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At least 451 records · Page 25Linked to original sources
PubMed2003

Computer model of passive signal integration based on whole-cell in vitro studies of rat lateral geniculate nucleus.

Computer models were used to investigate passive properties of lateral geniculate nucleus thalamocortical cells and thalamic interneurons based on in vitro whole-cell study. Two neurons of each type were characterized physiologically and morphologically. Thalamocortical cells transmitted 37% of steady-state signal orthodromically (distal dendrite to soma) and 93% antidromically (soma to distal dendrite); interneurons transmitted 18% orthodromically and 53% antidromically. Lowering membrane resistance caused a dramatic drop in steady-state signal transmission. Simulation of brief signals such as orthodromically transmitted postsynaptic potentials and antidromically transmitted action potentials showed relatively poor transmission due to the low-pass filtering property of dendrites. This attenuation was particularly pronounced in interneurons. By contrast, bursts of postsynaptic potentials or action potentials were relatively well transmitted as the temporal summation of these recurring signals gave prolonged depolarizations comparable to prolonged current injection. While synaptic clustering, active channels and reduction of membrane resistance by ongoing synaptic activity will have additional profound effects in vivo, the present in vitro modelling suggests that passive signal transmission in neurons will depend on type of signal conveyed, on directionality and on membrane state. This will be particularly important for thalamic interneurons, whose presynaptic dendrites may either work independently or function in concert with each other and with the soma. Our findings suggest that bursts may be particularly well transmitted along dendrites, allowing firing format to alter the functional anatomy of the cell.

Action Potentials↗
PubMed1984

Computer modeling of the recombination reaction of rhodopsin.

Various mechanistic schemes for the recombination reaction of rhodopsin were designed and tested using computer modeling and simulation with data from kinetics experiments. The reaction schemes were mathematically modeled by systems of nonlinear first-order ordinary differential equations (ODEs) with unknown rate constants. Each model was fitted to the experimental data by using a modified simplex algorithm for parameter (rate constant) estimation and Gear's method for solving stiff systems of ODEs. The recombination reaction of rhodopsin was best modeled by branched, multistep reaction schemes which included formation of noncovalent complexes, acid-base equilibria, and acid and base-catalyzed dehydration of a Schiff base intermediate. The biochemical bases for these models are discussed.

Animals↗
PubMedDate not supplied

[A computer model of generation of the motor cortex neuron processes seen in the course of execution of instrumental movement].

A computer model of neuronal processes in the motor cortex column is presented. The model is consisted of two pyramidal cell layers with two groups of inhibitory interneurons, selectively controlling pyramidal cell soma and dendrite, in each. Active Na, Ca and K conductances are included in the model of a single neuron. Horizontal excitatory connections between pyramidal cells in the upper layer are largely of NMDA-receptor type, that in the lower layer--of non-NMDA-type. All inhibitory synapses are of GABA(A)-type. The model reproduces the main phenomenon observed in the motor cortex during the execution of conditioned movements. Consequent to an early excitation the upper layer pyramidal cells generate a late NMDA-dependent reflexive response to afferent conditional stimulation, which as in a real case is diminished by GABA(A)-type synaptic inhibition and afferent stimulus strength increase. The characteristic inverse relation between the late response manifestation and the stimulus strength observed in the real cortex can be reproduced in the model only if NMDA-glutamate receptors were preferentially localized in the terminals of pyramidal cell backward collaterals, not in the terminals of the afferent fibers on pyramidal neurons. The intended component of motor cortex neuronal activity is generated in NMDA-independent manner by the pyramidal cells of lower layer. The slow time coarse of intended component as compared with short duration of AMPA epsp's is due to a consecutive relay-race--like activation of pyramidal neurons with different dendrit-to-soma ratio.

Animals↗
PubMed2003

Comparison of computational models of familiarity discrimination in the perirhinal cortex.

This study compares the efficiency and plausibility of published computational models of familiarity discrimination in the perirhinal cortex. Substantial evidence indicates that the perirhinal cortex is involved in both the familiarity discrimination aspect of recognition memory and in perceptual functions involved with representations of complete stimuli (i.e., object identification). Published models of how the perirhinal cortex may perform familiarity discrimination can be divided into two groups. The first group assumes that a proportion of perirhinal neurons form a network specialised just for familiarity discrimination (these models may be based on Hebbian or anti-Hebbian synaptic plasticity). In contrast, the second group assumes that both familiarity discrimination and learning representations of complete stimuli are performed within a single combined network. This study establishes that when the responses of neurons that provide input to the familiarity discrimination network are correlated (as indicated by experimental data), specialised networks based on anti-Hebbian learning may recognise the previous occurrence of many more stimuli (i.e., have a capacity up to thousands of times larger) than specialised networks based on Hebbian learning. The currently published combined models do not learn an optimal stimulus representation (they do not fully extract statistically independent features), and hence their capacities are even lower than those of the specialised models based on Hebbian learning. Hence, the combined models published thus far are critically less efficient than the specialised models based on anti-Hebbian learning. This study also compares the consistency of the models with experimental observations concerning what is known of synaptic plasticity in the perirhinal cortex and the responses of its neurons. Many theoretically important parameters remain undetermined, and experiments are suggested to provide information critical for refining and distinguishing between the various models. However, the above theoretical arguments and currently published data favour the existence of a separate network specialised for familiarity discrimination.

Animals↗
PubMed2003

[Stabilizing selection and computer models of the joint evolution of patterns of polygenes, transposable elements, and origin identity labels].

A computer model of the populations dynamics of the patterns of polygenes, transposable elements (TEs), and origin identity labels (OILs) in the course of stabilizing selection for an additive quantitative trait (with the target value being 0.4 of the maximum) was analyzed. It was demonstrated that the final plateaus of the trait value and the frequencies of the active values of polygenes are reached rapidly, namely, within five to seven generations (the effective selection period). The inbreeding coefficient during this period also grows rapidly and then gradually increases eventually reaching approximately 0.7. The inbreeding coefficient reaches plateau (at approximately 1.0) only in generations 300-350, which suggests the effect of gene drift. Dendrograms of the patterns of polygenes, TEs, and OILs were constructed for all generations. By generation 100 of selection, the final patterns of TEs and OILs were not formed completely. Fixations and losses, especially those of the OIL pattern, were delayed. In general, however, the population heterogeneity with respect to the patterns studied does not stabilize. This heterogeneity decreases the case of stabilizing selection, although more slowly than in the cases of positive and negative selections.

Animals↗
PubMed1994

Computer modelling of processes in ecosystems--general principles.

Concept of the mathematical modelling of ecosystems is presented, starting with a set of variables and a set of relations. Examples are given for the models of plant populations in terrestrial ecosystems. The differences between well-structured and ill-structured problems are shown with some methodological consequences for strategy of applications of computer models.

Computer Simulation↗
PubMed2002

A computational model for neocortical neuronogenesis predicts ethanol-induced neocortical neuron number deficits.

We have developed a computational model that allows for the evaluation of normal and perturbed neurodevelopmental processes. This mathematical construct is used to test the hypothesis that reduced neuronal production is the critical mechanism behind fetal alcohol syndrome. Model predictions of normal neurodevelopment match independent stereological measures but challenge estimates generated using a previously published model of normal neocortical neuronogenesis. Evaluation of data showing an increased cell cycle length after prenatal exposure to ethanol during neocortical neuronogenesis yields predictions of cellular deficits that can account for the permanent neocortical neuronal loss seen in rodents exposed to ethanol concentrations of public health relevance.

Animals↗
PubMed1996

An integrated computational model of three-dimensional vision.

This article presents the details of and background for a computational model of three-dimensional vision. The basic idea embodied in this model is that a veridical approximation to a three-dimensional scene can best be produced by combining several operators that act on acquired two-dimensional images to reconstruct surface shape and distance. Stereo, shape from shading (SFS), and shape from structured light (SFSL) operators are combined to produce a reconstruction that is superior to any that might be produced by one alone. The advantages and disadvantages of each independent operator and the generic difficulties faced by members of this class of operators are discussed. Collectively, this package of combined algorithms represents a functional model of human spatial vision.

Algorithms↗
PubMed1991

Computer model of excitation and recovery in the anisotropic myocardium. I. Rectangular and cubic arrays of excitable elements.

A computer model of propagated excitation and recovery in anisotropic cardiac tissue is presented that consists of a large number of excitable elements whose subthreshold interactions are governed by the anisotropic bidomain theory but whose suprathreshold behavior (action potential) is largely preassigned. The model's performance was first tested in a two-dimensional configuration with uniform anisotropy; this method allowed comparison of simulated isochrones of excitation and extracellular electrograms with the results of experimental in vitro studies of cardiac tissue. Next the model was used to study propagated excitation in a three-dimensional region representing the anisotropic properties of the ventricular wall, with attention to the effects produced by variable fiber direction from "endocardium" to "epicardium."

Action Potentials↗
PubMed1995

Computer model of current-induced early afterdepolarizations in guinea pig ventricular myocytes.

We tested the ability of a computer model of transmembrane current and intracellular Ca2+ flux in the isolated guinea pig myocyte (Nordin, C., Am. J. Physiol. 265 (Heart Circ. Physiol. 34): H2117-H2136, 1993) to reproduce data from prior experimental studies and new data presented in this study regarding the behavior of early afterdepolarizations induced by constant inward current, a response closely related to the effect of localized injury currents in damaged myocardial syncytia. The goals of the study were to confirm the model's capacity to reproduce relevant experimental responses for which it was not originally designed and to analyze the mechanisms underlying the experimental phenomena. Under normal conditions, current-induced early afterdepolarizations in the model developed only from membrane potentials associated with L-type Ca2+ channel window current, and the magnitude of upstrokes was unaffected by blockade of either delayed rectifier K+ current or sarcoplasmic reticulum Ca2+ release. After Ca2+ loading secondary to either reduced extracellular [K+] or inhibition of Na(+)-K(+)-adenosinetriphosphatase activity, the threshold potential for current-induced early afterdepolarizations in the model, as with experimental myocytes, shifted to membrane potentials negative to the threshold potential for Ca2+ channel activation. Upstrokes were initiated by inward currents generated by electrogenic Na/Ca exchange following oscillatory Ca2+ release from the sarcoplasmic reticulum. New experiments presented in this study demonstrate that bursts of rapid depolarizing stimulations terminate current-induced early afterdepolarizations. Termination is caused by transient hyperpolarizations, which increase as a function of number or duration of stimulations, and if strong enough, cross the all-or-none threshold and lead to full repolarization. This experimental response was accurately simulated by the model through interactions that led to activation of delayed rectifier current, inactivation of Ca2+ channel current, and a reduction in inward Na/Ca exchange current secondary to altered intracellular Ca2+ cycling. We confirm that the model accurately simulates a wide range of responses beyond its original experimental constraints and suggest that current-induced early afterdepolarizations are initiated and terminated by complex processes that vary with specific experimental conditions and involve multiple currents.

Animals↗
PubMedDate not supplied

Computer model of gastric electrical stimulation.

The aim of the study was to simulate gastric electrical stimulation using a computer model of gastric electrical activity and suggest a possible avenue toward reliable gastric pacing. Modeling was based on the conoidal dipole model of gastric electrical activity described earlier. It was assumed that local, nonpropagated contractions can be produced circumferentially using 4 rings of stimulating electrodes supplied with 2-sec phase-locked bipolar trains of 50 Hz, 15 V (peak to peak) rectangular voltage. Temporal and propagation organizations of gastric electrical activity described in the conoidal dipole model were used to derive the geometry of the stimulating electrodes and the time shifts for phase-locking of the electrical stimuli applied to the different circumferential electrode sets. The major assumptions and findings of the model were tested on two unconscious dogs. The model produced completely controllable simulated gastric contractions that could be propagated distally by phase-locking the stimulating voltage. The values of interelectrode distances in different rings, as well as the distances between the successive rings, were also derived. The concept of invoked circumferential contractions that are artificially propagated by phase-locking the stimulating voltage could be an avenue toward reliable gastric pacing of gastroparetic patients.

Animals↗
PubMed2004

A computer model to predict the outcome and duration of ureteral or renal calculous passage.

PURPOSE: We developed a computer model to predict the outcome and the duration until passage of ureteral/renal calculi. MATERIALS AND METHODS: A retrospective, randomized study was performed of the outcome in 301 patients presenting to the emergency room for renal colic. Presenting characteristics of those diagnosed with a single calculus by computerized tomography were recorded for analysis. Predictors of stone passage and passage duration were identified and then used to create a logistic regression model. The algorithm was trained on 141 randomly selected patients and then tested on a separate 160 patients. Model accuracy was compared to predictions from 10 experienced urologists and 9 urology residents in 77 randomly selected patients. The model was tested further in 30 randomly selected patients at a private hospital to assess its general applicability. RESULTS: The model prediction accuracy in 160 patients was 86.3% for passage and 87.3% for duration (less or greater than 2 weeks). In the comparison group the model, the 10 experienced urologists and the 9 urology residents had an overall prediction accuracy of 88.3%, 70.5% (p = 0.006) and 72% (p = 0.007) for passage, and 87.1%, 71.6% (p = 0.007) and 81% (p = 0.075) for duration, respectively. Prediction accuracy was 93.3% for passage and 90.3% for duration when tested at a private hospital. CONCLUSIONS: Our model provides outcome and duration of passage predictions for patients presenting acutely in the emergency room with a single ureteral/renal calculus. It performs better than experienced urologists and urology residents. It can be applied to a private practice setting with equal accuracy.

Adolescent↗
PubMed1991

Computer model of excitation and recovery in the anisotropic myocardium. III. Arrhythmogenic conditions in the simplified left ventricle.

A computer model of propagated excitation and recovery in anisotropic cardiac tissue has been described in the first two reports of this series. The model consists of a large number of excitable elements whose subthreshold interactions are governed by the anisotropic bidomain theory but whose suprathreshold behavior (action potential) is largely preassigned. As described in the previous two reports, the model's performance was tested in rectangular and cubic arrays of excitable elements and in the "normal" three-dimensional simplified left ventricle with anisotropy. The present report deals with arrhythmogenic conditions in the simplified left ventricle with anisotropy and ventricular-gradient properties; specifically, we studied activation and recovery in the presence of an ischemic region and under various stimulation protocols. The aim of these simulations was to elucidate the role of reentry in the genesis of ventricular tachycardia. Our simulations produced reentrant activation as a result of appropriate endocardial stimulation.

Action Potentials↗
PubMed2006

Testing computational models of dopamine and noradrenaline dysfunction in attention deficit/hyperactivity disorder.

We test our neurocomputational model of fronto-striatal dopamine (DA) and noradrenaline (NA) function for understanding cognitive and motivational deficits in attention deficit/hyperactivity disorder (ADHD). Our model predicts that low striatal DA levels in ADHD should lead to deficits in 'Go' learning from positive reinforcement, which should be alleviated by stimulant medications, as observed with DA manipulations in other populations. Indeed, while nonmedicated adult ADHD participants were impaired at both positive (Go) and negative (NoGo) reinforcement learning, only the former deficits were ameliorated by medication. We also found evidence for our model's extension of the same striatal DA mechanisms to working memory, via interactions with prefrontal cortex. In a modified AX-continuous performance task, ADHD participants showed reduced sensitivity to working memory contextual information, despite no global performance deficits, and were more susceptible to the influence of distractor stimuli presented during the delay. These effects were reversed with stimulant medications. Moreover, the tendency for medications to improve Go relative to NoGo reinforcement learning was predictive of their improvement in working memory in distracting conditions, suggestive of common DA mechanisms and supporting a unified account of DA function in ADHD. However, other ADHD effects such as erratic trial-to-trial switching and reaction time variability are not accounted for by model DA mechanisms, and are instead consistent with cortical noradrenergic dysfunction and associated computational models. Accordingly, putative NA deficits were correlated with each other and independent of putative DA-related deficits. Taken together, our results demonstrate the usefulness of computational approaches for understanding cognitive deficits in ADHD.

Adolescent↗
PubMed1988

A computer model to study norepinephrine-induced oscillations of contraction in tail arteries of spontaneously hypertensive stroke-prone rats.

The purpose of this study is to develop a computer model of oscillatory contractions in isolated arteries from the tails of spontaneously hypertensive, stroke-prone rats (SHRSP). The computer simulation incorporates biologic data from experiments and mathematic expressions derived from an electric circuit model of the biologic system. The model characterizes the cellular mechanisms which have been proposed to be responsible for the oscillatory activity. Results indicate the ability of the model to provide results which closely match experimentally obtained data.

Animals↗
PubMed1986

A computer model of spermatogenesis in the rat; correlation with flow cytometric data based on autoradiographic cell-cycle properties.

A computer model of rat spermatogenesis was created, based on autoradiographic studies of durations of the phases of the cell cycle (G1, S, G2 and mitotic phases) of each germ-cell type. With this model it is possible to predict and to gain insight into the changes of the DNA content occurring during the normal process of spermatogenesis. The relative proportions of haploid, diploid, S phase and tetraploid germ cells with increasing age of the rats were calculated. Calculated and actual experimental flow cytometry data were compared to test the accuracy of the model, and these show good agreement. The present work demonstrates that single-parameter DNA analysis of testicular cells is primarily a reflection of germ cells in the spermatocyte and spermatid stages of development, and of non-germ cells. The FCM single-parameter DNA analysis of testicular cells is relatively insensitive to changes in the stem cell and spermatogonial stages of germ-cell development.

Animals↗
PubMed1992

Effects of premature excitation and tachycardia on the spatial distribution of refractoriness and propagation of excitation in a computer model.

In this study, the spatial pattern of refractoriness and its effects on propagation of excitation during premature responses and tachycardia have been investigated using a computer model. The model simulated propagation, cycle length-dependent refractoriness, and slow propagation during the relative refractory period. Findings showed slow propagation near the origin of premature responses resulting in longer cycle lengths distal to the slowing. The nonuniform cycle lengths terminated by a premature response also represented the onset of the subsequent cycle, so the pattern of refractoriness was altered after both the premature and following cycle. This occurred even though cycle length affected only the immediately following refractory period in the model. The effect of nonuniform cycle lengths during a premature response on refractory periods after the subsequent response occurred with all cycle lengths of the later response. When the cycle length of that and further responses was sufficiently shortened to result in slowed propagation, changing spatial patterns of refractoriness and propagation occurred. The findings are evidence that responses with slow propagation during incomplete recovery of excitability can affect conduction velocity and refractoriness during multiple subsequent cycles. These effects are likely to occur in the heart but are modified by features such as sustained effects of cycle length on refractoriness, anisotropy, and electrotonic interactions.

Computer Simulation↗