Convergence of biological and psychological perspectives on cognitive coordination in 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

The coherent organization of mental life depends on mechanisms for context-sensitive gain-control that are impaired in schizophrenia

There is rapidly growing evidence that schizophrenia involves changes in context-sensitive gain-control and probabilistic inference. In addition to the well-known cognitive disorganization to which these changes lead, basic aspects of vision are also impaired, as discussed by other papers on this Frontiers Research Topic. The aim of this paper is to contribute to our understanding of such findings by examining five central hypotheses. First, context-sensitive gain-control is fundamental to brain function and mental life. Second, it occurs in many different regions of the cerebral cortex of many different mammalian species. Third, it has several computational functions, each with wide generality. Fourth, it is implemented by several neural mechanisms at cellular and circuit levels. Fifth, impairments of context-sensitive gain-control produce many of the well-known symptoms of schizophrenia and change basic processes of visual perception. These hypotheses suggest why disorders of vision in schizophrenia may provide insights into the nature and mechanisms of impaired reality testing and thought disorder in psychosis. They may also cast light on normal mental function and its neural bases. Limitations of these hypotheses, and ways in which they need further testing and development, are outlined

Réhabilitation cognitive de la schizophrénie : une approche pragmatique du processus d’intégration pour lutter contre les symptômes réfractaires

Les approches classiques de traitement des personnes présentant une schizophrénie s’accordent pour reconnaître que réussir à soigner cette condition requiert davantage qu’une simple réduction de fréquence, d’intensité et de durée des symptômes positifs tels que des hallucinations. En fait, une approche plus complète, dont le but est de réduire l’incapacité s’avère indiquée dans la plupart des cas (Silverstein et al., 2000). Il a été récemment proposé que les nouvelles approches en réhabilitation cognitive de la schizophrénie requièrent la reconnaissance de l’importance de 1) systématiquement aborder la motivation, l’estime de soi, et les facteurs affectifs au moment de concevoir des interventions qui augmentent la cognition ; 2) la nécessité d’aller au-delà des interventions « à taille unique » et de développer des traitements spécifiques à l’individu ; 3) la nécessité d’aborder les anomalies de l’expérience du soi lors de la conception même des interventions d’optimisation des accomplissements cognitifs et comportementaux. L’étude de cas présentée ci-dessous est un exemple d’une approche de la réhabilitation cognitive de la schizophrénie qui tente de promouvoir le processus d’intégration de soi par le recours à une gamme d’interventions spécifiques, en relation avec les trois caractéristiques notées plus haut. Les résultats préliminaires suggèrent que cette approche pourrait être grandement profitable aux patients souffrant de schizophrénie.Classical approaches of treatment of people with schizophrenia recognize that successful treatment of this illness requires more than simply reducing the frequency, intensity and duration of positive symptoms such as hallucinations. In fact, a more comprehensive approach aimed at reducing disability is indicated in most cases (Silverstein et al., 2000). It has recently been proposed that new approaches to the cognitive rehabilitation of schizophrenia need to recognize the importance of 1) systematically addressing motivation, self-esteem, and affective factors when designing cognition enhancing interventions ; 2) the need to move beyond one-size-fits-all interventions and develop individual-specific treatments ; and 3) the need to address abnormalities in the experience of the self when designing interventions to optimize cognitive and behavioural performance. The case study presented here is an example of a cognitive rehabilitation approach of schizophrenia that attempts to promote the self integration process by means of a range of specific interventions and addresses three issues noted above. Preliminary results suggest that it could be very beneficial for patients suffering of schizophrenia.Los enfoques clásicos de tratamiento de las personas que presentan esquizofrenia reconocen que tener éxito en sanar esta condición requiere más que una simple reducción de la frecuencia, intensidad y duración de los síntomas positivos como las alucinaciones. De hecho, un enfoque más completo, cuyo objetivo es reducir la incapacidad, se revela como indicado en la mayoría de los casos (Silverstein et al., 2000). Recientemente se ha propuesto que los nuevos enfoques en la rehabilitación cognitiva de la esquizofrenia requieren reconocer la importancia de 1) abordar sistemáticamente la motivación, la estima de sí mismo y los factores afectivos en el momento de concebir las intervenciones que aumentan la cognición; 2) la necesidad de ir más allá de las intervenciones “de talla única” y de desarrollar los tratamientos específicos para el individuo; 3) la necesidad de abordar las anomalías de la experiencia de sí mismo, en el momento de la concepción misma de las intervenciones de optimización de los logros cognitivos y comportamentales. El estudio de caso presentado a continuación es un ejemplo de un enfoque de rehabilitación cognitiva de la esquizofrenia, que intenta promover el proceso de integración de sí mismo por medio de una gama de intervenciones específicas, en relación con las tres características arriba señaladas. Los resultados preliminares sugieren que este enfoque podría ser de gran provecho para los pacientes que sufren de esquizofrenia.As abordagens clássicas de tratamento das pessoas que apresentam uma esquizofrenia reconhecem que conseguir curar este estado requer mais do que uma simples redução de freqüência, de intensidade e de duração dos sintomas positivos, como as alucinações. De fato, uma abordagem mais completa, cujo objetivo é reduzir a incapacidade, é indicada na maioria dos casos (Silverstein et al., 2000). Foi proposto, recentemente, que as novas abordagens em reabilitação cognitiva da esquizofrenia requeiram o reconhecimento da importância 1) de abordar sistematicamente a motivação, a estima de si e os fatores afetivos no momento de conceber intervenções que aumentem a cognição; 2) da necessidade de ir além das intervenções “de tamanho único” e de desenvolver tratamentos personalizados; 3) da necessidade de abordar as anomalias da experiência do “eu”, na concepção mesmo das intervenções de otimização das realizações cognitivas e comportamentais. O estudo de caso apresentado abaixo é um exemplo de uma abordagem da reabilitação cognitiva da esquizofrenia, que tenta promover o processo de integração de si pelo recurso a uma gama de intervenções específicas, em relação às três características anotadas acima. Os resultados preliminares sugerem que esta abordagem poderia ser muito benéfica para os pacientes que sofrem de esquizofrenia

Colocalization of F-actin and talin during Fc receptor-mediated phagocytosis in mouse macrophages

We have studied the distribution of talin in J774 cells and mouse peritoneal macrophages undergoing Fc receptor-mediated phagocytosis. At early stages of phagocytosis, talin accumulates in the cells' cortical cytoplasm adjacent to the forming phagosome and extends into pseudopods that are encircling the particle. Talin colocalizes with F-actin at these sites. After particle ingestion is completed, F-actin and talin are no longer concentrated adjacent to phagosomes. Thus, talin and F-actin undergo dynamic and coordinate changes in their cytoplasmic location during Fc receptor-mediated phagocytosis

On the functions, mechanisms, and malfunctions of intracortical contextual modulation

A broad neuron-centric conception of contextual modulation is reviewed and re-assessed in the light of recent neurobiological studies of amplification, suppression, and synchronization. Behavioural and computational studies of perceptual and higher cognitive functions that depend on these processes are outlined, and evidence that those functions and their neuronal mechanisms are impaired in schizophrenia is summarized. Finally, we compare and assess the long-term biological functions of contextual modulation at the level of computational theory as formalized by the theories of coherent infomax and free energy reduction. We conclude that those theories, together with the many empirical findings reviewed, show how contextual modulation at the neuronal level enables the cortex to flexibly adapt the use of its knowledge to current circumstances by amplifying and grouping relevant activities and by suppressing irrelevant activities

Implications of Information Theory for Computational Modeling of Schizophrenia

Information theory provides a formal framework within which information processing and its disorders can be described. However, information theory has rarely been applied to modeling aspects of the cognitive neuroscience of schizophrenia. The goal of this article is to highlight the benefits of an approach based on information theory, including its recent extensions, for understanding several disrupted neural goal functions as well as related cognitive and symptomatic phenomena in schizophrenia. We begin by demonstrating that foundational concepts from information theory—such as Shannon information, entropy, data compression, block coding, and strategies to increase the signal-to-noise ratio—can be used to provide novel understandings of cognitive impairments in schizophrenia and metrics to evaluate their integrity. We then describe more recent developments in information theory, including the concepts of infomax, coherent infomax, and coding with synergy, to demonstrate how these can be used to develop computational models of schizophrenia-related failures in the tuning of sensory neurons, gain control, perceptual organization, thought organization, selective attention, context processing, predictive coding, and cognitive control. Throughout, we demonstrate how disordered mechanisms may explain both perceptual/cognitive changes and symptom emergence in schizophrenia. Finally, we demonstrate that there is consistency between some information-theoretic concepts and recent discoveries in neurobiology, especially involving the existence of distinct sites for the accumulation of driving input and contextual information prior to their interaction. This convergence can be used to guide future theory, experiment, and treatment development

Tyrosine phosphorylation is required for Fc receptor-mediated phagocytosis in mouse macrophages

Although Fc receptor-mediated phagocytosis is accompanied by a variety of transmembrane signaling events, not all signaling events are required for particle ingestion. For example, Fc receptor-mediated phagocytosis in mouse inflammatory macrophages (Di Virgilio, F., B. C. Meyer, S. Greenberg, and S. C. Silverstein. 1988. J. Cell Biol. 106:657; Greenberg, S., J. El Khoury, F. Di Virgilio, and S. C. Silverstein. 1991. J. Cell Biol. 113:757) and neutrophils (Della Bianca, V., M. Grzeskowiak, and F. Rossi. 1990. J. Immunol. 144:1411) occurs in the absence of cytosolic calcium transients. We sought to identify transmembrane signaling events that are essential for phagocytosis. Here we show that tyrosine phosphorylation is an early event after Fc receptor ligation in mouse inflammatory macrophages, and that the formation of tyrosine phosphoproteins coincides temporally with the appearance of F-actin beneath phagocytic cups. The distribution of tyrosine phosphoproteins that accumulated beneath phagocytic cups was punctate and corresponded to areas of high ligand density on the surface of the antibody-coated red blood cells, which provided the phagocytic stimulus. A tyrosine kinase inhibitor, genistein, but not several inhibitors of protein kinase C, blocked the appearance of tyrosine phosphoproteins as assessed by immunofluorescence, the focal accumulation of F-actin beneath immunoglobulin G-opsonized particles, and the ingestion of these particles as well. We suggest that tyrosine phosphorylation is a critical signaling event that underlies Fc receptor-mediated phagocytosis in mouse macrophages, and is necessary for the engulfment per se

Traitement multimodal de l’agressivité et de la violence chez des personnes souffrant de psychose

Dans cet article, les auteurs décrivent les traitements non pharmacologiques qui ont fait preuve d’efficacité pour réduire l’agressivité et la violence chez les personnes souffrant de psychose. Ils présentent ensuite une approche de formulation/planification du traitement qui aborde les influences étiologiques complexes, et les facteurs multiples qui jouent sur le maintien du comportement agressif chez ces patients. Finalement, ils présentent en exemple un cas où l’on se sert de cette approche.In this article, the authors offer a description of nonpharmacological treatments which have demonstrated effectiveness in reducing aggression and violence in patient with psychosis ; present a case formulation/treatment planning approach which addresses the complex etiological influences and multiple factors affecting maintenance of aggressive behavior in PI ; finally, they provide a case example of this approach.En este artículo, los autores describen los tratamientos no farmacológicos que han demostrado ser eficaces en la reducción de la agresividad y la violencia en las personas que sufren de psicosis. Enseguida, presentan un enfoque de formulación/planificación del tratamiento que aborda las influencias etiológicas complejas y los múltiples factores que tienen un efecto en el mantenimiento del comportamiento agresivo en estos pacientes. Finalmente, presentan como ejemplo un caso en el que se sirven de este enfoque.Neste artigo, os autores descrevem os tratamentos não farmacológicos que provaram ser eficazes para reduzir a agressividade e a violência nas pessoas que sofrem de psicose. Eles apresentam em seguida uma abordagem de formulação/planificação do tratamento que aborda as influências etimológicas complexas, e os fatores múltiplos que influenciam sobre a manutenção do comportamento agressivo nestes pacientes. Finalmente, eles apresentam o exemplo de um caso onde esta abordagem foi utilizada

Computational Modeling of Contrast Sensitivity and Orientation Tuning in Schizophrenia

Computational modeling is being increasingly used to understand schizophrenia, but, to date, it has not been used to account for the common perceptual disturbances in the disorder. We manipulated schizophrenia-relevant parameters in the GCAL (gain control, adaptation, laterally connected) model (Stevens et al., 2013), run using the Topographica simulator (Bednar, 2012), to model low-level visual processing changes in the disorder. Our models incorporated: separate sheets for retinal, LGN, and V1 activity; gain control in the LGN; homeostatic adaptation in V1 based on a weighted sum of all inputs and limited by a logistic (sigmoid) nonlinearity; lateral excitation and inhibition in V1; and self-organization of synaptic weights based on Hebbian learning. Data indicated that: 1) findings of increased contrast sensitivity for low spatial frequency stimuli in first episode schizophrenia (FES) can be successfully modeled as a function of reduced retinal and LGN efferent activity within the context of normal LGN gain control and cortical mechanisms (see Figure 1); and 2) findings of reduced contrast sensitivity and broadened orientation tuning in chronic schizophrenia can be successfully modeled by a combination of reduced V1 lateral inhibition and an increase in the Hebbian learning rate at V1 synapses for LGN input (see Figures 1-3). These models are consistent with many current findings (Silverstein, 2016) and they predict relationships that have not yet been explored. They also have implications for understanding links between perceptual changes and psychotic symptom formation, and for understanding changes during the long-term course of the disorder