Suprathreshold Range Research Articles

The Maximal Lactate Steady State Workload Determines Individual Swimming Performance.

The lactate threshold (LT) and the strongly related maximal lactate steady state workload (MLSSW) are critical for physical endurance capacity and therefore of major interest in numerous sports. However, their relevance to individual swimming performance is not well understood. We used a custom-made visual light pacer for real-time speed modulation during front crawl to determine the LT and MLSSW in a single-exercise test. When approaching the LT, we found that minute variations in swimming speed had considerable effects on blood lactate concentration ([La−]). The LT was characterized by a sudden increase in [La−], while the MLSSW occurred after a subsequent workload reduction, as indicated by a rapid cessation of blood lactate accumulation. Determination of the MLSSW by this so-called “individual lactate threshold” (ILT)-test was highly reproducible and valid in a constant speed test. Mean swimming speed in 800 and 1,500 m competition (S-Comp) was 3.4% above MLSSW level and S-Comp, and the difference between S-Comp and the MLSSW (Δ S-Comp/MLSSW) were higher for long-distance swimmers (800–1,500 m) than for short- and middle-distance swimmers (50–400 m). Moreover, Δ S-Comp/MLSSW varied significantly between subjects and had a strong influence on overall swimming performance. Our results demonstrate that the MLSSW determines individual swimming performance, reflects endurance capacity in the sub- to supra-threshold range, and is therefore appropriate to adjust training intensity in moderate to severe domains of exercise.

Time-Frequency Analysis of Motor-Evoked Potential in Patients with Stroke vs Healthy Subjects: a Transcranial Magnetic Stimulation Study

Conventional analysis of motor-evoked potential (MEP) is performed in time domain using amplitude and latency, which encapsulates information relevant to the cortical excitability of the brain. The study investigated the importance of time-frequency analysis by comparing MEPs in time-frequency domains (TFD) of healthy versus stroke survivors. Six healthy subjects and ten patients with stroke were enrolled. Single-pulse transcranial magnetic stimulation (TMS) at resting motor threshold (RMT) was given at extensor digitorum communis muscle cortical representation to obtain MEP. MEPs were obtained at resting motor threshold (100% RMT subjects and patients), supra-threshold range (100–170% RMT), and different voluntary contractions (100% RMT) to subjects. Fast Fourier transform and continuous wavelet transform (CWT) were used for analysis. Frequency spectrum showed 98% and 66% of signal power in 0–100 Hz for subjects and patients, respectively. Top 10, top 25, and top 50 percentile power of CWT were calculated for each MEP. Frequency spectrum of top 10 and top 25 percentile power of subjects were different (p < 0.05) and dispersed to 0–500 Hz for patients; both groups having a 40-Hz peak. Total power of MEP was found to be low (p < 0.05) in patients as compared to subjects and top 10, top 25, and top 50 percentile power showed decrease. Clinical scores—MAS and FM—were observed to be correlated to frequency and time-frequency features (p < 0.05). Frequency spectrum belonging top 10 percentile power of different level voluntary contractions showed statistical significance (p < 0.05). However, no significant differences were observed for MEPs at different supra-threshold intensities. Results suggest time-frequency analysis might provide objective ways to quantify TMS measures for stroke patients.

Non-Decaying postsynaptics potentials and delayed spikes in hippocampal pyramidal neurons generated by a zero slope conductance created by the persistent Na+ current

ABSTRACTThe negative slope conductance created by the persistent sodium current (INaP) prolongs the decay phase of excitatory postsynaptic potentials (EPSPs). In a recent study, we demonstrated that this effect was due to an increase of the membrane time constant. When the negative slope conductance opposes completely the positive slope conductances of the other currents it creates a zero slope conductance region. In this region the membrane time constant is infinite and the decay phase of the EPSPs is virtually absent. Here we show that non-decaying EPSPs are present in CA1 hippocampal pyramidal cells in the zero slope conductance region, in the suprathreshold range of membrane potential. Na+ channel block with tetrodotoxin abolishes the non-decaying EPSPs. Interestingly, the non-decaying EPSPs are observed only in response to artificial excitatory postsynaptic currents (aEPSCs) of small amplitude, and not in response to aEPSCs of big amplitude. We also observed concomitantly delayed spikes with long latencies and high variability only in response to small amplitude aEPSCs. Our results showed that in CA1 pyramidal neurons INaP creates non-decaying EPSPs and delayed spikes in the subthreshold range of membrane potentials, which could potentiate synaptic integration of synaptic potentials coming from distal regions of the dendritic tree.

Pain thresholds, supra-threshold pain and lidocaine sensitivity in patients with erythromelalgia, including the I848Tmutation in NaV 1.7.

Nociceptive thresholds and supra-threshold pain ratings as well as their reduction upon local injection with lidocaine were compared between healthy subjects and patients with erythromelalgia (EM). Lidocaine (0.25, 0.50, 1.0 or 10mg/mL) or placebo (saline) was injected intradermally in non-painful areas of the lower arm, in a randomized, double-blind manner, to test the effect on dynamic and static mechanical sensitivity, mechanical pain sensitivity, thermal thresholds and supra-threshold heat pain sensitivity. Heat pain thresholds and pain ratings to supra-threshold heat stimulation did not differ between EM-patients (n=27) and controls (n=25), neither did the dose-response curves for lidocaine. Only the subgroup of EM-patients with mutations in sodium channel subunits NaV 1.7, 1.8 or 1.9 (n=8) had increased lidocaine sensitivity for supra-threshold heat stimuli, contrasting lower sensitivity to strong mechanical stimuli. This pattern was particularly clear in the two patients carrying the NaV 1.7 I848T mutations in whom lidocaine's hyperalgesic effect on mechanical pain sensitivity contrasted more effective heat analgesia. Heat pain thresholds are not sensitized in EM patients, even in those with gain-of-function mutations in NaV 1.7. Differential lidocaine sensitivity was overt only for noxious stimuli in the supra-threshold range suggesting that sensitized supra-threshold encoding is important for the clinical pain phenotype in EM in addition to lower activation threshold. Intracutaneous lidocaine dose-dependently blocked nociceptive sensations, but we did not identify EM patients with particular high lidocaine sensitivity that could have provided valuable therapeutic guidance. Acute pain thresholds and supra-threshold heat pain in controls and patients with erythromelalgia do not differ and have the same lidocaine sensitivity. Acute heat pain thresholds even in EM patients with the NaV 1.7 I848T mutation are normal and only nociceptor sensitivity to intradermal lidocaine is changed. Only in EM patients with mutations in NaV 1.7, 1.8 or 1.9 supra-threshold heat and mechanical pain shows differential lidocaine sensitivity as compared to controls.

Perceived global flow direction reveals local vector weighting by luminance

Global flow occurs when random dots, each selecting their direction of motion randomly each frame from a distribution of directions spanning up to 180°, appear to move as a whole in the mean direction of the components. This percept arises because the visual system integrates the many independent local motion signals over space and time. Through a series of direction discrimination experiments with random-dot cinematograms (RDCs), we show that varying the luminance of dots over a suprathreshold range profoundly affects perceived direction; the brightest dots appear to be weighted more and dimmer dots weighted less when determining perceived global direction. This effect is not observable if all dots in the display have the same luminance but only when the display contains dots with different luminance values. The results are consistent with energy models of motion detectors whose responses are contrast dependent. A Monte Carlo simulation of global direction discrimination employing a 12-mechanism line-element model that weighted the local motion vectors by the normalized squared contrast of the component dots (a proxy for contrast energy) captured well the features of the experimental data.

Non-linear laws of echoic memory and auditory change detection in humans.

BackgroundThe detection of any abrupt change in the environment is important to survival. Since memory of preceding sensory conditions is necessary for detecting changes, such a change-detection system relates closely to the memory system. Here we used an auditory change-related N1 subcomponent (change-N1) of event-related brain potentials to investigate cortical mechanisms underlying change detection and echoic memory.ResultsChange-N1 was elicited by a simple paradigm with two tones, a standard followed by a deviant, while subjects watched a silent movie. The amplitude of change-N1 elicited by a fixed sound pressure deviance (70 dB vs. 75 dB) was negatively correlated with the logarithm of the interval between the standard sound and deviant sound (1, 10, 100, or 1000 ms), while positively correlated with the logarithm of the duration of the standard sound (25, 100, 500, or 1000 ms). The amplitude of change-N1 elicited by a deviance in sound pressure, sound frequency, and sound location was correlated with the logarithm of the magnitude of physical differences between the standard and deviant sounds.ConclusionsThe present findings suggest that temporal representation of echoic memory is non-linear and Weber-Fechner law holds for the automatic cortical response to sound changes within a suprathreshold range. Since the present results show that the behavior of echoic memory can be understood through change-N1, change-N1 would be a useful tool to investigate memory systems.

The coding of noxious mechanical and thermal stimuli of deep dorsal horn neurones is attenuated in NK1 knockout mice

Previous behavioural evidence has shown that NK1 receptor gene knockout (NK1 −/−) mice display altered nociceptive responses following tissue or peripheral nerve injury. A single electrophysiological study reported an attenuation of wind-up and responses to mustard oil application. Although the behavioural results implicate SP and its receptor (NK1-R) in the transmission of noxious high intensity pain, little is known regarding the spinal neuronal substrates and the modalities involved. We have addressed this using in vivo electrophysiology and recordings of deep dorsal horn neurones in urethane-anaesthetised C57B6×129/sv mice to reveal a marked deficit in mechanical and thermal coding, selectively encompassing the suprathreshold range of noxious stimuli. The frequency-dependent increase in neuronal activity following repetitive C-fibre stimulation (wind-up) was also abolished in spinal neurones of NK1-R knockout mice. Quantification of the receptive field size of spinal neurones, mapped with low- and high-intensity mechanical punctate stimuli, revealed no differences between NK1 −/− and wildtype mice. We conclude that NK1-Rs are important in the high intensity noxious signalling of acute peripheral (mechanical/thermal) stimuli and this may result from the lack of wind-up and/or the disruption of spinal–bulbo-spinal loops.

The Piéron function in the threshold region.

The Piéron function (Piéron, 1914, 1920, 1952) describes the decay of reaction time (RT) when the intensity of the stimulus is increased. It is generally demonstrated within a suprathreshold range of intensities. However, in some studies, for the lowest range of intensities, the exponent of the function is clearly greater than that for the upper ranges of intensities. Such an increase in the exponent for the lowest intensities is assumed to result from a combined effect of stimulus intensity and of stimulis uncertainty in detection. Our first experiment used luminance levels that covered all the scotopic range and a spatial two-alternative forced-choice task in which both accuracy and RT were measured. It demonstrated a drastic increase in the exponent in the Piéron function when the intensities reached the threshold region. Since the estimates of the threshold region may have been biased by the use of a much larger range of luminances, a second experiment was conducted using luminances that covered only the threshold region. This experiment confirmed the previous estimates for the threshold region.

Effect of stimulus rise time and high-pass masking on early auditory evoked potentials

Problems of frequency-specific objective assessment of hearing threshold by means of auditory brainstem response (ABR) have been discussed recently. While a number of workers have recommended methods of selective masking to improve the frequency specificity, others believe that frequency-specific potentials can also be obtained without masking. In this context, the effects of rise-decay time and high-pass masking on ABRs were investigated. ABRs were recorded in normal-hearing subjects and patients with high and low frequency hearing loss by means of surface electrodes between the vertex and the ipsilateral mastoid. The frequency of the stimulus was 1 kHz, and the rise-decay time 1 ms (1-0-1) or 2 ms (2-0-2). High-pass filtered noise (cutoff frequency 1.5 kHz; filter slope 250 dB/octave) was employed for masking. Particular attention was paid to the problem of efficient masking. In normal-hearing subjects under the influence of high-pass masking compared to non-masked ABRs, longer mean latencies and diminished means of the amplitudes of wave V were found, with differences in the near-threshold domain being less pronounced. Similar results were observed in patients with high frequency hearing loss. In patients with low frequency hearing loss, the influence of high-pass masking was especially marked distinctly near to threshold. Furthermore, latency and amplitude differences of wave V of the 1-0-1 and the 2-0-2 stimuli were determined from the ABRs obtained with and without high-pass masking. The differences between the latency differences of both stimuli in the suprathreshold range (70 dB nHL) only were statistically significant. The results are suggestive of an inadequate frequency specificity of unmasked stimuli in the suprathreshold range. Evaluation of the latencies revealed for both rise-decay times a similar frequency specificity near the threshold and a higher frequency specificity of the longer stimulus in the suprathreshold range.

Electrophysiological properties of rat pontine nuclei neurons In vitro. I. Membrane potentials and firing patterns.

We used a new slice preparation of rat brain stem to establish the basic membrane properties of neurons in the pontine nuclei (PN). Using standard intracellular recordings, we found that pontine cells displayed a resting membrane potential of -63 +/- 6 mV (mean +/- SD), an input resistance of 53 +/- 21 MOmega, a membrane time constant of 5.3 +/- 2.4 ms and were not spontaneously active. The current-voltage relationship of most of the PN neurons showed the characteristics of inward rectification in both depolarizing and hyperpolarizing directions. A prominent feature of the firing of pontine neurons was a marked firing rate adaptation, which eventually caused the cells to cease firing. Several types of membrane conductances possibly contribute to this feature. For one, a medium and a slow type of afterhyperpolarization (AHP) control the pattern of firing. The medium AHP was partly susceptible to blockade of calcium influx, whereas it was abolished completely by blockade of potassium channels with tetraethylammonium, indicating that it is based on at least two conductances: a calcium-dependent and a calcium-independent one. The slow AHP was carried by potassium ions and could be blocked effectively by preventing calcium influx into the cell. It was present after single spikes but was strongest after a high-frequency spike train. Calcium entry into the cell was mediated by high-threshold calcium channels that were detected by the generation of calcium spikes under blockade of potassium channels. Furthermore, the early phase of the firing rate adaptation was shown to be related to the time course of a slow, tetrodotoxin (TTX)-sensitive, persistent sodium potential, which was activated already in the subthreshold range of membrane potentials. This potential was time dependent and imposed as a depolarizing "hump" with a maximum occurring in most cases between 50 and 100 ms after stimulus onset. In the suprathreshold range, it generated plateau potentials following fast spikes, if potassium channels were blocked. After the complete adaptation of the firing rate, PN neurons were observed to display irregular fluctuations of the membrane potential, which sometimes reached firing threshold thereby eliciting an irregular low-frequency spike train. As these fluctuations could be blocked with TTX, they probably are based on the persistent sodium currents. The opposing drive in hyperpolarizing direction may be provided by strong outward currents that generated a marked outward rectification in the current-voltage relationship under TTX. In conclusion, PN neurons show complex membrane properties that are reminiscent in many ways to cerebrocortical "regular firing" neurons.

Can the loudness function determine the shape of the Weber function?

A recent model relating measures of loudness and intensity discrimination [W. S. Hellman and R. P. Hellman, J. Acoust. Soc. Am. 87, 1255–1265 (1990)] is shown to reveal that the near threshold slope of +1 obtained for the loudness function requires the near threshold slope of the Weber function for intensity discrimination to be −1. This result is consistent with psychophysical intensity discrimination measurements for pure tones and broadband noise, as well as with theoretical considerations which predict that the Weber function should have a slope of −1 as the detection threshold is approached [N. F. Viemeister, Auditory Function, 213–241 (1988)]. The model also generates the overall shape of the Weber function over a suprathreshold range of sound pressure levels up to 80 dB. Empirical examples are provided. [Partially supported by the Rehab. R. &amp; D. Service of the VA.]

CHEMOSENSORY FUNCTION IN CHILDREN WITH RENAL FAILURE

Several studies performed in both adults and children with either chronic renal insufficiency (CRI) or end-stage renal disease (ESRD) receiving dialytic support have shown that these patients have abnormal taste acuity. Most of these abnormalities have been based on simple measurement of detection thresholds. The present studies examined taste and smell function in 10 CRI patients (mean creatinine 5.1 mg/dl), mean age 13.7 years; 9 ESRD patients, mean age 14.3 years; and 9 control subjects with chronic illness (C) (hospitalized child psychiatry patients) mean age 11.0 years. Two parameters of taste function were determined: 1) Intensity testing (IT) - perceived growth of intensity with increase in concentration; 2) Hedonic testing (HT) - relationship between concentration and perceived pleasantness. For IT and HT all subjects were given 5 concentrations each of NaCl (N), sucrose (S) and quinine hydrochloride (Q) in the suprathreshold range. The scaling technique utilized for IT was magnitude estimation with a tape measure and for HT was smiley-face scale. Data were analyzed by plotting standard psychophysical functions. Smell function was tested by UPSIT (Doty, RL: Univ. of Penn. Smell Identification Test), identification of 40 microencapsulated odors in scratch and sniff form. There were no differences between the 3 groups in IT; the slope of the line defined by magnitude estimation of the 5 concentrations of N, S, and Q was similar in the 3 groups. All renal patients and C patients had similar preferences and dislikes for the 5 concentrations of S and Q. However, renal patients had a substantially positive preference for higher concentrations of N compared to C patients. There were no significant differences between the 3 groups as to percent correct responses of the 40 odors in UPSIT. We conclude that patients with ESRD or CRI have normal IT, but seem to prefer N when compared to C patients. Also, ability to identify common odors is preserved in the two groups of renal patients.

Synaptic responses and electrical properties of cells in brain slices of the mouse anteroventral cochlear nucleus

Intracellular recordings were made from cells in brain slices of the anteroventral cochlear nucleus. Responses to electrical stimulation of the stump of the auditory nerve were: (1) all-or-none, following the stimulus with no delay, and insensitive to the removal of extracellular Ca2+, probably representing the firing of directly stimulated auditory nerve fibers, or (2) graded, excitatory postsynaptic potentials, with synaptic delays of about 0.7 msec, which were often followed by graded, inhibitory synaptic potentials with synaptic delays of 1.2 msec or longer. The excitatory and inhibitory synaptic potentials were abolished by the removal of extracellular Ca2+. The result that delays of inhibitory synaptic responses were at least 2 times as long as those of excitatory ones indicates that probably an additional synapse was interposed. Responses to intracellularly injected current pulses show that cells in the anteroventral cochlear nucleus have one of two types of electrical characteristics. Type I properties are characterized by linear current-voltage relationships in the subthreshold voltage range and large, regularly firing action potentials in the suprathreshold range. Type II properties are characterized by nonlinear current-voltage relationships; suprathreshold depolarization elicits only one or two small action potentials. Type II characteristics are particularly well suited for maintaining the information contained in the timing and patterns of firing of the auditory nerve fibers.

Control of repetitive firing in squid axon membrane as a model for a neuroneoscillator.

1. Repetitive firing in space-clamped squid axons bathed in low Ca and stimulated by a just suprathreshold step of current can be annihilated by a brief depolarizing or hyperpolarizing pulse of the proper magnitude applied at the proper phase. 2. In response to such perturbations, membrane potential and ionic currents show damped oscillations toward a steady state. 3. For other, non-annihilating, perturbations repetitive firing resumes with unaltered frequency but with phase resetting. 4. Experimental findings are compared with calculations for the space-and current-clamped Hodgkin-Huxley equations. Annihilation of repetitive firing to a steady state corresponds to a solution trajectory perturbed off a stable limit cycle and into the domain of attraction of a coexistent stable singular point. 5. Experimentally and theoretically the nerve exhibits hysteresis with two different stable modes of operation for a just suprathreshold range of bias current: the oscillatory repetitive firing state and the time-independent steady state. 6. Analogy is made to a brief synaptic input (excitatory or inhibitory) which may start or stop a biological pace-maker.

HETEROGENEITY AND TEMPERATURE EFFECTS ON FLAVOR SENSING OF ETHYL CAPRYLATE

ABSTRACTThe flavor thresholds of 25 panelists for ethyl caprylate dissolved in water were determined at 6, 25 and 43°C. Only the panel mean at 43°C was significantly higher. However, when panelists were partitioned into homogeneous sets, a majority of the panelists were shown to have different thresholds at the three temperatures. Magnitude estimation was used to test for sensitivity of 13 panelists in the supra threshold range. Some judges who were most sensitive at threshold levels were less sensitive than other judges at suprathreshold levels. Causes for heterogeneity among judges are discussed. It is proposed, that, for different judges, different processes in sensing are rate limiting. In part, energy of activation calculations support this supposition.