Neuronal Correlates to Consciousness. the _Hall of Mirrors_ Metaphor
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Transcript of Neuronal Correlates to Consciousness. the _Hall of Mirrors_ Metaphor
8/22/2019 Neuronal Correlates to Consciousness. the _Hall of Mirrors_ Metaphor
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Research Report
Neuronal correlates to consciousness. The “Hall of Mirrors”metaphor describing consciousness as an epiphenomenon of multiple dynamic mosaics of cortical functional modules
Luigi Francesco Agnat ia,⁎ , 1, 2, Diego Guidolinb, 1, Pietro Cortellic , 2, Susanna Genedanid,
Camilo Cela-Conde
e
, Kjell Fuxe
f
aFondazione IRCCS San Camillo, Venezia Lido, ItalybDepartment of Molecular Medicine, University of Padova, Padova, ItalycDepartment of Neurological Sciences, Alma Mater Studiorum, University of Bologna, ItalydDepartment of Biomedical Sciences, University of Modena and Reggio Emilia, Via Campi 287, Modena, ItalyeUniversity of the Balearic Islands, Palma de Mallorca, Spainf Department of Neuroscience, Karolinska Institutet, 17177 Stockholm, Sweden
A R T I C L E I N F O A B S T R A C T
Article history:
Accepted 4 January 2012
Available online 11 January 2012
Humans share the common intuition of a self that has access to an inner ‘theater of mind’
(Baars, 2003). The problem is how this internal theater is formed. Moving from Cook's view
(Cook, 2008), we propose that the ‘sentience’ present in single excitable cells is integratedinto units of neurons and glial cells transiently assembled into “functional modules”
(FMs) organized as systems of encased networks (from cell networks to molecular
networks). In line with Hebb's proposal of ‘cell assemblies’, FMs can be linked to form
higher-order mosaics by means of reverberating circuits. Brain-level subjective awareness
results from the binding phenomenon that coordinates several FM mosaics. Thus,
consciousness may be thought as the global result of integrative processes taking place at
different levels of miniaturization in plastic mosaics. On the basis of these neurobiological
data and speculations and of the evidence of ‘mirror neurons’ the ‘Hall of Mirrors’ is
proposed as a significant metaphor of consciousness.
This article is part of a Special Issue entitled: Brain Integration.
© 2012 Elsevier B.V. All rights reserved.
Keywords:
Consciousness
Cellular sentience
Functional module mosaic
Mirror neuron
Internal theater
Hall of Mirrors
1. Introduction
Humans seem to share a common intuition of a ‘self ’ that has
access to conscious sensations, inner speech, images and
thoughts (self-consciousness). This intuition may be
metaphorically described as a “theater of mind” (Baars et al.,
2003), and conscious events can be defined as those brain
activities a subject can accurately report in optimal conditions
(Baars et al., 2003). Once the assumption of a chemico-
physical basis of consciousness has been accepted, we are
B R A I N R E S E A R C H 1 4 7 6 ( 2 0 1 2 ) 3 – 2 1
⁎ Corresponding author at: Fondazione IRCCS San Camillo, Via Alberoni, 70, Venezia Lido, Italy. Fax: +39 041 731330.E-mail address: [email protected] (L.F. Agnati).
1 These authors equally contributed to the paper.2 Dedicated to Professor Angelo Pierangeli (1932–2010) and to Professor Pasquale Montagna (1950–2010), University of Bologna.
0006-8993/$ – see front matter © 2012 Elsevier B.V. All rights reserved.doi:10.1016/j.brainres.2012.01.003
A v a i l a b l e o n l i n e a t w w w . s c i e n c e d i r e c t . c o m
w w w . e l s e v i e r . c o m / l o c a t e / b r a i n r e s
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confronted with the question of how brain activity leads to
conscious experiences, i.e., what are the neuronal correlates
of consciousness (NCC). As Chalmers emphasizes, the search
for NCCs is the cornerstone of the recent resurgence of the
science of consciousness (Chalmers, 2000). NCCs have become
important in the wake of the enthusiasm generated by neuro-
imaging techniques, which correlate specific cognitive tasks
with the activation of restricted brain areas, making therelationships between psychology and neurobiology more
realistic and fruitful (Monti et al., 2010). This research effort
allowed to show that conscious perceptual processing
involves the sequential activation of cortical networks at
several brainlocationswith theonset of oscillatory synchronous
activity (Gray et al., 1989a, 1989b). Hence, studies on conscious-
ness must explore both a temporal and spatial dimension.
As far as the temporal dimension of conscious events is
concerned, Pöppel and Logothetis (1986) investigated reaction
times to visual stimuli, and proposed that perceptual proces-
sing operates in basic unitsof 30 ms, while conscious episodes
composing the “conscious present” can be extended to
periods of 2 or 3 s (Pöppel, 1994). Studies in humans based
on the event-related potential (ERP) paradigm allow an esti-
mate of the temporal dynamics of conscious perceptual pro-
cessing. ERP measures the temporal location of brain events
correlated with conscious processing evoked by stimulus pre-
sentation. These studies indicate that the ERP P300 and N400
components are related to working memory and/or attention
functions that probably involve conscious processing (Coull,
1998; Knight, 1997). The corresponding brain events occur
from 300 to 400 ms after stimulus presentation. According
to Pereira and Furlan (2009), these data suggest that 200 ms
can be a good estimation of the minimum temporal duration
from stimuli presentation to the formation of a conscious
percept.
Therefore, the neuronal activity required to support
conscious processing would need to be sustained from 200 ms
to 2/3 s. Consistently, studies on subliminal perception
(Murphy and Zajonc, 1993) reveal that a visual stimulus pre-
sented for only 5 ms and followed by a mask is not consciously
perceived, although it may have unconscious priming effects.
This implies that a threshold input firing for perceptual con-
sciousness has not been reached (Pereira and Furlan, 2010).
Since such an appropriate temporal dynamics (from
200 ms to 2/3 s) of conscious events is the result of processes
linking a large network of brain systems (Buzsáki, 2007;
Laureys, 2005), it follows that the spatial dimension (i.e. the
brain's morpho-functional organization) is a key feature to
consider in order to derive deductions on the communication
modes involved in brain integrative processes leading to
conscious percepts.
In the present review aspects of the brain's morpho-
functional organization corresponding to increasing levels of
integration will be addressed(also basedon data andhypotheses
proposed by our group). In particular, the following issues
and their relevance for consciousness formation will be
analyzed:
1. Recent findings on the special features of neurons and
astrocytes (Agnati et al., 1995; Allman et al., 2005; Pereira
and Furlan, 2010; Premack,2007 ) and the possibleexistence
of a proto-consciousness phenomenon founded on the
mechanism of cell ‘sentience’ (Cook, 2008; Sevush, 2006);
2. The Volume and Wiring Transmission (VT, WT) modes of
communication processes in the brain (Agnati et al.,
2005a, 2010a) will be briefly examined since they are the
fundamental neurobiological mechanisms that allow the
dynamic formation of cell assemblies and the integration
of their activity.3. The concept of mosaics of computational elements will be
introduced (Agnati et al., 1982, 1990, 2007a, 2008). In particu-
lar, the cellular mosaic (Functional Module, FM) formed by
neuron–astroglialinteractionswill be analyzed andproposed
to be capable of a first-level integrative sentience;
4. Mechanisms for large-scale integration of FMs into
mosaics of higher-order leading to the formation of the neu-
ronal correlates of consciousness allowing the integration of
different percepts will be analyzed from the neurobiological
perspective.
Finally, these aspects will be used to propose a new inter-
pretative metaphor of consciousness, namely the brain as a
‘Hall of Mirrors’.
2. Special features of neurons and astrocytesin the human brain
A neurobiological approach to the human capacity for
auto-reflection should start at the lower level to clarify the
fundamental question of what neural substrates make a
human being human (DeFelipe et al., 2002). Plainly, these
investigations focused on the amount of neurons and synaptic
contacts, the presence of some type of special neurons, the
properties of astrocytes and, of major potential interest, a
comparison of possible specific features in some transmitter-
identified neuronal systems such as monoamine systems
(for details see Fuxe et al., 2010).
2.1. Neuronal aspects specific to the human brain
Let us start by examining some data on the peculiarities of
neurons present in the human brain.
2.1.1. Quantitative evaluations of neural and synaptic densities
A crucial quantitativedifference in neuronaldensity (neurons/
mm3 in layers I–VI) distinguishes the human brain from other
species. Neuronal density in the cerebral cortex is lower in
humans (24186/mm3) than in rats (54483/mm3) and mice
(120315/mm3), whereas the number of synapses per neuron
is higher in humans (29807) than in rats (18018) and mice
(21133) (DeFelipe et al., 2002). The number of dendritic spines
of basal dendrites of layer III pyramidal neurons also differs
in mouse and human temporal cortex. The mean number
(mean± SEM) of spines per 10 μm segment is 10.9±0.5 for
cells in temporal cortex of mice and 14.2±0.4 with respect to
the temporal cortex of humans (Benavides-Piccione et al.,
2002). Study of the size of spine heads revealed that the
mean area in the temporal cortex of mice was smaller than
in humans (mean±SEM: 0.37±0.01 μm2 and 0.59±0.01 μm2,
respectively) and the spine necks in the temporal cortex of
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mice were shorter (0.73±0.01μm) than those of humans (0.94±
0.01 μm) (Benavides-Piccione et al., 2002).
From a functional standpoint, data on the density of spines
are in agreement with the observation of a higher number of
synapses in humans than in mice or rats. The larger volume
of the spine head again indicates a more efficient transfer of
information between neurons in the human brain as spine
head volume is directly proportional to postsynaptic density,the number of postsynaptic receptors, the pre-synaptic
number of docked synaptic vesicles and the rapidly releasable
pool of neurotransmitters. In addition, spines with longer
necks show longer time constants of calcium compartmental-
ization than spines with shorter necks. All these data can be
interpreted to reflect that thehuman brain containsthe highest
density of local circuits (Alonso-Nanclares et al., 2008; DeFelipe
et al., 2002) , which are likely involved in memory processes
(Douglas et al., 1995; Goldman-Rakic, 1995; Romo et al., 1999;
Wang, 2001 see Fig. 1). It should be noticed that a high density
of synaptic contacts per neuron allows several alternative path-
ways in the high density local circuits of the human brain.
2.1.2. Special types of neurons
The qualitative and quantitative aspects of special types of
neurons like the giant Betz nerve cells of the primate motor
cortex, and especially the von Economo neurons (or spindle
neurons) are worthy of attention. The giant Betz nerve cells
of the primate motor cortex are not clustered but evenly
distributed in the inner pyramidal cell layer (layer V), where-
as clusters of large giganto-cellular nerve cells exist in layer V
of the primary motor cortex of giraffe and sheep ( Badlangana
et al., 2007). This observation is certainly interesting, but for
the moment has no clear functional correlate with the pecu-
liar features of motor control in primates. More interesting
for their possible functional correlates are the observations
on the qualitative and quantitative aspects of the von
Economo neurons (VENs) since they serve to differentiate
the human brain from other species (Allman et al., 2005;
Premack, 2007).
VENs have also been described in the cortex of the
elephant (Hakeem et al., 2009) and in the cetacean brain
(Butti et al., 2009) hencein animalspecies that pass the ‘mirror
test’ of being able to recognize themselves in a mirror (de Veer
et al., 2003; Gallup, 1970; Plotnik et al., 2006).The VENs are large, bipolar cells located in layer 5 of the
anterior cingulate, fronto-insular and dorsolateral (dysgranular)
prefrontal cortex (Fajardo et al., 2008).
They are distinguished from pyramidal cells because VENs
have only a single large basal dendrite, whereas pyramidal
cells have an array of smaller basal dendrites extending
from the cell body. Among the morphological and functional
human differences, Premack (2007) cites evidence showing
that our species has many more and larger VENs than apes.
In particular, the perimeters of VENs are far wider: an average
of 51 μm in humans compared with 36 μm in chimpanzees
and in monkeys. This increase is produced by an enlarged
dendritic tree and higher density of synapses, leading to an
increased density of local circuits. As mentioned above,
human VENs are located in only two parts of the brain, the
anterior cingulate cortex and the fronto-insular cortex.
These areas appear to be involved in socially crucial tasks,
such as empathy, feelings of guilt, and embarrassment. In
addition, human columns (see below) in the left planum tem-
porale – an area involved in language and perhaps music – are
organized differently from those of chimpanzees and rhesus
monkeys. However, they may alternatively represent a struc-
tural plasticity process to cope with the demands of achieving
integration and communication in very large brains.
It is interesting to note that VENs develop late in ontogeny.
They first appear in very small numbers in the 35th week of
gestation, and the adult number is attained only at 4 years of
Fig. 1 – Schematic example showing how increasing the number of synaptic contacts per neuron also increases the number of
potentially available reverberant circuits. As illustrated, a higher number of synapses per neuron allows several alternative
pathways to be exploited for signal reverberation.
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age. In all great apes and in postnatal human brains, VENs are
around 30%more numerous in the fronto-insular cortexof the
right hemisphere compared with their number in the corre-
sponding cortex of the left side. It may therefore be surmised
that VEN predominance in the right hemisphere in the
postnatal period is related to the right hemisphere specializa-
tion – in humans, at least – to the social emotions that are of
basic importance for self-consciousness. VENs may also beinvolvedin the fast intuitive assessment of complex situations
(Allman et al., 2005).
2.2. Astrocytic aspects specific to the human brain
Astrocytes are also excitable cells and play important roles in
information processing as can be deduced from evolutionary
data showing increasing numbers and a more complex
organization of astrocytes in the human brain. The astrocyte/
neuron ratio increases in evolution from 1:25 in the leech to
3:2 in the human brain (Pereira and Furlan, 2010). These data
likely implicate these cells in the evolution of increasingly
complex brain functions.
2.2.1. Special types of astrocytes
Of major interest are recent findings by Oberheim et al. (2006,
2009) indicating the existence of different types of astrocytes,
besides the classical protoplasmic and fibrous astrocytes, the
so-called ‘varicose projection astrocytes’ that seem exclusive
to the human brain.
These cells present more spiny processes than exhibited
by typical protoplasmic astrocytes and extend one to five,
essentially unbranched, millimeter long fibers within the
deep layers of the cortex.
The evenly spaced varicosities suggest specialized struc-
tures or compartmentalization of cellular elements along the
great distance of the fibers. These astrocytes are connected to
each other and with protoplasmic astrocytes by gap junctions,
forming a brain-wide network allowing long-distance commu-
nication across cortical layers or even between gray and white
matter (Oberheim et al., 2009).
2.3. Possible existence of a proto-consciousness founded on
single-cell ‘ sentience’
According to Cook (2008) and Sevush (2006), a single-neuron
theory of consciousness can be proposed. In particular, Cook
analyses the capability of neurons, as excitable cells, of
sensing the extracellular environment during action potential
generation. In particular, these authors suggest that a sort of
neuronal sentience emerges as a consequence of themomentary
“openness” of the plasma membrane to the external world
during the action potential. This is not “feeling ” in the sense
of “a human being having emotional experiences”, but it is
“feeling ” at the cellular level: the neuron in isolation senses its
extracellular fluid by making contact with its surrounding
world (e.g. by absorbing a small part of the local ionic charge)
as it goes about its cognitive business of synaptic communica-
tions (Cook, 2008). Thus, in a very simplified way, Cook's
proposal canbe summarized by stating that whilethe synaptic
interconnections in a neuronal network are the biological sub-
strate of the proto-phenomenon of cognition, the ion-flows
during the action potential are the biological substrate of the
proto-phenomenon of sentience.
It can also be surmised that the ‘sensing capability’ of
neurons is likely broader than that proposed above since these
cells can derive information on their external environment
not only by ion-fluxes but also via extrasynaptic receptors that
decode a variety of ‘volume transmission’ signals (see below
and Agnati et al., 2010a).Similar concepts could apply to astrocytes as well. In fact,
they can “sense” their environment, converting such an infor-
mation into detailed wavelike patterns of calcium ions and
ATP signaling that can be directly communicated to other
astrocytes and neurons (Pereira and Furlan, 2010).
As a consequence, a peculiar combination of “cognition”
and “sensitivity” is present in the nervous tissue (Guidolin et
al., 2011), not only in neurons but also in glial cells, probably
representing, in agreementwith Cook'sproposal,a prerequisite
for the emergence of the highest functions performed by the
CNS, such as subjectivity and consciousness.
To further illustrate this point, other systems in which the
above two characteristics are not simultaneously present can
briefly be considered.
On the one side, it is well known that networks of artificial
devices with fixed activation thresholds, and connected by
simple excitatory or inhibitory “synapses” are able to perform
any cognitive task that can be adequately defined (Koblauch
et al., 2010; McCulloch and Pitts, 1943; Penrose and Gardner,
1999). Thus, at least in principle, all forms of information pro-
cessing (i.e. cognition) could be performed by such a circuitry.
However, whether something like subjectivity and conscious-
ness could emerge from such a computational system is far
from being obvious (Freeman, 1997; Werner, 2007).
On the other side, there are excitable cells, such as cardio-
myocytes, sharing with neurons the possibility to sense their
external environment, since they are opened to ion-fluxes
during their electrical activity. However, the lack of adequate
connectivity schemes, primarily the lack of both excitatory
and inhibitory connections, prevents the emergence of either
cognitive functions or subjectivity.
Summing up, a comment and three considerations can be
added to Cook's interesting proposal (see Fig. 2):
a.) The comment: to be properly tuned and to have long-
lasting effects the sentience of a neuron needs a term
of comparison and likely has to impinge on a core
neuronal structure. Thus, we suggest two environments
should be considered: the extracellular fluid as the
classical internal milieu andthe cytoplasm. TheEnergide
(formed by the nucleus, microtubules and other satellite
structures) is the basic unit of living organisms (see
Baluška et al., 2006). Thus, the Energide (i.e., the core
structure of the cell) interacts with the cytoplasm that,
in turn, interacts with the interstitial fluid, and hence
with themedium classically known as theinternalmilieu
(Agnati et al., 2009a). In neurons the cytoplasm around
the Energide may represent the term of comparison for
neuronal sentience. It could also be surmised that in
view of the fundamental functions carried out by the
Energide, especially by the nucleus, long-lasting effects
on a neuron's sentience are the result of the modulatory
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actions of the ‘private’ internal medium (i.e., the cyto-
plasm around the nucleus) on the Energide.
b.) First consideration: the presence of receptors for trans-
mitters outside the synapse and not only at soma and
dendritic level, but also at axonal levels (Aoki et al.,
1998; Riad et al., 2000; Semyanov and Kullmann, 2002)
points to the possible important role of ‘volume trans-
mission’ (see below and Agnati et al., 2010a) in the
sentience of single neurons by modulating not only thecomposition of the cytoplasm and the activation of
molecular networks, but also the generation of action
potentials at soma-dendritic level and hence the bio-
chemical features of the cytoplasm around the Energide.
c.) Second consideration: according to the ‘Tide Hypothesis’
(Agnati et al., 2005a), the piston-likemovements of the en-
tire brain towards the occipital foramen cause pulsatory
distortions of the cell membranes. Thus, mechano-
sensitive ion channels present at neuronal (Zurborg et al.,
2007) and astrocyte (Ostrow and Sachs, 2005) membrane
level are stimulated. Their activation can affect the ion
movements across the plasma membranes and hence
both the generation of action potentials (i.e., sentience of neurons) and the integrative action of astrocyte networks.
d.) Third consideration: visceral homeostatic processes can
affect brain function via neuronal visceral (especially
vagal) afferences or endocrine signals. It should also be
noted that astrocytic networks are in a privileged loca-
tion to respond to blood and cerebrospinal fluid signal-
ing mediated by endothelial and ependymal cells
respectively. These signals include small molecules
like hormones and neuropeptides.
All these aspects should be entertained in investigating the
integrative actions of the brain since they underpin the global
sentience that represents subjective awareness.
3. Wiring and Volume Transmission and thesupra-cellular organization of the cortex
A basic feature of all processes leading to consciousness is the
existence of communication modes between cells leading to
the formation of supracellular forms of organization allowing
the integration of information.
3.1. Communication modes in the brain
3.1.1. Wiring Transmission (WT)
This is basically a signaling process along a physically well-
delimited channel like a ‘wire’. Two types of WT have been
studied in detail, chemical synaptic transmission and gap-
junctions (for an updated discussion see Agnati et al., 2010a).
WT allows interneuronal connections in the millisecond
range and, in some instances, it even allows a sort of transient
syncytial functional organization of the CNS (Agnati et al.,
2007b; Hameroff, 2010). However, as mentioned above,
astrocyte networks arealsoconnected by WT since gapjunctions
between chains of astrocytes have been described. Thus, where-
as neurons are interconnected through chemical and electrical
synapses and their excitable response are basically electrical
signals, astrocytes are interconnected via gap junctions and
their excitable responses are basically intracellular calcium
waves (Oberheim et al., 2009; Pereira and Furlan, 2010).
Furthermore, the existence of three-dimensional molecular
networks has been proposed, mainly made of proteins and car-
bohydrates, which can be organized in a large Global Molecular
Network (GMN) pervading the intra- and extracellular environ-
ment of the central nervous system. The GMN might transmit
signals and connect different compartments through interac-
tions between extra- and intracellular molecular networks.
Thus, the GMN may be involved in the integrative actions of
Fig. 2 – Schematic representation of a neuron. Signal transmission is the essential function of the neuron, but what flows down
the axon is a sudden process of adjustment of the membrane potential. It is associated with a material flow of ions orthogonal to
the direction of signal transmission. According to Cook (2008) these two cellular processes could represent the protophenomenon
of cognition and sentience respectively. The scheme points out the key role that the comparison between the extra-cellular fluid
(i.e., the classical ‘internal milieu’ ) and the cytoplasm, the ‘private’ cellular internal environment around the Energide (see Baluška
et al., 2006 ) may have to realize such a cell sentience. Furthermore, the possible contribution of Volume Transmission (VT) signalsof both chemical and physical nature (as, for instance, the pressure waves caused by the arterial blood pressure pulses in cerebral
arteries) to the process is indicated. For further details, see text.
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the brain also in view of its plastic structure, in fact its extra-
cellular part is continuously under the remodeling action of
the matrix metalloproteinases (Agnati et al., 2006).
3.1.2. Volume Transmission (VT)
This is a diffuse mode of signalingprocess that hassimilarities
with radio broadcasting (for an updated discussion see Agnati
et al., 2010a). Thus, diffusible chemical signals can affect entirebrain regions. In this context the electromagnetic fields (EMFs)
could also be mentioned. The brain's endogenous electromag-
netic fields are generated by the fields induced by neuron
firing and the fields generated by the movement of ions into
and out of cells and within extracellular channels (McFadden,
2002; Pockett, 2000). Pressure waves due to arterial pulses in
the brain arteries may also operate as VT signals and/or affect
VT signal diffusion and mechano-sensitiveion channelsin the
plasma membranes of neurons and astrocytes (Agnati et al.,
2005a). Thus, this type of signaling can give a beat-to-beat
connection between cardiac activity and the functional state
of entire brain areas.
3.2. Supra-cellular organization of cortical neurons and
astrocytes
In 1938 Lorente de Nò (1938) suggested that the cortex is
organized in cortical cylinders composed of vertical chains of
neurons crossing all cortical layers and having specific afferent
fibers as their axis. These cylinders represent units of operation
(DeFelipe et al., 2002; Lorente de Nò, 1938). This concept wasfur-
ther developed by Mountcastle's investigations demonstrating
that neuronsare arranged vertically (or radiallyin theconvolut-
ed cerebrum) in the form of columns spanning the width of the
primate somatosensory cortex and responding to a single
receptive field in the periphery (Mountcastle et al., 1957; Rakic,
2008).
As stated by Rakic (2008), cortical columns can be considered
functional units consisting of an array of iterative neuronal
groups extending radially across the cortical cellular layers.
Rakic points out that it has been assumed that neurons within a
given column are stereotypically interconnected in the vertical dimen-
sion, share extrinsic connectivity, and hence act as basic functional
units subserving a set of common static and dynamic cortical opera-
tions that include not only sensoryand motor areas but also association
areas subserving the highest cognitive functions.
Even though there is no consensus on a single anatomical
columnar entity (da Costa and Martin, 2010), the concept of column is still supported by experimental evidence (Hubel
and Wiesel, 1977). Thus, when a physiological investigation
is carried out through the cortex of primates, ungulates and
carnivores in a trajectory perpendicular to its surface, it is
generally possible to detect a remarkable constancy in the
receptive field properties of the neurons regarding one set of
stimulus features (see Fig.3. and Carreira-Perpiñán and
Goodhill, 2002; da Costa and Martin, 2010; Miyawaki et al.,
2008). Of special relevance is the evidence of ontogenetic
columns and the proven validity of the radial unit hypothesis
as the basis for understanding the evolutionary expansion of
the cortex (Rakic, 2008).
However, some authors claim that the term ‘column’ does
not actually correspond to any single structure within the
cortex. Thus, it is impossible to find a canonical microcircuit
corresponding to the classical cortical column (Crick and
Koch, 2005; Rockland, 2010).
The concept could be clarified, on the basis of anatomical
findings (Peters and Sethares, 1996), by distinguishing mini-
columns (diameter of about 50 μm) from macrocolumns
(diameter in the range of 300–500 μm). A further theoretical
development of this important distinction can be found in a
recentpaper by Rinkus (2010) who proposes that minicolumns
do have a generic functionality, which only becomes clear
when seen in the context of the function of the higher level,
subsuming unit, the macrocolumn. Thus, Rinkus proposes
that a macrocolumn's functions are to store sparse distributed
representations of its inputs and to recognize those inputs;
while the generic function of the minicolumn is to enforce
macrocolumnar code sparseness.
Fig. 3 – Example of the organization of the visual cortex in functional columns (see Carreira-Perpiñán and Goodhill, 2002 ).
A. Schematic view of an area of visual cortex representing a particular place in the visual field. It appears organized as a
pinwheel of columns each reacting to a specific orientation of the edges at that visual field position. B. The surface of the visual
cortex appears as a topologically mapped mosaic. The different shades of gray indicate patches that have different orientation
preferences. Topologically arranged columns can similarly be identified for other characteristics of the visual field, such as
color and spatial frequency (see Miyawaki et al., 2008 ).
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Astrocytes can play an important role in the functional
organization of the cerebral cortex from specific interactions
with single synaptic contacts to modulatory interactions
with entire neuronal networks (Oberheim et al., 2009; Pereira
and Furlan, 2010).
The concept of ‘tripartite synapse’ has been introduced
since the extremity of a protoplasmic astrocyte process
wraps the synapticcleft in mostglutamatergic central synapses.It should be noted that astrocytes express membrane receptors
to neurotransmitters and can release their own chemical
messengers (gliotransmitters). Thus, they establish a cross-talk
with both pre- and post-synaptic neurons. It is important to
emphasize that VT and WT have a specialized point of contact
at the level of tripartite synapses hence it is possible to assess
that astrocyte networks regulate neural functions and vice
versa (Giaume et al., 2010).
Several astrocytes participate in this functional unit (i.e.,
the tripartite synapse) and are coupled with each other by
gap junctions forming a network that can support large-
scale integrative functions in the brain via a continuous
cross-talk with neurons. Thus, neuron–astroglial networks
do exist (see Agnati and Fuxe, 1984 the concept of ‘complex
cellular networks’) controlling not simply dynamic glucose
delivery (Rouach et al., 2008), but also cognitive information
processing (Robertson, 2002). In particular, astrocytes
connected via gap junctions represent not only a pathway
for direct intercellular exchange of ions,nutrientsand signaling
molecules (Parpura et al., 2004), but can even be an active
computing mechanism. This proposal is supported by findings
demonstrating that gap junction channels are regulated by
extra- and intracellular signals and allow exchange of
information, so that astrocyte networks can operate as a Turing
B-likedevicesince the gap junctions can beset inthe ‘pass-mode’
or in the ‘interrupt mode’ (Agnati and Fuxe, 2000; Giaume et al.,
2010).
4. The concept of functional module and its
integrative sentience
Altogether the abovementioned data give some evidence for
the existence of elementary processing units functionally
located between and hence bridging single cells and system
levels (Cutsuridis et al., 2009; Graybiel and Grillner, 2006).
They can be called ‘functional modules’ (FM) and can be
defined as micro-circuits in which nerve cells (neurons and
astrocytes) are organized into specific patterns to carry out a
specific processing activity (see Shepherd, 2011). As discussed
above, the ‘functional module’ concept is basicallyin agreement
with both Rinkus' (Rinkus, 2010) proposal andBuxhoeveden and
Casanova's (Buxhoeveden and Casanova, 2002) assumption that
cortical morphofunctional units (columns) have no fixedanatomical borders but only functional boundaries since the
precise combination of inhibition and excitation ‘creates’ units
of different size and function.
Following our group's previous proposal of the brain as a
system of nested networks (Agnati and Fuxe, 1984; Agnati et
al., 2007a, 2007b, 2008), it may also be surmised that within a
FM the information processing could occur at different levels
of miniaturization from the cell network level down to the
molecular network level (see Fig. 4). It follows that the final,
integrated, activity of the FM would emerge from the complex
Fig. 4 – Schematic representation of a functional module (FM). As illustrated, in the CNS it is possible to distinguish a horizontal
organization (mosaic pattern) and a vertical (hierarchical) organization, following a “Russian doll” pattern ( Agnati and Fuxe,
1984 ).
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dynamics of this hierarchical system of relations. In this
respect, of particular interest for the present discussion are
theso called ‘synaptic clusters’ (SC), in which multiple synapses
act cooperatively to modulate their strength (Golding et al.,
2002; Shepherd, 1979). Each FM can have one or more SC, often
organized around the dendritic spines and partially isolated
from the surrounding environment by glial cells (Cutsuridis et
al., 2009; Golding et al., 2002). SC were shown to be very plasticentities from both the structural (Holtmaat et al., 2005) and the
functional (Welzel et al., 2010) point of view. As a matter of
fact, it has been reported that plastic changes induced by Long
Term Potentiation (LTP) at one synaptic contact lower the
threshold for the induction of LTP at neighboring synapses at
a stimulation strength that did not cause any plastic changes
under control conditions. Theextent of this sensitized plasticity
zone spans about 10 μm of dendrite and lasts for 10 min and is
presumably due to the diffusional spread of the Ca2+ activated
small GTPase Ras to neighboring spines (Harvey and Svoboda,
2007). These characteristics allow the SC to act as a sort of
‘intelligent layer ’ between the activity at the cellular level and
the integrative functions performed at the molecular level by
supramolecular complexes such as those formed at the cell
membrane by G protein-coupled receptors, owing to direct
receptor –receptor interactions (see Agnati et al., 2010b; Fuxe et
al., 2007a; Kenakin et al., 2010 for reviews).
To summarize, we could illustrate the general structure of
a FM as a hierarchical assemblage of mosaics of different
miniaturization, where the term ‘mosaic’ (see Agnati et al.,
2009b) is defined as in figurative art, i.e. as the process of
making pictures by inlaying small bits of colored stones
(tesserae). Thus, it indicates how from a given set of elements
(cells, synapses or molecules in this case) it is possible to
achieve different patterns endowed with different emergent
properties (e.g. of computational type). It may be surmised
that recurrent (Hebb, 1949) WT- and/or VT-based communica-
tion processes within the different levels of miniaturization
may also help in keeping information on-line and hence
allow those integrative processes requiring a certain time
interval (see above) to reach the threshold of consciousness.
With reference to the abovementioned Cook's proposal
(Cook, 2008, see Section 2.3), this schematic representation
of the integrative processes occurring within each FM
indicates that FM could represent the first integrative level
of proto-cognition and proto-consciousness, i.e. a structure
able to convert the incoming fragments of sensation into a
particular ‘fragment of perception’ ( John, 2002).
As pointed out by some authors (see Cutsuridis et al., 2009;
Graybiel and Grillner, 2006), examples of such FM include
cortical minicolumns, glomeruli in the olfactory systems,
networks for the storage and recall of memories in the hippo-
campus and the prefrontal cortex, and neural microcircuits
generating different aspects of motor behavior. The presence
of this organization of the human brain can be discussed in
the frame of Jacob's (1977) proposal on evolution working not
as an engineer but as a tinkerer. Jacob claims that evolution
tinkers together contraptions in a natural selection process
that acts by adding direction to changes, orienting chance, and
slowly and progressively producing more complex structures,
new organs, and new species. Thus, novelties come from previ-
ously unseen associations of already available material.
In agreement with this proposal, it is suggested that FMs in
the human brain can be seen as the result of a tinkering
process carried out at different time-scales:
a.) long-term scale, by evolution
b.) intermediate-termscale, by life-long individual experience
c.) short-term scale, by the moment-to-moment external
and/or internal inputs impinging on each individual
human brain.
Evolution by natural selection gave rise to a human brain
having, at least in some areas, special FMs thanks to the
particular features of VENs, the high density and peculiar
biochemical characteristics of synaptic contacts, and the
presence of varicose projection astrocytes (see Section 2.2).
Moreover, it can be conjectured that special functional rules
for recruitment of computational elements and information
handling are present in the human brain and even if they
are genetically determined, they may differ to some extent
from subject to subject and can be made more efficient by
appropriate educational training.
5. Fundamental mechanisms for ‘large-scale’integration in the brain
The set of FMs corresponding to sensory inputs generates a
“fractured” representation of the world. The issue of perceptual
unit needs mechanisms that allow these different sensory
components to be gathered into one global image. In other
words, to provide the fine texture of consciousness and the
global nature of a momentary cognitive instant of experience,
a cooperative process is required. In line with the classical
Hebb hypothesis on the possible existence of cell assemblies
interconnected via reverberating circuits (Hebb, 1949; Wang,
2001), we propose that different FMs can be transiently inter-
connected to form a higher-order mosaic, representing the
further integrative step in the chain leading to cognition and
consciousness. It has been suggested ( John, 2002) that not only
a ‘binding phenomenon’, but also a ‘background tone’ (both
exploiting the communication processes of WT and VT) is
needed to integrate the information handled by the FMs.
5.1. Formation of the neuronal correlates of consciousness:
the background tone and the binding phenomenon
Classical paradigms relate neural activity to controlled sensory
stimuli, to the motor responses following stimulation of the
motor system or, more generally, to physiological responses in
controlled cognitive conditions. Besides these results, several
studies have investigated the temporally coherent activity in
cortical areas in the absence of overt goal-directed behavior. In
humans, this resting state has been suggested not simply to
represent “noise”, but rather to implicate spontaneous and
transient processes involved in task-unrelated imagery and
thought. The resting statenetworksnot associatedwith sensory
or motor regions, such as the medial prefrontal, parietal and
posterior and anterior cingulate cortices, seem to be most
engaged when persons are not involved in overt goal-directed
behavior. Thus, these networks have been thought to underlie
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certain aspects of conscious introspection, being specific to
humans (Ghosh et al., 2008).
However, other authors have recently shown that the
spatiotemporal patterns of the resting state also exist in anes-
thetized monkeys, thus demonstrating that they do not
reflect a state of consciousness (Shmuel and Leopold, 2008).
These dynamic resting states have been considered to
manifest the intrinsic characteristics of the underlying brainstructure, being useful for keeping the system in a highly
competitive state between different sub-networks that are
later used during different tasks (Deco et al., 2009). Following
this view, it can be suggested that the resting state might
represent the background tone on which binding mechanisms
(i.e. mechanisms capable of integrating different perceptions,
emotions, thoughts and memories in an unified conscious
experience) operate.
Different binding mechanisms have been proposed to
solve the problem of how our brain integrates information
distributed among billions of spatially separated neurons to
generate the unity of conscious experience. In the late 1980s,
Wolf Singer and colleagues (Gray et al., 1989a, 1989b) found a
specific, phase-synchronized EEG in cats' visual cortex which
was strongly correlated to a particular visual stimulation.
The phase synchrony they found in the gamma frequency
band (from 30 to 90 Hz) of the EEG becameknown as “coherent
40 Hz”. Subsequent studies have shown gamma synchrony in
various brain locations correlating with conscious perception.
This synchrony has been regarded as the electrophysiological
marker of the binding of different unconscious components in
a unified conscious percept. Location and distribution of
gamma synchrony within the brain can change dynamically,
shifting on timescales of hundreds of milliseconds or faster
(Hameroff, 2010).
However, this mechanism has been criticized as an expla-
nation of the crucial marker of the binding phenomenon. For
example, gamma band synchrony occurs in brains of both
conscious and unconscious animals in response to visually
presented objects (Canales et al., 2007).
Large-scale integration, or ‘binding ’, has then been
suggested to involve fluctuations around the background
state (Edelman and Tononi, 2000; John, 2002). What leads to
a binding of the fragmented information into a coherent
process would be the identification (by neuronal coincidence
detectors in the cortex) of synchrony within and coherence
among brain regions which deviate from the ground state. In
this respect, oscillations of local field potentials (in the beta,
alpha and theta/delta frequencies) also play an important
role in facilitating synchronization and coherence ( John, 2002).
In this context, a potentially important contribution of
astrocytes to the binding process was emphasized by
(Pereira and Furlan (2009). Accordingto their theory, thetrans-
fer of information patterns embodied in local field potentials
to astrocytic calcium waves would facilitate a “binding ” of
spatially distributed patterns into unitary conscious episodes.
According to the concept of FM illustrated in Section 4, a
view could also be proposed, in which the ‘background tone’
and the ‘binding phenomenon’ are considered as different
aspects of the collective dynamics of FMs. In fact, it can be sur-
mised that the background tone simply reflect reverberating
activity playing the leading role of continuously assembling
pools of FMs. In the absence of a salient internal and/or exter-
nal input this process results as a spontaneous chaotic activity
(recorded as a noise) present in many brain regions. Under
internal and/or external inputs triggering a binding phenome-
non, a self-organization occurs and this basal state moves
towards an attractor, eventually leading to a dynamic synchro-
nization and hence to the functional assemblage of several FMs
into specific high-order mosaics. A comment by Werner (2007)may be in line with this hypothesis: On the horizon I note promis-
ing new actors to count with in future: I draw attention to computa-
tional simulations of radically novel features of neural microcircuits
which function more like liquids responding to perturbations with
ripples of waves, rather than like digital gates ( … ) If proven real,
such microcircuits would adopt a system dynamics at the boundary
region of ordered and chaotic behavior. They would, thus, belong to
the class of natural systems operating at “ the edge of chaos”, which
are known for their capacity for critical self-organization.
Summing up, the existence of global synchrony in the
brain indicatesthe operationof a tuning mechanism accounting
for the coordination of local circuits and orienting some FMs to
form transient higher-order mosaics, which may represent the
NCCs.
The assemblage is not the result of any ‘conscious process’,
but on the contrary, is a largely unconscious process that
depends on genetically coded as well as learned interaction
rules, which integrate incoming inputs with short and long-
term memories stored in the FMs. In a recent interesting
study by Buzsáki (2010) possible mechanisms allowing the
identification and organization of cell assemblies are exten-
sively reviewed and discussed. FMs are recruited according
to different spatial patterns (locations of the FMs with respect
to each other) and temporal patterns (time sequences of their
activation). These two patterns also regulate the mosaic
networks of different miniaturization inside each FM. An
adaptation is, therefore, possible by shaping and activating
the mosaics to fit the specific task to fulfill.
5.2. The neuroanatomical bases of ‘ large-scale’ brain
integration
A crucial aspect is the characterization of the neuronal
systems selecting FMs and linking them together into the
abovementioned higher-order mosaics representing the
NCCs. Two of these, namely the thalamo-cortical and the
brainstem–subcortical/cortical interconnections will be briefly
described, since they are widely acknowledged to play a key
role in the formation of conscious events. Some comment
will be also deserved to the claustrum and to its proposed
(Crick and Koch, 2005) special integrative role.
5.2.1. Thalamo-cortical interconnections
Thalamo-cortical reverberating circuits are a highly relevant
topic for consciousness processes. Several lines of clinical
experience suggest that if we lack the thalamus, the cortex
is useless, leaving the patient in a state close to total coma.
Thus, as emphasizedby Llinasand Ribary (2001), consciousness
needs a continuous “dialog ” between the thalamus and the
cortex to arise.
As Llinas et al. (1998) pointed out, the thalamus represents
a sort of hub from which any site in the cortex can
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communicate with other sites. The corticothalamic pathway,
therefore, can selectively mediate coherence and synchronicity
of activity between selected groups of interconnected cortical
and thalamic neurons during particular functional states. A
second organizing principle, however, may be equally impor-
tant. It is based on the temporal rather than spatial relation-
ships among groups of neurons and the thalamo-cortical
iterative recurrent activity certainly plays a key role in such aprocess. In fact, as proposed by Llinas et al. (1998) two comple-
mentary loops between the thalamus and the cerebral cortex
work in conjunction to subserve temporal binding:
- a “specific” system formed by sensory or motor nuclei
projecting to layer IV of the cortex. It produces cortical
oscillations by direct activation and feed-forward inhibition
via inhibitory interneurons. These oscillations re-enter the
reticular nucleus of the thalamus via layer-VI pyramidal
cells;- a “non-specific” system, in which intralaminar nonspecific
thalamic nuclei project to cortical layers I and V and to the
reticular nucleus. Layer-V pyramidal cells return oscilla-tions to the reticular nucleus and intralaminar nuclei.
It is apparent from literature that neither of these circuits
alone can generate cognition: damage of the non-specific
system leads to deep disturbances of consciousness, while
damage of the specific system produces loss of some particular
cognitive modality. These observations led to the hypothesis
(Llinas and Ribary, 2001) that the specific system would provide
the content relating to the external world, and the non-specific
system would give rise to the temporal conjunction, or the con-
text (on thebasisof a moreinteroceptive background concerned
with alertness). Togetherthey would generate a single cognitive
experience.
An interesting structural feature of the interconnections
between cortex and thalamus is that a very large percentage
of this connectivity is recurrent, and that much of its activity
is related to such intrinsic connectivity not necessarily related
to the immediacy of sensory input. In particular, the thalamic
input from the cortex is larger than that from the peripheral
sensory system (Llinas et al., 1998). It is, therefore, reasonable
to assume that the brain is essentially a closed systemcapable
of self-generated activity based on the intrinsic electrical
properties of its component neurons and their connectivity.
In this respect Llinas et al. (1998) proposed an analogy with
the spinal cord based on the pioneering work of Brown
(1914) on locomotion. Brown demonstrated that sensory
inputs are mostly modifiers of the intrinsic activity of the
spinal cord since locomotion was still present after bilateral
dorsal root deafferentation, hence after the total removal of
sensory inputs. On that basis,Brown proposed that the complex
motor output required for locomotion is a property of the
spontaneous activity of the neuronal circuits in the spinal cord
and brainstem. Similarly, Llinas et al. (1998) suggested that
consciousness might be the result of the intrinsic activity of
brain circuits. As such, consciousness can be thought of as an
oneiric-like internal functional state modulated, rather than
generated, by the senses. This proposal is in line with the classi-
cal view that ‘perception is a model in the brain’ (Blakemore,
1976) and such a model is built up with inborn circuits and
hence is present at birth, and is “fine-tuned” later on during
normal maturation (see also Agnati et al., 2007c). In other
words, the CNS is a “reality”-emulating system in which only
some parameters of such “reality” are delineated by the senses.
Such a view of the brain as a closed system capable of an
autonomous creation of reality even in the absence of sensory
inputs, resembles the more recent proposal by Hobson (2009)
that during rapid eye movement (REM) sleep (i.e., in theabsence of sensory inputs) the brain may create a virtual reality
model of the world. Such a model could be of functional use in
the development and maintenance of waking consciousness.
Available experimental data comparing awake and REM sleep
state (Llinas and Paré, 1991) provide support to this idea. They
suggest that we do not perceive the external world during REM
sleep because the intrinsic activity of the corticothalamic
systems doesnot place sensory input in thecontext of thefunc-
tional state being generated by the brain. In other words, the
dreaming condition appears as a state of hyperattentiveness
to intrinsic activity in which sensory input cannot access the
machinery generating conscious experience.
In agreement with the crucial role played by corticothalamic
interconnections in consciousness formation are also the
neuropathological data on familial fatal insomnia (FFI)
(Montagna et al., 2003). Autopsy verification in FFI patients
disclosed atrophy of the mediodorsal and anterior ventral
thalamic nuclei. In these patients worsening of sleep and auto-
nomic disturbances are associated with the onset of peculiar
oneiric behaviors whereby patients, especially if left to them-
selves, fall into a hallucinatory state displaying motor gestures
related to the content of their dreams.
5.2.2. Thecortical and subcortical projections from thebrainstem
Moruzzi and Magoun (1949) obtained evidence of how distinct
nerve cell populations in the midbrain and pons could
produce a global activation of the cerebral cortex. Lesions to
these so-called reticular activating systems resulted in a
sleep-like state. The discovery of monosynaptic DA, NA and
5-HT nerve cell projections from the pons and midbrain to
the cerebral cortex and subcortical regions provided the
structural and neurochemical correlate to these pioneering
physiological observations (Andén et al., 1964, 1966; Chalmers,
2000; Dahlström and Fuxe, 1964; Fuxe, 1965; Fuxe et al., 2007b,
2010; Thierry et al., 1973).
In particular, it has been shown that the locus coeruleus
ascending NA projections from the pons to the cerebral cortex
play a significant role in tonic arousal ( Jouvet, 1972; Lidbrink
and Fuxe, 1973). Furthermore, the ascending 5-HT projections
from the mesencephalicraphenucleito corticaland subcortical
regions play a role, among others, in the maintenance of slow-
wave sleep and in preventing melancholy (Fuxe et al., 2007b;
Jouvet, 1972; Kiianmaa and Fuxe, 1977). The meso-limbic-
cortical DA neurons from the ventral tegmental area (Andén et
al., 1966; Dahlström and Fuxe, 1964; Thierry et al., 1973) inner-
vate the subcortical limbic forebrain, especially the nucleus
accumbens core and shell, and many cortical regions namely
the limbic cortex and prefrontal cortex. They play a major role
in reward and reward prediction, attention, working memory
and modulating the transfer of emotional information from
thesubcortical limbic forebrain to thecerebral cortex, especially
the prefrontal cortex (Fuxe et al., 2007b).
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The impact of these subcortical and cortical monoamine
projections for the performance of the FMs in the cerebral
cortex and, hence, for higher consciousness also becomes
clear from the fact that disturbances in these ascending
monoamine systems contribute to the development of schizo-
phrenia, attention deficit and hyperactivity disorders (Fuxe et
al., 2007b). Furthermore, hallucinogens of the indolalkylamine
type like d-LSD produce their hallucinations by activating distinct subtypes of 5-HT receptors, the 5-HT2A subtype located
in the cerebral cortex (Fuxe et al., 2009). These ascending mono-
synaptic monoamine projections from the pons and midbrain
innervating the cerebral cortex and subcortical regions serve
as important examples of the substantial impact the lower
brainstem afferents exert on the function of the cerebral cortex
directly or indirectly via innervations of subcortical regions like
the striatum, and thus on consciousness.
Summing up these data on the functional meaning of the
monoamine ascending systems, it can be stated that the
integration of the various functional cortical modules can no
longer develop well-tuned high brain function without their
global modulation and fine-tuning by cortical and subcortical
DA, NA and 5-HT nerve terminal networks acting mainly via
VT (see below and Agnati et al., 2007b; Fuxe et al., 2010).
The cortical cholinergic nerve terminal systems arising
from the basal forebrain probably have a similar role in con-
sciousness and can operate via both VT and WT (Descarries,
1998; Perry et al., 1999). Thus, while it is clear that the evolu-
tionary recent six-layered cerebral cortex plays a fundamental
role in the higher level consciousness, this evolutionarily
recent structure remains under the strong control of phyloge-
netically ancient brainstem systems that are, in fact, essential
for higher consciousness. As an intriguing example of such, it
has been proposed that a primary consciousness may exist in
children born without a cerebral cortex. Also, goal-directed
behavior has been observed in mammals after experimental
decortication (Merker, 2007).
5.2.3. The claustrum
As discussed above, it is widely accepted that there is no
single cortical area ‘where it all comes together ’ to produce
the conscious content. The elements of a coalition implicated
in the NCCs are widely distributed over both the back and the
front of the brain. Thus, effectively, they bind by interacting in
a widespread manner. However, claustrum, that according to
many authors should be considered the seventh layer of the
cortex in the insular region (Tanne-Gariepy et al., 2002), has
been proposed to play a special integrative role in view of its
vast interconnectivity with most allocortical and neocortical
regions (Crick and Koch, 2005). Important claustrum intercon-
nections have been described with the frontal lobe including
the cingulated cortex, andthe temporal,parietaland entorhinal
cortex. As mentioned by Crick and Koch (2005), the claustrum
also projects to thehippocampus, amygdala and caudate nucle-
us. It follows that it could have the possibility to bind disparate
events into a single percept experienced at one point in time
(Crick and Koch, 2005). Based on these data, Crick and Koch
(2005) suggested that it might be important to investigate the
functional role of the claustrum, namely whether it contains
specialized mechanisms capable of integrating the information
that travels widely within its anterior –posterior and ventral–
dorsal extent, thereby synchronizing different perceptual,
cognitive and motor modalities. Furthermore, they pointed out
that this postulated intra-claustrum integrative action differs
fromthatof thethalamus, which also haswidespread reciprocal
relations with most cortical regions but does not possess any
obvious mechanism to directly link its various constitutive
nuclei.
6. From NCCs to conscious episodes: the needfor metaphors
It is not yet possible to move from the NCCs to conscious
episodes introspectively obtained and some philosophers
even claim that some aspects of consciousness, such as
subjectivity, might be inherently inexplicable. As pointed out
by Baars (1998), however, we cannot know today whether or
not we will eventually understand problems like that,
although they might become clearer as more plausible
hypotheses are tested. In this respect, a useful thinking tool
is to suggest metaphors giving hints of some aspects of theNCCs-to-consciousness journey. A metaphor can be defined
as “the application of a word or phrase to an object or concept it
does not literally denote, suggesting comparison to that object or
concept” (Webster's College Dictionary, 1995).
How farcan wego along this journey by means of metaphors?
It is worth mentioning Werner's (2007) advice on the use of
metaphors in neuroscience of cognition and consciousness.
Werner discusses the strict limits within which the use of
metaphors can illuminate a target domain in cognitive neuro-
science. Thus, Werner delineates the risk of metaphors since
“they tend to carry with them the style of reasoning of the source
domain which may be (and often is) quite inappropriate for the target;
thus entailing the risk of tacitly contaminating the target with errone-
ous styles of reasoning” (Werner, 2007). Criteria for productive
metaphors, however, have been defined by Baars (1998), who
states: productive metaphors should help organize existing evidence,
yield testable hypotheses and suggest conceptual clarifications
(Baars, 1998). Any cognitive metaphor should, therefore, be
considered from Werner's and Baar's points of view. Thus,
metaphors should be used as instruments to grasp some
aspects of the still obscure physical processes relating NCCs to
consciousness, andnot as a ‘scientific’ descriptionof conscious-
ness itself. This is the case, thus far, to give any account of
internal, conscious experiences such as the so-called ‘qualia’.
No scientific description can be given. However, the way in
which the neurobiological pre-conscient issues are integrated
reaching subjective experiences of the ‘self ’ can benefit from a
metaphoric approach.
Many metaphors have been proposed to illustrate certain
features of ‘consciousness’. They basically reflect a common
theme that can be labeled the ‘theater metaphor ’ (Baars,
1988, 1997; Crick, 1984; Dennett and Kinsbourne, 1992) and
imply both convergence of input and divergent dissemination
of the integrated content. We would like to introduce a new
one, the “Hall of Mirrors”, to explain reverberating activity
between and within the FMs.
Our metaphor suggests that the mosaic of FMs, i.e., the
NCCs, can be viewed as a transient assembled Hall of Mirrors
(Fig. 5) where each mirror reflects the images of other mirrors.
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A temptative clarification of the term “mirror ” is given in
Section 6.1 for the moment let us discuss their fundamental
feature, namely the reflection process.
Thereflection process of a mirror is notachieved passively,
but by filtering and enriching the images with the memories
that it may store, and according to the peculiar integrative
capabilities with which the reflection is endowed. The final
result of these multiple reciprocal reflections among mirrors
is the creation of a ‘virtual space’ (the set of the internal
theater)and of a ‘virtual personage’ (the ‘self ’) who lives within
this theater. These are dynamic operations that allow the
stage of the theater and the attitudes and feelings of the
personage to be continuously rebuilt.
Of particular interest can be the discussion of the sugges-
tions proposed by the metaphor from the standpoint of the
abovementioned criteria indicated by Baars (1998).
6.1. ‘ Hall of Mirrors’ : existing evidence
The proposed metaphor shares with all the metaphors
illustrating the integrated brain activity as an ‘internal
theater ’ the view that the overall function of consciousness
is to provide very widespread access to unconscious brain
regions (the “audience” of the theater). As demonstrated by a
number of neuropsychological studies (Buchwald, 1974;
Kosslyn, 1994; Shiffrin et al., 1981) such access is needed for
coordination and control (see Baars, 1998 for a thoughtful
discussion). According to our proposal in a top-down
summing up, a rather stable organization of a fundamental
set of mirrors (leading to the “self ”) variably interconnected
with a plastic set of mirrors (building up a changeable ‘Hall
of Mirrors’, i.e. the stage of the internal theater) provides the
“tools” for such a coordination. Consciousness, therefore,
appears to emerge from this dynamic mirror effect, as well
as from the integrative actions inside of the FMs involved.
Thus, the present metaphor suggests that specific
morphofunctional features of cerebral cortex structures can
integrate, display, disseminate (‘reflect’) contents to other
brain structures and receive feedback from them.
Some hints to give a morpho-functional correlate to the
Mirror expression and hence to the Hall of Mirrors metaphor
could be deduced from recent studies on the parcellation of
the cortex, aimed to characterize its functional–anatomical
organization (Knösche and Tittgemeyer, 2011).
Parcellation leads to the subdivision of the cortical surface
into compact areas, which are internally relatively homoge-
neous and distinct from one another, with respect to the
considered structural and/or functional criteria. It could be
surmised that sometimes a Mirror is a mosaic of FMs within
one of these relatively homogenous and compact areas. As a
matter of fact, the importance of the cortex parcellation has
been proved also very useful for studying the organizational
principles of the brain and its ontogenetic and phylogenetic
development (Bystron et al., 2008; Rakic, 2009).
Given that brain regions frequently maintain characteristic
connectivity profiles and the functional repertoire of a cortical
area is closely related to its anatomical connections, long-
range connectivity may be used not only to define segregated
cortical areas (Knösche and Tittgemeyer, 2011) but also the
Hall of Mirrors associated to a certain function. This aspect
could be also discussed in the frame of Mesulam's proposal
(Mesulam, 2005) that many neurological and psychiatric
disorders are likely to be associated with altered anatomical
connectivity. Thus, it could be possible to investigate neuro-
logical and psychiatric disorders at least at three different
integrative levels: Functional Module, Mirror and Hall of Mirrors.
As discussedin the previous sections, this view is consistent
with existing experimental evidence of peculiar columnar map-
pings of the sensory receptive fields onto the somatosensory
(Mountcastle et al., 1957; Rakic, 2008; Woolsey and Van der
Loos, 1970), visual (Hubel and Wiesel, 1977), auditory
(Hromàdka and Zador, 2009), piriform (Gottfried, 2010) and
primary taste (Chen et al., 2011) brain cortex. Similar forms of
morphofunctional organization also exist outside the cortical
areas, such as in the brainstem (Erzurumlu et al., 2010), the
superior colliculus and the cerebellum (Arenz et al., 2009). As
proposed by Llinas et al. (1998) the activity involving resonant
columns could be the basis for cognitive events. According to
Fig. 5 – Consciousness as a virtual space and a virtual personage created by the existence of multiple interacting “mirrors”. The
metaphor of mirrors is simply a heuristic hypothesis to depict the metaphor of the internal theater in neurobiological terms.
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our model, these resonant columns are made up of FMs at
cortical level. FMs are microcircuits organized as nested
mosaics of different miniaturization (see Fig. 4). The columns
(the Mirrors) dynamically assemble to form a higher-order
mosaic where reverberating activity occurs along some of the
available wiring interconnections (such as the cortico-
thalamic pathways), leading to the formation of a NCC (Hall of
Mirrors). This view is in agreement with Edelman and Tononi's(2000) proposal on the existence of a ‘dynamical core’ formed
by shifting assemblies of spiking neurons throughout the
forebrain that are stabilized using massive re-entrant feed-
back connections (Edelman and Tononi, 2000). As also pointed
out by Crick and Koch (2003), competitions among rival cell
assemblies, i.e., potentially differently formed mosaics, occur as
a dynamic process (Crick and Koch, 2003). The winning coalition
is the one that makes the largest contribution to what we are
conscious of.
An interesting approach to investigate our hypothesis
could be based on the following question: what is it that
makes the human Hall of Mirrors (i.e., the mosaics of FMs)
so peculiar when compared to other mammalian species,
despite quite similar types of macro-anatomical cortical
regions? As mentioned in Section 2, the human brain
possesses not only special types of neurons (VEN) and astro-
cytes (varicose projection astrocytes) but also a higher density
of synaptic contacts per neuron and a higher astrocyte/neuron
ratio. Thus, data on neurons suggest more reverberating
circuits, while the data on astrocytes seem to indicate more
extended astrocyte networks and hence more complex
neuron–astroglial interactions. Altogether they open the possi-
bility for the formation of more complex FMs. Furthermore, it
may also be surmised that the hierarchical dimension of the
integrative processes occurring within human FMs could be
more complex. In this respect it would be of particular interest
to investigate whether the human brain has special protein
mosaics, e.g., special receptor mosaics (Agnati et al., 2005b,
2007d).
6.2. ‘ Hall of Mirrors’ : testable hypotheses
The ‘Hall of Mirrors’ metaphor yield testable hypotheses that
will be the focus of the present Section.
A common view in the cognitive neuroscience is that brain
areas are highlyselectiveandexhibit considerable specialization,
each responding to a set of inputs and contributing primarily to a
single cognitive domain. The here proposed metaphor would
suggest a different view in which the same basic modules (the
FMs) can be variably associated to realize a large spectrum of
NCCs, leading to the testable hypothesis that single brain regions
(even fairly small regions) could contribute to multiple cognitive-
emotional tasks.It is noteworthy that overthepast years increas-
ing evidence emerged pointing to this direction. Examples are
provided by studies on the Broca's area (see Poldrack, 2006),
showing that current evidence for the notion that Broca's area is
a “language” region is fairly weak, since it was more frequently
activated by non-language tasks than by language-related ones.
Similarly, a meta-analysis by Anderson et al. (2010)demonstrated
that most regions of the brain appear to be activated by multiple
tasks across diverse task categories. The results reported in that
study suggested that the brain achieves its variety of functions
by putting the same regions together in different patterns of
functional cooperation.
In this context, a cognitive task of particular interest is the
so-called ‘mirror ’ neuronal episodes. According to current
neurobiological research, a mirror neuron is a neuron that
fires both when an animal acts and when the animal observes
the same action performed by another subject (Rizzolatti and
Craighero, 2004). Thus, the neuron “mirrors” the behavior of the other, as though the observer were acting directly. Brain
activity consistent with that of mirror neurons has been
found in the premotor cortex and the inferior parietal cortex
in humans (Ferrari et al., 2006, 2009; Rizzolatti et al., 2009).
Such neurons have been observed in primates, and are
believed to occur in other species including birds. Functional
magnetic resonance imaging (fMRI) studies in humans
suggest that a much wider networkof brain areas shows mirror
properties in humans than was previously thought. These
additional areas include the somato-sensory cortex and are
thought to make the observer feel what it feels like to move in
the observed way (Gazzola and Keysers, 2009). fMRI experi-
ments suggest that rather than mirror neurons the human
brain areas have mirror neuron systems (Iacoboni et al., 1999).
Based on the ‘Hall of Mirrors’ metaphor, we suggest the
testable hypothesis thatmirror systems are an epiphenomenon
of a more fundamental feature of the functional organization of
the brain, i.e., the existence of computational units (mosaics of
FMs) acting like ‘mirrors’. These mosaics mirror a suitable
input, processing it according to their intrinsic functional char-
acteristics, namely connectivity and more generally to memory
stores, hence their ‘history’. The first set of mirrors is the FM
mosaics reflecting the relevant cues of the environment in an
‘analogic code’ that is the most useful code for the task the
brain should tackle in that instance—a motor code in the case
of a movement, an emotional code in the case of a feeling.
This assumption is not only in agreement with the data on
‘mirrorsystems’ but also with theimagery processes: to produce
an imagery movement the brain activates, at least in part,
networks in the motor area in order to produce an imagery
movement. Motor Imagery (MI) has been shown to involve the
conscious internal representation of movement, without overt
motor performance (Decety and Grezes, 1999; Fleming et al.,
2010). Similarities in brain activation between MI and actual
movement have also been demonstrated by fMRI (Gerardin et
al., 2000). In particular, fMRI studies have shown that during
imagined and executed finger movements, common areas of
brain activation can be observed in the premotor cortex, supple-
mentary motor area and parietal cortex, with activation peaks
slightly more rostral in frontal areas and slightly more superior
and caudal in parietal areas during MI compared with move-
ment execution (Gerardin et al., 2000). Both the right and left
parietal cortices show greater blood oxygen level-dependent
signals during imagery than during motor execution. In addi-
tion, the greater activation of the superior parietal cortex during
imagery than during preparation for movement, indicates that
MI is more than simply readiness to move (Stephan et al.,
1995). The ‘mirror ’ episodes stress the importance of reverberat-
ing phenomena in the brain. However, emphasis should be
placed on the difference between the ‘passive’ process of reflec-
tion of a beam of light by a mirror and the reverberation of
neuronal activity between two FM mosaics, which transform
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the incoming information not only according to their structural
organization but also according to their ‘history’.
The ‘hall of mirror metaphor ’ also suggests that the same
logic can be at the basis of a particularly important task such
as self-awareness. In other words, the continuous building of
a ‘virtual personage’ (the ‘self ’) living in the internal theater
would be the result of the mirror effect within some set of
FMs. An interesting possibility to test such an hypothesismay come from the fundamental study by Craig (2009)
where he proposes that the anterior insular cortex contains
interoreceptive representations of all subjective feelings
from the body and likely also emotional awareness, therefore
being able to play a fundamental role for self-awareness.
Thus, FMs that are key for high-level sentience may be located
in the insula and anterior cingulate cortex. Experiments on
self-recognition seemed to confirm the important role of
these regions in the generation of an abstract representation
of oneself. In other words, these regions appear to be deeply
involved in the creation of the ‘virtual sentient personage’
within the internal theater. As mentioned above, it is note-
worthy that these two regions exhibit an extraordinary
concentration of VENs, which are present only in few species
(namely those capable of passing the mirror test). These
neurons could be part of the circuitry supporting human
social networks. In particular, Allman et al. (2005) proposed
that the VENs relay an output from the fronto-insular and
anterior cingulatecortex to theparts of the frontaland temporal
cortex associated with theory-of-mind, where fast intuitions
are merged with slower, deliberative judgments (Allman et al.,
2005).
In agreement with such a view, it has been shown that the
loss of emotional awareness and self-consciousness in
patients with fronto-temporal dementia correlates with the
degeneration of VENs (Seeley et al., 2006).
6.3. ‘ Hall of Mirrors’ : suggested conceptual issues
As described in theforegoing Sections, thebasicidea concerning
the morphofunctional organization of the brain suggested by
the ‘Hall of Mirrors’ metaphor is a view of the cerebral cortex
as composed of FMs, i.e. microcircuits structured as a hierarchi-
cal series of networks (computational mosaics) of different
miniaturization. These basic units are able to perform a first-level integrative function by allowing the conversion of incom-
ing fragments of sensation into particular fragments of percep-
tion. They, in turn, can be dynamically linked to form mosaics
of increasing order, leading to the NCCs. A block diagram (see
Fig. 6) could indicate aspects of the main system components
involved in the present view A piano keyboard could also serve
as a simple analogy to illustrate the FM articulation in the
cerebral cortex. In fact, FMs can be represented by the keys of
the piano activated by interoceptive and/or external stimuli
but also by imagery. The complex mechanism behind a piano
key can be thought as the complex hierarchical articulation of
a FM. With the given set of piano keys a great many different
assemblies of sounds can be produced, since the keys can be
touched according to different spatial and temporal patterns.
Each specific melody, in other words, depends on the set of
keys used (spatial pattern) and the temporal sequence in
which these keys are activated (temporal pattern). Similarly,
the cognitive value of the mosaic of FMs depends on the selec-
tion of the activated FMs, and hence on their spatial and
temporal pattern, and on the possibility that the partial and
separated cognitive elements are properly integrated.
It follows that, according to the proposed ‘Hall of Mirrors’
metaphor, a key concept in the formation of the internal
theater is that of ‘reuse’ of the same basic circuits to build
the many different patterns of activity that lead to conscious
episodes. In this respect, the present neurobiological view
Fig. 6 – Possible merging of different available hypotheses in a unique schematic integrated view: (1) Coalitions of shifting
assemblies of brain cells stabilized by re-entrant feed-backs ( Edelman and Tononi, 2000 ) represent the NCCs. According to the
hypothesis here presentedthe basic element (tessera)of theassembly(mosaic) is a FM characterizedby a Russian doll structure;
(2) Special FMs could be found at the level of the insula and the anterior cingulate cortex ( Craig, 2009 ) giving the body an
emotional awareness; (3) as proposed by Llinas ( Llinas et al., 1998 ) thalamo-cortical interconnections should represent the main
system selecting and binding the FMs to form the NCCs; (4) the claustrum could contribute to the process by acting as a
‘conductor ’ giving the proper emphasis to each FM ( Crick and Koch, 2003 ).
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shows consistency with some general cognitive theories that
appeared in the last 5 years (Anderson, 2010; Dehaene, 2009;
Gallese, 2008; Hurley, 2008) suggesting that low-level neural
circuits are used and reused for various purposes in different
cognitive and task domains. The ‘massive redeployment
hypothesis’ (Anderson, 2007a, 2007b), for instance, explains
the observed patterns of scattered regions corresponding to
different cognitive tasks (such as language, visual perception,attention) with the suggestion that local circuits may have
low-level computational “workings” that can be put to many
different higher-level cognitive uses.
As pointed out by Anderson (2010) this represents a novel
concept, something about the brain that we are just now
beginning to notice. It offers a distinct perspective on several
general topics (such as the evolution and development of the
brain, the degree of modularity in brain organization and the
degree of localization of cognitive functions) and could also
have some practical implications in terms of rehabilitative
medicine.
7. Final comments
A basic assumption of the present paper is the building up of
mosaic networks made of elements (the FMs) that are
themselves hierarchically organized (like a Russian doll), i.e.
encasing mosaic networks each made of other mosaic
networks of a higher miniaturization. The relevance of this
‘vertical’ morphofunctional organization for the integrative
actions of the brain can be better appreciated when observing
that such an arrangement allows an enormous number of
possible configurations for each FM, providing it with an
extraordinary potential capability to process and store infor-
mation. The integrative power of the brain is further
enhanced if the above discussed mechanism of ‘neural
reuse’ (Anderson, 2010) is in operation. In fact, starting from
a given set of FMs, it allows the realization of a wide spectrum
of different assemblies, leading to the emergence of NCCs. As
mentioned above, parcellation leads to the subdivision of the
cortical surface into compact areas, which internally contain
relatively similar FMs. It is suggested that these FMs can
independently participate in the formation of different
mosaics. Thus, it can also be surmised that, by involving
different mosaics of FMs, thesame area canbe simultaneously
redeploymented for different tasks.
As pointed out in Section 5, the formation of these
conscious episodes could result from the interplay of two
basic components of the cerebral activity: the first one inter-
nal and withdrawn, the second one, being responsible for
sensorimotor actions, open to the external world. As
suggested by Llinas, “in principle one can see how the intrinsic
activity of neurons, which reflect a closed reference system, may be
the stage on which our image of the external world is ultimately
generated” (Llinas, 1988).
In conclusion, everyone lives in his own internal theater as
assessed by Chamfort: C'est là proprement l'homme; là se borne
son empire. Tout le reste lui est étranger (see Auguis, 1824–1825).
The internal theater, however, cannot be compared to a
prison since, as stated by Pessoa, there is an extraordinary
opening in its thick walls: “our imagination which allows us not
only to imagine skies above us but even non-existing skies”
(Pessoa, 1982).
As a final remark, the provided considerations clearly
delineate the restricted use of the ‘Hall of Mirrors’ metaphor
here proposed. It is suggested only as a pictorial or literary
image of the mechanisms building the set of our internal
theater. In the meantime,we believe that the ‘negative analogy’
of such a metaphor can be thought of as a useful way of illus-trating the complexity of the neurobiological problems involved
and the neurobiological investigations that should be carried
out, namely regarding:
• The rules for recruitment of the mosaics of different minia-
turization forming single FMs and those underlying the
logical operations carried out at each level.
• Theprocesses leading to therecruitmentof theFMs forming
the higher-order mosaics and the NCCs.
• The functional organization of the FMs: boundaries and
communication processes inside each FM and among FMs.
In particular, the different functional meaning of the back-
ground tone versus the binding phenomenon.
Acknowledgments
This workwas supported by grants fromIRCCS SanCamillo, Italy.
In addition, C. Cela-Conde's contribution was made
possible by project research grant HUM2007-64086/FISO
awarded by the Dirección General de Investigación del Ministerio
de Educación y Ciencia (Spain).
R E F E R E N C E S
Agnati, L.F., Fuxe, K., 1984. New concepts on the structure of theneuronal networks: the miniaturization and hierarchicalorganization of the central nervous system. Biosci. Rep. 4,93–98.
Agnati, L.F., Fuxe, K., 2000. Volume Transmission as a key featureof information handling in the central nervous systempossible new interpretative value of the Turing's B-typemachine. Prog. Brain Res. 125, 3–19.
Agnati, L.F., Fuxe, K., Zoli, M., Rondanini, C., Ogren, S.O., 1982. Newvistas on synaptic plasticity: the receptor mosaic hypothesis of the engram. Med. Biol. 60, 183–190.
Agnati, L.F., Zoli, M., Merlo Pich, E., Benfenati, F., Fuxe, K., 1990.Aspects of neural plasticity in the central nervous system. VII.Theoretical aspects of brain communication and computation.Neurochem. Int. 16, 479–500.
Agnati, L.F., Cortelli, P., Pettersson, R., Fuxe, K., 1995. The conceptof trophic units in the central nervous system. Prog. Neurobiol.46, 561–574.
Agnati, L.F., Fuxe, K., Ferré, S., 2005a. How receptor mosaicsdecode transmitter signals. Possible relevance of cooperativity.Trends Biochem. Sci. 30, 88–193.
Agnati, L.F., Genedani, S., Lenzi, P.L., Leo, G., Mora, F., Ferré, S., Fuxe,K., 2005b. Energy gradients for the homeostatic control of brainECF compositionand for VT signal migration: introduction of thetide hypothesis. J. Neural Transm. 112, 45–63.
Agnati, L.F., Zunarelli, E., Genedani, S., Fuxe, K., 2006. On theexistence of a global molecular network enmeshing the wholecentral nervous system: physiological and pathologicalimplications. Curr. Protein Pept. Sci. 7, 3–15.
17B R A I N R E S E A R C H 1 4 7 6 ( 2 0 1 2 ) 3 – 2 1
8/22/2019 Neuronal Correlates to Consciousness. the _Hall of Mirrors_ Metaphor
http://slidepdf.com/reader/full/neuronal-correlates-to-consciousness-the-hall-of-mirrors-metaphor 16/19
Agnati, L.F., Agnati, A., Mora, F., Fuxe, K., 2007a. Does the humanbrain have unique genetically determined networks coding logical and ethical principles and aesthetics? From Plato tonovel mirror networks. Brain Res. Rev. 55, 68–77.
Agnati, L.F., Genedani, S., Leo, G., Rivera, A., Guidolin, D., Fuxe, K.,2007b. One century of progress in neuroscience founded onGolgi and Cajal's outstanding experimental and theoreticalcontributions. Brain Res. Rev. 55, 167–189.
Agnati, L.F., Guidolin, D., Fuxe, K., 2007c. The brain as a system of nested but partially overlapping networks. Heuristic relevanceof the model for brain physiology and pathology. J. NeuralTransm. 114, 3–19.
Agnati, L.F., Guidolin, D., Leo, G., Fuxe, K., 2007d. A booleannetwork modelling of receptor mosaics relevance of topologyand cooperativity. J. Neural Transm. 114, 77–92.
Agnati, L.F., Guidolin, D., Carone, C., Dam, M., Genedani, S., Fuxe,K., 2008. Understanding neuronal molecular networks buildson neuronal cellular network architecture. Brain Res. Rev. 58,379–399.
Agnati, L.F., Baluška, F., Barlow, P.W., Guidolin, D., 2009a. Mosaic,self-similarity logic, and biological attraction principles: threeexplanatory instruments in biology. Commun. Integr. Biol. 2,552–563.
Agnati, L.F., Fuxe, K., Baluska, F., Guidolin, D., 2009b. Implicationsof the ‘Energide’ concept for communication and informationhandling in the central nervous system. J. Neural Transm. 116,1037–1052.
Agnati, L.F., Guidolin, D., Guescini, M., Genedani, S., Fuxe, K.,2010a. Understanding wiring and Volume Transmission. BrainRes. Rev. 64, 137–159.
Agnati, L.F., Guidolin, D., Leo, G., Carone, C., Genedani, S., Fuxe, K.,2010b. Receptor-receptor interactions: a novel concept in brainintegration. Prog. Neurobiol. 90, 157–175.
Allman, J.M., Watson, K.K., Tetreault, N.A., Hakeem, A.Y., 2005.Intuition and autism: a possible role for von economo neurons.Trends Cogn. Sci. 9, 367–373.
Alonso-Nanclares, L., Gonzalez-Soriano, J., Rodriguez, J.R.,DeFelipe, J., 2008. Gender differences in human cortical
synaptic density. Proc. Natl. Acad. Sci. U. S. A. 105,14615–14619.
Andén, N.E., Carlsson, A., Dahlström, A., Fuxe, K., Hillarp, N.A.,Larsson, K., 1964. Demonstration and mapping out of nigro-neostriatal dopamine neurons. Life Sci. 3, 523–530.
Andén, N.E., Dahlström, A., Fuxe, K., Larsson, K., Olson, L.,Ungerstedt, U., 1966. Ascending monoamine neurons to thetelencephalon and diencephalon. Acta Physiol. Scand. 67,313–326.
Anderson, M.L., 2007a. Evolution of cognitive function viaredeployment of brain areas. Neuroscientist 13, 13–21.
Anderson, M.L., 2007b. Massive redeployment, exaptation, and thefunctional integration of cognitive operations. Synthese 159,329–345.
Anderson, M.L., 2010. Neural reuse: a fundamental organizationalprinciple of the brain. Behav. Brain Sci. 33, 245–313.
Anderson, M.L., Brumbaugh, J., Suben, A., 2010. Investigating functional cooperation in the human brain using simplegraph-theoretic methods. In: Chaovalitwongse, A., P.M.Pardalos,V., Xanthopoulos, P. (Eds.), ComputationalNeuroscience. Springer,New York, pp. 31–42.
Aoki, C., Venkatesan, C., Go, C.-G., Forman, R., Kurose, H., 1998.Cellular and subcellular sites for noradrenergic action in themonkey dorsolateral prefrontal cortex as revealed by theimmunocytochemical localization of noradrenergic receptorsand axons. Cereb. Cortex 8, 269–277.
Arenz, A., Bracey, E.F., Margrie, T.W., 2009. Sensoryrepresentations in cerebellar granule cells. Curr. Opin.Neurobiol. 19, 445–451.
Auguis, P.R., 1824–1825. Chamfort, Oeuvres complètes, tome II.Chamerot, Paris.
Baars, B.J., 1988. A Cognitive Theory of Consciousness. CambridgeUniversity Press, Cambridge.
Baars, B.J., 1997. In the Theater of Consciousness. The Workspaceof the Mind. Oxford University Press, Oxford.
Baars, B.J., 1998. Metaphors of consciousness and attention in thebrain. Trends Neurosci. 21, 58–62.
Baars, B.J., Ramsoy, T.Z., Laureys, S., 2003. Brain, consciousexperience and the observing self. Trends Neurosci. 26, 671–675.
Badlangana, N.L., Bhagwandin, A., Fuxe, K., Manger, P.R., 2007.Observations on the giraffe central nervous system related tothe corticospinal tract, motor cortex and spinal cord: whatdifference does a long neck make? Neuroscience 148, 522–534.
Baluška, F., Volkmann, D., Barlow, P.W., 2006. Cell–cell channelsand their implication for cell theory. In: Baluška, F., Volkmann,D., Barlow, P.W. (Eds.), Cell–Cell Channels. Landes Bioscience,Georgetown, pp. 1–18.
Benavides-Piccione, R., Ballesteros-Yáñez, I., DeFelipe, J., Yuste, R.,2002. Cortical area and species differences in dendritic spinemorphology. J. Neurocytol. 31, 337–346.
Blakemore, C., 1976. Mechanics of the Mind. Cambridge UniversityPress, Cambridge.
Brown, G., 1914. The intrinsic factors in the act of progression inthe mammal. Proc. R. Soc. Lond. 84, 308–319.
Buchwald, J.S., 1974. Operant conditioning of brain activity — anoverview. In: Chase, M.H. (Ed.), Operant Conditioning of BrainActivity. University of California Press, Los Angeles, pp. 12–43.
Butti, C., Sherwood, C.C., Hakeem, A.Y., Allman, J.M., Hof, P.R.,2009. Total number and volume of Von Economo neurons inthe cerebral cortex of cetaceans. J. Comp. Neurol. 515, 243–249.
Buxhoeveden, D.P., Casanova, M.F., 2002. The minicolumnhypothesis in neuroscience. Brain 125, 935–951.
Buzsáki, G., 2007. The structure of consciousness. Nature 446, 267.
Buzsáki, G., 2010. Neural syntax: cell assemblies, synapsembles,and readers. Neuron 68, 362–385.
Bystron, I., Blakemore, C., Rakic, P., 2008. Development of thehuman cerebral cortex: Boulder Committee revisited. Nat. Rev.Neurosci. 9, 110–122.
Canales, A.F., Gómez, D.M., Maffe, C.R., 2007. A critical assessment
of the consciousness by synchrony hypothesis. Biol. Res. 40,517–519.
Carreira-Perpiñán, M.A., Goodhill, G.J., 2002. Are visual cortexmaps optimized for coverage? Neural Comput. 14, 1545–1560.
Chalmers, D.J., 2000. What is a neural correlate of consciousness?In: Metzinger, T. (Ed.), Neural Correlates of Consciousness:Empirical and Conceptual Questions. MIT Press, Cambridge,MA, pp. 17–40.
Chen, X., Gabitto, M., Peng, Y., Ryba, N.J.P., Zuker, C.S., 2011. Agustotopic map of taste qualities in the mammalian brain.Science 333, 1262–1266.
Cook, N.D., 2008. The neuron-level phenomena underlying cognition and consciousness: synaptic activity and the actionpotential. Neuroscience 153, 556–570.
Coull, J.T., 1998. Neural correlates of attention and arousal:insights from electrophysiology, functional neuroimaging andpsychopharmacology. Prog. Neurobiol. 55, 343–361.
Craig, A.D., 2009. How do you feel now? The anterior insula andhuman awareness. Nat. Rev. Neurosci. 10, 59–70.
Crick, F., 1984. Function of the thalamic reticular complex: thesearchlight hypothesis. Proc. Natl. Acad. Sci. U. S. A. 81,4586–4590.
Crick, F., Koch, C., 2003. A framework for consciousness. Nat.Neurosci. 6, 119–126.
Crick, F., Koch, C., 2005. What is the function of the claustrum?Philos. Trans. R. Soc. Lond. B Biol. Sci. 360, 1271–1279.
Cutsuridis, V., Wennekers, T., Graham, B.P., Vida, I., Taylor, J.G.,2009. Microcircuits: their structure, dynamics and role for brainfunction. Neural Netw. 22, 1037–1038.
da Costa, N.M., Martin, K.A., 2010. Whose cortical column wouldthat be? Front. Neuroanat. 4, 1–10.
18 B R A I N R E S E A R C H 1 4 7 6 ( 2 0 1 2 ) 3 – 2 1
8/22/2019 Neuronal Correlates to Consciousness. the _Hall of Mirrors_ Metaphor
http://slidepdf.com/reader/full/neuronal-correlates-to-consciousness-the-hall-of-mirrors-metaphor 17/19
Dahlström, A., Fuxe, K., 1964. Evidence for the existence of monoamine-containing neurons in the central nervoussystem. I. Demonstration of monoamines in the cell bodies of brain stem neurons. Acta Physiol. Scand. Suppl. 232, 1–55.
de Veer, M.W., Gallup Jr., G.G., Theall, L.A., van den Bos, R.,Povinelli, D.J., 2003. An 8-year longitudinal study of mirror self-recognition in chimpanzees (Pan troglodytes).Neuropsychologia 41, 229–234.
Decety, J., Grezes, J., 1999. Neural mechanisms subserving theperception of human actions. Trends Cogn. Sci. 3, 172–178.
Deco, D., Jirsa, V., McIntosh, A.R., Sporns, O., Kötter, R., 2009. Keyrole of coupling, delay, and noise in resting brain fluctuations.Proc. Natl. Acad. Sci. U. S. A. 106, 10302–10307.
DeFelipe, J., Alonso-Nanclares, L., Arellano, J.I., 2002.Microstructure of the neocortex: comparative aspects.
J. Neurocytol. 31, 299–316.
Dehaene, S., 2009. Reading in the Brain. Viking, New York.Dennett, D.C., Kinsbourne, M.J., 1992. Time and the observer: the
where and when of consciousness in the brain. Behav. BrainSci. 15, 183–247.
Descarries, L., 1998. The hypothesis of an ambient level of acetylcholine in the central nervous system. J. Physiol. 92,215–220.
Douglas, R.J., Koch, C., Mahowald, M., Martin, K.A., Suarez, H.H.,1995. Recurrent excitation in neocortical circuits. Science 269,981–985.
Edelman, G.M., Tononi, G., 2000. A Universe of Consciousness.Basic Books, New York.
Erzurumlu, R.S., Murakami, Y., Rijli, F.M., 2010. Mapping the facein the somatosensory brainstem. Nat. Rev. Neurosci. 11,252–263.
Fajardo, C., Escobar, M.I., Buriticá, E., Arteaga, G., Umbarila, J.,Casanova, M.F., Pimienta, H., 2008. Von Economo neurons arepresent in the dorsolateral (dysgranular) prefrontal cortex of humans. Neurosci. Lett. 435, 215–218.
Ferrari, P.F., Visalberghi, E., Paukner, A., Fogassi, L., Ruggiero, A.,Suomi, S.J., 2006. Neonatal imitation in rhesus macaques. PLoSBiol. 4, 1501–1508.
Ferrari, P.F., Bonini, L., Fogassi, L., 2009. From monkey mirror neurons to primate behaviours: possible ‘direct’ and ‘indirect’pathways. Philos. Trans. R. Soc. Lond. B Biol. Sci. 364,2311–2323.
Fleming, M.K., Stinear, C.M., Byblow, W.D., 2010. Bilateral parietalcortex function during motor imagery. Exp. Brain Res. 201,499–508.
Freeman, W.J., 1997. Three centuries of category errors in studiesof the neural basis of consciousness and intentionality. NeuralNetw. 7, 1175–1183.
Fuxe, K., 1965. Evidence for the existence of monoamine neuronsin the central nervous system. IV. Distribution of monoaminenerve terminals in the central nervous system. Acta Physiol.Scand. Suppl. 64 (Suppl. 247), 39–85.
Fuxe, K., Canals, M., Torvinen, M., Marcellino, D., Terasmaa, A.,Genedani, S., Leo, G., Guidolin, D., Diaz-Cabiale, Z., Rivera, A.,Lundstrom, L., Langel, U., Narvaez, J., Tanganelli, S., Lluis, C.,Ferre, S., Woods, A., Franco, R., Agnati, L.F., 2007a.Intramembrane receptor –receptor interactions: a novelprinciple in molecular medicine. J. Neural Transm. 114, 49–75.
Fuxe, K., Dahlstrom, A., Hoistad, M., Marcellino, D., Jansson, A.,Rivera, A., Diaz-Cabiale, Z., Jacobsen, K., Tinner-Staines, B.,Hagman, B., Leo, G., Staines, W., Guidolin, D., Kehr, J.,Genedani, S., Belluardo, N., Agnati, L.F., 2007b. From thegolgi–cajal mapping to the transmitter-based characterizationof the neuronal networks leading to two modes of braincommunication: Wiring and Volume Transmission. Brain Res.Rev. 55, 17–54.
Fuxe, K., Marcellino, D., Woods, A.S., Leo, G., Antonelli, T., Ferraro,L., Tanganelli, S., Agnati, L.F., 2009. Integrated signaling inheterodimers and receptor mosaics of different types of GPCRs
of the forebrain: relevance for schizophrenia. J. Neural Transm.116, 923–939.
Fuxe, K., Dahlström, A.B., Jonsson, G., Marcellino, D., Guescini, M.,Dam, M., Manger, P., Agnati, L.F., 2010. The discovery of centralmonoamine neurons gave Volume Transmission to the wiredbrain. Prog. Neurobiol. 90, 82–100.
Gallese, V., 2008. Mirror neurons and the social nature of language: the neural exploitation hypothesis. Soc. Neurosci. 3,
317–333.Gallup Jr., G.G., 1970. Chimpanzees: self-recognition. Science 167,
86–87.
Gazzola, V., Keysers, C., 2009. The observation and execution of actions share motor and somato-sensory voxels in all testedsubjects: single-subject analyses of unsmoothed fMRI data.Cereb. Cortex 19, 1239–1255.
Gerardin, E., Sirigu, A., Lehericy, S., Poline, J.B., Gaymard, B.,Marsault, C., Agid, Y., Le Bihan, D., 2000. Partially overlapping neural networks for real and imagined hand movements.Cereb. Cortex 10, 1093–1104.
Ghosh, A., Rho, Y., McIntosh, A.R., Kötter, R., Jirsa, V.K., 2008. Noiseduring rest enables the exploration of the brain's dynamicrepertoire. PLoS Comput. Biol. 4, e1000196.
Giaume, C., Koulakoff, A., Roux, L., Holcman, D., Rouach, N., 2010.
Astroglial networks: a step further in neuroglial andgliovascular interactions. Nat. Rev. Neurosci. 11, 87–99.
Golding, N.L., Staff, N.P., Spruston, N., 2002. Dendritic spikes as amechanism for cooperative long-term potentiation. Nature418, 326–331.
Goldman-Rakic, P.S., 1995. Cellular basis of working memory.Neuron 14, 477–485.
Gottfried, J.A., 2010. Central mechanisms of odour objectperception. Nat. Rev. Neurosci. 11, 628–641.
Gray, C.M., Engel, A.K., König, P., Singer, W., 1989a.Stimulus-dependent neuronal oscillations in cat visualcortex. Receptive field properties and featuredependence. Eur. J. Neurosci. 2, 607–619 .
Gray, C.M., König, P., Engel, A.K., Singer, W., 1989b. Oscillatoryresponses in cat visual cortex exhibit inter-columnar
synchronization which reflects global stimulus properties.Nature 338, 334–337.
Graybiel, A.M., Grillner, S., 2006. Microcircuits: The Interfacebetween Neurons and the Global Brain Function. MIT Press,Boston.
Guidolin, D., Albertin, G., Guescini, M., Fuxe, K., Agnati, L.F., 2011.Central nervous systemand computation. Q. Rev. Biol. 86,265–285.
Hakeem, A.Y., Sherwood, C.C., Bonar, C.J., Butti, C., Hof, P.R.,Allman, J.M., 2009. Von Economo neurons in the elephantbrain. Anat. Rec. (Hoboken) 292, 242–248.
Hameroff, S., 2010. The “conscious pilot”- dendritic synchronymoves through the brain to mediate consciousness. J. Biol.Phys. 36, 71–93.
Harvey, C.D., Svoboda, K., 2007. Locally dynamic synaptic learning rules in pyramidal neuron dendrites. Nature 450, 1195–1200.
Hebb, D.O., 1949. The Organization of Behavior. Wiley, New York.Hobson, J.A., 2009. Rem sleep and dreaming: towards a theory of
protoconsciousness. Nat. Rev. Neurosci. 10, 803–813.
Holtmaat, A.J., Trachtenberg, J.T., Wilbrecht, L., Shepherd, G.M.,Zhang, X.,Knott, G.W., Svoboda, K.,2005. Transientand persistentdendritic spines in the neocortex in vivo. Neuron 45, 279–291.
Hromàdka, T., Zador, A.M., 2009. Representations in auditorycortex. Curr. Opin. Neurobiol. 19, 430–433.
Hubel, D.H., Wiesel, T.N., 1977. Functional architecture of macaque monkey visual cortex. Proc. R. Soc. Lond. B 198, 1–59.
Hurley, S.L., 2008. The shared circuits model (SCM): how control,mirroring, and simulation can enable imitation, deliberation,and mindreading. Behav. Brain Sci. 31, 1–58.
Iacoboni, M., Woods, R.P., Brass, M., Bekkering, H., Mazziotta, J.C.,Rizzolatti, G., 1999. Cortical mechanisms of human imitation.Science 286, 2526–2528.
19B R A I N R E S E A R C H 1 4 7 6 ( 2 0 1 2 ) 3 – 2 1
8/22/2019 Neuronal Correlates to Consciousness. the _Hall of Mirrors_ Metaphor
http://slidepdf.com/reader/full/neuronal-correlates-to-consciousness-the-hall-of-mirrors-metaphor 18/19
Jacob, F., 1977. Evolution and tinkering. Science 196, 1161–1166.
John, E.R., 2002. The neurophysics of consciousness. Brain Res.Rev. 39, 1–28.
Jouvet, M., 1972. The role of monoamines and acetylcholine-containing neurons in the regulation of the sleep–waking cycle. Ergeb. Physiol. 64, 166–307.
Kenakin, T., Agnati, L.F., Caron, M., Fredholm, B., Guidolin, D.,Kobilka, B., Lefkowitz, R.W., Lohse, M., Woods, A., Fuxe, K.,
2010. International Workshop at the Nobel Forum, KarolinskaInstitutet on G protein-coupled receptors: finding the words todescribe monomers, oligomers, and their molecular mechanisms and defining their meaning. Can a consensus bereached ? J. Recept. Signal Transduct. Res. 30, 284–286.
Kiianmaa, K., Fuxe, K., 1977. The effects of 5,7-dihydroxytryptamine-induced lesions of the ascending 5-hydroxytryptamine pathways on the sleep wakefulnesscycle. Brain Res. 131, 287–301.
Knight, R.T., 1997. Distributed cortical network for visualattention. J. Cogn. Neurosci. 9, 75–91.
Knösche, T.R., Tittgemeyer, M., 2011. The role of long-rangeconnectivityfor the characterization of the functional–anatomicalorganization of the cortex Front. Syst. Neurosci. 5, 1–13.
Koblauch, A., Palm, G., Sommer, F.T., 2010. Memory capacities for
synaptic and structural plasticity. Neural Comput. 22, 289–341.
Kosslyn, S.M., 1994. Image and Mind. Harvard University Press,Harvard.
Laureys, S., 2005. The neural correlate of (un)awareness: lessonsfrom the vegetative state. Trends Cogn. Sci. 9, 556–559.
Lidbrink, P., Fuxe, K., 1973. Effects of intracerebral injections of 6-hydroxydopamine on sleep and waking in the rat. J. Pharm.Pharmacol. 25, 84–87.
Llinas, R., 1988. The intrinsic electrophysiological properties of mammalian neurons: insights into central nervous systemfunction. Science 242, 1654–1664.
Llinas, R., Paré, D., 1991. Of dreaming and wakefulness.Neuroscience 44, 521–535.
Llinas, R., Ribary, U., 2001. Consciousness and the brain. Thethalamocortical dialogue in health and disease. Ann. N Y Acad.
Sci. 929, 166–178.
Llinas, R., Ribary, U., Contreras, D., Pedroarena, C., 1998. Theneuronal basis for consciousness. Philos. Trans. R. Soc. Lond. BBiol. Sci. 353, 1841–1849.
Lorente de Nò, R., 1938. Architectonics and structure of thecerebral cortex. In: Fulton, J.F. (Ed.), Physiology of the NervousSystem. Oxford University Press, New York, pp. 291–330.
McCulloch, W.S., Pitts, W.H., 1943. A logical calculus of the ideasimmanent in nervous activity. Bull. Math. Biophys. 5, 115–133.
McFadden, J., 2002. Hebbian reverberations in emotional memoryelectromagnetic field: evidence for an electromagnetic theoryof consciousness. J. Conscious. Stud. 9, 23–50.
Merker, B., 2007. Consciousness without a cerebral cortex: achallenge for neuroscience and medicine. Behav. Brain Sci. 30,63–134.
Mesulam, M., 2005. Imaging connectivity in the human cerebralcortex: the next frontier? Ann. Neurol. 57, 5–7.
Miyawaki, Y., Uchida, H., Yamashita, O., Sato, M.A., Morito, Y.,Tanabe, H.C., Sadato, N., Kamitani, Y., 2008. Visual imagereconstruction from human brain activity using acombination of multiscale local image decoders. Neuron 60,915–929.
Montagna, P., Gambetti, P., Cortelli, P., Lugaresi, E., 2003. Familialand sporadic fatal insomnia. Lancet Neurol. 2, 167–176.
Monti, M.M., Vanhaudenhuyse, A., Coleman, M.R., Boly, M.,Pickard, J.D., Tshibanda, L., Owen, A.M., Laureys, S., 2010.Willful modulation of brain activity in disorders of consciousness. N. Engl. J. Med. 362, 579–589.
Moruzzi, G., Magoun, H.W., 1949. Brain stem reticular formationand activation of the EEG. Electroencephalogr. Clin.Neurophysiol. 1, 455–473.
Mountcastle, V.B., Davies, P.W., Berman, A.L., 1957. Responseproperties of neurons of cats somatic sensory cortex toperipheral stimuli. J. Neurophysiol. 20, 374–407.
Murphy, S.T., Zajonc, R.B., 1993. Affect, cognition, and awareness:affective priming with optimal and suboptimal stimulusexposures. J. Pers. Soc. Psychol. 64, 723–739.
Oberheim, N.A., Wang, X., Goldman, S., Nedergaard, M., 2006.Astrocytic complexity distinguishes the human brain. Trends
Neurosci. 29, 547–553.Oberheim, N.A., Takano, T., Han, X., He, W., Lin, J.H., Wang, F.,
Xu, Q., Wyatt, J.D., Pilcher, W., Ojemann, J.G., Ransom, B.R.,Goldman, S.A., Nedergaard, J., 2009. Uniquely hominid featuresof adult human astrocytes. Neuroscience 29, 3276–3287.
Ostrow, L.W., Sachs, F., 2005. Mechanosensation and endothelinin astrocytes—hypothetical roles in CNS pathophysiology.Brain Res. Rev. 48, 488–508.
Parpura, V., Scemes, E., Spray, D.C., 2004. Mechanisms of glutamate release from astrocytes: gap junction“hemichannels”, purinergic receptors and exocytotic release.Neurochem. Int. 45, 259–264.
Penrose, R., Gardner, M., 1999. The Emperor's New Mind:Concerning Computers, Minds and the Laws of Physics. OxfordUniversity Press, Oxford.
Pereira, A., Furlan, F.A., 2009. On the role of synchrony for neuron–astrocyte interactions and perceptual consciousprocessing. J. Biol. Phys. 35, 465–480.
Pereira, A., Furlan, F.A., 2010. Astrocytes and human cognition:modeling information integration and modulation of neuronalactivity. Prog. Neurobiol. 92, 405–420.
Perry, E.K., Walker, M., Grace, J., Perry, R., 1999. Acetylcholine inmind: a neurotransmitter correlate of consciousness? TrendsNeurosci. 22, 273–280.
Pessoa, F., 1982. Livro de desassossego por Bernardo Soares. Atica,Lisboa.
Peters, A., Sethares, C., 1996. Myelinated axons and the pyramidalcell modules in monkey primary visual cortex. J. Comp. Neurol.365, 232–255.
Plotnik, J.M., de Waal, F.B., Reiss, D., 2006. Self-recognition in an
Asian elephant. Proc. Natl. Acad. Sci. U. S. A. 103,17053–17057.
Pockett, S., 2000. The Nature of Consciousness: A Hypothesis.Writers Club Press, Lincoln.
Poldrack, R.A., 2006. Can cognitive processes be inferred fromneuroimaging data? Trends Cogn. Sci. 10, 59–63.
Pöppel, E., 1994. Temporal mechanisms in perception. Int. Rev.Neurobiol. 37, 185–202.
Pöppel, E., Logothetis, N., 1986. Neuronal oscillations in thehuman brain. Discontinuous initiations of pursuit eyemovements indicate a 30-Hz temporal framework for visualinformation processing. Naturwissenschaften 73, 267–268.
Premack, D., 2007. Human and animal cognition: continuityand discontinuity. Proc. Natl. Acad. Sci. U. S. A. 104,13861–13867.
Rakic, P., 2008. Confusing cortical columns. Proc. Natl. Acad. Sci.U. S. A. 105, 12099–12100.
Rakic, P., 2009. Evolution of the neo-cortex: a perspective fromdevelop-mental biology. Nat. Rev. Neurosci. 10, 724–735.
Riad, M., Garcia, S., Watkins, K.C., Jodoin, N., Doucet, E., Langlois,X., El Mestikawy, S., Hamon, M., Descarries, L., 2000.Somatodendritic localization of 5-HT1A and preterminalaxonal localization of 5-HT1B serotonin receptors in adult ratbrain. J. Comp. Neurol. 417, 181–194.
Rinkus, G.Y., 2010. A cortical sparse distributed coding modellinking mini- and macrocolumn-scale functionality. Front.Neuroanat. 4, 1–13.
Rizzolatti, G., Craighero, L., 2004. The mirror-neuron system.Annu. Rev. Neurosci. 27, 169–192.
Rizzolatti, G., Fabbri-Destro, M., Cattaneo, L., 2009. Mirror neuronsand their clinical relevance. Nat. Clin. Pract. Neurol. 5, 24–34.
20 B R A I N R E S E A R C H 1 4 7 6 ( 2 0 1 2 ) 3 – 2 1
8/22/2019 Neuronal Correlates to Consciousness. the _Hall of Mirrors_ Metaphor
http://slidepdf.com/reader/full/neuronal-correlates-to-consciousness-the-hall-of-mirrors-metaphor 19/19
Robertson, J.M., 2002. The astrocentric hypothesis: proposed roleof astrocytes in consciousness and memory formation.
J. Physiol. Paris 96, 251–255.
Rockland, K.S., 2010. Five points on columns. Front. Neuroanat. 4,1–10.
Romo, R., Brody, C.D., Hernández, A., Lemus, L., 1999. Neuronalcorrelates of parametric working memory in the prefrontalcortex. Nature 399, 470–473.
Rouach, N., Koulakoff, A., Abudara, V., Willecke, K., Giaume,C., 2008. Astroglial metabolic networks sustainhippocampal synaptic transmission. Science 322,1551–1555.
Seeley, W.W., Carlin, D.A., Allman, J.M., Macedo, M.N., Bush, C.,Miller, B.L., Dearmond, S.J., 2006. Early frontotemporaldementia targets neurons unique to apes and humans. Ann.Neurol. 60, 660–667.
Semyanov, A., Kullmann, D.M., 2002. Kainate receptor-dependentaxonal depolarization and action potential initiation ininterneurons. Nat. Neurosci. 4, 718–723.
Sevush, S., 2006. Single-neuron theory of consciousness. J. Theor.Biol. 238, 704–725.
Shepherd, G.M., 1979. The Synaptic Organization of the Brain.Oxford University Press, New York.
Shepherd, G.M., 2011. The microcircuit concept applied to corticalevolution: from three-layer to six-layercortex. Front. Neuroanat.5, 30.
Shiffrin, R.M., Dumais, S.T., Schneider, W., 1981. Characteristics of automatism. In: Long, J., Baddeley, A. (Eds.), Attention andPerformance IX. Erlbaum, Hillsdale (NJ), pp. 223–240.
Shmuel, A., Leopold, D.A., 2008. Neuronal correlates of spontaneous fluctuations in fMRI signals in monkey visualcortex: implications for functional connectivity at rest. Hum.Brain Mapp. 29, 751–761.
Stephan, K.M., Fink, G.R., Passingham, R.E., Silbersweig, D.,Ceballos-Baumann, A.O., Frith, C.D., Frackowiak, R.S., 1995.Functional anatomy of the mental representation of upper extremity movements in healthy subjects. J. Neurophysiol. 73,
373–386.Tanne-Gariepy, J., Boussaoud, D., Rouiller, E.M., 2002. Projections of
the claustrum to the primary motor, premotor, and prefrontalcortices in the macaque monkey. J. Comp. Neurol. 454, 140–157.
Thierry, A.M., Stinus, L., Blanc, G., Glowinski, J., 1973. Someevidence for the existence of dopaminergic neurons in the ratcortex. Brain Res. Rev. 50, 230–234.
Wang, X.-J., 2001. Synaptic reverberation underlying mnemonicpersistent activity. Trends Neurosci. 24, 455–463.
Webster's College Dictionary, 1995. Random House.Welzel, O., Tischbirek, C.H., Jung, J., Kohler, E.M., Svetlitchny, A., et
al., 2010. Synapse clusters are preferentially formed bysynapses with large recycling pool sizes. PLoS One 5, e13514.
Werner, G., 2007. Perspectives on the neuroscience of cognitionand consciousness. Biosystems 87, 82–95.
Woolsey, T.A., van der Loos, H., 1970. The structural organizationof layer IV in the somatosensory region (SI) of mouse cerebralcortex. Brain Res. 17, 205–242.
Zurborg, S., Yurgionas, B., Jira, J.A., Caspani, O., Heppenstall, P.A.,2007. Direct activation of the ion channel TRPA1 by Ca2+. Nat.Neurosci. 10, 277–279.
21B R A I N R E S E A R C H 1 4 7 6 ( 2 0 1 2 ) 3 – 2 1