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Absolute and relative sensitivity of the scotopic system of rat: electroretinography and behavior.

The goal of the present study was to relate the dark and light-adapted flash sensitivity of the scotopic threshold response (STR) and rod b-wave of the electroretinogram (ERG) to behaviorally measured rod increment threshold responses. Small amplitudes of the dark-adapted STR and b-wave, the latter after application of NMDA, were found to increase in proportion to flash intensity. The value obtained for the sensitivity of the b-wave would be expected if signals from rods were summed linearly by the rod bipolar cell. The sensitivity of the STR could not be accounted for in terms of rod signal convergence as the source of this ERG component is still unknown. Increment threshold responses of rats were measured behaviorally in an operant conditioning chamber. At absolute threshold, on average I in 2400 rods were activated by the test flash. Comparison of the adaptive effects of background lights on behaviorally measured scotopic sensitivity and rod ERG sensitivity suggest that the increment threshold sensitivity of rat is regulated at three different sites in the retina.

Adaptation, Ocular↗

The parahippocampal cortices and kindling.

The piriform and perirhinal cortices are parahippocampal structures with strong connections to limbic structures, including the amygdala and hippocampus, as well as other parahippocampal structures such as the entorhinal cortex. In this paper, we present results, based on anatomical, physiological, and kindling studies, that suggest that the perirhinal and piriform cortices might be very important in the secondary generalization of limbic seizures, particularly those with convulsive expression. These kindling data further suggest that the progressive lowering of afterdischarge thresholds in the parahippocampal structures, due to insult and/or genetic predisposition, might provide the neural basis for the clinical presentation of temporal lobe epilepsy.

Animals↗

Metabotropic glutamate receptor-mediated suppression of L-type calcium current in acutely isolated neocortical neurons.

1. The effects of metabotropic glutamate receptor (mGluR) stimulation on whole-cell Ca2+ currents were studied in pyramidal neurons isolated from the dorsal frontoparietal neocortex of rat. The selective mGluR agonist cis-(+/-)-1-aminocyclopentane-1,3-dicarboxylic acid [trans-ACPD (100 microM)] suppressed the peak high-threshold Ca2+ current by 21 +/- 1.7% (mean +/- SE) in 40 of 43 cells from 10- to 21-day-old rats. Consistent with previous findings for mGluR, glutamate, quisqualate, and ibotenate [but not alpha-amino-3-hydroxy-5-methyl-4-isoxazolepropionic acid (AMPA)] reduced the Ca2+ currents, and the responses were not blocked by the ionotropic glutamate receptor antagonists 6-cyano-7-nitro-quinoxaline-2,3-dione (CNQX) and DL-2-amino-5-phosphonovaleric acid (APV). EC50S for Ca2+ current suppression were 29 nM for quisqualate, 2.3 microM for glutamate, and 13 microM for trans-ACPD. 2. The low-threshold Ca2+ current was not modulated by trans-ACPD. The component of the high-threshold CA2+ current suppressed by mGluR was determined by pharmacology; the responses were not affected by omega-conotoxin GVIA but were occluded by the dihydropyridine Ca2+ antagonist nifedipine. Ca2+ tail currents prolonged by the dihydropyridine Ca2+ agonist (+)-SDZ 202-79] were suppressed by mGluR stimulation in parallel with the peak current. These findings strongly suggest that L-type Ca2+ channels are modulated by mGluR. 3. In neurons dialyzed with 100 microM guanosine 5'-(gamma-thio)triphosphate (GTP-gamma-S), Ca2+ current suppression was elicited by the first application of trans-ACPD (in 5 of 6 cells), but not by subsequent applications. Responses in neurons dialyzed with 2 mM guanosine 5'-(beta-thio)diphosphate (GDP-beta-S) were significantly smaller than controls. The results are consistent with mGluR acting via linkage to a G protein. 4. The responses to mGluR agonists were smaller when the external Ca2+ was replaced by Ba2+, indicating that some part of the mechanism underlying the current suppression is Ca2+ dependent. Because mGluR stimulates phosphoinositide turnover and release of Ca2+ from intracellular stores in other types of neurons, the possibility of released Ca2+ mediating inactivation of Ca2+ channels was considered. However, the Ca2+ current suppression was not attenuated by strong intracellular Ca2+ buffering [20 mM bis-(o-aminophenoxy)-N,N,N',N'-tetraacetic acid (BAPTA)], by dialysis with 100 microM inositol-1,4,5-triphosphate (IP3), or by external application of 1 microM thapsigargin. 5. We conclude that in neocortical neurons, one action of mGluR is to suppress the component of high-threshold Ca2+ current conducted by L-type Ca2+ channels.(ABSTRACT TRUNCATED AT 400 WORDS)

Animals↗

The human atrial strength-interval relation. Influence of cycle length and procainamide.

We defined the atrial strength-interval relation in 23 patients at cycle lengths of 600, 450, and 300 msec before and after procainamide. The atrial diastolic threshold was similar at cycle lengths of 600 and 450 msec, but the threshold at 300 msec was significantly higher than that determined at 600 and 450 msec both before and after procainamide. Procainamide significantly increased the diastolic threshold only at a cycle length of 300 msec. The strength-interval relation was nonlinear, showing progressively decreasing decrements in the measured refractory period as the stimulating current was increased. Progressive decreases in the drive cycle length from 600 to 450 to 300 msec caused similar decreases in refractory periods. The shape of the curves was similar at cycle lengths of 600 and 450 msex. However, at low current strengths, the slope of the curve determined at 300 msex was significantly more vertical than the slopes of the curves at the longer drive cycle lengths. Procainamide caused similar increases in apparent refractory periods at each paced cycle length. Procainamide did not alter the shape of the curves at any paced cycle length. These observations confirm the importance of stimulation frequency on atrial excitability. They suggest that the effects of procainamide on the effective refractory period of the atrium are not cycle length dependent, although the drug effects on threshold are dependent on the drive cycle length.

Adult↗

Laryngeal brainstem evoked response: a developmental study.

A developmentally receding laryngeal chemoreflex (LCR) has been described in infant animals of several species characterized by vocal cord adduction in response to laryngeal stimulation as well as a potentially fatal cardio-respiratory response. Age-related differences in the brainstem respiratory centers may account for differences in the LCR and play a role in such disorders as Sudden Infant Death Syndrome (SIDS) and infant apnea. Study of the LCR at the brainstem level could provide insights into normal maturation of respiratory centers and eventually the pathophysiology of these disorders. The present study evaluated the laryngeal brainstem response (LBR) evoked by electrical stimulation of the superior laryngeal nerve in kittens using a far-field technique similar to auditory brainstem response testing. Recordings were obtained via posterior pharyngeal and posterior cervical recording sites and compared to results previously obtained in our laboratory for adult cats. The LBR in kittens demonstrated differences in threshold, latencies, and morphology which suggests that postnatal maturation of laryngeal function at the brainstem level does occur.

Aging↗

Diurnal pattern of luminance discrimination in humans.

The visual discrimination threshold can be considered as an image of the resolution power of the visual system. Measured with a psychophysical method, it shows a diurnal pattern with a low threshold in the morning, i.e., high sensitivity and an increase in the afternoon that persists until the early evening.

Adult↗

Relation of transliminality and vividness of visual imagery.

Responses of 50 psychology undergraduates to scores on a measure of transliminality (psychological material crossing thresholds into and out of consciousness) and on a measure of vividness of visual imagery were correlated. 11. The value is positive but clearly not significant.

Adolescent↗

[Measurement of physical strength and rheumatoid arthritis patients' kinesitherapy].

It is difficult to examine the physical strength of patients with rheumatoid arthritis (RA). The graded exercise testing by bicycle ergometer was used for RA patients. The following factors were measured: 1) lactic acid in blood, 2) heart rate, 3) blood pressure and 4) expired gas analysis. Generally speaking, the index of physical strength of healthy human beings is attributed to the maximum oxygen consumption, aerobic threshold or anaerobic threshold. Although none of the nine patients' maximum oxygen consumption was able to be measured, three patients' anaerobic threshold and seven patients' aerobic threshold were measured. In this series the results suggested that aerobic threshold was useful as an index for physical strength. Three of the nine patients were treated by kinesitherapy at the aerobic threshold work load using a bicycle ergometer. The effect of kinesitherapy is discussed.

Adult↗

Analysis of "integrate-to-threshold" neural coding schemes.

Methods of analysis for some deterministic and stochastic variants of the integrate-to-threshold neural coding scheme are presented. Adaptation phenomena are modeled by means of feedforward and feedback adaptive threshold control. Simulations of sinusoidal and step responses reproduce satisfactorily the qualitative characteristics of adaptation as compared with physiological data. It is postulated that such adaptive threshold control may be accomplished by the release, or conformation change, of molecules involved in the control of excitable-channel dynamics.

Action Potentials↗

Effect of training on the rating of perceived exertion at the ventilatory threshold.

The purpose of this study was to determine the effect of training on the rating of perceived exertion (RPE) at the ventilatory threshold. College students were assigned to either training (n = 17) or control (n = 10) groups. Trainers completed 18 interval training sessions (five X 5 min cycling at 90-100% VO2max) and 8 continuous training sessions (40 min running or cycling) in 6 weeks. Pre- and post-training, cardiorespiratory, metabolic, and perceptual variables were measured at the ventilatory threshold during graded exercise tests on a cycle ergometer. Ventilatory threshold was that point above which VE X VO2-1 increased abruptly relative to work rate. Post-training means of trained and control subjects were compared using analysis of covariance, with pre-training values as covariates. Following training, the adjusted means for the trained subjects were significantly greater (p less than 0.05) than for controls for VO2max (6%), and for work rate (20%), VO2 (23%), and %VO2max (13%) at the ventilatory threshold. However, adjusted means for RPE at the ventilatory threshold were not significantly different (2%). Both before and after training, exercise at the ventilatory threshold was perceived as 'somewhat hard' to 'hard' (RPE = 13-15) by both groups. The relationship between RPE and %VO2max was altered by training, with trained subjects having a lower RPE at a given %VO2max. It is concluded that RPE at the ventilatory threshold is not affected by training, despite that after training the ventilatory threshold occurs at a higher work rate and is associated with higher absolute and relative metabolic and cardiorespiratory demands.

Adult↗

Recommendations for thresholds for cortical bone geometry and density measurement by peripheral quantitative computed tomography.

Peripheral quantitative computed tomography (pQCT) is widely used for clinical and research purposes. For accurate determination of bone geometry (bone cross-sectional area, cortical thickness, and cortical area), volumetric bone mineral density (vBMD) and cortical bone mineral content (BMC), it is important to select the appropriate thresholds. A Stratec XCT-2000 scanner was used to compare current standard practice with new optimized thresholds. Currently, a single threshold of 710 mg/mL for the measurement of cortical vBMD and geometry is used. We hypothesised that this threshold may not be optimal and used the European Forearm Phantom (EFP) and patient data to test more appropriate thresholds. A single slice (1.2 mm width, 0.4 mm pixel size) was made at section 4 of the EFP (representing the diaphyseal portion of a long bone). The EFP has a known cortical thickness of 2.5 mm and, therefore, the correct threshold for geometry would be that which measures cortical thickness as 2.5 mm. Thresholds were altered at approximately the 50% value between soft tissue (60 mg/mL) and peak density (879 mg/mL), and cortical thickness versus threshold was plotted; the correct threshold for geometry was 460 mg/mL. By expressing this threshold as a percentage of the range of density values in the EFP ([460-60]/[879-60] = 49%) and then applying this percentage to in vivo data, the optimum threshold for geometry can be determined: ([1240-79] x 0.49) + 79 = 648 mg/mL. For cortical vBMD of in vivo bone measurements at the midshaft site of the radius, thresholds were varied around the peak value (1240 mg/mL), and the threshold was set to that which gave a cortical density of 1240 mg/mL; the threshold for cortical density was, therefore, 1200 mg/mL. A subset of radius scans from a population of young healthy females was analyzed using the new thresholds (648 mg/mL for bone geometry, 1200 mg/mL for cortical vBMD) versus the current threshold (710 mg/mL). For bone geometry, the mean difference between the analysis based on the new threshold and that based on the manufacturer-recommended threshold ranged between 2.1% and 14% (total area = 2.1%, cortical thickness = 14%, cortical area = 3.7%). Although there was a 10% difference between the analysis based on the new threshold and that based on the manufacturer-recommended threshold, this difference was not systematic. Thresholds will significantly affect results obtained from pQCT. The current threshold of 710 mg/mL is inadequate for accurate determination of bone geometry and cortical vBMD. New thresholds of 648 mg/mL for geometry and 1,200 mg/mL for cortical vBMD should be used.

Absorptiometry, Photon↗

Effects of carbamazepine, clonazepam, and phenytoin on seizure threshold in amygdala and cortex.

This experiment was designed to determine whether or not the stronger effect of anticonvulsants on cortex than on amygdala focal seizures was due to a greater elevation of cortex seizure threshold. The effects of several doses of carbamazepine, clonazepam, and phenytoin were examined on the threshold for electrically induced afterdischarge in amygdala and cortex in 71 rats. All three drugs were found to be effective in increasing the seizure threshold with greater effects being produced in the cortex than in the amygdala. Carbamazepine produced the largest threshold increase in both foci, and clonazepam produced the weakest effects. These data are comparable to previous data on drug action against focal or partial seizures, and suggest that anticonvulsants may control partial attacks through their action on the local seizure threshold. This theory of anticonvulsant drug action adds to the common belief that carbamazepine and phenytoin act primarily by blocking seizure spread.

Amygdala↗

Speed discrimination of distal stimuli during smooth pursuit eye motion.

We evaluated the hypothesis that smooth pursuit eye movements affect speed discrimination thresholds of distal stimuli because they alter the retinal image speed. Subjects judged speed differences of sine-wave gratings while they simultaneously pursued a superimposed moving bar. Speed discrimination thresholds were measured, under conditions of controlled eye movements, for grating speeds of 0.5 and 2.0 deg/sec across a range of eye velocities. Thresholds were stimulated using a Monte Carlo method based on the retinal speed hypothesis, and the simulation predictions were compared to the psychophysically determined thresholds. The simulation results provided a good match to the psychophysical data for conditions where the eye moved at a slower speed than the grating, regardless of whether the eye moved in the same or opposite direction. However, when the eye moved at a faster speed than the grating in the same direction, the psychophysical thresholds were significantly higher than predicted by the simulation. Control experiments and analyses rule out explanations based on relative motion cues, saccadic involvement, and attentional demands.

Differential Threshold↗

An intermittent, controlled-rate, slow progressive degeneration model of Parkinson's disease: antiparkinson effects of Sinemet and protective effects of methylphenidate.

The causes of nigrostriatal neuron degeneration in Parkinson's disease (PD) are not known, but it has been suggested that exogenous or endogenous factors or neurotoxins may play a role. The degree of vulnerability to neurotoxins or other potential mediators of nigral dopamine cell death is thought to be important in understanding Parkinson's disease. In most animal models, the rate of terminal degeneration and corresponding functional impairment is too rapid to investigate effectively either cell vulnerability or the potential benefits of some neuroprotective treatments. In the present study, a new model of Parkinson's disease is described that might help in addressing the issue of nigral cell vulnerability and to evaluate interventions with clinical potential. 6-Hydroxydopamine (6-OHDA) was infused in escalating, intrastriatal doses over several weeks. Control animals received multiple infusions of vehicle at the same volume. Behavioral testing was carried out between each infusion, including forelimb-use and somatosensory function. A symptomatic threshold was established for each animal, indicating the amount of neurotoxin required to induce a stable deficit. Oral administration of L-DOPA (Sinemet) ameliorated limb-use asymmetries acutely. An immunocytochemical assay for tyrosine hydroxylase, a dopamine cell marker, revealed a partial loss of immunoreactive cells in the substantia nigra. Animals that were co-administered methylphenidate (MPH), a dopamine transport inhibitor, along with the 6-OHDA were spared from the behavioral and neurochemical effects of 6-OHDA, despite receiving more than twice as much neurotoxin as controls. These data suggest that establishing a symptomatic threshold preclinically may help researchers evaluate potential treatments and model individual and group resistance to nigrostriatal insults.

Animals↗

Cutaneous responsiveness of rat single motor units activated by natural stimulation.

Recordings of withdrawal reflexes have been used extensively to study sensory-motor integration and processing of nociceptive information in the spinal cord. We describe here a new technique for the manufacture of improved EMG electrodes that permit the characterisation of the physiological properties of single motor units as well as the easy location of the muscles studied. Individual motor units from three rat hind-limb muscles: peroneus longus, tibialis cranialis and extensor digitorum longus, were activated by thermal and mechanical stimulation applied to their cutaneous receptive fields, which were located mainly on the 4th and 5th toes. Thresholds for thermal and mechanical (Von Frey hairs) stimulation were similar in the three muscles studied, with a value of 44 +/- 1 degrees C and 100 mN (median), respectively. However, when a mechanical pincher with a stimulus area of 14 mm2 was used, the values seen were similar for peroneus longus and tibialis cranialis (342 +/- 23 and 330 +/- 71 mN, respectively, mean +/- S.E.M.) but lower for extensor digitorum longus (220 +/- 37 mN, mean +/- S.E.M.). The firing rate of the single motor units was similar for all types of stimulation at threshold intensity, and showed a linear relationship with stimulus intensity, except for units of the tibialis cranialis, which showed a greater degree of adaptation.

Adaptation, Physiological↗

The wavelength of light causing photophobia in migraine and tension-type headache between attacks.

OBJECTIVE: To ascertain the wavelength of light that patients with migraine and tension-type headache find uncomfortable between attacks. BACKGROUND: Photophobia is an abnormal perceptual sensitivity to light experienced by most patients with headache during and, also, between attacks. METHODS: We examined the discomfort threshold to light of low, medium, and high wavelengths in a group of patients with migraine (n=21), patients with tension-type headache (n=19), and healthy controls (n=21). RESULTS: The results indicate that the migraine group had significantly lower discomfort thresholds at the low (P=.001) and high (P=.031) wavelengths compared with both the tension-type headache and control groups; the latter two groups had similar average discomfort levels at these two wavelengths. With the medium wavelength, the control group had significantly higher discomfort thresholds than the migraine (P=.002) and tension-type headache (P=.031) groups; the latter two groups had similar discomfort levels at this wavelength. With unfiltered (white) light, the migraine group had the lowest discomfort threshold and the control group the highest (P=.026), whereas the tension-type headache group had an intermediate discomfort threshold. CONCLUSIONS: There were significant differences between migraineurs, patients with tension-type headache, and healthy controls in the wavelengths that are uncomfortable between attacks.

Adult↗

The relationship between stereoacuity and stereomotion thresholds.

There are in principle at least two binocular sources of information that could be used to determine the motion of an object towards or away from an observer; such motion produces changes in binocular disparities over time and also generates different image velocities in the two eyes. It has been argued in the past that stereomotion is detected by a mechanism that is independent of that which detects static disparities. More recently this conclusion has been questioned. If stereomotion detection in fact depends upon detecting disparities, there should be a clear correlation between static stereo-detection thresholds and stereomotion thresholds. If the systems are separate, there need be no such correlation. Four types of threshold measurement were performed by means of random-dot stereograms: (1) static stereo detection/discrimination; (2) stereomotion detection in random-dot stereograms (temporally uncorrelated); (3) stereomotion detection in temporally correlated random-dot stereograms; and (4) binocular detection of frontoparallel motion. Three normal subjects and five subjects with unusually high stereoacuities were studied. In addition, two manipulations were performed that altered stereomotion thresholds: changes in mean disparity, and image defocus produced by positive spectacle lenses. Across subjects and conditions, stereomotion thresholds were well correlated with stereo-discrimination thresholds. Stereomotion was poorly correlated with binocular frontoparallel-motion thresholds. These results suggest that stereomotion is detected by means of registering changes in the output of the same disparity detectors that are used to detect static disparities.

Cues↗

The relationship of facial two-point discrimination to applied force under clinical test conditions.

When an interside comparison is hampered, for example, in cases of bilateral trauma, normal threshold values of two-point discrimination from healthy subjects might be used to delineate abnormal from normal sensory function in patients. To determine threshold pin distances, two devices, the Disk-Criminator and the Aesthesiometer, have often been applied in a clinical setting. Because these devices are hand-operated, the force of applying a device might vary considerably. The general applicability of normal threshold values from the literature may therefore be questioned. Five subjects participated in experiments with two observers, in which a hand-operated device with a constant pin distance (5 or 10 mm) was pushed on a facial site, until the point at which blanching of the skin started, and the applied force was recorded. To that end, the devices were modified by providing them with force transducers. These recordings revealed a considerable variation in force variables (level, duration, and rate). Significant differences in mean force level, duration, and rate occurred, particularly between devices, pin distances, and/or sites (cheek, upper and lower lips, and mental region) and also in mean duration between observers (p < 0.01 to 0.001, analysis of variance). However, the observed force levels were always at an extremely supra-threshold stimulus intensity. The threshold pin distances in subsequent experiments (four subjects, the two devices and two sites: cheek and mental region) were therefore almost invariant to the difference in the extreme low and high force levels that were applied, using acoustic feedback on the force signal. Furthermore, these thresholds were also similar when one or two observers performed repeated measures on groups of 15 to 18 subjects under the influence of a usual variation of force level, using an interval of at least 1 week and both nonmodified devices. Because of invariance, normal values of threshold pin distance are generally applicable to any well-trained observer and are related to the density of afferent nerve fibers. In contrast, recently reported force thresholds determined at a constant pin distance might not be related to fiber density only. The findings regarding dependency on site and pin distance of the force level suggest that force thresholds will also be related to tissue stiffness and to the extent to which a pair of pins co-operate mechanically.

Adult↗