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Laser emitted radiant heat for pain research.

Controlled radiant heat stimulation for a combined psychophysical and electrophysiological research in pain was achieved by the use of an infrared Laser beam. The computer controlled stimuli, being of very brief duration (down to 5 msec) and sharply localized, are suitable for recording of averaged evoked responses as well as for determination of pain and thermal thresholds. These stimuli can be applied to any locus on the skin. The threshold energy delivered by this technique is similar to that obtained by the Hardy-Wolff-Goodell method. Special precautions were taken to avoid injury to the skin and the eyes.

Computers↗

Detection thresholds for spiral Glass patterns.

We measured thresholds for the detection of spiral Glass patterns in the presence of random noise. The patterns were constructed so that the orientation content did not vary as a function of spiral angle or signal level. We found that spiral patterns had higher thresholds than either radial or concentric Glass patterns. The results support the idea that the human visual system is specialized to detect radial and concentric patterns.

Adolescent↗

Long-term theophylline treatment changes the effects of angiotensin II and adenosinergic agents on the seizure threshold.

The effects of angiotensin II (ANG II), sarmesin, losartan, PD 123319, and adenosine A (1) receptor agonist N(6)-cyclopentyladenosine (CPA) administered i.c.v. in untreated and in theophylline-treated male mice (50 mg/kg i.p. twice daily for 14 days) were studied on the pentylenetetrazol (PTZ) seizure threshold. The threshold was increased after long-term theophylline treatment. ANG II, sarmesin, and CPA increased the threshold in theophylline-untreated mice, whereas it decreased the threshold in theophylline-treated animals. Losartan did not change the threshold in theophylline-untreated mice but decreased it in theophylline-treated animals. PD 123319 did not change the seizure threshold both in theophylline-untreated and -treated mice. Taken together, the data demonstrated that repeated exposure to theophylline selectively changes the effects of ANG II and adenosinergic agents on the PTZ seizure threshold. The results indicate that both angiotensin AT(1) and adenosine A(1) receptor subtypes could possess interactive mechanisms of adaptation to chronic theophylline treatment.

Adenosine↗

Stereociliary anomaly in the guinea pig: effects of hair bundle rotation on cochlear sensitivity.

Histological analysis of cochleas from 100 albino guinea pigs (Hartley strain) obtained from Charles River Laboratories revealed an apparently congenital anomaly in 24% of animals, with roughly equal prevalence in males and females. In affected animals, 15-50% of the first-row outer hair cells (OHCs) showed distinctly abnormal orientation of the W-shaped stereociliary array. These abnormal hair bundles could be rotated by up to 180 degrees from the normal quasi-radial orientation. Second- and third-row OHCs appeared normal in all cases. Cochlear sensitivity was assayed in a subset of animals via compound action potentials (CAPs): CAP thresholds in affected animals were, on average, elevated by 5-10 dB with respect to normal controls. If the contributions of individual OHCs to cochlear 'amplification' add linearly, and if the total OHC contribution corresponds to approximately 45 dB of 'gain', a quantitative correlation of the degree of stereociliary rotation and the degree of threshold shift in these ears suggests that first-row OHCs make a larger contribution to the cochlear amplifier than either of the other OHC rows.

Action Potentials↗

Decreased sensory cortical excitability after 1 Hz rTMS over the ipsilateral primary motor cortex.

OBJECTIVES: To study changes in the excitability of the sensory cortex by repetitive transcranial magnetic stimulation (rTMS) in humans. METHODS: Somatosensory evoked potentials (SEPs) and antidromic sensory nerve action potentials (SNAPs) were elicited by right median nerve stimulation at the wrist before and after low frequency (1 Hz) rTMS over the left motor cortex, lateral premotor cortex, sensory cortex, and also after sham stimulation. The intensity of rTMS was fixed at 1.1 times the active motor threshold at the hand area of motor cortex. RESULTS: N20 peak (N20p)-P25 and P25-N33 amplitudes were suppressed after rTMS over the motor cortex, whereas the N20 onset (N20o)-N20p and SNAP amplitudes were not affected. They recovered to the baseline about 100 min after the rTMS. rTMS over the premotor cortex or sensory cortex or sham stimulation had no suppressive effect on SEPs. CONCLUSIONS: The reduction of N20p-P25 and P25-N33 components without any changes of N20o-N20p amplitude suggests that the suppression occurs in the sensory cortex. rTMS (1 Hz) of the motor cortex induces a long-lasting suppression of the ipsilateral sensory cortex even at an intensity as low as 1.1 times the active motor threshold, probably via cortico-cortical pathways between motor and sensory cortex.

Action Potentials↗

Scotopic sensitivity in coyotes (Canis latrans).

The absolute scotopic limen for light intensity was measured for three 10-mo-old female coyotes. The methodology was similar to that used by Blough in determining psychophysical thresholds in pigeons. Three coyotes were operantly conditioned to depress one of two foot treadles, left or right, depending on the condition of the stimulus light. Scotopic adaptation curves for each coyote were generated. Nonlinear regression curves were then fitted to the raw data. The mean scotopic thresholds did not differ significantly. However, time to the curves' asymptotes did differ significantly for one of the coyotes. The adaptation curves showed a distinct rod-cone "break," and retinal histology confirmed that the coyote has a duplex retina with a preponderance of rods. In addition, electroretinographic analysis showed the relative contributions of rods and cones at various light intensities and indicated a rod-cone break at approximately 15 min. Scotopic spectral sensitivity curves were also generated. The coyotes' scotopic visual threshold is exceeded by the natural illumination available under many nocturnal conditions. The results are discussed in relation to the ecology of the species.

Animals↗

Evidence of an affinity threshold for IgE-allergen binding in the percutaneous skin test reaction.

BACKGROUND: Atopy is an aberrant immune response involving allergen-specific IgE production, though serum IgE concentration is not an entirely reliable diagnostic tool, particularly for epidemiological and genetic studies. There is no clear correlation between IgE and other indicators of atopy such as skin prick tests (SPT)s, and physiological associations are difficult to justify in cases with detectable IgE but negative SPT results. OBJECTIVE: IgE reflects the number of molecules available to produce an atopic response, but the degree of the response is determined by the binding strength (affinity) between receptor-bound IgE and the allergen. We sought to determine if there was an association between binding affinity and SPT results in people with histories of atopy. METHODS: Standard SPTs (whole allergen extracts) were administered to people with histories of sensitivities to ragweed and house dust mite. The concentrations and affinities of serum allergen-specific IgEs were determined using the purified allergens Amb a 1 and Der p 1. RESULTS: There was a positive correlation between weal area and allergen-specific IgE among SPT-positive donors. However, for those individuals with detectable amounts of allergen-specific IgE, there was considerable overlap of IgE values between SPT-positive and -negative groups. Among sensitized donors, IgE-allergen interactions were characterized by two or three specific reactions of very high affinity (K(A) range 10(8) -10(11) M). Negative SPT reactions were associated with lowered IgE binding affinities to major allergens. This delimited two groups with atopic disorders: specific IgE(+)/ SPT(+) and specific IgE(+)/SPT(-). CONCLUSION: The product of antibody affinity and concentration, which we define as antibody capacity (CAP = K(A) x IgE), is more informative with regard to describing allergen sensitivity than antibody concentration alone. Antibody binding capacity provides physiological evidence of atopy in some subjects who do not test positively by common methods and suggests an affinity threshold to produce a positive SPT reaction.

Allergens↗

Dynamic synaptic modification threshold: computational model of experience-dependent plasticity in adult rat barrel cortex.

Previous electrophysiological experiments have documented the response of neurons in the adult rat somatic sensory ("barrel") cortex to whisker movement after normal experience and after periods of experience with all but two whiskers trimmed close to the face (whisker "pairing"). To better understand how the barrel cortex adapts to changes in the flow of sensory activity, we have developed a computational model of a single representative barrel cell based on the Bienenstock, Cooper, and Munro (BCM) theory of synaptic plasticity. The hallmark of the BCM theory is the dynamic synaptic modification threshold, theta M, which dictates whether a neuron's activity at any given instant will lead to strengthening or weakening of the synapses impinging on it. The threshold theta M is proportional to the neuron's activity averaged over some recent past. Whisker pairing was simulated by setting input activities of the cell to the noise level, except for two inputs that represented untrimmed whiskers. Initially low levels of cell activity, resulting from whisker trimming, led to low values for theta M. As certain synaptic weights potentiated, due to the activity of the paired inputs, the values of theta M increased and after some time their mean reached an asymptotic value. This saturation of theta M led to the depression of some inputs that were originally potentiated. The changes in cell response generated by the model replicated those observed in in vivo experiments. Previously, the BCM theory has explained salient features of developmental experience-dependent plasticity in kitten visual cortex. Our results suggest that the idea of a dynamic synaptic modification threshold, theta M, is general enough to explain plasticity in different species, in different sensory systems, and at different stages of brain maturity.

Animals↗

Carotid baroreflex responsiveness during dynamic exercise in humans.

We utilized 5-s changes of neck pressure and neck suction (from 40 to -80 Torr) to alter carotid sinus transmural pressure in seven men with peak oxygen uptake (VO2peak) of 41.4 +/- 3.6 ml O2.kg-1.min-1. Peak responses of heart rate (HR) and mean arterial pressure (MAP) to each carotid sinus perturbation were used to construct open-loop baroreflex curves at rest and during exercise at 25.7 +/- 1.1 and 47.4 +/- 1.9% VO2peak. The baroreflex curves were fit to a logistic function describing the sigmoidal nature of the carotid sinus baroreceptor reflex. Maximal gain for baroreflex control of HR (-0.31 +/- 0.05 beats.min-1.mmHg-1) and MAP (-0.30 +/- 0.08 mmHg/mmHg) at rest was the same as during exercise at 25 and 50% VO2peak (-0.30 +/- 0.05, -0.39 +/- 0.13 beats.min-1.mmHg-1 for HR, P = NS; -0.23 +/- 0.04, -0.60 +/- 0.38 mmHg/mmHg for MAP, P = NS). Resetting of the baroreflex occurred during exercise at 50% VO2peak. The centering point, threshold, and saturation pressures were significantly increased for baroreflex control of HR (delta pressure = 26.3 +/- 6.8, 19.6 +/- 10.4, 33.0 +/- 5.6 mmHg, P < 0.05) and MAP (delta pressure = 27.1 +/- 7.7, 16.1 +/- 14.8, 38.2 +/- 8.5 mmHg, P < 0.05). The operating point (steady-state HR and MAP) was shifted closer to threshold of the baroreflex during exercise at 50% VO2peak, as reflected by differences in HR and MAP between the centering and operating points (delta HR = 12.5 +/- 4.7 beats/min, P = 0.10; delta MAP = 7.6 +/- 1.3 mmHg, P < 0.05). These findings suggest a resetting of the carotid baroreflex during exercise with no attenuation in maximal sensitivity. A shift in operating point toward threshold of the baroreflex enables effective buffering of elevations in systemic blood pressure via reflex alterations in HR and MAP.

Adolescent↗

Perception of respiratory sensation assessed by means of histamine challenge and threshold loading tests.

BACKGROUND: Some asthmatic patients perceive the severity of their disease rather poorly. These patients may not receive optimal therapy because of underpresentation of their respiratory symptoms. It is therefore important to identify these patients. The present study evaluates a new threshold loading device for measuring the perception of respiratory sensation. This method for measuring the perception of respiratory sensation may be a viable alternative to the bronchial provocation test. The aim of the present study was to investigate whether the assessment of the perception of respiratory sensation based on a threshold loading test (inspiratory and expiratory) identifies the same subjects as poor perceivers as compared to assessment by histamine bronchial provocation test. METHOD: In 36 subjects, the perception of respiratory sensation through a threshold loading device was compared to the perception of respiratory sensation during a histamine provocation test. Each test was performed with scoring of the magnitude of the respiratory sensation on a visual analog scale (VAS). The magnitude of the stimulus intensity was indicated by the percentage of decrease in FEV(1) during the histamine challenge test and by the percentage of the subject's maximum mouth pressure (percent maximal inspiratory pressure and percent maximal expiratory pressure) during the threshold loading test. The relationship between VAS values and the stimulus intensity was analyzed by determining the linear regression coefficient between the two parameters. RESULTS: No relationship was found between the perception of the sensation induced by the histamine challenge and that during breathing through a threshold loading device for both inspiration (Rs = 0.15; p = 0.40) and expiration (Rs = 0.13; p = 0.47). We did find a significant relation between the perception of respiratory sensation during the inspiratory and expiratory threshold loading test (Rs = 0.67; p = 0. 0001). Furthermore, we defined a subgroup of patients of special interest: those with low symptoms of breathlessness and high bronchial responsiveness. Compared to the inspiratory and expiratory threshold loading test, the histamine challenge test identified more patients in the special interest group as poorest perceivers. CONCLUSION: The measurement of perception by means of a threshold loading device and a histamine provocation test did not identify the same subjects as poor perceivers, probably because we did not measure the patient's perceptiveness for exactly the same stimuli. In the population with relatively more severe asthma and very low symptoms of breathlessness, the histamine-induced bronchoconstriction test identified more patients as poorest perceivers compared to the threshold loading test.

Adolescent↗

Pupillary responses evoked by electrical stimulation of area pretectalis in cats.

Pupillary responses evoked by electrical stimulation of the area pretectalis and neighboring midbrain structures were studied in the cat. The pupillary responses evoked were recorded using an infrared pupilloanalyzing system. Bilateral pupillary constriction was evoked with a low threshold current intensity by stimulation of the nucleus pretectalis medialis, nucleus pretectalis olivaris, rostral part of the nucleus pretectalis posterior, the most rostral part of the periaqueductal grey and the nucleus of posterior commissure. Bilateral pupillary dilation was induced with a low threshold current intensity by stimulating the nucleus pretectalis anterior, caudal periaqueductal grey and the midbrain tegmentum. The effects of changing stimulus intensity and stimulus frequency were also studied.

Animals↗

Characterization of two components of the N-like, high-threshold-activated calcium channel current in differentiated SH-SY5Y cells.

Retinoic acid differentiated SH-SY5Y cells exhibit only a high-threshold-activated (-30 to -20 mV) whole cell calcium channel current. When barium was used as the charge carrier, the high-threshold-activated current showed bi-exponential inactivation kinetics during a 500 ms voltage step from -90 to +10 mV. The time constants of inactivation were approximately 75 and 750 ms. The fast inactivating component was more sensitive than the slow inactivating component to steady-state inactivation at depolarized holding potentials. The calcium channel current was inhibited by externally applied cadmium (10-300 microM) and gadolinium (10-30 microM) as well as by high concentrations of nickel and cobalt. omega Conus toxin (1 microM) irreversibly blocked the calcium channel current. However, the dihydropyridine agonist, BAY K 8644 (3-10 microM) and antagonists, nifedipine (3-10 microM) and nimodipine (10 microM) did not affect either component of the calcium channel current. Agents which blocked the calcium channel current did not exhibit any selectivity for the fast inactivating over the slow inactivating component of the current. These results indicate that whilst the calcium channel current recorded in differentiated SH-SY5Y cells can be classified on the basis of the blocking agents as being of the N type, the current shows more than one form of inactivation.

Calcium Channel Agonists↗

Effect of age on detection of gaps in speech and nonspeech markers varying in duration and spectral symmetry.

Gap detection thresholds for speech and analogous nonspeech stimuli were determined in younger and older adults with clinically normal hearing in the speech range. Gap detection thresholds were larger for older than for younger listeners in all conditions, with the size of the age difference increasing with stimulus complexity. For both ages, gap detection thresholds were far smaller when the markers before and after the gap were the same (spectrally symmetrical) compared to when they were different (spectrally asymmetrical) for both speech and nonspeech stimuli. Moreover, gap detection thresholds were smaller for nonspeech than for speech stimuli when the markers were spectrally symmetrical but the opposite was observed when the markers were spectrally asymmetrical. This pattern of results may reflect the benefit of activating well-learned gap-dependent phonemic contrasts. The stimulus-dependent age effects were interpreted as reflecting the differential effects of age-dependent losses in temporal processing ability on within- and between-channel gap detection.

Adult↗

Importance of alpha 1-sympathetic activity for diurnal change in ischemic threshold in patients with stable angina.

BACKGROUND: Although ischemic threshold reportedly is lower in the early morning than in the afternoon, the mechanisms that account for the diurnal change in minimal coronary vascular resistance in the potentially ischemic area are unknown. HYPOTHESIS: We hypothesized that calcium-channel blockers and alpha 1 blockers may affect the ischemic threshold in the early morning and afternoon in patients with stable angina. METHODS: Before and after the administration of the calcium antagonist amlodipine (5 mg) alone and combined with the alpha 1 blocker prazosin (1 mg), a treadmill exercise test using the Balke-Ware protocol was undertaken in the morning (8:00 A.M.) and repeated in the afternoon (1:00 P.M.) with 15 stable angina patients. The ischemic threshold was defined as a reciprocal of minimal coronary vascular resistance in the presence of comparable levels of myocardial ischemia indicated by 0.1 mV ST depression. Minimal coronary vascular resistance was calculated as mean blood pressure divided by coronary blood flow. Since the coronary blood flow is closely related to myocardial oxygen consumption, which can be replaced by the double product of heart rate and systolic blood pressure, minimal coronary vascular resistance was approximated to 1/heart rate. RESULTS: At baseline, minimal coronary vascular resistance was significantly higher in the early morning than in the afternoon (8.5 +/- 0.3 x 10(-3) min/beats vs. 7.8 +/- 0.4 x 10(-3) min/beats, p < 0.01). Although treatment with amlodipine alone did not abolish the circadian pattern of minimal coronary vascular resistance (8.0 +/- 0.6 x 10(-3) min/beats vs. 7.7 +/- 0.6 x 10(-3) min/ beats, p < 0.05), the addition of prazosin virtually eliminated the diurnal difference in minimal coronary vascular resistance (7.4 +/- 0.5 x 10(-3) min/beats vs. 7.5 +/- 0.5 x 10(-3) min/beats, p = NS). CONCLUSIONS: These findings indicate that alpha 1-sympathetic activity may play a role in the pathogenesis of the diurnal change of ischemic threshold in patients with stable angina.

Adrenergic alpha-Antagonists↗

Binaural beats and frequency-coding.

Binaural beats were studied before and during a situation of temporary threshold shift, and no frequency shift could be found. In contrast, subjective binaural frequency comparison revealed a distinct shift. These findings demonstrate the two known modes of perception.

Audiometry↗

Pronounced overestimation of support surface tilt during stance.

A veridical internal notion of the kinematic state of the foot support is essential for postural control. The means by which this is obtained is still a matter of debate. We therefore measured the conscious perception of support tilt during transient anterior-posterior rotations of a motion platform in six healthy subjects, using a psychophysical matching procedure. Furthermore, we evaluated subjects' postural responses (in terms of displacement of subjects' center of mass, COM, and their ankle torque, as represented by the center of foot pressure, COP). The platform tilts were applied in absence of visual and auditory orientation cues. The platform rotations consisted of smoothed position ramps with different dominant frequencies (0.025, 0.05, 0.1, 0.2, 0.4, and 0.8 Hz) and different amplitudes (0.125 degrees, 0.25 degrees, 0.5 degrees, 1 degree, 2 degrees, 4 degrees, and 8 degrees) for the forward and backward directions, which yielded a 6x14 stimulus matrix. The stimuli were repeated five times in a random order. For the matching procedure, subjects tried to maintain an upright body orientation, while trying to orient a light-weight rod, which was attached to a belt around their waists, parallel to the perceived platform surface. We measured the stimulus-evoked angular excursions of the rod and of the subjects' COM as well as the COP shift. We found that the subjects' rod indications overestimated the platform tilts, particularly with small stimulus amplitudes. To characterize the overestimation, we compared the rod indications obtained while subjects stood on the tilting platform, to rod indications in a situation in which they stood next to the platform and tried to match the rod angle to the now visually perceived platform angle. From this comparison, we inferred that the subjects' kinesthetically derived notion of platform tilt overestimates the actual tilt by a factor of approximately 4. The estimates were linearly related to the angle between body (COM) and platform, i.e., to approximately the angle of the ankle joint, a finding which suggests a proprioceptive source of the overestimation. Further analyses supported this view; they showed that the onset latencies of the rod indications could be approximated by a theoretical indication mechanism with a reaction time of about 0.31 s, a velocity threshold of 0.099 degrees/s, and a displacement threshold of 0.12 degrees. These threshold values are well in line with previous work on the leg proprioceptive detection threshold of conscious perception of body sway. We therefore assume that the phenomenon of support tilt overestimation reflects a still unknown mechanism of leg proprioception in postural control.

Adaptation, Physiological↗

Evaluation of antifibrillatory effects of drugs.

Several electrical stimulation techniques have been used to measure ventricular fibrillation (VF) threshold such as single pulse stimulation, train of pulses stimulation, continuous 50-Hz stimulation and sequential pulse stimulation. This study was undertaken to clarify the difference in VF threshold values obtained by each method. The development of VF was classified into 4 stages. Stage 1 is the phase in which fragmented activities are generated at the stimulated area of the ventricular muscle. In stage 2, the local activities propagate to surrounding ventricular muscle, causing ventricular excitation. Stage 3 is characterized by repetitive ventricular excitations. In state 4, repetitive ventricular responses in a form of accelerating tachycardia induce disorganized excitations that finally degenerate into fibrillation. Based on this classification of stages between local excitation and fibrillation, single pulse stimulation is considered to measure VF threshold for stages 1 to 4, continuous 50-Hz stimulation for stages 2 to 4 and sequential pulse stimulation for stages 3 and 4. Thus, the antifibrillatory effect of drugs can be interpreted with some significance by using different stimulation methods. The sequential pulse stimulation method revealed that some antiarrhythmic agents caused a dissociation between repetitive nonstimulated excitation (RE) threshold and VF threshold. Procainamide and disopyramide increased RE threshold while decreasing VF threshold. Mexiletine and lidocaine elevated both RE and VF thresholds. Local infusion of procainamide at the site of test stimulation reduced both thresholds. However, after the application of procainamide to the whole heart, RE threshold remained decreased but VF threshold was elevated. It is likely that the antifibrillatory effect of the drug includes 2 different processes: antireentrant and antimultiple reentrant effects.

Animals↗

Threshold phenomena in chemoreception and taxis in slime mold Physarum polycephalum.

The plasmodium of Physarum polycephalum reacts to various kinds of chemicals substances and moves towards or away from them. Threshold concentration of recognition of chemicals was examined in terms of membrane potential and of the averaged motive force of tactic movement by using a double-chamber method, i.e., a single plasmodium was placed between two compartments through a narrow ditch, and differences in membrane potential and in pressure between two compartments were measured. Results are summarized as follows: (a) By increasing the concentration of various substances in one compartment, the membrane potential started to change at a certain threshold concentration, C-th, for each chemical. Chemotactic movement of the plasmodium took place at the same threshold concentration. These results held both for attractants (glucose, galactose, phosphates, pyrophosphates, ATP, c-AMP, etc) and for repellents (various inorganic salts, sucrose, fructose, etc.). (b) The threshold concentration, Cth, for inorganic salts decreased remarkably with increase of the valences of cations, zeta, and was proportional to Z-6, I.E., THE Shultze-Hardy rule known in the field of colloid chemistry was found to be applicable. (c) The plasmodium distinguished the species of monovalent cations in the following order: H(Li(K(Na(Rb(Cs(NH-4 Plots of log Cth against the lyotropic number of anion fell on different straight lines for each monovalent cation species. (d) Plots of log Cth, against the reciprocal of the absolute tempe lines were almost the same and gave a value of 12 kcal/mol for the enthalpy change. These results suggest that the recognition of chemical substances appears as the result of a structural change of the membrane at the threshold point, and that the change in membrane structure is transmitted simultaneously to the motile system of the plasmodium.

Adenosine Triphosphate↗