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PubMed2006

Statistics of subthreshold neuronal voltage fluctuations due to conductance-based synaptic shot noise.

Neurons in the central nervous system, and in the cortex in particular, are subject to a barrage of pulses from their presynaptic populations. These synaptic pulses are mediated by conductance changes and therefore lead to increases or decreases of the neuronal membrane potential with amplitudes that are dependent on the voltage: synaptic noise is multiplicative. The statistics of the membrane potential are of experimental interest because the measurement of a single subthreshold voltage can be used to probe the activity occurring across the presynaptic population. Though the interpulse interval is not always significantly smaller than the characteristic decay time of the pulses, and so the fluctuations have the nature of shot noise, the majority of results available in the literature have been calculated in the diffusion limit, which is valid for high-rate pulses. Here the effects that multiplicative conductance noise and shot noise have on the voltage fluctuations are examined. It is shown that both these aspects of synaptic drive sculpt high-order features of the subthreshold voltage distribution, such as the skew. It is further shown that the diffusion approximation can only capture the effects arising from the multiplicative conductance noise, predicting a negative voltage skew for excitatory drive. Exact results for the full dynamics are derived from a master-equation approach, predicting positively skewed distributions with long tails in voltage ranges typical for action potential generation. It is argued that, although the skew is a high-order feature of subthreshold voltage distributions, the increased probability of reaching firing threshold suggests a potential role for shot noise in shaping the neuronal transfer function.

Action Potentials↗
PubMed1975

Taste thresholds for salt in fasting patients.

Since it has been controversial whether in man changes in taste sensitivity for salt occur in relation to changes in extracellular volume, as has been described in animals, we assessed saline acuity in human volunteers undergoing a predictable pattern of external sodium balance. Our results demonstrate that taste thresholds for salt did not vary despite oppositely directed changes in renal sodium excretion and sodium balance.

Animals↗
PubMed1982

Contrast thresholds of diabetic patients determined by VECP and psychophysical measurements.

VECPs to checkerboard pattern reversal (12 Hz reversal) at different contrast levels were measured in normal subjects and in patients suffering from diabetes mellitus, with visual acuities above 0.8. VECP contrast threshold was obtained by extrapolating VECP amplitude vs contrast on a log scale to zero microV. Results were compared with psychophysical thresholds. It was shown that both VECP and psychophysical contrast thresholds were significantly higher in the diabetic patients than in the normal subjects.

Adolescent↗
PubMed1990

Reversibility of baroreceptor hyposensitivity during reversal of hypertension.

The extent and characteristics of reversal of baroreceptor resetting after pressure normalization were studied in rats with renal hypertension of 2 months' duration. During the control period, the displacement of the entire baroreceptor function curve was accompanied by a decrease slope, indicating that the gain sensitivity was depressed by 36% in the renal hypertensive rats. In response to changes of +10 and -10 mm Hg in the control pressure, the gain sensitivity was attenuated by 56% and 42%, respectively. Two minutes after unclipping and bleeding when necessary, mean arterial pressure decreased from 171 +/- 11 to 134 +/- 11 mm Hg and remained at approximately the same level for the 2-hour period of observation. The extent of reversal of the mean pressure threshold for activation of the baroreceptors was approximately constant (approximately 60%) in the time range of 2-120 minutes. The extent of reversal was slightly higher when the changes in systolic pressure threshold divided by the total change in control diastolic pressure were calculated (maximal of 83%). During the first 20 minutes, the displacements of the curves were parallel with no change in the depressed gain sensitivity. Complete normalization of gain sensitivity was observed after 90-120 minutes. The data indicate that, within the first 2 hours of pressure normalization of chronic renal hypertensive rats, 1) reversal of the resetting of pressure threshold is pronounced (60-80%) but still incomplete and 2) gain sensitivity returns completely to normal.

Animals↗
PubMed2003

Permitted and forbidden sets in symmetric threshold-linear networks.

The richness and complexity of recurrent cortical circuits is an inexhaustible source of inspiration for thinking about high-level biological computation. In past theoretical studies, constraints on the synaptic connection patterns of threshold-linear networks were found that guaranteed bounded network dynamics, convergence to attractive fixed points, and multistability, all fundamental aspects of cortical information processing. However, these conditions were only sufficient, and it remained unclear which were the minimal (necessary) conditions for convergence and multistability. We show that symmetric threshold-linear networks converge to a set of attractive fixed points if and only if the network matrix is copositive. Furthermore, the set of attractive fixed points is nonconnected (the network is multiattractive) if and only if the network matrix is not positive semidefinite. There are permitted sets of neurons that can be coactive at a stable steady state and forbidden sets that cannot. Permitted sets are clustered in the sense that subsets of permitted sets are permitted and supersets of forbidden sets are forbidden. By viewing permitted sets as memories stored in the synaptic connections, we provide a formulation of long-term memory that is more general than the traditional perspective of fixed-point attractor networks. There is a close correspondence between threshold-linear networks and networks defined by the generalized Lotka-Volterra equations.

Animals↗
PubMed1975

Behavioral assessment of peripheral nerve function.

Behavioral psychophysical techniques were used to obtain strength-duration curves for the ulnar nerve at both threshold and suprathreshold levels. The functions well match those obtained with electrophysiologic procedures, but overcome many of the difficulities associated with traditional electrodiagnosis. An alternate means of presenting the data provides a parameter, the critical duration, that describes the ability of the stimulated nerve to integrate or summate energy over time. The very brief criticial duration for normal ulnar nerve and the similar functions at threshold and suprathreshold levels suggest possible mechanisms for the transduction and coding of percutaneous electrical stimuli.

Acoustic Stimulation↗
PubMed1992

The effect of selective beta 1-blockade on glucose thresholds for release of counterregulatory hormones and symptoms in insulin-dependent diabetes mellitus.

To evaluate the effect of beta 1-blockade (metoprolol) on the plasma glucose thresholds initiating counterregulatory hormone responses and symptoms of hypoglycemia, we used a modified glucose clamp technique to produce a standardized gradual glucose decline from 5.0 to 2.0 mmol/l in nine patients with insulin-dependent diabetes mellitus (IDDM) (HbAlc range 6.7-10.3%, duration of diabetes 5-18 years, autonomous neuropathy present in three of the patients). The responses were studied once with metoprolol and once with placebo, in random order. With the beta 1-selective blockade, epinephrine release was triggered at a significantly higher (p less than 0.02) plasma glucose level (3.5 mmol/l) than it was with placebo (3.0 mmol/l). Metoprolol did not change thresholds for growth hormone (3.7/3.5 mmol/l), cortisol (2.9/2.9 mmol/l), glucagon (2.8/2.8 mmol/l) or for pancreatic polypeptide (2.8/2.7 mmol/l). The peak responses of epinephrine and growth hormone were significantly higher (p less than 0.01) with the beta 1-blockade. Metoprolol did not change the thresholds for neuroglycopenic and autonomic symptoms. Six out of the seven patients who answered yes to having hypoglycemia did so at a higher blood glucose with metoprolol than without. In our study, the beta 1-selective blockade altered the responses of counterregulatory hormones, but it did not change the thresholds for hypoglycemic symptoms.

Adrenergic beta-Antagonists↗
PubMed2004

Threshold estimation in two-alternative forced-choice (2AFC) tasks: the Spearman-Kärber method.

The Spearman-Kärber method can be used to estimate the threshold value or difference limen in two-alternative forced-choice tasks. This method yields a simple estimator for the difference limen and its standard error, so that both can be calculated with a pocket calculator. In contrast to previous estimators, the present approach does not require any assumptions about the shape of the true underlying psychometric function. The performance of this new nonparametric estimator is compared with the standard technique of probit analysis. The Spearman-Kärber method appears to be a valuable addition to the toolbox of psychophysical methods, because it is most accurate for estimating the mean (i.e., absolute and difference thresholds) and dispersion of the psychometric function, although it is not optimal for estimating percentile-based parameters of this function.

Choice Behavior↗
PubMed1992

[Cutaneous thermal-cooling and -warming detection thresholds in distal extremities of normal subjects].

The cutaneous thermal-cooling and -warming detection thresholds were evaluated on the dorsal side of the right distal forearm and on the dorsum of the right foot in 134 normal subjects (66 men and 68 women) without sensory symptoms and signs, aged from 11 to 87 years by using a Thermal Threshold Tester (Vickers Medical International, England). The normative data for the clinical evaluation of the severity and the pathologic process of the sensory disturbance of the patients were obtained. The data obtained included 1) the mean of each threshold and 2) its upper limit value of 95% confidence interval for each decade. The mean of each threshold was significantly increased with aging (P less than 0.0001). Therefore, the cutaneous thermal-cooling and -warming detection thresholds of the patients with sensory disturbances should be compared with the normative data adjusted for the age of each subject obtained in this study. Based on the evaluation, repeated six times for three weeks, of each threshold of six volunteers (ages from 21 to 66), high reliability of each threshold (intraclass correlation coefficient from 0.78 to 0.96) was observed.

Adolescent↗
PubMed1999

Arousal threshold to respiratory stimuli in OSA patients: evidence for a sleep-dependent temporal rhythm.

It has recently been described that the maximal respiratory effort developed at the end of an apnea (Pesmax)--which is regarded as an index of arousal threshold in patients with obstructive sleep apnea syndrome (OSA)--increases progressively during the night, probably as a consequence of associated sleep fragmentation. In order to find out whether the nocturnal trend of Pesmax may be more influenced by a sleep-dependent circadian rhythm than by sleep fragmentation, we revised the polygraphic recordings of 37 patients in whom obstructive apneas were recorded for at least 7 hours. In 15 of these patients, analysis was made for eight hours of the night. During each hour we analyzed at least 7 obstructive apneas, in which we measured the minimal esophageal pressure at the start of the apnea, the maximum value recorded at the end of the apnea (Pesmax), the difference from the minimum to the maximum (delta Pes), and the rate of increase in esophageal pressure (RPes). As indices of sleep fragmentation, we defined the number of arousals, awakenings and sleep state transitions. In the group of patients as a whole, we found a trend toward a gradual increase for apnea duration (F = 98.8, p < 0.001) and Pesmax F = 31.6, p < 0.001) which was significant from the first to the last hour. The time-dependent evolution of apnea duration and Pesmax showed that the rise in these two variables peaked during the first 3 hours of sleep, followed by a plateau and a decrease in the last hour of the night. This temporal profile was more evident when the analysis was available for 8 hours. No significant changes across the night were found for nocturnal hypoxemia and number of arousals. Considering the slope of Pesmax changes across the night, we saw that neither the apnea+hypopnea index nor the indices of sleep fragmentation affected the nocturnal trend. The present data demonstrate the presence of a nocturnal trend in arousal threshold in OSA patients independent of sleep fragmentation. The biphasic evolution of the arousal threshold may be caused by factors that influence the circadian and homeostatic processes.

Adult↗
PubMed1987

The afferent pupillary defect in asymmetric glaucoma.

The OCTOPUS 2000 perimeter and a central 30 degrees program were used to study consecutively 27 patients with glaucoma who had either a relative afferent pupillary defect (APD) or asymmetric optic nerve cupping without an APD. The mean difference in visual field sensitivity between fellow eyes was 48.2% (range, 13% to 93%) for the APD group and 5.5% (range, 0% to 9.0%) for the non-APD group. The mean difference in cup-disc ratio was 0.43 (range, 0.2 to 0.6) for the APD group and 0.24 (range, 0.2 to 0.3) for the non-APD group. The APD depth was quantitated with neutral density filters and correlated with visual field asymmetry but not with cup-disc ratio asymmetry. There was no overlap between the APD and non-APD groups in the amount of visual field asymmetry: Every patient with a sensitivity difference of 13% or greater had an APD. The presence of an APD indicates that a threshold of asymmetric optic nerve damage has been exceeded. With automated perimetry, this threshold can be quantitated and may improve the assessment of patients with glaucoma.

Afferent Pathways↗
PubMed1994

Electrophysiological and psychophysical quantification of temporal summation in the human nociceptive system.

Animal experiments have shown that the nociceptive reflex can be used as an indicator of central temporal integration in the nociceptive system. The aim of the present study on humans was to investigate whether the nociceptive reflex, evoked by repetitive strong electrical sural nerve stimuli, increased when summation was reported by the volunteers. The reflexes were recorded from the biceps femoris and rectus femoris muscles in eight volunteers following a series of stimulations at 0.1, 1, 2, and 3 Hz. Each series consisted of five consecutive stimuli. Using 0.1- and 1-Hz stimulation, the reflex was not facilitated in the course of the five consecutive stimuli. Following 2- and 3-Hz stimulation, the reflex size (root mean square amplitude) increased significantly during the course of the fifth stimulus. This reflex facilitation was followed by a significant increase (summation) in the pain magnitude when compared with 1- and 0.1-Hz stimulation. Furthermore, the threshold for psychophysical summation could be determined. This threshold (stimulus intensity) decreased when the stimulus frequency (1-5 Hz) of the five consecutive stimuli was increased. The nociceptive reflex and the psychophysical summation threshold might be used to clarify and quantify aspects of temporal summation within the human nociceptive system.

Adult↗
PubMed2004

Why are insect olfactory receptor neurons grouped into sensilla? The teachings of a model investigating the effects of the electrical interaction between neurons on the transepithelial potential and the neuronal transmembrane potential.

Insect olfactory receptor neurons are compartmentalized in sensilla. In a sensillum, typically two receptor neurons are in close contact and can influence each other through electrical interaction during stimulation. This interaction is passive, non-synaptic and a consequence of the electrical structure of the sensillum. It is analysed in a sensillum model and its effects on the neuron receptor potentials are investigated. The neurons in a sensillum can be both sensitive to a given odorant compound with the same sensory threshold or with different thresholds, or only one neuron be sensitive to the odorant. These three types of sensilla are compared with respect to maximum amplitude, threshold and dynamic range of the potentials. It is found that gathering neurons in the same sensillum is disadvantageous if they are identical, but can be advantageous if their thresholds differ. Application of these results to actual recordings from pheromone and food-odour olfactory sensilla is discussed.

Animals↗
PubMed1986

Is electrical stimulation of the rat incisor an appropriate experimental nociceptive stimulus?

The purpose of this study was to determine whether or not tooth pulp stimulation in the rat can selectively activate the pulp nerve fibers without excitation of the periodontium and to decide if the nerve fibers situated in the pulp of the rat's incisor are involved in the nociceptive reactions caused by an intrapulpal stimulation. The experiments were carried out on 20 awake and freely moving Sprague-Dawley rats. Bipolar stimulating electrodes were inserted into the pulp of the left lower incisor and in the right incisor after removal of the pulp. Special cares were taken to avoid, on the right side, direct stimulation of the stump of the apical nerve. The jaw opening reflexes were recorded from the digastric muscles ipsilaterally to the stimulated teeth and the thresholds were compared. Using the same animals, four typical and reproducible nociceptive behavioral reactions caused by a long tooth pulp stimulation were also observed (shock of 0.5 ms at 50 Hz during 1 s). The stimulus intensity was progressively increased, and the threshold of each reaction was recorded. For each of the 20 rats tested, the jaw opening reflex and the nociceptive reactions did not disappear after removal of the pulp, but the threshold of the responses to the stimulation of the nonvital tooth were significantly above the threshold of the responses to the stimulation of the vital incisor. The conclusion was tooth pulp stimulation activates the periodontal nerve fibers in the rat, and stimulation of the incisor pulp is significant in pain study in the rat because the thresholds of the jaw opening reflex and the nociceptive reactions were increased after the tooth pulp tissue was removed.

Animals↗
PubMed2002

Click-evoked potentials on the neck of the guinea pig.

Vestibulocollic reflex in humans is called vestibular evoked myogenic potential. To try to establish an animal model of the acoustically evoked vestibulocollic reflex, 18 guinea pigs were used in this study. Eight of the 18 guinea pigs received intramuscular injection of amikacin for 18 days (450 mg/kg/day) before recording to destroy the cochlea pharmacologically. Under general anesthesia with intraperitoneal injection of pentobarbital sodium (40 mg/kg body weight), auditory brainstem responses (ABRs) were recorded. Then potentials on the neck evoked by loud clicks were recorded on the pre-vertebral muscle or on the spinal cord at the level of third cervical vertebral bone using a silver-ball electrode. As a result, a negative peak (NP) with a latency of 6 approximately 8 ms was observed on the neck muscle or on the spinal cord in the control group. The thresholds of the NP were 90-100 dB above those of ABRs. The NP was also observed in the amikacin-administered group using clicks with the same intensity as that for the control group, while the ABR thresholds were highly elevated. These results are in agreement with a vestibular origin of the NP potential.

Acoustic Stimulation↗
PubMed2004

Interlaminar differences of spike activation threshold in the auditory cortex of the rat.

The neural circuits of the auditory cortex are a substrate for the dual purpose of representing and storing the auditory signal on one hand, and sending its relevant features to other cortical and subcortical areas on the other hand. The ability to process and transform the signal crucially depends on achievement of the neuronal spike threshold following spatiotemporal summation of the synaptic signals. We used patch-clamp recording in a thin slice preparation to compare neuronal responses to current injection of layer II/III and layer V neurons. We found that while the two classes of neurons do not differ in passive neuronal properties, layer II/III neurons possess a lower firing threshold relative to layer V neurons (-44.8 +/- 2.4 mV vs. -34.3 +/- 4.0 mV). We speculate that a lower spiking threshold in layer II/III neurons might favor local intracolumnar activation for representation and storage of the auditory information whereas a more positive spiking threshold for layer V neurons may prevent unnecessary cortical spread of a scarcely processed signal.

Action Potentials↗
PubMed2000

Two-point discrimination thresholds and schizotypy: illuminating a somatosensory dysfunction.

The current study sought to determine if somatosensory deviations, assessed by determining two-point discrimination thresholds, were associated with schizotypic features in non-psychotic subjects (N=100). It was hypothesized that elevated two-point discrimination thresholds would be associated with an increased likelihood of higher levels of schizotypy features. The results of the study suggested that at the level of individual differences, higher two-point discrimination thresholds (ascending series assessments) were associated with higher levels of schizotypy as operationalized by several prominent measures of schizotypy. A deviant subgroup analysis clearly suggested that, for ascending series two-point threshold assessments, those persons requiring the greatest distance (i.e. highest thresholds) to detect two-point stimulation were substantially more schizotypic than a contrast group. Control analyses that focused on psychological state (depression, anxiety) and intellectual functioning variables revealed that these factors were, more or less, unrelated to two-point discrimination thresholds and they did not account for the observed significant relations between the schizotypy scales and two-point threshold values. The results of this study are discussed within a neuropsychological context implicating parietal cortex involvement with schizotypy and schizophrenia.

Adult↗