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PubMed1984

Evidence implicating substantia nigra in regulation of kindled seizure threshold.

We studied the effects of microinjected drugs and brainstem lesions on motor and limbic seizures in the kindling model of epilepsy. The duration of motor seizures was determined by timing the colonic and tonic movements of the extremities. The duration of limbic seizures was determined by measuring afterdischarge recorded on the electroencephalogram. Bilateral microinjection of a gamma-aminobutyric acid (GABA) agonist, muscimol, into the area of the substantia nigra (SN) markedly suppressed both motor and limbic seizures induced by stimulation of amygdala, olfactory structures, or lateral entorhinal cortex. Microinjection of saline did not suppress seizures. The suppressive effect of muscimol: (i) dissipated after several hours and was dependent on dose; (ii) was due to an elevation of the seizure threshold, since typical seizures could be elicited with electrical current far exceeding the threshold; and (iii) exhibited spatial specificity since muscimol injections 1 to 2 mm dorsal to the SN or into neocortex did not suppress the seizures. The actions of muscimol were probably mediated by its GABA agonist properties, since microinjection of an irreversible inhibitor of GABA transaminase (gamma-vinyl GABA) into the area of the SN also suppressed kindled seizures. Destruction of brainstem structures was produced by microinjection of the neurotoxin, N-methyl-D,L-aspartate. Seizures were markedly suppressed in animals with bilateral destruction of the SN but not in animals in which the SN was spared bilaterally. We interpret the data to indicate that the SN is the site at which the GABA agonists and lesions act to raise the threshold for kindled seizures. The suppression of limbic seizures indicates that this brainstem nucleus can regulate the intrinsic neuronal excitability of hemispheric sites.

Aminocaproates↗
PubMed1978

Studies of visual function and its decay in mice with hereditary retinal degeneration.

Functional implications of mouse hereditary retinal degeneration have been studied at the level of the superior colliculus and visual cortex in the C57BL/6J-le rd strain. On autoradiography at a light-microscopic level, following eye injection with radioactive compounds, central visual structures appeared normal. A slight reduction in ipsilateral retinal projection was probably related to reduced retinal pigmentation associated with the light ear (le) mutation. In recordings from visual cortex and tectum in rd mice older than five months the cells discharged with highly rhythmic maintained activity. This ongoing activity depended on retinal input, since temporary asphyxia of the eye stopped it immediately. The frequency of the rhythm was influenced by the anesthesia. In these older mice no visual receptive fields could be mapped, but in a few tectal recordings it was possible to suppress the maintained activity by diffuse, very intense illumination. As in normal mice, no auditory or somatosensory responses were observed in the visual cortex or upper tectal layers. In recordings from tectum before the age of three weeks retinotopic topography and receptive fields were normal. By day 24 no receptive fields could be recorded from parts of the tectum representing the central 90--100 degrees of the visual field, whereas within a peripheral ring responses were still roughly normal under photopic conditions. Over the following four months these peripheral responses faded away slowly. Incremental thresholds, especially in the scotopic range, were elevated, rising slowly to unmeasurable values. Similarly during dark adaptation the thresholds fell to values several log units above those reached in normal mice; these values of dark adapted thresholds in rd mice rose with age. This is consistent with morphological changes known to occur in the retina as a consequence, of the rd mutation the rods degenerating before the cones.

Animals↗
PubMed1984

Plasma beta-endorphin, pain thresholds and anxiety levels across the human menstrual cycle.

Nine normally cycling women and seven other women employing oral contraception were tested during five phases (menstrual, follicular, ovulatory, luteal and premenstrual) of their menstrual cycle. The procedure consisted of administration of an anxiety inventory and determination of pain detection and pain thresholds in response to electric shock and the cold pressor task. Venipunctures were also performed and the plasma of normally menstruating women later assayed for beta-endorphin. Analyses revealed that the variance but not the mean levels in peripheral beta-endorphin levels significantly differed (p less than 0.01) across the menstrual cycle with the greatest amount of variance found during the ovulatory phase and the least during the luteal phase. The high variance during the period around ovulation was due to several subjects having extremely elevated beta-endorphin levels which possibly may have resulted from the occurrence of ovulation. Furthermore, a significant positive correlation between anxiety levels and beta-endorphin levels was found only during the menstrual phase. The absence of findings concerning cyclic variation in pain thresholds is contrary to earlier reports and indicates that such a phenomenon may be dependent upon the paradigm employed.

Adult↗
PubMedDate not supplied

Threshold procedures for assessing the impact of agents on brain reward systems.

Chemical effects on the reinforcing quality of electrical stimulation of the rat brain can be assessed using a variety of methods, most commonly by observing changes in response rates maintained under specific schedules of reinforcement. We present results demonstrating the utility of procedures for assessing the minimum amount of electrical stimulation required to support rat leverpress responding, that is, the brain-stimulation reward (BSR) threshold. In these threshold procedures, each leverpress produced by the rat decreases the duration of the electrical stimulus delivered to the posterior lateral hypothalamus until the rat fails to respond. The stimulus duration is then reset to its initial value and the procedure begins again. The last stimulus duration in a series supporting a response is defined as the stimulus duration (SD) threshold, and the mean SD threshold is determined daily. Stable SD thresholds are achieved within 2 weeks, and this measure is sensitive to agent-induced changes in rats' response to BSR. To illustrate the utility of this approach, data are presented showing that rats' BSR thresholds changed significantly following exposure to triethyltin or carbon monoxide. The results support the view that threshold methods can be used to dissociate agent-induced effects on brain reward systems and BSR quality from changes in performance or effects on other behavioral processes.

Animals↗
PubMed2005

Increased taste intensity perception exhibited by patients with chronic back pain.

There is overlap between brain regions involved in taste and pain perception, and cortical injuries may lead to increases as well as decreases in sensitivity to taste. Recently it was shown that chronic back pain (CBP) is associated with a specific pattern of brain atrophy. Since CBP is characterized by increased sensitivity to pain, we reasoned that the sense of taste might also be enhanced in CBP. Detection and recognition thresholds were established for a sour taste and ratings of both suprathreshold taste intensity and pleasantness-unpleasantness perception were collected for sweet, sour, salty and bitter stimuli in 11 CBP patients and 11 matched control subjects. As a control, ratings were also collected for visual assessment of degree of grayness. There was no difference between CBP and control subjects for visual grayness rating. On the other hand, CBP patients in comparison to control subjects rated gustatory stimuli as significantly more intense but no more or less pleasant and showed a trend towards a lower detection threshold (i.e. increased sensitivity). The selectivity of the taste disturbance suggests interaction between pain and taste at specific brain sites and provides further evidence that CBP involves specific brain abnormalities.

Adult↗
PubMed2005

The effects of amplitude-spectrum statistics on foveal and peripheral discrimination of changes in natural images, and a multi-resolution model.

Psychophysical thresholds were measured for discriminating small changes in spatial features of naturalistic scenes (morph sequences), for foveal and peripheral vision, and under M-scaling. Sensitivity was greatest for scenes with near natural Fourier amplitude slope, perhaps implying that human vision is optimised for natural scene statistics. A low-level model calculated differences in local contrast between pairs of images within a few spatial frequency channels with bandwidth like neurons in V1. The model was "customised" to each observer's contrast sensitivity function for sinusoidal gratings, and it could replicate the "U-shaped" relationships between discrimination threshold and spectral slope, and many differences between picture sets and observers. A single-channel model and an ideal-observer analysis both failed to capture the U-shape.

Contrast Sensitivity↗
PubMed1996

Lowering the threshold for the diagnosis of gestational diabetes.

OBJECTIVE: Our purpose was to determine whether lowering the diagnostic threshold for gestational diabetes mellitus on 3-hour 100 gm oral glucose tolerance testing will select a population at risk for adverse perinatal outcome. STUDY DESIGN: In this retrospective study 434 patients with an abnormal 50 gm glucose screen result (> or = 140 mg/dl) underwent a standardized 3-hour oral glucose tolerance test. The results were stratified according to maternal weight and the criteria recommended by Sacks or Carpenter. Birth weight and rate of macrosomia were the primary perinatal outcome variables analyzed. RESULTS: Analysis of the data set stratified according to the Sacks criteria revealed results very similar to the Carpenter criteria data set. Patients who would have been newly diagnosed with gestational diabetes mellitus only if the lowered criteria were used (group 2) were older and heavier. No other variable comparisons achieved statistical significance. When the same patients were stratified according to prepregnancy weight, overweight patients were older, gained less weight during the third trimester, underwent cesarean section more often, and had higher cumulative maternal morbidity. Regression analysis showed that the degree of hyperglycemia did not predict macrosomia or influence birth weight, but prepregnant maternal body mass index was associated with macrosomia. CONCLUSIONS: Fetal macrosomia is influenced by maternal prepregnant body mass index. Lowering the glucose tolerance test threshold would result in overdiagnosis of gestational diabetes mellitus without improving perinatal outcome.

Birth Weight↗
PubMed1997

Intrinsic and extrinsic factors affecting phrenic motoneuronal excitability in neonatal rats.

We examined intrinsic and extrinsic factors affecting phrenic motoneuron (PMN) excitability in neonatal rats. Using an in vitro brainstem-spinal cord en bloc, 127 PMNs were recorded under whole-cell patch-clamp conditions. Inspiratory synaptic drives and passive membrane properties, including whole-cell membrane capacitance (Cm), input resistance (Rn), and time constant (tau), were measured with either voltage- or current-clamp techniques. On the basis of firing behavior during inspiration, two types of PMNs could be distinguished: active (107/127 = 84%) and silent PMNs (20/127 = 16%). Active PMNs always produced multiple spikes during inspiration, while silent PMNs remained silent for most inspiratory cycles. Compared to silent PMNs, active PMNs had significantly higher Rn, inspiratory drive potential, and more depolarized resting membrane potential (RMP). With respect to inspiratory drive current, no significant difference was observed between the two types of PMN. Analysis of action potential waveforms did not show a significant difference between their threshold levels. Our results suggest that in addition to size-related properties, RMP determines the recruitment of PMNs and consequently, of motor units in the diaphragm.

Action Potentials↗
PubMed2003

Tone burst-evoked myogenic potentials in rat neck extensor and flexor muscles.

Vestibular evoked myogenic potential (VEMP) has been used to test the vestibulocollic reflex. This study establishes a stable recording of VEMPs of animals, and presents useful parameters for vestibular ability. In an acute experiment, rats were decerebrated, and myogenic potential from neck extensor muscles was recorded. The myogenic potentials elicited by a tone-burst stimulus showed a biphasic response in the ipsilateral muscle, and the mean latency of the response was 3.56 ms, the positive peak appearing at 4.63 ms. The onset latencies of the response lengthen as the stimulus becomes weaker; this is the most suitable parameter of vestibular ability. The latencies of the monophasic response from the spinal cord were shorter than those of muscle. After injection of a muscle relaxant, myogenic potentials disappeared immediately, but the spinal cord response remained. We succeeded in recording responses not only from acute experimental animals but also from free-moving animals for the first time. These myogenic potentials were similar to VEMPs in humans; because the threshold of the response was higher than the auditory brainstem response threshold by 40-45 dB, the response could only be recorded with very high spontaneous muscle activity and the latency was shorter than the startle reflex.

Acoustic Stimulation↗
PubMed1997

Magnetic stimulation of the descending and ascending tracts at the foramen magnum level.

To test the possibility that stimulation over the foramen magnum activates ascending tracts as well as descending tracts, we studied 4 patients with myoclonic epilepsy all of whom had enhanced cortical long loop reflexes (LLRs) and 10 normal subjects, using our previously reported method (Ugawa et al., Ann. Neurol., 1994, 36: 618-624). For latency comparisons, peripheral nerve stimulation at the elbow and spinal motor root were also performed. In all patients, magnetic stimulation at the foramen magnum consistently elicited long loop reflexes as well as direct responses caused by stimulation of the descending tracts. In contrast, no LLRs were ever seen in any normal subjects. The latencies of both types of response were the same whether stimulation used upward or downward current in the brain, although the former was always more effective. This indicates that stimulation at the level of the foramen magnum activates ascending tracts as well as descending tracts at a fixed position. The threshold for LLRs was lower than that for activation of the descending tracts. This threshold difference is compatible with the hypothesis that large diameter fibers from muscle afferent conduct the central afferent volley for LLRs (Marsden et al., Brain, 1977, 100: 185-200).

Afferent Pathways↗
PubMed1984

Thresholds for biological effects of time-varying magnetic fields.

Investigations of the biological effects of time-varying magnetic fields in the extremely low frequency range have been carried out with particular reference to NMR imaging. One effect encountered is the stimulation of nerves and muscles by induced eddy currents. The nature of this effect has been studied in rats exposed to whole body homogeneous fields and in the human forearm with local exposures. Electromyography was used to provide quantitative measurements of thresholds and responses for human exposures. The field exposures required to produce a detectable response are dependent upon the pulse period, pulse waveform and the current path in tissue. For the rat experiments the lowest threshold occurred for a damped sinusoidal pulse of period 0.33 ms with a maximum rate of change of field of 2400 T s-1. The lowest threshold for sensation in the human experiments was 2100 T s-1 for a similar type of field. Simple theory for conduction is considered and current densities induced are estimated as 5 A m-2.

Animals↗
PubMed2004

Spike-triggered average torque and muscle fiber conduction velocity of low-threshold motor units following submaximal endurance contractions.

The motor unit twitch torque is modified by sustained contraction, but the association to changes in muscle fiber electrophysiological properties is not fully known. Thus twitch torque, muscle fiber conduction velocity, and action potential properties of single motor units were assessed in 11 subjects following an isometric submaximal contraction of the tibialis anterior muscle until endurance. The volunteers activated a target motor unit at the minimum discharge rate in eight 3-min-long contractions, three before and five after an isometric contraction at 40% of the maximal torque, sustained until endurance. Multichannel surface electromyogram signals and joint torque were averaged with the target motor unit potential as trigger. Discharge rate (mean +/- SE, 6.6 +/- 0.2 pulses/s) and interpulse interval variability (33.3 +/- 7.0%) were not different in the eight contractions. Peak twitch torque and recruitment threshold increased significantly (93 +/- 29 and 12 +/- 5%, P <0.05) in the contraction immediately after the endurance task with respect to the preendurance values (0.94 +/- 0.26 mN.m and 3.7 +/- 0.5% of the maximal torque), whereas time to peak of the twitch torque did not change (74.4 +/- 10.1 ms). Muscle fiber conduction velocity decreased and action potential duration increased in the contraction after the endurance (6.3 +/- 1.8 and 9.8 +/- 1.8%, respectively, P <0.05; preendurance values, 3.9 +/- 0.2 m/s and 11.1 +/- 0.8 ms), whereas the surface potential peak-to-peak amplitude did not change (27.1 +/- 3.1 microV). There was no significant correlation between the relative changes in muscle fiber conduction velocity or surface potential duration and in peak twitch torque (R2= 0.04 and 0.10, respectively). In conclusion, modifications in peak twitch torque of low-threshold motor units with sustained contraction are mainly determined by mechanisms not related to changes in action potential shape and in its propagation velocity.

Action Potentials↗
PubMed1983

Time thresholds for increments and decrements in luminance.

Time thresholds, i.e., the minimal durations necessary to just detect a change in brightness, were measured for light increments and decrements of a 1 degree test spot centered on a background of 20 degrees. Background luminance varied from -1 to 3 log td and retinal eccentricity from 0 degree to 50 degrees. Step size ranged from 0.04 to 1.5 log units and was the same in absolute units for both directions. Two types of stimuli were used: Type A, in which increments and decrements emerge from the same uniform background, and Type B, in which increments are the same as in Type A but decrements consist of a brief interruption of the test spot. Type A stimulation resulted in similar time thresholds for increments and decrements or, under some conditions, slightly shorter decrement thresholds. Type B stimulation resulted in similar thresholds for foveal vision. However, with increasing step size, decreasing background luminance, and increasing eccentricity, the time threshold for the decrement progressively exceeded that for the increment (up to 80 msec). This difference is attributed to different rise and fall times of the photoreceptor response as well as to Troxler's effect.

Adult↗
PubMed1993

Visual performance of the toad (Bufo bufo) at low light levels: retinal ganglion cell responses and prey-catching accuracy.

The accuracy of toad snapping towards moving worm dummies under various levels of dim illumination (from absolute threshold to "moonlight") was video-recorded and related to spike responses of retinal ganglion cells exposed to equivalent stimuli. Some toads (at ca. 16 degrees C) successfully snapped at dummies that produced only one photoisomerization per 50 rods per second in the retina, in good agreement with thresholds of sensitive retinal ganglion cells. One factor underlying such high sensitivity is extensive temporal summation by the ganglion cells. This, however, is inevitably accompanied by very long response latencies (around 3 s near threshold), whereby the information reaching the brain shows the dummy in a position where it was several seconds earlier. Indeed, as the light was dimmed, snaps were displaced successively further to the rear of the dummy, finally missing it. The results in weak but clearly supra-threshold illumination indicate that snaps were aimed at the advancing head as seen by the brain, but landed further backwards in proportion to the retinal latency. Near absolute threshold, however, accuracy was "too good", suggesting that the animal had recourse to a neural representation of the regularly moving dummies to correct for the slowness of vision.

Animals↗
PubMed2002

Increased transcranial magnetic motor threshold after ECT. A case report.

Electroconvulsive therapy (ECT) is a powerful antidepressive treatment, but its mechanism of action remains poorly understood. To clarify the influence of ECT on corticospinal tract excitability we tested the motor threshold, the motor evoked potential (MEP) input/output curve, and the intracortical excitability using transcranial magnetic stimulation in a depressed patient before and after successful treatment with ECT. Resting motor thresholds were increased bilaterally after treatment, and the input/output curve less steep. These results point to a decreased excitability of the corticospinal motor tract after successful ECT.

Aged↗
PubMed1982

The spatial grain of the perifoveal visual field.

Measurements for normal human photopic vision in the fovea and in 2.5, 5 and 10 degree positions in the periphery reveal that hyperacuity thresholds rise faster with eccentricity than visual resolution thresholds. On the other hand, the retinal distances over which hyperacuity detection remains optimal show a much slower rise. At 10 degrees eccentricity, hyperacuity thresholds are 10 times higher visual resolution thresholds 4-5 times higher, and optimal processing distances for hyperacuity only 2-3 times larger than at the fovea. Psychophysical procedures do not, therefore, provide a single unambiguous measure for the changes of spatial grain across the visual field.

Differential Threshold↗
PubMed1990

Diversity of characteristic frequency rate-intensity functions in guinea pig auditory nerve fibres.

Rate-intensity functions at characteristic frequency (CF) were recorded from single fibres in the auditory nerve of anaesthetised guinea pigs. Within the same animal, CF rate-intensity functions, although probably forming a continuum, could be conveniently divided into three groups; (1) Saturating; reach maximum discharge rate within 30 dB of threshold, (2) Sloping-saturation; initially rapid growth in discharge rate leading to a slower growth in discharge rate but not saturating and (3) Straight; approximately constant increase in firing rate per decibel increase in sound pressure up to the maximum sound pressures used. Thresholds for individual fibres were plotted relative to compound action potential thresholds at the appropriate frequency. Fibres with straight CF rate-intensity functions had the highest thresholds. Fibres of the saturating CF sloping-saturation CF rate-intensity type had thresholds intermediate between saturating and straight. There was a close relationship between the type of CF rate-intensity function exhibited by a fibre and its spontaneous discharge rate. Fibres with saturating CF rate-intensity functions generally had high spontaneous discharge rates (greater than 18/s), whereas those with straight CF rate-intensity functions generally had low spontaneous discharge rates (less than 0.5/s). The majority of fibres with sloping-saturation CF rate-intensity functions had spontaneous rates between 0.5/s and 18/s. There was a negative correlation (r = -0.59) between the logarithm of the spontaneous discharge rate and relative threshold at CF with the lowest spontaneous rate fibres having the highest thresholds and vice-versa. This diversity of CF rate-intensity functions has functional implications for both frequency and intensity coding at high sound pressures in the mammalian auditory system.

Action Potentials↗
PubMed2006

Effect of defibrillation testing on management during implantable cardioverter-defibrillator implantation.

BACKGROUND: Verification of defibrillation efficacy by defibrillation threshold (DFT) testing during implantable cardioverter-defibrillator implantation is the current standard. Generally, defibrillation of ventricular fibrillation at 10 J below the maximum output of a device is felt to establish an adequate safety margin. Nonetheless, DFT testing adds to cost and carries some potential for morbidity, whereas its impact on outcomes in the modern era of defibrillator technology is unclear. We aimed to determine the frequency that DFT testing resulted in a change at device implant and to identify clinical and echocardiographic predictors of the need for DFT testing. METHODS: We reviewed all implantable cardioverter-defibrillators that were implanted at the London Health Sciences Centre (Ontario, Canada) from June 1999 to August 2003 and used multivariate analysis to determine variables associated with DFT test failures and elevated DFT values. When a defibrillation failure was not observed, a lowest energy to defibrillate (LED) was recorded. RESULTS: Among 168 implants, DFT testing was successful with a minimum 10-J safety margin in 152 (90%), whereas the remaining 16 required changes at device implant. In a multivariate analysis, use of amiodarone was independently associated with DFT failure (odds ratio, 4.6; 95% confidence interval, 1.2-17.0). Significantly higher mean DFT/LED values were observed among patients on amiodarone (1.36 J; P = .0041). Those with nonischemic cardiomyopathy had a higher mean DFT/LED compared with those with ischemic cardiomyopathy (1.44 J; P = .028). CONCLUSIONS: Use of amiodarone is associated with a 4-fold increase in risk of DFT failure and subsequent need for changes at implant to achieve a safe threshold. Defibrillation threshold testing appears to be most useful for patients taking amiodarone.

Amiodarone↗