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PubMed2003

Functional imaging of perceptual learning in human primary and secondary somatosensory cortex.

Cellular mechanisms underlying synaptic plasticity are in line with the Hebbian concept. In contrast, data linking Hebbian learning to altered perception are rare. Combining functional magnetic resonance imaging with psychophysical tests, we studied cortical reorganization in primary and secondary somatosensory cortex (SI and SII) and the resulting changes of tactile perception before and after tactile coactivation, a simple type of Hebbian learning. Coactivation on the right index finger (IF) for 3 hr lowered its spatial discrimination threshold. In parallel, blood-oxygen level-dependent (BOLD) signals from the right IF representation in SI and SII enlarged. The individual threshold reduction was linearly correlated with the enlargement in SI, implying a close relation between altered discrimination and cortical reorganization. Controls consisting of a single-site stimulation did not affect thresholds and cortical maps. Accordingly, changes within distributed cortical networks based on Hebbian mechanisms alter the individual percept.

Adult↗

PubMed2001

The effects of atrial electrical remodeling on atrial defibrillation thresholds.

Electrical remodeling of atrial fibrillation may account for the increase in atrial defibrillation thresholds over time. The aim of this study was to examine the time course of electrical remodeling and the benefit of early defibrillation on the defibrillation threshold. Twenty-six mongrel dogs weighing 27.6 +/- 3.3 kg were induced into AF by repeated high output burst atrial pacing. Eight dogs were paced for multiple time periods of 5, 20, 40, and 60 minutes. Five dogs each had burst pacingfor 4 hours and 8 hours, and eight dogs were paced at a high rate (640 beats/min) for 48 hours. Biphasic atrial defibrillation shocks with a pulse width of 3/3 ms synchronized to the left apical electrogram were delivered to coil electrode catheters positioned in the lateral left and right atria. Defibrillation voltage was increased from 50 V in 20- to 30-V steps until defibrillation was successful. As the pacing period increased, a decrease in atrial fibrillation cycle lengths and atrial effective refractory period was not observed before 8 hours. Similarly, the defibrillation threshold did not change significantly until the 8-hour pacing period was reached. The defibrillation thresholds were 69 +/- 28 V for 5 minutes, 64 +/- 20 V for 20 minutes, 99 +/- 85 V for 40 minutes, 78 +/- 51 V for 60 minutes, 78 +/- 38 V for 4 hours, 124 +/- 33 V for 8 hours, and 133 +/- 32 V for 48 hours (mean +/- SD) (P < 0.05). Atrial electrical remodeling in a rapid atrial pacing canine model is not observed until after 4 hours of burst atrial pacing. The atrial defibrillation threshold increases with increasing duration of burst atrial pacing, and follows a similar time course to other parameters of electrical remodeling.

Animals↗

PubMed1976

Method for quantitative estimation of thermal thresholds in patients.

A quantitative method for the examination of thermal sensibility was applied in 26 normal subjects and in patients with various neurological disorders. The stimulation technique resembled Békésy audiometry: the patient reversed the direction of the temperature change of a thermode whenever warm, cold, or thermal pain thresholds were reached. The resulting temperature curve enables a quantitative description of the subject's thermal sensibility and of the degree of impairment displayed by neurological patients.

Abdomen↗

PubMed2003

Thresholds for stereo-slant discrimination between spatially separated targets are influenced mainly by visual and memory factors but not oculomotor instability.

Surface-slant variations can be sensed either simultaneously with steady fixation or sequentially with saccadic gaze shifts. Stereo-slant discrimination thresholds are affected by visual, oculomotor, and memory factors. We have investigated the effects of fixation strategy, target separation, and exposure duration on stereo-slant discrimination. With long exposure durations (734 ms), stereo-slant discrimination thresholds measured with simultaneous presentation of test and reference stimuli were lower with gaze shifts than without them when target separations exceeded 4 deg. Above 4-deg target separations, the benefits of improved disparity resolution with foveal gaze shifts outweighed the costs of oculomotor variability associated with saccades. With short exposure durations (167 ms), as target separation increased, stereo-slant discrimination thresholds measured without gaze shifts increased with both sequential and simultaneous stimulus presentations, whereas thresholds with gaze shifts remained constant. This indicates that oculomotor errors are not an important factor in stereo-slant discrimination. In contrast to stereo-slant thresholds, sequential stereo-depth thresholds between two dots, measured with gaze shifts, increased with target separation. Thus, oculomotor error increases with target separation, and it is an important factor in stereo-depth discrimination.

Depth Perception↗

PubMed2000

Baclofen increases the soleus stretch reflex threshold in the early swing phase during walking in spastic multiple sclerosis patients.

The effect of baclofen on walking performance was examined in nine spastic multiple sclerosis patients. In addition, nine healthy subjects were tested as controls. The modulation of the short latency soleus stretch reflex was closer to normal with baclofen compared to the recordings without baclofen, the modulation index being 74% (range: 60 - 100) with baclofen and 62% (range: 20 - 100) without baclofen, P=0.03. In healthy subjects the modulation index was 100% (range: 52 - 100). In the early swing phase the threshold of the soleus stretch reflex was significantly higher during baclofen medication being 139 deg/s (range: 63 - 302) compared with 93 deg/s (range: 37 - 187) without baclofen, P=0.004. The relation between the stretch velocity (input) and the amplitude of the stretch reflex (output) in early swing phase was unchanged being 0. 27 microVs/deg (range: 0.1 - 1.51) in patients with baclofen and 0. 24 microVs/deg (range: 0.08 - 0.79) without baclofen, P=0.25. Baclofen induced no change in input - output properties of the stretch reflex during walking compared with findings in a sitting position at matched EMG activity. There was a significant correlation between clinical spasticity score and stretch reflex threshold in the early swing phase (rho=-0.61, P=0.04) and between clinical spasticity score and the slope of the best linear fit in the early swing phase (rho=0.72, P=0.009).

Adult↗

PubMed1995

Preservation of peristaltic reflex in hypertrophied ileum of guinea pig.

Chronic obstruction of the guinea pig ileum leads to distension and muscular hypertrophy, but how this affects passive biomechanical and nerve-mediated contractions and clearance known as peristaltic reflex is unclear. Ileum of controls had a diameter of 3.0 +/- 1.1 mm and a circular muscle thickness of 37.2 +/- 11.2 microns; 4 wk after placement of a nonconstricting Gore-Tex band, the ileum was distended to 10.0 +/- 0.19 mm, and its muscle had hypertrophied to 195.0 +/- 61.2 microns. Hypertrophied segments exceeded controls in capacity (e.g., 5.1 +/- 1.1 vs. 1.1 +/0 0.2 ml at 6 cm), compliance, and hysteresis. Threshold volumes and pressures that triggered the reflex were 3.3 +/- 1.3 ml and 3.1 +/- 0.01 mmHg in hypertrophied vs. 0.7 +/- 0.2 ml and 1.5 +/- 0.2 mmHg in controls. The diameter increase that triggered the reflex was 1.4 +/- 0.1 mm in hypertrophied segments and 0.6 +/- 0.1 mm in controls. Hypertrophied segments generated fewer contractions of virtually double the amplitude and failed to generate a pressure differential between up- and downstream sites as controls did. Hypertrophied segments generated larger stroke volumes and cumulative clearance than controls. The ratio of antegrade to retrograde clearance was similar in hypertrophied and control segments. The length of the occluding segment in hypertrophied preparations exceeded that of controls. Control contractions indented the antimesenteric border and propagated antegrade from their site of origin; bizarre writhing movements of hypertrophied segments made their contractions difficult to monitor. Thus distension and muscular hypertrophy do not interfere with the ability of the chronically obstructed guinea pig ileum to generate a peristaltic reflex at least as readily and as powerful and as effective in clearing the lumen as controls.

Animals↗

PubMed2005

Re-defining the ischemic threshold for jugular venous oxygen saturation--a microdialysis study in patients with severe head injury.

Neurological change is more likely to occur when jugular venous oxygen saturation (SjvO2) is less than 50%. However, the value indicating cellular damage has not been clearly defined. We determined the critical SjvO2 value below which intracerebral extracellular metabolic abnormalities occurred in 25 patients with severe head injury. All patients received standard treatment with normoventilation and maintenance of intracranial pressure < 20 mmHg. SjvO2 was measured from the dominant jugular bulb using a calibrated fibreoptic catheter. Intracerebral metabolic monitoring was performed by collecting perfusate from a microdialysis probe placed in the frontal lobe anterior to the intracranial catheter. Excitotoxin (glutamate) and other extracellular metabolites (lactate, glucose and glycerol) were measured frequently using enzymatic and colorimetric methods. We observed biphasic relationships between SjvO2 and all intracerebral metabolites. Analysis of variance showed that there were rapid increases in glutamate, glycerol and lactate when SjvO2 dropped below 40, 43 and 45% respectively. Extracellular glucose decreased when SjvO2 dropped below 42%. Our findings suggested that the ischemic threshold for SjvO2 in patients with severe head injury is 45%, below which secondary brain damage occurred.

Adolescent↗

PubMed1981

Motion mechanisms in strobe-reared cats: psychophysical and electrophysical measures.

Cats were reared from birth to at least 12 months of age in a visually static environment (illuminated 40/min by a 3 mu sec strobe flash). Single unit recordings from these animals revealed abnormalities in spatial and directional properties of cortical neurons. In an attempt to find psychophysical correlates of these neural deficits, spatial contrast sensitivity and motion detection thresholds were measured behaviorally. Both spatial vision and motion detection were greatly impaired. While spatial deficits failed to recover, motion thresholds improved greatly following extended training. These improvements in behavioral motion response were accompanied by the recovery of cortical directional selectivity. The recovery of motion thresholds and directional selectivity was direction specific: the distribution of the preferred directions of cortical neurons and motion thresholds were sharply biased towards the direction first seen in training. Thus, directional mechanisms of adult motion deprived cats may be modified if following deprivation the animals are trained to detect moving stimuli.

Animals↗

PubMed1978

Orienting behaviour during aerial and underwater visual discrimination by the mink (Mustela vison schreber).

Orienting responses by mink during aerial and underwater visual discrimination tests were most frequent when the grating lines subtended angles at the eye near the visual threshold angle. Factorial analysis showed that in air and in water at ranges from 10 to 90 cm most responses occurred at 30 cm discrimination distance and more occurred to marginally supra-threshold than to marginally sub-threshold stimuli. Between media, more responses occurred in air than in water. At longer ranges the mink oriented less readily than at 30 cm but if orienting occurred better discrimination followed than if the mink did not orient.

Animals↗

PubMed1989

Effects of ventricular fibrillation and defibrillation on pacing threshold in the anesthetized dog.

The effects of transthoracic and internal defibrillation on the bipolar ventricular pacing threshold in 20 anesthetized dogs were examined. Ventricular pacing was accomplished with a computer-controlled, constant voltage pacemaker that permitted rapid determination of pacing threshold. Defibrillation at various energy levels was administered during ventricular pacing and after ventricular fibrillation of 5, 15, 30, 45, 60 or 120 s duration in the 20 dogs. Defibrillation during pacing or within 15 s after initiation of ventricular fibrillation did not significantly increase threshold, regardless of defibrillation energy or mode of delivery. Defibrillation after ventricular fibrillation lasting greater than or equal to 30 s increased (p less than 0.05) threshold determined 6 s after defibrillation. The increase in threshold (in volts) determined 6 s after defibrillation was an exponential function of fibrillation duration (30 s = 0.30 +/- 0.09 V; 45 s = 0.53 +/- 0.13 V; 60 s = 2.24 +/- 1.05 V), but was independent of defibrillation energy or mode of delivery. Threshold returned to control values 15 to 30 s after defibrillation. Cardiopulmonary bypass to maintain coronary perfusion prevented the increase in pacing threshold even after ventricular fibrillation of up to 2 min duration. Pacing threshold is not increased by transthoracic or internal defibrillation, but is increased by ventricular fibrillation of sufficient duration to create substantial myocardial hypoxemia.

Anesthesia↗

PubMed2005

Therapeutic thresholds in methadone maintenance treatment: a receiver operating characteristic analysis.

Twenty-four-hour trough (R)- and (R,S)-methadone plasma concentrations were measured on 94 methadone maintenance treatment (MMT) patients classified as 'responders' or 'non-responders', based on urine toxicology evidence of recent illicit opiate use. Receiver operating characteristic (ROC) curves for daily dose, dose/bodyweight, and (R)- and (R,S)-methadone trough plasma concentrations were used to identify optimal thresholds; areas under the curve (AUC) were used to compare predictive power. Non-responders (n=37) had a lower mean dose (73 mg/day versus 147 mg/day; p<0.001), (R)-methadone concentration (136 ng/ml versus 223 ng/ml; p<0.005) and (R,S)-methadone concentration (266 ng/ml versus 409 ng/ml; p=0.001) than responders. On multivariate regression, duration of treatment and methadone dose were significantly associated with treatment response. After backward stepwise regression, each year of treatment increased the odds of abstinence from illicit opioid use by 34% (OR 1.34; 95% CI 1.14-1.57)); each 20mg of methadone dose by 36% (OR 1.36 CI; 95% CI 1.11-1.67). On ROC analysis, AUC for daily dose (0.77, 95% CI 0.68-0.87), dose/bodyweight (0.76, 95% CI 0.66-0.85), (R)-methadone (0.73, 95% CI 0.63-0.84) and (R,S)-methadone concentration (0.70, 95% CI 0.59-0.81) did not differ significantly. Dose/bodyweight, and trough plasma concentrations of (R)- or (R,S)-methadone were no better predictors of treatment response than daily dose, and did not improve the fit of the model for treatment outcome as judged by the likelihood ratio test (p=0.21, 0.88, and 0.97, respectively). Optimal therapeutic thresholds (sensitivity, specificity) were: daily dose 100mg/day (67%, 81%); (R)-methadone 200 ng/ml (51%, 78%); (R,S)-methadone 400 ng/ml (40%, 81%). Thresholds with specificity near 90% (dose 140 mg/day; (R)-methadone 250 ng/ml; (R,S)-methadone 500 ng/ml) may help guide dose titration for patients continuing to use illicit opiates.

Adult↗

PubMed2001

Atrial defibrillation thresholds of electrode configurations available to an atrioventricular defibrillator.

INTRODUCTION: Little investigation has been conducted to assess the atrial defibrillation thresholds of electrode configurations using electrodes designed for internal ventricular defibrillation (right ventricle [RV], superior vena cava [SVC], and pulse generator housing [Can]) combined with coronary sinus (CS) electrodes. We hypothesized that a CS-->SVC+Can electrode configuration would have a lower atrial defibrillation threshold than a standard configuration for defibrillation, RV-->SVC+Can. We also tested the atrial defibrillation thresholds of five other configurations. METHODS AND RESULTS: In 12 closed chest sheep, we situated a two-coil (RV, SVC) defibrillation catheter, a left-pectoral subcutaneous Can, and a CS lead. Atrial fibrillation was burst induced and maintained with continuous infusion of intrapericardial acetyl-beta-methylcholine chloride. Using fixed-tilt biphasic shocks, we determined the atrial defibrillation thresholds of seven test configurations in random order according to a multiple-reversal protocol. The peak voltage and delivered energy atrial defibrillation thresholds of CS-->SVC+Can (168+/-67 V, 2.68+/-2.40 J) were significantly lower than those of RV-->SVC+Can (215+/-88 V, 4.46+/-3.40 J). The atrial defibrillation thresholds of the other test configurations were RV+CS-->SVC+Can: 146+/-59 V, 1.92+/-1.45 J; RV-->CS+SVC+Can: 191+/-89 V, 3.53+/-3.19 J; CS-->SVC: 188+/-98 V, 3.77+/-4.14 J; SVC-->CS+ Can: 265+/-145 V, 7.37+/-9.12 J; and SVC-->Can: 516+/-209 V, 24.5+/-15.0 J. CONCLUSIONS: The atrial defibrillation threshold of CS-->SVC+Can is significantly lower than that of RV-->SVC+Can. In addition, the low atrial defibrillation threshold of RV+CS-->SVC+Can merits further investigation. Based on corroboration of low atrial defibrillation thresholds of CS-based configurations in humans, physicians might consider using CS leads with atrioventricular defibrillators.

Alabama↗

PubMed1991

Cocaine enhances the reward value of medial prefrontal cortex self-stimulation.

Intracranial self-stimulation (ICSS) of at least some brain sites is thought to be mediated by mesolimbic dopamine (DA) neurons. However other ICSS sites, especially those in the medial prefrontal cortex (MFC), have been shown to be relatively insensitive to drugs (e.g. amphetamine, neuroleptics) that alter DA synaptic transmission. In the present study, rats with ICSS electrodes implanted in both the medial forebrain bundle (MFB) and the MFC were treated once per day for 10 days with cocaine (15.0 mg kg-1). Cocaine decreased the thresholds for both MFB (-51.4%) and MFC (-23.0%) ICSS. Cocaine also increased rates of responding for MFC but not MFB ICSS. These data provide additional support for the view that the MFC contributes to the rewarding effects of cocaine.

Animals↗

PubMed1985

Effect of stimulus parameters on fusional and stereoscopic performance.

The effect of stimulus size and complexity on the horizontal divergent diplopia threshold, stereoscopic range, reappearance of stereopsis, and re-fusion point was examined. It was found that the addition of random-dot (RD) backgrounds significantly increased both the diplopia threshold and re-fusion point, whereas the further addition of multiple depth planes did not. Stereopsis and diplopia were found to coexist in RD stereograms both when the disparity increased past the diplopia threshold and when it was decreasing toward the re-fusion point. This suggests that monocularly distinguishable contours must be added to RD stereograms to render them suitable for the measurement of fusional amplitudes.

Adult↗

PubMed1985

Effect of skin temperature on selective vascular injury caused by pulsed laser irradiation.

The effect of skin temperature on vascular-specific injury caused by pulsed laser irradiation was examined. Ten healthy human volunteers were exposed to 1.5 microsecond pulses from a dye laser tuned to 577 nm. Compared to normothermic conditions (33 degrees C skin temperature) significantly more laser energy (p less than 0.01) was required to produce grossly visible purpura when the skin was cooled to 20 degrees C or heated to 40 degrees C. Histologically, laser-induced damage was confined to blood vessels at all three skin temperatures studied. At purpura threshold dose, there was intravascular agglutination without extravasation of red blood cells at 20 degrees C whereas at 33 degrees and 40 degrees C there was extravasation of red blood cells.

Adolescent↗

PubMed2002

Measurement of excitability of tonically firing neurones tested in a variable-threshold model motoneurone.

A new measure of excitability of tonically firing neurones termed the 'estimated potential' (EP) was tested on a model motoneurone (MN) with a voltage-dependent threshold; the threshold followed the noisy membrane potential with an exponential delay. First, the model MN's after-hyperpolarisation (AHP) was deduced from its interval histogram for tonic firing, using a recently described transform. This provided a 'distance-to-threshold' measure which underestimated the AHP's absolute size but had the same time course, thereby providing the time constant of the AHP's decay of conductance. The 'estimated potential' was then obtained from the classical 'firing index' (no. of responses/no. of stimuli) by using the estimated AHP to create a fixed threshold 'daughter' model MN to mimic its variable threshold parent and reproduce its input-output non-linearities. The EP gave a linear measure of the parent's stimulus-evoked depolarisation for firing indices up to about 60 %, corresponding to depolarisations of three to four times the noise S.D. The EP was scaled in units of voltage whose absolute value will usually be unknown for real neurones, since it depended upon the details of the parent model. The EP's virtue is that, within its range, combining stimuli gives arithmetical addition and subtraction, thereby improving on the firing index which scales sigmoidally with the input. Moreover, with weak stimuli, the EP for a given input did not change on varying the parent model's firing rate. The estimated 'distance-to-threshold' AHP did not, however, give an accurate measure of the recovery of excitability following a spike during tonic firing. Excitability then depends upon the 'survivors' trajectory' giving the mean membrane potential, relative to threshold, of those intervals which have 'survived' up to the time in question rather than upon the AHP per se; the survivors' mean is more hyperpolarised because spiking preferentially eliminates trajectories with noise-induced depolarisation.

Animals↗

PubMed2002

Mechanisms of neuronal hyperexcitability caused by partial inhibition of Na+-K+-ATPases in the rat CA1 hippocampal region.

Extra- and intracellular records were made from rat acute hippocampal slices to examine the effects of partial inhibition of Na(+)-K(+)-ATPases (Na(+)-K(+) pumps) on neuronal hyperexcitability. Bath application of the low-affinity cardiac glycoside, dihydroouabain (DHO), reversibly induced interictal-like epileptiform bursting activity in the CA1 region. Burst-firing was correlated with inhibition of the pumps, which was assayed by changes in [K(+)](o) uptake rates measured with K(+)-ion-sensitive microelectrodes. Large increases in resting [K(+)](o) did not occur. DHO induced a transient depolarization (5-6 mV) followed by a long-lasting hyperpolarization (approximately 6 mV) in CA1 pyramidal neurons, which was accompanied by a 30% decrease in resting input resistance. Block of an electrogenic pump current could explain the depolarization but not the hyperpolarization of the membrane. Increasing [K(+)](o) from 3 to 5.5 mM minimized these transient shifts in passive membrane properties without preventing DHO-induced hyperexcitability. DHO decreased synaptic transmission, but increased the coupling between excitatory postsynaptic potentials and spike firing (E-S coupling). Monosynaptic inhibitory postsynaptic potential (IPSP) amplitudes declined to approximately 25% of control at the peak of bursting activity; however, miniature TTX-resistant inhibitory postsynaptic current amplitudes were unaffected. DHO also reduced the initial slope of the intracellular excitatory postsynaptic potential (EPSP) to approximately 40% of control. The conductances of pharmacologically isolated IPSPs and EPSPs in high-Ca/high-Mg-containing saline were also reduced by DHO by approximately 50%. The extracellular fiber volley amplitude was reduced by 15-20%, suggesting that the decrease in neurotransmission was partly due to a reduction in presynaptic fiber excitability. DHO enhanced a late depolarizing potential that was superimposed on the EPSP and could obscure it. This potential was not blocked by antagonists of NMDA receptors, and blockade of NMDA, mGlu, or GABA(A) receptors did not affect burst firing. The late depolarizing component enabled the pyramidal cells to reach spike threshold without changing the actual voltage threshold for firing. We conclude that reduced GABAergic potentials and enhanced E-S coupling are the primary mechanisms underlying the hyperexcitability associated with impaired Na(+)-K(+) pump activity.

Action Potentials↗

PubMed1989

Exercise training after experimental myocardial infarction increases the ventricular fibrillation threshold before and after the onset of reinfarction in the isolated rat heart.

Previous work has shown that exercise training increases the ventricular fibrillation threshold of the isolated perfused rat heart. The aim of our study was to determine whether exercise training that begins after myocardial infarction can similarly increase the ventricular fibrillation threshold. Rats that had suffered an experimental myocardial infarction were subject to a running training program. Thereafter, the ventricular fibrillation threshold was measured before and after the onset of acute reinfarction induced by a second coronary artery ligation. Ventricular fibrillation thresholds were significantly elevated in trained rats during normoxia (13.7 +/- 2.2 vs. 4.7 +/- 0.8 mA, p less than 0.01) and during acute ischemia (6.8 +/- 1.6 vs. 3.0 +/- 0.7 mA, p less than 0.02). The myocardial cyclic AMP level was lower in the nonischemic zone of the trained hearts (0.21 +/- 0.01 vs. 0.28 +/- 0.01 nmol/g, p less than 0.05), which also had lower cyclic AMP levels after epinephrine challenge (0.50 +/- 0.05 vs. 0.73 +/- 0.09 nmol/g, p less than 0.01; 1.41 +/- 0.11 vs. 1.85 +/- 0.09 nmol/g, p less than 0.02 after epinephrine 10(-7) M and 5 x 10(-6) M injection, trained vs. untrained). Both propranolol 10(-6) M and epinephrine 5 x 10(-7) M attenuated the difference in ventricular fibrillation thresholds before and after second coronary artery ligation and eliminated any difference in cyclic AMP content of both the nonischemic and ischemic myocardial tissue.(ABSTRACT TRUNCATED AT 250 WORDS)

Animals↗