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An automated apparatus is described that permits precise and reliable measurements of visual thresholds in turtles using a conditioned avoidance technique. The entire sequence of stimulus management and the collection of response data are under programmed control.
Saturation discrimination has been reported to be affected early in the course of a disease. Our empirical data show a compressive curvi-linear relationship between opponent/nonopponent channel activity and saturation thresholds in normal trichromatic observers. This relationship can be explained by a model based on the Hurvich and Jameson saturation coefficient (1957), Psychology Reviews, 64, 384-404. The model considers effects of both selective and nonselective channel losses on saturation processing based on the assumption that disease produces elevated thresholds while maintaining normal psychometric response functions. Both the model and data support clinical observations of saturation losses occurring early in disease. However, the results also indicate that saturation may not be the best modality for monitoring long-term progression of such conditions. We suggest that the different processing characteristics for blue-yellow thresholds may yield added information for saturation testing under some circumstances and that saturation processing occurs at a higher cortical level.
Previously, we showed that the neuropeptide galanin hyperpolarizes and decreases membrane excitability of mudpuppy parasympathetic neurons [Konopka L. M., McKeon T. W. and Parsons R. L. (1989) J. Physiol. 410, 107-122]. We also demonstrated that membrane excitability remains depressed when the agonist-induced potential change is negated electrotonically. We hypothesized that galanin inhibits the membrane conductances associated with spike generation. However, we cannot rule out the possibility that the decreased excitability is due to a galanin-induced increase in membrane potassium conductance which reduces the effectiveness of subsequent depolarizing stimuli. Therefore, in the present study we tested, with the galanin-induced hyperpolarization negated, whether the galanin-induced increased membrane potassium conductance was responsible for the decreased excitability. The results showed that the galanin-induced decreased excitability was not dependent on the peak amplitude of the galanin-induced hyperpolarization. Furthermore, the decreased excitability occurred in cells in which there was no measurable galanin-induced hyperpolarization. Moreover, in most cells the galanin-induced decrease in input resistance, measured at the peak of the hyperpolarization (3-25 mV), was less than 15% and when the hyperpolarization was negated electronically, the decrease was even less (approximately 2%). These results indicated that when the hyperpolarization was negated, the galanin-induced increase in potassium conductance was not responsible for the decreased excitability. In preparations pretreated with 5 mM tetraethylammonium, galanin decreased excitability which indicated that a galanin-induced decrease in the calcium-dependent potassium current was not necessary for the decreased excitability. Galanin also decreased excitability in preparations exposed to either 1-3 microM tetrodotoxin or 100-200 microM cadmium. Following galanin application, the threshold for initiation of tetrodotoxin-insensitive spikes was shifted to more positive membrane potentials. Galanin also decreased the amplitude and hyperpolarizing afterpotential of barium spikes in the absence of any agonist-induced hyperpolarization. These observations confirmed that galanin decreased the voltage-dependent calcium conductance. In the present study, we showed that when the hyperpolarization was negated, galanin decreased excitability by shifting the threshold for spike generation regardless of whether voltage-dependent sodium or calcium currents were primarily responsible for the depolarizing component of the action potential.
Spinal interneurons are essential integrators of descending and peripheral input that receive profuse monoaminergic influence from brainstem nuclei. In this study, the effects of the monoamines serotonin and norepinephrine on the intrinsic properties of ventral horn interneurons were investigated in a slice preparation of the lumbar cord of 7-19 day old rats. Three cell groups with distinct firing patterns in response to steps of injected current were observed and classified as repetitive-firing, initial-burst or single-spiking. Input conductance tended to be largest in single-spiking cells whereas repetitive-firing cells showed the greatest tendency for spontaneous firing and had the fastest rate of rise for the action potential. Rhythmic firing behaviors were defined by the frequency-current relation evoked by linearly increasing current ramps. The monoaminergic modulation of firing patterns and frequency-current relations was primarily studied in repetitive-firing cells. The frequency-current threshold current was decreased in cells with high pre-drug values and increased in cells with low pre-drug values. Therefore, monoamine administration decreased the input-output heterogeneity of the repetitive-firing cells by compressing the range of frequency-current threshold currents. This action of monoamines may have a key role in the suppression of sensory-evoked reflexes and the production of coordinated movement.
Quantitative Thermotesting evaluates peripheral small nerve fiber function. The method of limits is a widely used algorithm of perception threshold determination. Normative data are needed to apply the method of limits in children and juveniles. In 225 healthy boys and girls, aged 7 to 17.9 years, warm and cold perception thresholds were established with the method of limits at the volar distal forearm, the thenar eminence, the lower medial calf, the lateral dorsal foot, and the cheek. A 1 degree C/s stimulus velocity, a 32 degrees C thermode baseline, and a 1.5-cm x 2.5-cm Thermotest stimulator were used. Accuracy of stimulus perception was studied by comparing the lowest to the highest response of five consecutive stimuli. The influence of different stimulator sizes on thresholds was tested at the lower calf and distal forearm with an additional 2.5-cm x 5.0-cm thermode. To determine the impact of the pretest skin temperature on thresholds, skin temperature was correlated with thresholds. Results showed good intratrial reproducibility of thresholds. The large thermode yielded lower thresholds than the small probe. Skin temperature had only minor influence on thresholds. The large probe should be used at body sites where it adjusts planely.
This study shows that the loss of contrast sensitivity in the amblyopic eye does not result from abnormal spatial frequency selective channels. Knowledge of the sine-wave sensitivity of the amblyopic eye may allow accurate predictions of the detection threshold for more complex stimuli. More effective amblyopia treatment strategies may be designed when the amblyope's sensitivity to spatial contrast and relative phase are better understood.
It has recently been shown that the probability of successful defibrillation as a function of energy has a sigmoidal dose-response relationship. Determination of a defibrillation "dose-response curve" is time consuming and requires multiple defibrillation attempts. On the other hand, determination of a defibrillation threshold is achieved rapidly and would be better suited to study the effect of interventions on the ability to defibrillate patients. We assessed the relationship of defibrillation threshold to the defibrillation "dose-response curve" in twelve open chest, halothane anesthetized pigs. Ventricular fibrillation was induced electrically, and defibrillation was attempted by passing sequential pulse shocks through an indwelling catheter and plaque electrodes. Defibrillation threshold was determined by decreasing the stored voltage of the initial shock until it failed to defibrillate the heart. Five different stored voltage levels distributed around defibrillation threshold were then randomly administered, six times for each level. A "dose-response curve" was obtained for each animal. Defibrillation threshold superimposed on the "dose-response curve" at 76 +/- 7.2 percent (mean +/- SEM) defibrillation success. Energy delivered at 1.5 times average defibrillation threshold was predicted to achieve 100 percent defibrillation success for a single shock in all animals. We conclude that defibrillation threshold provides a simple and quantitative estimate of the ability to defibrillate with a predictable relationship to the "dose-response curve."
1. The capacity of prostaglandin E2 (PGE2) to enhance the excitatory response elicited by bradykinin in embryonic rat sensory neurones grown in culture was investigated using the whole-cell patch-clamp recording technique. 2. The focal application of bradykinin (BK) produced a small concentration-dependent depolarization that was associated with an inward current and was described by a ligand-binding isotherm having an EC50 of 230 nM. Typically the depolarization was accompanied by action potentials (APs). 3. After pretreatment with 1 microM PGE2 for 10 min, the number of APs elicited by 100 nM BK was increased by about 3-fold. However, PGE2 had no effect on the amplitude of either the BK-elicited depolarization or inward current. The addition of 1 or 10 microM PGE2 had no effect on the resting membrane potential. 4. In all neurones exhibiting PGE2-enhanced excitability, there was a decrease in the amount of injected current necessary to elicit an AP. 5. The enhanced excitability was not due to repeated exposure to BK since neither the amplitude of the BK-evoked depolarization nor the number of APs was altered by the application of BK at 2 min intervals over a period of 30 min. 6. These results are consistent with the notion that PGE2 acts directly on sensory neurones to enhance the response to chemical excitatory agents, like BK, by lowering the AP firing threshold. The PGE2-mediated sensitization does not result from an alteration of the resting potential or modulation of the neuronal response to the chemical agonist.
The initial skin blood flow response to rapid local heating is an axon reflex, which may be mediated by calcitonin gene-related peptide and substance P released from C-fibres. We investigated the role of nitric oxide (NO) and noradrenaline on the temperature threshold for the axon reflex during gradual local heating. 36 subjects participated in two studies. Using microdialysis, we examined the following interventions: NO synthase inhibition (10 mM N(G)-nitro-L-arginine methyl ester, L-NAME); low-dose NO infusion (1.0 microM sodium nitroprusside, SNP); adrenergic blockade (10 mM bretylium tosylate); and low-dose (0.1 microM) noradrenaline infusion. Laser-Doppler flowmetry was used to measure red blood cell flux. Skin was heated at a rate of 0.1 degrees C min(-1) from 33 degrees C to 40 degrees C. Compared to control skin sites, the axon reflex response was shifted to a higher temperature in 4 subjects in the L-NAME sites (control, 37.0 +/- 0.3 degrees C, n = 16; L-NAME, 39.8 +/- 0.1 degrees C, n = 4; P < 0.001) and absent in 12 subjects. The response was also absent in L-NAME plus low-dose SNP sites and not altered by low-dose SNP infusion alone. Adrenergic blockade, with and without low-dose noradrenaline infusion, also abolished the axon reflex response in all subjects. Low-dose noradrenaline infusion alone shifted the axon reflex to a significantly lower temperature threshold compared to control sites (control, 38.2 +/- 0.5 degrees C; noradrenaline, 37.7 +/- 0.4 degrees C, P < 0.05, n = 5). These results suggest that endogenous NO and noradrenaline contribute to the temperature threshold of the axon reflex response during gradual local heating of the skin.
The purpose of this study was to evaluate the ability of touch to discriminate fine-surface textures and to suggest possible mechanisms of the discriminations. Two experiments were performed. In experiment 1, aluminum-oxide abrasive papers were adopted as stimuli, and psychometric functions and difference thresholds were determined in fine-surface-texture discrimination tasks. The grit values of abrasive papers were 400, 600, 1200, 2000, 3000, 4000, and 8000; corresponding average particle sizes were 40, 30, 12, 9, 5, 3, and 1 micron, respectively. Ten subjects participated in experiment 1. The difference thresholds obtained in experiment 1 were between 2.4 and 3.3 microns. In experiment 2, the tasks were discriminations of ridge height. The cross sections of the etched ridges were rectangular and the ridge heights were 6.3, 7.0, 8.6, 10.8, 12.3, 18.5, and 25.0 microns. Six subjects participated in experiment 2. The difference thresholds in experiment 2 were between 0.95 and 2.0 microns. It was reasoned, based on the Weber fraction values calculated from the difference thresholds and on the limit of neural information-processing ability of humans, that the subjects discriminate fine roughness only from the amplitude information presented in surface unevenness.
To clarify mechanisms of hypothermia in lipopolysaccharide (LPS) shock, four experiments were conducted in 72 chronically instrumented Wistar rats. They were intended to accomplish the following: experiment 1, determine the dose of intravenous Escherichia coli LPS that induces a body temperature (Tb) fall at a minimal mortality [the dose chosen (0.5 mg/kg) was then used in experiments 2-4]; experiment 2, identify the time course of the arterial blood pressure (BP) fall (shock) during the response to LPS; experiment 3, measure threshold Tb values for skin vasodilation and activation of metabolic heat production (M) during the LPS shock; and experiment 4, ascertain behavioral thermoregulation in LPS shock. For experiments 1-3, rats were kept in restrainers; ambient temperature (Ta) was 26 degrees C. In experiment 4, rats freely moved in a thermogradient (18-33 degrees C). Variables monitored were colonic (Tc) and tail skin (Tsk) temperatures (experiment 1); BP (experiment 2); hypothalamic temperature (Thy), M (from oxygen consumption), and Tsk (experiment 3); and preferred Ta (Tpr) and abdominal temperature (experiment 4). In experiment 1, LPS induced no Tc changes at 0 mg/kg, a biphasic fever (no mortality) at 0.05 mg/kg, a biphasic hypothermia (42% mortality) at 0.5 mg/kg, and a rapid fall of Tc (100% mortality) at 5 mg/kg. LPS-induced (0.5 mg/kg) hypotension (experiment 2) occurred simultaneously with the first hypothermic phase; both Tc and BP reached their nadirs (-0.8 +/- 0.1 degrees C and -34 +/- 12 mmHg) at approximately 1.5 h post-LPS. The major autonomic mechanism of the shock hypothermia was a shift in the threshold Thy for M from 37.9 +/- 0.3 to 36.0 +/- 0.3 degrees C (experiment 3; P < 0.05). In experiment 4, rats selected Tpr below 25 degrees C (vs. 28-30 degrees C in control; P < 0.05) throughout the duration of the shock; their Tb dropped to 36.2 +/- 0.3 degrees C (P < 0.05). In sum, the LPS shock-associated hypothermia involves a decrease in the threshold Tb for M, the resultant widening of the interthreshold zone, and cold-seeking behavior.
Platelet-leukocyte adhesion may contribute to thrombosis and inflammation. We examined the heterotypic interaction between unactivated neutrophils and either thrombin receptor activating peptide (TRAP)-stimulated platelets or P-selectin-bearing beads (Ps-beads) in suspension. Cone-plate viscometers were used to apply controlled shear rates from 14 to 3000/s. Platelet-neutrophil and bead-neutrophil adhesion analysis was performed using both flow cytometry and high-speed videomicroscopy. We observed that although blocking antibodies against either P-selectin or P-selectin glycoprotein ligand-1 (PSGL-1) alone inhibited platelet-neutrophil adhesion by approximately 60% at 140/s, these reagents completely blocked adhesion at 3000/s. Anti-Mac-1 alone did not alter platelet-neutrophil adhesion rates at any shear rate, though in synergy with selectin antagonists it abrogated cell binding. Unstimulated neutrophils avidly bound Ps-beads and activated platelets in an integrin-independent manner, suggesting that purely selectin-dependent cell adhesion is possible. In support of this, antagonists against P-selectin or PSGL-1 caused dissociation of previously formed platelet-neutrophil and Ps-bead neutrophil aggregates under shear in a variety of experimental systems, including in assays performed with whole blood. In studies where medium viscosity and shear rate were varied, a shear threshold for P-selectin PSGL-1 binding was also noted at shear rates <100/s when Ps-beads collided with isolated neutrophils. Results are discussed in light of biophysical computations that characterize the collision between unequal-size particles in linear shear flow. Overall, our studies reveal an integrin-independent regime for cell adhesion and weak shear threshold for P-selectin PSGL-1 interactions that may be physiologically relevant.
The effects of 2-a-3-arsonopropionate and 2-a-4-arsonobutyrate, the arsono analogues of aspartate and glutamate respectively, on the development of electrically-induced kindling in the amygdala, and on seizures induced in fully kindled rats, were compared to the effects of 3-amino-propylarsonate the arsono analogue of GABA. Intra-amygdaloid micro-injection of 2-a-3-arsonopropionate and 2-a-4-arsonobutyrate (10 nmol in 0.5 microl buffer phosphate) reduced the rate of epileptogenesis without preventing the development of generalized seizure responses, after 14 daily stimulations. In fully electrically kindled animals with stage 5 amygdala-kindled seizures, 3-aminopropy-larsonate (10 nmol/0.5 microl) increased after-discharge threshold (ADT) by 82% (P< or =0.005) without having any effect on mean seizure score or after-discharge duration. Chemical reduction of 3-aminopropylarsonate with glutathione diminished the anti-seizure activity of the drug. 2-a-3-arsonopropionate and 2-a-4-arsonobutyrate the arsono analogues of aspartate and glutamate were not effective when they were micro-injected into the amygdala of fully kindled animals at equivalent doses i.e. (10 nmol/0.5 microl). Higher doses (100 nmol/0.5 microl) of 2-a-3-arsonopropionate the analogue of aspartate increased the generalized seizure threshold by 40% (P < or = 0.025), while 2-a-4-arsonobutyrate was not effective even at high doses.
STUDY DESIGN: In a prospective study of 90 patients undergoing lumbar pedicle screw instrumentation, 512 screws were tested intraoperatively using electrical stimulation. The accuracy of this technique was verified after surgery by computed tomography. OBJECTIVES: Computed tomographic scans taken after surgery were used to evaluate the efficacy of intraoperative screw stimulation and electromyographic monitoring of pedicle screw placement. SUMMARY OF BACKGROUND DATA: Previous cadaveric and clinical studies showed the risk of pedicle screw malposition and the inadequate reliability of intraoperative radiographs to identify misplaced screws. METHODS: Screws (total, 512) in 90 patients were stimulated intraoperatively, and stimulation threshold was recorded. Computed tomographic scans were taken after surgery to document pedicle screw position. Electromyographic thresholds and computed tomographic data were evaluated independently and compared to assess the accuracy of the electromyographic screw stimulation technique. RESULTS: Intraoperative screw stimulation was extremely accurate in confirming the adequacy of screw position. A stimulation threshold greater than 15 mA provided a 98% confidence that the screw was within the pedicle. In eight of 90 patients (9%), electromyographic monitoring detected a screw malposition that was not identified on lateral radiograph. CONCLUSIONS: Screw stimulation monitoring is a valuable and efficacious adjunct to lumbar pedicle screw instrumentation. A stimulation threshold greater than 15 mA reliably indicates adequate screw position. A stimulation threshold between 10 and 15 mA was generally associated with adequate screw position, although exploration of the pedicle is recommended. A stimulation threshold less than 10 mA was associated with a significant cortical perforation in most instances.
The ability to detect changes in respiratory resistance, which may be important in acute and chronic adaptations to airways obstruction, has not been measured previously in children. Two methods were used to measure the resistive-load detection thresholds (the added resistance that produced a "just noticeable difference" in perception) in a group of 38 healthy children and adolescents aged 7-16 years. Total respiratory system resistance (Rrs), as measured by forced oscillation, was used as an index of each child's intrinsic baseline (pre-test) resistance. To determine thresholds a computer program added various percentages of baseline resistance according to response (first method) and then in random order (second method). Thresholds by at least one of the two methods were detectable in 32 of the children (84%), and failure to detect a threshold was less common in older than in young children. Thresholds obtained by each method were significantly related to one another (r = 0.54, P < 0.05). Baseline resistance accounted for a marginally significant proportion of the variation in thresholds as assessed by the tracking method (R2 = 0.12, P < 0.10) and a large proportion of the variation in thresholds as assessed by the random method (R2 = 0.66, P < 0.0001). Thresholds expressed in terms of percent of baseline resistance were found to have mean values of 100.4-105.0%, regardless of gender or age. Results from a comparison group of adults (n = 10) indicated lower threshold by both procedures (mean values, 71.90-76.50%). We conclude that perceptual thresholds for added resistive loads are determined, in part, by growth-related changes in intrinsic resistance.
Twenty-eight right-handed, young adults participated in a sensory testing experiment to evaluate spatial resolution at 10 positionally matched sites on the right- and left-hand sides of the face. An adaptive psychophysical (i.e. tracking) procedure was used to estimate the threshold spatial separation for perceiving two points of contact at each site. Estimates of the threshold at one site on both sides of the face were also obtained with a method-of-limits procedure similar to that employed for clinical evaluation of patients. In addition, each individual was asked to rate (i) his(her) overall facial sensitivity to touch and (ii) the degree to which he(she) could discern subtle changes in lip, cheek and chin position during speech, chewing and facial expression. Analysis of the estimates of the threshold separation obtained with the tracking procedure revealed a significant effect of gender (p < 0.04) and of site (p < 0.001). Females were more spatially sensitive than males: average threshold separations were 1.55 mm less. Most notably, the threshold increased ninefold with distance posterolaterally from the oral opening. The vermilion of the upper lip was the most spatially sensitive site (population geometric mean = 2.4 mm) and the preauricular skin the least spatially sensitive site (20.9 mm). Significant effects of side and of interactions among gender, side and site were not observed. The estimates obtained with the method-of-limits procedure were very similar to those obtained with the tracking procedure: the latter were 0.67 mm less on the average. Individuals' ratings of overall facial sensitivity to touch were similar for males and females (p > 0.70). Females, however, reported greater ability to discern subtle changes in lip, cheek and chin position than males (p < 0.03). The ratings of this sensory function correlated negatively with the estimates of the threshold separation on the vermilion of the upper lip (p < 0.03).
Psychophysical area-intensity functions of individual 10-week-old human infants and adults were obtained in the dark adapted state, and in the presence of a steady background that elevated threshold 1 log unit above the dark adapted level. For dark adapted infants, the mean diameter for complete spatial summation (4.42 degrees; SD: 1.67 degrees) was significantly larger than that of adults (2.32 degrees; SD: 0.09 degrees). The background reduced the mean critical diameter to 2.67 degrees for infants (SD: 0.64 degrees) and to 1.16 degrees for adults (SD: 0.08 degrees). Spatial probability summation has similar effects on infant and adult thresholds, and, therefore, does not appear to account for the developmental decrease in critical diameters. Rather, decreases in receptive field size are suspected.
Frequency-following responses (FFRs) to a low-frequency stimulus in 16 normal-hearing human subjects were cross-correlated with the stimulus in an attempt to yield more easily recognizable FFRs at lower intensity levels and increase threshold sensitivity. Cross-correlation of these responses with the stimulus did not improve threshold sensitivity and latencies obtained from the cross-correlated FFRs showed more variability and were uniformly shorter than those of standard FFR measurement.