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PubMed1991

Numerical tests of a method for simulating electrical potentials on the cortical surface.

A mathematical imaging method for simulating cortical surface potentials was introduced at recent neurosciences meetings [1a], [1b], [2] and was applied to elucidate the neural origins of evoked responses in normal volunteers and certain patient populations. This method consists of the solution of an inward harmonic continuation problem and its effect is to simulate data that has not been attenuated and smeared by the skull. This cortical imaging technique (CIT) is validated by applying it to artificially derived data. Pairs of dipolar sources with different depths and separations are introduced into a spherical conducting medium simulating the head. Scalp potential maps are constructed by interpolating the simulated data between 28 "scalp" electrode positions. Noise is added to the data to approximate the variability in measured potentials that would be observed in practice. CIT is used in each case to construct potential maps on layers concentric to and within the layer representing the scalp. In several instances when the dipole pair is deep and closely spaced, the sources cannot be separated by the scalp topographical maps but are easily separated by the "cortical" topographical maps. CIT is also applied to scalp-recorded potentials evoked by bilateral median nerve stimulation and pattern-reversal visual stimulation.

Brain Mapping↗
PubMed2005

Reconstruction of nonuniformly sampled images in spline spaces.

This paper presents a novel approach to the reconstruction of images from nonuniformly spaced samples. This problem is often encountered in digital image processing applications. Nonrecursive video coding with motion compensation, spatiotemporal interpolation of video sequences, and generation of new views in multicamera systems are three possible applications. We propose a new reconstruction algorithm based on a spline model for images. We use regularization, since this is an ill-posed inverse problem. We minimize a cost function composed of two terms: one related to the approximation error and the other related to the smoothness of the modeling function. All the processing is carried out in the space of spline coefficients; this space is discrete, although the problem itself is of a continuous nature. The coefficients of regularization and approximation filters are computed exactly by using the explicit expressions of B-spline functions in the time domain. The regularization is carried out locally, while the computation of the regularization factor accounts for the structure of the nonuniform sampling grid. The linear system of equations obtained is solved iteratively. Our results show a very good performance in motion-compensated interpolation applications.

Algorithms↗
PubMed2006

Structured additive regression for categorical space-time data: a mixed model approach.

Motivated by a space-time study on forest health with damage state of trees as the response, we propose a general class of structured additive regression models for categorical responses, allowing for a flexible semiparametric predictor. Nonlinear effects of continuous covariates, time trends, and interactions between continuous covariates are modeled by penalized splines. Spatial effects can be estimated based on Markov random fields, Gaussian random fields, or two-dimensional penalized splines. We present our approach from a Bayesian perspective, with inference based on a categorical linear mixed model representation. The resulting empirical Bayes method is closely related to penalized likelihood estimation in a frequentist setting. Variance components, corresponding to inverse smoothing parameters, are estimated using (approximate) restricted maximum likelihood. In simulation studies we investigate the performance of different choices for the spatial effect, compare the empirical Bayes approach to competing methodology, and study the bias of mixed model estimates. As an application we analyze data from the forest health survey.

Bayes Theorem↗
PubMed2000

Simulated seizures and spreading depression in a neuron model incorporating interstitial space and ion concentrations.

Sustained inward currents in neuronal membranes underlie tonic-clonic seizure discharges and spreading depression (SD). It is not known whether these currents flow through abnormally operating physiological ion channels or through pathological pathways that are not normally present. We have now used the NEURON simulating environment of Hines, Moore, and Carnevale to model seizure discharges and SD. The geometry and electrotonic properties of the model neuron conformed to a hippocampal pyramidal cell. Voltage-controlled transient and persistent sodium currents (I(Na,T) and I(Na,P)), potassium currents (I(K,DR) and I(K,A)), and N-methyl-D-aspartate (NMDA) receptor-controlled currents (I(NMDA)), were inserted in the appropriate regions of the model cell. The neuron was surrounded by an interstitial space where extracellular potassium and sodium concentration ([K(+)](o) and [Na(+)](o)) could rise or fall. Changes in intra- and extracellular ion concentrations and the resulting shifts in the driving force for ionic currents were continuously computed based on the amount of current flowing through the membrane. A Na-K exchange pump operated to restore ion balances. In addition, extracellular potassium concentration, [K(+)](o), was also controlled by a "glial" uptake function. Parameters were chosen to resemble experimental data. As long as [K(+)](o) was kept within limits by the activity of the Na-K pump and the "glial" uptake, a depolarizing current pulse applied to the cell soma evoked repetitive firing that ceased when the stimulating current stopped. If, however, [K(+)](o) was allowed to rise, then a brief pulse provoked firing that outlasted the stimulus. At the termination of such a burst, the cell hyperpolarized and then slowly depolarized and another burst erupted without outside intervention. Such "clonic" bursting could continue indefinitely maintained by an interplay of the rise and fall of potassium and sodium concentrations with membrane currents and threshold levels. SD-like depolarization could be produced in two ways, 1) by a dendritic NMDA-controlled current. Glutamate was assumed to be released in response to rising [K(+)](o). And 2) by the persistent (i.e., slowly inactivating) Na-current, I(Na,P). When both I(NMDA) and I(Na,P) were present, the two acted synergistically. We conclude that epileptiform neuronal behavior and SD-like depolarization can be generated by the feedback of ion currents that change ion concentrations, which, in turn, influence ion currents and membrane potentials. The normal stability of brain function must depend on the efficient control of ion activities, especially that of [K(+)](o).

Action Potentials↗
PubMed1980

Dynamic continuous computed tomography: study of retroaortic left renal vein.

A circumaortic left renal vein simulated a retroperitoneal lymph node metastasis on computed tomography (CT). An intravenous bolus injection of contrast medium followed by dynamic CT scanning and analysis of the attenuation coefficients and the anatomic course revealed the vascular nature of the circumaortic left renal vein. The recognition of this anomaly is important in the differential diagnosis of retroperitoneal lymphadenopathy. A similar analysis should be useful in identifying other retroperitoneal arteries and veins.

Adult↗
PubMed2000

An IBM PC-based system for the assessment of cardio-respiratory function using oscillating inert gas forcing signals.

OBJECTIVE: An IBM PC-based real-time data acquisition, monitoring and analysis system was developed for the assessment of cardio-respiratory function, i.e. airway dead space, alveolar volume and pulmonary blood flow, using oscillating inert inspired gas forcing signals. METHODS: The forcing gas mixture was generated by an in-house sinusoid gas delivery unit. The system interfaced with a mass spectrometer and an airway flow transducer, and performed real-time tracking of the breath-by-breath end-inspired, end-expired and mixed-expired concentrations. It calculated the cardiorespiratory parameters using two, i.e. continuous and tidal, in-house mathematical models of the lungs. The system's performance was evaluated using a mechanical bench lung, laboratory subjects and awake adults breathing spontaneously. Its predictive accuracy was compared with the measured volumes of the bench lung; single breath CO2 test for airway dead space and N2 washout for alveolar volume in laboratory subjects and awake adults; and thermal dilution technique for pulmonary blood flow in laboratory subjects. RESULTS: Close agreements were found between the true and predicted airway dead space, i.e. mean differences of -12.39%, 14.47% and -17.49%, respectively, and that of alveolar volume, i.e. -8.03%, -3.62% and 7.22%, respectively, in the bench lung, laboratory subject and awake adult studies; and that of pulmonary blood flow (-23.81%) in the laboratory subjects using the continuous lung model. Even closer agreements were observed for airway dead space (-5.8%) and alveolar volume (-4.01%) of the bench lung and for pulmonary blood flow (-8.47%) in the laboratory subjects using the tidal lung model. CONCLUSIONS: A system was developed to deliver, monitor and analyse on-line, and in real-time, output data from the sinusoid forcing technique. The technique was administered using the system in various subjects, and produced favourable predictions.

Adult↗
PubMed2005

The hypervolume under the ROC hypersurface of "near-guessing" and "near-perfect" observers in N-class classification tasks.

We express the performance of the N-class "guessing" observer in terms of the N2-N conditional probabilities which make up an N-class receiver operating characteristic (ROC) space, in a formulation in which sensitivities are eliminated in constructing the ROC space (equivalent to using false-negative fraction and false-positive fraction in a two-class task). We then show that the "guessing" observer's performance in terms of these conditional probabilities is completely described by a degenerate hypersurface with only N-1 degrees of freedom (as opposed to the N2-N-1 required, in general, to achieve a true hypersurface in such a ROC space). It readily follows that the hypervolume under such a degenerate hypersurface must be zero when N > 2. We then consider a "near-guessing" task; that is, a task in which the N underlying data probability density functions (pdfs) are nearly identical, controlled by N-1 parameters which may vary continuously to zero (at which point the pdfs become identical). With this approach, we show that the hypervolume under the ROC hypersurface of an observer in an N-class classification task tends continuously to zero as the underlying data pdfs converge continuously to identity (a "guessing" task). The hypervolume under the ROC hypersurface of a "perfect" ideal observer (in a task in which the N data pdfs never overlap) is also found to be zero in the ROC space formulation under consideration. This suggests that hypervolume may not be a useful performance metric in N-class classification tasks for N > 2, despite the utility of the area under the ROC curve for two-class tasks.

Algorithms↗
PubMed2001

Pair approximation for lattice models with multiple interaction scales.

Pair approximation has frequently proved effective for deriving qualitative information about lattice-based stochastic spatial models for population, epidemic and evolutionary dynamics. Pair approximation is a moment closure method in which the mean-field description is supplemented by approximate equations for the frequencies of neighbor-site pairs of each possible type. A limitation of pair approximation relative to moment closure for continuous space models is that all modes of interaction between individuals (e.g., dispersal of offspring, competition, or disease transmission) are assumed to operate over a single spatial scale determined by the size of the interaction neighborhood. In this paper I present a multiscale pair approximation which allows different sized neighborhoods for each type of interaction. To illustrate and test the approximation I consider a spatial single-species logistic model in which offspring are dispersed across a birth neighborhood and established individuals have a death rate depending on the population density in a competition neighborhood, with one of these neighborhoods nested inside the other. Analysis of the steady-state equations yields several qualitative predictions that are confirmed by simulations of the model, and numerical solutions of the dynamic equations provide a close approximation to the transient behavior of the stochastic model on a large lattice. The multiscale pair approximation thus provides a useful intermediate between the standard pair approximation for a single interaction neighborhood, and a complete set of moment equations for more spatially detailed models.

Animals↗
PubMed2004

On the origin of reproducible sequential activity in neural circuits.

Robustness and reproducibility of sequential spatio-temporal responses is an essential feature of many neural circuits in sensory and motor systems of animals. The most common mathematical images of dynamical regimes in neural systems are fixed points, limit cycles, chaotic attractors, and continuous attractors (attractive manifolds of neutrally stable fixed points). These are not suitable for the description of reproducible transient sequential neural dynamics. In this paper we present the concept of a stable heteroclinic sequence (SHS), which is not an attractor. SHS opens the way for understanding and modeling of transient sequential activity in neural circuits. We show that this new mathematical object can be used to describe robust and reproducible sequential neural dynamics. Using the framework of a generalized high-dimensional Lotka-Volterra model, that describes the dynamics of firing rates in an inhibitory network, we present analytical results on the existence of the SHS in the phase space of the network. With the help of numerical simulations we confirm its robustness in presence of noise in spite of the transient nature of the corresponding trajectories. Finally, by referring to several recent neurobiological experiments, we discuss possible applications of this new concept to several problems in neuroscience.

Action Potentials↗
PubMed1994

Atmospheric dynamics and bioregenerative technologies in a soil-based ecological life support system: initial results from Biosphere 2.

Biosphere 2 is the first man-made, soil-based, bioregenerative life support system to be developed and tested. The utilization and amendment of local space resources, e.g. martian soil or lunar regolith, for agricultural and other purposes will be necessary if we are to minimize the requirement for Earth materials in the creation of long-term off-planet bases and habitations. Several of the roles soil plays in Biosphere 2 are 1) for air purification 2) as a key component in created wetland systems to recycle human and animal wastes and 3) as nutrient base for a sustainable agricultural cropping program. Initial results from the Biosphere 2 closure experiment are presented. These include the accelerated cycling rates due to small reservoir sizes, strong diurnal and seasonal fluxes in atmospheric CO2, an unexpected and continuing decline in atmospheric oxygen, overall maintenance of low levels of trace gases, recycling of waste waters through biological regeneration systems, and operation of an agriculture designed to provide diverse and nutritionally adequate diets for the crew members.

Agriculture↗
PubMed1979

Gravity as a biochemical determinant.

The existence of obvious morphological and physiological changes in living systems exposed to altered gravity immediately informs us that prior changes have taken place in the chemistry of exposed cells, tissues and organs. These changes include transients that return more or less promptly to the norm when the system is restored to the terrestrial g-field. For example, altered serum hormone and electrolyte levels in man, which appear to reflect successful adaptation to the conditions of orbital weightlessness, disappear shortly after return to Earth. Other changes--in mineral and protein constituents of the skeletal system in man, and cell wall composition in plants--are more persistent or even permanent. Hypogravitational departures from the norm include not only "weightlessness" as achieved in orbit, but also experimental modes of compensation, on the clinostat or by flotation. These techniques are useful in the study of hypogravity but cannot replace fully the weightless environment. Plant ethylene and peroxidase both increase under orbital, clinostat and/or flotation conditions whereas 3-phosphoglyceraldehyde-dehydrogenase increases under orbital but not clinostat conditions; cytochrome reductase and malic dehydrogenase levels are affected by the clinostat, but not by actual weightless conditions. How do the altered organismal biochemistries induced by the centrifuge and the clinostat relate to one another? Does gravity operate on living systems as a continuous variable from 0 to superterrestrial values, or do deviations from g(earth) generate non-uniform, discontinuous stress responses, irrespective of sign? In plants, measurements of wall lignin content and peroxidase activity yield opposite answers. Given the limited data so far available we will consider the meaning of these contradictions.

Adaptation, Physiological↗
PubMed2000

Neural and neuroendocrine adaptations to microgravity and ground-based models of microgravity.

The functional properties of the motor system of humans and non-human primates are readily responsive to microgravity. There is a growing body of evidence that significant adaptations occur in the spinal cord and muscle in response to prolonged exposure to microgravity. Further, there is evidence that the processing of sensory information from the periphery, particularly that input associated with the function of muscle tendons and joints, is significantly altered as a result of prolonged microgravity. We present evidence that the fundamental neural mechanisms that control the relative activity of the motor pools of a slow and fast extensor muscle is changed such that a slow, postural muscle is less readily activated during locomotion following spaceflight. Another type of change observed in mammals exposed to spaceflight relates to the release of a growth factor, called bioassayable growth hormone, which is thought to be released from the pituitary. When an individual generates a series of isometric plantarflexor contractions, the plasma levels of bioassayable growth hormone increases significantly. This response is suppressed after several days of continuous bedrest or spaceflight. These results suggest a unique neuroendocrine control system and demonstrate its sensitivity to chronic patterns of proprioceptive input associated with load-bearing locomotion.

Adaptation, Physiological↗
PubMed1997

Protein structure prediction force fields: parametrization with quasi-newtonian dynamics.

We present an unusual method for parametrizing low-resolution force fields of the type used for protein structure prediction. Force field parameters were determined by assigning each a fictitious mass and using a quasi-molecular dynamics algorithm in parameter space. The quasi-energy term favored folded native structures and specifically penalized folded nonnative structures. The force field was generated after optimizing less than 70 adjustable parameters, but shows a strong ability to discriminate between native structures and compact misfolded alternatives. The functional form of the force field was chosen as in molecular mechanics and is not table-driven. It is continuous with continuous derivatives and is thus suitable for use with algorithms such as energy minimization or newtonian dynamics.

Algorithms↗
PubMed1998

Lipid uptake in expanded polytetrafluoroethylene vascular grafts.

PURPOSE: The mechanisms of vascular prosthesis failure are reported to be associated, in part, with an atherosclerotic degenerative process that is related to an abnormal lipid infiltration. The lipid uptake in expanded polytetrafluoroethylene (ePTFE) vascular grafts was reproduced in vitro, and the effect of time on the permeability of these prostheses was studied. METHODS: Water permeability tests were carried out under dynamic flow conditions at various hydrostatic pressures. Lipid uptake was simulated by circulating a phosphatidylcholine suspension inside an expanded Teflon prosthesis under pulsatile or continuous transmural pressure ranging between 80 mm Hg and 180 mm Hg, at a flow rate of 500 mL/min and 2000 mL/min, for a duration ranging from 2 hours to 1 month. RESULTS: Water permeability tests indicated that under hydrostatic pressures of 180 mm Hg and 300 mm Hg, water percolated through the prosthesis wall after an exposure of 720 minutes and 75 minutes, respectively. After exposing the prostheses to the lipid dispersion under the various flow conditions, the fluid convection through the wall occurred. Preferential convection pathways with a constant periodicity were observed across the length of each prosthesis and were, therefore, associated with regularly spaced perforations depicted in the structure of the devices. Phospholipids gradually agglomerated within the prosthesis wall, allowing a restrictive molecular mobility. Infrared spectroscopy results indicated that the lipid uptake depended on the transmural pressure and time of exposure. CONCLUSION: The occurrence of the membrane permeability may be associated with the dilatation and plastic deformation of the prosthesis. Lipid uptake occurs in ePTFE grafts after an aggressive kinetic process.

Blood Vessel Prosthesis↗
PubMed1996

Restoration of plasma volume after 16 days of head-down tilt induced by a single bout of maximal exercise.

Seven healthy men performed maximal exercise 24 h before the end of 16 days exposure to 6 degrees head-down tilt (HDT) to test the hypothesis that such an exercise technique could restore plasma volume (PV) at the end of a simulated space mission. Exercise consisted of supine cycling with graded work rates increasing by 16 W/min to volitional fatigue and required an average of 16 min. The experimental protocol was a standard cross-over design in which the order of treatment (exercise or control) was counterbalanced across all seven subjects. PV, fluid intake (ad libitum), urine output, renal function, and hormones associated with fluid homeostasis were measured before HDT, 24 h before the end of HDT just prior to exercise, and at the end of HDT 24 h after exercise. HDT reduced PV by 16% in both control and exercise conditions. Maximal exercise completely restored plasma volume within 24 h to 3.9 +/- 3.2% of pre-HDT levels despite continued HDT. Compared with control, exercise induced a 660-ml larger positive fluid balance because of greater fluid intake and reduced urine volume during the 24 h after exercise. These results suggest that one bout of maximal leg exercise before return from 16 days of spaceflight may be completely effective in stimulating thirst and restoring plasma volume to preflight levels.

Adult↗
PubMed2002

Testing association of statistically inferred haplotypes with discrete and continuous traits in samples of unrelated individuals.

There have been increasing efforts to relate drug efficacy and disease predisposition with genetic polymorphisms. We present statistical tests for association of haplotype frequencies with discrete and continuous traits in samples of unrelated individuals. Haplotype frequencies are estimated through the expectation-maximization algorithm, and each individual in the sample is expanded into all possible haplotype configurations with corresponding probabilities, conditional on their genotype. A regression-based approach is then used to relate inferred haplotype probabilities to the response. The relationship of this technique to commonly used approaches developed for case-control data is discussed. We confirm the proper size of the test under H(0) and find an increase in power under the alternative by comparing test results using inferred haplotypes with single-marker tests using simulated data. More importantly, analysis of real data comprised of a dense map of single nucleotide polymorphisms spaced along a 12-cM chromosomal region allows us to confirm the utility of the haplotype approach as well as the validity and usefulness of the proposed statistical technique. The method appears to be successful in relating data from multiple, correlated markers to response.

Algorithms↗
PubMed2004

The French language virtual medical university.

The work program of the French Language Virtual Medical University started about 2 years ago, and entered into a real active phase of development and implementation in 2002. Various national programs and organizational initiatives should accelerate and facilitate further appropriation of modem pedagogical approaches by knowledge providers and all users of the FSVMU, so as to advance on the way of virtual education. The French Language Virtual Medical University under the auspices of both the National Conference of Deans of Medical Schools and the International Conference of Deans of French-Speaking Medical Schools has been developed to create a major Internet portal for French-speaking distance medical learning and teaching. This construct should be representative of all medical schools in France and French-speaking countries. Contents will also be translated into English, Spanish and Arabic. All medical disciplines with their various levels of teaching are to be included. Cross-related fields are also going to be present in order to offer full range programs. The latter are intended to provide both initial and continuing education for medical students as well as all other categories of health professionals and medical and scientific research workers. To develop the appropriate technology and make such a portal, on one hand correspond to the specific educational requirements and proper training for health professionals, and on the other hand provide a general access to e-learning in all schools of medicine; in keeping with such goals, the following approaches should be stressed upon. To build a virtual space where individual patients, their families, patient associations as well as the general public, can obtain medical information of good quality for the purposes of both education and prevention. Providing such categories with reliable and validated sources of information, and offering an ethical basis for the increasing practice of e-medicine, represent in today's and tomorrow's world one of the great modern challenges for the medical community. Beyond the sole medical domain, the model offered by the FSVMU should be useful for the French-speaking Universities in all the fields of knowledge and training which are candidate to benefit from new educational means and methods.

Computer Simulation↗
PubMed1987

A model study of the effects of the discrete cellular structure on electrical propagation in cardiac tissue.

The effects of the discrete cellular structure on propagation of electrical excitation in cardiac muscle were studied in a one-dimensional fiber model containing a periodic intercalated disk structure. Globally, the macroscopic velocity of propagation follows the behavior associated with propagation in a continuous tissue (except for high values of disk resistance). In addition, the computed spatial extracellular potential along the fiber is a smooth biphasic waveform and does not reflect the underlying discrete cellular structure of the tissue. Other results of the simulations demonstrate the discontinuous nature of propagation and the importance of the structure in arrhythmogenesis. Vmax displays a biphasic behavior as a function of increasing intercalated disk resistance. An initial "paradoxical" increase in Vmax (with a simultaneous decrease in conduction velocity) is followed by a decrease that leads to decremental propagation and conduction block. The time constant of the foot of the action potential (tau foot) increases monotonically with increasing intercalated disk resistance. An increase in the leakage current to extracellular space brings about a significant decrease in the action potential duration and a loss of the plateau. This major effect is accompanied by a relatively smaller decrease in conduction velocity. Collision of two activation wavefronts results in a significant (100%) increase in Vmax and a very small (0.6%) decrease in tau foot.

Action Potentials↗