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PubMedDate not supplied

Semantic disturbance in schizophrenia and its relationship to the cognitive neuroscience of attention.

We view schizophrenia as producing a failure of attentional modulation that leads to a breakdown in the selective enhancement or inhibition of semantic/lexical representations whose biological substrata are widely distributed across left (dominant) temporal and frontal lobes. Supporting behavioral evidence includes word recall studies that have pointed to a disturbance in connectivity (associative strength) but not network size (number of associates) in patients with schizophrenia. Paralleling these findings are recent neural network simulation studies of the abnormal connectivity effect in schizophrenia through 'lesioning' network connection weights while holding constant network size. Supporting evidence at the level of biology are in vitro studies examining N-methyl-D-aspartate (NMDA) receptor antagonists on recurrent inhibition; simulations in neural populations with realistically modeled biophysical properties show NMDA antagonists produce a schizophrenia-like disturbance in pattern association. We propose a similar failure of NMDA-mediated recurrent inhibition as a candidate biological substrate for attention and semantic anomalies of schizophrenia.

Attention↗
PubMed1982

Somatostatin: localization and distribution in the cortex and the subcortical white matter of human brain.

Examination of the cortex and the subcortical white matter by use of an immunocytochemical technique--the per oxidase anti-per oxidase method--shows that somatostatin is located in a widespread neuron system with cell bodies localized in both the cortex and the subcortical white matter of the human brain. In the cortex, the somatostatin cell bodies and fibers are found in all layers, but the fibers are especially numerous in layer I located tangentially to the brain surface. The fibers are very long and subdivide into many branches which form a network of pathways in the deeper cortical layers. There are numerous varicosities along the fibers and they come into close contact with other non-immunoreactive neuronal cells. The somatostatin cells located in the white matter are larger than the somatostatin cells in gray matter. They are giant cells with a size ranging from 50 to 120 micrometers. The fibers from these cells are varicose and can be followed both rostrally into the cortical gray matter and caudally in the subcortical white matter. The localization and the morphology of the somatostatin neurons in the cortex and the subcortical white matter indicate that somatostatin may be able to exert sustained influence in various brain areas and thereby modulate integrative and/or specific functions, not only via connection in the gray matter but also by influencing the neuronal circuits passing through the subcortical white matter.

Brain↗
PubMed2000

Synaptic plasticity and memory: an evaluation of the hypothesis.

Changing the strength of connections between neurons is widely assumed to be the mechanism by which memory traces are encoded and stored in the central nervous system. In its most general form, the synaptic plasticity and memory hypothesis states that "activity-dependent synaptic plasticity is induced at appropriate synapses during memory formation and is both necessary and sufficient for the information storage underlying the type of memory mediated by the brain area in which that plasticity is observed." We outline a set of criteria by which this hypothesis can be judged and describe a range of experimental strategies used to investigate it. We review both classical and newly discovered properties of synaptic plasticity and stress the importance of the neural architecture and synaptic learning rules of the network in which it is embedded. The greater part of the article focuses on types of memory mediated by the hippocampus, amygdala, and cortex. We conclude that a wealth of data supports the notion that synaptic plasticity is necessary for learning and memory, but that little data currently supports the notion of sufficiency.

Amygdala↗
PubMed2006

Role of persistent sodium current in bursting activity of mouse neocortical networks in vitro.

Most types of electrographic epileptiform activity can be characterized by isolated or repetitive bursts in brain electrical activity. This observation is our motivation to determine mechanisms that underlie bursting behavior of neuronal networks. Here we show that the persistent sodium (Na(P)) current in mouse neocortical slices is associated with cellular bursting and our data suggest that these cells are capable of driving networks into a bursting state. This conclusion is supported by the following observations. 1) Both low concentrations of tetrodotoxin (TTX) and riluzole reduce and eventually stop network bursting while they simultaneously abolish intrinsic bursting properties and sensitivity levels to electrical stimulation in individual intrinsically bursting cells. 2) The sensitivity levels of regular spiking neurons are not significantly affected by riluzole or TTX at the termination of network bursting. 3) Propagation of cellular bursting in a neuronal network depended on excitatory connectivity and disappeared on bath application of CNQX (20 microM) + CPP (10 microM). 4) Voltage-clamp measurements show that riluzole (20 microM) and very low concentrations of TTX (50 nM) attenuate Na(P) currents in the neural membrane within a 1-min interval after bath application of the drug. 5) Recordings of synaptic activity demonstrate that riluzole at this concentration does not affect synaptic properties. 6) Simulations with a neocortical network model including different types of pyramidal cells, inhibitory interneurons, neurons with and without Na(P) currents, and recurrent excitation confirm the essence of our experimental observations that Na(P) conductance can be a critical factor sustaining slow population bursting.

Animals↗
PubMed1998

Statistically efficient estimation using population coding.

Coarse codes are widely used throughout the brain to encode sensory and motor variables. Methods designed to interpret these codes, such as population vector analysis, are either inefficient (the variance of the estimate is much larger than the smallest possible variance) or biologically implausible, like maximum likelihood. Moreover, these methods attempt to compute a scalar or vector estimate of the encoded variable. Neurons are faced with a similar estimation problem. They must read out the responses of the presynaptic neurons, but, by contrast, they typically encode the variable with a further population code rather than as a scalar. We show how a nonlinear recurrent network can be used to perform estimation in a near-optimal way while keeping the estimate in a coarse code format. This work suggests that lateral connections in the cortex may be involved in cleaning up uncorrelated noise among neurons representing similar variables.

Computer Simulation↗
PubMed2006

A neural network reflecting individual differences in cognitive processing of emotions during perceptual decision making.

Even simple perceptual decisions are influenced by the emotional content of a stimulus. Recent neuroimaging studies provide evidence about the neural mechanisms of perceptual decision making on emotional stimuli. However, the effect of individual differences in cognitive processing of emotions on perceptual decision making remains poorly understood. Here, we investigated how changes in the fMRI signal during perceptual decision making on facial stimuli covaried with individual differences in the ability to identify and communicate one's emotional state. Although this personality trait covaried with changes in activity in the dorsal anterior cingulate cortex (dACC) during gender decisions on facial expressions, there was no correlation during emotion decisions. Further, we investigated whether individual differences in the ability to cognitively process emotions depend on differences in the functional integration of emotional and cognitive brain regions. We therefore compared task-dependent changes in effective connectivity of dACC in individuals with good and with poor ability to cognitively process emotions using a psychophysiological interaction analysis. We found greater coupling of dACC with prefrontal regions in individuals with good ability to identify and communicate their emotional state. Conversely, individuals with poor ability in this domain showed greater coupling of dACC with the amygdala. Our data indicate that individual differences in the ability to identify and communicate one's emotional state are reflected by altered effective connectivity of the dACC with prefrontal and limbic regions. Thus, we provide neurophysiological evidence for a theoretical model that posits that a discommunication between limbic areas and the neocortex impairs cognitive processing of emotions.

Adult↗
PubMedDate not supplied

[The ultrastructural changes in the collagenous-elastic skeleton of the wall of the cerebral vessels in spasm in the acute period of a subarachnoid hemorrhage].

Electron microscopic study of arteries in spasm and ischemia of the brain revealed substantial ultrastructural changes in the vascular wall. The changes are characterized by varying thickness, edema, dissociation of fibrillar and amorphous components of internal elastic membrane of the arterial wall, by lesion in the network of collagen fibers on its inner surface, by the presence of defibrotic and uncoiled collagenous fibers of the adventitia. The changes are followed by the impairment of the arterial skeleton and hence they lead to their altered elastic properties.

Acute Disease↗
PubMed1995

Gap junctions in the vertebrate retina.

The vertebrate retina is a highly laminated assemblage of specialized neuronal types, many of which are coupled by gap junctions. With one interesting exception, gap junctions are not directly responsible for the 'vertical' transmission of visual information from photoreceptors through bipolar and ganglion cells to the brain. Instead, they mediate 'lateral' connections, coupling neurons of a single type or subtype into an extended, regular array or mosaic in the plane of the retina. Such mosaics have been studied by several microscopic techniques, but new evidence for their coupled nature has recently been obtained by intracellular injection of biotinylated tracers, which can pass through gap junctional assemblies that do not pass Lucifer Yellow. This evidence adds momentum to an existing paradigm shift towards a population-based view of the retina, which can now be envisaged both as an array of semi-autonomous vertical processing modules, each extending right through the retina, and as a multi-layered stack of interacting planar mosaics, bearing some resemblance to a set of interleaved neural networks. Junctional conductance across mosaics of horizontal cells is known to be controlled dynamically with a circadian rhythm, and other dynamically-regulated conductance changes are also likely to make important contributions to signal processing. The retina is an excellent system in which to study such changes because many aspects of its structure and function are already well understood. In this review, we summarize the microscopic appearance, coupling properties and functions of gap junctions for each cell type of the neural retina, the regulatory properties that could be provided by selective expression of different connexin proteins, and the evidence for gap junctional coupling in retina development.

Animals↗
PubMed2005

Neuroligins and neurexins: linking cell adhesion, synapse formation and cognitive function.

Cell adhesion represents the most direct way of coordinating synaptic connectivity in the brain. Recent evidence highlights the importance of a trans-synaptic interaction between postsynaptic neuroligins and presynaptic neurexins. These transmembrane molecules bind each other extracellularly to promote adhesion between dendrites and axons. This signals the recruitment of presynaptic and postsynaptic molecules to form a functional synapse. Remarkably, neuroligins alone can induce the formation of fully functional presynaptic terminals in contacting axons. Conversely, neurexins alone can induce postsynaptic differentiation and clustering of receptors in dendrites. Therefore, the neuroligin-neurexin interaction has the unique ability to act as a bi-directional trigger of synapse formation. Here, we review several recent studies that offer clues as to how these proteins form synapses and how they might function in the brain to establish and modify neuronal network properties and cognition.

Activated-Leukocyte Cell Adhesion Molecule↗
PubMed2001

Area 3a: topographic organization and cortical connections in marmoset monkeys.

The functional organization of area 3a, a cortical field proposed to be involved in somato-motor-vestibular integration, has never been described for any primate. In the present investigation, the topographic organization and connections of area 3a were examined in marmosets using electrophysiological recording and anatomical tracing techniques. Multi-unit neuronal activity was recorded at a number of closely spaced sites; receptive fields (RFs) for neurons were determined, and the optimal stimulus was identified. In all cases, neurons in area 3a responded to the stimulation of deep receptors on the contralateral body. The representation of the body in area 3a was from the toes and foot, to the hindlimb, trunk, forelimb, hand and face in a mediolateral progression. In all cases electrophysiological results were related to myeloarchitecture, and the map in area 3a was found to be coextensive with a strip of lightly to moderately myelinated cortex just rostral to the darkly myelinated 3b. To examine the cortical connections of area 3a, injections of anatomical tracers were made into electrophysiologically identified body part representations. Area 3a has dense intrinsic connections and receives substantial inputs from the primary motor cortex (M1), the supplementary motor area (SMA), areas 1 and 2, the second somatosensory area (S2), and areas in posterior parietal cortex (PP). The connections of area 3a indicate that integration of cortical representations of body parts occurs both within area 3a and between area 3a and other somatosensory and motor areas. In addition, there are differential patterns of interconnections between behaviorally relevant body part representations of area 3a, such as the forelimb, compared to other body part representations (hindlimb/ trunk), especially with 'higher order' cortical fields. This suggests that 3a may be an important component in a network that generates a common frame of reference for hand and eye coordinated reaching tasks.

Animals↗
PubMed1999

Coupling of organotypic brain slice cultures to silicon-based arrays of electrodes.

Fetal or early postnatal brain tissue can be cultured in viable and healthy condition for several weeks with development and preservation of the basic cellular and connective organization as so-called organotypic brain slice cultures. Here we demonstrate and describe how it is possible to establish such hippocampal rat brain slice cultures on biocompatible silicon-based chips with arrays of electrodes with a histological organization comparable to that of conventional brain slice cultures grown by the roller drum technique and on semiporous membranes. Intracellular and extracellular recordings from neurons in the slice cultures show that the electroresponsive properties of the neurons and synaptic circuitry are in accordance with those described for cells in acutely prepared slices of the adult rat hippocampus. Based on the recordings and the possibilities of stimulating the cultured cells through the electrode arrays it is anticipated that the setup eventually will allow long-term studies of defined neuronal networks and provide valuable information on both normal and neurotoxicological and neuropathological conditions.

Animals↗
PubMed2003

The evolutionary origin of the mammalian isocortex: towards an integrated developmental and functional approach.

The isocortex is a distinctive feature of mammalian brains, which has no clear counterpart in the cerebral hemispheres of other amniotes. This paper speculates on the evolutionary processes giving rise to the isocortex. As a first step, we intend to identify what structure may be ancestral to the isocortex in the reptilian brain. Then, it is necessary to account for the transformations (developmental, connectional, and functional) of this ancestral structure, which resulted in the origin of the isocortex. One long-held perspective argues that part of the isocortex derives from the ventral pallium of reptiles, whereas another view proposes that the isocortex originated mostly from the dorsal pallium. We consider that, at this point, evidence tends to favor correspondence of the isocortex with the dorsal cortex of reptiles. In any case, the isocortex may have originated partly as a consequence of an overall "dorsalizing" effect (that is, an expansion of the territories expressing dorsal-specific genes) during pallial development. Furthermore, expansion of the dorsal pallium may have been driven by selective pressures favoring the development of associative networks between the dorsal cortex, the olfactory cortex, and the hippocampus, which participated in spatial or episodic memory in the early mammals. In this context, sensory projections that in reptiles end in the ventral pallium, are observed to terminate in the isocortex (dorsal pallium) of mammals, perhaps owing to their participation in these associative networks.

Anatomy, Comparative↗
PubMed2000

Actin-based plasticity in dendritic spines.

The central nervous system functions primarily to convert patterns of activity in sensory receptors into patterns of muscle activity that constitute appropriate behavior. At the anatomical level this requires two complementary processes: a set of genetically encoded rules for building the basic network of connections, and a mechanism for subsequently fine tuning these connections on the basis of experience. Identifying the locus and mechanism of these structural changes has long been among neurobiology's major objectives. Evidence has accumulated implicating a particular class of contacts, excitatory synapses made onto dendritic spines, as the sites where connective plasticity occurs. New developments in light microscopy allow changes in spine morphology to be directly visualized in living neurons and suggest that a common mechanism, based on dynamic actin filaments, is involved in both the formation of dendritic spines during development and their structural plasticity at mature synapses.

Actin Cytoskeleton↗
PubMed2004

Visual attention as a multilevel selection process.

Natural visual scenes are cluttered and contain many different objects that cannot all be processed simultaneously. Therefore, attentional mechanisms are needed to select relevant and to filter out irrelevant information. Evidence from functional brain imaging reveals that attention operates at various processing levels within the visual system and beyond. First, the lateral geniculate nucleus appears to be the first stage in the processing of visual information that is modulated by attention, consistent with the idea that it may play an important role as an early gatekeeper in controlling neural gain. Second, areas at intermediate cortical-processing levels, such as V4 and TEO, appear to be important sites at which attention filters out unwanted information by means of receptive field mechanisms. Third, the attention mechanisms that operate in the visual system appear to be controlled by a distributed network of higher order areas in the frontal and parietal cortex, which generate top-down signals that are transmitted via feedback connections to the visual system. And fourth, the pulvinar of the thalamus may operate by integrating and coordinating attentional functions in concert with the fronto-parietal network, although much needs to be learned about its functional properties. The overall view that emerges from the studies reviewed in this article is that neural mechanisms of selective attention operate at multiple stages in the visual system and beyond and are determined by the visual processing capabilities of each stage. In this respect, attention can be considered in terms of a multilevel selection process.

Attention↗
PubMed1984

Computer-assisted morphometry and microdensitometry of transmitter- identified neurons with special reference to the mesostriatal dopamine pathway. Methodological aspects.

New morphometrical and microdensitometrical approaches for evaluation of transmitter-identified neurons in the central nervous system have been developed. These rely at the presynaptic level on the use of immunocytochemistry and at the postsynaptic level on the use of receptor autoradiography. The immunocytochemical analysis involves the indirect immunofluorescence method and the indirect immunoperoxidase method utilizing cryostat and vibratome sections, respectively. In the postsynaptic analysis cryostat sections and tritium-sensitive film were employed. A block diagram representation of the system of the image analyzer used and its connection with its host computer is given. Furthermore, flow charts of the original software developed by our group in presented. The morphometrical analysis has been performed on coronal sections of rat brain resulting in determinations of cell body and cell group parameters. Based on this information, objective criteria have been introduced to assess the existence of a cell group of transmitter-identified neurons in a three-dimensional frame and to give a morphometrical description of this group in the space. Moreover, new quantitative approaches to describe the dendritic and terminal fields have been introduced and for the first time in this type of morphometrical analysis, the Lorenz curves and the Gini index have been utilized in the description of the pattern of dendritic and terminal networks. By means of these morphometrical approaches it became possible to analyze topological and biochemical heterogeneities within cell groups defined in the rostrocaudal frame. In particular, it has been possible to develop a quantitative method for the evaluation of coexistence in nerve cell bodies. This method has been called the overlap method and allows an analysis cell by cell of the possible coexistence of two or more antigens.

Animals↗
PubMedDate not supplied

A connectionist model of left-right sound discrimination by the Mauthner system.

Artificial neural networks were used to explore the auditory function of the Mauthner system, the brainstem circuit in teleost fishes that initiates fast-start escape responses. The artificial neural networks were trained with backpropagation to assign connectivity and receptive fields in an architecture consistent with the known anatomy of the Mauthner system. Our first goal was to develop neurally specific hypotheses for how the Mauthner system discriminates right from left in the onset of a sound. Our model was consistent with the phase model for directional hearing underwater, the prevalent theory for sound source localization by fishes. Our second goal was to demonstrate how the neural mechanisms that permit sound localization according to the phase model can coexist with the mechanisms that permit the Mauthner system to discriminate between stimuli based on amplitude. Our results indicate possible computational roles for elements of the Mauthner system, which has provided us a theoretical context within which to consider past and future experiments on the cellular physiology. Thus, these findings demonstrate the potential significance of this approach in generating experimentally testable hypotheses for small systems of identified cells.

Acoustic Stimulation↗
PubMed1993

The acupuncture point and its connecting central pathway for producing acupuncture analgesia.

Characteristics of the acupuncture point in producing acupuncture analgesia (AA) were examined by the inhibition of noxious responses in the brain stem reticular formation, potentials, and neuronal activity in the dorsal periaqueductal central gray (D-PAG), and analgesia caused by low frequency stimulation of the acupuncture point. As a result, stimulation of the muscle beneath the acupuncture point was found to be effective in producing AA. AA measured by tail flick, vocalization, and writhing tests was abolished by hypophysectomy, and by antiserum of beta-endorphin administered into the 3rd ventricle. The pathway from the D-PAG to the anterior hypothalamus (AA-AH) in the AA afferent pathway from the acupuncture point to the pituitary gland was determined. The lateral hypothalamus, lateral septum, cingulate bundle, dorsal-hippocampus, and habenulo-interpeduncular tract were found, in addition to regions previously found, to belong to the AA afferent pathway. A network of divergence and convergence in their rostral and caudal relations was observed. The AA afferent pathway diverges from the D-PAG, converges to the HP, and then projects to the AA-AH.

Acupuncture Analgesia↗
PubMed1996

A complexity measure for selective matching of signals by the brain.

We have previously derived a theoretical measure of neural complexity (CN) in an attempt to characterize functional connectivity in the brain. CN measures the amount and heterogeneity of statistical correlations within a neural system in terms of the mutual information between subsets of its units. CN was initially used to characterize the functional connectivity of a neural system isolated from the environment. In the present paper, we introduce a related statistical measure, matching complexity (CM), which reflects the change in CN that occurs after a neural system receives signals from the environment. CM measures how well the ensemble of intrinsic correlations within a neural system fits the statistical structure of the sensory input. We show that CM is low when the intrinsic connectivity of a simulated cortical area is randomly organized. Conversely, CM is high when the intrinsic connectivity is modified so as to differentially amplify those intrinsic correlations that happen to be enhanced by sensory input. When the input is represented by an individual stimulus, a positive value of CM indicates that the limited mutual information between sensory sheets sampling the stimulus and the rest of the brain triggers a large increase in the mutual information between many functionally specialized subsets within the brain. In this way, a complex brain can deal with context and go "beyond the information given."

Animals↗