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Release of LHRH is linearly related to the time integral of presynaptic Ca2+ elevation above a threshold level in bullfrog sympathetic ganglia.

To study the Ca2+ dependency of luteinizing hormone-releasing hormone (LHRH) release in the bullfrog sympathetic ganglia, a method was developed to fill the preganglionic nerve terminal boutons with membrane-impermeant fura-2. We found that as stimulation frequency increased from 0.5 to 40 Hz, the peak [Ca2+]i ([Ca2+]p) and the rate of rise in [Ca2+]i increased, the decay of [Ca2+]i transients followed up to three exponentials, and release of LHRH was linearly related to integral of ([Ca2+]i--[Ca2+]t)dt. The threshold level of [Ca2+]i for LHRH release for a given set of boutons on a C cell, [Ca2+]t, was estimated by the [Ca2+]p evoked by 0.5 Hz stimulation that does not induce LHRH release.

Animals↗

Difference thresholds for automobile seat vibration.

Reductions in vehicle vibration that may contribute to improvements in overall vehicle ride could individually be too small to be detected by drivers or passengers. This study investigated the 'difference threshold' (the difference in magnitude between two stimuli which is just sufficient for their difference to be detected) required for a change in vehicle ride to be perceived and whether this was consistent with Weber's Law. Ten male and 10 female subjects sat in a car seat and were exposed to four different reproductions of the vertical vibration recorded on the seat of a car. Three of the stimuli had the same waveform recorded while the car traversed a tarmac surface. This waveform was reproduced using three different magnitudes of vibration at the seat: 0.2, 0.4 and 0.8 m s(-2) r.m.s. (Wb weighted). The other stimulus was recorded with the car traversing a 'pavé' surface that gave a different waveform that was reproduced at a magnitude of 0.4 m s(-2) r.m.s. (Wb weighted). There were significant differences in the absolute difference thresholds measured using the same waveform at the three different magnitudes. When the difference thresholds were expressed in relative terms (the proportion by which two stimuli must differ in magnitude to be discriminated), the relative difference thresholds were approximately 13%, and independent of both the vibration magnitude and the vibration waveform. The results are therefore consistent with Weber's Law. No consistent differences were observed between the responses of male and female subjects.

Adult↗

Chromatic detection and discrimination analyzed by a Bayesian classifier.

Detection and threshold-level discrimination of Gabor patches were studied under the conditions of noise masking, in an attempt to isolate 'higher-order' or nonclassical color mechanisms. Detection contours in the equiluminant plane of cone contrast space were measured by varying test chromaticity in the presence of chromatic masking noise. Three equiluminant noise directions were used, in separate experiments. In the discrimination experiment, observers had to discriminate between pairs of stimuli that were fixed at their masked threshold contrasts. A Bayesian color classifier model was used to analyze the discrimination data, with no free parameters. There was no evidence of nonclassical color mechanisms in either the detection or discrimination data.

Bayes Theorem↗

Changes in electrophysiological properties of axon terminals of locus coeruleus neurons with age in F344 rat.

Age-dependent changes in electrophysiological properties of locus coeruleus (LC) neurons were studied in urethane anesthetized male F344 rats aged 8, 17 and 22 months. These properties, such as spontaneous firing rate, conduction time, and threshold currents were measured for individual LC neurons antidromically activated from terminals in the frontal cortex. We found no change in the electrophysiological properties with age except for an increased number of low-threshold LC neurons in 22-month-old rats compared to that of 8-month-old rats. These results suggested that the electrophysiological properties of cortical axon terminals of LC neurons changed with age.

Action Potentials↗

Prediction of myelinated nerve fiber stimulation thresholds: limitations of linear models.

Computer models of neurons are used to simulate neural behavior, and are important tools for designing neural prostheses. Computation time remains an issue when simulating large numbers of neurons or applying models to real time applications. Warman et al. developed a method to predict excitation thresholds for axons using linear models and a predetermined critical voltage. We calculated threshold prediction error as a function of the location of an extracellular electrode using two different axon models to examine further threshold prediction using linear models. Threshold prediction error was low (<3% error) under the conditions examined by Warman et al., but under more general conditions, threshold prediction error was as high as 23.6%. Linear models were limited as effective tools for single fiber threshold prediction because accuracy was dependent on the nonlinear and linear models used, and any parameter that affected the extracellular potential distribution. Threshold prediction could be improved by appropriately choosing the membrane conductance of the linear model, but determination of an optimal conductance was computationally expensive. Finally, although single fiber threshold prediction error was partially masked when considering the input-output (I/O) properties of populations of axons, relatively large errors still occurred in population I/O curves generated with linear models.

Axons↗

Asymmetrical reduction of the nociceptive flexion reflex threshold in cluster headache.

The nociceptive flexion reflex (NFR) of the lower limbs (RIII reflex) was examined bilaterally in 54 cluster headache (CH) patients suffering from episodic CH (ECH) and chronic CH (CCH). Fifteen ECH patients were examined in both remission and active phases. The RIII reflex threshold (Tr) and the threshold of pain sensation (Tp) were significantly reduced on the symptomatic side in patients with episodic CH during the bout. During the active phase of episodic CH an inverse correlation was found between the severity of CH (ratio: number of cluster periods/years of illness duration) and the Tp, which may suggest a role for secondary central sensitization in pain pathways. The lower Tr and Tp on the symptomatic side is in keeping with previous observations exploring pain mechanisms using different methods (i.e. corneal reflex, pain pressure threshold). On the whole, these data tie in with the view of an impairment of the pain control system, which parallels the periodicity of the disorder in the episodic form.

Adult↗

Effects of amrinone on the electromechanical coupling in frog skeletal muscle fibres.

The contractile effects of 1.1 mM amrinone were studied on isolated skeletal muscle fibres of the frog (2-5 degrees C, slack length). Amrinone potentiated the twitch amplitude and the maximum tetanic tension and also enhanced the maximum contracture response elicited by 117.5 mM K+ (mean increase 6.3 +/- 1.8%, n = 6, P less than 0.02). The time to half-relaxation of the potassium contracture was slightly increased (mean change 13.8 +/- 3.5%, n = 7, P less than 0.01). Amrinone furthermore shifted the S-shaped curve relating contracture tension to log K+ to the left, and thus reduced the threshold depolarization (the mechanical threshold) needed to elicit a contracture (mean reduction 11 +/- 1 mV). The duration of the action potential at the -25 mV level was slightly increased by amrinone, whereas the resting membrane potential was unaffected.

Action Potentials↗

Effect of pixel size on detectability of low-contrast signals in digital radiography.

The effect of pixel size and other physical parameters on the detectability of simple signals in digital radiography was investigated using a signal-to-noise ratio (SNR) that is based on statistical decision theory and takes into account the characteristics of the human observer. The calculation of the SNR includes two-dimensional displayed digital signal spectra and noise Wiener spectra as well as the visual-response function and internal noise of the human observer. Threshold contrasts derived from calculated SNR's agreed well with results of an 18-alternative forced-choice observer study. Since a digital imaging system is not shift invariant, the threshold contrasts were determined for a range of alignments of the object relative to the sampling coordinates. The results indicate that a 0.2-mm pixel size may be adequate for visual detection of necessary detail in most digital radiographic examinations.

Differential Threshold↗

Effects of high stimulation current on the induction of ventricular tachycardia.

Programmed stimulation at 2 right ventricular sites with 1 to 3 extrastimuli was performed at current strengths of twice diastolic threshold (1.0 +/- 0.2 mA, mean +/- standard deviation) and 10 mA in 41 patients undergoing an electrophysiologic study because of sustained ventricular tachycardia (VT) (11 patients), nonsustained VT (19 patients) or unexplained syncope (11 patients). In 26 patients, VT was not induced by programmed stimulation at twice diastolic threshold. Programmed stimulation at 10 mA induced VT or ventricular fibrillation in 16 of these 26 patients (62%). In 4 of 16 patients, the coupling intervals of the extrastimuli that induced VT/ventricular fibrillation at 10 mA were all equal to or longer than the shortest coupling intervals resulting in ventricular capture at twice diastolic threshold. Fifteen patients had inducible VT at twice diastolic threshold. Programmed stimulation at 10 mA induced a similar VT in 12 of these patients, but resulted in no VT induction in 3 of 15 patients (20%), despite ventricular capture at the same coupling intervals that had induced VT at twice diastolic threshold. This study shows that programmed stimulation at a high current strength may either facilitate or prevent induction of VT. Facilitation of VT induction usually is attributable to a shortening of ventricular refractoriness and the ability of extrastimuli at 10 mA to capture the ventricle at shorter coupling intervals than possible at twice diastolic threshold. However, in 25% of cases, the facilitation of VT induction by 10-mA stimuli is not explained by a shortening of ventricular refractoriness.(ABSTRACT TRUNCATED AT 250 WORDS)

Adult↗

Long term visual deprivation in a human.

D.C. had a congenital monocular cataract removed at 19 years of age. Preoperatively, he was virtually blind in the deprived eye. By 4 months after surgery he could resolve about 1.4 c/deg by acuity did not improve further over the next 7 months. Immediately postoperatively, the temporal retina was blind, but over the next 4 months its visual field increased to 20. The temporal retina continued, however, to have elevated thresholds. D.C. also exhibited a peculiar form of binocular competition. Thresholds of the deprived binocular portions of the nasal retina were greatly elevated by light falling on the non-deprived eye. Visual function in the non-deprived eye was normal.

Adolescent↗

Velocity discrimination in chromatic gratings and beats.

It is commonly assumed that the ability to discriminate velocity in a stimulus directly reflects the properties of the underlying directionally-selective mechanism. The results presented here show that this assumption is not always correct. Speed discrimination tasks over a range of base velocities were carried out for luminance gratings, chromatic gratings and contrast (beat) gratings of equivalent periodicity and contrasts. At low contrasts (0.5 log units above detection threshold), speed discrimination in luminance gratings was at least twice as good (when expressed as a Weber fraction), than in either chromatic gratings or beats. This is similar to the situation seen for tasks of direction discrimination using these stimuli [e.g. Cropper and Derrington (1990) Perception, 19, A31]. When the stimulus contrasts were increased to 1.5 log units above detection threshold, the ability to discriminate speed in both chromatic and beat stimuli improved to a performance level comparable to that shown for luminance gratings at all contrasts. This effect is not seen for tasks of direction discrimination when the same increase in stimulus contrast has little effect on the lower threshold of motion (LTM) measured for beat patterns. These results indicate that the ability to discriminate velocity in a stimulus does not necessarily directly reflect the characteristics of the ability to discriminate the direction of motion of that stimulus.

Color Perception↗

Half sine, monophasic and biphasic transcranial magnetic stimulation of the human motor cortex.

OBJECTIVE: To compare half sine transcranial magnetic stimuli (TMS) with conventional monophasic and biphasic stimuli, measuring resting and active motor threshold, motor evoked potential (MEP) input/output curve, MEP latency, and silent period duration. METHODS: We stimulated the dominant hand representation of the motor cortex in 12 healthy subjects utilising two different MagPro stimulators to generate TMS pulses of distinct monophasic, half sine and biphasic shape with anteriorly or posteriorly directed current flow. RESULTS: The markedly asymmetric monophasic pulse with a posterior current flow in the brain yielded a higher motor threshold, a less steep MEP input/output curve and a longer latency than all other TMS types. Similar but less pronounced results were obtained with a less asymmetric half sine pulses. The biphasic stimuli yielded the lowest motor threshold and a short latency, particularly with the posterior current direction. CONCLUSIONS: The more asymmetric the monophasic pulse, the stronger the difference to biphasic pulses. The 3rd and 4th quarter cycle of the biphasic waveform make it longer than any other waveform studied here and likely contribute to lowering motor threshold, shortening MEP latency and reversing the influence of current direction. SIGNIFICANCE: This systematic comparison of 3 waveforms and two current directions allows a better understanding of the mechanisms of TMS.

Adult↗

Contribution of glutamate receptors to spontaneous and stimulus-evoked discharge in afferent fibers innervating hair cells of the Xenopus lateral line organ.

The relative contributions of NMDA (N-methyl-D-aspartate) and non-NMDA glutamate receptors to spontaneous and stimulus-evoked transmission at the hair cell/afferent fiber synapse were determined in the Xenopus laevis lateral line organ. The non-NMDA receptor antagonist, CNQX (6-cyano-7-nitroquinoxaline-2,3-dione), reversibly reduced both spontaneous and stimulus-evoked discharge rate with an EC(50) of 0.5 microM. NMDA receptor antagonism with the combination of chlorokynurenic acid (100 microM) and elevated magnesium (1.1 mM), or elevated magnesium alone, blocked responses to NMDA without significantly altering spontaneous or stimulus-evoked discharge rate or the responses to kainate. All non-NMDA receptor agonists tested increased discharge rate at low concentrations and, at higher concentrations, increased, then suppressed discharge rate. The EC(50)s were: domoic acid (2.4 mcM)<quisqualic acid (6 mcM)<kainic acid (18 mcM)<AMPA (82 mcM)<<glutamate (1150 mcM). NMDA and ibotenic acid also produced an increase in discharge followed by a suppression, but the suppressive phase of the response predominated and maximum increases in discharge rates were low compared to effects of the non-NMDA agonists. The EC(50)s were: NMDA (148 mcM)<ibotenic acid (463 mcM). The EC(50) for the suppression of afferent discharge that followed the initial excitatory effect was similar to the EC(50) for excitation. Perfusion with active concentrations of kainate, AMPA, or NMDA did not alter the threshold for electrical stimulation of these nerve fibers. We conclude that most of the postsynaptic signal normally seen in afferent fibers is mediated by non-NMDA receptors.

6-Cyano-7-nitroquinoxaline-2,3-dione↗

Outer hair cells functionally and structurally deteriorate during reperfusion.

Transient ischemia of the cochlea was induced in 65 albino guinea pigs by pressing the labyrinthine artery, and the effects of cochlear reperfusion on cochlear potentials (endocochlear potential, compound action potential and cochlear microphonics (CM)) and structural changes in hair cells were examined. Although 15 min ischemia did not elevate the post-ischemic CM pseudo-threshold as compared with the pre-ischemic value, ischemia of 30 min or longer significantly elevated the CM pseudo-threshold. CM amplitude tended to progressively decrease during the reperfusion period in the animals subjected to 45 or 60 min ischemia. After transient ischemia, outer hair cells (OHCs) were swollen and exhibited alterations of the nucleus. Severer structural deterioration of OHCs was induced by 4 h reperfusion than ischemia itself when the ischemic period was 45 or 60 min. Perilymphatic perfusion of dimethylthiourea, a hydroxyl radical scavenger, partially ameliorated the elevation of the CM pseudo-thresholds and the structural changes of OHCs. These results indicate that cochlear reperfusion induces functional and structural deterioration of OHC probably by hydroxyl radical generation.

Action Potentials↗

Deficient passive and one-way active avoidance acquisition following medial forebrain bundle lesions in rats.

Cathodal electrolytic lesions of the medial forebrain bundle (MFB) at posterior hypothalamic levels in male hooded rats produced a mild, transient hypodipsia and lowered jump thresholds to footshock. The lesions produced marked deficits in passive avoidance performance in a paradigm that paired discrete, linearly incrementing footshock intensities with contact of a water spout following 48 hr of water deprivation. Intraperitoneal injections of DL-5-hydroxytryptophan (75 mg/kg), the immediate metabolic precursor of serotonin, had no effect on the passive avoidance performance of either experimental or operated control subjects. Lesions of the MFB also resulted in deficient acquisition in a one-trial step-through passive avoidance paradigm not using motivation to drink and caused a severe acquisition deficit in a one-way active avoidance task. Lesions of the septal nuclei produced lowered jump thresholds but did not affect acquisition in the first passive avoidance task. The results are interpreted as indicating a lesion-induced deficiency in fear learning, independent of the serotonergic functions of the MFB.

5-Hydroxytryptophan↗

C- and Adelta-fibre mediated thermal perception: response to rate of temperature change using method of limits.

Studies investigating the effect of rate of temperature change on thermal thresholds have used a variety of different methods and threshold combinations, and many display incomplete reporting of statistical analyses. It has been suggested that C- and Adelta-fibre mediated thresholds differ in their reaction to different rates of temperature change. Ten healthy female volunteers (aged 18-26 years; mean 21 +/- S.D. 2.53) undertook cold sensation (CS), warm sensation (WS), cold pain (CP) and heat pain (HP) threshold determinations on the thenar eminence of the dominant hand. Rates of temperature change of 0.5, 1, 2.5 and 4 degrees C/s were used, with a modified method of limits. Adaptation temperature was 32 degrees C and thermode size 3 cm x 3 cm. Results showed a significant increase in WS, HP and CP thresholds with increased rates of temperature change (all p < 0.001), but no significant change for CS (p = 0.653). These results suggest that thresholds with a C-fibre component (WS, HP and CP) and those that are Adelta-fibre mediated (CS) behave differently. A traditional explanation of measurement artefact alone is insufficient in rationalizing these results, with additional factors potentially involved. Slow rates of temperature change were shown to reduce mean intra-individual differences in recorded threshold values, and also to abolish ceiling effects with HP threshold determinations. Clinically, therefore, using slow rates of temperature change with method of limits has a range of benefits over and above simply minimizing measurement artefact.

Adaptation, Physiological↗

Desensitization of skate photoreceptors by bleaching and background light.

Through extracellular measurements of photoreceptor responses to flashed stimuli, we examined how the bleaching of rhodopsin affects increment receptor threshold in the isolated retina of the skate (Raja oscellata and R. erinacea). Both initially unbleached and previously bleached photoreceptors, when exposed to full-field luminous backgrounds of fixed intensity, attain approximately stable levels of increment threshold that vary with the intensity of the background light. Values of stabilized increment thresholds measured after various extents of bleaching (less than approximately 50%), when plotted against background intensity in log-log coordinates, tend to converge with increasing intensity of the background; this relationship of the increment threshold functions resembles that which Blakemore and Rushton (1965b) found to describe the transient effect of bleaching on psychophysical increment threshold for the human rod mechanism. Our data are consistent with the possibility that related photochemical processes govern the stabilized levels of receptor sensitivity exhibited by the isolated retina (a) during steady illumination and (b) long after substantial bleaching.

Animals↗

TPD-based evaluation of near threshold mono-energetic proton energies for the (7)Li(p,n)(7)Be production of neutrons for BNCT.

An evaluation of mono-energetic proton energies ranging from 1.885 MeV to 1.920 MeV was carried out to determine the viability of these near threshold energies in producing neutrons for BNCT via the (7)Li(p,n)(7)Be reaction. Neutron fields generated at these proton energies were assessed using the treatable protocol depth (TPD) and the maximum TPD (TPD(max)) as evaluation indices. The heavy charged particle (HCP) dose rate to tumour was likewise applied as a figure of merit in order to account for irradiation time and required proton current. Incident proton energies closer to the reaction threshold generated deeper TPDs compared to higher energy protons when no boron dose enhancers (BDE) were placed in the irradiation field. Introducing a BDE resulted in improved TPDs for high proton energies but their achievable TPD(max) were comparatively lower than that obtained for lower proton energies. In terms of the HCP dose rate to tumour, higher proton energies generated neutron fields that yielded higher dose rates both at TPD(max) and at fixed depths of comparison. This infers that higher currents are required to deliver the prescribed treatment dose to tumours for proton beams with energies closer to the (7)Li(p,n)(7)Be reaction threshold and more achievable proton currents of around 10 mA or less for proton energies from 1.900 MeV and above. The dependence on incident proton energy of the TPD, TPD(max) and the HCP dose rate to tumour with respect to the (10)B concentration in tumour and healthy tissues were also clarified in this study. Increasing the (10)B concentration in tumour while maintaining a constant T/N ratio resulted in deeper TPD(max) where a greater change in TPD(max) was obtained for proton energies closer to the (7)Li(p,n)(7)Be reaction threshold. The HCP dose rates to tumour for all proton energies also went up, with the higher proton energies benefiting more from the increased (10)B concentration.

Beryllium↗