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PubMed2001

Spatial unmasking of nearby speech sources in a simulated anechoic environment.

Spatial unmasking of speech has traditionally been studied with target and masker at the same, relatively large distance. The present study investigated spatial unmasking for configurations in which the simulated sources varied in azimuth and could be either near or far from the head. Target sentences and speech-shaped noise maskers were simulated over headphones using head-related transfer functions derived from a spherical-head model. Speech reception thresholds were measured adaptively, varying target level while keeping the masker level constant at the "better" ear. Results demonstrate that small positional changes can result in very large changes in speech intelligibility when sources are near the listener as a result of large changes in the overall level of the stimuli reaching the ears. In addition, the difference in the target-to-masker ratios at the two ears can be substantially larger for nearby sources than for relatively distant sources. Predictions from an existing model of binaural speech intelligibility are in good agreement with results from all conditions comparable to those that have been tested previously. However, small but important deviations between the measured and predicted results are observed for other spatial configurations, suggesting that current theories do not accurately account for speech intelligibility for some of the novel spatial configurations tested.

Adult↗
PubMed1982

A new model of partial status epilepticus based on kindling.

In this experiment, a new model of partial status epilepticus (SE) is described which is based on the antecedent development of a kindled focus. Following kindling, the amygdala was stimulated continuously for 60 min with the previous kindling stimulus (60 Hz sine wave, 50 microA peak-to-peak). This treatment provoked SE in 22 of 35 rats. Without drug intervention, rats spontaneously recovered (SR group) from the seizure between 10 and 24 h. After recovery from SE, after discharge (AD) thresholds were elevated and remained so for the 2 weeks before sacrifice. The histologies of these SR rats indicated massive gliosis and degeneration of the ipsilateral hemisphere, extending from the medial olfactory bulb, through the amygdala-pyriform cortex to the ventral hippocampus. Damage was observed frequently in the midline thalamic nuclei and hippocampal CA1 fields. Interruption of the SE with Nembutal 30 min after the stimulation offset (30 Min group) was occasionally associated with slight gliosis at the kindled electrode, whereas interruption after 4 h of SE (4 Hr group) resulted in more extensive cell loss. The AD thresholds of the 30 Min group, like those of the rats which did not develop SE (NSE group), returned to near-normal values by 2 weeks after SE; only the NSE rats exhibited generalized seizures to their AD threshold stimulus. This model of SE results in brain pathology similar to that found in other models, but has the advantage of being uncontaminated by exogenous chemicals and toxins.

Amygdala↗
PubMed2006

A neurocomputational hypothesis for nicotine addiction.

We present a hypothetical neurocomputational model that combines a set of neural circuits at the molecular, cellular, and system levels and accounts for several neurobiological and behavioral processes leading to nicotine addiction. We propose that combining changes in the nicotinic receptor response, expressed by mesolimbic dopaminergic neurons, with dopamine-gated learning in action-selection circuits, suffices to capture the acquisition of nicotine addiction. We show that an opponent process enhanced by persistent nicotine-taking renders self-administration rigid and habitual by inhibiting the learning process, resulting in long-term impairments in the absence of the drug. The model implies distinct thresholds on the dosage and duration for the acquisition and persistence of nicotine addiction. Our hypothesis unites a number of prevalent ideas on nicotine action into a coherent formal network for further understanding of compulsive drug addiction.

Behavior↗
PubMed2026

Artificial Intelligence for Diagnosis, Risk Stratification, and Prognosis of Neuroblastoma - A Systematic Review and Meta-Analysis.

PURPOSE: To synthesizes evidence on artificial intelligence (AI) performance in neuroblastoma (NB) diagnosis, risk stratification, prognosis, and genomic characterization. MATERIALS AND METHODS: A systematic review and meta-analysis was conducted following PRISMA 2020 guidelines (PROSPERO: CRD42024539475) across five databases. Meta-analyses used random-effects models with logit-transformed Area Under the Curve (AUCs) and cluster-robust standard errors. AI models were classified as Machine Learning Models (MLM) or Hybrid Nomograms (HN) based on their construction methodology. RESULTS: Of 3,742 articles identified, 53 were included. MLMs demonstrated higher point estimates than radiologists in differential diagnosis (AUC: 0.87 vs. 0.83), though this difference was not statistically significant and carried substantial uncertainty. HNs achieved stronger performance in risk stratification (AUC: 0.87). AI-derived nomograms (AUC: 0.9) and gene signatures (AUC: 0.8) outperformed conventional prognostic markers descriptively. Chemotherapy response prediction remained below clinical utility thresholds across all model types. Only 33.9% of models reported calibration and 24.5% underwent external validation. CONCLUSIONS: AI demonstrates proof-of-concept across multiple NB clinical domains. However, clinical adoption remains premature given persistent gaps in external validation, calibration, dataset size, and pediatric-specific model development. Future studies should test these models prospectively in multicenter pediatric cohorts, ideally through COG or SIOPEN, using shared definitions for diagnosis, risk group, treatment response, and survival outcomes.

Humans↗
PubMed1997

Quantification of area at risk in acute myocardial infarction by tomographic imaging.

UNLABELLED: The purpose of this study was twofold: to validate, in a phantom heart model, a simple threshold technique for the quantification of defect size using 123I-15-(p-iodophenyl)-3-(R,S)-methyl pentadecanoic acid (BMIPP) imaging and to compare, in patients with acute myocardial infarction, defect size as shown by BMIPP imaging, with the extent of severe hypokinesis shown by left ventriculography. METHODS: In a phantom study, defect size was calculated using a standard geometric formula. In a clinical study, BMIPP imaging was performed in 20 patients 10 +/- 5 days after the onset of their infarction. Using the centerline method, the area at risk was defined by contrast ventriculography as the percentage of chords with wall motion >2 s.d. below normal. RESULTS: In the phantom study, a threshold value of 60% yielded the best agreement between true and measured defect size. In the clinical study, the defect size shown by BMIPP imaging was greater in anterior than in inferior infarcts (p < 0.001) and correlated well with the risk area revealed by contrast ventriculography (r = 0.80, p < 0.0001) CONCLUSION: The above preliminary data, admittedly from a small group of patients, suggest that tomographic BMIPP imaging provides an accurate quantification of defect size by means of a simple threshold technique and, in the subacute phase, permits determination of the amount of myocardium at risk after acute myocardial infarction.

Coronary Angiography↗
PubMed2004

Lasing in a random amplifying medium: spatiotemporal characteristics and nonadiabatic atomic dynamics.

We study the dynamics of lasing from photonic paints excited by short, localized, optical pulses, using a time-dependent diffusion model for light propagating in the medium containing active atoms. The full time-dependent, nonadiabatic nonlinear response of the atomic system to the local optical field intensity is described using the Einstein rate equations for absorption and emission of light. Solving the time-dependent diffusion equation for the light intensity in the medium with nonlinear gain and loss, we derive detailed information on the spectral, spatial, and temporal properties of the emitted laser light. Our model recaptures the effects of scatterers to narrow the emission spectral linewidth and to narrow the emitted pulse duration, at a specific threshold pump intensity. Our model also describes how this threshold pump intensity decreases with scatterer density and excitation spot diameter, in excellent agreement with experimental results.

Journal Article↗
PubMed2002

Multiple-pool cell lifespan model of hematologic effects of anticancer agents.

The leukopenic effects of anticancer agents are described using a semi-physiologic multiple-pool cell lifespan model. The time course of myelosuppression in relation to the drug concentration vs. time profile was characterized using a three pool indirect model. The proliferation and maturation stages of myeloid cells in the bone marrow and cell removal from the circulation were quantitated with a cell life-span concept. Drug effects were assumed to take place in the bone marrow based on irreversible linear or capacity-limited cytotoxicity. Mathematical derivations and computer simulations (Adapt II) were used to examine the properties of the model. Data from the literature were also analyzed. Cell response profiles after therapy typically exhibit a lag period, reduction to a nadir, and return to baseline. The predicted values of the time periods of granulopoiesis were 10-14 days for proliferation, and 1-6 days for maturation of progenitor cells in the bone marrow. The proposed irreversible mechanism of cell killing by anticancer drugs explains previously observed relationships between leukocyte nadir counts and exposure to the drug and/or duration of drug concentrations above some threshold level. The model was applied to literature data for paclitaxel and etoposide effects on leukocyte counts. The predicted value of KC50 for paclitaxel ranged from 0.004 to 0.2 microgram/mL and for etoposide 2 micrograms/mL. The present model accounts for drug-induced leukopenia using a physiologic cell production and loss model and irreversible cytotoxicity in a precursor pool.

Animals↗
PubMed2001

Biotic ligand model of the acute toxicity of metals. 2. Application to acute copper toxicity in freshwater fish and Daphnia.

The biotic ligand model (BLM) was developed to explain and predict the effects of water chemistry on the acute toxicity of metals to aquatic organisms. The biotic ligand is defined as a specific receptor within an organism where metal complexation leads to acute toxicity. The BLM is designed to predict metal interactions at the biotic ligand within the context of aqueous metal speciation and competitive binding of protective cations such as calcium. Toxicity is defined as accumulation of metal at the biotic ligand at or above a critical threshold concentration. This modeling framework provides mechanistic explanations for the observed effects of aqueous ligands, such as natural organic matter, and water hardness on metal toxicity. In this paper, the development of a copper version of the BLM is described. The calibrated model is then used to calculate LC50 (the lethal concentration for 50% of test organisms) and is evaluated by comparison with published toxicity data sets for freshwater fish (fathead minnow, Pimephales promelas) and Daphnia.

Animals↗
PubMed1990

Mechanisms for nonuniform propagation along excitable cables.

We have discussed two classes of mechanisms that can lead to propagation with nonconstant velocity, and to disruption of temporal patterning of action potentials. Inhomogenieties along the cable due to geometrical change or to altered cell coupling can result in conduction delays, with the possibility of block or reflection. Such conduction irregularities have been considered relevant to cardiac reentry phenomena. Our simulations with a discrete number of excitable cells, coupled by gap junctions, showed that the underlying mathematical structure of a saddle point threshold in an ionic model also contributes in an important way to creating a long delay. Such threshold behavior, although not yet demonstrated for some of the most well-studied models of excitability, should not be viewed as extraordinary; we have seen it in models other than those of references 6 and 7, and have produced it in the Hodgkin-Huxley model with reasonable parameter variations (but have not yet checked for reflections with these modifications). We are unaware of any computations with theoretical models of cardiac membrane that yield robust reflection behavior. Perhaps modifications of these models will be necessary in order to obtain adequate delays for reflection. The mechanism we have described here may serve as a guideline for additional features to seek in such parametric tuning. A different class of factors that contribute to interferring with action potential timing include the effects of previous activity on propagation speed. These influences may be described in terms of the dispersion relation, c(T), the dependence of speed on time between action potentials. The form of this function, for large T, reflects the exponential behavior of the action potential's return to rest. Supernormal conduction reveals itself in the dispersion relation when there is an overshoot of excitability in the return to rest, either a single overshoot or an alternating sequence of over- and undershoots (as seen in some nerve membrane models). A simple kinematic recipe was described for quantitatively predicting timing changes during propagation without having to solve the full cable equations. To apply these concepts to cardiac models it will be necessary to compute the dispersion relation for these models. By studying the dependence of c(T) and the waveform trajectory (including conductances as well as membrane potential) on various parameters one may gain insight into the ionic basis for experimentally observed supernormal conduction.

Action Potentials↗
PubMed1997

Detection of second-order structure in optical flow fields.

We investigate how well the direction of the expansion gradient and the direction of a spatial step in expansion can be extracted from a complex optical flow field. The expansion gradient is an invariant of the second-order structure under rotations of the image plane. Our stimuli consist of sparse random dot patterns in a circular window with a diameter of 20 degrees. We find that translational velocity masks the direction of both the expansion gradient and the step in expansion. Thresholds for both the expansion gradient and the step in expansion are found to be similar for a wide range of expansions. We introduce two simple models that use the thresholds for the step in expansion to predict thresholds for the expansion gradient. Results of these models are comparable with the results of our subjects, showing that we do not need a hypothetical separate mechanism for the detection of second-order structure to explain the data.

Female↗
PubMed2003

Contribution of benzenemethanethiol to smoky aroma of certain Vitis vinifera L. wines.

Benzenemethanethiol, a volatile thiol with a strong empyreumatic aroma reminiscent of smoke, has been identified in boxwood (Buxus sempervirens L.) as well as in red and white Vitis vinifera L. wines. The perception threshold in a model hydroalcoholic solution is approximately 0.3 ng/L. All of the wines analyzed for this study contained this compound in concentrations of several dozen nanograms per liter. The Chardonnay wines had 30-40 ng/L. Sensory discrimination between a wine containing 7 ng/L benzenemethanethiol and the same wine with an additional 4 ng/L is very significant; the difference in smell is described as "empyreumatic". This compound can therefore significantly contribute to the aroma of certain wines (Sauvignon Blanc, Semillon, Chardonnay, etc.) containing concentrations as high as 30-100 times higher than their perception threshold.

Benzaldehydes↗
PubMed2005

Vergence target selection in rhesus monkeys: behavior and modeling.

Previous studies have shown that a LATER (Linear Approach to Threshold with Ergodic Rate) race model can be used to explain saccadic target selection and latencies. The goal of the present study was to determine whether a comparable model could be applied to the underlying decision-making processes involved in target selection for transient vergence eye movements in rhesus monkeys. Luminance contrast of near and far Gabor pair stimuli were manipulated in a forced-choice paradigm to investigate their influence on vergence target selection. The distributions of responses and their latencies were evaluated by cumulative recinormal and reciprobit plots. With all targets set to 20% luminance contrast, animals showed a bias for the divergent target. Increasing luminance contrast of the near Gabor pair, while holding the far Gabor at the base contrast, resulted in increasing selection of the convergent target. This change in bias from divergent to convergent target selection correlated with decreases in convergent latency and increases in divergent latency. Monte Carlo simulations were used to estimate the internal rates of the divergent and convergent decision-making processes which, given a fixed threshold, would result in the observed distributions of vergence responses and their latencies. Statistical tests show that the LATER race model can predict observed values, and strongly suggests that competition between internal convergent and divergent target selection processes determines relative frequencies and latencies of these movements.

Animals↗
PubMed2004

Modeling the relationship between psychophysical perception and electrically evoked compound action potential threshold in young cochlear implant recipients: clinical implications for implant fitting.

OBJECTIVE: In cochlear implant recipients, the threshold of the electrically evoked compound action potential (ECAP) has been shown to correlate with the perceptual detection threshold and maximum comfortable loudness levels (respectively, T- and C-levels) used for implant programming. Our general objective was to model the relationship between ECAP threshold and T/C-levels by taking into account their relative changes within each subject. In particular, we were interested in investigating further the validity of ECAP threshold as a predictor of psychophysical levels, depending on intra-cochlear electrode location and time of testing (from 1 to 18 months post-implantation). METHODS: A total of 370 ECAP thresholds, measured in 49 children, using a Nucleus 24 cochlear implant, were compared with the corresponding T- and C-levels obtained at the same visit, for the same electrode. Response profiles for the whole group of patients were modeled across four test electrodes spaced equally along the electrode array from base towards apex. A linear regression model was constructed and the quality of the ECAP threshold-based predictions was assessed by testing for correlation between measured and predicted psychophysics. Comparison was made with a more simplistic model (described here as the 'parallel profiles method') stipulating, within each subject, a 1 microA increase in psychophysical levels for every 1 microA increase in ECAP threshold. RESULTS: Offset between ECAP threshold and psychophysics profiles was found to vary significantly along the electrode array for the T-, but not for the C-level. In contrast with the parallel profiles method, our regression model predicted, within each subject, an average increase of 0.23 microA (95% confidence interval: 0.18-0.28) in T-level for every 1 microA increase in ECAP threshold. This correction improved the quality of T-level prediction when our model was run using measured T-level and ECAP threshold from a reference electrode (r=0.77 vs. r=0.62). The shorter the distance between the electrode for which T-level was predicted and the one used as reference, the stronger the correlation between measured and predicted T-levels. In addition, poorer T-level predictions were obtained at the basal end of the array during the first 3 months post-implantation. In contrast to T-level, individual changes in C-level with ECAP threshold exhibited heterogeneous patterns across subjects so that no common coefficient could account for these changes. However, applying the parallel profiles method led to high-quality C-level prediction. CONCLUSIONS AND SIGNIFICANCE: The results suggest that covariation between ECAP thresholds and psychophysics plays a decisive role in the relationship of ECAP threshold with T-, but not with C-level. Therefore, our regression model and the parallel profiles method should both be used for predicting, respectively, the T- and the C-levels. Although the predictability of our regression model seems to be better for middle and apical electrodes, its utilization should be extended to basal electrodes after 6 months' implant use.

Action Potentials↗
PubMed1987

Effect of cross cylinder power on cylinder axis sensitivity.

Astigmatic errors (0.50 D to 1.50 D in 0.25 D steps) were induced in each of 5 subjects, and cylinder axis thresholds were assessed from 12 reversals of a 2.5 degrees stepsize staircase for 0.50 D and 1.00 D cross cylinders (CC). Equivalent power thresholds were 0.077 D (0.05 SD) for the 0.50 D CC and 0.104 D (0.05 SD) for the 1.00 D CC. Findings are significantly different from predictions of a "linear" blur detection model, but are consistent with a model assuming constant blur thresholds and power-dependent distortion thresholds. Our results support the use of minimal CC power in refining cylinder axis.

Adult↗
PubMed2005

Toxicological awakenings: the rebirth of hormesis as a central pillar of toxicology.

This paper assesses historical reasons that may account for the marginalization of hormesis as a dose-response model in the biomedical sciences in general and toxicology in particular. The most significant and enduring explanatory factors are the early and close association of the concept of hormesis with the highly controversial medical practice of homeopathy and the difficulty in assessing hormesis with high-dose testing protocols which have dominated the discipline of toxicology, especially regulatory toxicology. The long-standing and intensely acrimonious conflict between homeopathy and "traditional" medicine (allopathy) lead to the exclusion of the hormesis concept from a vast array of medical- and public health-related activities including research, teaching, grant funding, publishing, professional societal meetings, and regulatory initiatives of governmental agencies and their advisory bodies. Recent publications indicate that the hormetic dose-response is far more common and fundamental than the dose-response models [threshold/linear no threshold (LNT)] used in toxicology and risk assessment, and by governmental regulatory agencies in the establishment of exposure standards for workers and the general public. Acceptance of the possibility of hormesis has the potential to profoundly affect the practice of toxicology and risk assessment, especially with respect to carcinogen assessment.

Animals↗
PubMed2000

Simulation of axonal excitability using a Spreadsheet template created in Microsoft Excel.

The objective of this present study was to implement an established simulation protocol (A.M. Brown, A methodology for simulating biological systems using Microsoft Excel, Comp. Methods Prog. Biomed. 58 (1999) 181-90) to model axonal excitability. The simulation protocol involves the use of in-cell formulas directly typed into a spreadsheet and does not require any programming skills or use of the macro language. Once the initial spreadsheet template has been set up the simulations described in this paper can be executed with a few simple keystrokes. The model axon contained voltage-gated ion channels that were modeled using Hodgkin Huxley style kinetics. The basic properties of axonal excitability modeled were: (1) threshold of action potential firing, demonstrating that not only are the stimulus amplitude and duration critical in the generation of an action potential, but also the resting membrane potential; (2) refractoriness, the phenomenon of reduced excitability immediately following an action potential. The difference between the absolute refractory period, when no amount of stimulus will elicit an action potential, and relative refractory period, when an action potential may be generated by applying increased stimulus, was demonstrated with regard to the underlying state of the Na(+) and K(+) channels; (3) temporal summation, a process by which two sub-threshold stimuli can unite to elicit an action potential was shown to be due to conductance changes outlasting the first stimulus and summing with the second stimulus-induced conductance changes to drive the membrane potential past threshold; (4) anode break excitation, where membrane hyperpolarization was shown to produce an action potential by removing Na(+) channel inactivation that is present at resting membrane potential. The simulations described in this paper provide insights into mechanisms of axonal excitation that can be carried out by following an easily understood protocol.

Action Potentials↗
PubMed1977

Spatial propagation of associations in a cortex-like neural network model.

A neural network model is studied, having associative memory properties and allowing retrieved associations to propagate within the network. It is intended as a tentative description of the cerebral cortex consisting of "pyramidal cells" with modifiable synapses and "stellate cells" providing feedback through excitatory and inhibitory recurrent pathways. The model is based on some general assumptions: Learning occurs through facilitation of synapses which depends on simultaneous pre- and postsynaptic activity (two-conditional facilitation). Connections within the network are realizations of a random process, implying that nearby cells are more likely to be connected than distant one. The two-conditional facilitation makes it possible for an output signal pattern which occurred in conjunction with a certain input pattern to be retrieved later by reapplying the particular input, the model working as an associative memory. The random connections and the operation of the stellate cell models as linear threshold units give rise to pattern separation in the feedback link. This, in addition to the fact that patterns form associations with themselves, is of importance during the associative recall enabling the network to attain alternative stable modes of activity each corresponding to a learned association. It is shown that a learned pattern of activity which is retrieved, ie, a stable mode, can propagate across the surface of the network. The mode of activity evoked through a certain association may get into contact with modes originating from different associations, forming a stable or slowly moving boundary between the interacting modes. The model is discussed in relation to some properties of the visual system.

Association↗