This commentary compares clinical aspects of ketamine with the amphetamine model of schizophrenia. Hallucinations and loss of insight, associated with amphetamine, seem more schizophrenia-like. Flat affect encountered with ketamine is closer to the clinical presentation in schizophrenia. We argue that flat affect is not a sign of schizophrenia, but rather, a risk factor for chronic schizophrenia.

Phillips & Silverstein's focus on schizophrenia as a failure of “cognitive coordination” is welcome. They note that a simple hypothesis of reduced Gamma synchronisation subserving impaired coordination does not fully account for recent observations. We suggest that schizophrenia reflects a dynamic compensation to a core deficit of coordination, expressed either as hyper- or hyposynchronisation, with neurotransmitter systems and arousal as modulatory mechanisms.

In the current literature on scientific explanation unification became unfashionable in favour of causal approaches. We want to bring unification back into the picture. In this paper we demonstrate that resemblance questions do occur in scientific practice and that they cannot be properly answered without unification. Our examples show that resemblance questions about particular facts demand what we call causal network unification, while resemblance questions about regularities require what we call mechanism unification. We clarify how these types of unification relate (...) to Philip Kitcher’s account, but also to causal and mechanistic accounts of explanation. (shrink)

I propose that primary conscious awareness arises from synchronized activity in dendrites of neurons in dorsal thalamic nuclei, mediated particularly by inhibitory interactions with thalamic reticular neurons. In support, I offer four evidential pillars: consciousness is restricted to the results of cortical computations; thalamus is the common locus of action of brain injury in vegetative state and of general anesthetics; the anatomy and physiology of the thalamus imply a central role in consciousness; neural synchronization is a neural correlate of consciousness.

The conclusions drawn by Benjamin Libet from his work with collegues on the timing of somatosensorial conscious experiences has met with a lot of praise and criticism. In this issue we find three examples of the latter. Here I attempt to place the divide between the two opponent camps in a broader perspective by analyzing the question of the relation between physical timing, neural timing, and experiential timing. The nervous system does a sophisticated job of recombining and recoding messages from (...) the sensorial surfaces and if these processes are slighted in a theory, it might become necessary to postulate weird operations, including subjective back-referral. Neuroscientifically inspired theories are of necessity still based on guesses, extrapolations, and philosophically dubious manners of speech. They often assume some neural correlate of consciousness as a part of the nervous system that transforms neural activity in reportable experiences. The majority of neuroscientists appear to assume that the NCC can compare and bind activity patterns only if they arrive simultaneously at the NCC. This leads to a search for synchrony or to theories in terms of the compensation of differences in neural delays . This is the main dimension of the Libet discussion. Examples from vision research, such as “temporal-binding-by-synchrony” and the “flash-lag” effect, are then used to illustrate these reasoning patterns in more detail. Alternatively one could assume symbolic representations of time and space that are not coded in their own dimension . Unless such tags are multiplexed with the quality message , one gets a binding problem for tags. One of the hidden aspects of the discussion between Libet and opponents appears to be the following. Is the NCC smarter than the rest of the nervous system, so that it can solve the problems of local sign and timing on its own, or are these pieces of information coded symbolically early on in the system? A supersmart NCC appears to be the assumption of Libet's camp . The wish to distribute the smartness evenly across all stages of processing in the nervous system appears to motivate the opponents. I argue that there are reasons to side with the latter group. (shrink)

Phillips & Silverstein offer an exciting synthesis of ongoing efforts to link the clinical and cognitive manifestations of schizophrenia with cellular accounts of its pathophysiology. We applaud their efforts but wonder whether the highly inclusive notion of “context” adequately captures some important details regarding schizophrenia and NMDA/glutamate function that are suggested by work on language processing and cognitive electrophysiology.

Phillips & Silverstein's ambitious link between receptor abnormalities and the symptoms of schizophrenia involves a certain amount of fuzziness: No detailed mechanism is suggested through which the proposed abnormality would lead to psychological traits. We propose that detailed simulation of brain regions, using model neural networks, can aid in understanding the relation between biological abnormality and psychological dysfunction in schizophrenia.

Although interesting, the hypotheses proposed by Phillips & Silverstein lack unifying structure both in specific mechanisms and in cited evidence. They provide little to support the notion that low-level sensory processing and high-level cognitive coordination share dynamic grouping by synchrony as a common processing mechanism. We suggest that more realistic large-scale modeling at multiple levels is needed to address these issues.

In chronic schizophrenic patients with both positive and negative symptoms (see Table 1), interhemispheric connections at the high frequency beta2-rhythm are absent during cognitive tasks, in contrast to normal controls, who have many interhemispheric connections at this frequency in the same situation. Connectivity is a fundamental brain feature, evidently greatly promoted by the NMDA system. It is a more reliable measure of brain function than the spectral power of this rhythm.

Neural Darwinism (ND) is a large scale selectionist theory of brain development and function that has been hypothesized to relate to consciousness. According to ND, consciousness is entailed by reentrant interactions among neuronal populations in the thalamocortical system (the ‘dynamic core’). These interactions, which permit high-order discriminations among possible core states, confer selective advantages on organisms possessing them by linking current perceptual events to a past history of value-dependent learning. Here, we assess the consistency of ND with 16 widely recognized (...) properties of consciousness, both physiological (for example, consciousness is associated with widespread, relatively fast, low amplitude interactions in the thalamocortical system), and phenomenal (for example, consciousness involves the existence of a private flow of events available only to the experiencing subject). While no theory accounts fully for all of these properties at present, we find that ND and its recent extensions fare well. (shrink)

Impairments in cognitive coordination in schizophrenia are supported by phenomenological data that suggest deficits in the processing of visual context. Although the target article is sympathetic to such a phenomenological perspective, we argue that the relevance of phenomenological data for a wider understanding of consciousness in schizophrenia is not sufficiently addressed by the authors.

Numerous searches have failed to identify a single co-occurrence of total blindness and schizophrenia. Evidence that blindness causes loss of certain NMDA-receptor functions is balanced by reports of compensatory gains. Connections between visual and anterior cingulate NMDA-receptor systems may help to explain how blindness could protect against schizophrenia.

Phillips & Silverstein argue that schizophrenia is a result of a deficit of the contextual coordination of neuronal responses. The authors propose that NMDA-receptors control these modulatory effects. However, hallucinations, which are among the principle symptoms of schizophrenia, imply a flaw in the interactions between neurons that is more fundamental than just a general weakness of contextual modulation.

Phillips & Silverstein emphasize the gain-control properties of NMDA synapses in cognitive coordination. We endorse their view and suggest that NMDA synapses play a crucial role in biased attentional competition and (visual) working memory. Our simulations show that NMDA synapses can control the storage rate of visual objects. We discuss specific predictions of our model about cognitive effects of NMDA-antagonists and schizophrenia.

The concept of locally specialized functions dominates research on higher brain function and its disorders. Locally specialized functions must be complemented by processes that coordinate those functions, however, and impairment of coordinating processes may be central to some psychotic conditions. Evidence for processes that coordinate activity is provided by neurobiological and psychological studies of contextual disambiguation and dynamic grouping. Mechanisms by which this important class of cognitive functions could be achieved include those long-range connections within and between cortical regions that (...) activate synaptic channels via NMDA-receptors, and which control gain through their voltage-dependent mode of operation. An impairment of these mechanisms is central to PCP-psychosis, and the cognitive capabilities that they could provide are impaired in some forms of schizophrenia. We conclude that impaired cognitive coordination due to reduced ion flow through NMDA-channels is involved in schizophrenia, and we suggest that it may also be involved in other disorders. This perspective suggests several ways in which further research could enhance our understanding of cognitive coordination, its neural basis, and its relevance to psychopathology. Key Words: attention; cerebral cortex; cognitive coordination; cognitive neuropsychiatry; cognitive neuropsychology; context disorganization; Gamma rhythms; Gestalt theory; glutamate; grouping; memory; NMDA-receptors; PCP-psychosis; perceptual organization; schizophrenia. (shrink)

This commentary highlights methods for using scalp EEG to make inferences about contextual field interactions, which, in view of the target article, may be specially relevant to the study of schizophrenia. Although scalp EEG has limited spatial resolution, prior knowledge combined with experimental manipulations may be used to strengthen inferences about underlying brain processes. Both spatial and temporal context are discussed within the framework of nonlinear interactions. Finally, results from a visual contour integration EEG pilot study are summarized in view (...) of a hypothesis that relates receptive field and contextual field processing to evoked and induced activity, respectively. (shrink)

Although context-processing deficits may be core features of schizophrenia, context remains a poorly defined concept. To test Phillips & Silverstein's model, we need to operationalize context more precisely. We offer several useful ways of framing context and discuss enhancing or facilitating schizophrenic patients' performance under different contextual situations. Furthermore, creativity may be a byproduct of cognitive uncoordination.

Context, connection, and coordination (CCC) describe well where the problems that apply to thought-disordered patients with schizophrenia lie. But they may be part of the experience of those with other symptom constellations. Switching is an important mechanism to allow context to be applied appropriately to changing circumstances. In some cases, NMDA-voltage modulations may be central, but gain and shift are also functions that monoaminergic systems express in CCC.

This commentary challenges the authors to use their computational modeling techniques to support one of their central claims: that schizophrenic deficits in bottom-up (Gestalt-type tasks) and top-down (cognitive control tasks) context processing tasks arise from the same dysfunction. Further clarification about the limits of cognitive coordination would also strengthen the hypothesis.

Schizophrenics exhibit a deficit in theory of mind (ToM), but an intact theory of biology (ToB). One explanation is that ToM relies on an independent module that is selectively damaged. Phillips & Silverstein's analyses suggest an alternative: ToM requires the type of coordination that is impaired in schizophrenia, whereas ToB is spared because this type of coordination is not involved.

The ongoing steady nature of consciousness in everyday life implies that the underlying neural activity possesses a high level of stability. The prolonged cognitive events of sustained attention, imagery, and working memory also imply high stability of underlying neural activity. This paper proposes that stabilization of neural activity is produced by apical dendrite activity in pyramidal neurons within recurrent corticothalamic circuits, and proposes that the wave activities of apical dendrites that stabilize ongoing activity constitute the subjective impressions of an attended (...) object and the entire sensory background. The cortical minicolumn, as the functional unit of the cortex, is separated into an axis consisting of layer 5 pyramidal neurons and a surrounding shell consisting of layer 2/3 pyramidal neurons. It is proposed that apical dendrites of the axis generate sensory impressions, and basal dendrites of the shell process the brief-lasting input–output identifications of objects that give rise to ideas. (shrink)

Neurophysiological investigations of the past two decades have consistently demonstrated a deficit in sensory gating associated with schizophrenia. Phillips & Silverstein interpret this impairment as being consistent with cognitive coordination dysfunction. However, the physiological mechanisms that underlie sensory gating have not been shown to involve gamma-band oscillations or NMDA-receptors, both of which are critical neural elements in the cognitive coordination model.

The goal of this work is to compile the basic components for the construction of an electromagnetic field theory of consciousness that meets the standards of a fundamental theory. An essential cornerstone of the conceptual framework is the vacuum state of quantum electrodynamics which, contrary to the classical notion of the vacuum, can be viewed as a vibrant ocean of energy, termed zero-point field (ZPF). Being the fundamental substrate mediating the electromagnetic force, the ubiquitous ZPF constitutes the ultimate bedrock of (...) all electromagnetic phenomena. In particular, resonant interaction with the ZPF is critical for understanding rapidly forming, long-range coherent activity patterns that are characteristic of brain dynamics. Assuming that the entire phenomenal color palette is rooted in the vibrational spectrum of the ZPF and that each normal mode of the ZPF is associated with an elementary shade of consciousness, it stands to reason that conscious states are caused by the coupling of the brain to a particular set of normal modes selectively filtered from the full frequency spectrum of the ZPF. From this perspective, the brain is postulated to function as a resonant oscillator that couples to a specific range of ZPF modes, using these modes as a keyboard for the composition of an enormous variety of phenomenal states. Theoretical considerations suggest that the brain-ZPF interface is controlled by altering the concentrations of neurotransmitters, placing the detailed study of the neurotransmitter-ZPF interaction at the center of future research activities. (shrink)

Continuous recordings of brain electrical activity were obtained from a group of 176 patients throughout surgical procedures using general anesthesia. Artifact-free data from the 19 electrodes of the International 10/20 System were subjected to quantitative analysis of the electroencephalogram (QEEG). Induction was variously accomplished with etomidate, propofol or thiopental. Anesthesia was maintained throughout the procedures by isoflurane, desflurane or sevoflurane (N = 68), total intravenous anesthesia using propofol (N = 49), or nitrous oxide plus narcotics (N = 59). A set (...) of QEEG measures were found which reversibly displayed high heterogeneity of variance between four states as follows: (1) during induction; (2) just after loss of consciousness (LOC); (3) just before return of consciousness (ROC); (4) just after ROC. Homogeneity of variance across all agents within states was found. Topographic statistical probability images were compared between states. At LOC, power increased in all frequency bands in the power spectrum with the exception of a decrease in gamma activity, and there was a marked anteriorization of power. Additionally, a significant change occurred in hemispheric relationships, with prefrontal and frontal regions of each hemisphere becoming more closely coupled, and anterior and posterior regions on each hemisphere, as well as homologous regions between the two hemispheres, uncoupling. All of these changes reversed upon ROC. Variable resolution electromagnetic tomography (VARETA) was performed to localize salient features of power anteriorization in three dimensions. A common set of neuroanatomical regions appeared to be the locus of the most probable generators of the observed EEG changes. (shrink)

N-methyl-d-aspartate receptor (NMDAR) dysfunction plays a crucial role in schizophrenia, leading to impairments in cognitive coordination. NMDAR agonists (e.g., glycine) ameliorate negative and cognitive symptoms, consistent with NMDAR models. However, not all types of cognitive coordination use NMDAR. Further, not all aspects of cognitive coordination are impaired in schizophrenia, suggesting the need for specificity in applying the cognitive coordination construct.

We propose that the primary cause of schizophrenia is a pathological extension of synaptic pruning involving local connectivity that unfolds ordinarily during adolescence. Computer simulations suggest that this pathology provides reasonable accounts of a range of symptoms in schizophrenia, and is consistent with recent postmortem and genetic studies. NMDA-receptors play a regulatory role in maintaining and/or eliminating cortical synapses, and therefore may play a pathophysiological role.

This commentary addresses: (a) the problems of definition which have been prominent in the use of the term context in schizophrenia research; (b) potentially useful distinctions and links with other theories of schizophrenic cognition; and (c) possible pathways to schizophrenic symptoms. It is suggested that at least two major aspects of the operation of context may be distinguished and that both may be impaired in schizophrenia.

_Figure 1. Dendrites and cell bodies of schematic neurons connected by dendritic-dendritic gap junctions form a laterally connected input_ _layer (“dendritic web”) within a neurocomputational architecture. Dendritic web dynamics are temporally coupled to gamma synchrony_ _EEG, and correspond with integration phases of “integrate and fire” cycles. Axonal firings provide input to, and output from, integration_ _phases (only one input, and three output axons are shown). Cell bodies/soma contain nuclei shown as black circles; microtubule networks_ _pervade the cytoplasm. According to the (...) Orch OR theory, gamma EEG-synchronized integration phases include quantum computations in_ _microtubule networks which culminate with conscious moments. Insert closeup shows a gap junction through which microtubule quantum_ _states entangle among different neurons, enabling macroscopic quantum states in dendritic webs extending throughout cortex and other_ _brain regions._. (shrink)

To understand schizophrenia, a linking hypothesis is needed that shows how brain mechanisms lead to behavioral functions in normals, and also how breakdowns in these mechanisms lead to behavioral symptoms of schizophrenia. Such a linking hypothesis is now available that complements the discussion offered by Phillips & Silverstein (P&S).

The Phillips & Silverstein model of NMDA-mediated coordination deficits provides a useful heuristic for the study of schizophrenic cognition. However, the model does not specifically account for the development of schizophrenia-spectrum disorders. The P&S model is compared to Meehl's seminal model of schizotaxia, schizotypy, and schizophrenia, as well as the model of schizophrenic cognitive dysfunction posited by McCarley and colleagues.

The claim that the disorganized subtype of schizophrenia results from glutamate hypofunction is enhanced by consideration of current subtypology of schizophrenia, symptom definition, interdependence of neurotransmitters, and the nature of the data needed to support the hypothesis. Careful specification clarifies the clinical reality of disorganization as a feature of schizophrenia and increases the utility of the subtype.

The value of resting electroencephalogram (EEG) in revealing neural constitutes of consciousness (NCC) was examined. We quantified the dynamic repertoire, duration and oscillatory type of EEG microstates in eyes-closed rest in relation to the degree of expression of clinical self-consciousness. For NCC a model was suggested that contrasted normal, severely disturbed state of consciousness and state without consciousness. Patients with disorders of consciousness were used. Results suggested that the repertoire, duration and oscillatory type of EEG microstates in resting condition quantitatively (...) related to the level of consciousness expression in brain-damaged patients and healthy-conscious subjects. Specifically, results demonstrated that (a) decreased number of EEG microstate types was associated with altered states of consciousness, (b) unawareness was associated with the lack of diversity in EEG alpha-rhythmic microstates, and (c) the probability for the occurrence and duration of delta-, theta- and slow-alpha-rhythmic microstates were associated with unawareness, whereas the probability for the occurrence and duration of fast-alpha-rhythmic microstates were associated with consciousness. In conclusion, resting EEG has a potential value in revealing NCC. This work may have implications for clinical care and medical–legal decisions in patients with disorders of consciousness. (shrink)

Unconscious processes, by whatever name they may be known , are invariably operationalized by the dissociation paradigm, any situation involving the dissociation between two indicators , one of availability and the other, of accessibility , such that, ε>α. Subliminal perception has been traditionally defined by a special case of the dissociation paradigm in which availability exceeds accessibility when accessibility is null . Construct validity issues bedevil all dissociation paradigms since it is not clear what might constitute appropriate indicators that, moreover, (...) are pure and exhaustive. Semantic and theoretic drifts in the recent literature—e.g., the confusion of different versions of the dissociation paradigm, the equation of conscious–unconscious with direct–indirect tests, and the foisting of the criterion of qualitative differences—have tended to undermine emerging theoretic parsimony. On the other hand, a crucial factor has been left out of theory development: time. Both ε and α can rise and fall over time, often asynchronously, and so dissociations may wax and wane and, even, reverse over time. Some laboratory evidence suggests that accessibility measures , as they approach chance, may actually dip below chance . If so, d′=0 , could be an averaging artifact of positive and negative d′s. Conscious accessibility is not either–or but more or less, and variable over time. (shrink)

By reviewing most of the neurobiology of consciousness, this article highlights some major reasons why a successful emulation of the dynamics of human consciousness by artificial intelligence is unlikely. The analysis provided leads to conclude that human consciousness is epigenetically determined and experience and context-dependent at the individual level. It is subject to changes in time that are essentially unpredictable. If cracking the code to human consciousness were possible, the result would most likely have to consist of a temporal pattern (...) code simulating long-distance signal reverberation and de-correlation of all spatial signal contents from temporal signals. In the light of the massive evidence for complex interactions between implicit (non-conscious) and explicit (conscious) contents of representation, the code would have to be capable of making implicit (non-conscious) processes explicit. It would have to be capable of a progressively less and less arbitrary selection of temporal activity patterns in a continuously developing neural network structure identical to that of the human brain, from the synaptic level to that of higher cognitive functions. The code’s activation thresholds would depend on specific temporal signal coincidence probabilities, vary considerably with time and across individual experience data, and would therefore require dynamically adaptive computations capable of emulating the properties of individual human experience. No known machine or neural network learning approach has such potential. (shrink)

How do I know that I am the person who is moving? According to Wittgenstein (1958), the sense of agency involves a primitive notion of the self used as subject, which does not rely on any prior perceptual identification and which is immune to error through misidentification. However, the neuroscience of action and the neuropsychology of schizophrenia show the existence of specific cognitive processes underlying the sense of agency—the ‘‘Who'' system (Georgieff & Jeannerod, 1998) which is disrupted in delusions of (...) control (Frith, 1992). Yet, we have to be careful in the interpretation of such clinical symptoms, which cannot be so easily reduced to deficit of action monitoring or to lack of action awareness. Moreover, we should refine the definition of the sense of agency by distinguishing the sense of initiation and the sense of one's own movements. A conceptual analysis of the empirical data will lead us to establish the taxonomy of the different levels of action representations. (shrink)

This article extends the brief description of cognition previously offered in the adaptational theory of consciousness (ATC). Here I suggest how unconscious and conscious minds interact to achieve mutual cognitive development. Interactions occur in an extended moment of subjective time consisting of perceptual, associational, and affective scenes. During the extended moment, the conscious self becomes time-agile, shuttling between the past, present, and future in order to assemble ideas within global awareness that produce pleasure. The products of its cognitive journeys are (...) saved as synaptic modifications by the unconscious mind's mnemonic functions. As this occurs, instincts and the conscious self's implementation of cultural values are brought into better alignment. (shrink)

Mechanisms that contribute to perceptual processing dysfunction in schizophrenia were examined by Phillips & Silverstein, and formulated as involving disruptions in both local and higher-level coordination of signals. We agree that dysfunction in the coordination of cognitive functions (disconnection) is also indicated for many of the linguistic processing deficits documented for schizophrenia. We suggest, however, that it may be necessary to add a timing mechanism to the theoretical account.

Evidence for a dysfunction in cognitive coordination in schizophrenia is emerging, but it is not specific enough to prove (or disprove) this long-standing hypothesis. Many aspects of the external world are spatially mapped in the brain. A comprehensive internal representation relies on integration of information across space. Focus on spatial integration in the perceptual and cognitive processes will generate empirical data that shed light on the pathophysiology of schizophrenia.

The main objective of this essay is to validate some of the principal, currently competing, mammalian consciousness-brain theories by comparing these theories with data on both cognitive abilities and brain organization in birds. Our argument is that, given that multiple complex cognitive functions are correlated with presumed consciousness in mammals, this correlation holds for birds as well. Thus, the neuroanatomical features of the forebrain common to both birds and mammals may be those that are crucial to the generation of both (...) complex cognition and consciousness. The general conclusion is that most of the consciousness-brain theories appear to be valid for the avian brain. Even though some specific homologies are unresolved, most of the critical structures presumed necessary for consciousness in mammalian brains have clear homologues in avian brains. Furthermore, considering the fact that the reptile-bird brain transition shows more structural continuity than the stem amniote-mammalian transition, the line drawn at the origin of mammals for consciousness by several of the theorists seems questionable. An equally important point is that consciousness cannot be ruled out in the absence of complex cognition; it may in fact be the case that consciousness is a necessary prerequisite for complex cognition. (shrink)

It is proposed that cortical activity is normally coordinated across synaptically connected areas and that this coordination supports cognitive coherence relations. This view is consistent with the NMDA- hypoactivity hypothesis of the target article in regarding disorganization symptoms in schizophrenia as arising from disruption of normal interareal coordination. This disruption may produce abnormal contextual effects in the cortex that lead to anomalous cognitive coherence relations.

Phillips & Silverstein argue that a range of cognitive disturbances in schizophrenia result from a deficit in cognitive coordination attributable to NMDA receptor dysfunction. We suggest that the viability of this hypothesis would be further supported by explicit implementation in a computational framework that can produce quantitative estimates of the behavior of both healthy individuals and individuals with schizophrenia.

The target article presents a model for schizophrenia extending four levels of abstraction: molecules, cells, cognition, and syndrome. An important notion in the model is that of coordination, applicable to both the level of cells and of cognition. The molecular level provides an “implementation” of the coordination at the cellular level, which in turn underlies the coordination at the cognitive level, giving rise to the clinical symptoms.

The rise of Artificial Intelligence (AI) has produced prophets and prophecies announcing that the age of artificial consciousness is near. Not only does the mere idea that any machine could ever possess the full potential of human consciousness suggest that AI could replace the role of God in the future, it also puts into question the fundamental human right to freedom and dignity. This position paper takes the stand that, in the light of all we currently know about brain evolution (...) and the never-stopping formation of adaptive neural circuitry for learning, memory, decision making and, ultimately, fully conscious reasoning and creativity in the human species, the idea of an artificial consciousness appears misconceived. The paper highlights some of the major reasons why. While awareness to external stimuli for processes such as perception, recognition, and operational problem solving is under the direct control of functionally specific brain networks associated with sensory and cognitive functions across animal species, consciousness is a unique property of the human mind. (shrink)

This article provides a retrospective, current and prospective overview on developments in brain research and neuroscience. Both theoretical and empirical studies are considered, with emphasis in the concept of multivariability and metastability in the brain. In this new view on the human brain, the potential multivariability of the neuronal networks appears to be far from continuous in time, but confined by the dynamics of short-term local and global metastable brain states. The article closes by suggesting some of the implications of (...) this view in future multidisciplinary brain research. (shrink)