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Neuroscience and Biobehavioral Reviews 37 (2013) 726–738

Contents lists available at SciVerse ScienceDirect

Neuroscience and Biobehavioral Reviews

journa l h o me pa g e: www.elsev ier .com/ locate /neubiorev

ommentary

hat the brain’s intrinsic activity can tell us about consciousness? tri-dimensional view

eorg Northoff ∗

niversity of Ottawa Institute of Mental Health Research, Canada

r t i c l e i n f o

rticle history:eceived 9 October 2012ccepted 3 December 2012

eywords:onsciousnessontentevelorm

a b s t r a c t

Current neuroscience applies a bi-dimensional model to consciousness. Content and level of conscious-ness have been distinguished from each other in their underlying neuronal mechanisms. This thoughleaves open the role of the brain’s intrinsic activity and its particular temporal and spatial structure inconsciousness. I here review and investigate the spatial and temporal features of the brain’s intrinsicactivity in detail and postulate what I describe as spatiotemporal structure that implies a virtual (e.g.,statistically based) spatiotemporal continuity. Such spatiotemporal continuity is supposed to structureand organize the neural processing of the incoming extrinsic stimuli and their potential association withconsciousness. I therefore conclude that the current bi-dimensional view of consciousness focusing only

patiotemporal continuityntrinsic activityepressionchizophreniaeural correlateseural prerequisites

on content and level may need to be complemented by a third dimension, the form, e.g., spatiotemporalstructure, as provided by the intrinsic activity. In short, I here opt for tri-rather than bi-dimensional viewof consciousness.

© 2012 Elsevier Ltd. All rights reserved.

eural predisposition

. Introduction

Consciousness is a multidimensional phenomenon. Philoso-hers emphasize the subjective and phenomenal-qualitativeimension when they characterize it by ‘What it is like’, i.e.,ualia (see Nagel, 1974; Chalmers, 1996). This concerns what

s described as phenomenal consciousness as distinguished fromther more cognitive forms like access consciousness, reflectiveonsciousness, etc. (see Block, 2005). While there have been manyuggestions for the different cognitive forms of consciousnesssee for instance, Augustenborg, 2010, for recent overview), theeuronal mechanisms underlying the subjective and phenomenal-ualitative dimension and thus phenomenal consciousness remainnclear. The focus in this paper will therefore be on phenomenalonsciousness in the following which is also implied when usinghe term consciousness by itself.

Several suggestions for neuronal mechanisms underlying phe-omenal consciousness have been made. These range fromeuronal synchronization (Buzsáki, 2006; Llinas et al., 1998; Koch,

∗ Correspondence address: Royal Ottawa Healthcare Group, University of Ottawanstitute of Mental Health Research, 1145 Carling Avenue, Room 6467, Ottawa, ON1Z 7K4, Canada. Tel.: +1 613 722 6521x6801; fax: +1 613 798 2982.

E-mail address: georg.northoff@theroyal.caURL: http://www.theroyal.ca/northoff.

149-7634/$ – see front matter © 2012 Elsevier Ltd. All rights reserved.ttp://dx.doi.org/10.1016/j.neubiorev.2012.12.004

2004; Crick and Koch, 2003) over thalamo-cortical re-entrantprocessing (Edelman, 2003, 2005) to global workspace (Baars,2005; Dehaene and Changeux, 2011; Dehaene et al., 2006) andinformation integration (see Seth et al., 2011a,b; Tononi, 2004;Tononi and Koch, 2008). These neuronal mechanisms describe thesufficient neural conditions of consciousness, the neural correlatesof consciousness (NCC). As such the NCC focus on those neuronalmechanisms that underlie the difference between conscious andunconscious content. Some authors (Hohwy, 2009) therefore alsospeak of content-based NCC.

In addition to the sufficient neural conditions, there may yetbe another set of neural conditions involved in consciousness.Namely those neural conditions that need to be fulfilled while theythemselves alone are not sufficient to induce consciousness. Theseconcern for instance neural activity in the brain stem or midbrainthat by themselves may be necessary but not sufficient for con-sciousness. These regions have been mainly associated with arousaland awakening and thus with what is often described as level; thelevel complements the contents thus leading to a bi-dimensionalview of consciousness (see Cavanna et al., 2008; Cavanna andMonaco, 2009; Laureys et al., 2005; Hohwy, 2009).

In addition to the content- and level-based NCC, recent sugges-

tions also considered the brain’s intrinsic activity to be relevant forconsciousness. One proposal suggests the low frequency fluctua-tions and their long time windows to be ideally suited to integratemuch information and to consecutively yield consciousness (see He

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nd Raichle, 2009). Another suggestion focuses more on the gammascillations (40 Hz) and their reactivity to external stimuli as cen-ral for consciousness (Llinas et al., 1998; Llinás, 2002). Finally, theevel of intrinsic activity in especially fronto-parietal networks mayerve as threshold and thus gate for the induction of neural activityhanges during extrinsic stimuli (see Dehaene and Changeux, 2005,011, see also Kleinschmidt et al., 2012).

The possible relevance of the brain’s intrinsic activity for con-ciousness is further underscored by results from functional brainmaging. Several studies demonstrated that the pre-stimulus levelf neural activity in either the same or another region predictedhe degree of stimulus-induced activity elicited by an extrinsictimulus (see, Boly et al., 2008; Hesselmann et al., 2008a,b, 2009;leinschmidt et al., 2012; Northoff et al., 2011a,b, for reviews).

n addition to the stimulus-induced activity itself, its associatedehaviour (e.g., reaction time) and perception (e.g., selection of aarticular content as in bistable perception) were also predicted byhe level and degree of the pre-stimulus activity.

Taken together, these results suggest a central for the brain’sntrinsic activity in consciousness. What this role is remains unclearhough. The intrinsic activity itself occurs prior to the onset ofxtrinsic stimuli that form the basis for the subsequent contentsf consciousness. The intrinsic activity itself can thus not be con-idered a sufficient condition of the contents of consciousness andhus NCC. This raises the question whether the intrinsic activitys an enabling condition, e.g., a neural prerequisite (deGraaf et al.,012; Aru et al., 2012) or even a neural cause of consciousness (seeeisser, 2012).

How though and in which way does the brain’s intrinsic activityake possible the association of consciousness to mere extrinsic

timulus-induced activity? We currently do not know. The presentaper takes a detailed look at the brain’s intrinsic activity andore specifically its spatial and temporal features. Based on recent

mpirical data I suggest the brain’s intrinsic activity to constitute airtual statistically based neural continuum between different dis-rete points in time and space. The low frequency fluctuations andhe (resting state) functional connectivity as neuronal hallmarks ofhe intrinsic activity may thereby be central. This leads to a virtualtatistically based intrinsic spatiotemporal continuity that struc-ures and organizes the incoming extrinsic stimuli in space andime.

By employing its spatiotemporal continuity, the intrinsic activ-ty and its spatiotemporal structure imposes a template, grid or

atrix on its own subsequent neural processing of extrinsic stimuli.ne may therefore speak of a form, e.g., structure or organization,

hat is provided by the intrinsic activity. Such form in the gestaltf spatiotemporal continuity may make possible and thus predis-ose the extrinsic stimulus-induced activity to be associated withonsciousness.

Why and how can the intrinsic activity and its spatiotemporaltructure predispose consciousness? Because such spatiotemporaltructure is also manifest in our subjective experience of extrinsictimuli and thus in the temporal and spatial features of conscious-ess. In other terms, the neuronally constituted spatiotemporaltructure of the intrinsic activity may be transferred to and thusanifest in our phenomenal states of consciousness. I propose that

uch transfer first and foremost makes possible the generationf consciousness. Without such form consciousness may remainmpossible at all. One may therefore want to complement the cur-ent bi-dimensional view of consciousness, e.g., level and content,y a third dimension, e.g., form, leading to a tri-dimensional view.

The aim of this paper is to discuss the possible role of the

rain’s intrinsic activity in yielding consciousness, e.g., phenomenalonsciousness. I hypothesize that by constituting spatiotemporalontinuity via its functional connectivity and frequency fluc-uations, the intrinsic activity predisposes the association of

ioral Reviews 37 (2013) 726–738 727

consciousness to extrinsic stimulus-induced activity. This makesnecessary the assumption of form as third dimension of conscious-ness besides content and level. In short, I here opt for a tri-ratherthan bi-dimensional view of consciousness.

This has also major implications for how to define the conceptof the neural correlates of consciousness (NCC) which is soughtrecently to be complemented by other concepts like neural pre-requisites, neural causes, and neural consequences (see deGraafet al., 2012; Aru et al., 2012; Neisser, 2012) (see below for details).The NCC and its recent differentiation into neural prerequisites,neural causes, and neural consequences concern the realizationand manifestation of actual consciousness. They do therefore focuson those neuronal mechanisms related to extrinsic activity, e.g.,stimulus-induced activity, that must occur in order to realize actualconsciousness.

This is different in the case of the intrinsic activity and its spa-tiotemporal structure. Here the focus is more on those conditionsthat first and foremost make possible any kind of consciousnessreflecting those neural mechanisms that predispose rather thanrealize consciousness. I will therefore characterize the intrinsicactivity and the form it provides as neural predisposition of con-sciousness (NPC) rather than as neural correlate of consciousness(NCC).

2. Intrinsic activity and spatiotemporal continuity

2.1. Intrinsic activity and consciousness

How does the brain’s intrinsic activity relate to consciousness?The term intrinsic activity describes spontaneous activity gener-ated inside the brain itself (see Logothetis et al., 2009; Northoff,2012a for details). Since the observation of spontaneous activityimplies the absence of extrinsic stimuli and is thus mere rest, theterm intrinsic activity is often used interchangeably with ‘restingstate activity’ in especially an experimental-operational context(see also Logothetis et al., 2009 for a discussion on the concept ofthe resting state). The brain’s intrinsic activity has recently alsobeen considered a candidate mechanism of consciousness (seeLundervold, 2010 for a more technical overview as well as Northoff,2012b for a detailed discussion of the different theories).

One recent proposal suggests that the resting state’s slow wavefluctuations in the frequency ranges between 0.001 and 4 Hz arecentral in yielding consciousness (He et al., 2008; He and Raichle,2009; Raichle, 2009): due to the long time windows of their ongo-ing cycles, i.e., phase durations, the slow wave fluctuations may beparticularly suited to integrate different information together. Suchinformation integration may then allow for the respective con-tent to become associated with consciousness (see also Fingelkurtset al., 2010 for the consideration of the resting state’s functionalconnectivity and low frequency fluctuations in the context of con-sciousness).

Another suggestion for the central role of the resting state inconsciousness comes from Llinas et al. (1998) and Llinás (2002). Heinvestigated subjects in the awake state and during sleep. Conduct-ing MEG studies, he observed that 40 Hz oscillations are presentin both the awake and sleeping (REM sleep) states. Both statesdiffered from each other though in that a sensory stimulus couldreset (and thus modulate) the 40 Hz oscillations only in the awakestate but not during REM-sleep state (where we dream). Hence,the neural reactivity of the resting state to external stimuli seemsto distinguish the awake state from REM sleep.

The same was observed in NREM-sleep that showed a similarnon-reactivity to external stimuli. In addition, NREM-sleep alsoexhibited reduced amplitude in the 40 Hz oscillations which dis-tinguished it from REM-sleep. Hence, the reactivity of the 40 Hz

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scillations and their amplitude seems to distinguish REM- andREM-sleep. This underlines the central importance of the resting

tate and especially of its interaction with stimuli, i.e., rest-stimulusnteraction (see also Freeman, 2003, 2010 as well as Northoff et al.,010a,b as well as Volume I, Part IV, Chapter 2), in yielding con-ciousness.

Another theory central for connecting intrinsic activity to con-ciousness comes from Dehaene (Dehaene and Changeux, 2005,011). Depending on the timing of the stimulus relative to the ongo-

ng spontaneous phase fluctuations, the stimulus may or may notead to the recruitment of the fronto-parietal neurons and network

hich they consider to be central in allowing for conscious access.If for instance the spontaneous firing activity in the fronto-

arietal network is too strong and continuous, it can block and thusrevent its ignition by the external stimulus. Since Dehaene andhangeux assume the fronto-parietal network to be a global neu-onal workspace that is necessary for consciousness, the stimulusay consecutively be ‘denied’ conscious access and remain thus

nconscious, i.e., pre-conscious (see also, Kleinschmidt et al., 2012,or the relevance of pre-stimulus resting state activity).

Taken together these proposals provide support for a centralole of the brain’s intrinsic activity in consciousness. They thougheave open why and how the intrinsic activity, the brain’s input, canreate the tendency or predisposition to generate consciousness:ithout intrinsic activity consciousness, e.g., its special subjective

nd phenomenal-qualitative features, would not even be possible.ence, the intrinsic activity is necessary and thus indispensable

or the possibility of consciousness, while the intrinsic activity isusually) not sufficient by itself to generate actual, e.g., manifest,onsciousness.

The intrinsic activity seems to add a special feature to the neuralrocessing of extrinsic stimuli that predisposes their possible asso-iation with consciousness in the ‘right’ circumstances. What is thispecial feature? For that we may want to shed a more detailed viewn the temporal and spatial organization of the brain’s intrinsicctivity. This is the focus in the next sections.

.2. Intrinsic activity and temporal continuity

There seems to be also quite an elaborate temporal structure inhe brain’s intrinsic activity. Such a temporal structure seems to beased upon the fluctuations of the intrinsic activity in different fre-uency ranges. Spontaneous fluctuations of neural activity in theesting state are often observed in especially the default-mode net-ork (DMN) where they are characterized predominantly by low

requencies (<0.1 Hz).However, low (and high) frequency fluctuations in neural activ-

ty can also be observed in regions other than the DMN like sensoryortices, motor cortex, insula, and subcortical regions (like basalanglia and thalamus) (see Freeman, 2003; Buckner et al., 2008;ang et al., 2007; Hunter et al., 2006; Zhou et al., 2011). Rather

han being a specific of the DMN per se, low frequency fluctuationseem to be a hallmark feature of neural activity in general.

Further support for spontaneous resting state activity acrosshe whole brain comes from electrophysiological studies showingpontaneous neuronal oscillations and synchronizations in variousarts of the brain including the hippocampus and visual cortexBuzsáki, 2006; Buzsaki and Draguhn, 2004; Arieli et al., 1996;linas et al., 1998; Singer, 2009; Fries et al., 2001, 2007). This sug-ests that spontaneous fluctuations and thus intrinsic activity maye prevalent throughout the whole brain in both humans and ani-als and not be limited to the DMN.

Let us be more specific. The spontaneous BOLD fluctuations as

bserved in FMRI are to be found in lower frequency ranges includ-ng the delta band (1–4 Hz), up- and -down states (0.8 Hz) andnfra-slow fluctuations (ISFs) (0.001–0.1 Hz). The slow frequency

ioral Reviews 37 (2013) 726–738

fluctuations observed in fMRI have been assumed to correspond towhat is measured as slow cortical potentials (SCP) in EEG (Khaderet al., 2008; He and Raichle, 2009).

The SCP are not easy to obtain in EEG because they are subjectto artefact caused by sweating, movements, and electrode drift;their measurement therefore requires more direct measurementby so-called DC (Direct current) recording. There is some evidencefor that what is measured as SCP in EEG corresponds to, is relatedto, or even identical to the low frequency fluctuations obtained inFMRI (see He and Raichle, 2009 as well as Khader et al., 2008 forreviews).

In addition to such low frequency fluctuations, there are alsohigher frequency fluctuations in the brain’s resting state activity.These fluctuations cover frequency ranging from 1 Hz and higherthus including delta (1–4 Hz), theta (4–8 Hz), alpha (8–12 Hz),beta (12–30 Hz), and gamma (>30 Hz) (see Mantini et al., 2007;Sadaghiani et al., 2010).

This raises the question how low and high frequencies arerelated to each other in the brain’s resting state (see also the recentreviews by Fries, 2005; Canolty and Knight, 2010; Sauseng andKlimesch, 2008; Fell and Axmacher, 2011). For instance, Vanhataloet al. (2004) conducted an EEG study in healthy and epileptic sub-jects during sleep and thus during rest where, using DC-EEG, theywere able to record low frequency oscillations. All subjects showedinfraslow oscillations (0.02–0.2 Hz); these were seen widespreadover all electrodes and thus the whole brain without showing anyspecific visually obvious spatial distribution.

Most interestingly, they observed phase-locking or phase-synchronization between the slow (0.02–0.2 Hz) oscillations andthe amplitudes of the faster (1–10 Hz) oscillations: the ampli-tudes of the high frequency oscillations (1–10 Hz) were the highestduring the negative deflection of the slow frequency oscillations(0.02–0.2 Hz). Even the higher-frequent K-complexes that are char-acteristic for sleep as well as interictal epileptiform events werephase-locked to the slow frequency oscillations in that the formeroccurred preferentially in the negative deflection phases of the lat-ter.

An analogous phase-locking of high frequency oscillations’power to the phases of lower ones can also be described as phase-power coupling (with phase-phase and power-power coupling alsobeing possible) (see Canolty and Knight, 2010 as well as Sausengand Klimesch, 2008 for excellent reviews). Such low-high fre-quency entrainment may not only occur during the resting stateas described by the above mentioned study but also during rest-stimulus interaction (Northoff et al., 2010a,b) where it may becentral in integrating and embedding the stimuli (and their respec-tive contents) into the ongoing temporal structure of the brain’sintrinsic activity (Fig. 1).

Taken together, there seems to be a complex temporal structureand organization of the brain’s intrinsic activity. Most importantly,this temporal structure seems to bridge the temporal gaps betweendifferent discrete points in time. By linking together neural activi-ties at different discrete points in time, a certain degree of temporalcontinuity in the brain’s intrinsic activity is constituted. How isthe intrinsic activity’s temporal continuity related to the abovedescribed temporal continuity of consciousness? Before addressingthis question, I need to briefly explore the constitution of spatialcontinuity in the brain’s intrinsic activity.

2.3. Intrinsic activity and spatial continuity

The resting state activity can be characterized by both spatial

and temporal dimensions. This is reflected in functional con-nectivity and low frequency fluctuations (see above as well asRaichle, 2009; Northoff, 2012a). Functional connectivity describesthe linkage between the neural activities of different regions

G. Northoff / Neuroscience and Biobehavioral Reviews 37 (2013) 726–738 729

Fig. 1. The figure illustrates schematically the constitution of the supposed generation of temporal (a) and spatial (b) continuity by the brain’s intrinsic activity. (a) Thebrain shows intrinsic activity independent of the extrinsic stimuli from the environment. The intrinsic activity shows fluctuations in different frequency ranges ranging frominfraslow to fast (000.1–60 Hz) (red lines). High and low frequency fluctuations are connected to each other via their phases and power (yellow lines). For instance, the phasesof low frequency fluctuations align themselves to the power of higher ones resulting in phase shifting and phase-power coupling. This makes it possible for the intrinsicactivity to bridge the temporal gaps between the neural activities at different discrete points in physical time within the brain itself. There is consequently continuity ofneural activity across different time points, a neuro-temporal continuity as one may say, as constituted by the brain’s intrinsic activity itself. (b) The brain shows intrinsicactivity independent of the extrinsic stimuli from the environment. The neural activities at different regions, reflecting different discrete points in physical space, are linkedand connected to each other via functional connectivity as illustrated by the red arrows. This allows to bridge the spatial gaps between the neural activities at differentd uentlyo of theo

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iscrete points in physical space, i.e., regions, within the brain itself. There is conseqne may say, as constituted by the brain’s intrinsic activity itself. (For interpretationf the article.)

cross the space of the brain (see also Fingelkurts et al.,

004, 2005, 2010 for the discussion of this issue), while lowrequency fluctuations concern the fluctuations in neural activ-ty across time. Most importantly, both functional connectivity

continuity of neural activity across different regions, a neuro-spatial continuity as references to colour in this figure legend, the reader is referred to the web version

and low frequency fluctuations reflect neural activity across

different discrete points in time and space rather than corre-sponding to different single discrete points in physical time andspace.

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Spatially, the brain’s intrinsic activity can be characterized byifferent neural networks like the default-mode network (DMN),he cognitive-executive network (CEN), and the salience networkSN) (see Raichle et al., 2001; Menon, 2011; Raichle, 2009). TheMN concerns mainly cortical midline regions and the bilateralosterior parietal cortex (Buckner et al., 2008; Raichle et al., 2001).hese regions seem to show high resting state activity, denseunctional connectivity, and strong low frequency fluctuations0.001–0.1 Hz) in the resting state, while the executive networkomprises the lateral prefrontal cortex, the supragenual anterioringulate, and posterior lateral cortical regions as core regions ashey are involved in higher-order cognitive and executive func-ions.

Finally, the salience network includes regions like the insula,he ventral striatum, and the dorsal anterior cingulate cortex thatre associated with reward, empathy, intero/exteroception andther processes involving salience (see Menon, 2011; Wiebkingt al., 2011; Yan et al., 2009). All three neural networks, DMN, CEN,nd SN, show strong intrinsic functional connectivity among theirespective regions, while the functional connectivity to regionsxtrinsic to the respective network are usually much weaker inhe resting state. That though can change during stimulus-inducedctivity when the relationship and thus the functional connectivityetween the three networks are rebalanced (see Menon, 2011).

Most importantly, neither network acts in an isolated way dur-ng both resting state and stimulus-induced activity. Instead, allhree neural networks are mutually dependent on each other inheir level of neural activity and intrinsic functional connectivity viaheir functional connectivity to extrinsic regions in the respectivether networks (see Menon, 2011).

Taken together, this characterization of the spatial structure ofhe brain’s intrinsic activity may provide a neuronal mechanismo the constitution of spatial continuity that allows transitions (or,

etaphorically speaking, glue) between different discrete points inhysical space. Hence, the brain’s intrinsic activity seems to con-titute (the exact mechanisms remain unclear though) both spatialnd temporal continuity thereby bridging the gaps between differ-nt discrete points in time and space.

. Spatiotemporal continuity and consciousness

.1. Spatiotemporal continuity in consciousness

Experience of contents in consciousness presupposes a dynamicnd continuous flow of time extending from the past over theresent to the future, all of which are crystallized and condensed

n the present moment. This is what James (1890a,b) described asspecious present’ or ‘dynamic flow’: the concept of the ‘dynamicow’ describes the organization of time as a continuum rather thans a discontinuum in consciousness. This leads to the experience ofhat Williams James described as the ‘stream of consciousness’,

continuous temporal flow analogous to the flow of water in aiver.

Most importantly, any content we experience in consciousnessecomes integrated and embedded within this ‘dynamic flow’ ofime and becomes thereby part of the ongoing stream of conscious-ess. Consciousness of contents can thus be compared to the boat

n a river: in very much the same way, the boat could not functions a boat without the flowing water of the river, the contents can-ot become conscious without the underlying dynamic flow, e.g.,he ‘stream of consciousness.

To reframe from another perspective, the contents themselvesccur at specific discrete points in physical time. At most they mayast for a few fleeting seconds after which they are replaced by oth-rs. One content goes and the next one comes, each at their distinct

ioral Reviews 37 (2013) 726–738

and discrete points in physical time. Despite their occurrence at dif-ferent discrete points in physical time, we nevertheless experiencea temporal continuum, a transition, between the different contents.

This temporal continuum in consciousness does not seem toobey to the laws of physical time and its discrete points in time.Instead, it constitutes a continuum between the different discretepoints in physical time and thus what phenomenally is describedas ‘dynamic flow’ (James) or ‘phenomenal time’ (E. Husserl) as dis-tinguished from physical time.

While there has been much debate about time and conscious-ness (see Northoff, 2012b, Part I/Chapters 1–3 for details), therehas been less discussion about the experience of space in con-sciousness. Analogously to time, one may want to make a similardistinction. The contents in consciousness are not experienced attheir different discrete points in physical space. Instead, they areembedded and integrated into a spatial continuum with multipletransitions between the different discrete points in physical space.As in the case of time, the contents are woven into a spatial grid ortemplate that emphasizes continuity and transition over disconti-nuity and segregation (see Chapter 4 in Part I in Northoff, 2012b fordetails) (Fig. 2).

Taken together, consciousness may phenomenally be charac-terized by an underlying temporal and spatial template or gridinto which the different contents are woven. This underlying spa-tiotemporal grid or template seems to provide continuity betweenthe different discrete points in time and space at which the differ-ent contents occur. The spatiotemporal grid or template can thusbe characterized by spatiotemporal continuity in the phenomenalrealm of consciousness as distinguished from the spatiotemporaldiscontinuity in the realm of physical time and space.

3.2. Spatiotemporal continuity in intrinsic activity andconsciousness

How now is the intrinsic activity’s spatiotemporal continuityrelated to the spatiotemporal continuity on the phenomenal level,e.g., in consciousness as described above? All we showed so far isthat the intrinsic activity bridges the gaps between different dis-crete points in time and space by low frequency fluctuations andfunctional connectivity, while we left open how such neuronal spa-tiotemporal continuity of the brain’s intrinsic activity is related tothe phenomenal spatiotemporal continuity in consciousness.

We currently do not know how neuronal and phenomenal spa-tiotemporal continuity are linked to each other. What kind ofexperimental data would be needed to link both spatiotemporalcontinuities? Let us give an example from the temporal domain.

Stimulus-induced higher frequency fluctuations like gamma(30–50 Hz) are aligned and entrained to the phases of the lowerones in the intrinsic activity (delta: 1–44 Hz or even infraslow ones:000.1–0.1 Hz). This may integrate the stimulus and its actual dis-crete point in time, as signified by the gamma oscillations, into alonger temporal stretch as provided by the longer phase durationof the resting state’s ongoing low frequency fluctuations. By beingintegrated in a longer temporal stretch, i.e., the low frequency’sphase duration, the stimulus’ discrete point in time is resolved intothe intrinsic activity’s temporal continuum.

How is this now related to consciousness? As described abovewe experience stimuli in consciousness not at their discrete point intime but rather as part of an ongoing dynamic flow of time, as part ofa temporal continuum. This temporal continuum in consciousnessmay now be traced back to the temporal continuum provided bythe intrinsic activity and its low frequency’s phase durations.

One would consecutively expect the following. First, one wouldassume that the predominant phase durations match, at least inpart, the subjectively experienced time durations of events in con-sciousness. For instance, an extrinsic stimulus a at time point x may

G. Northoff / Neuroscience and Biobehavioral Reviews 37 (2013) 726–738 731

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occurring at di fferent discrete poi nts i n �me and space

Integ ra�on of s�muli into contents an d spa�otempo ral con�nuity: ‘Dynamic flow’ of contents in consciousness

Linkage between different discrete points in �me and space into the intrinsic ac�vit y’s spa�o temporal con�nuity: ‘I nner �me and space consciousness’

Phase du ra�on of low frequency fluc tua�ons in intr ins ic ac�vity

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Tempo ral du ra�on of s�mu lus -rel ated contents in consciou sness

Fig. 2. The figure illustrates schematically the constitution of spatiotemporal continuity in consciousness (a) and its relation to neuronal features in the intrinsic activity(b and c). (a) The upper part of the figure shows the occurrence of different stimuli (vertical lines) at different discrete points in physical time and space. Middle part:independent of the respective stimuli themselves, consciousness seems to be based on the extraction of their purely spatial and temporal points linking and connectingthem. A spatiotemporal grid, template, or matrix is generated thereby resulting in spatiotemporal continuity. Phenomenally, this is manifest in the occurrence of ‘inner timeand space consciousness’. Lower part: following their occurrence in space and time, the different stimuli are linked to objects, events or persons which appear as contents(upper dashed green lines) in consciousness. Most importantly, these contents are integrated and embedded into the spatiotemporal grid or continuity (lower blue dashedline) which makes possible their association with consciousness. (b) The x-axis shows the temporal durations as experienced in ‘inner time consciousness’, while the y-axisstands for the phase durations of the strong low frequency fluctuations dominating in the intrinsic activity. The longer the phase durations during the intrinsic activity, thelonger the temporal durations subjects can experience in ‘inner time consciousness’. (c) The x-axis shows the temporal durations during the experience of stimulus-relatedc rinsicT he loni to th

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ontents in consciousness, while the y-axis stands for the coupling between the inthe better the low-high frequency coupling, the longer the phase durations, and tnterpretation of the references to colour in this figure legend, the reader is referred

ccur at the phase onset of a predominant low frequency fluctua-ion in the delta/theta range at around 5 Hz. One may now assumehat the duration of the discrete time point x and thus the stimu-us a itself may be extended in time in orientation on the temporal

activities’ low frequency phases and the stimulus-induced high frequency power.ger subjects can experience the stimulus-related contents in consciousness. (For

e web version of the article.)

duration of the respective phase. Thereby the degree of temporalextension may also be dependent whether the stimulus falls intothe positive or negative peaks and/or the falling or rising slopes ofthe phase.

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Secondly, one would expect the degree of phase-power couplingetween low and high frequency fluctuations to at least in parthe degree to which a particular stimulus can enter consciousness.he stimulus itself may induce higher frequency fluctuations likeamma (30–50 Hz). The power of such gamma fluctuations mayow need to be aligned and thus coupled to the phases of the low

requency fluctuations in for instance the delta range. Only by thathe extrinsic stimulus gains access to the brain’s intrinsic activitynd its temporal and spatial structure. One would consequentlyxpect the degree of low-high frequency phase-power coupling toredict the degree of consciousness of a particular stimulus.

An analogous scenario may hold in the case of the spatial dimen-ion. The degree of spatial continuity and thus the spatial distanceetween different neural activities in the resting state may pre-ispose how the stimulus’ discrete point in space is integratednd embedded into the spatial context. Future investigations areeeded though to more closely link both neuronal and phenomenaleasures of spatial distance and temporal duration. If successful

his would lead to what may be described as neuro-phenomenalccount of consciousness (see Northoff, 2012b).

Taken together the assignment of consciousness to extrinsictimuli may thus be strongly dependent on the degree and kind ofnteraction between the extrinsic stimulus’s spatial and temporaleatures on the one hand and the intrinsic resting state’s spatiotem-oral continuity on the other. We may thus want to explore thexact neural mechanisms underlying the different kinds of suchest-stimulus interaction in further detail as for instance whethert is linear or non-linear (see for instance Hesselmann et al., 2009;leinschmidt et al., 2012; Northoff, 2012a). This though will be a

ask for the future.For now though we aim to gather further support for the link

etween the intrinsic activity’s spatiotemporal structure and thexperience of time and space in consciousness. I propose thatuch neuro-phenomenal link is strongly supported by the con-omitant alterations in both intrinsic activity and consciousnessn psychiatric disorders like schizophrenia and depression. This

ill be the focus in the next sections, in a very abbreviated wayhough.

.3. Spatiotemporal continuity in psychiatric disorders –chizophrenia

How can we garner further support for our assumption of therain’s intrinsic activity’s spatial and temporal features being cen-ral for consciousness and its spatiotemporal continuity? For thate may want to turn to psychiatric disorders like schizophrenia andepression where abnormalities in the spatiotemporal continuityf both intrinsic activity and consciousness have been described.

Schizophrenia is a complex disorder where patients sufferrom hallucinations (mostly auditory), delusions, thought disor-ers, ego- and identity disorders, and abnormal, mostly bluntedffect and avolition, while depressive patients can be character-zed by abnormal negative effect and mood, anxiety, sleeplessness,ncreased ruminations and cognition circulating around their ownelf (‘increased self-focus’), and lack of initiative and motivation.here have been many studies on the subjective experience andhus the phenomenology of especially ‘inner time consciousness’ inoth disorders (see Fuchs, 2011 for an excellent summary). Ratherhan going into detail, I briefly summarize the main points follow-ng Fuchs (2011).

Instead of providing a grid or template of spatiotemporal conti-uity, ‘inner time and space consciousness’ in schizophrenia seems

o be characterized by spatiotemporal fragmentation, and disrup-ion. These patients no longer experience temporal continuity andhus a dynamic flow of time (and space) in their consciousness.nstead, the stream of consciousness is disrupted and blocked with

ioral Reviews 37 (2013) 726–738

the three temporal dimensions of past, present and future beingdisconnected from each other.

The glue between the different discrete points in physical timeseems to be missing in the ‘inner time and space consciousness’.This implies that the different contents including their distinct dis-crete points in physical time and space can no longer be linked toeach other in their consciousness, the glue and thus the spatiotem-poral continuity is lost. This is for instance very apparent in thefollowing quote of a schizophrenic patient by Fuchs (2011): “WhenI move quickly, it is a strain on me. Things go too quickly for mymind. They get blurred and it is like being blind. It’s as if you wereseeing a picture one moment and another picture the next.”

The schizophrenic patient describes here that the contents of hisconsciousness, the different pictures, are no longer linked together.There are no transitions anymore between the different discretepoints in time and space associated with the different pictures.The pictures are then experienced as pearls without an underlyingchain. Since the underlying chain, the spatiotemporal continuity,seems to be disrupted by itself, the pearls can no longer be puttogether, structured, ordered, and organized in consciousness.

In other terms, both the schizophrenic patients’ ‘inner time andspace consciousness’ and their ‘consciousness of contents’ becomedisordered and disorganized leading to what may be described as‘spatiotemporal disruption’. This leads these patients to experiencethe contents of consciousness in an abnormal way as is manifestedin many of the schizophrenic symptoms like ego-disorders, thoughtdisorder, hallucinations and delusions.

3.4. Spatiotemporal continuity in psychiatric disorders –depression

How about depression? Major depressive disorder (MDD) is asevere psychiatric disorder where patients suffer from excessiveruminations, increased self-focus, anhedonia, suicidal thoughts,bodily symptoms, and sleepiness (see Northoff et al., 2011a,b;Hasler and Northoff, 2011). How about their ‘inner time and spaceconsciousness’? While schizophrenia can be characterized by spa-tiotemporal disruption, the balance between past, present andfuture in the spatiotemporal continuity of consciousness seems tobe abnormally shifted towards the past in depression (see Fuchs,2011; Northoff et al., 2011a,b; Grimm et al., 2009, 2011).

The depressed patients experience themselves as being ‘lockedinto the past’ while at the same time ‘seeing and experiencingno future anymore’. This is well manifest in their extremely highdegree of hopelessness and consecutive suicidal thoughts. Hence,unlike in schizophrenic patients, the spatiotemporal continuityis not disrupted in depression. It though is abnormally shiftedtowards the past at the expense of the future so that one may wantto speak of ‘spatiotemporal dysbalance’ in depression.

The spatiotemporal dysbalance is not only manifest in theabnormally past-focused ‘inner time (and space) consciousness’in depression. It also affects the ‘consciousness of contents’ bothbodily and environmental. One’s own body is experienced as staticand powerless while environmental contents are experienced asdisconnected very much like distant objects from the far past.Hence, as in schizophrenia, the abnormal changes in the spatiotem-poral continuity seem to affect the experience of both ‘inner timeand space consciousness’ and ‘contents of consciousness’.

How are these phenomenal, e.g., subjective-experiential abnor-malities related to the brain and its intrinsic activity? I assumeda central role for the brain’s intrinsic activity in constituting spa-

tiotemporal continuity in consciousness. If so, one would expectspatial and temporal abnormalities in the intrinsic activity inschizophrenia and depression. This is indeed the case as it shallbe indicated here briefly.

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Numerous studies have recently shown resting state abnormal-ties in both depression (see Alcaro et al., 2010; Northoff et al.,011a,b for review) and schizophrenia (see for instance Northoffnd Qin, 2011 for review). These concern abnormal regional pat-erns of neural activity and altered functional connectivity. Thisuggests changes in the spatial continuity of the brain’s intrinsicctivity. And especially in schizophrenia changes in gamma oscil-ations (and low delta oscillations) have been reported (see fornstance Javitt, 2009) indicating abnormal temporal continuity inhe brain’s intrinsic activity.

Much though remains unclear at this point. First, the exactature of these spatial and temporal resting state abnormalitiesemains to be established. And secondly, their link to the aboveescribed phenomenal abnormalities in the consciousness of timend space in these patients is not at all clear at this point.

The extrinsic stimuli may encounter an already altered tem-oral and spatial continuity when interacting with the brain’s

ntrinsic activity. The latter’s spatial and temporal abnormalitiesay be imposed upon the former, the extrinsic stimuli, which are

hen experienced in abnormal spatial and temporal ways in con-ciousness. And that in turn may account for some of the bizarreymptoms as described above. The bizarre symptoms may thusltimately be described as abnormal spatiotemporal constellationsetween intrinsic activity and extrinsic stimuli, e.g., abnormal rest-timulus interaction. However, as in the case of healthy subjects,uch future work is needed to establish direct links between the

euronal and the phenomenal levels in these patients.

. Tri-dimensional view of consciousness

.1. Content and level of consciousness – bi-dimensional view

Consciousness is usually considered in a bi-dimensional way byontent and level. How can we describe content and level of con-ciousness? The content refers to events, persons, or objects that aressociated with consciousness. Much neuroscientific research hasocused on the neural mechanisms that allow to transfer contentrom the unconscious to consciousness.

Several suggestions have been made that include cyclichalamo-cortical reentrant processing (Edelman, 2003, 2005),nformation integration (Tononi, 2004; Tononi and Koch, 2008;eth et al., 2011a,b), global neuronal workspace (Baars, 2005;ehaene and Changeux, 2011; Dehaene et al., 2006), pre-stimulus

esting state activity (see Kleinschmidt et al., 2012; Kleinschmidt,011), low frequency fluctuations (He and Raichle, 2009), and neu-onal synchronization (Fries, 2005; Varela et al., 2001; Koch, 2004;inger, 1999; Llinas et al., 1998; Llinás, 2002; Buzsáki, 2006; John,005).

These neuronal mechanisms are assumed to be sufficient tossociate contents with consciousness. They are thus consideredhat is typically described as ‘neural correlates of consciousness’

see Crick, 1994; Crick and Koch, 2003; Koch, 2004; Chalmers,010). Since they refer specifically to the contents of conscious-ess, one may also speak of content-based NCC (see for instanceohwy, 2009). This is also relevant in neurological disorders thatost often can be characterized by lesions in specific regions that

rocess specific contents. The visual content-based NCC are fornstance impaired in patients with selective lesions in V1 or V5see Zeki, 2003).

In addition to the content, the level of consciousness describes

he different degrees or states of consciousness. More specifically,he level of arousal and awakening as indicated by active reactionnd behaviour towards the environment signifies the level of con-ciousness. The level of consciousness has been associated with

ioral Reviews 37 (2013) 726–738 733

neural activity in the brain stem/midbrain (see for instance Parviziand Damasio, 2003; Schiff, 2010) and the brain’s global metabolism.

The assumed role of these neuronal mechanisms is mainly basedon observations in the ‘disorders of consciousness’ where patientssuffer from loss of consciousness. Disorders of consciousness likevegetative state (VS) and epilepsy do indeed show changes inthe brain stem/midbrain as well as reduced global metabolism(see Laureys and Schiff, 2012; Cavanna et al., 2008; Cavanna andMonaco, 2009).

4.2. Form of consciousness – tri-dimensional view

How are the brain’s intrinsic activity and its spatiotemporalcontinuity related to the contents of consciousness? The spatiotem-poral continuity seems to structure and organize the contents intime and space. The contents are embedded into a spatial andtemporal context. More specifically, the discrete points in timeand space associated with particular contents are integrated andembedded into a context of ongoing spatiotemporal continuity.

The spatiotemporal continuity may be central in integrating andthus structuring and organizing the contents of consciousness intime and space. As described above, space and time provide a matrixof spatiotemporal continuity. Such a matrix allows us to integrate,structure and organize the various contents within a spatiotem-poral context. One may thus say that the spatiotemporal matrixprovides a form, the form of spatiotemporal continuity, for con-sciousness and its various contents.

What exactly do I mean by ‘form’ of consciousness? The conceptof form dates back to a long use in philosophy since the ancientGreece where it was distinguished from the contents or the actualmaterial. Nowadays one may want to describe the concept of formby the terms structure and organization as they provide some kindof grid or template. The form allows us to ‘put together’ the differentcontents in and across their different discrete points in time andspace. One may thus want to define the form of consciousness as‘putting together’. Such ‘putting together’ may be specified as the‘structuring and organizing of contents in time and space’.

How is such form related to the level of consciousness? As dis-cussed above the level of consciousness concerns the state or degreeof consciousness as manifest in arousal and awakening. This is tobe distinguished from the form that concerns the spatiotemporalorganization of consciousness. Hence form may need to be distin-guished from the level of consciousness as distinct dimension.

However, both form and level may be closely related to eachother. Neuronally, the level of consciousness seems to be closelyrelated to the global metabolism and the energy supply of the brain.For instance, patients in vegetative state suffer usually from about a50% decrease in their global metabolism (Laureys and Schiff, 2012)and the same holds true in the case of anaesthesia (Shulman et al.,2003). While it is well known that that the brain’s intrinsic activ-ity consumes much of the energy demand with extrinsic activityonly inducing small changes (Shulman et al., 2003), it is unclearhow much that is related to the constitution of spatiotemporalcontinuity.

While this is speculative at this point, it nevertheless sheds anovel light on how level and content of consciousness are related.They may be mediated by the form, e.g., the spatiotemporal con-tinuity. The level of consciousness provides the energy that isnecessary for the intrinsic activity to constitute its spatiotemporalcontinuity. And that spatiotemporal continuity is in turn necessaryto structure and organize, e.g., ‘put together’, the contents in spaceand time in order for them to become associated with conscious-

ness.

Taken together, in addition to the content and level of conscious-ness, I here described yet another dimension of consciousnessopting for a tri-rather than bi-dimensional view. The form of

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onsciousness refers to the structure and organization of conscious-ess and more specifically to how the different contents are ‘putogether’ in time and space.

Thereby the content’s discrete points in time and space wereupposed to be integrated and embedded into the spatiotempo-al continuity that can be considered as an organizational matrixr structure. Neuronally, such spatiotemporal continuity may bessumed to be traced back to the intrinsic activity. And morepecifically to the intrinsic activity’s constitution of spatiotempo-al continuity across neural activities at different discrete points inime and space.

.3. Form in psychiatric disorders

How about the form of consciousness in psychiatric disorders?ased on the above discussed considerations, one may assumeltered spatiotemporal continuity in both intrinsic activity andonsciousness in schizophrenic and depressed patients. They mayhus suffer from abnormalities in the form of consciousness, whileheir level and content of consciousness seem to be primarily morer less preserved by themselves, e.g., when considered in an iso-ated way (while they may be secondarily affected by the abnormalorm).

The primary alterations in the form distinguish psychiatricatients from both neurological lesion patients and those withisorders of consciousness. Neurological lesions patients show pri-ary alterations in specific contents of consciousness while both

evel and form seem to remain more or less intact by themselvesthough their spatiotemporal continuity may also be affected byhe regional lesion).

Patients with disorders of consciousness, in contrast, showmpaired level of consciousness, while their form and contenteem to somehow remain intact given the recent findings of ‘nor-al’ stimulus induced activity during for instance imaginary tasks

ike tennis playing or house navigation (see Owen et al., 2006,onti et al., 2010; Laureys and Schiff, 2012, for a recent review).

his distinguishes them from both neurological and psychiatricatients.

Given such possible dissociation between the three kind of dis-rders and their respective neuronal mechanisms, e.g., disordersf consciousness, neurological disorders, psychiatric disorders, oneay want to complement the current dimensions of conscious-

ess, content and level, by a third one, the form of consciousness.he form of consciousness describes the spatial and temporal orga-ization of the contents of consciousness. Since all three, level,ontent, and form, seem to be associated with distinct neuronalechanisms, e.g., specific regions, global metabolism, and intrinsic

ctivity’s spatiotemporal continuity, one may assume them to beistinct (Fig. 3).

Taken together, the tri-dimensional view on consciousness goeslong with consideration of three different types of disorders.he dimension of content is usually illustrated by neurologi-al patients with selective regional brain lesions in those areashere the supposed content is to be processed. The intro-uction of the level of consciousness as second dimensionrought the disorders of consciousness like the vegetative state

nto the view as paradigmatic example for changes in theevel.

Now the suggestion of form as third dimension of consciousnessrings with it yet another type of disorders, psychiatric disorders

ike depression and schizophrenia where the form and its under-ying spatiotemporal intrinsic activity pattern seems to be altered.

he distinction between the three different domains of conscious-ess, e.g., content, level, and form, is thus not only supported byheir different neuronal mechanisms but also by their associationith different kinds of disorders.

ioral Reviews 37 (2013) 726–738

5. Neural predisposition of consciousness (NPC)

5.1. Neural prerequisites and neural substrates of consciousness

The concept of the neural correlates of consciousness (NCC)describes the non-necessary sufficient neural conditions of con-sciousness. Thereby most of the suggestions for the NCC (see above)focused mainly on the content of consciousness when aiming forthe neural mechanisms that allow to distinguish unconscious andconscious content.

In addition to the NCC, some authors also delineate those neu-ral conditions that by themselves are not related to the neuralprocessing of conscious content but are nevertheless indispensable.For instance neural activity in the brain stem and midbrain maybe such condition which has been described as ‘enabling condi-tion’ or ‘background NCC’ (as distinguished from ‘core NCC’) (Koch,2004; Haynes, 2009). Hence, the concept of NCC may need to beconsidered in a more complex way.

This has been taken up most recently by authors suggesting thedistinction between neural prerequisites, neural substrates, andneural consequences of consciousness (see deGraaf et al., 2012; Aruet al., 2012). Neural prerequisites describe neural processes thatare necessary but not sufficient by themselves for consciousnessto occur. As such neural perquisites must be distinguished fromneural substrates that concern those neural mechanisms directlyrelated to the conscious experience itself. Finally, neural conse-quences describe those neural processes that directly result fromthe neural activity underlying consciousness.

How does that stand here suggested central role of the intrinsicactivity providing the form of consciousness? One may consider theintrinsic activity and its spatiotemporal activity pattern as neuralperquisite that is necessary for consciousness to occur. While at thesame time it may not be sufficient by itself so that it would fulfilthe definition of being a neural perquisite of consciousness. Thathowever would confuse the neural conditions underlying the prin-cipal possibility of consciousness with those related to the actualmanifestation of consciousness in a specific case.

Let me detail this point. The neural prerequisite concerns theneural conditions that must precede the onset of a specific extrinsicstimulus in order for it to become conscious rather than remainingunconscious. This is different in the case of the intrinsic activityand its spatiotemporal structure. Rather than concerning a partic-ular extrinsic stimulus and its actual manifestation as consciousrather than unconscious, the intrinsic activity and its spatiotem-poral structure concern the principal possibility of the associationof any extrinsic stimulus with consciousness. The intrinsic activ-ity and its spatiotemporal structure thus make first and foremostpossible consciousness as distinguished from nonconscious. Morephilosophically put, the intrinsic activity and its form concernpossible consciousness as distinct from nonconscious rather thanactual consciousness as distinct from unconscious (see, Northoff,2012b, for details).

5.2. Neural predisposition of consciousness (NPC)

How can we more properly account in our concepts for thespecific role of the form of consciousness? One may now suggestdouble differentiation.

On the one hand one could argue that consciousness can occurin the resting state as for instance during dreams. If so the intrinsicactivity may be regarded to be sufficient by itself and thus a neural

substrate rather than a mere neural perquisite. However, for that,as the literature on dreams suggests (see Northoff, 2011, 2012b),major activity change within the intrinsic activity itself is required.This activity change within the intrinsic activity may then be

G. Northoff / Neuroscience and Biobehavioral Reviews 37 (2013) 726–738 735

Fig. 3. (a) The three dimensions of consciousness, content (x-axis), level (y-axis), and form (z-axis) and their relationship to each other in healthy subjects (a). Healthysubjects show availability and thus degree of all three, content, level, and form of consciousness in the awake state, while in the sleeping state their level of consciousnessis decreased with though the contents, at least in REM-sleep during dreaming, are still accessible. (b) The three main dimensions of consciousness (left middle row), theirrole in consciousness (left row), their underlying neuronal mechanisms (right middle row), and their alterations in corresponding disorders (right row). Contents refer tothe objects and events in consciousness, the phenomenal contents as the philosophers say. The contents are the main focus in the various neuroscientific suggestions forthe neural correlates of consciousness (NCC). They imply stimulus-induced activity and altered in patients with selective brain lesions. Level refers to the different degreesof arousal and awakeness and thus to the state of consciousness. The level or state of consciousness is related to global metabolism and energy supply which are found tobe impaired and highly reduced in disorders of consciousness like vegetative state and coma. Moreover, neural activity in brain stem and midbrain is supposed to play anessential role in maintaining arousal. This reflects that what is described as ‘enabling conditions’ or ‘neural prequisites’ of consciousness. Form describes the spatiotemporalorganization and structuring (‘putting together’) of contents in consciousness. As such they make for the neural predisposition of consciousness (NPC) and are related to ther rmal ia onscior bridge

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esting state activity and its spatial and temporal structure. This seems to be abnond lower parts of the figure the concepts of phenomenal consciousness and noncespective previous one. Hence, the move from neural predisposition may allow to

onsidered the neural substrate while the spatiotemporal patterntself may still be regarded a neural prerequisite.

On the other hand, we need to make some further distinctionsithin the neural prerequisite itself. Neural prerequisite refer tore-stimulus onset fluctuations in resting state activity as well aso neural activity in for instance the brain stem and/or midbrain (seebove as well as deGraaf et al., 2012; Aru et al., 2012). Those kindsf neural processes provide the necessary though non-sufficientondition for the realization of a particular actual conscious state.

This is slightly different in the here suggested role of the brain’s

ntrinsic activity and its spatiotemporal pattern. The intrinsic activ-ty is necessary though not for a particular actual conscious stateut rather for consciousness in general. The claim is that withouthe intrinsic activity and its spatiotemporal pattern consciousness

n for instance psychiatric disorders like depression or schizophrenia. In the upperus are signified. The upward arrows shall indicate that each level is based on the

the gap between nonconscious and consciousness.

would be altogether impossible as such. There would simply beno consciousness at all. Instead there would only be what thephilosopher John Searle calls the ‘deep unconscious’ as form ofnonconscious. Using philosophers’ terms, the possibility of con-sciousness would then be simply no longer given at all.

The brain’s intrinsic activity may then not only be a neces-sary condition for the manifestation of a particular conscious statebut for consciousness in general. As expressed in philosophicalterms, the intrinsic activity is a necessary condition of possi-ble consciousness. As such it may be regarded what I described

recently as neural predisposition of consciousness (NPC) (Northoff,2011, 2012a,b,c,d). The concept of neural predisposition of con-sciousness describes the conditions that makes or designs thebrain’s states favourable (rather than non-favourable) to constitute

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onsciousness (rather than nonconscious). The NPC can thus be saido underlie the brain’s tendency to create or constitute conscious-ess.

Lets draw the analogy to the heart. Analogously to the hearthose intrinsic muscle structure predisposes it to pump (rather

han not to pump), the brain’s intrinsic activity predisposes therain to constitute consciousness (rather than nonconscious). Thenalogy goes even further. In the case of the heart, additionaleatures are needed to make the heart pump blood namely elec-rical discharges to activate the muscles’ contraction which thenllows for pumping. Hence, by itself, the muscle structure cannoto anything. However, at the same time, pumping would be alto-ether impossible if there were no such muscle structure as theeart’s intrinsic feature. The muscle structure thus makes possi-le or predisposes possible pumping without actually realizing oranifesting it.Analogously, this may apply too in the case of the brain and its

ntrinsic activity. In addition to the intrinsic activity and its spa-iotemporal pattern, additional neural processes like the neuralrerequisites and the neural substrates are needed to instanti-te consciousness. However, the neural prerequisites and neuralubstrates alone would not be able by themselves to realize, mani-est and instantiate consciousness without the underlying intrinsicctivity and its spatiotemporal structure. The intrinsic activity andts spatiotemporal structure do therefore make first and foremostossible and thus predispose possible consciousness (as distinctrom nonconscious) thus being an NPC as distinguished from theCC and its threefold distinction into neural prerequisites, neural

ubstrates, and neural consequences.

.3. Form as neural predisposition of consciousness (NPC)

How do the NPC stand to the here suggested threefold dis-inction between content, form, and level of consciousness?he NCC have focused much on content of consciousness. Thismplies the distinction between content-variant and content-nvariant processes. Content-invariant processes are those thatemain independent of the specific content of consciousness likehe neural activity preceding the actual onset of the stimulus,hile content-variant processes are related to the specific stim-lus itself like the stimulus-induced activity starting at stimulusnset.

The intrinsic activity and its spatiotemporal pattern is certainlyontent-invariant neural activity which is supported by the facthat it occurs way prior to any kind of content entering conscious-ess. The NPC thus does not concern the constitution of contentst all and must therefore be distinguished from all related neuralrocesses as described in the NCC.

How about the NPC and the level of consciousness? As dis-ussed above, the intrinsic activity and its spatiotemporal patternre dependent upon the energy and glucose metabolism associatedith the level of consciousness. However, imagine the case that

here would be complete and sufficient energy and metabolic sup-ly though without the constitution of a spatiotemporal pattern inhe brain’s intrinsic activity. In that case, consciousness would stillemain absent and be principally impossible. This strongly suggestshat the NPC cannot be determined by the level of consciousness.

Taken together, the NPC are strongly aligned to the formf consciousness, the intrinsic activity and spatiotemporal pat-ern. Without the intrinsic activity’s spatiotemporal patternroviding the form of consciousness, consciousness would beltogether impossible. There would only be nonconscious which,

nlike the unconscious, has no longer the principal possibil-

ty of ever becoming conscious. In more technical terms, thePC account for the form and its underlying neural mecha-isms as the necessary condition of the principal possibility of

ioral Reviews 37 (2013) 726–738

consciousness, e.g., as distinguished from nonconscious ratherthan accounting for actual consciousness as distinct fromunconscious.

6. Conclusion

Current neuroscience takes a bi-dimensional view on con-sciousness when distinguishing between level and content ofconsciousness. Both level and content of consciousness are asso-ciated with different neuronal mechanisms. In contrast to thestrong focus on extrinsic stimulus-induced activity and its dis-tinction between conscious and unconscious content, the roleof intrinsic activity has only recently been thematized. Theexact neuronal mechanisms by means of which the brain’sintrinsic activity makes possible consciousness remain unclearthough.

Our review of the spatial and temporal features of the brain’sintrinsic activity suggests the constitution of a virtual spatiotem-poral continuity. Thereby, the extrinsic stimuli and their discretepoints in time and space may be embedded into the brain’s intrin-sic activity and its spatial and temporal continuum. That in turnmay make possible the association of the extrinsic stimulus withconsciousness.

Future investigations may want to focus on the functionalconnectivity and the low and high frequency fluctuations in theintrinsic activity. And how they are related to the subjective-experiential features, e.g., the embedding of extrinsic stimuliand their respective contents in the spatiotemporal continuity ofconsciousness. Future investigation may thus focus on how theintrinsic activity’s spatiotemporal structure is transformed into andmanifest in the temporal and spatial structure of our subjectiveexperience, e.g., in consciousness.

Our suggestion of a link and integration between the intrin-sic activity’s spatial and temporal features with the spatial andtemporal features of consciousness opens a novel way of investigat-ing the neuronal mechanisms of consciousness. Due to such directlink between neuronal and phenomenal features, one may speakof neuro-phenomenal hypothesis of consciousness (see Northoff,2012b,c). These neuro-phenomenal hypotheses may not only allowto better understand the neuronal mechanisms of conscious-ness but also those of psychiatric disorders (like depression andschizophrenia) where both the intrinsic activity and the form ofconsciousness seem to be abnormally altered.

Taken together, I here propose that the intrinsic activity andits spatiotemporal continuity structure and organize the extrin-sic stimuli in time and space. This is supposed to make possibleand thus predispose the association of extrinsic stimuli withconsciousness rather than remaining nonconscious. As distin-guished from both content and level, the intrinsic activity maythus provide what I here describe as form of consciousness.This implies a tri-rather than bi-dimensional view including con-tent, level and form of consciousness. Since such form, e.g., thespatiotemporal continuity, predisposes consciousness, one mayspeak here of neural predispositions of consciousness (NPC) asdistinguished from the NCC and their most recent threefold dis-tinction into neural perquisites, neural substrates, and neuralconsequences.

Acknowledgments

I am thankful to David Hayes, Niall Duncan, and Ziri Huang who

commented in a very helpful way on prior versions of this paper.Financially I am grateful to the CIHR, the ISAN-HDRF, the CIHR-EJLB, and the Michael Smith Foundation for generous financialsupport.

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