamo-frontal white matter alterations in chronic schizophrenia: a quantitative diffusion tractography study[END_REF]. The cingulate fasciculus disconnection would, secondarily, impair the link to reward and emotional systems [START_REF] Holland | Amygdala-frontal interactions and reward expectancy[END_REF] thus possibly accounting for the known effect of dopaminergic neuroleptics.

Schizophrenia thus provides another possible test of the hypothesis that disruption of PFC longdistance connections impairs conscious access. Indeed, there is direct evidence for impaired neural signatures of conscious access, together with normal subliminal processing, in schizophrenic patients (Dehaene et al., 2003a;[START_REF] Del Cul | Preserved subliminal processing and impaired conscious access in schizophrenia[END_REF][START_REF] Luck | The speed of visual attention in schizophrenia: electrophysiological and behavioral evidence[END_REF]. As in frontal patients, the threshold for conscious access to masked visual stimuli is elevated in schizophrenia [START_REF] Del Cul | Preserved subliminal processing and impaired conscious access in schizophrenia[END_REF]. The P3b wave is typically delayed and reduced in amplitude, in both chronic and first-episode schizophrenics [START_REF] Demiralp | N2 and P3 components of event-related potential in first-episode schizophrenic patients: scalp topography, medication, and latency effects[END_REF][START_REF] Van Der Stelt | Impaired P3 generation reflects highlevel and progressive neurocognitive dysfunction in schizophrenia[END_REF] and their siblings [START_REF] Groom | Event-related potentials in adolescents with schizophrenia and their siblings: a comparison with attentiondeficit/hyperactivity disorder[END_REF]. Frontal slow waves associated with working memory are similarly impaired [START_REF] Kayser | ERP/CSD indices of impaired verbal working memory subprocesses in schizophrenia[END_REF]. Gamma-and beta-band power and long-distance phase synchrony are drastically reduced, even during simple perceptual tasks (Uhlhaas et al., 2006;Uhlhaas and Singer, 2006). By applying graph-theoretical tools to MEG recordings, [START_REF] Bassett | Cognitive fitness of cost-efficient brain functional networks[END_REF] observed that activation in the beta and gamma bands failed to organize into long-distance parieto-frontal networks that were "cost-efficient", i.e. had close to the minimal number of connections needed to confer a high efficiency of information transmission.

In summary, the neuronal processes of conscious access appear systematically deteriorated in schizophrenia.

Anesthesia. A classical question concerns whether general anesthetics alter consciousness by binding to molecular target sites, principally ion channels and ligand gated ion channels [START_REF] Forman | Anesthetic sites and allosteric mechanisms of action on Cysloop ligand-gated ion channels[END_REF][START_REF] Li | Numerous classes of general anesthetics inhibit etomidate binding to gamma-aminobutyric acid type A (GABAA) receptors[END_REF][START_REF] Nury | X-ray structures of general anaesthetics bound to a pentameric ligand-gated ion channel[END_REF] present all over the cortex, in specific and non-specific thalamic nuclei, or, as suggested by intracerebral microinjections [START_REF] Sukhotinsky | Neural pathways associated with loss of consciousness caused by intracerebral microinjection of GABA A-active anesthetics[END_REF], localized to specific sets of brain stem neurons (for review, see [START_REF] Alkire | Consciousness and anesthesia[END_REF][START_REF] Franks | General anaesthesia: from molecular targets to neuronal pathways of sleep and arousal[END_REF]. Anaestheticinduced loss of consciousness usually coincides with the disruption of activity in extensive regions of cerebral cortex, particularly the precuneus, posterior cingulate cortex, cuneus, localized regions of the lateral frontal and parietal cortices and occasionally the cerebellum [START_REF] Franks | General anaesthesia: from molecular targets to neuronal pathways of sleep and arousal[END_REF][START_REF] Kaisti | Effects of surgical levels of propofol and sevoflurane anesthesia on cerebral blood flow in healthy subjects studied with positron emission tomography[END_REF][START_REF] Veselis | Thiopental and propofol affect different regions of the brain at similar pharmacologic effects[END_REF]) (figure 9). Consistent with these views, [START_REF] Velly | Differential dynamic of action on cortical and subcortical structures of anesthetic agents during induction of anesthesia[END_REF] found that during induction of anesthesia by sevofurane and propofol in human patients with Parkinson disease, cortical EEG complexity decreased dramatically at the precise time where consciousness was lost, while for several minutes there was little change in subcortical ESCoG, and eventually a slow decline (figure 9). These data suggest that in humans, the early stage of anesthesia correlates with cortical disruption, and that the effects on the thalamus are indirectly driven by cortical feedback [START_REF] Alkire | Consciousness and anesthesia[END_REF]. Indeed, in the course of anesthesia induction, there is a decrease in EEG coherence in the 20 to 80 Hz frequency range between right and left frontal cortices and between frontal and occipital territories [START_REF] John | The anesthetic cascade: a theory of how anesthesia suppresses consciousness[END_REF]. Quantitative analysis of EEG under propofol induction further indicates a reduction of mean information integration, as measured by Tononi's Phi measure, around the γ-band (40Hz) and a breakdown of the spatiotemporal organisation of this particular band (Lee et al., 2009b). In agreement with experiments carried out with rats [START_REF] Imas | Volatile anesthetics enhance flash-induced gamma oscillations in rat visual cortex[END_REF][START_REF] Imas | Isoflurane disrupts anterio-posterior phase synchronization of flash-induced field potentials in the rat[END_REF], quantitative EEG analysis in humans under propofol anesthesia induction noted a decrease of directed feedback connectivity with loss of consciousness and a return with responsiveness to verbal command (Lee et al., 2009a). Also, during anesthesia induced by the benzodiazepine midazolam, an externally induced transcranial pulse evoked reliable initial activity monitored by ERPs in humans, but the subsequent late phase of propagation to distributed areas was abolished [START_REF] Ferrarelli | Breakdown in cortical effective connectivity during midazolam-induced loss of consciousness[END_REF].

These observations are consistent with the postulated role of top-down frontal-posterior amplification in conscious access (see also [START_REF] Super | Two distinct modes of sensory processing observed in monkey primary visual cortex (V1)[END_REF].

Coma and vegetative state. The clinical distinctions between coma, vegetative state [START_REF] Laureys | The neural correlate of (un)awareness: lessons from the vegetative state[END_REF], and minimal consciousness [START_REF] Giacino | The minimally conscious state: defining the borders of consciousness[END_REF] remain poorly defined, and even fully conscious but paralyzed patients with locked-in syndrome can remain undetected. It is therefore of interest to see if objective neural measures and GNW theory can help discriminate them. In coma and vegetative state, as with general anesthesia, global metabolic activity typically decreases to ~50% of normal levels [START_REF] Laureys | The neural correlate of (un)awareness: lessons from the vegetative state[END_REF]. This decrease is not homogeneous, however, but particularly pronounced in GNW areas including lateral and mesial prefrontal and inferior parietal cortices (figure 9). Spontaneous recovery from VS is accompanied by a functional restoration of this broad frontoparietal network [START_REF] Laureys | Cerebral metabolism during vegetative state and after recovery to consciousness[END_REF] and some of its cortico-thalamo-cortical connections [START_REF] Laureys | Restoration of thalamocortical connectivity after recovery from persistent vegetative state[END_REF]; see also [START_REF] Voss | Possible axonal regrowth in late recovery from the minimally conscious state[END_REF].

Anatomically, prediction of recovery from coma relies on the comprehensive assessment of all structures involved in arousal and awareness functions, namely, the ascending reticular activating system located in the postero-superior part of the brainstem and structures encompassing thalamus, basal forebrain, and fronto-parietal association cortices [START_REF] Tshibanda | Magnetic resonance spectroscopy and diffusion tensor imaging in coma survivors: promises and pitfalls[END_REF]. Lesion or inhibition of part of this system suffices to cause immediate coma (e.g. [START_REF] Parvizi | Neuroanatomical correlates of brainstem coma[END_REF]. Studies on traumatic coma patients with conventional MRI showed that lesions of the pons, midbrain, and basal ganglia were predictive of poor outcome especially when they were bilateral [START_REF] Tshibanda | Magnetic resonance spectroscopy and diffusion tensor imaging in coma survivors: promises and pitfalls[END_REF].

In relation with the GNW model, it is noteworthy that prediction of non-recovery after 1 year could be calculated with up to 86% sensitivity and 97% specificity when taking into account both diffusion tensor and spectroscopic measures of cortical white matter integrity [START_REF] Tshibanda | Magnetic resonance spectroscopy and diffusion tensor imaging in coma survivors: promises and pitfalls[END_REF].

The objective neural measures of conscious processing demonstrated earlier in this review should be applicable to the difficult clinical problem of detecting consciousness in non-communicating patients. Using fMRI, a few patient initially classified as vegetative by clinical signs showed essentially normal activations of distributed long-distance cortical networks during speech processing and mental imagery tasks [START_REF] Owen | Detecting awareness in the vegetative state[END_REF] and one patient proved able to voluntarily control them to provide yes/no answers to simple personal questions, clearly indicating some degree of preserved conscious processing (Monti et al.). In an effort to isolate a more theoretically validated scalp signature of conscious sensory processing, Bekinschtein et al. (2009a) recorded ERPs to local versus global violations of an auditory regularity. When hearing a deviant tone after a sequence of repeated standard tones (sequence XXXXY), a local mismatch response was elicited non-consciously even in coma and vegetative-state patients, as previously demonstrated (e.g. [START_REF] Fischer | Predictive value of sensory and cognitive evoked potentials for awakening from coma[END_REF]. However, when this sequence XXXXY was repeatedly presented, such that the final tone change could be expected, the presentation of a deviant monotonic sequence (XXXXX) engendered a P3b wave in normal subjects which was absent in coma patients and in most vegetative-state patients, but could still be observed in minimally conscious and locked-in patients. This paradigm, founded upon previous identification of the P3b component as a signature of conscious processing, is now undergoing validation as a means of identifying residual conscious processing in patients [START_REF] Faugeras | Probing consciousness in clinically defined vegetative patients with event-related potentials Neurology submitted[END_REF].

V. Conclusion and future research directions

The present review was deliberately limited to conscious access. Several authors argue however for additional, higher-order concepts of consciousness. For [START_REF] Damasio | Consciousness: An overview of the phenomenon and of its possible neural basis[END_REF], core consciousness of incoming sensory information requires integrating it with a sense of self (the specific subjective point of view of the perceiving organism) to form a representation of how the organism is modified by the information; extended consciousness occurs when this representation is additionally related to the memorized past and anticipated future (see also [START_REF] Edelman | The remembered present[END_REF]. For Rosenthal ( 2004), a higher-order thought, coding for the very fact that the organism is currently representing an information, is needed for that information to be conscious. Indeed, metacognition, or the ability to reflect upon thoughts and draw judgements upon them, is often proposed as a crucial ingredient of consciousness [START_REF] Cleeremans | Consciousness and metarepresentation: a computational sketch[END_REF][START_REF] Lau | A higher order Bayesian decision theory of consciousness[END_REF] (although see [START_REF] Kanai | Subjective discriminability of invisibility: A framework for distinguishing perceptual and attentional failures of awareness[END_REF], for evidence that metacognitive judgements can occur without conscious perception). In humans, as opposed to other animals, consciousness may also involve the construction of a verbal narrative of the reasons for our behavior [START_REF] Gazzaniga | Language, praxis, and the right hemisphere: clues to some mechanisms of consciousness[END_REF]. Although this narrative can be fictitious [START_REF] Wegner | The illusion of conscious will[END_REF], it would be indispensable to inter-individual communication [START_REF] Bahrami | Optimally interacting minds[END_REF][START_REF] Frith | Making up the mind. How the brain creates our mental world[END_REF].

Metacognition and self-representation have only recently begun to be studied behaviorally with paradigms simple enough to extend to non-human species [START_REF] Kiani | Representation of confidence associated with a decision by neurons in the parietal cortex[END_REF][START_REF] Terrace | Comparative metacognition[END_REF], and to be related to specific brain measurements, notably anterior prefrontal cortex [START_REF] Fleming | Relating introspective accuracy to individual differences in brain structure[END_REF]. Thus, our view is that these concepts, although essential, have not yet received a sufficient empirical and neurophysiological definition to figure in this review. Following Crick and Koch [START_REF] Crick | Some reflections on visual awareness[END_REF], we focussed solely here on the simpler and well-studied question of what neurophysiological mechanisms differentiate conscious access to some information from nonconscious processing of the same information. Additional work will be needed to explore, in the future, these important aspects of higher-order consciousness.

In the present state of investigations, experimental measures of conscious access identified in this review include: (1) sudden, all-or-none ignition of prefronto-parietal networks; (2) concomitant all-or-none amplification of sensory activation; (3) a late global P3b wave in eventrelated potentials; (4) late amplification of broad-band power in the gamma range; (5) enhanced long-distance phase synchronization, particularly in the beta range; (6) enhanced causal relations between distant areas, including a significant top-down component. Many of these measures are also found during complex serial computations and in spontaneous thought. There is evidence that they rely on an anatomical network of long-distance connections that is particularly developed in the human brain. Finally, pathologies of these networks or their long-distance connections are associated with impairments of conscious access.

In the future, as argued by [START_REF] Haynes | Decoding visual consciousness from human brain signals[END_REF], the mapping of conscious experiences onto neural states will ultimately require, not only a neural distinction between seen and not-seen trials, but a proof that the proposed conscious neural state actually encodes all the details of the participant's current subjective experience. Criteria for a genuine one-to-one mapping should include verifying that the proposed neural state has the same perceptual stability (for instance over successive eye movements) and suffers from the same occasional illusions as the subject's own report. Multivariate decoding techniques provide pertinent tools to address this question, and have already been used to infer conscious mental images from early visual areas (Haynes and Rees, 2005;[START_REF] Thirion | Inverse retinotopy: inferring the visual content of images from brain activation patterns[END_REF] and from inferotemporal cortex [START_REF] Schurger | Reproducibility distinguishes conscious from nonconscious neural representations[END_REF][START_REF] Sterzer | Fine-scale activity patterns in high-level visual areas encode the category of invisible objects[END_REF]. However, decoding the more intermingled neural patterns expected from PFC and other associative cortices is clearly a challenge for future research (though see [START_REF] Fuentemilla | Theta-coupled periodic replay in working memory[END_REF].

Another important question concerns the genetic mechanisms that, in the coure of biological evolution, have led to the development of the GNW architecture, particularly the relative expansion of PFC, higher associative cortices and their underlying long-distance white-matter tracts in the course of hominisation (see [START_REF] Avants | Lagrangian frame diffeomorphic image registration: Morphometric comparison of human and chimpanzee cortex[END_REF][START_REF] Schoenemann | Prefrontal white matter volume is disproportionately larger in humans than in other primates[END_REF][START_REF] Semendeferi | Humans and great apes share a large frontal cortex[END_REF].

Finally, now that measures of conscious processing have been identified in human adults, it should become possible to ask how they transpose to lower animal species [START_REF] Changeux | The Ferrier Lecture 1998. The molecular biology of consciousness investigated with genetically modified mice[END_REF][START_REF] Changeux | Nicotine addiction and nicotinic receptors: lessons from genetically modified mice[END_REF] and to human infants and foetuses [START_REF] Dehaene-Lambertz | Functional neuroimaging of speech perception in infants[END_REF][START_REF] Gelskov | Psychophysical thresholds of face visibility during infancy[END_REF][START_REF] Lagercrantz | The emergence of human consciousness: from fetal to neonatal life[END_REF], in whom genuine but immature long-distance networks have been described [START_REF] Fair | Functional brain networks develop from a "local to distributed" organization[END_REF][START_REF] Fransson | Resting-state networks in the infant brain[END_REF]. A. An early fMRI experiment contrasting the fMRI activations evoked by brief presentations of words that were either readable (left) or made invisible by masking (right) (Dehaene et al., 2001).

Figure legends

Non-conscious word processing activated the left occipito-temporal visual word form area, but conscious perception was characterized by (a) an intense amplification of activation in relevant nonconscious processors, here the visual word form area (left occipito-temporal cortex; see middle graph); (b) an additional spread of activation to a distributed, though restricted set of associative cortices including inferior parietal, prefrontal and cingulate areas. B. fMRI study of threshold-level noises, approximately half of which were consciously detected [START_REF] Sadaghiani | Distributed and antagonistic contributions of ongoing activity fluctuations to auditory stimulus detection[END_REF]. Bilateral auditory areas showed a non-conscious activation, which was amplified and spread to distributed inferior parietal, prefrontal and cingulated areas (for similar results with tactile stimuli, see [START_REF] Boly | Baseline brain activity fluctuations predict somatosensory perception in humans[END_REF]. C, fMRI study of inhibitory control by a visible or invisible cue (van Gaal et al., 2010a).

Subjects were presented with masked visual shapes, at the threshold for conscious perception, some of which occasionally required inhibiting a response (go/nogo task). Small activations to the nonconscious no-go signal were detected in the inferior frontal and preSMA cortices, but inhibitory control by a conscious no-go signal was associated with fMRI signal amplification (see the difference between no-go and go signals in middle graphs), and massive spread of the activation to additional and more anterior areas including prefrontal, anterior cingulate and inferior parietal cortices. during the attentional blink, as a function of whether it was reported as seen or unseen [START_REF] Sergent | Timing of the brain events underlying access to consciousness during the attentional blink[END_REF]. Early events (P1 and N1) were strictly identical, but the N2 event was amplified and the P3 events (P3a and P3b) were present essentially only during conscious perception. B. Manipulation of visibility by varying the temporal asynchrony between a visual stimulus and a subsequent mask [START_REF] Del Cul | Brain dynamics underlying the nonlinear threshold for access to consciousness[END_REF]. A non-linearity, defining a threshold value for conscious access, was seen in both subjective visibility reports and the P3b event amplitude. Source modelling related this P3b to a sudden non-linear ignition, about 300 ms after stimulus presentation, of distributed sources including inferior prefrontal cortex, with a simultaneous re-activation of early visual areas. Note the two-stage pattern of fusiform activation, with an early linear activation followed by a late non-linear ignition. C. Magneto-encephalography correlates of the attentional blink [START_REF] Gross | Modulation of long-range neural synchrony reflects temporal limitations of visual attention in humans[END_REF]. On perceived trials, induced power and phase synchrony increased in the low beta band (13-18 Hz), in a broad network dominated by right inferior parietal and left prefrontal sites.

Figure 3. Intracranial potentials during conscious access

Intracranial local-field potentials were recorded during stimulation with masked or unmasked words from a total of 10 patients implanted with deep intracortical electrodes [START_REF] Gaillard | Converging intracranial markers of conscious access[END_REF].

Four intracranial signatures of conscious access were identified. A. Although invisible words elicited event-related potentials, mostly early (<300 ms) and at posterior sites, only visible words elicited massive and durable voltages in a late time window, particularly from the few available frontal electrodes. B. Gamma-band power increases were detectable for invisible words, but in a late time window (>300 ms) gamma power was massively amplified when the words were visible, particularly in the high-gamma range (50-100 Hz). C. Phase synchrony increased for invisible words in a late time window (300-500 ms) in the beta frequency range (13-30 Hz). D. Causal relations across distant electrodes, assessed by Grainger causality gain due to word presence, increased massively during the same time window. The inset shows causal gain for a particular electrode pair as a function of time.

Increases were bidirectional but dominant in the bottom-up direction (e.g. occipital-to-frontal), compatible with the idea of posterior information "accessing" more anterior sites. All time scales are relative to stimulus onset. Single cells were recorded from the human medial temporal lobe and hippocampus during presentation of masked pictures, with a variable target-mask delay [START_REF] Quiroga | Human single-neuron responses at the threshold of conscious recognition[END_REF]. The example at left shows a single cell that fired specifically to pictures of the World Trade Center, and did so only on trials when the patient recognized the picture (dark blue raster plots), not on trials when recognition failed (red raster plots). Graphs at right show the average firing rate across all neurons. Although a small transient firing could be seen on unrecognized trials, conscious perception was characterized by a massive and durable amplification of activity (for complementary results in occipito-temporal areas, see also [START_REF] Fisch | Neural ''Ignition'': Enhanced Activation Linked to Perceptual Awareness in Human Ventral Stream Visual Cortex[END_REF]. the effortful execution of a novel task (but not after its routinization); (c) after errors, or whenever higher control is needed. B, C, D. Example of corresponding global fronto-parietal activations as seen with fMRI. B, Strong activation of a distributed network involving PFC during effortful search for the solution of a "master-mind" type problem, with a sudden collapse as soon as a routine solution is found (adapted from [START_REF] Landmann | Dynamics of Prefrontal and Cingulate Activity during a Reward-Based Logical Deduction Task[END_REF]. C, Activation of inferior PFC during dual-task performance which diminishes with training (adapted from [START_REF] Dux | Training improves multitasking performance by increasing the speed of information processing in human prefrontal cortex[END_REF]. D, activation of a distribution parieto-prefrontal-cingulate network on error and conflict trials (adapted from the metaanalysis by [START_REF] Klein | Neural correlates of error awareness[END_REF]. According to [START_REF] Baars | A cognitive theory of consciousness[END_REF], conscious access occurs once information gains access to a global workspace (bottom left) which broadcasts it to many other processors. The global neuronal workspace (GNW) hypothesis (right) proposes that associative perceptual, motor, attention, memory and value areas interconnect to form a higher-level unified space where information is broadly shared and broadcasted back to lower-level processors. The GNW is characterized by its massive connectivity, made possibly by thick layers II/III with large pyramidal cells sending long-distance cortico-cortical axons, particularly dense in prefrontal cortex [START_REF] Dehaene | A neuronal model of a global workspace in effortful cognitive tasks[END_REF]. A. Massive drops in cortical metabolism observed with PET rCBF measurements in slow-wave sleep [START_REF] Maquet | Functional neuroanatomy of human slow wave sleep[END_REF], anesthesia [START_REF] Kaisti | Effects of surgical levels of propofol and sevoflurane anesthesia on cerebral blood flow in healthy subjects studied with positron emission tomography[END_REF] and vegetative state [START_REF] Laureys | Brain function in coma, vegetative state, and related disorders[END_REF].

B. Reduced activity in a "resting-state" distributed cortical network in three vegetative state patients, as measured by independent component analysis of fMRI data [START_REF] Cauda | Disrupted intrinsic functional connectivity in the vegetative state[END_REF]. C. Sudden change in dimensional activation, a non-linear dynamics measure of EEG complexity, at the precise point of loss of consciousness during anesthesia [START_REF] Velly | Differential dynamic of action on cortical and subcortical structures of anesthetic agents during induction of anesthesia[END_REF]. Signals were measured from the scalp as well as from the thalamus using depth electrodes (left). Only the scalp (cortical) EEG showed a dramatic and discontinuous change accompanying loss of consciousness (right).

  architecture can explain the close similarity of the brain activations seen during (a) conscious access to a single external stimulus; (b) effortful serial processing; (c) spontaneous fluctuations in the absence of any stimulus or task.

Figure 1 .

 1 Figure 1. fMRI measures of conscious access

Figure 2 .

 2 Figure 2. Electro-and magneto-encephalography measures of conscious access

Figure 4 .

 4 Figure 4. Human single-cell recordings during conscious access

Figure 5 .

 5 Figure 5. Recruitment of global fronto-parietal networks in effortful serial tasks

Figure 6 .

 6 Figure 6. Historical steps in the development of models of conscious processing

Figure 7 .

 7 Figure 7. Schematic representation of the hypothesized events leading to conscious access

Figure 9 .

 9 Figure 9. Cortical measures of loss of consciousness in sleep, anesthesia and vegetative state.

Dehaene & Changeux, Figure2.

Dehaene & Changeux, Figure 4.

Dehaene & Changeux, Figure5.

Dehaene & Changeux, Figure9.

Acknowledgements

We gratefully acknowledge extensive discussions with Lionel Naccache, Sid Kouider, Jérôme Sackur, Bechir Jarraya and Pierre-Marie Lledo as well as commentaries on previous drafts by Stuart Edelstein, Raphaël Gaillard, Biyu He, Henri Korn and two expert referees. Supported by Collège de France, INSERM, CNRS, European Research Council (SD), and Skaggs Research Foundation at UCSD School of Pharmacy (JPC).

interpretations of the stimuli. Multiple signals converge to support each other's interpretation in higher-level cortical areas. Higher areas feedback onto lower-level sensory representations, favoring a convergence towards a single coherent representation compatible with current goals. Such a selfconnected system exhibits a dynamical threshold: if the incoming activity carries sufficient weight, it leads to the ignition of a self-supporting, reverberating, temporary, metastable, and distributed cell assembly that represents the current conscious contents and broadcasts it to virtually all distant sites.

B. Architecture of an explicit neuronal simulation model of a small part of the GNW architecture (adapted from [START_REF] Dehaene | Ongoing spontaneous activity controls access to consciousness: a neuronal model for inattentional blindness[END_REF]Dehaene et al., 2003b). The model contains thalamic and cortical excitatory and inhibitory neurons, organized in layers with realistic interconnections (inset). Stimuli T1 and T2 can be presented at the lower level of a hierarchy of four successive areas, linked by feedforward (AMPA) nearest-neighbor connections and by global feedback (NMDA connections).

C. Simulation of two single trials in which a identical pulse of brief stimulation was applied to sensory inputs for T1 [START_REF] Dehaene | Ongoing spontaneous activity controls access to consciousness: a neuronal model for inattentional blindness[END_REF]. Fluctuations in ongoing activity prevented ignition in the left diagram, resulting in a purely feedforward propagation dying out in higher-level areas. In the right diagram, the same stimulus crossed the threshold for ignition, resulting in selfamplification, a global state of activation, oscillation and synchrony, and a late long-lasting wave of late activation reaching back to early sensory areas.