Contemporary psychiatry is becoming more biologically oriented in the attempt to elicit a biological rationale of mental diseases. Although mental disorders comprise mostly functional abnormalities, there is a substantial overlap between neurology and psychiatry in addressing cognitive disturbances. In schizophrenia, the presence of cognitive impairment prior to the onset of psychosis and early after its manifestation suggests that some neurocognitive abnormalities precede the onset of psychosis and may represent a trait marker. These cognitive alterations may arise from functional disconnectivity, as (...) no significant brain damage has been found. In this review we aim to revise A.R. Luria’s systematic approach used in the neuropsychological evaluation of cognitive functions, which was primarily applied in patients with neurological disorders and in the cognitive evaluation in schizophrenia and other related disorders. As proposed by Luria, cognitive processes, associated with higher cortical functions, may represent functional systems that are not localized in narrow, circumscribed areas of the brain, but occur among groups of concertedly working brain structures, each of which makes its own particular contribution to the organization of the functional system. Current developments in neuroscience provide evidence of functional connectivity in the brain. Therefore, Luria’s approach may serve as a frame of reference for the analysis and interpretation of cognitive functions in general and their abnormalities in schizophrenia in particular. Having said that, modern technology, as well as experimental evidence, may help us to understand the brain better and lead us towards creating a new classification of cognitive functions. In schizophrenia research, multidisciplinary approaches must be utilized to address specific cognitive alterations. The relationships among the components of cognitive functions derived from the functional connectivity of the brain may provide an insight into cognitive machinery. (shrink)

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.

Recent research in cognitive and computational neuroscience portrays the neocortex as a hierarchically structured prediction machine. Several theorists have drawn on this research to challenge the traditional distinction between perception and cognition – specifically, to challenge the very idea that perception and cognition constitute useful kinds from the perspective of cognitive neuroscience. In place of this traditional taxonomy, such theorists advocate a unified inferential hierarchy subject to substantial bi-directional message passing. I outline the nature of this challenge and then raise (...) two objections to the cognitive architecture it proposes as a replacement: first, standard ways of characterising this inferential hierarchy are in tension with the representational reach of conceptual thought; second, there is compelling evidence that commonsense reasoning is structured around highly domain-specific intuitive theories that are difficult to situate within a single hierarchy. (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.

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.

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.

The ability to predict is the most importantability of the brain. Somehow, the cortex isable to extract regularities from theenvironment and use those regularities as abasis for prediction. This is a most remarkableskill, considering that behaviourallysignificant environmental regularities are noteasy to discern: they operate not only betweenpairs of simple environmental conditions, astraditional associationism has assumed, butamong complex functions of conditions that areorders of complexity removed from raw sensoryinputs. We propose that the brain's basicmechanism for discovering such complexregularities is implemented in (...) the dendritictrees of individual pyramidal cells in thecerebral cortex. Pyramidal cells have 5–8principal dendrites, each of which is capableof learning nonlinear input-to-outputtransfer functions. We propose that eachdendrite is trained, in learning its transferfunction, by all the other principal dendritesof the same cell. These dendrites teach eachother to respond to their separate inputs with matching outputs. Exposed to differentbut related information about the sensoryenvironment, principal dendrites of the samecell tune to functions over environmentalconditions that, while different, are correlated . As a result, the cell as awhole tunes to the source of the regularitiesdiscovered by the cooperating dendrites,creating a new representation. When organizedinto feed-forward/feedback layers, pyramidalcells can build their discoveries on thediscoveries of other cells, graduallyuncovering nature's hidden order. Theresulting associative network is powerfulenough to meet a troubling traditionalobjection to associationism: that it is toosimple an architecture to implement rationalprocesses. (shrink)

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.

The parietal cortex is divided into two major functional regions: the anterior parietal cortex that includes primary somatosensory cortex, and the posterior parietal cortex (PPC) that includes the rest of the parietal lobe. The PPC contains multiple representations of space. In Dijkerman & de Haan's (D&dH's) model, higher spatial representations are separate from PPC functions. This model should be developed further so that the functions of the somatosensory system are integrated with specific functions within the PPC and higher spatial representations. (...) Through this further specification of the model, one can make better predictions regarding functional interactions between somatosensory and visual systems. (shrink)

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.

Dijkerman & de Haan (D&dH) propose a somatosensory perceptual pathway that informs a consciously accessible body image, and an action pathway that provides information to a body schema, which is not consciously accessible. We argue that the body schema may become accessible to consciousness in some circumstances, possibly resulting from cross talk, but that this may be detrimental to skilled movement production.

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.

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.

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.

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 understanding of the interrelationship between brain and mind remains far from clear. It is well established that the brain's capacity to integrate information from numerous sources forms the basis for cognitive abilities. However, the core unresolved question is how information about the "objective" physical entities of the external world can be integrated, and how unifiedand coherent mental states (or Gestalts) can be established in the internal entities of distributed neuronal systems. The present paper offers a unified methodological and conceptual (...) basis for a possible mechanism of how the transient synchronization of brain operations may construct the unified and relatively stable neural states, which underlie mental states. It was shown that the sequence of metastable spatial EEG mosaics does exist and probably reflects the rapid stabilization periods of the interrelation of large neuron systems. At the EEG level this is reflected in the stabilization of quasi-stationary segments on corresponding channels. Within the introduced framework, physical brain processes and psychological processes are considered as two basic aspects of a single whole informational brain state. The relations between operational process of the brain, mental states and consciousness are discussed. (shrink)

The functions of the somatosensory system are multiple. We use tactile input to localize and experience the various qualities of touch, and proprioceptive information to determine the position of different parts of the body with respect to each other, which provides fundamental information for action. Further, tactile exploration of the characteristics of external objects can result in conscious perceptual experience and stimulus or object recognition. Neuroanatomical studies suggest parallel processing as well as serial processing within the cerebral somatosensory system that (...) reflect these separate functions, with one processing stream terminating in the posterior parietal cortex (PPC), and the other terminating in the insula. We suggest that, analogously to the organisation of the visual system, somatosensory processing for the guidance of action can be dissociated from the processing that leads to perception and memory. In addition, we find a second division between tactile information processing about external targets in service of object recognition and tactile information processing related to the body itself. We suggest the posterior parietal cortex subserves both perception and action, whereas the insula principally subserves perceptual recognition and learning. (shrink)

We discuss two problems for a general scientific understanding of language, sequences and synergies: how language is an intricately sequenced behavior and how language is manifested as a multidimensionally structured behavior. Though both are central in our understanding, we observe that the former tends to be studied more than the latter. We consider very general conditions that hold in human brain evolution and its computational implications, and identify multimodal and multiscale organization as two key characteristics of emerging cognitive function in (...) our species. This suggests that human brains, and cognitive function specifically, became more adept at integrating diverse information sources and operating at multiple levels for linguistic performance. We argue that framing language evolution, learning, and use in terms of synergies suggests new research questions, and it may be a fruitful direction for new developments in theory and modeling of language as an integrated system. (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.

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.

A fundamental claim associated with parallel distributed processing theories of cognition is that knowledge is coded in a distributed manner in mind and brain. This approach rejects the claim that knowledge is coded in a localist fashion, with words, objects, and simple concepts, that is, coded with their own dedicated representations. One of the putative advantages of this approach is that the theories are biologically plausible. Indeed, advocates of the PDP approach often highlight the close parallels between distributed representations learned (...) in connectionist models and neural coding in brain and often dismiss localist theories as biologically implausible. The author reviews a range a data that strongly challenge this claim and shows that localist models provide a better account of single-cell recording studies. The author also contrast local and alternative distributed coding schemes and argues that common rejection of grandmother cell theories in neuroscience is due to a misunderstanding about how localist models behave. The author concludes that the localist representations embedded in theories of perception and cognition are consistent with neuroscience; biology only calls into question the distributed representations often learned in PDP models. (shrink)

Deep neural networks (DNNs) have had extraordinary successes in classifying photographic images of objects and are often described as the best models of biological vision. This conclusion is largely based on three sets of findings: (1) DNNs are more accurate than any other model in classifying images taken from various datasets, (2) DNNs do the best job in predicting the pattern of human errors in classifying objects taken from various behavioral datasets, and (3) DNNs do the best job in predicting (...) brain signals in response to images taken from various brain datasets (e.g., single cell responses or fMRI data). However, these behavioral and brain datasets do not test hypotheses regarding what features are contributing to good predictions and we show that the predictions may be mediated by DNNs that share little overlap with biological vision. More problematically, we show that DNNs account for almost no results from psychological research. This contradicts the common claim that DNNs are good, let alone the best, models of human object recognition. We argue that theorists interested in developing biologically plausible models of human vision need to direct their attention to explaining psychological findings. More generally, theorists need to build models that explain the results of experiments that manipulate independent variables designed to test hypotheses rather than compete on making the best predictions. We conclude by briefly summarizing various promising modeling approaches that focus on psychological data. (shrink)

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.

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.

Concepts of space and time are widely developed in physics. However, there is a considerable lack of biologically plausible theoretical frameworks that can demonstrate how space and time dimensions are implemented in the activity of the most complex life-system – the brain with a mind. Brain activity is organized both temporally and spatially, thus representing space-time in the brain. Critical analysis of recent research on the space-time organization of the brain’s activity pointed to the existence of so-called operational space-time in (...) the brain. This space-time is limited to the execution of brain operations of differing complexity. During each such brain operation a particular short-term spatio-temporal pattern of integrated activity of different brain areas emerges within related operational space-time. At the same time, to have a fully functional human brain one needs to have a subjective mental experience. Current research on the subjective mental experience offers detailed analysis of space-time organization of the mind. According to this research, subjective mental experience (subjective virtual world) has definitive spatial and temporal properties similar to many physical phenomena. Based on systematic review of the propositions and tenets of brain and mind space-time descriptions, our aim in this review essay is to explore the relations between the two. To be precise, we would like to discuss the hypothesis that via the brain operational space-time the mind subjective space-time is connected to otherwise distant physical space-time reality. (shrink)

What type of artificial systems will claim to be conscious and will claim to experience qualia? The ability to comment upon physical states of a brain-like dynamical system coupled with its environment seems to be sufficient to make claims. The flow of internal states in such system, guided and limited by associative memory, is similar to the stream of consciousness. Minimal requirements for an artificial system that will claim to be conscious were given in form of specific architecture named articon. (...) Nonverbal discrimination of the working memory states of the articon gives it the ability to experience different qualities of internal states. Analysis of the inner state flows of such a system during typical behavioral process shows that qualia are inseparable from perception and action. The role of consciousness in learning of skills, when conscious information processing is replaced by subconscious, is elucidated. Arguments confirming that phenomenal experience is a result of cognitive processes are presented. Possible philosophical objections based on the Chinese room and other arguments are discussed, but they are insufficient to refute claims articon’s claims. Conditions for genuine understanding that go beyond the Turing test are presented. Articons may fulfill such conditions and in principle the structure of their experiences may be arbitrarily close to human. (shrink)