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PubMed1984

Temporal integration in self-stimulation: a paradox.

Temporal summation of the rewarding effects of medial forebrain stimulation in the rat was investigated by varying the interval separating the two short bursts of stimulation given as a reward in a runway. One finding--that the reinforcing effect of the two bursts is independent of interburst interval--supports a model in which there is perfect summation of the portion of the reward signal that exceeds some threshold. However, the constant-threshold form of this model is not reconcilable with the results of a second experiment, which shows that charge-duration functions obtained with different levels of performance differ by a multiplicative (scalar) factor, that is, the ratio between the values of the two functions is everywhere the same. (The charge-duration function gives the charge required as a function of the train duration.) None of the models of postsynaptic integration so far suggested is capable of explaining simultaneously the fact that the strength-duration function is a perfect hyperbola that has nearly reached its rheobase at a train duration no greater than 2 s, that there is no statistically detectable effect of interburst interval on summation between bursts separated by intervals up to 2 s and longer, and that the strength-duration functions (or, equivalently, the charge-duration functions) derived by using different performance criteria differ by a multiplicative factor.

Animals↗

PubMed2000

Incorporating observability thresholds of tumors into the two-stage carcinogenesis model.

This paper discusses a general way of incorporating the growth kinetics of malignant tumors with the two-stage carcinogenesis model. The model is presented using time-homogeneous rate parameters. In that case, the differential equations comprising the model are straightforward to solve using standard numerical techniques and software. An extension of the method to time-dependent rate parameters is included in Appendix A. Allowing the rate parameters to be time-dependent does incur computational cost. An expression is given for the expected time without visible tumor, a generalization of the expected time to an observable tumor that includes the possibility of tumor regression. The model is illustrated using incidental liver tumor data in control rats from NTP rodent carcinogenicity studies, using linear birth-death kinetics of tumors combined with a non-absorbing detection limit. The approach is also shown to be potentially useful with tumor observability thresholds having more complicated features.

Animals↗

PubMed1999

Auditory temporal integration in the rhesus macaque (Macaca mulatta).

Temporal integration for pure tones was examined in two rhesus macaques. The subjects were required to respond to a brief sound (a tone burst) that deviated from a previous series of sounds (noise bursts) on a trial (a deviant-stimulus detection paradigm). Psychometric functions and thresholds were determined from correct detections (hit proportions) alone, and from d' scores. Two models describing the decline in threshold as a function of stimulus duration, one a power function the other an exponential, were tested against the data. When the decline (slope) in threshold per log stimulus duration is used as a rate measure, our results yield a lower estimate of temporal integration rate in rhesus than did a previous study [Clack, J. Acoust. Soc. Am. 40, 1140-1146 (1966)]. Both studies, however, gave slope estimates of integration rate that were higher than in most other species. Comparison of the models using data from several species, revealed that the exponential, but not the power model, could account for two sources of variation in threshold measurement. One source is due to the range across threshold as a function of duration (the linear rate component), and is described by the constant of proportionality Ik in the model. The other source of variation arises from the rate of decline within this range (the nonlinear rate component), and is described by the time constant tau. In terms of this model, differences in rate estimates between Clack's study and ours (and between rhesus and other species) are primarily due to the linear component. The nonlinear rate component was about equal for our study and Clack's (tau = approximately 150 ms): a time constant that is just slightly larger (indicating a rate of temporal integration slightly slower) than for most other species examined.

Animals↗

PubMed2001

A re-examination of the possibility of controlling the firing rate gain of neurons by balancing excitatory and inhibitory conductances.

It has been suggested that balancing excitatory and inhibitory conductance levels can control the firing rate gain of single neurons, defined as the slope of the relation between discharge frequency and excitatory conductance. According to this view the increase in firing rate produced by an input pathway can be controlled independently of the ongoing firing rate by adjusting the mixture of excitatory and inhibitory conductances produced by other pathways converging onto the neuron. These conclusions were derived from a simple RC-neuron model with no active conductances, or firing threshold mechanism. The analysis of that model considered only the subthreshold behaviour and did not consider the relation between total trans-membrane conductance and firing rate. Similar conclusions were also derived from a simple parallel conductance based model. In this paper I consider, as an example of a repetitively firing neuron, a generic model of cat lumbar alpha-motoneurons with excitatory and inhibitory inputs and a second independent excitatory pathway. The excitatory and inhibitory inputs can be thought of as central descending controls while the second excitatory pathway may represent, for example, the monosynaptic Ia-afferent pathway. I have re-examined the possibility that the firing rate gain of the "afferent" pathway can be controlled independently of the ongoing firing rate by balancing the excitatory and inhibitory conductances activated by the descending inputs. The steady state firing rate of the model motoneuron increased nearly linearly with the excitatory current, as it does in real motoneurons (primary firing range). The model motoneuron also showed a secondary firing range, whose slope was steeper than in primary range. The firing rate gain was measured by increasing the conductance of the "afferent" pathway. The firing rate gain (in the primary and secondary firing range) of the "afferent" pathway was found to be the same regardless of the particular mixture of excitatory and inhibitory conductances acting to produce the ongoing firing rate. This result was obtained for a single-compartment model, as well as for a two-compartment model consisting of an active somatic compartment and a dendritic compartment containing an L-type calcium conductance. Put simply, the firing rate gain of an input to a neuron cannot be controlled by balancing excitatory and inhibitory conductances produced by other independent input pathways, or by the spatial distribution of excitation and inhibition across the neuron. Three potential ways of controlling the firing rate gain are presented in the "Discussion". Firing rate gain can be controlled by actions at the presynaptic terminal, by inhibitory feedback, which is a function of the neuron's firing rate, or by neuromodulator substances that affect intrinsic inward or outward currents.

Action Potentials↗

PubMed2004

Hormesis: from marginalization to mainstream: a case for hormesis as the default dose-response model in risk assessment.

The paper provides an account of how the hormetic dose response has emerged in recent years as a serious dose-response model in toxicology and risk assessment after decades of extreme marginalization. In addition to providing the toxicological basis of this dose-response revival, the paper reexamines the concept of a default dose model in toxicology and risk assessment and makes the argument that the hormetic model satisfies criteria (e.g., generalizability, frequency, application to risk assessment endpoints, false positive/negative potential, requirements for hazard assessment, reliability of estimating risks, capacity for validation of risk estimates, public health implications of risk estimates) for such a default model better than its chief competitors, the threshold and linear at low dose models. The selection of the hormetic model as the default model in risk assessment for noncarcinogens and specifically for carcinogens would have a profound impact on the practice of risk assessment and its societal implications.

Animals↗

PubMed2000

A comparison of nonlinear regression and neural network models for ground-level ozone forecasting.

A hybrid nonlinear regression (NLR) model and a neural network (NN) model, each designed to forecast next-day maximum 1-hr average ground-level O3 concentrations in Louisville, KY, were compared for two O3 seasons--1998 and 1999. The model predictions were compared for the forecast mode, using forecasted meteorological data as input, and for the hindcast mode, using observed meteorological data as input. The two models performed nearly the same in the forecast mode. For the two seasons combined, the mean absolute forecast error was 12.5 ppb for the NLR model and 12.3 ppb for the NN model. The detection rate of 120 ppb threshold exceedances was 42% for each model in the forecast mode. In the hindcast mode, the NLR model performed marginally better than the NN model. The mean absolute hindcast error was 11.1 ppb for the NLR model and 12.9 ppb for the NN model. The hindcast detection rate was 92% for the NLR model and 75% for the NN model.

Forecasting↗

PubMedDate not supplied

A physiological ear model for the emulation of masking.

Auditory masking is exploited in technical audio systems for transmission and storage to improve the perceived audio quality. In this respect, perception models are necessary for a masked threshold prediction to quantify the threshold of audibility for a given signal or distortion. The presented ear model emulates those parts of the auditory sound processing which are relevant to masking. The physiological modeling approach is not limited to simple masker-test-signal configurations as usually employed in psychoacoustical measurements, but it is valid for complex signals as well, which is desired in the aforementioned applications. The ear model includes a nonlinear active cochlear model which emulates the basic mechanisms effective in masking: excitation and suppression. Nonlinear mechanical amplification by means of the outer hair cells plays a crucial role in proper modeling of these effects. In addition to physiological measurements at the mechanical level of sound processing in the cochlea, classical masking patterns and nonlinear masking effects are demonstrated by the ear model.

Acoustic Stimulation↗

PubMed1991

[Combined pharmacokinetic-pharmacodynamic model of procainamide in rabbits with induced ventricular fibrillation threshold (VFT) changes].

The change of electrically induced VFT was chosen as index of effect in anesthetized rabbits for study of pharmacodynamics of PA and NAPA. We analyzed the pharmacokinetic properties of PA and NAPA and elucidated their effect kinetics with a pharmacokinetic-pharmacodynamic (PK/PD) model in view of different transfer qualities. A linear-addition effect model was used to describe the relationship between the effect and the amount of drug and its metabolite in the effect compartment. PA was found to be eliminated faster than NAPA and distributed more extensively in rabbits. The effect per unit concentration of PA was shown to be larger than that of NAPA.

Acecainide↗

PubMed2005

Medical rapid prototyping technologies: state of the art and current limitations for application in oral and maxillofacial surgery.

PURPOSE: We describe state-of-the-art software and hardware requirements for the manufacture of high quality medical models manufactured using medical rapid prototyping. The limitations of medical models, the source of artefacts, and their physical appearance are illustrated along with remedies for their removal. MATERIALS AND METHODS: Medical models were built using predominantly stereolithography and fused deposition modeling at both institutions over a period of 6 years. A combined total of 350 models have been produced for a range of maxillofacial, neurosurgical, and orthopedic applications. Stereolithography, fused deposition modeling, computerized numerical milling, and other technologies are described along with computer software requirements. RESULTS: A range of unwanted artefacts that create distortions on medical models have been identified. These include data import, computed tomography gantry distortion, metal, motion, surface roughness due to support structure removal or surface modeling, and image data thresholding. The source of the artefact has been related to the patient, imaging modality performance, or the modeling technology. Discussion as to the significance of the artefacts on clinical use is provided. CONCLUSIONS: It is recommended that models of human anatomy generated by medical rapid prototyping are subject to rigorous quality assurance at all stages of the manufacturing process. Clinicians should be aware of potential areas for inaccuracies within models and review the source images in cases where model integrity is in doubt.

Artifacts↗

PubMed1978

An improved design of temporary myocardial electrode.

A new temporary myocardial electrode has a short piece of needle at one end of an electrode wire. Thus the electrode leaves no exposed areas when implanted. Only the tip is stiched into the myocardium. The device, tested in 20 patients who underwent cardiac operation, has significantly reduced the increase in myocardial threshold to pacing that occurs with the commonly used electrode. This new electrode can be much more easily fixed on both atrial and ventricular myocardium. On postoperative day 7 the threshold measured by Medtronic Model 5880 A was 1.6 mA. on the ventricle and 1.3 mA. on the atrium. The stimulation threshold of the right atrium is almost equal to that of the right ventricle.

Adolescent↗

PubMed1992

Additivity of threshold losses produced by acute acoustic trauma.

We have previously [Patuzzi and Rajan, Hear. Res. 60, 165-177, 1992] formulated a model to describe how the threshold elevations produced by a variety of independent, short-term cochlear manipulations add when the manipulations are combined. The manipulations were presumed to affect only the 'active process' in the cochlea. The present report applied this model to the effects observed after acute acoustic trauma in normal-hearing guinea pigs and in guinea pigs with idiopathic threshold losses. Successive loud pure-tone exposures were presented to the normal-hearing guinea pigs, while only a single exposure was presented to the guinea pigs with idiopathic hearing losses. Various parameters of exposure and inter-exposure delays were used to create a variety of threshold elevations, and the total hearing losses observed in the various groups were compared to the total hearing losses predicted by the model. In most cases a statistically-valid 1:1 relationship was obtained between the predicted values and the observed values. In cases where the model's predictions were found not to fit the data, this appeared to be due to inclusion of data previously defined to be outside the scope of the model. When such data were excluded, there was good agreement between the model's predictions and the observed data. The model was further tested by comparing its predictions with data obtained in studies of acute noise trauma in chinchillas and humans by other researchers. The model's predictions were found to agree with these data as well. Thus, across a number of different types and conditions of exposures, the model appears to provide a very good description of the additivity of threshold losses produced by acute acoustic trauma. The generality of and constraints on the model are discussed.

Acoustic Stimulation↗

PubMed2006

The asymptotic behavior of solutions of the buffered bistable system.

In this paper, we study a model for calcium buffering with bistable nonlinearity. We present some results on the stability of equilibrium states and show that there exists a threshold phenomenon in our model. In comparing with the model without buffers, we see that stationary buffers cannot destroy the asymptotic stability of the associated equilibrium states and the threshold phenomenon. Moreover, we also investigate the propagation property of solutions with initial data being a disturbance of one of the stable states which is confined to a half-line. We show that the more stable state will eventually dominate the whole dynamics and that the speed of this propagation (or invading process) is positive.

Animals↗

PubMed1983

A phenomenological model of the perceived intensity of single odorants.

The response of a model olfactory system to a single odorant is quantified by interconnecting three separate stimulus-response relationships. Together, these relationships encompass the deposition of odorant molecules onto an olfactory organ, their movement to the dendrite of the olfactory receptor neuron, their subsequent induction of action potentials, and the processing of induced and spontaneous action potentials by the central nervous system, resulting in perception and a behavioral response. Phenomena discussed within the context of the model include the behavioral threshold, central summation of responses from a number of olfactory neurons, and the effect of organ shape on olfactory detection. The intent of the model is to provide a quantitative conceptual framework for designing and interpreting experiments relating sensory input to perception and behavior. Its utility is particularly evident for insect olfaction since it enables insect sex pheromone behavioral thresholds to be estimated from the literature when bioassays or electrophysiological studies are not possible. It also derives a physiologically meaningful method for comparing behavioral thresholds among different animals, and permits comparisons of different kinds of behavioral responses in the same species. Vertebrate olfaction is treated briefly in a discussion of the effect of sniffing on the threshold of detection.

Action Potentials↗

PubMed1982

Interpreting the role of suppression in psychophysical tuning curves.

We describe two models which make different assumptions about the factors determining threshold for psychophysical tuning curves (PTCs) determined in simultaneous masking. The models make different predictions about the amount of activity evoked by off-frequency maskers in the frequency region of the signal. The predictions were tested by using a forward-masking technique to estimate the amount of this activity. The data support a model which assumes that threshold in simultaneous masking corresponds to a "swamping" of the signal activity by that of the masker, rather than a suppression of the low-level signal to its absolute threshold. To explain the fact that PTCs in forward masking are sharper than those in simultaneous masking, the model requires that suppression acts to sharpen the excitation pattern of the masker. This sharpening is not seen in simultaneous masking, since suppression in a given frequency region affects both signal and masker.

Auditory Threshold↗

PubMed1988

The impact of varying diagnostic thresholds on affected sib pair linkage analysis.

For Mendelian disorders, it is usually simple to classify individuals as either affected or unaffected. By contrast, for "complex" phenotypes, the diagnostic boundary of the disorder is often uncertain. This paper explores the following question: to most efficiently detect linkage in such a complex phenotype by the affected sib pair method, where should the diagnostic threshold be drawn? The model assumes that the disorder is due to a generalized two-allele single major locus (SML) where liability in each genotype is normally distributed. Evidence for linkage between the marker and disease loci is highly dependent on the location of the threshold. The relationship between the placement of the threshold and population linkage information (PLI) is Gaussian-like. At high thresholds, linkage efficiency (LE) (or the amount of linkage information per affected sib pair) is high but PLI is low because the number of affected sib pairs is very small. At low thresholds, the number of affected sib pairs is high, but PLI is low because LE is very low. The model is applied to published SML parameters for schizophrenia, and maximal PLI is achieved at thresholds broader than those for schizophrenia alone.

Disease Susceptibility↗

PubMed2000

Increment and decrement detection on temporally modulated fields.

Increment and decrement probe thresholds were measured during the presentation of two types of temporal masking stimuli. In Experiment 1, we measured thresholds for increment or decrement rectangular probes presented during the presentation of an increment or decrement Gaussian masking stimulus. We find that thresholds are higher when the probe and the Gaussian mask are of the same sign (e. g. both increments). However, both types of Gaussian mask raised increment and decrement probe thresholds above steady state conditions. In Experiment 2, we presented increment or decrement probes at one of eight possible phases of a 1 Hz luminance-modulated sine wave. For both increment and decrement probes, threshold variation with phase is non-sinusoidal in shape, but increment and decrement probe thresholds vary as a function of the sinusoid phase. These experiments show that increment and decrement thresholds vary as a function of the adaptation state of the visual system, and as a function of the direction of change in the adaptation state. Data from both experiments are discussed in terms of a recent neurophysiological model [Hood & Graham (1998). Threshold fluctuations on temporally modulated backgrounds: a possible physiological explanation based upon a recent computational model. Visual Neuroscience, 15 (5), 957-967]. We find that the predicted ON- and OFF-pathway responses do not correlate in a straightforward manner with the psychophysical thresholds, suggesting that detection of increment and decrement probes may not be performed exclusively by one pathway. Our data have implications for modeling visual performance under conditions where visual adaptation is dynamic, such as when scanning complex images or natural scenes.

Adaptation, Physiological↗

PubMed1992

Modeling the effects of electric fields on nerve fibers: determination of excitation thresholds.

We have developed a method to predict excitation of axons based on the response of passive models. An expression describing the transmembrane potential induced in passive models to an applied electric field is presented. Two terms were found to drive the polarization of each node. The first was a source term described by the activating function at the node, and the other was an ohmic term resulting from redistribution of current from sources at other nodes. A total equivalent driving function including both terms was then defined. We found that the total equivalent driving function can be used to provide accurate predictions of excitation thresholds for any applied field. The method requires only knowledge of the intracellular strength-duration relationship of the axon, the passive step response of the axon to an intracellular current, and the values of the extracellular potentials. Excitation thresholds for any given applied field can then be calculated using a simple algebraic expression. This method eliminates the errors associated with use of the activating function alone, and greatly reduces the computation required to determine fiber response to applied extracellular fields.

Axons↗

PubMed1992

Comparison of mathematically determined blood lactate and heart rate "threshold" points and relationship with performance.

The purpose of this study was to investigate the relationship between threshold points for heart rate (Thfc) and blood lactate (Thla) as determined by two objective mathematical models. The models used were the mono-segmental exponential (EXP) model of Hughson et al. and the log-log (LOG) model of Beaver et al. Inter-correlations of these threshold points and correlations with performance were also studied. Seventeen elite runners (mean, SD = 27.5, 6.5 years; 1.73, 0.05 m; 63.8, 7.3 kg; and maximum oxygen consumption of 67.8, 3.7 ml.kg-1.min-1) performed two maximal multistage running field tests on a 183.9-m indoor track with inclined turns. The initial speed of 9 km.h-1 (2.5 m.s-1) was increased by 0.5 km.h-1 (0.14 m.s-1) every lap for the fc test and by 1 km.h-1 (0.28 m.s-1) every 4 min for the la test. After fitting the la or the fc data to the two mathematical models, the threshold speed was assessed in the LOG model from the intersection of the two linear segments (LOG-la; LOG-fc) and in the EXP model from a tangent point (TI-la; TI-fc). Thla and Thfc speeds computed with the two models were significantly different (P less than 0.001) and poorly correlated (LOG-la vs LOG-fc: r = 0.36, TI-la vs TI-fc: r = 0.13). In general, Thfc were less well correlated with performance than Thla. With two different objective mathematical models, this study has shown significant differences and poor correlations between Thla and Thfc.(ABSTRACT TRUNCATED AT 250 WORDS)

Adult↗