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PubMed1996

[Neural pathways--neural networks].

During the past two decades, the introduction of several modern neuroanatomical approaches resulted in a rapidly growing body of informations about neuronal pathways in the central nervous system. Several new neuronal connections between brain areas have been discovered, and the chemical nature (neurotransmitter content) of pathways has been determined by using highly specific neurochemical and immunohistochemical techniques. On the basis of these new informations, our knowledge and attitude to the general organization of neuronal connections have been changed substantially: 1. Neuronal pathways are multi-neuronal networks rather than simple chain of neurons, wherein informations are forwarded between two brain areas bidirectionally, meanwhile several additional brain regions are inter-connected by axon-collaterals. 2. A single neuronal cell may synthesize several neuropeptides which co-localized in and released from nerve terminals, and depending on the target sites they may act as neurotransmitters or neurohormones. In certain conditions, neuropeptides may also function as nerve growth factors by supporting the survival or the restitution of neuronal cells. 3. By the introduction of molecular imaging in neuroscience (visualization of oncogenes, specific mRNA's, etc), topographical studies on neuronal pathways are more and more completed by functional informations.

Brain↗
PubMed1989

Immunoreactivity in Limulus: III. Morphological and biochemical studies of FMRFamide-like immunoreactivity and colocalized substance P-like immunoreactivity in the brain and lateral eye.

FMRFamide-like immunoreactivity (FLI) and the colocalization of FMRFamide and substance P-like (SPLI) immunoreactivities were examined in the brain and lateral eye of the horseshoe crab with FITC- and TRITC-labeled secondary antibody techniques. In the brain, fibers with FLI were localized in the neuropils of the lamina, medulla, central body, corpus pedunculatum, optic tract, circumesophageal connective, and central neuropil. An extensive network of reactive fibers innervatives the brain's vascular sheath. Somata with FLI were found in the dorsal medial group, dorsal lateral posterior groups #1 and #2, and ventral posterior lateral groups #1 and #2. Several distinct subgroups of reactive somata were noted in both the medullar and ventral medial groups. The distribution of fibers in the brain with colocalized FLI and SPLI includes those which innervate the vascular sheath and widespread populations of small-diameter beaded fibers in the central neuropil and circumesophageal connective. Somata with colocalized FLI and SPLI constitute minority populations in the medullar and dorsal medial groups but form the majority population of a subgroup in the ventral medial group. Overall localization of SPLI was reevaluated and is reported here according to the nomenclature of the new Chamberlain and Wyse brain atlas. In addition to those previously reported, somata with SPLI were found in the dorsal lateral posterior groups #1 and #2, the ventral lateral posterior groups #1 and #2, and several distinct subgroups of the medial and ventral medial groups. In the retina of the lateral eye, fibers with both FLI and SPLI ramify in the lateral plexus and ultimately innervate the corneal epidermis. Brain homogenates were examined for immunoreactive (ir) FMRFamide and ir-substance P with radioimmunoassay techniques. Ir-FMRFamide and ir-substance P eluted in different fractions from both gel filtration chromatography and HPLC. Furthermore, the binding curves for both substances were similar to those of the corresponding synthetic compounds. Brain homogenates were also bioassayed on the lateral eye. Three gel filtration fractions mimic natural circadian activity by increasing the sensitivity of the lateral eye, but they were not coincident with ir-FMRFamide or ir-substance P. Although it is not completely resolved what the active molecules in these fractions are, it is clear that neither ir-FMRFamide nor ir-substance P is a possible candidate.

Animals↗
PubMed2006

Dynamic causal modeling: a generative model of slice timing in fMRI.

Dynamic causal modeling (DCM) of functional magnetic resonance imaging (fMRI) data allows one to make inferences about the architecture of distributed networks in the brain, in terms of effective connectivity. fMRI data are usually acquired using echo planar imaging (EPI). EPI sequences typically acquire slices at different times over a few seconds. DCM, in its original inception, was not informed about these slice timings and assumed that all slices were acquired simultaneously. It has been shown that DCM can cope with slice timing differences of up to 1 s. However, many fMRI studies employ a repetition time (TR) of 3 to 5 s, which precludes a straightforward DCM of these data. We show that this limitation can be overcome easily by including slice timing in the DCM. Using synthetic data we show that the extended DCM furnishes veridical posterior means, even if there are large slice-timing differences. Model comparisons show that, in general, the extended DCM out-performs the original model. We contrast the modeling of slice timing, in the context of DCM, with the less effective approach of 'slice-timing correction', prior to modeling. We apply our procedure to real data and show that slice timings are important parameters. We conclude that, generally, one should use DCM with slice timing.

Humans↗
PubMed2006

Substance P and neurokinin-1 immunoreactivities in the neural circadian system of the Alaskan northern red-backed vole, Clethrionomys rutilus.

The suprachiasmatic nucleus (SCN) of the hypothalamus houses the main mammalian circadian clock. This clock is reset by light-dark cues and stimuli that evoke arousal. Photic information is relayed directly to the SCN via the retinohypothalamic tract (RHT) and indirectly via the geniculohypothalamic tract, which originates from retinally innervated cells of the thalamic intergeniculate leaflet (IGL). In addition, pathways from the dorsal and median raphe (DR and MR) convey arousal state information to the IGL and SCN, respectively. The SCN regulates many physiological events in the body via a network of efferent connections to areas of the brain such as the habenula (Hb) in the epithalamus, subparaventricular zone (SPVZ) of the hypothalamus and locus coeruleus of the brainstem-areas of the brain associated with arousal and behavioral activation. Substance P (SP) and the neurokinin-1 (NK-1) receptor are present in the rat SCN and IGL, and SP acting via the NK-1 receptor alters SCN neuronal activity and resets the circadian clock in this species. However, the distribution and role of SP and NK-1 in the circadian system of other rodent species are largely unknown. Here we use immunohistochemical techniques to map the novel distribution of SP and NK-1 in the hypothalamus, thalamus and brainstem of the Alaskan northern red-backed vole, Clethrionomys rutilus, a species of rodent currently being used in circadian biology research. Interestingly, the pattern of immunoreactivity for SP in the red-backed vole SCN was very different from that seen in many other nocturnal and diurnal rodents.

Alaska↗
PubMed2005

Patterning and plasticity of the cerebral cortex.

The cerebral cortex of the human brain is a sheet of about 10 billion neurons divided into discrete subdivisions or areas that process particular aspects of sensation, movement, and cognition. Recent evidence has begun to transform our understanding of how cortical areas form, make specific connections with other brain regions, develop unique processing networks, and adapt to changes in inputs.

Animals↗
PubMed2002

[A conjecture about Jingluo and suggestions on its research].

The Jingluo is a great hypothesis and theory of Chinese traditional medicine. The physical existence of Jingluo phenomena has been proved by many medical practices, but its real mechanism is still unknown. Here is a conjecture about Jingluo: "The essence of Jingluo is in CNS, the lines of Jingluo on soma is only actually a mapping of some strong connection networks in cortex or white matter of brain". Many new modalities of medical imaging like fMRI, PET, SPECT and Mapping MEG can do a good job on functional brain imaging. If we improve their spatial resolution and develop new methods to indicate brain activities, maybe we can unveil the secret of Jingluo.

Central Nervous System↗
PubMed1980

Distributed processing by visual interneurons of crayfish brain. II. Network organization and stimulus modulation of synaptic efficacy.

1. Multiple interactions were examined between five or six visual neurons simultaneously monitored in the circumesophageal connective. 2. A single neuron can make divergent connections to at least five other visual interneurons. 3. Conversely, a single cell may receive convergent inputs from up to four visual interneurons. 4. The convergent interactions are sufficiently intense so that 80--90% of a postsynaptic cell's visual activity can be attributed to observed network interactions. 5. Connectivity diagrams suggest that the descending interneurons, which arise in the visual neuropil of the brain, are organized into three interconnected layers: a) neurons that receive input from the optic nerve and project to other visual interneurons, b) neurons that both receive input and project to other descending interneurons in the brain--these cells exhibit a preponderance of reciprocal interactions, c) neurons that receive input from both the first and second network layers and project exclusively to the more caudal ganglia of the ventral nerve cord. 6. The network is systematically organized with respect to visual and nonvisual responsiveness. The cells of the first layer exhibit the strongest visual responses. The cells of the third layer exhibit spontaneous activity and the strongest tactile and/or proprioceptive responses. 7. The intensity of the network interactions is under stimulus control. The synaptic efficacy of a presynaptic spike can vary by over 100-fold as a consequence of stimulus presentation and/or location. The expressed organization of the network thus exhibits a dynamic, stimulus-dependent, plasticity. 8. The results indicate that the descending visual interneurons of the brain rather than forming a parallel tract actually constitute a complex distributed network. Furthermore, the results indicate the feasibility of population neural coding based on stimulus-dependent inpulse coordination in an array of neurons.

Animals↗
PubMed2005

Cerebral pathways in processing of affective prosody: a dynamic causal modeling study.

This study was conducted to investigate the connectivity architecture of neural structures involved in processing of emotional speech melody (prosody). 24 subjects underwent event-related functional magnetic resonance imaging (fMRI) while rating the emotional valence of either prosody or semantics of binaurally presented adjectives. Conventional analysis of fMRI data revealed activation within the right posterior middle temporal gyrus and bilateral inferior frontal cortex during evaluation of affective prosody and left temporal pole, orbitofrontal, and medial superior frontal cortex during judgment of affective semantics. Dynamic causal modeling (DCM) in combination with Bayes factors was used to compare competing neurophysiological models with different intrinsic connectivity structures and input regions within the network of brain regions underlying comprehension of affective prosody. Comparison on group level revealed superiority of a model in which the right temporal cortex serves as input region as compared to models in which one of the frontal areas is assumed to receive external inputs. Moreover, models with parallel information conductance from the right temporal cortex were superior to models in which the two frontal lobes accomplish serial processing steps. In conclusion, connectivity analysis supports the view that evaluation of affective prosody requires prior analysis of acoustic features within the temporal and that transfer of information from the temporal cortex to the frontal lobes occurs via parallel pathways.

Adult↗
PubMedDate not supplied

Population oscillations in a discrete model of neural networks of the brain.

A discrete model of biological neural networks is used to find out how synchronized firing of neurons emerges in a randomly connected neural population. The objective is to understand the mechanisms underlying brain waves and to find and characterize conditions which support spontaneous switching from disordered to rhythmic population activity as in case of an epileptic seizure. The model is kept as simple as possible to achieve on one hand a fast performance of computer simulations of networks with up to 10,000 neurons and to keep on the other hand an overview of parameter dependences. Dynamics of the model can be classified into different regimes: random fluctuations, rhythmic oscillations and silence. When the ratio of the inhibitory/excitatory connectivity is raised the system crosses from the fluctuating regime through the rhythmic oscillating region to the silence regime. Close to the boundary between the fluctuating and the oscillating regimes the network shows spontaneous bursting of high amplitude rhythmic oscillations, which is characteristic of epileptiform behavior. The simulation results are in agreement with recent theories saying that focal epilepsy after injury of the brain could result from axonal sprouting of GABAergic neurons in the injured region.

Brain↗
PubMed2005

Neural pattern dynamics in an oscillator model of the thalamo-reticular system.

One of development issues for information processing with synchronous oscillations in the brain is how new information is coded and how a comparison with already existing information is performed. In the present work we study a simple neural network model of the thalamo-reticular system based on the Wilson-Cowan model of neuronal oscillatory behavior. Our results show that both cortical control over the thalamus and external sensory input are essential in coordinating and generating spatio-temporal patterns of synchronous activity. A main finding of the numerical simulations is that the network connectivity and the intrinsic oscillatory properties of the neurons result in distinct collective behaviors within the network. By varying the connectivity schemes comparable with lesionated or damaged brain regions our results are in good agreement with in vivo experimental results. Suppressing the sensory input results in temporal oscillatory activity in the beta and gamma range and a strong spatial dependence of the network activity.

Algorithms↗
PubMed2004

Functional holography of recorded neuronal networks activity.

We present a new approach for analyzing multi-channel recordings, such as ECoG (electrocorticograph) recordings of cortical brain activity and of individual neuron dynamics, in cultured networks. The latter are used here to illustrate the method and its ability to discover hidden functional connectivity motifs in the recorded activity. The cultured networks are formed from dissociated mixtures of cortical neurons and glia-cells that are homogeneously spread over multi-electrode array for recording of the neuronal activity. Rich, spontaneous dynamical behavior is detected, marked by the formation of temporal sequences of synchronized bursting events (SBEs), partitioned into statistically distinguishable subgroups, each with its own characteristic spatio-temporal pattern of activity.In analogy with coherence connectivity networks for multi-location cortical recordings, we evaluated the inter-neuron correlation-matrix for each subgroup. Ordinarily such matrices are mapped onto a connectivity network between neuron positions in real space. In our functional holography, the correlations are normalized by the correlation distances Euclidian distances between the matrix columns. Then, we project the N-dimensional (for N channels) space spanned by the matrix of the normalized correlations, or correlation affinities, onto a corresponding 3D manifold (3D Cartesian space constructed by the three leading principal vectors of the principal component algorithm). The neurons are located by their principal eigenvalues and linked by their original (not normalized) correlations. By looking at these holograms, hidden causal motifs are revealed: each SBEs subgroup generates its characteristic connectivity diagram (network) in the 3D manifold, where the neuron locations and their links form simple structures. Moreover, the computed temporal ordering of neuron activity, when projected onto the connectivity diagrams, also exhibits simple patterns of causal propagation. We show that the method can expose functional connectivity motifs like the co-existence of subneuronal functional networks in the space of affinities. The method can be directly utilized to construct similar causal holograms for recorded brain activity. We expect that by doing so, hidden functional connectivity motifs with relevance to the understanding of brain activity might be discovered.

Animals↗
PubMed1999

Multiple constraint organization in the brain: a theory for schizophrenia.

Schizophrenia may be reconceptualized as disturbances in the multiple constraint organization between and within neurological subsystems in the brain. In disorganized schizophrenia the disturbances of multiple constraint organization encompass most if not all brain systems. In reality-distortion schizophrenia, auditory unimodal and their connections with heteromodal networks are primarily affected. Delusions are related to disturbances of constraints among higher transmodal systems that involve conceptual processes of ideas. Poverty symptoms of schizophrenia presumably emerge from disturbances in constraint satisfaction of the networks located at the highest levels of the hierarchy; these are the networks that connect sensation with action. The reconceptualizations proposed in this work could generate testable predictions relevant to brain research in schizophrenia and may prove useful for devising a more etiologically oriented diagnostic system for the disorder.

Brain↗
PubMed2004

Motifs in brain networks.

Complex brains have evolved a highly efficient network architecture whose structural connectivity is capable of generating a large repertoire of functional states. We detect characteristic network building blocks (structural and functional motifs) in neuroanatomical data sets and identify a small set of structural motifs that occur in significantly increased numbers. Our analysis suggests the hypothesis that brain networks maximize both the number and the diversity of functional motifs, while the repertoire of structural motifs remains small. Using functional motif number as a cost function in an optimization algorithm, we obtain network topologies that resemble real brain networks across a broad spectrum of structural measures, including small-world attributes. These results are consistent with the hypothesis that highly evolved neural architectures are organized to maximize functional repertoires and to support highly efficient integration of information.

Algorithms↗
PubMedDate not supplied

[Reactions of a neuronal network model with stochastic connections to frequency variations and interval structure of input signals].

A computer model of neuron network with stochastic ally organized connections was studied. The constructed neural network found to be highly sensitive to the interval structure of input signals and is capable of integrating and encoding them by the ratio of frequencies of pulsations of neurons comprising the network. The results obtained suggest that essential in modelling real brain structures is both the stochastic distribution of interneuron connections and specific configuration of anatomic connections of the real neural network. The proposal is made to assess these two possibilities separately.

Computer Simulation↗
PubMed2006

Dendritic pathology in mental retardation: from molecular genetics to neurobiology.

Mental retardation (MR) is a developmental brain disorder characterized by impaired cognitive performance and adaptive skills that affects 1-2% of the population. During the last decade, a large number of genes have been cloned that cause MR upon mutation in humans. The causal role of these genes provides an excellent starting point to investigate the cellular, neurobiological and behavioral alterations and mechanisms responsible for the cognitive impairment in mentally retarded persons. However, studies on Down syndrome (DS) reveal that overexpression of a cluster of genes and various forms of MR that are caused by single-gene mutations, such as fragile X (FraX), Rett, Coffin-Lowry, Rubinstein-Taybi syndrome and non-syndromic forms of MR, causes similar phenotypes. In spite of the many differences in the manifestation of these forms of MR, evidence converges on the proposal that MR is primarily due to deficiencies in neuronal network connectivity in the major cognitive centers in the brain, which secondarily results in impaired information processing. Although MR has been largely regarded as a brain disorder that cannot be cured, our increased understanding of the abnormalities and mechanisms underlying MR may provide an avenue for the development of therapies for MR. In this review, we discuss the neurobiology underlying MR, with a focus on FraX and DS.

Animals↗
PubMed2002

Effective connectivity and intersubject variability: using a multisubject network to test differences and commonalities.

This article is about intersubject variability in the functional integration of activity in different brain regions. Previous studies of functional and effective connectivity have dealt with intersubject variability by analyzing data from different subjects separately or pretending the data came from the same subject. These approaches do not allow one to test for differences among subjects. The aim of this work was to illustrate how differences in connectivity among subjects can be addressed explicitly using structural equation modeling. This is enabled by constructing a multisubject network that comprises m regions of interest for each of the n subjects studied, resulting in a total of m x n nodes. Constructing a network of regions from different subjects may seem counterintuitive but embodies two key advantages. First, it allows one to test directly for differences among subjects by comparing models that do and do not allow a particular connectivity parameter to vary over subjects. Second, a multisubject network provides additional degrees of freedom to estimate the model's free parameters. Any neurobiological hypothesis normally addressed by single-subject or group analyses can still be tested, but with greater sensitivity. The common influence of experimental variables is modeled by connecting a virtual node, whose time course reflects stimulus onsets, to the sensory or "input" region in all subjects. Further experimental changes in task or cognitive set enter through modulation of the connections. This approach allows one to model both endogenous (or intrinsic) variance and exogenous effects induced by experimental design. We present a functional magnetic resonance imaging study that uses a multisubject network to investigate intersubject variability in functional integration in the context of single word and pseudoword reading. We tested whether the effect of word type on the reading-related coupling differed significantly among subjects. Our results showed that a number of forward and backward connections were stronger for reading pseudowords than words, and, in one case, connectivity showed significant intersubject variability. The discussion focuses on the implications of our findings and on further applications of the multisubject network analysis.

Adult↗
PubMed2004

Astrocytic adrenoceptors: a major drug target in neurological and psychiatric disorders?

Considerable attention has recently been paid to astrocyte functions, which are briefly summarized. A large amount of data is available about adrenoceptor expression and function in astrocytes, some of it dating back to the 1970's and some of it very recent. This material is reviewed in the present paper. The brain is innervated by noradrenergic fibers extending from locus coeruleus in the brain stem, which in turn is connected to a network of adrenergic and noradrenergic nuclei in the medulla and pons, contributing to the control of (nor)adrenergic, serotonergic, dopaminergic and cholinergic function, both in the central nervous system (CNS) and in the periphery. In the CNS astrocytes constitute a major target for noradrenergic innervation, which regulates morphological plasticity, energy metabolism, membrane transport, gap junction permeability and immunological responses in these cells. Noradrenergic effects on astrocytes are essential during consolidation of episodic, long-term memory, which is reinforced by beta-adrenergic activation. Glycogenolysis and synthesis of glutamate and glutamine from glucose, both of which are metabolic processes restricted to astrocytes, occur at several time-specific stages during the consolidation. Astrocytic abnormalities are almost certainly important in the pathogenesis of multiple sclerosis and in all probability contribute essentially to inflammation and malfunction in Alzheimer's disease and to mood disturbances in affective disorders. Noradrenergic function in astrocytes is severely disturbed by chronic exposure to cocaine, which also changes astrocyte morphology. Development of drugs modifying noradrenergic receptor activity and/or down-stream signaling is advocated for treatment of several neurological/psychiatric disorders and for neuroprotection. Astrocytic preparations are suggested for study of mechanism(s) of action of antidepressant drugs and pathophysiology of mood disorders.

Adrenergic Agents↗