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PubMed1984

Length summation in simple cells of cat striate cortex.

We have examined two models for the preference displayed by cortical simple cells for elongated stimuli having a particular orientation. Both assume that geniculate afferents with aligned receptive fields pool to form the receptive field of the cortical unit. The first model [Marr and Hildreth, Proc. R. Soc. Lond. Ser. B 200, 269-294 (1980)], includes AND gating along the length axis so that a simple cell does not fire unless a critical number of its afferents with adjacent receptive fields are firing. The second model assumes that geniculate input is simply summed over subunits and then passed through a firing threshold. Both models account for the unresponsiveness of simple cells to spots of light, but the AND model predicts a discontinuous length threshold, while the summation model predicts that length and contrast should be interchangeable in the determination of the response threshold. Experiments in which length and contrast were systematically varied support the summation model, and extend the notion of linear spatial summation to the length axis in simple cells.

Animals↗
PubMed1992

Manifestations of intense noise stimulation on spontaneous otoacoustic emission and threshold microstructure: experiment and model.

Comparison between changes that occur simultaneously on spontaneous otoacoustic emissions (SOAEs) and on other cochlear origin phenomena can contribute to the understanding of cochlear micromechanical activity. The temporary changes that arise after short noise exposure are investigated in the following paper. The effects of noise exposure on the threshold microstructure near an SOAE and on the amplitude and frequency of the SOAE were measured. These experimental results indicate the following: (1) exposure to wideband noise for a short time causes a temporary reduction in the SOAE frequency and amplitude, and alters reversibly the threshold microstructure in the vicinity of the SOAE. The difference between the minimum and maximum in the threshold microstructure is reduced, and the frequency that yields the minimum threshold decreases; (2) the threshold at the SOAE frequency is most sensitive to noise exposure; (3) intense stimulation causes a relatively small increase, or even a decrease, in threshold at frequencies near the SOAE. The experimental results are interpreted in terms of a nonlinear transmission line model which includes nonlinear amplifiers. The effect of the noise exposure is modeled by reduction in the cochlear partition amplification term. Most of the experimental results are predicted by this model.

Auditory Fatigue↗
PubMedDate not supplied

[Mathematical model of the immune response. IV. Threshold character of the infectious process].

A model of immune reaction is described which takes into account the agressive behaviour of infectious microorganisms in the macroorganism. The model allows a description of threshold relationship between the infection process and the initial dose of the antigen. According to the model depending on the parameters and initial data the following regimes are possible: destruction of the antigen without a disease, its destruction after a disease, coexistence of the antigen with specific antibodies, recurrent course of the disease, unlimited multiplication of the antigen.

Antibody Formation↗
PubMed2003

Corrections in the atomic bomb data to examine low dose risk.

Cancer incidence and mortality data from the cohort of Japanese atomic bomb survivors in Hiroshima have been adjusted for the uncertainty that exists in the dose estimates, the systematic error in the neutron dose estimates, and a dose-dependent relative biological effectiveness. Once the adjustments were incorporated in the dose estimates, the data were modeled with a threshold term to allow for the possibility of a threshold dose response. The dose response models that were fit to the data were otherwise the same models used in the original papers. The threshold term was included in the model allowing for possible threshold values ranging from 0 to 0.35 Sv. These analyses suggest that the fit of the A-bomb solid tumor and leukemia incidence data are significantly improved by the addition of a threshold term in comparison with the purely linear or linear quadratic model. The results from the mortality data suggest that the leukemia data agree more with the threshold model than the linear quadratic model although the linear quadratic model is statistically equivalent, while the solid tumor data does not suggest any improvement with a threshold.

Algorithms↗
PubMed2003

Feasibility and effects of transcutaneous phrenic nerve stimulation combined with an inspiratory impedance threshold in a pig model of hemorrhagic shock.

OBJECTIVE: Intrathoracic pressure changes are of particular importance under hypovolemic conditions, especially when central venous blood pressure is critically low. Accordingly, the purpose of this study was to assess the feasibility of transcutaneous phrenic nerve stimulation, used in conjunction with an inspiratory impedance threshold, on hemodynamic variables during hemorrhagic shock. DESIGN: Prospective, randomized laboratory investigation using a porcine model for measurement of hemodynamic variables, left and right ventricular diameter, and transmitral, transpulmonary, and transaortic blood flow employing transesophageal echo-Doppler technique. SETTING: University hospital laboratory. SUBJECTS: Thirteen female pigs weighing 28-36 kg. INTERVENTIONS: The anesthetized pigs were subjected to profound hemorrhagic shock by withdrawal of 55% of estimated blood volume over 20 mins. After a 10-min recovery period, the diaphragm was stimulated with a prototype transcutaneous phrenic nerve stimulator at a rate of ten per minute while the airway was intermittently occluded with an inspiratory threshold valve between positive pressure ventilations. Hemodynamic variables were monitored for 30 mins. MEASUREMENTS AND MAIN RESULTS: Phrenic nerve stimulation in combination with the inspiratory threshold valve significantly (p <.001) improved right and left ventricular diameter compared with hypovolemic shock values by 34 +/- 2.5% and 20 +/- 2.5%, respectively. Moreover, phrenic nerve stimulation together with the inspiratory threshold valve also increased transaortic, transpulmonary, and transmitral valve blood flow by 48 +/- 6.6%, 67 +/- 13.3, and 43 +/- 8.2%, respectively (p <.001 for comparisons within group). Mean +/- sem coronary perfusion and systolic aortic blood pressures were also significantly (p <.001) higher compared with values before stimulation (30 +/- 2 vs. 20 +/- 2 mm Hg, and 37 +/- 2 vs. 32 +/- 3 mm Hg, respectively). CONCLUSIONS: This feasibility study suggests that phrenic nerve stimulation with the inspiratory threshold valve may improve cardiac preload and, subsequently, key hemodynamic variables in porcine model of severe hemorrhagic shock.

Animals↗
PubMed2003

Regression-based sib pair linkage analysis for binary traits.

The Haseman-Elston (HE) regression method offers a mathematically and computationally simpler alternative to variance-components (VC) models for the linkage analysis of quantitative traits. However, current versions of HE regression and VC models are not optimised for binary traits. Here, we present a modified HE regression and a liability-threshold VC model for binary-traits. The new HE method is based on the regression of a linear combination of the trait squares and the trait cross-product on the proportion of alleles identical by descent (IBD) at the putative locus, for sibling pairs. We have implemented both the new HE regression-based method and have performed analytic and simulation studies to assess its type 1 error rate and power under a range of conditions. These studies showed that the new HE method is well-behaved under the null hypothesis in large samples, is more powerful than both the original and the revisited HE methods, and is approximately equivalent in power to the liability-threshold VC model.

Data Interpretation, Statistical↗
PubMed1993

Coincidence detectors and two-pulse visual temporal integration: new theoretical results and comparison with data.

Exact predictions for two-pulse visual temporal integration data are derived from the Bouman-van der Velden quantum coincidence model for threshold vision. The predictions of the model start with complete summation for superposed pulses, then pass to a transition zone of partial integration, and finally reach the level of probability summation for pulses presented with large interstimulus intervals. From our results we can clearly reject the assumption of constant integration times with the basic model. We thus generalize the coincidence model to allow for variable integration times, derive the corresponding predictions for two-pulse integration data, and compare these predictions to published data currently available. It is shown that detectors of low order of coincidence generally underestimate the actual reduction of threshold intensity (or equivalently the corresponding increase of the detection probability) for two pulses as compared to the simple-pulse performance.

Cybernetics↗
PubMed1999

Pattern detection in the presence of maskers that differ in spatial phase and temporal offset: threshold measurements and a model.

Four experiments are described in which brief Gabor patterns are detected in the presence of full-field gratings or Gabor patterns that are superimposed in space, but vary in spatial phase and temporal offset (SOA). E1: Threshold versus masker contrast (TvC) functions were determined for relative phases of 0, 90, 180 and 270 degrees at SOA = 0. For 0 degree relative phase, TvC functions decrease (facilitation) and then increase (masking) as contrast increases. For 90 degrees, there is little or no facilitation and thresholds increase with masker contrast. For 180 degrees, the form of the TvC function varies with observer and conditions. E2: Like E1, except that maskers are Gabor patterns. TvC functions are similar in form to those for full-field maskers, but there is less masking. E3: Forward masking. TvC functions were determined for relative phases of 0, 90, and 180 degrees at SOA = -33 ms. The forms of the TvC functions for 0 and 180 degrees are reversed relative to those at SOA = 0. E4: TvP (threshold versus phase) functions were determined for SOA's of -100, -67, -33, 0 and 33 ms at a constant masker contrast of 0.063. Masking occurs at all relative phases. For simultaneous and backward masking, the threshold is minimum for a relative phase of 0 and maximum at 180 degrees. For forward masking, the form of the function is inverted. A model of pattern masking and facilitation (Foley, J. M. (1994a) Journal of the Optical Society of America A, 11, 1710-1719) is extended to account for masker phase and SOA effects. The model assumes four mechanisms tuned to phases 90 degrees apart, and divisively inhibited by stimuli of all phases. Performance depends on the detection strategy of the observer.

Contrast Sensitivity↗
PubMed1998

Comparison of the in vivo photodynamic threshold dose for photofrin, mono- and tetrasulfonated aluminum phthalocyanine using a rat liver model.

The photodynamic threshold dose in normal rat liver was determined from the measured depth of necrosis following surface irradiation. The threshold was determined for the photosensitizing drugs Photofrin and monosulfonated aluminum chlorophthalocyanine, AlPcS1, at 24 h postinjection and was found to be (3.4 x/divided by 1.3) x 10(18) and (8.2 x/divided by 1.5) x 10(18) photons cm-3, respectively, compared with the previously reported value of (38 +/- 2) x 10(18) photons cm-3 for the tri/tetrasulfonated phthalocyanine, AlPcS4. These values were independent of drug concentration or total light fluence. For all three drugs the depth of tissue necrosis decreased as the time between drug and light administration increased from 10 min to 72 h. This decrease can be attributed both to the change in the tissue drug concentration as well as to changes in the efficiency of photodynamic therapy for producing tissue damage, related to the photodynamic necrosis threshold. The threshold values for all three photosensitizers were lowest at 10 min post injection: (1.4 x/divided by 1.4) x 10(18), (1.6 x/divided by 1.3) x 10(18) and (23 x/divided by 1.3) x 10(18) photons cm-3 for Photofrin, AlPcS1 and AlPcS4, respectively. The changes in necrosis threshold with time may be due to an initial change from entirely vascular to a combination of vascular and cellular damage, with later redistribution of the photosensitizer to targets at the subcellular level.

Animals↗
PubMed2004

Distinct mechanisms of bidirectional activity-dependent synaptic plasticity in superficial and deep layers of rat entorhinal cortex.

The entorhinal cortex plays a key role in processing memory information in the brain; superficial layers relay information to, and deep layers receive information from, the hippocampus. The cellular mechanisms of memory are thought to include a number that produce long-term potentiation (LTP) and depression (LTD) of synaptic strength. Our work presents evidence that LTP and LTD occur simultaneously at memory-relevant synapses. We report here that low frequency stimulation generates NMDA receptor-dependent LTD in Wistar rat superficial (layers II and III), and LTP in the deep entorhinal cortex layers (layers V and VI). LTP in deep layers is masked by simultaneously occurring voltage-gated calcium channel-dependent LTD. Our data support a novel mechanism for the sliding-threshold (BCM) model of synaptic plasticity: The sliding thresholds for induction of LTP and LTD in entorhinal cortex deep layers will be driven by the relative activation state of NMDA receptors and voltage-gated calcium channels. The co-expression of LTD and LTP at presynaptic sites in the entorhinal cortex deep layers reveals an intriguing mechanism for differential processing of synaptic information, which may underlie the vast dynamic capacity for information storage by this cortical structure.

Animals↗
PubMed1996

Evidence for curvilinearity in the cancer incidence dose-response in the Japanese atomic bomb survivors.

The recently released data on cancer incidence in the Japanese atomic bomb survivors are analysed using a variety of relative risk models which take account of errors in estimates of dose to assess the dose-response at low doses. For all solid cancers analysed together there is a significant positive dose-response (at the one-sided 2.5% significance level) if all survivors who received < 0.5 Sv are considered, but the significance vanishes if doses of < 0.2 Sv are considered. If a relative risk model with a threshold (the dose-response being assumed linear above the threshold) is fitted to the solid cancer data, a threshold of more than about 0.2 Sv is inconsistent with the data, whereas these data are consistent with there being no threshold. Linear-quadratic models and linear-quadratic models with an exponential cell-sterilization term provide no better fit than the linear model. For the three main radiation-inducible leukaemia subtypes analysed together (acute lymphatic leukaemia, acute myeloid leukaemia and chronic myeloid leukaemia) there is a significant positive dose-response (at the one-sided 2.5% significance level) if all survivors who received < 0.5 Sv are considered, but the significance vanishes if doses of < 0.2 Sv are considered. If a relative risk model with a threshold (the dose-response being assumed linear above the threshold) is fitted to the leukaemia data, a thresh-old of more than about 0.3 Sv is inconsistent with the data. In contrast with the solid cancer data, the best estimate for the threshold level in the leukaemia data is significantly different from zero, even when allowance is made for a possible quadratic term in the dose-response, albeit at borderline levels of statistical significance (p = 0.04). There is little evidence for curvature in the leukaemia dose-response from 0.2 Sv upwards. However, the possible underestimation of the errors in the estimates of the dose threshold as a result of confounding and uncertainties not taken into account in the analysis, together with the lack of biological plausibility of a threshold, makes the interpretation of this finding questionable.

Humans↗
PubMed2004

Corrections to scaling in random resistor networks and diluted continuous spin models near the percolation threshold.

We investigate corrections to scaling induced by irrelevant operators in randomly diluted systems near the percolation threshold. The specific systems that we consider are the random resistor network and a class of continuous spin systems, such as the x-y model. We focus on a family of least irrelevant operators and determine the corrections to scaling that originate from this family. Our field theoretic analysis carefully takes into account that irrelevant operators mix under renormalization. It turns out that long standing results on corrections to scaling are respectively incorrect (random resistor networks) or incomplete (continuous spin systems).

Journal Article↗
PubMed1990

Cyclosporine lowers seizure threshold in an experimental model of electroshock-induced seizures in Munich-Wistar rats.

We have developed a model of cyclosporin A (CsA) central nervous system toxicity in the Munich-Wistar rat in which CsA, 20 mg/kg/day i.p., produces significant EEG abnormalities and mortality. In the present study we used cohorts of Munich-Wistar rats to assess effects of CsA on the threshold for tonic-clonic electroshock-induced seizures. Rat cohorts were begun on cremephore, CsA-10 mg/kg/day, or CsA-20 mg/kg/day. On day 7 and day 14 of the dosing protocol, cohorts of animals were exposed to maximal electroshock (MES) using a minimal staircase method within each cohort. Multiple logistic regression models were used to determine differences between groups on the relative odds of producing a MES-induced seizure while controlling for other variables. Seizure threshold was significantly affected by shock amperage and body weight, but not by SUN, creatinine, bilirubin, sodium, potassium, weight loss or day the shock was delivered. The odds ratios of seizure induction in the CsA-treated groups versus placebo group were 1.91 for CsA-10 mg/kg/day and 3.63 for CsA 20-mg/kg/d, both statistically significant. These results suggest that cyclosporine lowers seizure threshold and probably increases susceptibility to seizures, the etiology of which may be multifactorial clinically.

Animals↗
PubMed1999

Current clamp and modeling studies of low-threshold calcium spikes in cells of the cat's lateral geniculate nucleus.

Current clamp and modeling studies of low-threshold calcium spikes in cells of the cat's lateral geniculate nucleus. All thalamic relay cells display a voltage-dependent low-threshold Ca2+ spike that plays an important role in relay of information to cortex. We investigated activation properties of this spike in relay cells of the cat's lateral geniculate nucleus using the combined approach of current-clamp intracellular recording from thalamic slices and simulations with a reduced model based on voltage-clamp data. Our experimental data from 42 relay cells showed that the actual Ca2+ spike activates in a nearly all-or-none manner and in this regard is similar to the conventional Na+/K+ action potential except that its voltage dependency is more hyperpolarized and its kinetics are slower. When the cell's membrane potential was hyperpolarized sufficiently to deinactivate much of the low-threshold Ca2+ current (IT) underlying the Ca2+ spike, depolarizing current injections typically produced a purely ohmic response when subthreshold and a full-blown Ca2+ spike of nearly invariant amplitude when suprathreshold. The transition between the ohmic response and activated Ca2+ spikes was abrupt and reflected a difference in depolarizing inputs of <1 mV. However, activation of a full-blown Ca2+ spike was preceded by a slower period of depolarization that was graded with the amplitude of current injection, and the full-blown Ca2+ spike activated when this slower depolarization reached a sufficient membrane potential, a quasithreshold. As a result, the latency of the evoked Ca2+ spike became less with stronger activating inputs because a stronger input produced a stronger depolarization that reached the critical membrane potential earlier. Although Ca2+ spikes were activated in a nearly all-or-none manner from a given holding potential, their actual amplitudes were related to these holding potentials, which, in turn, determined the level of IT deinactivation. Our simulations could reproduce all of the main experimental observations. They further suggest that the voltage-dependent K+ conductance underlying IA, which is known to delay firing in many cells, does not seem to contribute to the variable latency seen in activation of Ca2+ spikes. Instead the simulations indicate that the activation of IT starts initially with a slow and graded depolarization until enough of the underling transient (or T) Ca2+ channels are recruited to produce a fast, "autocatalytic" depolarization seen as the Ca2+ spike. This can produce variable latency dependent on the strength of the initial activation of T channels. The nearly all-or-none nature of Ca2+ spike activation suggests that when a burst of action potentials normally is evoked as a result of a Ca2+ spike and transmitted to cortex, this signal is largely invariant with the amplitude of the input activating the relay cell.

Action Potentials↗
PubMed1986

Insulin action and dynamics modelled in patients taking the anabolic steroid methandienone (Dianabol).

Plasma glucose and insulin concentrations were measured during oral (OGTT) and intravenous (IVGTT) glucose tolerance tests in nine patients off- and on-treatment with the anabolic steroid, methandienone (Dianabol). On-treatment, the tolerance tests showed a markedly increased insulin response accompanied by impairment of glucose tolerance, characteristics normally attributed to insulin resistance. However, fasting plasma glucose (FPG) and insulin (FPI) concentrations were significantly reduced, whereas the pattern normally associated with insulin resistance is for both to be raised. IVGTT glucose and insulin profiles were analysed using an algorithm derived from the minimal models of glucose and insulin dynamics originally proposed by R. Bergman and co-workers. Measures for the following parameters were thus obtained: Si, the sensitivity of glucose disposal to insulin; Sg, net insulin independent glucose disposal; phi 1, the integral concentration of insulin delivered during the first phase of insulin secretion relative to the initial increase in glucose concentration above a model-derived threshold; phi 2, the sensitivity of the rate of rise of insulin concentration in the second phase of insulin secretion to the concentration of glucose above a model-derived threshold; kappa, the fractional clearance rate of insulin; and tau 1/2, the insulin half-life. S1 was significantly reduced on treatment by a factor of 4. Sg, phi 1, phi 2 and tau 1/2 were all significantly increased, and kappa was significantly reduced. The increases in Sg and phi 1 both showed significant correlations with the increase in weight on-treatment. The reduction in FPG and FPI can be explained by the combined effects of the increase in Sg and Dianabol-induced resistance to glucagon.(ABSTRACT TRUNCATED AT 250 WORDS)

Adult↗
PubMed2005

Integrate-and-fire neurons with threshold noise: a tractable model of how interspike interval correlations affect neuronal signal transmission.

Many neurons exhibit interval correlations in the absence of input signals. We study the influence of these intrinsic interval correlations of model neurons on their signal transmission properties. For this purpose, we employ two simple firing models, one of which generates a renewal process, while the other leads to a nonrenewal process with negative interval correlations. Different methods to solve for spectral statistics in the presence of a weak stimulus (spike train power spectra, cross spectra, and coherence functions) are presented, and their range of validity is discussed. Using these analytical results, we explore a lower bound on the mutual information rate between output spike train and input stimulus as a function of the system's parameters. We demonstrate that negative correlations in the baseline activity can lead to enhanced information transfer of a weak signal by means of noise shaping of the background noise spectrum. We also show that an enhancement is not compulsory--for a stimulus with power exclusively at high frequencies, the renewal model can transfer more information than the nonrenewal model does. We discuss the application of our analytical results to other problems in neuroscience. Our results are also relevant to the general problem of how a signal affects the power spectrum of a nonlinear stochastic system.

Action Potentials↗