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Intracranial pressure processing with artificial neural networks: classification of signal properties.

Intracranial pressure (ICP) is commonly used by neurosurgeons as a source of valuable information about the current condition of the neurosurgical patient. Nevertheless, despite years of effort, extracting clinically valuable information from the ICP signal is still problematical. Approaches, using current values of ICP, may fail to disclose imminent risk, because unpredictable factors can rapidly change the properties of the signal. An alternative approach is to determine some global characteristics of the signal within a longer time interval and such statistical analyses have been proposed by several authors. A further, rarely considered, problem is assessment of the results obtained from the point of view of their practical utility and/or such classification of the obtained properties of the signal that they correspond to certain clinical states of the patient. While this might be a typical task for discriminant analysis, we approached the analysis using an alternative methodology, that of computational intelligence, implemented in artificial neural networks (ANN). We tested two variants of the ANN algorithms for classification and discrimination of global properties of the ICP signal. In a "dynamic pattern classification" the network was presented with several sections of ICP records together with information from the expert-neurosurgeon, classifying 4 risk groups. In this mode no data pre-processing was carried out, in contrast to our second approach, in which the signal had been pre-processed using published statistical analyses and only these intermediate coefficients were fed into the ANN classifier. The results obtained with both classification methods at their current stage of training were similar and approximated to a 70% rate of judgements consistent with the expert scoring. Nevertheless, the method based on the assessment of global parameters from the ICP record looks more promising, because it leaves the possibility for modification of the set of parameters analysed. The new parameters may include information extracted not only from the ICP signal, but also from other diagnostic modalities, like colour coded Doppler ultrasonography. The ultimate goal of this work is to build up a pseudo-intelligent computer expert system, which would be able to reason from a reduced set of input information, available from a standard monitoring modality, because it had been taught salient links between these data and higher-order data, upon which expert scoring was based.

Cerebral Hemorrhage↗

Design of a network with state stability.

Designing a network with given functions or reconstruct a network based on its dynamical behavior is an important problem in the study of complex systems. In this paper, we put forward certain principles in constructing a network with state stability. We show that a necessary and sufficient condition to design networks with a global fixed point is that active nodes inhibit inactive nodes, while the latter activate the former directly or indirectly. We also designed networks based on basic modules, where each basic module consists a sub-network, they communicate through the inhibition link from each activator in lower module to the inhibitor of upper module. We found that long activation links, i.e. indirect activation links are important to the formation of convergence trajectory. We believe that these principles may help us to understand the topology of biological networks.

Animals↗

Associative memory neural network with low temporal spiking rates.

We describe a modified attractor neural network in which neuronal dynamics takes place on a time scale of the absolute refractory period but the mean temporal firing rate of any neuron in the network is lower by an arbitrary factor that characterizes the strength of the effective inhibition. It operates by encoding information on the excitatory neurons only and assuming the inhibitory neurons to be faster and to inhibit the excitatory ones by an effective postsynaptic potential that is expressed in terms of the activity of the excitatory neurons themselves. Retrieval is identified as a nonergodic behavior of the network whose consecutive states have a significantly enhanced activity rate for the neurons that should be active in a stored pattern and a reduced activity rate for the neurons that are inactive in the memorized pattern. In contrast to the Hopfield model the network operates away from fixed points and under the strong influence of noise. As a consequence, of the neurons that should be active in a pattern, only a small fraction is active in any given time cycle and those are randomly distributed, leading to reduced temporal rates. We argue that this model brings neural network models much closer to biological reality. We present the results of detailed analysis of the model as well as simulations.

Animals↗

Two-category model of task allocation with application to ant societies.

In many network models of interacting units such as cells or insects, the coupling coefficients between units are independent of the state of the units. Here we analyze the temporal behavior of units that can switch between two 'category' states according to rules that involve category-dependent coupling coefficients. The behaviors of the category populations resulting from the asynchronous random updating of units are first classified according to the signs of the coupling coefficients using numerical simulations. They range from isolated fixed points to lines of fixed points and stochastic attractors. These behaviors are then explained analytically using iterated function systems and birth-death jump processes. The main inspiration for our work comes from studies of non-hierarchical task allocation in, e.g., harvester ant colonies where temporal fluctuations in the numbers of ants engaged in various tasks occur as circumstances require and depend on interactions between ants. We identify interaction types that produce quick recovery from perturbations to an asymptotic behavior whose characteristics are function of the coupling coefficients between ants as well as between ants and their environment. We also compute analytically the probability density of the population numbers, and show that perturbations in our model decay twice as fast as in a model with random switching dynamics. A subset of the interaction types between ants yields intrinsic stochastic asymptotic behaviors which could account for some of the experimentally observed fluctuations. Such noisy trajectories are shown to be random walks with state-dependent biases in the 'category population' phase space. With an external stimulus, the parameters of the category-switching rules become time-dependent. Depending on the growth rate of the stimulus in comparison to its population-dependent decay rate, the dynamics may qualitatively differ from the case without stimulus. Our simple two-category model provides a framework for understanding the rich variety of behaviors in network dynamics with state-dependent coupling coefficients, and especially in task allocation processes with many tasks.

Animals↗

Enlazin, a natural fusion of two classes of canonical cytoskeletal proteins, contributes to cytokinesis dynamics.

Cytokinesis requires a complex network of equatorial and global proteins to regulate cell shape changes. Here, using interaction genetics, we report the first characterization of a novel protein, enlazin. Enlazin is a natural fusion of two canonical classes of actin-associated proteins, the ezrin-radixin-moesin family and fimbrin, and it is localized to actin-rich structures. A fragment of enlazin, enl-tr, was isolated as a genetic suppressor of the cytokinesis defect of cortexillin-I mutants. Expression of enl-tr disrupts expression of endogenous enlazin, indicating that enl-tr functions as a dominant-negative lesion. Enlazin is distributed globally during cytokinesis and is required for cortical tension and cell adhesion. Consistent with a role in cell mechanics, inhibition of enlazin in a cortexillin-I background restores cytokinesis furrowing dynamics and suppresses the growth-in-suspension defect. However, as expected for a role in cell adhesion, inhibiting enlazin in a myosin-II background induces a synthetic cytokinesis phenotype, frequently arresting furrow ingression at the dumbbell shape and/or causing recession of the furrow. Thus, enlazin has roles in cell mechanics and adhesion, and these roles seem to be differentially significant for cytokinesis, depending on the genetic background.

Amino Acid Sequence↗

A stochastic differential equation model for quantifying transcriptional regulatory network in Saccharomyces cerevisiae.

MOTIVATION: The explosion of microarray studies has promised to shed light on the temporal expression patterns of thousands of genes simultaneously. However, available methods are far from adequate in efficiently extracting useful information to aid in a greater understanding of transcriptional regulatory network. Biological systems have been modeled as dynamic systems for a long history, such as genetic networks and cell regulatory network. This study evaluated if the stochastic differential equation (SDE), which is prominent for modeling dynamic diffusion process originating from the irregular Brownian motion, can be applied in modeling the transcriptional regulatory network in Saccharomyces cerevisiae. RESULTS: To model the time-continuous gene-expression datasets, a model of SDE is applied to depict irregular patterns. Our goal is to fit a generalized linear model by combining putative regulators to estimate the transcriptional pattern of a target gene. Goodness-of-fit is evaluated by log-likelihood and Akaike Information Criterion. Moreover, estimations of the contribution of regulators and inference of transcriptional pattern are implemented by statistical approaches. Our SDE model is basic but the test results agree well with the observed dynamic expression patterns. It implies that advanced SDE model might be perfectly suited to portray transcriptional regulatory networks. AVAILABILITY: The R code is available on request. CONTACT: cykao@csie.ntu.edu.tw SUPPLEMENTARY INFORMATION: http://www.csie.ntu.edu.tw/~b89x035/yeast/

Gene Expression Regulation↗

The protein folding network.

The conformation space of a 20 residue antiparallel beta-sheet peptide, sampled by molecular dynamics simulations, is mapped to a network. Snapshots saved along the trajectory are grouped according to secondary structure into nodes of the network and the transitions between them are links. The conformation space network describes the significant free energy minima and their dynamic connectivity without requiring arbitrarily chosen reaction coordinates. As previously found for the Internet and the World-Wide Web as well as for social and biological networks, the conformation space network is scale-free and contains highly connected hubs like the native state which is the most populated free energy basin. Furthermore, the native basin exhibits a hierarchical organization, which is not found for a random heteropolymer lacking a predominant free-energy minimum. The network topology is used to identify conformations in the folding transition state (TS) ensemble, and provides a basis for understanding the heterogeneity of the TS and denatured state ensemble as well as the existence of multiple pathways.

Models, Molecular↗

Mining time-dependent gene features.

This paper presents an application of the Independent Component Analysis (ICA) method to genomic data. In particular, experimentally produced perturbation effects over the E.coli bacterium are monitored through the changes of gene expression values observed at regular times, and until steady state has been reached. The aim is to control the response of the SOS system to DNA damage. We might assume that only part of the genetic regulatory network is affected directly by the perturbation conditions, as indirect cascade effects might also be present, and some genes may change just because of randomness. ICA decomposes the gene matrix and identifies groups of genes belonging to a certain estimated component by virtue of co-expression; it is of course of interest to establish co-regulation dynamics, which might underlie the captured correlation. Stronger forms of dependence, like Mutual Information, are thus computed and compared with linear correlation in order to validate the results and establish the role of the identified components in determining the network dynamics.

Algorithms↗

Pattern recall in networks of chaotic neurons.

This research investigates the potential utility of chaotic dynamics in neural information processing. A novel chaotic spiking neural network model is presented which is composed of non-linear dynamic state (NDS) neurons. The activity of each NDS neuron is driven by a set of non-linear equations coupled with a threshold based spike output mechanism. If time-delayed self-connections are enabled then the network stabilises to a periodic pattern of activation. Previous publications of this work have demonstrated that the chaotic dynamics which drive the network activity ensure that an extremely large number of such periodic patterns can be generated by this network. This paper presents a major extension to this model which enables the network to recall a pattern of activity from a selection of previously stabilised patterns.

Algorithms↗

Modeling spontaneous activity in the developing spinal cord using activity-dependent variations of intracellular chloride.

We investigated how spontaneous activity is generated in developing, hyperexcitable networks. We focused our study on the embryonic chick spinal cord, a preparation that exhibits rhythmic discharge on multiple timescales: slow episodes (lasting minutes) and faster intraepisode cycling (approximately 1 Hz frequency). For this purpose, we developed a mean field model of a recurrent network with slow chloride dynamics and a fast depression variable. We showed that the model, in addition to providing a biophysical mechanism for the slow dynamics, was able to account for the experimentally observed activity. The model made predictions on how interval and duration of episodes are affected when changing chloride-mediated synaptic transmission or chloride flux across cell membrane. These predictions guided experiments, and the model results were compared with experimental data obtained with electrophysiological recordings. We found agreement when transmission was affected through changes in synaptic conductance and good qualitative agreement when chloride flux was varied through changes in external chloride concentration or in the rate of the Na+-K+-2Cl- cotransporter. Furthermore, the model made predictions about the time course of intracellular chloride concentration and chloride reversal potential and how these are affected by changes in synaptic conductance. Based on the comparison between modeling and experimental results, we propose that chloride dynamics could be an important mechanism in rhythm generation in the developing chick spinal cord.

2-Amino-5-phosphonovalerate↗

Recent developments in neurodynamics and their impact on the design of neuro-chips.

Neurons can be modeled either by equations or differential equations. For the latter, a low-pass filter must be added to the analog function blocks associated with the McCullogh and Pitts type of static neuron in order to provide the time-dependent neuron solution. The low-pass filter enhances stability and enables a time-continuous analog implementation much more compact than that attained with time-discrete analog or pure digital design. A few examples of equations as well as differential equations are known for that part of learning. However, much less than for the recall mode, it is clear how to design learning neuro-chips for temporal pattern processing. It is shown here that a partial differential equation can be used to provide a unified description of both the recall and learning dynamics of a neural network as well as to investigate systematically the VLSI potential for analog time-continuous neuro-chips. It turns out that the recall and learning dynamics can be divided into causal as well as noncausal solutions. The first type of solution includes oscillating or spiking neurons. The second type of solution allows for a much simpler signal representation but leads to the problem of storing the temporal signal of each neuron for as long a time as a single pattern lasts. As this is prohibitive for larger networks and time-varying patterns, the analog VLSI implementation of causal neuron models is suggested.

Artificial Intelligence↗

Prisoners' dilemma in real-world acquaintance networks: spikes and quasiequilibria induced by the interplay between structure and dynamics.

We study Nowak and May's spatial prisoners' dilemma game driven by mutations (random choices of suboptimal strategies) on empirical social networks. The time evolution of the cooperation level is highly complex containing spikes and steps between quasistable levels. A statistical characterization of the quasistable states and a study of the mechanisms behind the steps are given. We argue that the crucial structural ingredients causing the observed behavior is an inhomogeneous degree distribution and that the connections within vertices of highest degree are rather sparse. Based on these observations we construct model networks with a similar complex time evolution of the cooperation level.

Journal Article↗

Regional planning implementation and its impact on integration of a mental health care network.

This article questions the effectiveness of a managerial tool in changing a health-care system. The process of implementing regional planning and its impact on creating integrated service networks is examined, using a case study and a multi-dimensional analytic model. This model highlights the influence of contextual, structural, cultural and dynamic factors on forming networks. The regional planning developed in the province of Québec (Canada), aimed at a major transformation of the mental health-care system. In each district, organizations working with people who have serious mental disorders were mobilized to plan and implement a more coordinated, continuous and diversified supply of services, under the direction of a regional health body. This study outlines the limitations of regional planning as a tactic for transforming the system. It recommends instead developing more diversified integration strategies to further the process of forming integrated service networks within a complex system. In conclusion, a brief discussion deals with the difficulties related to the study of systemic change implementation.

Delivery of Health Care, Integrated↗

Binding and segmentation of multiple objects through neural oscillators inhibited by contour information.

Temporal correlation of neuronal activity has been suggested as a criterion for multiple object recognition. In this work, a two-dimensional network of simplified Wilson-Cowan oscillators is used to manage the binding and segmentation problem of a visual scene according to the connectedness Gestalt criterion. Binding is achieved via original coupling terms that link excitatory units to both excitatory and inhibitory units of adjacent neurons. These local coupling terms are time independent, i.e., they do not require Hebbian learning during the simulations. Segmentation is realized by a two-layer processing of the visual image. The first layer extracts all object contours from the image by means of "retinal cells" with an "on-center" receptive field. Information on contour is used to selectively inhibit Wilson-Cowan oscillators in the second layer, thus realizing a strong separation among neurons in different objects. Accidental synchronism between oscillations in different objects is prevented with the use of a global inhibitor, i.e., a global neuron that computes the overall activity in the Wilson-Cowan network and sends back an inhibitory signal. Simulations performed in a 50 x 50 neural grid with 21 different visual scenes (containing up to eight objects + background) with random initial conditions demonstrate that the network can correctly segment objects in almost 100% of cases using a single set of parameters, i.e., without the need to adjust parameters from one visual scene to the next. The network is robust with reference to dynamical noise superimposed on oscillatory neurons. Moreover, the network can segment both black objects on white background and vice versa and is able to deal with the problem of "fragmentation."The main limitation of the network is its sensitivity to static noise superimposed on the objects. Overcoming this problem requires implementation of more robust mechanisms for contour enhancement in the first layer in agreement with mechanisms actually realized in the visual cortex.

Artifacts↗

Multifunctional laryngeal motoneurons: an intracellular study in the cat.

We studied the patterns of membrane potential changes in laryngeal motoneurons (LMs) during vocalization, coughing, swallowing, sneezing, and the aspiration reflex in decerebrate paralyzed cats. LMs, identified by antidromic activation from the recurrent laryngeal nerve, were expiratory (ELMs) or inspiratory (ILMs) cells that depolarized during their respective phases in eupnea. During vocalization, most ELMs depolarized and most ILMs hyperpolarized. Some ILMs depolarized slightly during vocalization. During coughing, ELMs depolarized abruptly at the transition from the inspiratory to the expiratory phase. In one-third of ELMs, this depolarization persisted throughout the abdominal burst. In the remainder ("type A"), it was interrupted by a transient repolarization. ILMs exhibited a membrane potential trajectory opposite to that of type A ELMs during coughing. During swallowing, the membrane potential of ELMs decreased transiently at the onset of the hypoglossal burst and then depolarized strongly during the burst. ILMs hyperpolarized sharply at the onset of the burst and depolarized as hypoglossal activity ceased. During sneezing, ELMs and ILMs exhibited membrane potential changes similar to those of type A ELMs and ILMs during coughing. During the aspiration reflex, ELMs and ILMs exhibited bell-shaped hyperpolarization and depolarization trajectories, respectively. We conclude that central drives to LMs, consisting of complex combinations of excitation and inhibition, vary during vocalization and upper airway defensive reflexes. This study provides data for analysis of the neuronal networks that produce these various behaviors and analysis of network reorganization caused by changes in dynamic connections between the respiratory and nonrespiratory neuronal networks.

Animals↗

[Analysis of intracranial pressure signals using artificial neural networks].

Intracranial pressure (ICP) is influenced by an array of predictable and unpredictable factors. Statistical modelling of this signal has only limited applicability because of the significant load of stochastic components. We tested the efficiency of an alternative approach, based on the methodology of artificial neural networks (ANNs) in the on-line prediction of future values of ICP and in the classification of signal properties. Satisfactory accuracy of forecasting was achieved with the ANNs for a 3-minute prediction horizon, while the prediction quality with autoregressive models of statistical origin was proved unsatisfactory. The results obtained with the ANNs were further improved when signal pre-processing with wavelet transform was employed. Nevertheless, even with the ANN methodology, no sudden breakdowns in the ICP signal (which in this respect might be compared to a "catastrophe") can be forecast with any practical applicability. We therefore applied two ANN algorithms, oriented at classification and discrimination of the global properties of the ICP signal. The neural network was expected to discriminate those sets of signal properties, which were assumed to correspond to certain clinical conditions of the patient. In a "dynamic pattern classification" the network was presented with several sections of ICP records. This was combined with information about the assignment of a given record to one of four arbitrary classes of danger. In this mode no data pre-processing was carried out, in contrast to our second approach, in which the signal was pre-processed with statistical analyses and only these intermediate coefficients were fed to the ANN classifier. The results obtained with both classification methods at their present stage of training were similar and approximated to a 70% rate of judgements consistent with expert scoring. Nevertheless, the method based on the assessment of global parameters of the ICP record seems more promising, because it leaves the possibility of extending the set of training data by information from other diagnostic modalities. The study aims towards the development of a pseudo-intelligent computer expert system, which has would be taught salient links between data extracted from the ICP signal and higher- order data, which contributed to the expert score. Hence the system would be able to make decisions on the basis of a reduced set of input information, available from a standard monitoring modality.

Algorithms↗

Asymptotic states and topological structure of an activation-deactivation chemical network.

The influence of the topology on the asymptotic states of a network of interacting chemical species has been studied by simulating its time evolution. Random and scale-free networks have been designed to support relevant features of activation-deactivation reactions networks (mapping signal transduction networks) and the system of ordinary differential equations associated to the dynamics has been numerically solved. We analysed stationary states of the dynamics as a function of the network's connectivity and of the distribution of the chemical species on the network; we found important differences between the two topologies in the regime of low connectivity. In particular, only for low connected scale-free networks it is possible to find zero activity patterns as stationary states of the dynamics which work as signal off-states. Asymptotic features of random and scale-free networks become similar as the connectivity increases.

Animals↗

Networks and epidemic models.

Networks and the epidemiology of directly transmitted infectious diseases are fundamentally linked. The foundations of epidemiology and early epidemiological models were based on population wide random-mixing, but in practice each individual has a finite set of contacts to whom they can pass infection; the ensemble of all such contacts forms a 'mixing network'. Knowledge of the structure of the network allows models to compute the epidemic dynamics at the population scale from the individual-level behaviour of infections. Therefore, characteristics of mixing networks-and how these deviate from the random-mixing norm-have become important applied concerns that may enhance the understanding and prediction of epidemic patterns and intervention measures. Here, we review the basis of epidemiological theory (based on random-mixing models) and network theory (based on work from the social sciences and graph theory). We then describe a variety of methods that allow the mixing network, or an approximation to the network, to be ascertained. It is often the case that time and resources limit our ability to accurately find all connections within a network, and hence a generic understanding of the relationship between network structure and disease dynamics is needed. Therefore, we review some of the variety of idealized network types and approximation techniques that have been utilized to elucidate this link. Finally, we look to the future to suggest how the two fields of network theory and epidemiological modelling can deliver an improved understanding of disease dynamics and better public health through effective disease control.

Animals↗