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[Dynamic range of acoustic reflex and its importance for hearing aid evaluation (author's transl)].

It is reported on the dynamic range of acoustic reflex in the case of normal hearing. Stimulation is carried out with speech noise under free field conditions. The sensitivity of impedance measurement is increased by using an averager, which enables acoustic reflex measurements at sound pressure levels of about 70 dB. Further an exact evaluation of input-output-characteristics becomes possible by this procedure. Basing on this consideration the possibility of objective hearing aid evaluation is discussed. The fundamental point of this technique should be the compensation of pathological input-output-characteristics by suitable hearing aids.

Ear, Middle

Hypersensitivity of dorsal horn wide dynamic range neurons to cutaneous mechanical stimuli after transient spinal cord ischemia in the rat.

The responsiveness of dorsal horn wide dynamic range (WDR) neurons to cutaneous mechanical stimuli was studied in decerebrate, spinalized, unanesthetized rats before and after transient photochemically induced spinal cord ischemia. In normal rats, the discharges of dorsal horn WDR neurons to the graded mechanical stimuli applied with calibrated von Frey hairs increase linearly. One to four days after spinal ischemia, when the rats exhibit a strong allodynia-like behavioral reaction to cutaneous stimuli, the sensitivity of dorsal horn WDR neurons to mechanical pressure is greatly increased. There is a significant decrease in the threshold pressure to evoke neuronal discharges and the exponential stimulus-response curve is shifted to the left. Thus, transient ischemia of the spinal cord results in hyperexcitability of dorsal horn WDR neurons, which may underly the allodynia-like sensory abnormalities observed in behaving animals. The present results may contribute to understanding the mechanism of the development of chronic central pain in patients after central nervous system injury involving ischemia.

Animals

Intrathecal clonidine suppresses noxiously evoked activity of spinal wide dynamic range neurons in cats.

The analgesic effectiveness of perispinal clonidine administration prompted us to evaluate clonidine effects on spinal dorsal horn wide dynamic range neurons. Intrathecal clonidine produced a dose-dependent (10 and 30 micrograms), yohimbine-reversible suppression of noxiously evoked activity in decerebrate, spinal cord-transected cats. In addition, combining ineffective intrathecal doses of morphine (25 micrograms) and clonidine (5 micrograms) produced statistically significant, reversible suppression of noxiously evoked activity. The time course of suppression was similar to that observed behaviorally. These results support the role of spinal alpha 2-adrenergic receptors in clonidine analgesia.

Analgesics

Identification of afferents contributing to sympathetically evoked activity in wide-dynamic-range neurons.

The purpose of this study was to determine which types of mechanoreceptor afferents contribute to sympathetically evoked activity in wide-dynamic-range (WDR) neurons--the spinal neurons thought to mediate sympathetically maintained pain. The experimental approach was to record and compare activity evoked in single WDR neurons, hair afferents, and slowly adapting type I (SAI) afferents in anesthetized cats. During electrical stimulation of the sympathetic trunk, WDR neurons responded with either an early transient burst of activity, sustained activity, or both. The early transient response was observed only in neurons with piloerection in the receptive field; this response had a similar time course to sympathetically evoked activity in hair afferents with piloerection in the receptive field. The sustained response that occurred in some WDR neurons was independent of piloerection and was similar in time course to the response evoked in SAI afferents by sympathetic stimulation. We conclude that hair and SAI afferents contribute to different components of sympathetically evoked activity in WDR neurons and that both types of afferents are likely to be involved in sympathetically maintained pain in humans.

Adrenergic Fibers

Prediction of dynamic range from stapedius reflex in cochlear implant patients.

Amplitude growth functions of the electrically elicited stapedius reflex were compared with behavioral estimates of dynamic range in seven patients using multielectrode cochlear implants. The range between threshold and saturation level of the amplitude growth function usually either encompassed or fell between the preferred and uncomfortable listening levels. Implications of these findings for the initial mapping of electrodes in young children are discussed.

Adult

Wide-dynamic-range dorsal horn neurons participate in the encoding process by which monkeys perceive the intensity of noxious heat stimuli.

The role of dorsal horn wide-dynamic-range (WDR) and nociceptive-specific (NS) neurons in the encoding of the perceived intensity of noxious stimuli was determined while monkeys detected near-threshold changes in the intensity of noxious heat stimuli. Behavioral detection latencies were a reliable measure of the perceived intensity of these stimuli. There was a significant correlation between behavioral detection latency and neuronal discharge of WDR, but not NS neurons. In addition, WDR neurons exhibited greater activity on correctly detected vs non-detected trials, whereas NS neurons did not. We conclude that WDR neurons are involved in the encoding process by which monkeys perceive the intensity of noxious heat stimuli near detection threshold.

Animals

Inhibition of nociceptive responses of wide-dynamic-range neurons by peripheral nerve stimulation.

Of 107 neurons from the sacral and coccygeal levels of the spinal cord in anesthetized intact rats examined, 62 wide-dynamic-range (WDR) neurons that responded to noxious heating of the tail were recorded. On the basis of their inhibitory responses through A-beta or A-delta afferent fibers to noxious stimulation, these neurons were classified into one of the following three types: Type I--neurons inhibited only by A-beta afferent nerve impulses; Type II--neurons inhibited only by A-delta afferent nerve impulses; Type III--neurons inhibited by both. The present results are compared with previously reported behavioral results.

Animals

Prolonged discharge of wide-dynamic-range spinal neurons evoked by formaldehyde injected in their cutaneous receptive fields.

In decerebrate, unanesthetized cats, subcutaneous injection of formaldehyde solutions (0.05 ml, 2.5%) in the receptive fields of spinal wide-dynamic-range neurons elicited an immediate and continuous discharge or burst activity in the neurons that lasted 10 to 55 min. This discharge was reduced by conditioning stimulation of the medial raphe nucleus and was completely abolished by morphine (3 mg/kg, i.v.). Low-threshold cutaneous mechanoreceptive neurons in the dorsal horn and dorsal column nuclei did not show a sustained response.

Animals

Intensity coding and the dynamic range problem.

The psychophysical data on intensity discrimination indicate that certain schemes are unlikely as general intensity codes at the level of the auditory nerve and indirectly suggest that the most likely code is one based upon the firing rates of frequency-localized groups of fibers. A detection-theory analysis of a rate-based intensity code indicates that information from very few fibers can, if the information is appropriately combined, account for psychophysical discrimination even at high intensities. This suggests that fibers with similar CFs can code intensity over a wide range and that complex spectra can be represented at the level of the auditory nerve by a rate-CF code over the dynamic range of hearing. The analysis also indicates, however, a substantial discrepancy between the psychophysical data on the dependence of discrimination thresholds on level and the predicted discrimination behavior of a representative population of auditory nerve fibers. Thus, if intensity coding is based on localized firing rate, this fundamental psychophysical behavior does not result solely from peripheral processes.

Differential Threshold

Transient spinal cord ischemia induces temporary hypersensitivity of dorsal horn wide dynamic range neurons to myelinated, but not unmyelinated, fiber input.

1. The activity of 197 single dorsal horn neurons was recorded extracellularly in the spinal cord of decerebrate, spinalized, unanesthetized rats. The response properties of 174 wide dynamic range (WDR) neurons to electrical, mechanical, and thermal stimulation in three groups of rats were studied:normal, 1-4 days after transient spinal cord ischemia induced photochemically by laser irradiation when the rats exhibited behavioral hypersensitivity to mechanical stimuli (allodynia), and 10-20 days after spinal ischemia when the allodynia had ceased. 2. In normal rats, the responses of dorsal horn WDR neurons to suprathreshold electrical stimulation of their receptive fields consisted of a short-latency (A) and a long-latency (C) response. In 77% of the neurons (57/74), there was a separation between the A- and C-fiber responses. The response threshold (defined as 20% increase in neuronal discharges above background activity) to mechanical stimulation applied with calibrated von Frey hairs was 13.8 g, and the discharges of these neurons to graded stimulation increased linearly. 3. In 68% of WDR neurons in allodynic rats (38/56), the response to suprathreshold electrical stimuli was a single burst with no separation between A- and C-fiber responses. The magnitude and duration of the response were significantly increased compared with those recorded in normal rats. The sensitivity of these neurons to mechanical stimulation was also greatly increased, expressed by a lowered threshold (2.1 +/- 0.3 g, mean +/- SE) and a shift to the left of the nonlinear stimulus-response curve. The background activity of the neurons and the size of the receptive fields were, however, unchanged.(ABSTRACT TRUNCATED AT 250 WORDS)

Animals

Baclofen reverses the hypersensitivity of dorsal horn wide dynamic range neurons to mechanical stimulation after transient spinal cord ischemia; implications for a tonic GABAergic inhibitory control of myelinated fiber input.

1. In the companion paper, we described a state of hypersensitivity that developed in dorsal horn wide dynamic range (WDR) neurons in rats after transient spinal cord ischemia. Thus the WDR neurons exhibited lower threshold and increased responses to low-intensity mechanical stimuli. The response pattern of these neurons to suprathreshold electrical stimulation was also changed. Notably, the response to A-fiber input was increased. No change in response to thermal stimulation was found before and after spinal cord ischemia. 2. In normal rats, the gamma-aminobutyric acid (GABA)B agonist baclofen (0.1 mg/kg ip) administered 1-3 h before neuronal recording suppressed the responses of WDR neurons to high-intensity mechanical pressure without influencing the threshold and the responses to lower-intensity stimuli. 3. In allodynic rats, similar pretreatment with baclofen totally reversed the hypersensitivity of the WDR neurons to mechanical stimuli and normalized the response pattern of neurons to electrical stimulation. 4. The GABAA receptor agonist muscimol (1 mg/kg ip) did not influence the response of WDR neurons in either normal or allodynic animals. 5. The present results demonstrated that the GABAB agonist baclofen is effective in reversing the hypersensitivity of dorsal horn WDR neurons to low-intensity mechanical stimulation after transient spinal cord ischemia, indicating that dysfunction of the GABAergic inhibitory system may be responsible for the development of neuronal hypersensitivity. 6. It is suggested that GABAergic interneurons exert a tonic presynaptic inhibitory control, through baclofen-sensitive B-type GABA receptors, on input from low-threshold mechanical afferents, and that disruption of this control may result in painful reaction to innocuous stimuli (allodynia).

Animals

Spinal recordings suggest that wide-dynamic-range neurons mediate sympathetically maintained pain.

In order to determine which classes of spinal neurons are capable of mediating sympathetically maintained pain, recordings were made from single somatosensory neurons in spinal cords of anesthetized cats. Each neuron was functionally identified with mechanical stimuli, and its responses to electrical stimulation of the sympathetic trunk were recorded. Nearly half (45%) of the wide-dynamic-range (WDR) neurons tested were activated by sympathetic stimulation, but none of the high threshold (nociceptor-specific) neurons and only 17% of the low threshold neurons were activated. Sympathetic activation was most common for WDR neurons that had the following: receptive fields proximal to the toes, low thresholds for mechanical activation, and both rapidly and slowly adapting responses to pressure. The predominant WDR response to sympathetic stimulation was long latency (greater than 1 sec) excitation. Sympathetic activation of WDR neurons was abolished by each of the following procedures: subcutaneous injection of local anesthetic, cooling of the receptive field with ice, and intravenous injection of the alpha-adrenergic blocker, phentolamine. The axons of some sympathetically activated WDR were shown to project to higher centers. These results indicate that WDR neurons are the only spinal nociceptive neurons activated by sympathetic efferent activity in this preparation. Therefore, WDR neurons, rather than high threshold neurons, are most likely to mediate the spinal component of sympathetically maintained pain. These results provide supporting evidence for our previous hypothesis that sympathetically maintained pain is mediated by myelinated mechanoreceptors acting on sensitized WDR neurons. Our results also demonstrate that sympathetic activation of WDR neurons is mediated by an alpha-adrenergic mechanism in the skin.

Adaptation, Physiological

Systemic tocainide relieves mechanical hypersensitivity and normalizes the responses of hyperexcitable dorsal horn wide-dynamic-range neurons after transient spinal cord ischemia in rats.

In the present study we examined the effect of systemic tocainide on sensory hypersensitivity in rats after spinal cord ischemia induced by a photochemical technique. After induction of spinal cord ischemia the rats exhibited a sensory disturbance which was mainly expressed as vocalization to innocuous cutaneous mechanical stimuli (allodynia) in the flank area during the following several days. Tocainide at 75 mg/kg i.p., but not 50 mg/kg i.p., significantly increased the vocalization threshold to mechanical pressure for 2 h. The effect of intraarterial (i.a.) tocainide on the responses of dorsal horn wide-dynamic-range (WDR) neurons to suprathreshold electrical stimulation of their receptive fields was also examined in normal rats and after transient spinal cord ischemia, at a time when the animals exhibited typical behavioral allodynia in the dermatomes innervated by the ischemic spinal segments. In normal rats, tocainide (50 mg/kg i.a.) strongly suppressed the responses of WDR neurons to C fiber input with lesser effect on A fiber input. In allodynic rats, tocainide suppressed the augmented A and C fiber mediated responses of WDR neurons to the extent that their responses were similar to those seen in normal rats without tocainide. There was no difference in the overall depression of A and C fiber mediated input by tocainide between normal and allodynic rats. The present results demonstrated the analgesic effect of systemic tocainide in relieving allodynia in rats and indicated that systemic local anesthetics, at doses that do not block nerve conduction, can be effective in suppressing dorsal horn WDR neuronal activity.(ABSTRACT TRUNCATED AT 250 WORDS)

Animals

Liposome flow injection immunoassay: implications for sensitivity, dynamic range, and antibody regeneration.

We have developed a liposome-based flow injection immunoassay (FIIA) system for quantitation of a clinical analyte, theophylline. With very minor changes in assay format, this procedure can also be used for the quantitation of anti-theophylline. Automated sequential analyses were performed at room temperature with picomole sensitivity and a day-to-day coefficient of variation of less than 5% for aqueous solutions. The system components include liposomes that contain fluorophores in their aqueous centers and an immobilized-antibody reactor column. The immunoreactor was regenerated hundreds of times over 3 months of continuous use with no measurable loss of antibody activity. The two assay formats studied produced distinct dynamic ranges for their respective analytes. The special advantages of using flow injection analysis for immunoassays and of using liposomes in FIIA are discussed.

Antibodies

Basilar membrane nonlinearity determines auditory nerve rate-intensity functions and cochlear dynamic range.

In a previous paper (Winter et al., 1990) we demonstrated the existence of a new type of auditory-nerve rate-intensity function, the straight type, as well as a correlation between rate-level type, threshold and spontaneous rate. In this paper we now show that the variation in rate-intensity functions has its origin in the basilar membrane nonlinearity. Comparison of rate-intensity functions at characteristic frequency and at a tail-frequency show that the rate-intensity functions are identical at low firing rates and that the sloping-saturation and straight types deviate from the standard function only at higher firing rates. The frequencies at which the deviations occur, and the change from saturating to sloping-saturation or straight, are closely correlated with the characteristic frequency of the fibre. Using the tail-frequency rate-intensity function as a calibration, it is possible to derive the basilar membrane input-output function at characteristic frequency from the characteristic frequency rate-intensity function. The resulting derived basilar membrane input-output functions are of a simple form and agree well with published direct measurements of basilar membrane motion. They show that the wide dynamic range to which the cochlea responds, about 120 decibels, is compressed by the basilar membrane nonlinearity into a much smaller range of about 30-35 decibels. General characteristics of the derived basilar membrane input-output curves show features which agree well with psychoacoustic studies of loudness estimation.

Acoustic Stimulation

Low cost storing of two electrical biosignals from DC to 20 kHz at more than 80 dB dynamic range.

An instrumentation for storing electrical analog signals (DC to 20 kHz) was composed from a video recorder and a slightly modified pulse code modulation processor. As these components are mass products of the consumer electronics industry, the system price could be kept below 5000 DM. The setup allows one to register simultaneously two signals at DC to 20 kHz at a dynamic amplitude resolution of 16 bit [corresponding to a signal to noise ratio (S/N-ratio) of 96 dB] and AC-signals on the audiochannels of the stereo-video recorder. This is exemplified by recordings of insect chemoreceptors.

Bioelectric Energy Sources

Modified Box-Cox transform for modulating the dynamic range of flow cytometry data.

We describe an algorithm, Vout = Integer ([2(12)-1/2(12 lambda)-1] V lambda in-1) + 1; lambda greater than 0 based upon Box-Cox transformations as an alternative to nonlinear electronic amplifiers to expand or compress high- or low-amplitude flow cytometer-derived signals. If the indexing parameter lambda less than 1, input channels in the high-amplitude input range are compressed in the output range as occurs when an electronic logarithmic amplifier is used. However, if lambda greater than 1, input channels in the low-amplitude input range are compressed in the output range as occurs when an electronic power amplifier is used. Our modified Box-Cox transform can be implemented either during data collection or off-line for the transformation of previously collected raw data. The transform is the equivalent of an infinite class of nonlinear amplifiers. As the transform is implemented in software, it does not suffer from many of the disadvantages of nonlinear electronic amplifiers.

Algorithms