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PubMed1995

Action potential generation in rat slow- and fast-twitch muscles.

1. In skeletal muscle fibres, voltage-gated sodium channels are concentrated at the neuromuscular junction. The effect of this accumulation of sodium channels on action potential generation was investigated in rat slow- and fast-twitch muscle fibres. 2. Intracellular microelectrodes were used to generate and record action potentials, from an imposed membrane potential of -75 and -90 mV, in junctional and extrajunctional regions of the muscle fibre. To identify junctional regions, preparations were incubated with 5 x 10(-7) M d-tubocurarine (dTC) to block muscle contraction in response to nerve stimulation whilst allowing endplate potentials (EPPs) to be recorded. Injection of rectangular depolarizing current pulses initiated action potentials at the endplate with threshold values several millivolts lower than those generated elsewhere in the fibre. In addition, the maximum rate of rise of the action potential was greater at the endplate than in extrajunctional regions. 3. In other muscles, neuromuscular transmission was partially blocked with dTC (2 x 10(-7) M), such that repetitive nerve stimulation evoked action potentials and EPPs in the same fibre. The threshold of these nerve-evoked action potentials was approximately 50% lower than values derived from action potentials generated by current injection. 4. It is concluded that the threshold for action potential generation is significantly lower at the neuromuscular junction than in extrajunctional regions of skeletal muscle fibres. Furthermore, nerve-evoked current is more effective at generating an action potential than is injected current.

Action Potentials↗
PubMedDate not supplied

Pump-probe detection of laser-induced microbubble formation in retinal pigment epithelium cells.

Microsecond laser pulses are currently being investigated in a new ophthalmic procedure for treatment of disorders associated with the retinal pigment epithelium (RPE). The precise mechanism for microsecond laser-induced RPE damage, however, has not been determined. We have previously shown that short pulse laser irradiation in the nanosecond to picosecond time domain causes transient microbubble formation around melanin granules in pigmented cells. Nanosecond time-resolved microscopy was previously used to visualize the intracellular cavitation dynamics. However, this technique is difficult to use with microsecond laser exposures, especially when multiple laser pulses are applied in a rapid sequence as in the clinical setting. Here we describe a simple pump-probe method for detecting transient light scattering signal from individual RPE cells when they are irradiated with nanosecond and microsecond laser pulses. For single 12 ns pulses the threshold for bubble detection was the same as the ED(50) threshold for cell death. For 6 micros pulse duration the threshold for bubble detection was about 10% higher than the threshold for cell death. With repetitive pulse trains at 500 Hz the ED(50) decreased about 25% for 10 and 100 pulses. Cells die when a single bubble was detected in a multiple pulse sequence.

Air↗
PubMed2002

Primitive stream segregation of tone sequences without differences in fundamental frequency or passband.

Peripheral-channeling theorists argue that differences in excitation pattern between successive sounds are necessary for stream segregation to occur. The component phases of complex tones comprising unresolved harmonics (F0=100 Hz) were manipulated to change pitch and timbre without changing the power spectrum. In experiment 1, listeners compared two alternating sequences of tones, A and B. One sequence was isochronous (tone duration=60 ms, intertone interval=40 ms). The other began isochronously, but the progressive delay of tone B made the rhythm irregular. Subjects had to identify the sequence with irregular rhythm. Stream segregation makes this task more difficult. A and B could differ in passband (1250-2500 Hz, 1768-3536 Hz, 2500-5000 Hz), component phase (cosine, alternating, random), or both. Stimuli were presented at 70 dB SPL in pink noise. Dissimilarity in either passband or phase increased discrimination thresholds. Moreover, phase differences raised threshold even when there was no passband difference. In experiment 2, listeners judged moment-by-moment the grouping of long ABA-ABA-... sequences. The measure was the proportion of time a sequence was heard as segregated. The factors that increased segregation were very similar to those that increased threshold in experiment 1. Overall, the findings indicate that substantial stream segregation can occur without differences in power spectrum. It is concluded that differences in peripheral channeling are not a requirement for stream segregation.

Adult↗
PubMed1997

Use of a decibel threshold in detecting Doppler embolic signals.

BACKGROUND AND PURPOSE: To improve reproducibility and reliability in the identification of embolic signals detected with the use of Doppler ultrasound, many studies have used an intensity threshold. However, variable thresholds between 3 and 12 dB have been used, and often the method of measurement of intensity is not stated. Potentially different methods of measurement could result in different intensity measurements for the same embolic signal. We determined the effect of these differences using commercial transcranial Doppler systems. METHODS: We analyzed 81 embolic signals recorded from the middle cerebral arteries of patients with carotid artery disease using three different methods of measuring intensity that had been previously used in research studies. In method 1 individual time frames of the frequency spectra were analyzed, in method 2 a color-coded intensity scale was used, and in method 3 automated software was used. RESULTS: There was a highly significant correlation between measurements made by the different techniques (method 1 versus method 2: r = .68, P < .0001; method 1 versus method 3: r = .66, P < .0001; method 2 versus method 3: r = .70, P < .0001). However, the absolute values of intensity for the same embolic signals varied markedly for the different methods. For example, a 4-dB threshold according to method 1 was equivalent to an approximately 7-dB threshold measured by method 2. These differences had major effects on the proportion of embolic signals detected with the use of the same decibel threshold but with intensity measured in the different ways. For example, using a threshold of 7 dB would result in only 4.9% of signals being missed by method 2 but 42.2% and 51.4% being missed by methods 1 and 3, respectively. CONCLUSIONS: Our results demonstrate that the intensities of the same embolic signals, recorded with the same parameters, are markedly different when analyzed in the different ways used in previous studies. This has important implications when a decibel threshold is used and emphasizes that criteria developed by one investigator on one machine cannot be used by another investigator without initial reevaluation. This could account for some of the differences in frequencies of embolic signals reported in previous clinical studies.

Differential Threshold↗
PubMedDate not supplied

Intensity discrimination, temporal integration and gap detection by normally-hearing subjects with weak and strong otoacoustic emissions.

It is unlikely that the overall status of a cochlea and middle ear which produces strong otoacoustic emissions (OAEs), i.e. high-level evoked emissions (EOAEs) and spontaneous emissions (SOAEs), has a generalized effect on peripheral auditory processing if the sensitivity is normal. Current data do not support the hypothesis that a weak OAE profile (low-level EOAEs and no SOAEs) is indicative of subclinical damage to the cochlea. Nevertheless, the ability of a subject to perform some psychoacoustical tasks may be influenced by the interaction between OAEs and test signals. The present experiments investigated the influence of strong or weak OAEs on: (1) intensity just-noticeable differences for pure tones; (2) temporal integration in the vicinity of SOAEs; (3) gap detection thresholds for broad-band noise bursts. The results show that OAEs can influence performance on these psychoacoustical tasks, especially for low-level stimuli with spectral components in the vicinity of high-level SOAEs.

Audiometry, Pure-Tone↗
PubMed1996

[Influences of orthognathic surgery to facial skin sensation--an analysis with a new testing method].

This study introduces an original testing method on facial skin sensation and describes the results obtained by its application to patients after orthognathic surgery. The alterations of skin sensation in lower lip and chin area were examined in 135 patients who had undergone orthognathic surgery, by application of electrical stimulation through an original pencil shaped probe. Detection threshold of the same area before surgery were used as control, and the location and size of the area with thresholds higher than control levels were measured. The control thresholds ranged from 0.13 mA to 0.21 mA. The higher threshold area was found in 86.3% of all the patients in 1 month after surgery, in 27.7% after 1 year. The threshold levels declined with the time, and in none of the patients the threshold level was higher than 1.0 mA more than 2 years after surgery. The patients whose threshold level was more than 1.0 mA in 1 month postoperatively showed a tendency to have the area with a threshold higher than the control level even 1 year later (p < 0.0001). The threshold of the younger patients tended to improve smoothly than the older. In addition, the patients with a shorter set-back or advance distance had a slighter sensory disturbance and recovered more smoothly than those with a longer distance.

Adolescent↗
PubMed1985

Convulsive thresholds in mice: action of 6-hydroxydopamine and eboracin.

The neurotoxin, 6-hydroxydopamine, when injected intraperitoneally, protected mice from seizures induced by pentylenetetrazol (Metrazol) and altered the nature of the convulsive response induced by an auditory stimulus. Conversely, the indenopyrrole, eboracin, protected mice from seizures induced by auditory stimulation and altered the response to Metrazol. In each case the altered response was characterized by a marked prolongation of the clonic component without progression to the generalized tonic phase. It appeared, therefore, that 6-hydroxydopamine raised the threshold to tonus in audiogenic seizures, and eboracin raised it in Metrazol seizures. Eboracin raised threshold to clonic phase in audiogenic seizures whereas 6-hydroxydopamine raised it in Metrazol seizures. Our findings showed that in Metrazol and audiogenic seizures thresholds to clonus and progression to the tonic phase were mediated by different biochemical mechanisms and suggested that agents controlling induction of clonic manifestations in one seizure model may be those involved in controlling seizure spread in the other.

Acoustic Stimulation↗
PubMed1992

The human visual system averages speed information.

It has been known for many years that human observers are unable to detect modest accelerations and decelerations in moving visual stimuli. We find that human observers can integrate speeds over many dots, moving at different speeds, producing a global speed percept analogous to the global direction percept first reported by Williams, D. W. and Sekuler, R. (1984, Vision Research, 24, 55-62). We measured speed discrimination for random dot stimuli which contained many different speeds. Our results show that observers always base their discrimination on the mean speed of the stimulus; changes in other stimulus characteristics (e.g. mode) are not detected. Moreover, discrimination thresholds for the global mean speed derived from many different speeds are comparable to those obtained with stimuli in which all dots move at the same speed suggesting that the internal noise associated with the encoding of speed information is quite high.

Differential Threshold↗
PubMed1994

Effects of stimulus level on nonspectral frequency discrimination by human subjects.

Frequency difference limens were determined as a function of reference-stimulus level for pulsatile electrical stimuli in 5 postlingually deaf human subjects with Nucleus-22 cochlear implants and for sinusoidally amplitude-modulated acoustic white noise stimuli in 4 normal-hearing humans. Subjects were tested at levels throughout the dynamic range and extending to the lowest detectable levels. Response stability was measured over the course of 10 sessions. For electrical stimulation in the deaf ears, difference limens decreased as a function of level throughout much or all of the dynamic range of hearing. This result contrasts with the case for nonspectral acoustic stimulation of normal-hearing subjects, where nonspectral frequency difference limens were strongly affected by level only near the detection threshold. These data suggest differences in the acoustic and electrical response spaces that must be considered in the design of auditory prosthesis processors.

Acoustic Stimulation↗
PubMed2002

Central and peripheral chemoreflexes in panic disorder.

Klein (Arch Gen Psychiatry, 50, 1993, 306-317) has suggested that panic disorder patients have a false suffocation alarm that may be associated with a lowered threshold for carbon dioxide detection. We compared the thresholds and sensitivities of the central and peripheral chemoreflexes between panic disorder patients and age- and sex-matched healthy volunteers to test this aspect of the hypothesis. We used a modified version of Read's rebreathing technique in 11 panic disorder patients and 10 healthy volunteers to examine the peripheral and central chemoreflex characteristics in these two populations. Subjects were examined during three rebreathing tests: training, hyperoxic (central chemoreflex alone) and hypoxic (combined central and peripheral chemoreflex). Panic symptoms were retrospectively assessed between groups using a DSM-IV derived Panic Symptom Scale. Comparisons of panic disorder patients with agoraphobia and healthy volunteers showed no significant differences in sensitivities or thresholds. Klein's hypothesis is not supported by these data. If a false suffocation alarm exists, its triggering may not be implemented within the respiratory chemoreflexes.

Adult↗
PubMed1998

Frontal versus transcorneal stimulation to induce maximal electroshock seizures or kindling in mice and rats.

Frontal stimulation, i.e. electrical stimulation where electrodes are pressed on the skin of the intact frontal skull of mice or rats, may represent a more humane alternative to the widely used transcorneal stimulation to induce electroshock seizures. The aim of this work was to directly compare transcorneal and frontal stimulation in eliciting maximal electroshock-induced seizures (MES) in mice and the anticonvulsant effect of carbamazepine (CBZ) and phenytoin (PHT) on thus produced seizures. In addition, we stimulated mice and rats repeatedly via transcorneal and frontal electrodes to see whether kindling is produced by this procedure. Two electroshock tests were used in mice, i.e. maximal electroshock seizure threshold (MEST) test and MES generated by supramaximal stimulation (50 mA). Frontal stimulation resulted in lower convulsive threshold than in the case of corneal stimulation. Both CBZ and PHT produced dose-dependent increases in seizure threshold for both sites of stimulation, i.e. transcorneal and frontal. As regards type of electrodes, higher doses of PHT were required to increase seizure threshold in the case of frontal than transcorneal stimulation. Supramaximal stimulation (50 mA) yielded comparable ED50 values regardless of the site of stimulation. Furthermore, once-daily stimulation of mice, regardless of the placement of electrodes, did not induce any changes in convulsive threshold. We also attempted to kindle mice and rats via corneal and frontal electrodes by repetitive electrical stimulation using currents which initially did not produce generalized clonic seizures. Mice were stimulated once daily for 2 s with 3 mA (corneal electrodes) or 2 mA (frontal electrodes) and rats were stimulated twice daily for 4 s at 8 mA (corneal electrodes) or 5 mA (frontal electrodes). With corneal stimulation in rats there was a clear progression of kindling development which was not the same in nature when compared with corneally-stimulated mice. Frontal stimulation did not produce kindling. Moreover, corneal stimulation was better tolerated by rats, while in mice high mortality was seen after either method of current delivery. Our data indicate that frontal electrodes can be used as an alternative to transcorneal stimulation to produce MES by supramaximal or threshold current intensities as screening procedures in antiepileptic drug (AED) development. Nevertheless, this type of stimulation cannot be used to produce minimal electroshock seizures and seems not to be useful to produce kindling in rats and mice.

Animals↗
PubMed1978

Contrast summation effects and stereopsis.

Contrast thresholds for stereopsis were measured for a variety of bandpass-filtered random-dot stereograms in a series of experiments. The principal finding was that contrast thresholds for stereopsis from 'complex' stereograms composed of mixtures of (a) two widely different spatial frequencies or (b) two or more widely different oriented random textures, are considerably lower than would be expected if stereopsis from such stimuli is mediated by the first component to rise above its own stereopsis contrast threshold. Instead, it appears that stereopsis comes about whenever the supradetection-threshold contrast of a stereogram exceeds a certain level, regardless of whether this contrast is provided by a single component or by a mix of two different ones. The implications of these findings for models of stereopsis are discussed.

Depth Perception↗
PubMed2001

Motor unit behaviour and contractile changes during fatigue in the human first dorsal interosseus.

1. In 67 single motor units, the mechanical properties, the recruitment and derecruitment thresholds, and the discharge rates were recorded concurrently in the first dorsal interosseus (FDI) of human subjects during intermittent fatiguing contractions. The task consisted of isometric ramp-and-hold contractions performed at 50 % of the maximal voluntary contraction (MVC). The purpose of this study was to examine the influence of fatigue on the behaviour of motor units with a wide range of activation thresholds. 2. For low-threshold (< 25 % MVC) motor units, the mean twitch force increased with fatigue and the recruitment threshold either did not change or increased. In contrast, the twitch force and the activation threshold decreased for the high-threshold (> 25 % MVC) units. The observation that in low-threshold motor units a quick stretch of the muscle at the end of the test reset the unit force and recruitment threshold to the prefatigue value suggests a significant role for fatigue-related changes in muscle stiffness but not twitch potentiation or motor unit synchronization. 3. Although the central drive intensified during the fatigue test, as indicated by an increase in surface electromyogram (EMG), the discharge rate of the motor units during the hold phase of each contraction decreased progressively over the course of the task for motor units that were recruited at the beginning of the test, especially the low-threshold units. In contrast, the discharge rates of newly activated units first increased and then decreased. 4. Such divergent behaviour of low- and high-threshold motor units could not be individually controlled by the central drive to the motoneurone pool. Rather, the different behaviours must be the consequence of variable contributions from motoneurone adaptation and afferent feedback from the muscle during the fatiguing contraction.

Adult↗
PubMedDate not supplied

Porcine skin visible lesion thresholds for near-infrared lasers including modeling at two pulse durations and spot sizes.

With the advent of such systems as the airborne laser and advanced tactical laser, high-energy lasers that use 1315-nm wavelengths in the near-infrared band will soon present a new laser safety challenge to armed forces and civilian populations. Experiments in nonhuman primates using this wavelength have demonstrated a range of ocular injuries, including corneal, lenticular, and retinal lesions as a function of pulse duration. American National Standards Institute (ANSI) laser safety standards have traditionally been based on experimental data, and there is scant data for this wavelength. We are reporting minimum visible lesion (MVL) threshold measurements using a porcine skin model for two different pulse durations and spot sizes for this wavelength. We also compare our measurements to results from our model based on the heat transfer equation and rate process equation, together with actual temperature measurements on the skin surface using a high-speed infrared camera. Our MVL-ED50 thresholds for long pulses (350 micros) at 24-h postexposure are measured to be 99 and 83 J cm(-2) for spot sizes of 0.7 and 1.3 mm diam, respectively. Q-switched laser pulses of 50 ns have a lower threshold of 11 J cm(-2) for a 5-mm-diam top-hat laser pulse.

Animals↗
PubMed2003

Endothelin-1 modulates hemoglobin-mediated signaling in cerebrovascular smooth muscle via RhoA/Rho kinase and protein kinase C.

Endothelin-1 (ET-1) and oxyhemoglobin (OxyHb) have been implicated in the pathogenesis of cerebral vasospasm after subarachnoid hemorrhage. However, the contribution of ET-1 to this condition has not been definitely established. In this study, we investigated whether threshold concentration of ET-1 enhances cerebrovascular smooth muscle (CVSM) contraction to OxyHb by activating the RhoA/Rho kinase and protein kinase C (PKC) pathways. CVSM contraction was measured in endothelium-denuded rabbit basilar arteries. Cytosolic and particulate fractions of CVSM cells were examined for RhoA and PKC reactivity with specific antibodies using immunoblotting procedures. ET-1 (0.1 nM) alone did not produce any significant contraction, but it markedly potentiated the magnitude (223% of control) and rate (149% of control) of contraction in response to OxyHb, which was attenuated by the inhibitors of Rho kinase Y-27632 and HA-1077. ET-1-mediated potentiation of the contraction was also inhibited by inhibitors of PKC, Ro-32-0432, and GF-109203X. BQ-123 prevented potentiation of vasoconstriction mediated by ET-1, indicating that the action of ET-1 was mediated by the endothelin type A receptor. Pretreatment with ET-1 significantly enhanced OxyHb-mediated RhoA translocation in CVSM cells and intact basilar arteries. ET-1 also caused potentiation of PKC-epsilon expression in membranes of CVSM cells exposed to OxyHb for 10 and 60 min but did not markedly change the distribution of PKC-alpha. Thus, in CVSM, threshold concentration of ET-1 potentiates contraction induced by OxyHb via RhoA/Rho kinase- and PKC-epsilon-dependent mechanisms. This process may contribute to the pathological contraction of cerebral arteries observed after subarachnoid hemorrhage.

Animals↗
PubMed1996

Pharmacological and kinetic characterization of two functional classes of serotonergic modulation in Aplysia sensory neurons.

1. Modulation of mechanoafferent sensory neurons (SNs) by the neutrotransmitter serotonin (5HT) plays a significant role in behavioral sensitization of several withdrawal reflexes in Aplysia. The modulatory effects of 5HT on these SNs include increased excitability, increased input resistance, action potential broadening, and increased synaptic transmission. Based on a previously described dissociation of some of these modulatory effects, revealed with the 5HT-receptor antagonist, cyproheptadine, we investigated whether a similar dissociation could be found by systematically varying the concentration of the endogenous agonist, 5HT. 2. We first applied a range of 5HT concentrations to isolated pleural/pedal ganglia (containing tail SNs and tail motor neurons, respectively), and measured the magnitude of 5HT-induced modulation of spike broadening and increased excitability. The resulting dose-response curve showed that both forms of modulation increase monotonically as a function of 5HT concentration, but that excitability has a lower threshold for modulation by 5HT than does spike duration. 3. We further characterized the modulatory effects of 5HT on Aplysia SNs by comparing the time course of onset of modulation by 5HT and the time course of recovery after washout. Independent of 5HT concentration, modulation of excitability increases rapidly in the presence of 5HT and recovers rapidly (< 3 min) after washout. Similarly, input resistance increases and recovers rapidly, mirroring the profile of increased excitability. However, modulation of spike duration exhibits two profiles, dependent on 5HT concentration. Low concentrations of 5HT (0.5 and 1 microM) induce a rapid-onset and transient-recovery form of spike broadening, which resembles the kinetics of increased excitability and increased input resistance. Higher concentrations of 5HT (2.5 and 5 microM) induce a more slowly developing and prolonged-recovery form of spike broadening (> 9 min). At these higher concentrations, the recovery profile for prolonged spike broadening is significantly different from those observed for both increased excitability and increased input resistance. 4. We next compared the relationship between spike broadening and short-term synaptic facilitation. We found that significant facilitation of synaptic transmission requires a high 5HT concentration, which is comparable with that required to induce prolonged spike broadening. Similarly, the recovery profiles for spike broadening and synaptic facilitation are strikingly similar, recovering in parallel. 5. Our experiments show that the modulatory effects of 5HT in the tail SNs can be dissociated both by their sensitivity to different concentrations of 5HT and by their kinetics of serotonergic modulation. Based on these results, together with extensive evidence from other laboratories, we propose that the short-term modulatory effects of 5HT fall into two distinct functional classes. The first class, which includes excitability, input resistance, and transient spike broadening, has a low threshold for 5HT modulation and recovers rapidly. The second class, which includes prolonged spike broadening and short-term synaptic facilitation, has a higher threshold for modulation and recovers more slowly. It now will be of interest to determine the functional contribution of each of these classes to different aspects of sensitization.

Action Potentials↗
PubMed1987

Retinal noise, the performance of retinal ganglion cells, and visual sensitivity in the dark-adapted frog.

By extracellular recording of action potentials from single ganglion cells in the dark-adapted eyecup of the frog, we show that four different characteristics of a cell, the frequency-of-response function, the variability in responses to low suprathreshold stimulation, the maintained discharge, and the susceptibility to desensitization by weak background lights, all seem to reflect the same intrinsic noise. In a small fraction of reliable cells this noise is close to that expected from dark isomerizationlike events in rods, but it differs by orders of magnitude between cells. We have also determined a threshold intensity for the phototactic jumping behavior of frogs in darkness. This intensity, while below the human threshold, is still above the threshold for an appreciable fraction of frog retinal ganglion cells, and the sensitivity of this visually guided behavior at 16 degrees C is not strictly limited by dark events in rods.

Animals↗
PubMed2002

Current perception threshold and sympathetic skin response in diabetic and alcoholic polyneuropathies.

OBJECTIVE: Correlation between current perception threshold and sympathetic skin response was investigated in patients with diabetic or alcoholic polyneuropathy. METHODS: Current perception threshold was measured using Neurometer CPT/C, and the sympathetic skin response was measured using Neuropack sigma. PATIENTS: Fourteen patients with diabetic polyneuropathy and 10 patients with alcoholic polyneuropathy were studied. RESULTS: There was a significant negative correlation between the current perception threshold to 5 Hz stimulation and the amplitude of sympathetic skin response. CONCLUSION: Since both current perception threshold to 5 Hz stimulation and sympathetic skin response are related to C fibers, these two are considered to be impaired concurrently in diabetic and alcoholic polyneuropathies.

Adrenergic Fibers↗