SINGLE-NEURON THEORY OF CONSCIOUSNESS

 

Journal of Theoretical Biology (2005, In Press)

 

Steven Sevush

 

Departments of Psychiatry and Neurology

University of Miami School of Medicine

1400 NW 10 Ave, Suite 702

Miami, Florida 33136, USA

ssevush@med.miami.edu

Tel: 305-243-4082

 

This work was presented in abstract form at

"Toward a Science of Consciousness" held in Tucson, April 2002.

 

ABSTRACT:

 

     By most accounts, the mind arises from the integrated activity of large populations of neurons distributed across multiple brain regions.  A contrasting model is presented in the present paper that places the mind/brain interface not at the whole brain level but at the level of single neurons.  Specifically, it is proposed that each neuron in the nervous system is independently conscious, with conscious content corresponding to the spatial pattern of a portion of that neuron's dendritic electrical activity.  For most neurons, such as those in the hypothalamus or posterior sensory cortices, the conscious activity would be assumed to be simple and unable to directly affect the organism's macroscopic conscious behavior.  For a subpopulation of layer 5 pyramidal neurons in the lateral prefrontal cortices, however, an arrangement is proposed to be present such that, at any given moment:  i) the spatial pattern of electrical activity in a portion of the dendritic tree of each neuron in the subpopulation individually manifests a complexity and diversity sufficient to account for the complexity and diversity of conscious experience; ii) the dendritic trees of the neurons in the subpopulation all contain similar spatial electrical patterns; iii) the spatial electrical pattern in the dendritic tree of each neuron interacts nonlinearly with the remaining ambient dendritic electrical activity to determine the neuron's overall axonal response; iv) the dendritic spatial pattern is reexpressed at the population level by the spatial pattern exhibited by a synchronously firing subgroup of the conscious neurons, thereby providing a mechanism by which conscious activity at the neuronal level can influence overall behavior.  The resulting scheme is one in which conscious behavior appears to be the product of a single macroscopic mind, but is actually the integrated output of a chorus of minds, each associated with a different neuron.

 

Key Words:  binding problem; consciousness; hard problem; neural correlate of consciousness; single-neuron theory.

 

1. INTRODUCTION

 

     The purpose of this paper is to suggest a shift in emphasis from the large to the small in the search for a brain correlate for the mind.  Currently, the general view is that the mind arises from the integrated activity of large populations of neurons distributed across multiple cortical and subcortical brain regions (Sperry 1969; Crick and Koch 1990a; Llinas et al. 1998; Damasio 1999, Edelman and Tononi 2000, John 2001, Singer 2001).  Dynamic mechanisms, such as those involving reentrant flow of information (Edelman and Tononi 200), synchronous electrical oscillatory activity (Singer 1998; Engel et al. 1999; Sauve 1999; Sewards and Sewards 2001), and top-down attentional effects (Reynolds and Desimone 1999; Wolfe and Cave 1999), have then been invoked to provide for the "binding" of the dispersed neuronal activity into a unified stream of consciousness.  The perspective, according to this view, is that the activity within any single neuron correlates with merely a fragment of the total conscious experience; it is only through the integration of these fragments that a single whole-brain consciousness is assumed to emerge.

 

     A contrasting model is outlined in the present paper that places the mind/brain interface not at the whole brain level but at the level of the single neuron.  According to the model, a single brain at any given moment harbors many separate conscious minds, each being associated with the activity of a different neuron.  For most neurons, only a simple conscious experience is assumed to be present.  For a subpopulation of neurons populating the lateral prefrontal cortices, however, a complex consciousness is assumed to be separately present in each neuron, with each of the neurons having a similar conscious experience, and with that conscious experience being that which in most models is attributed to the joint action of vast numbers of neurons distributed throughout the brain.  The theory posits a mechanism that explains how the separately conscious neurons might express their output in terms of whole brain behavior.  The resulting scheme is one in which conscious behavior, while appearing to be the product of a single macroscopic mind, is actually the result of the assembled output of a chorus of minds, each associated with a different individual neuron.

 

     The main features of the theory can be summarized as follows:

 

     a) Each neuron in the nervous system is assumed to be independently conscious, with a component of the electrical activity in the neuron's dendritic tree serving as the neural correlate of consciousness (NCC) for that neuron.

 

    b) For most neurons, such as those in the hypothalamus or those in the posterior sensory cortices, or for cortical interneurons, the conscious activity of the neuron is assumed to be simple and unable to directly affect the organism's macroscopic behavior.  Such neurons would not, therefore, contribute to what is usually taken as a person’s conscious behavior.

 

      c) For layer 5 pyramidal neurons in the lateral prefrontal cortices, however, the electrical activity within a portion of the apical dendritic tree is presumed to be by itself complex and diverse enough to account for the complexity and diversity of conscious experiences usually ascribed to the activity of the brain as a whole.  Additionally, as a result of the diversity of afferent input that uniquely characterizes the lateral prefrontal cortices, the layer 5 pyramidal neurons in these areas can plausibly be regarded as recipients of input pertaining to all of the sensations, thoughts, feelings, and memories that make up conscious experience.

 

     d) A mechanism can be delineated by which a subgroup of synchronously firing layer 5 lateral PFC neurons with similar conscious experiences can express that experience by means of the spatial pattern they manifest at the neuronal population level.  The axonal output of these neurons then transmits the conscious content to other brain regions, including those that control behavior.

 

     e) As a result, while the content of conscious experience is seen to correlate with activity in individual neurons, the production of conscious behavior results from population activity at the network level.

 

     The most immediate implication of this arrangement is that it offers a novel approach to solving the "binding problem," the problem of explaining how spatially dispersed neuronal activity can correlate with an apparently seamless single experience.  The currently popular views are that either:  a) perceptual unity is achieved through temporal synchrony of the component elements, perhaps via 40 Hz gamma frequency oscillations (Singer 1998; Engel et al. 1999; Sauve 1999; Sewards and Sewards 2001); or b) perceptual unity is an illusion, with only coordinated behavioral output being in need of an explanation (Dennett 1991; Shadlen and Movshon 1999).  These approaches have their difficulties, however.  The evidence for temporal synchrony as a basis for binding has been criticized on both technical and conceptual grounds (Hardcastle 1994, 1997; Gold 1999; Revonsuo 1999; Bieberich 2002; Edwards 2005), while the argument that perceptual unity is an illusion has been challenged both empirically and philosophically (Chalmers 1996; Robertson 2003; Bayne and Chalmers 2003).  The theory presented in this paper proposes an alternative explanation for perceptual binding, with perceptual unity being achieved through spatial convergence of incoming signals upon single neurons.

 

     In what follows I present an outline of the single-neuron model and argue for its feasibility given what we know of brain architecture and function at both the macroscopic and microscopic levels.  I will then compare the model with other popular theories of consciousness and describe the empirical predictions made by the model that might adjudicate between the competing perspectives.  I will conclude by offering a brief speculation as to how the model might be extended to an ultramicroscopic domain, and how this extension might be used to formulate a framework for addressing the philosophically difficult aspects of the mind/brain problem.

 

     The model, it should be stressed, is at this point presented as a hypothesis, not a proven theory.  The contention, given the data presently available, is not that the proposed single-neuron mechanism is necessarily the way the brain processes information, only that it is a possible way for it to accomplish the task and that it should not be dismissed out of hand.  There is no question that the theory takes a stance that is at odds with prevailing intuitions.  Yet, the stakes are high and, in view of the difficulties inherent in the mind/brain problem, unusual approaches to its solution may be warranted.

 

2. TERMINOLOGY AND THE POSSIBILITY OF MULTIPLE CONSCIOUSNESSES

 

     With regard to terminology, when the terms "mind" and "consciousness" appear in this paper, they are being used in the specific sense that Chalmers uses the term "experience" in his discussion of the easy and hard problems of consciousness (Chalmers 1996).  As described by Chalmers, the "easy" problems of consciousness are those that appear tractable by the usual methods of science and include the ways in which the brain focuses attention, integrates information, controls behavior, and so on.  In contrast, the "hard" problem of consciousness is the problem of accounting for the content of subjective experience, that elusive datum that appears to accompany certain high level brain processes.  Why does the electrical processing in the brain that ensues when one looks at the sky give rise to the experience of "blue" and not to the experience of some other color, or to no color experience at all?  In what follows, it will be to consciousness in this sense that a neural correlate will be sought.

 

     An additional matter is the potential ambiguity associated with the proposal that multiple minds are present in a single brain, a feature that plays centrally in the proposed theory at both the macroscopic and microscopic levels.  The problem is that since multiple consciousnesses are assumed to be present in a single brain, and since these include consciousnesses of varying types, how will we know what is to be denoted by the term "consciousness?"  That is, to which of the different kinds of consciousness will the term refer?

 

     In order to minimize the potential for ambiguity of this kind, the theory will initially be developed for the restricted case of verbally reportable consciousness (designated in this paper as "VR-consciousness"), by which I mean consciousness that has direct access to verbal report.  It must be stressed that this restriction is a temporary one, and will be introduced only as a convenience to minimize ambiguity in the initial presentation of the theory.  It is not implied that VR-consciousness is the only type of consciousness present in the brain, nor that VR-consciousness is even the only high level consciousness present in the brain.  Nor is it implied that verbal output is the only form of behavior that can be influenced by VR-consciousness.  VR-consciousness has been chosen for this purpose because it is around this form of consciousness that the debate over the hard problem of consciousness has been primarily focused.  Once the theory has been examined for the special case of VR-consciousness, the argument will then be expanded to account for the presence of other types of consciousness.

 

     Armed with these preliminaries, we can now turn to the presentation of the model.  A sketch of the single-neuron theory for VR-consciousness will be developed in two steps, one macroscopic, the other microscopic.  At both levels, a divergent/convergent feedforward model of information flow (Abeles 1991) will be adopted.  In the macroscopic step, the suggestion will be made that within a divergent/convergent feedforward framework, much of the distributed brain processing usually taken as the correlate of VR-consciousness can be recast as either previous or subsequent to VR-conscious experience.  Plausibility arguments will be offered in support of the contention that only when the information flow reaches the left[1] lateral prefrontal cortex (PFC) does it achieve VR-conscious status.  In the microscopic step, the argument will be made that it is not the left lateral PFC as a whole that mediates VR-consciousness, but rather that VR-consciousness is mediated separately and redundantly by individual pyramidal neurons inhabiting the region.  A divergent/convergent feedforward model of information flow involving a subset of individual neuron within the population will be offered.  Finally, the theory will be extended to account for consciousness of a nonverbally reportable variety.

 

3.  THE MACROSCOPIC STEP:  PLAUSIBILITY OF A FOCAL MODEL

 

     The first objective in developing the single-neuron theory is to determine, on a macroscopic level, just which brain region or regions participate directly in VR-conscious experience.  The commonly held view is that it is the activity of neuronal populations dispersed across multiple cortical and subcortical brain regions that mediates VR-consciousness (Llinas et al. 1998; Damasio 1999, Edelman and Tononi 2000, John 2001).  Importance is usually placed not only on cortical processing but also on thalamocortical loops (Llinas et al. 1998; Edelman and Tononi 2000) and involvement of the upper brainstem and other subcortical structures (Damasio 1999).  With regard to cortical information flow, while there is general acknowledgment of a hierarchical arrangement for posterior cortical subregions (Hubel and Wiesel 1962, 1965; Rockland and Pandya 1979; Maunsell and Essen 1983; Felleman and Van Essen 1991; Barbas and Rempel-Clower 1997; Lamme and Roelfsema 2000; Inui et al. 2004), the flow of information between posterior and frontal cortex is usually regarded as inherently bidirectional and lacking any feedforward directional bias (Fuster 1998).

 

     On the face of it, this multifocal view of conscious information processing seems unavoidable.  It is indeed difficult to imagine how a single brain region could serve as a focus of convergent inputs sufficiently rich to account for the manifest intricacy and multifarious nature of VR-conscious experience.  Additionally, the multifocal view is encouraged by data obtained from brain ablation, neuroimaging, and single-cell electrical recording studies, each of which has demonstrated the importance of widely dispersed brain regions in even the simplest VR-conscious tasks.  Thus, the ablation paradigm, which regards a brain region as important for a given task only if damage to that brain region regularly results in the loss of ability to perform the task, has implicated brainstem, thalamic, limbic, and widespread cortical regions in VR-conscious processing (Crick and Koch 1990a; Damasio 1998; Parvizi and Damasio 2001).  More recently, neuroimaging studies employing functional MRI and related imaging techniques or with those utilizing single-cell recordings from pyramidal neurons in various brain areas have provided direct evidence of a role for widespread cortical and subcortical regions in VR-consciously mediated behavior (Crick and Koch 1990a; Dehaene et al. 1998; Llinas et al. 1998; Raichle 2000).

 

     Despite these arguments, it remains possible that while a distributed model is consistent with the available data, so might be a convergent model.  It may be possible that just a subset or even only one of the areas delineated in the above studies actually subserves VR-conscious experience and that the other areas function only to provide information to this convergent region.  For example, during a VR-conscious visual task, ablation, neuroimaging, and single-cell recording data have together implicated activity spread across primary and secondary occipital cortices, tertiary temporal and parietal association cortices, PFC, and multiple diencephalic and brainstem structures in the context of VR-conscious experience.  Since, however, these disparate regions are highly interconnected, the possibility that only one of the identified regions actually subserves VR-conscious experience and that the other regions serve only to provide input to this focal region cannot be dismissed without further consideration.

 

     For a focal model to gain serious consideration, a brain region would need to be identified that could serve as a locus of convergence for the full set of stimuli that feed VR-conscious experience.  Such a region should manifest certain empirically demonstrable features.  First, the area should be the recipient of afferent connections from brain localities corresponding to each of the sensory, emotional, mnemonic, and other components that make up VR-conscious experience.  Second, it should be the case that the area is adequately connected with brain regions capable of mediating VR-conscious behavioral output.  Third, the area should show activation with neuroimaging or single-cell recording techniques during engagement in VR-consciously mediated tasks.  And fourth, ablation of the area should result in loss of VR-conscious experience.  In the following, the argument will be made that the left lateral PFC (corresponding to portions of Brodmann areas 9, 10, 11, 46, 47) appears to satisfy each of the enumerated requirements.

 

     Afferent Connections:  The first question is whether the left lateral PFC is appropriately positioned to be the recipient of afferent connections pertaining to each of the sensory, emotional, and mnemonic components that comprise VR-conscious experience.  This possibility is often dismissed summarily, but invariably without an accompanying in-depth analysis (eg, see Dehaene 1998).  Yet a review of the neuroanatomical literature suggests that the idea of a convergence zone should not be so casually disregarded.  It has been suggested, for example, that the PFC as a whole functions as a convergence zone, receiving input from most other brain regions (Miller and Cohen 2001; Elston 2003).  Since PFC subregions are strongly interconnected (Barbas and Pandya 1991), any one PFC subregion could be capable of serving as a convergence target for all the other PFC subregions.  In the single-neuron theory, it is the left lateral PFC that is assumed to serve as the final convergence area for the sensory, emotional, and mnemonic components of VR-consciousness, with evidence in support of this contention available for each of these components.

 

     With regard to sensory input, the lateral PFC has long been established to receive input from the occipital, temporal, and parietal association cortices that process the incoming visual, acoustic, and tactile signals that provide the organism with information about its extrapersonal and proprioceptive space (Kuypers et al. 1965; Pandya and Kuypers 1969; Goldman-Rakic and Schwartz 1982;  Petrides and Pandya 1984, 1999; Seltzer and Pandya 1989; Barbas and Pandya 1989; Pandya and Yeterian 1990), including simultaneous convergent input from multiple modalities (Jones and Powell 1970; Chavis and Pandya 1976; Bruce et al. 1981).  Additionally, the lateral PFC receives inputs from the caudal orbitofrontal cortical regions that function as association areas for taste and smell (Baylis et al. 1995, Johnson et al. 2000), with inputs for the latter bypassing the thalamus and projecting solely to the frontal lobes.

 

     With regard to emotion, ablation and activation studies have each supported a role for both anterior cingulate and ventromedial orbitofrontal cortices in assessing the emotional significance of stimuli (Baleydier and Mauguiere 1980, Bush et al. 2000, Phan et al. 2002).  Anatomically, these regions are the recipients of input from the amygdala, the hypothalamus, and the hippocampus (Porrino et al. 1981; Amaral and Price 1984; Goldman-Rakic et al. 1984; Barbas and DE Olmos 1990) which carry the processed visceral stimuli from which emotions are proposed to be comprised (Damasio 1999).  Both regions project strongly to lateral PFC (Eslinger and Damasio 1985) where, it is suggested (Damasio 1999; Gray et al. 2002), emotion and cognition become integrated, with feelings providing “value,” which is needed for decision-making.

 

     With regard to memory, links to lateral PFC are well established for both short-term working memory and long-term distraction-stable memory.  For short-term working memory, findings from ablation, neuroimaging, and single-cell recording studies point to the lateral PFC as a principal site (along with temporal and parietal tertiary association cortex) wherein information is retained for brief periods during the performance of complex problem-solving tasks (Fuster and Alexander 1971; Kubota and Niki 1971; Goldman-Rakic 1992; Cohen et al. 1997; Courtney et al. 1997; D'Esposito et al. 1998; Rainer et al. 1998, 1999; Romo et al. 1999; Fletcher and Henson 2001; Constantinidis and Goldman-Rakic 2001; Constantinidis et al. 2002).

 

     For long-term distraction-stable memory, the lateral PFC plays a key role in the retrieval of episodic memories stored in posterior neocortex and hippocampus (Goldman-Rakic 1992; Fuster 1999), a component of memory that is inherently conscious (Tulving 2002).  Direct connections between the hippocampus and the lateral prefrontal cortex have been established, and ablation (Wheeler 1995) and neuroimaging studies (Fletcher and Henson 2001; Braver et al. 2001, Slotnick et al. 2003) have provided direct evidence of a relationship between lateral PFC and long-term memory function.

 

     Efferent Connections:  On the efferent side, the question is whether the left lateral PFC is able to access the motor programs that presumably mediate VR-conscious behavioral output.  There is ample evidence that this is the case for lateral PFC, which sends outputs to the frontal eye fields, the premotor frontal cortex, the basal ganglia, cerebellum, and superior colliculus (Goldman and Nauta 1976; Alexander et al. 1986, Bates and Goldman-Rakic 1993; Lu et al. 1994; Schmahmann and Pandya 1997).  For VR-consciousness in particular, a critical issue is whether the left lateral PFC is connected adequately with Broca's area, the brain region that provides for syntactical linguistic output.  The pivotal role of Broca's area, situated in the posterior part of the inferior frontal gyrus (Brodmann's areas 44 and 45) of the left frontal lobe, in language expression was established first in 1861 (Broca 1861) and has been amply confirmed in the one and a half centuries that have followed.  For logical, grammatical output, which is the type involved in verbally reporting on VR-conscious experience, the situation is asymmetric, with only the "dominant" hemisphere (the left hemisphere in most humans and almost all right-handers) capable of performing the function.  Left lateral PFC is ideally positioned to influence Broca's area and thereby express verbal reports pertaining to VR-conscious experience since it lies immediately adjacent to it and projects to it strongly (Deacon 1992).

 

     Activation Studies:  The principal evidence for activation of the left lateral PFC during VR-conscious tasks comes from studies of working memory, a cognitive function that is usually regarded as VR-conscious (Baddeley 2003).  As noted above, neuroimaging and single-cell recording studies indicate that lateral PFC is a principal mediating site for working memory.  Additionally, left lateral PFC has been shown directly to become active in neuroimaging studies during tasks involving VR-conscious experience (McIntosh et al. 1999; Kjaer et al. 2001, Stephan et al. 2002).  Event-related potential measurements in humans have shown further that lateral PFC is activated subsequent to posterior cortex in association with performance of VR-conscious tasks, with a mean latency of activity in response to visual stimuli over occipital areas measured at 56 msec and over lateral PFC at 80 msec (Foxe and Simpson 2002).  This temporal sequence of events would be in keeping with a model in which posterior cortex provides preliminary processing of stimuli for subsequent VR-conscious processing by lateral PFC.

 

     Results of Ablation:  If the left lateral PFC were, by itself, the mediator of VR-conscious experience, then ablation of the region should result in its elimination.  Care is needed, however, in applying this syllogism in clinical situations.  To begin with, since the focus up to this point has been specifically on VR-consciousness, not on higher consciousness in general, clinical cases would need to be assessed for the presence or absence of this particular form of consciousness if they were to serve as an appropriate test of the proposed theory as presented so far.  As we will see when we extend the discussion of the theory beyond the confines of consciousness of the verbally reportable variety, it would be damage to the lateral PFC bilaterally that would be expected to eliminate higher consciousness in general.

 

     There is also a methodological concern having to do with the extent of the cortical damage incurred in reported cases.  As will be evident when the theory is described on the microscopic level, only nearly complete inactivation of the left lateral PFC would be predicted to eliminate VR-consciousness, and only complete inactivation of the lateral PFC bilaterally would be predicted to eliminate higher consciousness more generally.  Thus, we note that some authors (Bogen 1995; Alexander and Stuss 2000; Taylor 2001) have cited clinical examples in the literature, such as the celebrated case of Phineas Gage (Damasio 1999), where extensive prefrontal lesions failed to eliminate higher conscious experience, and have used these to argue that the lateral PFC by itself cannot be the sole mediator of higher consciousness.  As pointed out by Crick and Koch (1998), however, in none of these cases did the damage include the entirety of the lateral PFC, rendering their significance uncertain.  With only partial removal of the relevant cortex, the remaining tissue might have been able to maintain residual higher conscious function.  On the other hand, situations in which the lateral PFC is known to have been entirely destroyed bilaterally, such as in patients with advanced Pick's disease, massive bilateral strokes, extensive anoxic damage, or massive surgical bilateral frontal lobe ablations as reported by Walter Dandy (1946), the clinical picture is of a persistent vegetative state in which the victim is devoid of any higher level consciousness (Sato et al. 1989; Laureys et al. 1999; Heilman and Valenstein 1993; Laureys 2004).  And in cases in which the left lateral PFC is known for certain to have been destroyed entirely, such as in global aphasia from a massive left middle cerebral artery stroke, VR-consciousness is clearly lost, with the right hemisphere providing residual, nonverbal higher conscious function (Heilman and Valenstein 1993).  While such cases are consistent with the notion that VR-consciousness is mediated solely by the left lateral PFC, and that higher consciousness in general is mediated solely by the lateral PFC bilaterally, the extensive nature of the damage in these reports ruins the specificity of the correlation.

 

      Cases are needed in which the left lateral PFC (or the lateral PFC bilaterally) has been completely removed or rendered inoperative while other structures have been left intact, and an assessment made specifically for the presence or absence of VR-consciousness (or higher consciousness more generally).  Such cases have yet to be reported.

 

     In summary, anatomical and functional studies have been reviewed that point to the importance of left lateral PFC for VR-conscious experience.  Other authors have also emphasized the importance of the lateral PFC to consciousness (Crick and Koch 1998; Rees et al. 2002; Stephan et al. 2002).  The present theory goes further, however, in proposing that the left lateral PFC, situated within a divergent/convergent feedforward information processing system, serves by itself as the direct neural correlate for VR-consciousness.  On the other hand, suggestions have occasionally been made favoring other brain regions as a center for consciousness (Dandy 1946; Taylor 2001).  The parietal tertiary association cortex is an attractive possibility (Taylor 2001), but the parietal lobes do not receive direct information pertaining to smell, which is a common component of VR-conscious experience.  Alternatively, the orbitofrontal cortex, which is a region that receives convergent input from all modalities, might be considered to be a candidate for a localized NCC.  However, complete orbitofrontal ablations, while they impair emotional processing, do not eliminate VR-consciousness (Eslinger and Damasio 1985; Heilman and Valenstein 1993; Damasio 1999).   

 

     The localization to the left lateral PFC proposed in this paper, it should be noted, may not be the full extent to which VR-consciousness is localized.  The lateral PFC might itself be further divisible.  In fact, support has been garnered for the lateral PFC encompassing two functionally distinct subregions, one dorsolateral (portions of Brodmann 9, 46) the other ventrolateral (portions of Brodmann 10, 11, 47), the two subregions differing with respect to both anatomical connections and type of information being processed (Oliveri et al. 2001).  It has been suggested that the established division of the posterior cortex into "dorsal" and "ventral" streams (Ungerleider and Mishkin 1982; Goodale and Milner 1992; Milner and Goodale 1993; Foxe and Simpson 2002) continues into the frontal lobes, with the dorsolateral PFC receiving input from the dorsal stream via the parietal association cortex and the ventrolateral PFC receiving input from the ventral stream via the temporal association cortex (Milner and Goodale 1995).  Since both areas are strongly connected to Broca's area, both are in a position to affect verbal output.  Further, since both areas are strongly interconnected, either could ultimately be the sole mediator of VR-conscious experience with the one serving to provide input to or receive output from the other.  In fact, Milner and Goodale (1995) have argued for just this possibility, suggesting that only the ventral stream is associated with VR-conscious experience and that the dorsal stream processes information VR-unconsciously.

 

     In the discussion that follows, the question of which subregion by itself might mediate VR-conscious experience will be left undecided and the generic term "lateral PFC" will be used to refer to the area in general.  In any case, whatever the final localization of the macroscopic anatomical substrate for VR-consciousness might be, all that is needed for the further development of the single-neuron theory is that a macroscopically focal correlate for VR-consciousness exists that is relatively homogeneous and is in a position to receive all the sensory, emotional, and mnemonic stimuli that characterize the VR-conscious experience.

 

4. THE MICROSCOPIC STEP:  THE SINGLE-NEURON THEORY

 

     Subsequent to the question of which macroscopic brain region mediates VR-consciousness is the question of how the neurons populating this region accomplish the task.  According to the generally accepted view, the participating neurons join their activity into a single VR-conscious experience via dynamic interactive mechanisms.  The single-neuron theory posits instead that a subpopulation of neurons in the left lateral PFC, rather than joining their activity into a single VR-consciousness, remain separately VR-conscious and produce the illusion of a joint VR-consciousness by virtue of the joint action of their outputs.  In the model, each of the VR-conscious neurons at any moment is proposed to experience not merely a fragment of a higher-order joint VR-consciousness but, rather, the whole range and complexity of VR-conscious experience generally attributed to the population as a whole.  Plausible candidates for the role of VR-conscious neurons are the layer 5 pyramidal cells of the left lateral PFC.  A pivotal role for these neurons in conscious processing has been suggested by other investigators (Crick 1994; Orpwood 1994; Gilbert 1998; Bieberich 2002).  It will be useful to briefly review the main characteristics of these neurons before describing how they might individually serve as neural correlates of VR-consciousness.

 

Anatomical and Functional Characteristics of Lateral PFC Layer 5 Pyramidal Neurons

 

     Like all neurons, layer 5 pyramidal cells function by integrating the electrical responses of an enormous array of dendritic synaptic inputs, the result of which determines a single channel of axonal output consisting of sequences of action potentials of identical shape and amplitude.  Early on, the dendritic tree was modeled as a single entry point (McCullough and Pitts 1943), with inputs simply summing linearly to produce axonal output.  In the late 1950s, Rall (1959, 1967) introduced the passive cable model, in which the spatial extent of the dendritic tree was taken into account and accommodation was made for the effects of location and amplitude of postsynaptic potentials on the neuron's axonal response.  The passive cable model provided for a degree of intradendritic information processing that was not possible with the earlier "point neuron" model.  In recent years, the presence of significant nonlinear intersynaptic effects occurring on multiple levels has been discovered (Cash and Yuste 1999; Magee 1999; Koch 1999; Larkum et al. 1999a; Magee and Cook 2000; Spruston 2000; Hausser et al. 2001; Wei et al. 2001), suggesting that considerable intradendritic computational processing precedes the eventual generation of axonal action potential.

 

     Additionally, there is evidence that intradendritic processing occurs independently in separated compartments before an overall effect is delivered to the soma (Koch 1997).  For layer 5 pyramidal neurons, a unique anatomy facilitates this compartmentalization.  Most notable is the long ascending dendritic shaft, extending 1.3 mm from the cell body in layer 5 to the apical tip in layer 1, that separates the proximal basal dendrites from the distal apical dendrites.  Midway along the shaft are the oblique dendrites, both proximal and distal.  Recent evidence suggests that the output of the various compartments interact via two intraneuronal dendritic action potentials.  The first is a forward propagating, calcium-mediated potential originating at the distal end of the dendritic stalk that is produced as a result of nonlinear integration of apical dendritic inputs.  This action potential courses from the apical end of the dendritic shaft to the soma where it induces a burst of axonal action potentials (Helmchen et al. 1999; Schiller et al. 1995, 1997; Schwindt and Crill 1999; Larkum et al. 1999a; Williams and Stuart 2002).  The second is a backpropagating sodium-mediated action potential that is triggered by axonal firing and that courses from the soma back into each of the dendritic arbors (Stuart and Sakmann 1994).  The two action potentials appear to be coupled, with the backpropagating potential lowering the threshold for triggering of the forward propagating potential, provided the two potentials occur within a few milliseconds of each other (Larkum et al.1999a, 1999b; Larkum et al. 2001; Schaefer et al. 2003; Larkum et al. 2004).  The coupling has been shown to depend crucially on the morphology of the participating dendritic branches (Mainen and Sejnowski 1996; Schaefer et al. 2003; Vetter et al. 2001).

 

     Aside from the nonlinear interactions present at the intercompartmental level, nonlinear interactions have been found within the dendritic arbors as well (Cash and Yuste 1999; Magee 1999; Koch 1999; Larkum et al. 1999a; Magee and Cook 2000; Spruston 2000; Hausser et al. 2001; Wei et al. 2001; see Magee 2000 for a review).  It has been suggested that nonlinear interactions between neighboring synapses provide for increased computational capability in dendritic trees (Segev and London 2000; Van Ooyen et al. 2002; see Hausser and Mel 2000 for a review).

 

     Because of the anatomy and compartmentalization of the layer 5 pyramidal neurons, they are ideally positioned to integrate input from the different cortical layers (Spratling 2002; Thomsen et al. 2002a; Briggs and Callaway 2005).  Thus, the basal dendrites, which are situated near the cell body in layer 5, receive intralaminar input from other pyramidal neurons in the same layer (Lubke et al. 1996; Thomson et al. 2002b; Douglas and Martin 2004).  Higher up, the oblique dendrites receive inputs from layers 2, 3 and 4 (Schaefer et al. 2003).  Still more distally, the apical dendrites receive inputs from layers 1, 2 and 3 (Schaefer et al. 2003).

 

     A functional interpretation of these inputs is provided by a proposed microscopic feedforward circuit that includes the layer 5 pyramidal neurons (Gilbert and Wiesel 1986; Thomson et al. 2002a,b; Thomson and Bannister 2003).  The main pathway in this circuit is characterized by a feedforward flow beginning with the layer 4 stellate (granular) neurons, which receive incoming feedforward signals from other cortical and thalamic regions, and moving on to the pyramidal neurons in layers 2 and 3, then on to layer 5 pyramidal neurons, and finally out to pyramidal neurons in layers 1 and 5 elsewhere in the prefrontal cortex, as well as to premotor cortex, posterior cortex, thalamus, basal ganglia, and superior colliculus.  Return input from these distant targets arrive via diffusely projecting layer 1 fibers, whose signals are received by the pyramidal neurons in layers 2 and 3, and 5 (the latter receiving inputs from layer 1 both directly and also indirectly via inputs from layers 2 and 3).  In this scheme, the input from layer 1 consists of diffusely encoded signals derived from thalamus, hippocampus, and posterior and frontal limbic areas (Barbas and Rempel-Clower 1997; Rempel-Clower and Barbas 2000; Mitchell and Cauller 2001; Barbas and Hilgetag 2002).  These inputs have been postulated to be associated with attention, feedback, and context (Williams and Stuart 2002; Douglas and Martin 2004)).  The inputs to layer 2 and 3 pyramidal neurons derive from both local and distant layer 2 and 3 pyramidal neurons located throughout the lateral PFC.  These layer 2 and 3 pyramidal neurons are, especially in the lateral PFC, highly interconnected and have been proposed to serve an important role in the maintenance of reverberatory circuits underlying working memory (Kritzer and Goldman-Rakic 1995; Gonzalez-Burgos et al. 2000; Melchitzky et al. 2001).

 

     An important implication of these pathways and connections (see Larkum 2001), and one that will be used in developing the single-neuron model, is that the apical dendrites of layer 5 pyramidal neurons, by virtue of being recipients of layer 2/3 pyramidal cell output, are in a position to receive inputs representing the full range of VR-conscious content.  In the following sections, we will build on this and the other characteristics of layer 5 pyramidal neurons to present a specific way in which the single-neuron theory of consciousness might play out at the microscopic level.  It should be noted that it is not contended that the model to be presented is the only way a single-neuron theory can be instantiated.  For example, it may be that neurons other than the layer 5 pyramidals might equally well serve as loci for VR-consciousness, or it may turn out that the details of layer 5 pyramidal function as described above need modification.  The purpose of the presentation is mainly to provide a specific instantiation of the theory in order to demonstrate that a single-neuron model is in principle feasible.  The model will be built upon a framework of convergent/divergent feedforward information flow, in which feedback and reentrant circuits play only an adjunctive role.  The features of the model will be presented in a feedforward sequence:  A) first, a mechanism of information encoding at the neuronal population level will be described for the network of neurons that will serve as the afferent input for VR-conscious neurons; B) second, the process by which signals converge upon the dendritic trees of VR-conscious neurons and induce intradendritic NCCs will be considered; C) third, a mechanism by which the dendritic NCCs reexpress themselves at the neuronal population level will be suggested.

 

A) Population Encoding of the Information to be Inputted to the VR-Conscious Neurons:

 

     We begin by examining the information processing characteristics of layer 2 and 3 pyramidal neurons in left lateral PFC, which will be presumed to be the source of the inputs to layer 5 pyramidal neurons that lead to VR-consciousness.  In overview, it is hypothesized that the convergent input to the left PFC as a whole, argued in the previous section to contain the sensory, emotional, and mnemonic signals that feed VR-consciousness, passes from layer 4 stellate neurons to layer 2/3 pyramidal neurons, and that the relevant information is encoded in the spatial arrangement of a synchronously firing subpopulation of these layer 2/3 neurons.  We now consider this process in more detail.

 

     As a preliminary, we need first to address the nature of the neural code.  There has been an ongoing debate over how information is encoded by neuronal populations in neocortex.  The principal questions have to do with the relative importance of individual neuronal spikes in cortical processing and whether spikes derived from different neurons are bound by means of temporal synchrony.  The early view was that information is encoded in the cortex by the average rate of axonal action potential production over a given time interval, typically between 20 and 200 msec, and that the exact timing of individual spikes is unimportant. (Adrian 1926; Barlow 1972; Shadlen and Newsome 1994; Shadlen and Newsome 1998; Shadlen and Movshon 1999; Yazdanbakhsh et al. 2002; Rolls et al. 2003).  In recent years, however, the alternative possibility, that each spike individually carries relevant information, has gained a growing following (Softky and Koch 1993; Gray 1999; Borst and Theunissen 1999; Williams and Stuart 2000; Abeles 2004).  A related idea, that brain neuronal activity can be synchronized, and that synchrony is in fact a widely occurring and robust phenomenon that might serve to define functional relationships between spatially distributed cortical neurons, has also gained considerable support (Abeles 1991; Konig et al. 1995; Singer and Gray 1995; Lumer et al. 1997; Stevens and Zador 1998; Lachaux JP et al. 1999; Usrey and Reid 1999; Grammont and Riehle 2003).  The possible mechanisms underlying the induction of temporal synchrony of cortical neuronal activity have been explored (Niebur et al. 2002; Reyes 2003; Segev 2003; Nowotny and Huerta 2003), as has its possible behavioral relevance (Sougne and French 2001).  In particular, it has been suggested that synchronous firing promotes synergy between spikes arriving simultaneously at target neurons, thereby providing a powerful signal selection mechanism (Niebur et al. 2002; Averbeck and Lee 2004).

 

     For the theory presented in this paper, it will be assumed that individual spikes do matter, and that synchronous firing identifies subpopulations of neurons that encode salient information in their spatial arrangement.  The model employed is an adaptation of the well-studied "synfire chain" mode of cortical signal transmission (Abeles 1991, 2004; Aviel et al. 2002), which invokes the importance of both individual spike timing and the synchronization of spatially dispersed neuronal activity.  The synfire chain theory describes a process of synchronous convergent/divergent feedforward signal transmission through multiple neuronal layers.  Synchrony is hypothesized to result from an arrangement in which, for each layer, there is a pool of neurons with the property that each neuron in the pool:  a) receives afferent inputs from all the neurons in the pool in the previous layer, and b) projects its output to all the neurons in the pool in the next layer.  Empirical observations supporting the presence of synfire chain activity in the brain have been reported by a number of investigators (Abeles 1991; Miller 1996; Prut et al. 1998; Abeles 2004; Ikegaya et al. 2004) and their properties have been analyzed through theoretical simulations (Abeles 1991; MacGregor et al. 1995; Aertsen et al. 1996; Hertz and Prugel-Bennett 1996; Diesmann et al. 1999; Arnoldi et al. 1999; Gewaltig et al. 2001; Sougne and French 2001; Yazdanbakhsh et al. 2002).  Theoretical simulations have indicated how, in a multilayered feedforward neural network consisting of integrate-and-fire neurons, synchronous firing on a millisecond time scale arises in successive layers, even if the initial input to the chain are asynchronous (Pinsky 1995; Arnoldi and Brauer 1996; Hertz and Prugel-Bennett 1996; Marsalek et al. 1997; Rudd and Brown 1997; Campbell et al. 1999; Neltner et al. 2000; Niebur et al. 2002; Reyes 2003; Segev 2003; Nowotny and Huerta 2003).  The synchronous chains have been shown to be stable against noise, provided a sufficient number of neurons populate each pool, estimated to be on the order of 100 neurons (Abeles 1991; Postma et al. 1996; Diesmann et al. 1999; Gewaltig et al. 2001; 2001).  In the stable state, essentially all response spikes in a volley fall within ±1 ms, which is within the precision of experimentally observed neuronal firing patterns, despite the presence of a membrane time constant of 10 ms or more (Diesmann et al. 1999; Gewaltig et al. 2001).

 

     In the proposed single-neuron theory, the presence of a synfire chain comprising two consecutive pools of neurons is hypothesized:  one pool in lateral PFC layer 2/3, the other pool in lateral PFC layer 5.  The pool in layer 2/3 is taken to comprise a subpopulation of synchronously firing pyramidal neurons that have received feedforward input from layer 4 pertaining to VR-consciousness, with that information being encoded in the spatial arrangement of the participating neurons.  The presence of identifiable spatial patterns of neuronal excitation in cortical neuronal populations has been reported in a variety of contexts.  These include the peculiar complex logarithmic relationship between spatial patterns of excitation in the retina and those in area V1 pyramidal neurons (Schwartz 1980; Alexander et al. 2004), the specific topographic pattern of layer 5 pyramidal neurons in cat visual cortex that exhibited repeating temporal spike sequences (Ikegaya et al 2004), the specific spatial patterns of neuronal response to air currents in the cricket cercal system (Jacobs and Theunissen 2000), and the work of Grossberg et al. (1999), which implicates an important role for the topography of primate visual cortex in shaping neuronal responses at subsequent levels of cortical visual processing.  In the single-neuron theory, it is the topography of neuronal activation in the synchronously firing layer 2/3 pyramidal population that is assumed to carry the information to be delivered to the layer 5 pyramidal neurons.

 

B) Conversion of Afferent Population Patterns into Intradendritic Neuronal Electrical Patterns:

 

     The next issue in the feedforward progression is the matter of how the afferent signals from the synchronously firing layer 2/3 pyramidal neurons converge upon layer 5 pyramidal neurons and lead to intradendritic electrical activity that serves as the neural correlate for VR-consciousness.  Consideration will be given first to the synaptic activation patterns induced in the layer 5 pyramidal neurons, and then to the conversion of these synaptic activation patterns into spatial electrical patterns within the dendrites.  For the model to work, two hypotheses are needed:

 

HYPOTHESIS 1: THE MAPPING FROM POPULATION TO DENDRITIC IS HOMOTOPIC AND INFORMATION PRESERVING:  Despite its vital importance to an understanding of neuronal information processing, there is little available data pertaining to the neurons of origin for particular synaptic inputs within a dendritic tree.  That is, while neurons of origin have been identified with respect to one or another overall dendritic compartment, similar information with respect to individual synaptic inputs within a compartment are not yet available.  In the absence of such empirical clues, I would suggest that a plausible possibility is that the topographic mapping of inputs from the synchronously firing layer 2/3 pyramidal neurons onto layer 5 pyramidal dendrites is homotopic (the shape of the one can be continuously transformed into the shape of the other) and information preserving.  Homotopic, information preserving mappings have been found elsewhere in the nervous system, such as in the complex logarithmic mapping of retina onto V1 already mentioned (Schwartz 1980; Alexander et al. 2004), and in the homotopic connections between the cerebral hemispheres via the corpus callosum (Mitchell and Macklis 2005).  The suggestion is that the axons arriving from the synchronously firing layer 2/3 pyramidals retain their relative positions and preserve topological information in coursing toward their targets and do not "criss-cross" on their way to innervating the dendritic tree of the layer 5 pyramidals.  Whether this is in fact the case will need to be determined experimentally.  Since it plays a key role in the hypothesized theory, testing for its presence will serve as an empirical test for the plausibility of the proposed theory.

 

HYPOTHESIS 2: SIMILAR PATTERNS ARE RECEIVED BY MULTIPLE NEURONS:  A second assumption is that the projections from layers 2 and 3 to layer 5 involve convergence of a similar pattern onto multiple neurons.  If the topographic pattern of synaptic excitation is relevant in determining whether it induces axonal firing or not, then this is in effect the central assumption of the synfire chain theory that was discussed in detail above, and upon which the currently proposed model is based.

 

     With these hypotheses in hand, a mechanism can be described by which the spatially encoded pattern at the population level in layer 2/3 reappears as a spatially encoded pattern of intradendritic electrical activity in layer 5 pyramidal cells, this pattern serving as the neural correlate for VR-consciousness.  We start by proposing that the spatial electrical pattern corresponding to VR-consciousness forms within the thin distal branches of the apical dendritic tree.  While alternative locations, such as the thin oblique dendritic branches, could also be chosen, the apical branches are selected here to provide a concrete example of how the overall model would work.  By hypothesis 1, it is assumed that a specific pattern of synaptic excitation is induced by convergent input from a synchronously firing pool of layer 2/3 pyramidal neurons, and that this pattern of synaptic excitation is a homotopic, information preserving transform of the spatial pattern of the layer 2/3 neuronal pool.  By hypothesis 2, it is assumed that a similar pattern of input is received by a pool of layer 5 pyramidal cells.

 

     The shape of the electrical response within the dendritic branches of each neuron receiving this pattern of synaptic input will, in turn, be an ordered transformation of the shape of the incoming signals (Bieberich 2002, Orpwood 1994, and Livingstone 1998), modified by the effects of synapse efficiency and local nonlinear effects (including those due to the state of depolarization of the synapses at the time of signal input, the interactive effects between synapses due to induced local chemical and electrical changes, and the morphology of the dendritic tree itself), each of which is likely somewhat different for each of the neurons in the receiving pool (Spruston et al. 1995; Mainen and Sejnowski 1996; Hoffman et al. 1997; Agmon-Snir et al. 1998; Cash and Yuste 1999; Magee 1999; Koch 1999; Larkum et al. 1999a; Magee and Cook 2000; Spruston 2000; Magee 2000; Vetter et al. 2001; Hausser et al. 2001; Wei et al. 2001;; Schaefer et al. 2003; Polsky et al. 2004).  The variations in the shape of the intradendritic electrical responses across the different neurons would be assumed to be relatively small, so that variations in VR-conscious experiences of the different neurons would be relatively small as well.  I will consider later the potential impact that large variations might have on the single-neuron theory.

 

     Of critical importance to the singe-neuron theory is the assumption that the intradendritic electrical pattern that forms in the distal apical branches, which is proposed to serve as the direct neural correlate for VR-consciousness, extends through only a portion of the neuronal dendritic tree.  It is hypothesized that its ultimate effect on axonal firing therefore comes only after it combines nonlinearly with other intradendritic electrical activity, both within the more proximal apical tuft in generating a calcium-mediated dendritic action potential and in the subsequent interaction between the different dendritic compartments.  That is, the local electrical activity that serves as the neural correlate for VR-consciousness in the distal apical tree of a given neuron is assumed to affect neuronal output only in the context of other inputs received by the neuron at the same time.  Again, this effect is presumed to be different for the different layer 5 pyramidal neurons in the pool, and therefore the responses of the different neurons to the same (more or less) VR-conscious electrical activity forming in the distal apical dendrites will be different.  In the next section, this fact will be used in proposing a mechanism by which the intradendritic VR-conscious shape reexpresses itself at the neuronal population level.  Before turning to that mechanism, it is important to consider whether the electrical activity purported to serve as the neural correlate for VR-consciousness has the right type and degree of complexity to encode for conscious experience.

 

COMPLEXITY OF INPUTS TO THE LAYER 5 PYRAMIDAL NEURONS:   For the single-neuron theory to be plausible, it needs to be the case that the electrical activity in the distal apical branches of an individual neuron is by itself complex enough to support the complexity of VR-conscious experience.  The relevant observation pertaining to this requirement is that cortical pyramidal neurons receive a huge number of afferent signals over their dendritic trees.  It is estimated that for humans each cortical pyramidal neuron incorporates between 20,000 and 40,000 synapses within its dendritic tree (Abeles 1991), a number larger than is usually appreciated and one that allows for an impressive complexity of information encoding.  For example, if only one tenth of one percent of the synapses of a cortical pyramidal neuron were assumed to participate in a given VR-conscious experience, and if only a simple binary code were being used (that is, one in which the synapse is either active or inactive), then 240 or about one trillion different patterns could be encoded by that neuron.

 

     Alternatively, as noted by Bieberich (2002), if it is assumed that 5,000 simultaneously arriving synaptic input bytes, corresponding to 5,000 active spines in the dendritic tree, are turned over with a frequency of 50 Hz, then a single neuron would be capable of processing 5 mB of information per second.  This, Bieberich argues, constitutes a rate of information processing adequate to plausibly account for the complexity of VR-conscious experience.

 

     By either of these calculations, individual cortical pyramidal neurons appear capable of processing information of a complexity greater than often appreciated, and quite possibly sufficient to mediate the entirety of the VR-conscious experience.

 

CONVERGENCE OF MODALITIES UPON INDIVIDUAL LAYER 5 NEURONS:  Another requirement that the single-neuron theory must meet is that the dendritic trees of the VR-conscious neurons would need to individually be recipients of all of the kinds of inputs that make up the VR-conscious experience.  If it is assumed that the lateral PFC as a whole receives all of the inputs that comprise VR-conscious experience, then the question is whether it plausible that there are individual pyramidal neurons within the region that do likewise?  That is, is it plausible that the information that converges upon the region as a whole converges separately on each of a subgroup of pyramidal neurons populating the region?  In support of the presence of such an arrangement is the clinical observation that focal lesions within lateral PFC do not result in modality-specific deficits but only diminish the region's function in a general manner.  This suggests at least some degree of microscopically redundant convergence throughout the extent of the region.  Additionally, individual cortical neurons typically receive inputs from thousands of other neurons (Koch 1997, Schuz 1998) and so are in a position to serve as nodes of converging information.  Aside form general considerations, however, are the reports that direct single-cell recordings have identified neurons in lateral PFC that respond selectively to conjoint visual and auditory stimuli (Aou et al. 1983), to conjoint visual, auditory and tactile stimuli (Tanila et al. 1992), and to conjoint object and location features (Rao et al. 1997). Whether a subgroup of lateral prefrontal neurons exists in which each neuron in the subgroup receives convergent input from all the sensory, emotional, and mnemonic stimuli that comprise VR-conscious experience is yet to be empirically determined.

 

C) Generation of the Outgoing Signal:

 

     Supposing that the spatial pattern of distal apical intradendritic electrical activity of left PFC layer 5 pyramidal neurons serves as the neural correlate for VR-conscious experience, there is then the vexing question of how the information encoded at the dendritic level is passed on to brain output mechanisms that control behavior.  In particular, how can dendritic signal patterns of high complexity converge into a single axonal output channel without a drastic loss of information?  On the face of it, it would appear that such information loss is unavoidable, since axons transmit action potentials that are uniform in shape and amplitude and therefore only the timing of the transmitted spikes can be used to encode information (Adrian 1926).  Across a range of settings, the information contributed by individual axonal spikes has been measured to be on the order of one bit to 3 bits per spike, with an axonal information transmission rate therefore reaching no more than several hundred bits per second (Bialek et al. 1991, Borst and Theunissen 1999).  This rate of information processing is far smaller than that performed by the dendritic tree.  How, then, can a gross loss of information be averted?

 

     A possible solution to this problem may reside in another application of synchronous neuronal firing, one that is inspired by a model of neuronal information processing recently proposed by Bieberich (2002).  The idea is that a mechanism by which the VR-conscious electrical activity present within the layer 5 pyramidal dendrites might be reexpressible at the population level in the form of the spatial arrangement of a synchronously active subset of the layer 5 pyramidal cells.  Conceptually, the sequence is as follows:

 

   1) First, as described above, similar VR-conscious spatial patterns of electrical activity are formed in the distal apical trees of a population of synchronously activated layer 5 pyramidal neurons in the left lateral PFC.

 

   2) Next, the VR-conscious spatial patterns interact nonlinearly, at both the intracompartmental and intercompartmental levels, with the other inputs received by these layer 5 neurons.

 

   3) The results of these interactions are assumed to differ across neurons in the population and therefore to have different effects on the propensity for axonal spike generation in the different neurons in the population, such that some neurons fire while others remain silent.

 

   4) As a consequence of (3), only a subgroup of neurons in the population respond with synchronous firing, with the active subgroup marking out a spatial pattern at the population level.  The spatial pattern, it will be noted, would in part have been dictated by the spatial pattern of the VR-conscious dendritic electrical activity in the neurons of the population.

 

   5) If there are N neurons in the starting population and only M neurons fire (M<N), then the number of different subgroups that can be formed (and therefore the number of different spatial arrangements of firing neurons that can arise) is given by the combination of N things taken M at a time: N!/M!(N-M)!  For even small populations, this is a huge number.  For example, say there are 100 layer 5 pyramidal neurons that receive synchronous dendritic inputs of similar shape from the layer 2/3 neurons, and that half of these 100 neurons fire.  Then the number of different spatial patterns that can form would be equal to the combination of 100 things taken 50 at a time, or (100!)/(50!)(2) = 4 x 1012, an enormous number that matches the complexity of dendritic input as calculated above.

 

   6) The spatial pattern formed by the subpopulation of synchronously firing left lateral PFC layer 5 pyramidal neurons, which incorporates the interaction between VR-conscious information and other information received by the layer 5 pyramidal neurons, serves as the source of conscious output from the left lateral PFC to other brain regions.

 

     While this mechanism may provide a means for the information contained in the intradendritic VR-conscious electrical patterns to be re-expressed at the population level, there is the additional question of whether enough neurons are present in the proposed synchronous populations in layers 2/3 and 5 to affect gross behavior.  As so far described, this would appear unlikely, since previous work with synfire chains has usually associated the phenomenon with relatively small neuronal groups (Abeles 1991).  A realistic model would need to incorporate the possible presence of many small competing synchronous neuronal groups.  For a single dominant synchronous group to arise, still additional assumptions would have to be made.  This issue is, of course, not unique to the theory presented here.  It is a challenge that must be faced by most current neuronal network models of consciousness.

 

     A plausible approach to solving this problem may be to invoke the concept of attention as a mechanism for amplifying the effects of selected synchronously firing neuronal pools.  Studies have, in fact, been reported that suggest a role for attention in increasing the synchrony of neuronal firing (Steinmetz 2000; Fries et al. 2001), possibly mediated by gamma frequency oscillations (Crick and Koch 1990a,b; Niebur et al. 1993; Niebur and Koch 1994).  In this way, attention might serve as an "on-off" switch for lateral PFC conscious function.  The detailed nature of the attentional mechanism by which the small population of synchronously firing neurons might gain control over VR-conscious output systems can only be speculated on at present.  One possibility is that the "bursty" output of the layer 5 pyramidal neurons (Crick 1994; Schiller et al. 1995, 1997; Helmchen et al. 1999; Schwindt and Crill 1999; Larkum et al. 1999a; Williams and Stuart 2002), in association with cortico-thalamo-cortical loops (Llinas et al. 1998), may provide for the proliferation of the synchronous groups.  This could conceivably be accomplished through competition, as in the "neural darwinism" mechanism described by Edelman (1993), or perhaps via merging of separate synfire chains (Arnoldi et al. 1999; Hayon et al. 2005).  Yet another possibility might involve the creation of a fractal architecture in which multiple copies of the synfire neuronal pool arise as a result of the fractal geometry of axonal branching (Bieberich 2002).  With each of these proposed mechanisms, the lateral PFC would be envisioned as functioning in a “holographic” manner, with the same information represented repeatedly in neurons dispersed across the full extent of the region.  As a result, it would be expected that damage to the entire lateral PFC would be required to eliminate the corresponding conscious functioning, a point that was stressed earlier in Section 3.

 

     In summary, a case has been made for the possibility that, at the microscopic level, VR-consciousness is mediated by single neurons rather than by a neuronal population.  The macroscopic step was necessary to provide for individual neurons that receive all the inputs comprising VR-conscious experience and for the supposition that there might be groups of such neurons that individually receive similar input.  In the microscopic step, it was argued additionally that individual neurons are by themselves sufficiently complex to account for the complexity of VR-conscious experience and that a mechanism may be present that translates the spatial pattern of dendritic activation within synchronously firing neurons into the spatial arrangement formed by those neurons at the population level.

 

5. ADDITIONAL CONSIDERATIONS:

 

     Other Conscious Regions:  The discussion so far has been limited to the case of VR-consciousness, that form of consciousness largely responsible for the debate over the "hard" problem of consciousness.  It was useful to invoke this restriction in order to narrow the focus of the presentation.  The theory can, however, be extended to include forms of consciousness that are not verbally reportable.  Indeed, patients with lesions that result in the loss of VR-consciousness often appear to manifest residual nonverbal consciousness, presumably mediated by structures outside the left lateral PFC.  Damasio (1998, 1999) has suggested that the residual consciousness observed in such patients be regarded as one of two overlapping types of consciousness, a non-verbal "core consciousness" mediated by midline cortical and subcortical structures, and a linguistically competent "extended consciousness" mediated by lateral neocortical structures.  The notion that a single brain might contain multiple centers of consciousness has been suggested by other investigators as well (Geschwind 1981, Edelman and Tononi 2000).

 

     A particularly intriguing possible center of nonverbal consciousness is the right lateral PFC. Since this region is anatomically homologous to the left lateral PFC, being anatomically distinguishable from the latter principally by its lack of direct connections with Broca's area and related structures, it might be possible that it mediates a nonverbal form of higher consciousness separate from that mediated by the left hemisphere.  In 1973, Rolando Puccetti suggested exactly this possibility (Puccetti 1973), proposing that the apparent duplication of consciousness that results from corpus callosum resection (the so-called "split-brain" procedure) is best explained by assuming that the right and left hemispheres maintain separate conscious streams not only after callosal disconnection but before the disconnection as well.  According to his hypothesis, the callosal section merely serves to uncouple what are already, in the normal state, two anatomically separate consciousnesses.  Such a notion would fit well with the single-neuron theory, which readily admits to the existence of multiple anatomically separate centers of conscious experience.

 

     In Puccetti's model, it should be noted, the hypothesis is that there are no more than two conscious centers present, and the discussion is limited to the macroscopic level only.  With the presently proposed theory, an additional step is taken, that of proposing that many macroscopic conscious centers may be present in a single brain, and that the multiplicity of consciousnesses extends to the microscopic single-neuron level as well.  The overall picture would be one in which multiple macroscopic centers of consciousness are proposed to exist, including ones located throughout neocortical, subcortical, and brainstem regions, with each center composed, in turn, of populations of neurons that individually and redundantly mediate the conscious activity appropriate to the brain region within which they reside.

 

     Relationship between the Single-Neuron Theory and Other Anatomical Theories of

Consciousness:  The theory presented in this paper is compatible with many of the anatomical and functional features that characterize other recently proposed theories of consciousness.  For example, Dehaene (1998) places the lateral PFC in a prominent position in his description of Baars' global workspace theory (Baars 1988; Baars and Franklin 2003), Llinas (1998) focuses on thalamo-cortico-thalamic oscillating loops, Damasio (1998) distinguishes between a brainstem mediated core consciousness and a cortically mediated extended consciousness, Dandy (1946) favors a striatal dominance in his theory of consciousness, and Edelman (1993) proposes a theory based on “neural darwinism.”  The neuroanatomical and functional proposals made in these theories are for the most part compatible with the single-neuron theory.  The principal differences are that with the single-neuron theory, the lateral PFC by itself is assumed to serve as the macroscopic correlate for higher consciousness, with the other structures playing only an adjunctive role, and the individual neuron is assumed to serve as the microscopic correlate for consciousness of all kinds, while in the other models, consciousness is always a network property.

 

     Philosophical Caveat:  The legitimacy of employing "experience" as a target of scientific investigation is not, it should be noted, universally accepted.  It has, for example, been argued by Dennett (1991) and others that "subjective experience" as illusory and that once all the brain processes associated with a given behavior are objectively described there is nothing left to be explained.  Dennett's arguments, if correct, would eliminate the need to localize a mind/brain interface or to solve a "binding problem."   If, on the other hand, subjective experience is a phenomenon in need of explanation, then the proposed single-neuron theory, which shifts the locus of the mind/brain interface from a macroscopic to a microscopic domain, might provide fresh avenues for addressing Chalmers' "hard problem."  In the section of the paper entitled “Speculative Implications” I will provide a specific example of how this might play out.

 

    Other Single-Neuron Models: Comparison of the single-neuron theory with other models that focus on single neurons may help clarify just what the single-neuron theory does and does not propose.  For example, it is important to distinguish the function of the single neurons in the single-neuron theory from those referred to as "grandmother cells," single neurons whose activation corresponds to the experience of a single memory (Thorpe 1998).  The grandmother cell concept has in common with the single-neuron theory the notion that a single neuron may contain sufficient complexity to account for the complexity of a complete conscious experience.  It differs, however, in that the grandmother cell is assumed, in the context of explaining memory function, to be forever attached to a single experience, whereas the single neurons of the single-neuron theory flexibly change their experiences over time.  Among other consequences of this distinction, the limitations in processing capacity that plague grandmother cell models, referred to variously as the "combinatorial problem" (Singer and Gray 1995) or the "problem of exponential explosion" (Gold 1999), do not apply to the single-neuron theory.

 

     Zeki's Model:  Another single-neuron based model was described by William James (1890) in his discussion of what he called the "theory of polyzoism or multiple monadism."  According to this view, "every brain-cell has its own individual consciousness, which no other cell knows anything about, all individual consciousnesses being 'ejective' to each other."  Along similar lines, Zeki and Bartels (1999) have recently proposed that a primate visual brain consists of many separate functionally specialized processing systems comprising hierarchical nodes that each generate a "microconsciousness."  Neither of these schemes, however, explains how the individual microconsciousnesses are able to induce macroscopically evident behavior.  Zeki attempts to solve this problem by suggesting that the many microconsciousnesses participate in a higher order integrative activity that produces macroscopic consciousness.  This, however, returns us to the received view that consciousness is ultimately mediated by multiple neurons linked through dynamic mechanisms.  James, on the other hand, considers the possibility that a single pontifical arch-cell by itself might mediate the totality of one's consciousness but he goes on to assert that there is no evidence for such a single "center of gravity" in the brain.  Both authors appear to overlook the possibility that multiple separately and redundantly conscious neurons might summate their outputs so as to produce the illusion of a single mind.

 

     Bieberich's Model:  Two other investigators have published models featuring single-neuron consciousness.  Edwards (2005) proposes a model of individual neuron consciousness not unlike the one presented here, but he approaches the subject from the point of view of philosophy and physics and offers no specific neuroanatomical mechanisms.  Bieberich (2002), on the other hand, gives a detailed anatomical account of his single-neuron theory.  He proposes a theory of "recurrent fractal neural networks" in which spatial information encoded at the neuronal network level is reflected in the spatial activity patterns exhibited in the dendritic trees at the single neuron level.  As with the single-neuron theory proposed in the present paper, the individual neurons in Bieberich's model are assumed to mediate the entirety of a subject's conscious experience at a given moment.

 

     Bieberich's theory has certain difficulties