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Multiple thresholds in a model system of noisy ion channels.

Voltage-activated ion channels vary randomly between open and closed states, influenced by the membrane potential and other factors. Signal transduction is enhanced by noise in a simple ion channel model. The enhancement occurs in a finite range of signals; the range can be extended using populations of channels. The range increases more rapidly in multiple-threshold channel populations than in single-threshold populations. The diversity of ion channels may thus be present as a strategy to reduce the metabolic costs of handling a broad class of electrochemical signals.

Cell Membrane↗

Visual orientation and spatial frequency discrimination: a comparison of single neurons and behavior.

Neurons in the visual cortex respond selectively to stimulus orientation and spatial frequency. Changes in response amplitudes of these neurons could be the neurophysiological basis of orientation and spatial frequency discrimination. We have estimated the minimum differences in stimulus orientation and spatial frequency that can produce reliable changes in the responses of individual neurons in cat visual cortex. We compare these values with orientation and spatial frequency discrimination thresholds determined behaviorally. Slopes of the tuning functions and response variability determine the minimum orientation and spatial frequency differences that can elicit a reliable response change. These minimum values were obtained from single cells using receiver operating characteristic (ROC) analysis. The average minimum orientation and spatial frequency differences that could be signaled reliably by cells from our sample were 6.4 degrees (n = 22) and 21.3% (n = 18), respectively. These values are approximately 0.20 of the average full tuning width at one-half height of the cells. Although these average values are well above the behaviorally determined thresholds, the most selective cells signaled orientation and frequency differences of 1.84 degrees and 5.25%, respectively. These values are of the same order of magnitude as the behavioral thresholds. We show that, because of slow fluctuations in a cell's responsivity, ROC analysis overestimates response variability. We estimate that these slow response fluctuations elevated our estimates of single cell "thresholds" by, on average, 30%. Our data point to an approximate correspondence between orientation and spatial frequency discrimination "thresholds" determined behaviorally and those estimated from the most selective single cortical cells. Interpretation of this quantitative correspondence is considered in the discussion.

Animals↗

Changes in core temperature and thermoeffector thresholds in exercise-trained rats.

Spontaneous running in a running wheel has emerged as an alternative method of exercise in small animals. The present study investigated how exercise training with a running wheel affects core temperature level and thermoeffector thresholds in rats. Female rats were allowed to run freely in the wheel for 6 months. Sedentary controls did not exercise during the same period. After the exercise training period, they were loosely restrained and their threshold core temperatures for tail skin vasodilation and cold-induced thermogenesis were determined by warming or cooling the animals by use of a chronically implanted intravenous thermode. Resting and threshold core temperatures of the exercise-trained rats were higher than those of the sedentary controls. The results suggest that in rat, exercise training with a running wheel shifts threshold temperatures for heat loss and heat production to high levels, which may result in a rise in core temperature level.

Animals↗

Foveal threshold of one eye when illuminated by contralateral steady light.

The effect of luminance of the contralateral steady light upon the foveal threshold was examined in the situation where both test-field and contralateral background (or surround) appeared to be completely fused when both were exposed simultaneously. The relation between the test threshold (defined as log Lt/Lto) and the luminance of the contralateral background (or surround) (I) was expressed by log (Lt/Lto) = a(1 - e-b log I), where a and b are constants.

Adaptation, Ocular↗

A simple stimulator for periodontal mechanoreceptors in human subjects.

Mechanoreceptors in the periodontal ligament are activated by tooth movements as little as 1-3 microns. It has been difficult in the past to move a tooth only over this small distance in order to activate the periodontal receptors without at the same time activating other receptors in related structures. This paper describes a simple solution to this problem based on the use of von Frey hairs (in the form of nylon filaments) rather than a rigid probe, to move the tooth. Filaments of different stiffness are mounted on the moving coil of a loudspeaker to apply different forces to the tooth. The timing of the contact of the filament with the tooth is measured precisely with a simple impact detector. The sensation elicited by this stimulator is abolished by local alveolar anaesthesia, indicating that the stimulation was localised to the periodontal area. The flexible probe is an important safety feature, as it limits the force applied to the tooth, and therefore the distance that the tooth can be displaced. The stimulator, suitable for psychophysical studies on the thresholds of periodontal receptors, on the reflex responses to stimulation of periodontal mechanoreceptors, and teaching applications, can be constructed from readily available components at minimal cost.

Adult↗

A calibrated paper clip is a reliable measure of two-point discrimination.

OBJECTIVES: The primary objective of this study was to compare two different instruments for assessing digital nerve function; a secondary aim was to determine interobserver agreement among emergency physicians by using static two-point testing of digital nerve function. METHODS: This was a prospective, blinded, observational study of static two-point discrimination involving healthy volunteers aged 18-59 years. The authors compared two instruments (paper clip set or Disk-Criminator) to assess two-point discrimination of the index and long fingers of the dominant hand. For each subject, the initial investigator and initial testing instrument were randomized. Two-point testing was conducted at 4, 5, and 6 mm by using six randomly selected stimuli (1 or 2 points) for each distal phalanx tested. The study was designed to detect a 25% difference in mean two-point distance with a power of 80%. RESULTS: Seventy-five subjects were entered into the study, of which two were excluded. Interinstrument agreement for a given investigator ranged from 77% to 84% for absolute agreement and 98% to 100% within 2 mm. Weighted kappa values for interobserver differences of 2 mm or less was 0.79 to 1.00. There was no statistically significant difference between instruments. CONCLUSIONS: Using a clinically relevant threshold of 2 mm, the authors found that a properly calibrated set of paper clips performed as well as the Disk-Criminator.

Adolescent↗

Long-term ischaemic preconditioning of the heart induced by repeated beta-adrenergic stress.

In the present study we tested the preconditioning effect of repeated beta adrenergic stress induced by Isoproterenol in chronically instrumented, conscious rabbits. We have found that at least 5 intravenous administrations of Isoproterenol, repeated at 10 min intervals, were necessary to induce a long-term cardiac adaptation manifested by a significant reduction of the harmful ischaemic changes due to cardiac stress 24 and 48 hours after preconditioning. These results suggest that a well-defined threshold level of the preconditioning stress is needed to trigger induction of metabolic changes leading to development of delayed and long-term cardiac adaptation.

Adrenergic beta-Agonists↗

Assessing myocardial viability and infarct transmurality with left ventricular electromechanical mapping in patients with stable coronary artery disease: validation by delayed-enhancement magnetic resonance imaging.

BACKGROUND: This study was designed to define myocardial viability and establish practical cut-off values for differentiating normal myocardial tissue from subendocardial and transmural scar tissue by using electromechanical mapping (EMM). We validated our results by delayed-enhancement cardiac MRI (DE-MRI). METHODS AND RESULTS: We prospectively studied 15 ambulatory patients with stable coronary disease who were candidates for cardiac catheterization. Within 48 hours of EMM, DE-MRI was performed. Using EMM software, we created a bull's eye precisely matched to that generated by DE-MRI. Segment by segment, we compared the MRI results to the corresponding unipolar voltage value for that same segment in the EMM bull's eye. Of 300 total segments, 275 were compared. The segments were divided into normal (n=211), subendocardial scar (n=49), and transmural scar (n=15). We found that subendocardial (6.8+/-2.9 mV) and transmural (4.6+/-1.9 mV) scar segments had significantly less unipolar voltage than normal (11.6+/-4.5 mV) segments (P<0.05 for each comparison). When normal myocardium was compared with myocardium with subendocardial scar, the threshold for differentiating between the two areas was 7.9 mV (sensitivity, 80%; specificity, 80%). Comparison of normal tissue to transmural scar yielded a threshold of 6.9 mV (sensitivity, 93%; specificity, 88%). CONCLUSIONS: Our results demonstrate that normal myocardium can be accurately distinguished from myocardium with subendocardial or transmural infarcts on the basis of unipolar voltage values obtained through EMM. This is the first study to validate these results by using cardiac DE-MRI in humans.

Adult↗

Triggered electromyographic threshold for accuracy of thoracic pedicle screw placement in a porcine model.

STUDY DESIGN: A porcine model of thoracic pedicle screw insertion was used to determine the effect of screw position on triggered electromyographic response. OBJECTIVE: To develop a model of intraoperative detection of misplaced thoracic pedicle screws. SUMMARY OF BACKGROUND DATA: Triggered electromyographic stimulation has been a valuable aid in determining appropriate placement of lumbar pedicle screws. The use of pedicle screws is increasing in the thoracic spine. Misplaced thoracic pedicle screws may have significant implications if the spinal cord is injured. This study was an attempt to determine whether the established lumbar model can be used for thoracic pedicle screws. METHODS: Five 120- to 150-lb domestic pigs had 85 pedicle screws placed bilaterally in the thoracic spine at each level from T6 to T15. Screws were inserted entirely in the pedicle (Group A). After removal of the medial pedicle wall, the screws were reinserted in the pedicle with no neural contact (Group B). The screws were then placed with purposeful contact with the neural elements (Group C). The screws were stimulated, eliciting an electromyographic response in the intercostal muscles for each instrumented level. The type of response noted was classified as either primary (response from appropriate nerve root), secondary (response at different root) or no response (response at different root, no response at appropriate root). RESULTS: Two hundred fifty responses were recorded. A primary response was noted in 72% of recordings. There was a relatively consistent decrease in the triggered electromyographic response from Group A (mean 4.15 +/- 1.80 mA) to Group C (mean 3.02 +/- 2.53 mA) screws (P = 0.0003). There was little difference in the response obtained from Group A to Group B (mean 4.37 +/- 2.48 mA) screws (P > 0.05). When a primary response was recorded, the mean threshold electromyographic response recorded was significantly lower than recordings with secondary and no response recordings (P < 0.05). CONCLUSION: Even though there was a consistent decrease between the A and C screws that was more definitively separated when a primary response was elicited, it was not possible to determine a cutoff trigger electromyographic level that would consistently differentiate intraosseous from epidural pedicle screw placement. Furthermore, this method could not differentiate screws clearly in the pedicle from screws with medial pedicle wall breakthrough. A more direct method of spinal cord monitoring must be established to provide the surgeon with early warning of the potential of neural injury in the placement of thoracic pedicle screws.

Animals↗

Mechanical response properties of ventroposterior medial thalamic neurons in the alert monkey.

The properties of trigeminal cutaneous thalamic neurons were explored in alert cynomolgous monkeys to determine receptive field and response characteristics. Two monkeys received juice reward for sitting quietly while an investigator probed the monkey's face with mechanical stimuli. Extracellular single unit recordings were made from the ventroposterior medial thalamic nucleus (VPM), and mechanical response properties were evaluated for each cell having an extraoral cutaneous receptive field. Of 89 cells examined, 90% responded best to innocuous tactile stimulation, and were classified as low threshold. The other 10%, classified as wide dynamic range, showed a graded response to increasingly intense stimuli, with a maximum discharge to noxious pinch. Of the low threshold neurons, most exhibited excitatory responses, with about half being rapidly adapting and the others slowly adapting. The spontaneous activity of 11% of the low threshold neurons was inhibited by stimulation of the neuron's receptive field. There was no systematic difference in receptive field size for the various types of neurons, but the receptive fields of wide dynamic range cells were smaller than those previously observed in trigeminopthalamic neurons of the medullary dorsal horn. The wide dynamic range and inhibitory low threshold neurons were located primarily in the caudal third of VPM, while the excitatory low threshold neurons were located throughout. In summary, response characteristics of VPM neurons show more diversity in the alert monkey than has been reported in paralyzed and/or anesthetized animals.

Adaptation, Physiological↗

A study of spontaneous and evoked activity in the rat hippocampus under helium-oxygen high pressure.

High pressures affect the physiology of the central nervous system. For a better understanding of this effect, we examined the hippocampal activity in the rat under high pressures (91 bars) of helium-oxygen. Effects of high pressure on hippocampal physiology are: an abnormally sustained 5-8 Hz pattern of spontaneous activity, followed, in some cases, by seizures; a marked decrease in the responses of CA1 pyramidal cells to stimulation of their commissural afferents; and a 50% decrease in the afterdischarge threshold. On the basis of the relatively well understood hippocampal physiology in normobaric conditions, our observations suggest that high pressures induce hypoexcitability of afferents and/or target cells.

Animals↗

Can the sensory threshold toward electrical stimulation be used to quantify the subjective perception of bladder filling? A study in young healthy volunteers.

OBJECTIVES: To evaluate whether electrosensation can be used as a quantitative measurement for the sensations felt during bladder distension. METHODS: A total of 48 healthy volunteers were examined. Sensations of bladder distension were evaluated during medium-fill cystometry. Electrosensation was quantified by obtaining electrical thresholds at different sites in the lower urinary tract with constant current stimulation at 2.5 and 95 Hz. RESULTS: Both currents were perceived differently. Thresholds at 95 Hz were significantly higher than at 2.5 Hz for each location. With neither current could a significant correlation be found between the parameters of filling perception and electrosensation in the lower urinary tract. CONCLUSIONS: Although the use of electrical thresholds is a valuable technique in the diagnosis of neuropathic disorders in the lower urinary tract, at the current settings it cannot be used to quantify the perception of bladder filling.

Adult↗

Response properties of hind limb single motor units in normal rats and after carrageenan-induced inflammation.

The properties of single motor units from hind limb muscles and the changes in situations of hyperalgesia are not known in detail. We have therefore characterized the properties of single motor units in normal Wistar male rats and in rats with carrageenan-induced inflammation, under alpha-chloralose anaesthesia. Units were studied from three different muscles: peroneus longus, tibialis anterior and extensor digitorum longus. The properties of single motor units were not homogeneous in the three muscles studied in normal animals, showing different sizes of cutaneous receptive fields, thresholds for natural and electrical stimulation, and encoding of responses at different intensities of stimulation. Intraplantar injections of carrageenan induced a significant inflammation of the paw and a change in spontaneous behaviour observed in open field experiments. After inflammation, the responses to cutaneous stimulation of the single motor units became more homogeneous. The threshold for mechanical stimulation was lower for peroneus longus and tibialis anterior but not for extensor digitorum longus units when compared to normal animals. The receptive fields were larger when mapped with a 500 mN von Frey hair but not when mapped using a threshold intensity hair. The threshold for thermal stimulation was lower after inflammation than in normal conditions in all cases, whereas the threshold for electrical stimulation was lower in tibialis anterior and extensor digitorum longus units. An enhancement of responses related to the increase of stimulus intensity was seen in normal animals in all muscles for mechanical and electrical stimuli (but not for thermal). After inflammation, a relationship between firing rate and intensity of stimulation was seen in all cases studied. The firing of single motor units showed over 50% adaptation in the normal condition and over 75% after inflammation when stimulated for 10 s at mechanical threshold intensity. After inflammation, the rate of adaptation was significantly lower when suprathreshold intensity was used for mechanical stimulation. No differences were seen in the adaptation of units to thermal stimulation. We conclude that, in situations of hyperalgesia due to inflammation, the threshold, encoding of stimulus intensity and adaptation of single motor units from different muscles changed, resulting in a narrower range of responses and a more homogeneous population of units.

Adaptation, Physiological↗

Measurement of color thresholds.

It is generally believed that some degree of defective color vision is frequently acquired along with certain ocular and systemic disorders. Precise definition of the nature and extent of the color defects has not been possible because of the limitations inherent in the tests currently available for clinical use. We undertook to define the defects in terms of thresholds of discrimination to each color, plotted on a color circle similar to Munsell's uniform chromaticity scale diagram. Furthermore, we were able to construct a symmetrical-type of colorimeter which plots thresholds directly on a printed circle without having to read and interpret scales or dials. Good correlation of subtle defects with certain disorders was confirmed, and may eventually be helpful in diagnosing and following some types. This system of threshold measurement was found to provide more information about color vision than any one of the conventional tests, or all of them combined.

Adult↗

Prediction of neural excitation during magnetic stimulation using passive cable models.

A method for predicting neural excitation during magnetic stimulation using passive cable models has been developed. This method uses the information of the threshold capacitor voltage for magnetic stimulation coils to determine the equivalent excitation thresholds for the passive transient (PT) and passive steady-state (PSS) cable models as well as for the activating function. The threshold values for the PT, PSS models, and the activating function vary only with the pulsewidth of the stimulus for a variety of coils at different locations and orientations. Furthermore, the excitation threshold for the PSS model is also independent of axon diameter and best fitted to a simple mathematical function. By comparing the transmembrane potential of the PSS model with the corresponding threshold, the prediction of excitation during magnetic stimulation can be made. Similarly, it is also possible to predict excitation using the PT model and the activating function with the corresponding thresholds provided. By taking advantage of the weighted pulsewidth, this method can even predict the excitation for stimuli with various waveforms, greatly simplifying the determination of neural excitation for magnetic stimulation.

Axons↗

A computer linear regression model to determine ventilatory anaerobic threshold.

The anaerobic threshold has generally been determined by simple visual inspection of ventilation or other gas-exchange data obtained during incremental exercise. To establish objective criteria for the determination of anaerobic threshold, a computer algorithm has been developed that models the ventilatory response to exercise using multisegment linear regression. The best-fit regression model is chosen by minimizing the pooled residual sum of squares . The anaerobic threshold is reported as the first break point in that model. The computer-determined anaerobic threshold values for 37 subjects were compared with subjectively determined values as chosen by four independent observers. The observers' estimates, when pooled to yield a single a single value for each subject, gave a mean value for the gas-exchange anaerobic threshold of 2.26 +/- 0.69 l/min. The estimates by the computer method averaged 2.21 +/- 0.65 l/min. The correlation coefficient for these two methods was 0.94.

Adult↗

Computer simulations of motoneuron firing rate modulation.

1. As a human subject slowly increases the amount of force exerted by a muscle, the discharge rates of low-threshold motor units saturate at a rather low level, whereas higher-threshold units continue to be recruited and undergo increases in their discharge rates. The presently known intrinsic properties of motor units do not produce this "rate limiting." 2. Using computer simulations of a model motoneuron pool, we tested the hypothesis that rate limiting can be accounted for on the basis of the known distributions of synaptic input from different sources. The properties of the simulated motor units and their synaptic inputs were based as closely as possible on the available experimental data. A variety of simulated synaptic input organizations were applied to the pool, and the resulting outputs were compared with the data on rate limiting in human subjects. 3. We found that the data on rate limiting in human subjects greatly constrained the possible organizations of characterized synaptic input systems. Only when the synaptic organization included a gradual "crossover" between two specific types of input systems could the human data be accurately reproduced. Low input/output levels relied on a system organized like the monosynaptic Ia input, which produces greater effective synaptic currents in low- than in high-threshold motor units. Above a sharply defined crossover level, all further increases in output were produced by a system organized like the oligosynaptic rubrospinal input, which generates the opposite pattern.

Computer Simulation↗

Defibrillation efficacy. Comparison of defibrillation threshold versus dose-response curve determination.

When an automatic defibrillator is implanted, it is essential to determine the efficacy of the defibrillating system accurately, while balancing the need to keep the number of fibrillation episodes to a minimum. Two methods have evolved to assess defibrillation efficacy: 1) the "defibrillation threshold," which requires few ventricular fibrillation episodes, and 2) the "dose-response curve," which requires many ventricular fibrillation episodes and relates percent success to energy. The purpose of this study was to compare these two methods directly. Twenty open-chest anesthetized pigs had triplicate defibrillation threshold determinations. To produce a dose-response curve, six shocks then were delivered at 0.5, 0.75, 1.0, 1.25, 1.5, and 2.0 times the mean defibrillation threshold, in a balanced randomized order, during separate episodes of ventricular fibrillation. The data were fitted by logistic regression, conversions of the logistic regression, and a saturable exponential and nonsaturable growth exponential. A comparison was made of the mean defibrillation threshold and the 50% point on the dose-response curve (ED50) for each model, for each animal. In addition, the reliability of each measure was assessed by comparing the coefficients of variation. There was no statistical difference between the group defibrillation threshold (6.6 +/- 0.5 J) and group ED50 values (ED50 range of the models, 5.7 +/- 1.9 to 7.0 +/- 0.9 J). However, the variability about the defibrillation threshold was less than that of the ED50 values for all mathematical models except the true logistic equation, which was virtually the same.(ABSTRACT TRUNCATED AT 250 WORDS)

Animals↗