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Finite state model of locomotion for functional electrical stimulation systems.

A finite state model of locomotion was developed to simplify a controller design for motor activities of handicapped humans. This paper presents a model developed for real time control of locomotion with functional electrical stimulation (FES) assistive systems. Hierarchical control of locomotion was adopted with three levels: voluntary, coordination and actuator level. This paper deals only with coordination level of control. In our previous studies we demonstrated that a skill-based expert system can be used for coordination level of control in multi-joint FES systems. Basic elements in this skill-based expert system are production rules. Production rules have the form of If-Then conditional expressions. A technique of automatic determination of these conditional expressions is presented in this paper. This technique for automatic synthesis of production rules uses fuzzy logic and artificial neural networks (ANN). The special class of fuzzy logic elements used in this research is called preferential neurons. The preferential neurons were used to estimate the relevance of each of the sensory inputs to the recognition of patterns defined as finite states. The combination of preferential neurons forms a preferential neural network. The preferential neural network belongs to a class of ANNs. The preferential neural network determined the set of finite states convenient for a skill-based expert system for different modalities of locomotion.

Ankle Joint↗

Zonulae occludentes in junctional complex-enriched fractions from mouse liver: preliminary morphological and biochemical characterization.

A bile canaliculus-derived preparation containing junctional complexes has been obtained from mouse livers using subcellular fractionation techniques. The junctional complexes include structurally intact zonulae occludentes (ZOs). Extraction of this preparation with the anionic detergent sodium deoxycholate (DOC) left junctional ribbons, the detergent-insoluble zonular remnants of the junctional complexes. When visualized in negative stain electron microscopy, each of these ribbons contained a branching and anastomosing network of fibrils which appears similar to that of ZOs in freeze-fractured whole liver. Comparative measurements of freeze-fracture and negative stain fibril diameters and network densities support this relationship. SDS polyacrylamide gel analysis shows the DOC-insoluble junctional ribbons to be characterized by major polypeptides at 37,000 and at 48,000, with minor bands at 34,000, 41,000, 71,000, 86,000, 92,000, and 102,000. The ZO-containing membrane fractions have been isolated in the presence of EGTA in concentrations and under conditions shown by others to disrupt normal ZO morphology and physiology in whole living epithelia. The network of fibrils visualized in these fractions by negative staining is structurally resistant to treatment with DOC, but is either solubilized or disrupted by N-lauroylsarcosine.

Animals↗

A stochastic population approach to the problem of stable recruitment hierarchies in spiking neural networks.

Synchrony-driven recruitment learning addresses the question of how arbitrary concepts, represented by synchronously active ensembles, may be acquired within a randomly connected static graph of neuron-like elements. Recruitment learning in hierarchies is an inherently unstable process. This paper presents conditions on parameters for a feedforward network to ensure stable recruitment hierarchies. The parameter analysis is conducted by using a stochastic population approach to model a spiking neural network. The resulting network converges to activate a desired number of units at each stage of the hierarchy. The original recruitment method is modified first by increasing feedforward connection density for ensuring sufficient activation, then by incorporating temporally distributed feedforward delays for separating inputs temporally, and finally by limiting excess activation via lateral inhibition. The task of activating a desired number of units from a population is performed similarly to a temporal k-winners-take-all network.

Feedback, Physiological↗

Physiological effects of sustained blockade of excitatory synaptic transmission on spontaneously active developing neuronal networks--an inquiry into the reciprocal linkage between intrinsic biorhythms and neuroplasticity in early ontogeny.

Spontaneous bioelectric activity (SBA) taking the form of extracellularly recorded spike trains (SBA) has been quantitatively analyzed in organotypic neonatal rat visual cortex explants at different ages in vitro, and the effects investigated of both short- and long-term pharmacological suppression of glutamatergic synaptic transmission. In the presence of APV, a selective NMDA receptor blocker, 1-2- (but not 3-)week-old cultures recovered their previous SBA levels in a matter of hours, although in imitation of the acute effect of the GABAergic inhibitor picrotoxin (PTX), bursts of action potentials were abnormally short and intense. Cultures treated either overnight or chronically for 1-3 weeks with APV, the AMPA/kainate receptor blocker DNQX, or a combination of the two were found to display very different abnormalities in their firing patterns. NMDA receptor blockade for 3 weeks produced the most severe deviations from control SBA, consisting of greatly prolonged and intensified burst firing with a strong tendency to be broken up into trains of shorter spike clusters. This pattern was most closely approximated by acute GABAergic disinhibition in cultures of the same age, but this latter treatment also differed in several respects from the chronic-APV effect. In 2-week-old explants, in contrast, it was the APV+DNQX treated group which showed the most exaggerated spike bursts. Functional maturation of neocortical networks, therefore, may specifically require NMDA receptor activation (not merely a high level of neuronal firing) which initially is driven by endogenous rather than afferent evoked bioelectric activity. Putative cellular mechanisms are discussed in the context of a thorough review of the extensive but scattered literature relating activity-dependent brain development to spontaneous neuronal firing patterns.

Action Potentials↗

The lymphatic system in body homeostasis: physiological conditions.

The lymphatic system is an organized network composed of functionally interrelated lymphoid tissue, and transportation pathways of tissue fluid/lymph and lymphoid cells. Its main components are 1. migrating dendritic cells, macrophages and lymphocytes, organized lymphoid tissue such as lymph nodes, thymus, spleen, bone marrow, and lymphoid tissue in gut and lungs, liver lymphoid cells, and the dendritic cell network of nonlymphoid organs; 2. vessels (intercellular space, lymphatics, and perivascular spaces); 3. fluids (tissue fluid and lymph). The lymphatic system can be divided into the following compartments: peripheral (from the interstitial space to and within the nearest lymph node), and central (efferent lymphatics, cysterna chyli, and thoracic duct, all lymphoid organs). Organs and tissues with the most active afferent arm of the lymphatic system are skin, gut, and lungs. These are the body structures exposed to the external environment. All other nonlymphoid bodily tissues are also percolated by tissue fluid/lymph, and contain a network of dendritic cells and macrophages. Data obtained from normal human subjects on lymph composition and flow are presented. Future trends in lymphatic research are outlined.

Animals↗

Construction of concepts by the nervous system: from neurons to cognition.

Neurophysiological studies have recently identified a pattern of synchronized slow-wave activity in the visual cortex which characteristically encompasses groups of neurons activated by similar or closely related stimulus attributes. This slow-wave activity appears to tag clusters of neurons to form aggregates representing in their totality more complex, higher-order stimulus attributes across disparate positions in the cortical representation. The notion is advanced that the function of these aggregates is analogous to that ascribed to the subsymbolic computational level in connectionist networks. On this basis, the argument is presented that the synchronized cortical activity is an important aspect of the construction of symbolic representation by the nervous system and, thus, a step from neural information processing to the symbolic processes stipulated by classical cognitivism.

Animals↗

Dual role of GABA in the neonatal rat hippocampus.

The effects of modulators of GABA-A receptors on neuronal network activity were studied in the neonatal (postnatal days 0-5) rat hippocampus in vitro. Under control conditions, the physiological pattern of activity of the neonatal hippocampal network was characterized by spontaneous network-driven giant depolarizing potentials (GDPs). The GABA-A receptor agonist isoguvacine (1-2 microM) and the allosteric modulator diazepam (2 microM) induced biphasic responses: initially the frequency of GDPs increased 3 to 4 fold followed by blockade of GDPs and desynchronization of the network activity. The GABA-A receptor antagonists bicuculline (10 microM) and picrotoxin (100 microM) blocked GDPs and induced glutamate (AMPA and NMDA)-receptor-mediated interictal- and ictal-like activities in the hippocampal slices and the intact hippocampus. These data suggest that at early postnatal ages GABA can exert a dual - both excitatory and inhibitory - action on the network activity.

Animals↗

[A multiparametric monitoring network system based on windows operation system].

This paper introduces the general structure and implementary method both in hardware and software of a monitoring network system, which is developed for monitoring physiological multi-parameter under Windows operation system and based on personal computer. The parameters monitored by the system include Electrocardiogram (ECG), Noninvasive Blood Pressure (NIBP), Oxygen Saturation (SpO2), Respiration (RESP) and Body Temperature. Monitoring data can be shared by internal hospital network. The system has the advantages of easy operation and flexible structure. It is a new kind of hospital monitoring equipment.

Blood Pressure Determination↗

Morphological evidence of the shedding of chondrocytes from the articular surface in neonatal rats: relationship to the interlacunar network.

The superficial zone of the femoral head articular cartilage of 5- to 15-day old rats was examined by light and electron microscopy for evidence of shedding into the joint space. Chondrocytes deepest in the superficial zone were round, surrounded by a capsule, and connected to adjacent chondrocytes by the interlacunar network, whereas cells in the middle of the zone appeared similar but with less cytoplasm. At the circular surface, chondrocytes were small, with pyknotic nuclei and poorly defined organelles. These cells occasionally protruded from the articular surface but maintained at least partial connection with the network and their capsule. Depressions in the articular surface were lined with material similar to that of the network and were the only locations found where the network did not terminate at a cell surface. This static evidence suggested at least two hypotheses: 1) Degenerating chondrocytes moved up through the superficial zone to the articular surface and were shed into the joint space. This movement may be facilitated by the network as part of neonatal cartilage development. 2) During joint formation, the surface of the articular cartilage was eroded down to the chondrocytes, which were exposed to the joint fluid, causing cell degeneration, death, and shedding. Evidence of cell shedding was rarely seen after 2 weeks of age. Likewise, the interlacunar network disappeared from the superficial zone during this period. A physiological as well as structural relationship may exist between the chondrocytes and interlacunar network.

Animals↗

Mutational analysis and biochemical characterization of the Burkholderia thailandensis DW503 quorum-sensing network.

Numerous gram-negative bacteria communicate and regulate gene expression through a cell density-responsive mechanism termed quorum sensing (QS), which involves the synthesis and perception of diffusible N-acyl-homoserine lactones (AHL). In this study we genetically and physiologically characterized the Burkholderia thailandensis DW503 QS network. In silico analysis of the B. thailandensis genome revealed the presence of at least three AHL synthases (AHS) and five transcriptional regulators belonging to the LuxIR family of proteins. Mass spectrometry demonstrated that wild-type B. thailandensis synthesizes N-hexanoyl-homoserine lactone (C6-HSL), N-octanoyl-homoserine lactone (C8-HSL), and N-decanoyl-homoserine lactone (C10-HSL). Mutation of the btaI1 (luxI) AHS gene prevented accumulation of C8-HSL in culture supernatants, enhanced beta-hemolysis of sheep erythrocytes, increased lipase production, and altered colony morphology on swarming and twitching motility plates. Disruption of the btaI3 (luxI) AHS prevented biosynthesis of C6-HSL and increased lipase production and beta-hemolysis, whereas mutagenesis of the btaI2 (luxI) allele eliminated C10-HSL accumulation and reduced lipase production. Complementation of the btaI1 and btaI3 mutants fully restored the synthesis of C8-HSL and C6-HSL to parental levels. In contrast, mutagenesis of the btaR1, btaR3, btaR4, and btaR5 (luxR) transcriptional regulators had no effect on AHL accumulation, enhanced lipase production, and resulted in extensive beta-hemolysis on sheep blood agar plates. Furthermore, interruption of the btaI1, btaR1, and btaR3 genes altered colony morphology on twitching and swarming motility plates and induced pigmentation. Additionally, phenotypic microarray analysis indicated that QS in B. thailandensis both positively and negatively affects the metabolism of numerous substrates, including citric acid, formic acid, glucose 6-phosphate, capric acid, gamma-hydroxybutyric acid, and d-arabinose. These results demonstrate that mutagenesis of the B. thailandensis QS system affects various cellular processes, including lipase production, swarming and twitching motility, beta-hemolysis of sheep erythrocytes, and carbon metabolism and/or transport.

4-Butyrolactone↗

Cortical oscillations and temporal interactions in a computer simulation of piriform cortex.

1. A large-scale computer model of the piriform cortex was constructed on the basis of the known anatomic and physiological organization of this region. 2. The oscillatory field potential and electroencephalographic (EEG) activity generated by the model was compared with actual physiological results. The model was able to produce patterns of activity similar to those recorded physiologically in response to both weak and strong electrical shocks to the afferent input. The model also generated activity patterns similar to EEGs recorded in behaving animals. 3. In addition to replicating known physiological responses, it has been possible to use the simulations to explore the interactions of network components that might underlie these responses. This analysis suggests that the physiological properties of the cortex are dependent on the complex interaction of both network and cellular properties. In particular, we have found that the relationship between conduction velocities in intrinsic cortical fiber systems and the time constants of excitatory and inhibitory effects are critical for replicating physiological results. 4. Analysis of the model also suggests a correspondence between the 40-Hz oscillatory patterns of activity induced by low levels of odor-like stimulation and oscillatory patterns seen in lightly anesthetized cortex in response to weak electrical shocks to the afferent fiber system. 5. The specific relationships we have found between the different components of the model also support several speculations on their functional significance. The simulations suggest that during each 40-Hz cycle of EEG activity there is a convergence in rostral cortex of afferent information from the olfactory bulb and recurrent association fiber information from caudal cortex. This convergence could underlie an iterative process central to the recognition of complex olfactory stimuli.

Animals↗

A neural network model of temporal code generation and position-invariant pattern recognition.

Numerous studies have suggested that the brain may encode information in the temporal firing pattern of neurons. However, little is known regarding how information may come to be temporally encoded and about the potential computational advantages of temporal coding. Here, it is shown that local inhibition may underlie the temporal encoding of spatial images. As a result of inhibition, the response of a given cell can be significantly modulated by stimulus features outside its own receptive field. Feedforward and lateral inhibition can modulate both the firing rate and temporal features, such as latency. In this article, it is shown that a simple neural network model can use local inhibition to generate temporal codes of handwritten numbers. The temporal encoding of a spatial pattern has the interesting and computationally beneficial feature of exhibiting position invariance. This work demonstrates a manner by which the nervous system may generate temporal codes and shows that temporal encoding can be used to create position-invariant codes.

Nervous System Physiological Phenomena↗

Figure-ground segregation in a recurrent network architecture.

Here we propose a model of how the visual brain segregates textured scenes into figures and background. During texture segregation, locations where the properties of texture elements change abruptly are assigned to boundaries, whereas image regions that are relatively homogeneous are grouped together. Boundary detection and grouping of image regions require different connection schemes, which are accommodated in a single network architecture by implementing them in different layers. As a result, all units carry signals related to boundary detection as well as grouping of image regions, in accordance with cortical physiology. Boundaries yield an early enhancement of network responses, but at a later point, an entire figural region is grouped together, because units that respond to it are labeled with enhanced activity. The model predicts which image regions are preferentially perceived as figure or as background and reproduces the spatio-temporal profile of neuronal activity in the visual cortex during texture segregation in intact animals, as well as in animals with cortical lesions.

Feedback↗

Information transfer between rhythmically coupled networks: reading the hippocampal phase code.

There are numerous reports on rhythmic coupling between separate brain networks. It has been proposed that this rhythmic coupling indicates exchange of information. So far, few computational models have been proposed that explore this principle and its potential computational benefits. Recent results on hippocampal place cells of the rat provide new insight; it has been shown that information about space is encoded by the firing of place cells with respect to the phase of the ongoing theta rhythm. This principle is termed phase coding and suggests that upcoming locations (predicted by the hippocampus) are encoded by cells firing late in the theta cycle, whereas current location is encoded by early firing in the theta cycle. A network reading the hippocampal output must inevitably also receive an oscillatory theta input in order to decipher the phase-coded firing patterns. In this article, I propose a simple physiologically plausible mechanism implemented as an oscillatory network that can decode the hippocampal output. By changing only the phase of the theta input to the decoder, qualitatively different information is transferred: the theta phase determines whether representations of current or upcoming locations are read by the decoder. The proposed mechanism provides a computational principle for information transfer between oscillatory networks and might generalize to brain networks beyond the hippocampal region.

Action Potentials↗

Artificial neural networks estimate the contribution of taste neurons to coding.

Taste qualities are believed to be coded in the activity of populations of taste neurons. However, it is not clear whether all neurons are equally responsible for coding. To clarify the point the relative contribution of each taste neuron to coding was assessed by constructing simple three-layer neural networks with input neurons that represent cortical taste neurons of the rat. The networks were trained by the back-propagation learning algorithm to classify the neural response patterns to the basic taste stimuli (sucrose, HCl, quinine-hydrochloride, and NaCl). The networks had four output neurons representing the basic taste qualities, the values of which provide a measure for similarity of test stimuli to the basic taste stimuli. We estimated relative contributions of input neurons to the taste discrimination of the network by examining their significance S(j), which is defined as the sum of the absolute values of the connection weights from the jth input neuron to the hidden layer. When the input neurons with a smaller S(j) (e.g., 15 out of 39 input units) were "pruned" from the trained network, the ability of the network to discriminate the basic taste qualities was not greatly affected. On the other hand, the taste discrimination of the network progressively deteriorated much more rapidly with pruning of input neurons with a larger S(j). These results suggest that cortical taste neurons differentially contribute to the coding of taste qualities. Input neurons with a larger S(j) tended to be with a larger variation of neural discharge rates to the basic taste stimuli. The variation of neural discharges may be important in the coding of taste qualities.

Algorithms↗

Large-scale 13C-flux analysis reveals mechanistic principles of metabolic network robustness to null mutations in yeast.

BACKGROUND: Quantification of intracellular metabolite fluxes by 13C-tracer experiments is maturing into a routine higher-throughput analysis. The question now arises as to which mutants should be analyzed. Here we identify key experiments in a systems biology approach with a genome-scale model of Saccharomyces cerevisiae metabolism, thereby reducing the workload for experimental network analyses and functional genomics. RESULTS: Genome-scale 13C flux analysis revealed that about half of the 745 biochemical reactions were active during growth on glucose, but that alternative pathways exist for only 51 gene-encoded reactions with significant flux. These flexible reactions identified in silico are key targets for experimental flux analysis, and we present the first large-scale metabolic flux data for yeast, covering half of these mutants during growth on glucose. The metabolic lesions were often counteracted by flux rerouting, but knockout of cofactor-dependent reactions, as in the adh1, ald6, cox5A, fum1, mdh1, pda1, and zwf1 mutations, caused flux responses in more distant parts of the network. By integrating computational analyses, flux data, and physiological phenotypes of all mutants in active reactions, we quantified the relative importance of 'genetic buffering' through alternative pathways and network redundancy through duplicate genes for genetic robustness of the network. CONCLUSIONS: The apparent dispensability of knockout mutants with metabolic function is explained by gene inactivity under a particular condition in about half of the cases. For the remaining 207 viable mutants of active reactions, network redundancy through duplicate genes was the major (75%) and alternative pathways the minor (25%) molecular mechanism of genetic network robustness in S. cerevisiae.

Carbon↗

A portable microelectrode array recording system incorporating cultured neuronal networks for neurotoxin detection.

Cultured neuronal networks, which have the capacity to respond to a wide range of neuroactive compounds, have been suggested to be useful for both screening known analytes and unknown compounds for acute neuropharmacologic effects. Extracellular recording from cultured neuronal networks provides a means for extracting physiologically relevant activity, i.e. action potential firing, in a noninvasive manner conducive for long-term measurements. Previous work from our laboratory described prototype portable systems capable of high signal-to-noise extracellular recordings from cardiac myocytes. The present work describes a portable system tailored to monitoring neuronal extracellular potentials that readily incorporates standardized microelectrode arrays developed by and in use at the University of North Texas. This system utilizes low noise amplifier and filter boards, a two-stage thermal control system with integrated fluidics and a graphical user interface for data acquisition and control implemented on a personal computer. Wherever possible, off-the-shelf components have been utilized for system design and fabrication. During use with cultured neuronal networks, the system typically exhibits input referred noise levels of only 4-6 microVRMS, such that extracellular potentials exceeding 40 microV can be readily resolved. A flow rate of up to 1 ml/min was achieved while the cell recording chamber temperature was maintained within a range of 36-37 degrees C. To demonstrate the capability of this system to resolve small extracellular potentials, pharmacological experiments with cultured neuronal networks have been performed using ion channel blockers, tetrodotoxin and tityustoxin. The implications of the experiments for neurotoxin detection are discussed.

Action Potentials↗

Production of reflex cough by brainstem respiratory networks.

Delineation of neural mechanisms involved in reflex cough is essential for understanding its many physiological and clinical complexities, and the development of more desirable antitussive agents. Brainstem networks that generate and modulate the breathing pattern are also involved in producing the motor patterns during reflex cough. Neurones of the ventrolateral medulla respiratory pattern generator mutually interact with neural networks in the pons, medulla and cerebellum to form a larger dynamic network. This paper discusses evidence from our laboratory and others supporting the involvement of the nucleus tractus solitarii, midline raphe nuclei and lateral tegmental field in the medulla, and the pontine respiratory group and cerebellum in the production of reflex cough. Gaps in our knowledge are identified to stimulate further research on this complicated issue.

Brain Stem↗