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At least 1,711 records · Page 95Linked to original sources
PubMed2004

Estimation of the level and phase of the simple distortion tone the modulation domain.

These experiments were designed to test the idea that nonlinearities in the auditory system can introduce a distortion component into the internal representation of the envelope of a sound, and to estimate the phase of the hypothetical distortion component. In experiment 1, a two-alternative forced-choice (2AFC) task with feedback was used to measure psychometric functions for detecting 5-Hz probe modulation of a 4-kHz sinusoidal carrier in the presence of a masker modulator with components at 50 and 55 Hz (m=0.3 for each component). Performance was measured as a function of the relative phase, delta[symbol see text], of the probe relative to the "venelope" (envelope of the envelope) of the masker. Performance was poorest for delta[symbol see text]= 135 degrees. In experiment 2, delta[symbol see text] was fixed at 135 degrees, m was set to 0.48 for each masker component, and psychometric functions for detecting probe modulation were measured using a 2AFC task without feedback. For small probe modulation depths (m approximately 0.03), the detectability index, d', was consistently negative, consistent with the existence of a weak distortion product which can "cancel" the probe modulation. The distortion component for the conditions of the experiment was estimated to have a phase of about -25 degrees relative to the venelope.

Acoustic Stimulation↗
PubMed2005

Forward masking of amplitude modulation: basic characteristics.

In this study we demonstrate an effect for amplitude modulation (AM) that is analogous to forward making of audio frequencies, i.e., the modulation threshold for detection of AM (signal) is raised by preceding AM (masker). In the study we focused on the basic characteristics of the forward-masking effect. Functions representing recovery from AM forward masking measured with a 150- ms 40- Hz masker AM and a 50- ms signal AM of the same rate imposed on the same broadband-noise carrier, showed an exponential decay of forward masking with increasing delay from masker offset. Thresholds remained elevated by more than 2 dB over an interval of at least 150 ms following the masker. Masked-threshold patterns, measured with a fixed signal rate (20, 40, and 80 Hz) and a variable masker rate, showed tuning of the AM forward-masking effect. The tuning was approximately constant across signal modulation rates used and consistent with the idea of modulation-rate selective channels. Combining two equally effective forward maskers of different frequencies did not lead to an increase in forward masking relative to that produced by either component alone. Overall, the results are consistent with modulation-rate selective neural channels that adapt and recover from the adaptation relatively quickly.

Acoustic Stimulation↗
PubMed2006

Discrimination of depth of sinusoidal amplitude modulation with and without roved carrier levels.

Thresholds for the discrimination of the depth of sinusoidal amplitude modulation with a broadband noise carrier were measured for three listeners in a two-alternative, forced-choice task for modulation frequencies of 8, 32, and 128 Hz. Thresholds were measured with the spectrum level of the carrier fixed at 20 dB across all trials and, separately, with the carrier spectrum level roved randomly over a 20-dB range (10-30 dB) in each interval. Mean thresholds were equal or slightly lower (but not significantly so) for the fixed conditions relative to the roved conditions, and the differences between thresholds were too small to be explained by assuming that listeners compared instantaneous intensity at corresponding phases of the modulation cycle (for example, in the troughs). Rather, it appears that listeners discriminated modulation depth by extracting an estimate of the modulation depth within each interval that was independent of the overall level. Consequently, models of envelope extraction must include normalization of the envelope fluctuations to the envelope dc.

Acoustic Stimulation↗
PubMed2006

Hybrid measurement of auditory steady-state responses and distortion product otoacoustic emissions using an amplitude-modulated primary tone.

A maximum auditory steady-state response (ASSR) amplitude is yielded when the ASSR is elicited by an amplitude-modulated tone (f(c)) with a fixed modulation frequency (f(m) = 40 Hz), whereas the maximum distortion product otoacoustic emission (DPOAE) level is yielded when the DPOAE is elicited using a fixed frequency ratio of the primary tones (f2/f1 = 1.2). When eliciting the DPOAE and ASSR by the same tone pair, optimal stimulation is present for either DPOAE or ASSR and thus adequate simultaneous DPOAE/ASSR measurement is not possible across test frequency f2 or f(c), respectively. The purpose of the present study was to determine whether the ASSR and DPOAE can be measured simultaneously without notable restrictions using a DPOAE stimulus setting in which one primary tone is amplitude modulated. A DPOAE of frequency 2f1-f2 and ASSR of modulation frequency 41 Hz were measured in ten normal hearing subjects at a test frequency between 0.5 and 8 kHz (f2 = f(c)). The decrease in the DPOAE level and the loss in ASSR amplitude during hybrid mode stimulation amounted, on average, to only 2.60 dB [standard deviation (SD) = 1.38 dB] and 1.83 dB (SD = 2.38 dB), respectively. These findings suggest simultaneous DPOAE and ASSR measurements to be feasible across all test frequencies when using a DPOAE stimulus setting where the primary tone f2 is amplitude modulated.

Acoustic Impedance Tests↗
PubMed1984

Amplitude modulation thresholds in chinchillas with high-frequency hearing loss.

Estimates of auditory temporal resolution were obtained from normal chinchillas using sinusoidally amplitude modulated noise. Afterwards, the animals were exposed to noise whose bandwidth was progressively increased toward the low frequencies in octave steps. The first exposure was to an octave band of noise centered at 8 kHz. Three additional octave bands of noise were subsequently added to the original exposure in order to progressively increase the extent of the high-frequency hearing loss. The first exposure produced a temporary hearing loss of 50 to 60 dB near 8 kHz and elevated the amplitude modulation thresholds primarily at intermediate (128 Hz) modulation frequencies. Successive noise exposures extended the temporary hearing loss toward lower frequencies, but there was little further deterioration in the amplitude modulation function until the last exposure when the hearing loss spread to 1 kHz. The degradation in the amplitude modulation function observed after the last exposure, however, was due to a reduction in the sensation level of the test signal rather than to a decrease in the hearing bandwidth. The results of this study suggest that the high-frequency regions of the cochlea may be important for temporal resolution.

Animals↗
PubMed1984

Detection of frequency and rate modulation by the chinchilla.

Thresholds for detection of frequency modulation were obtained from three chinchillas at seven frequencies between 320 Hz and 12.75 kHz and at three sensation levels (20, 40, 60, dB SL). These were compared with human thresholds at 40 dB SL obtained under the same conditions. Our data show no significant impact of sensation level and confirm Nelson and Kiester 's [J. Acoust. Soc. Am. 64, 114-126 (1978)] report that the chinchilla has much poorer frequency discrimination than man. In an attempt to assess separately the chinchilla's capacity for temporal coding of frequency, thresholds for detection of a change in the modulation rate of amplitude modulated noise were obtained for nine modulation frequencies between 10 and 320 Hz. The chinchillas needed a larger rate change for detection than most humans but the relative difference was less than that found for frequency modulation detection.

Animals↗
PubMed1988

Modulation and gap detection for broadband and filtered noise signals.

Modulation detection thresholds (as a function of sinusoidal amplitude modulation frequency) and temporal gap detection thresholds were measured for three low-pass-filtered noise signals (fc = 1000, 2000, and 4000 Hz), a high-pass-filtered noise signal (fc = 4000 Hz), and a broadband signal. The two latter noise signals were effectively low-pass filtered (fc = 6500 Hz) by the earphone. Each of the filtered signals was presented with a complementary filtered noise masker. Modulation and gap detection thresholds were lowest for the broadband and high-pass signals. Thresholds were significantly higher for the low-pass signals than for the broadband and high-pass signals. For these tasks and conditions, the high-frequency content of the noise signal was more important than was the signal bandwidth. Sensitivity (s) and time constant (tau) indices were derived from functions fitted to the modulation detection data. These indices were compared with gap detection thresholds for corresponding signals. The gap detection thresholds were correlated inversely (rho = -1.0, p less than 0.05) with s (i.e., smaller gap detection thresholds were correlated with greater sensitivity to modulation), but were not correlated significantly with tau, which was relatively invariant across signal conditions.

Adult↗
PubMed1992

A computer model of a cochlear-nucleus stellate cell: responses to amplitude-modulated and pure-tone stimuli.

A computer model of a ventral-cochlear-nucleus (VCN) stellate cell with chop-S type response properties is presented and evaluated. The model is based on a simplified model of spike generation preceded by a stage that simulates dendritic low-pass filtering. Input to the model is in the form of simulated auditory-nerve spikes produced by a model of the auditory periphery [Meddis and Hewitt, J. Acoust. Soc. Am. 89, 2866-2882 (1991)]. Outputs from the stellate-cell model are shown to qualitatively replicate a wide range of typical in vivo responses. These include: (a) realistic onset and steady-state rate-level functions, (b) "chopper"-type post-stimulus time histogram responses; (c) typical "chop-S"-type neuron responses characterized by a low coefficient of variance (CV less than 0.3) of interspike intervals as a function of time; (d) level-dependent amplitude-modulation transfer functions; (e) intrinsic oscillations in responses to pure-tone stimuli; (f) amplitude-modulation encoding over a wide dynamic range; and (g) frequency-limited phase locking to pure tones. It is shown that these responses can be explained primarily by the membrane properties of the cells. More specifically, how the model encodes signal amplitude modulation was studied and an explanation was suggested for the generation of the bandpass modulation transfer functions. Such functions are observed neurally in response to amplitude-modulated stimuli presented at moderate to high signal levels.

Animals↗
PubMed1994

Detection of interaural delay in high-frequency sinusoidally amplitude-modulated tones, two-tone complexes, and bands of noise.

Listeners' ability to detect interaural temporal disparities (ITDs) was investigated for 160-ms, sinusoidally amplitude modulated (SAM) tones, two-tone complexes, and bands of noise at center frequencies of 4, 8, or 12 kHz. Rates of modulation for the 100%-modulated SAM tones and frequency separation for the equal-amplitude, two-tone complexes ranged from 32-768 Hz, depending on center frequency. Noise bandwidths ranged from 50-2000 Hz, also depending on center frequency. The data indicate, consistent with previous results, that sensitivity to ITD with the SAM and two-tone complexes decreases as the rate of envelope fluctuation increases beyond about 400 Hz. The decline in performance is not due simply to reduced depths of modulation produced by critical-band-like filtering, but is consistent with an inability to "follow" or encode high rates of modulation. For bands of noise, sensitivity to ITD was relatively constant as a function of bandwidth. Generally, sensitivity to ITD decreased as center frequency was increased from 4 to 8 kHz, but the relations among the data were essentially unchanged. Increasing the center frequency to 12 kHz resulted in very poor performance.

Acoustic Stimulation↗
PubMed1994

The perception of frequency peaks and troughs in wide frequency modulations.

This work was concerned with the perception of "instantaneous pitch" in continuously frequency modulated sounds. In experiment 1, a 70-dB sinusoidal carrier, close to 1 kHz, was modulated by the exponential of periodic functions corresponding to the sum of a few sinusoids [e.g., sin(at)+sin(3at)]. Each modulation had a fundamental frequency (a/2 pi) of 1.5 Hz and was symmetric on the dimensions of time and log frequency. Thirty listeners identified discrete melodic motifs within these stimuli. The pitches of the identified notes mainly corresponded to the local frequency maxima; generally, the local minima were not heard as auditory "events" (pitch singularities). A similar perceptual asymmetry was not observed for comparable sequences of discrete tones. In experiments 2-4, frequency difference limens were measured for the maxima and minima of continuous frequency modulations, using an adaptive forced-choice method. Sinusoidal carriers were modulated by the exponential of one cycle of a 5-Hz cosine function, starting at phase pi or phase 0 and giving an overall frequency swing of about 0.5 oct. For maxima and minima around 1 kHz, frequency shifts of maxima were better detected than frequency shifts of minima, by an average factor of 2. Generally, this asymmetry did not decrease as a function of subjects' training in the discrimination task, and was still present when frequency minima were given a 6-dB intensity advantage over frequency maxima. No explanation was found for the advantage of frequency maxima with respect to perceptual salience (experiment 1) or discriminability (experiments 2-4).

Adolescent↗
PubMed1995

Auditory steady-state responses to tones amplitude-modulated at 80-110 Hz.

Steady-state responses can be recorded from the human scalp in response to tones that are sinusoidally modulated in amplitude at rates between 60 and 120 Hz. For 60 dB SPL 1000-Hz tones the maximum baseline-to-peak amplitude of about 0.06 microV occurs for modulation rates between 80 and 95 Hz. The phase of the response does not change with modulation depths greater than 25% and the amplitude saturates at modulation depths greater than 50%. The presence or absence of a response can be accurately determined by frequency-domain statistics and the response becomes clearly recognizable at intensities that are 16 +/- 8 dB above behavioral thresholds. With increasing intensity the response increases in amplitude at 1.9 nV/dB until an intensity of 70 dB SPL. As the intensity increases above 70 dB SPL the response increases in amplitude more rapidly at 7.8 nV/dB (at 1000 Hz) and contains significant energy at harmonics of the modulation frequency. This second stage of the intensity function is more prominent for stimuli with lower carrier frequencies (500 more than 1000 more than 2000 Hz) and is attenuated by high-pass masking. These steady-state responses should be helpful in evaluating human auditory physiology and in objective audiometry.

Adult↗
PubMed1997

Masking of a brief probe by sinusoidal frequency modulation.

Contrary to level detection models, the thresholds for a brief-duration probe masked by a sinusoidal frequency modulation (FM) masker increases as the modulation index (beta) of FM increases [Zwicker, Acustica 31, 243-256 (1974)]. In this paper the reason for this phenomenon is investigated. In experiment 1, a 10-ms, 1-kHz probe was detected in the presence of an FM masker centered at 1 kHz and sinusoidally modulated at 16 Hz. Thresholds increased by over 15 dB with increasing beta, consistent with Zwicker's findings. In experiment 2, the instantaneous frequency changes of the masker used in experiment 1 were clipped and the resulting thresholds indicated that detection was determined primarily by the masker's total frequency excursion rather than by its instantaneous sweep rate. In experiment 3, the FM maskers from the first two experiments were passed through a roex filter centered at 1 kHz and the resulting envelope was used to amplitude modulate a 1-kHz tone, producing approximately the same effective envelope at 1 kHz as the FM maskers. Threshold functions for the amplitude modulated (AM) maskers were similar to those for their corresponding FM maskers. Thresholds increased by over 15 dB while the total energy of the AM masker decreased by over 10 dB, again contrary to standard level-detection models. The results from these experiments can be explained, at least qualitatively, by a model based on envelope shape discrimination: similarities between the envelopes of the masker alone and masker-plus-probe at the output of an auditory filter centered on the frequency of the probe are primarily responsible for the observed masking, particularly at large beta's.

Auditory Perception↗
PubMed1997

Amplitude modulation depth discrimination of a sinusoidal carrier: effect of stimulus duration.

Discrimination of the change in depth of sinusoidal amplitude modulation (AM) was investigated as a function of stimulus duration. The carrier frequency was 4000 Hz, the standard modulation depth (m) was either 0.1, 0.18, or 0.3, and the modulation rate was either 10, 20, 40, or 80 Hz. For all standard depths and modulation rates, threshold (delta m) decreased by more than a factor o two as stimulus duration doubled from the shortest duration used up to a certain duration (critical duration), beyond which the threshold decreased only slightly or remained constant. The critical duration corresponded to about four cycles of modulation. Psychometric functions were measured for different stimulus durations to examine the extent to which a multiple-looks model could explain the present data. This model provided a reasonable prediction of the change in AM depth discrimination threshold as a function of stimulus duration.

Adult↗
PubMed1999

Quantifying the distortion products generated by amplitude-modulated noise.

When sinusoidal amplitude modulation (SAM) is applied to noise or tone carriers, the stimuli can generate audible distortion products in the region of the modulation frequency. As a result, when bandpass-filtered SAM noise is used to investigate temporal processing, a band of unmodulated noise is typically positioned at the modulation frequency to mask any distortion products. This study was designed to investigate the distortion products for bandpass noise carriers, and so reduce ambiguity about the form of this distortion and its role in perception. The distortion consists of two distortion-noise bands and a distortion tone at the modulation frequency. In the first two experiments, the level and phase of the distortion tone are measured using two different experimental paradigms. In the third experiment, modulation-frequency difference limens are measured for filtered SAM noise and it is shown that performance deteriorates markedly when the distortion tone is canceled. In a fourth experiment, masked threshold is measured at low frequencies for bands of high-frequency, unmodulated noise with the same levels and spectra as the SAM noises in the earlier experiments. The results confirm that unmodulated noise also produces quadratic distortion which may explain some aspects of earlier reports on remote masking.

Adolescent↗
PubMed2000

Binaural effects in center-frequency modulation detection interference for vowel formants.

The detection of slow (5 Hz) center-frequency modulations of formants (signals) can be impaired by the simultaneous presentation of off-frequency modulated formants (maskers) to the same ear [J. Lyzenga and R. P. Carlyon, J. Acoust. Soc. Am. 105, 2792-2806 (1999)]. In the present study we examine this "formant-frequency modulation detection interference (FMDI)" for various binaural masker presentation schemes. Signals and maskers were formantlike complex tones, centered around 1500 and 3000 Hz, respectively. Fundamentals of 80 and 240 Hz were used. The signals were presented to the right ear. The maskers were presented either to the right, the left, or to both ears, and they were either unmodulated or modulated at a slow rate (10 Hz). They had the same fundamental as the signals. Hardly any interference was found for the unmodulated maskers. For modulated maskers, the amount of FMDI depended strongly on the binaural masker presentation scheme. Substantial interference was found for the ipsilateral maskers. Interference was smaller for the contralateral maskers. In both cases the FMDI increased with increasing masker level. Substantial interference was also found for the binaural maskers. Imposing different interaural time and level differences (ITDs and ILDs) on maskers and signals did not affect FMDI. The same was true for the ITD condition when the maskers had different fundamentals than the signals, though FMDI was slightly smaller here. The amount of interference for the binaural maskers was roughly equal to that of the corresponding monaural masker with the largest effect. The data could not be described accurately using a model based on the loudness of the maskers. On the other hand, they were well described by a model in which the amount of FMDI was predicted from a "weighted combination" of the monaural masker levels.

Humans↗
PubMed2004

Application of a kinetic model to the apparently complex behavior of negative and positive allosteric modulators of muscarinic acetylcholine receptors.

The binding of allosteric modulators to G protein-coupled receptors (GPCRs) is often described by an equilibrium allosteric ternary complex model (ATCM). This study evaluated the effects of three modulators on the binding of [(3)H]N-methylscopolamine ([(3)H]NMS) to the human M(2) muscarinic acetylcholine receptor (mAChR). The binding of each modulator was more complex than predicted by the ATCM; the inhibitors heptane-1,7-bis-(dimethyl-3-phthalimidopropyl)-ammonium bromide and gallamine yielded biphasic curves that were described empirically by a two-site binding model, whereas the enhancer alcuronium yielded a bell-shaped curve. Radioligand dissociation assays revealed that the modulators retarded [(3)H]NMS kinetics such that the system never attained equilibrium. Subsequent application of a kinetic ATCM accommodated and quantified all experimental observations. Our findings confirm and extend previous studies on the use of a kinetic ATCM for mAChR allosteric enhancers, but also highlight how complex curves displayed by allosteric inhibitors can be misinterpreted in terms of multisite orthosteric binding. It is possible that similar behavior of other allosteric modulators at GPCRs may reflect nonequilibrium binding artifacts rather than deviation from an ATCM.

Allosteric Regulation↗
PubMed2006

Modulation of pro- and antiapoptotic molecules in double-positive (CD4+CD8+) thymocytes following dexamethasone treatment.

Glucocorticoids play a role in regulation of T lymphocytes homeostasis and development. In particular, glucocorticoid treatment induces massive apoptosis of CD4(+)CD8(+) double-positive (DP) thymocytes. This effect is due to many mechanisms, mainly driven by modulation of gene transcription. To find out which genes are modulated, we analyzed DP thymocytes treated for 3 h with dexamethasone (a synthetic glucocorticoid) by global gene expression profiling. Results indicate modulation of 163 genes, also confirmed by either RNase protection assay or real-time polymerase chain reaction. In particular, dexamethasone caused down-regulation of genes promoting DP thymocyte survival (e.g., Notch1, suppressor of cytokine signaling 1, and inhibitor of DNA binding 3) or modulation of genes activating cell death through the ceramide pathway (UDP-glucose ceramide glucosyltransferase, sphingosine 1-phosphate phosphatase, dihydroceramide desaturase, isoform 1, and G protein-coupled receptor 65) or through the mitochondrial machinery. Among the latter, there are Bcl-2 family members (Bim, Bfl-1, Bcl-xL, and Bcl-xbeta), genes involved in the control of redox status (thioredoxin reductase, thioredoxin reductase inhibitor, and NADP(+)-dependent isocitrate dehydrogenase) and genes belonging to Tis11 family that are involved in mRNA stability. Our study suggests that dexamethasone treatment of DP thymocytes modulates several genes belonging to apoptosis-related systems that can contribute to their apoptosis.

Animals↗
PubMed2006

Complete inhibition of P-glycoprotein by simultaneous treatment with a distinct class of modulators and the UIC2 monoclonal antibody.

P-glycoprotein (Pgp) is one of the active efflux pumps that are able to extrude a large variety of chemotherapeutic drugs from the cells, causing multidrug resistance. The conformation-sensitive UIC2 monoclonal antibody potentially inhibits Pgp-mediated substrate transport. However, this inhibition is usually partial, and its extent is variable because UIC2 binds only to 10 to 40% Pgp present in the cell membrane. The rest of the Pgp molecules become recognized by this antibody only in the presence of certain substrates or modulators, including vinblastine, cyclosporine A (CsA), and SDZ PSC 833 (valspodar). Simultaneous application of any of these modulators and UIC2, followed by the removal of the modulator, results in a completely restored steady-state accumulation of various Pgp substrates (calcein-AM, daunorubicin, and 99mTc-hexakis-2-methoxybutylisonitrile), indicating near 100% inhibition of pump activity. Remarkably, the inhibitory binding of the antibody is brought about by coincubation with concentrations of CsA or SDZ PSC 833 approximately 20 times lower than what is necessary for Pgp inhibition when the modulators are applied alone. The feasibility of such a combinative treatment for in vivo multidrug resistance reversal was substantiated by the dramatic increase of daunorubicin accumulation in xenotransplanted Pgp+ tumors in response to a combined treatment with UIC2 and CsA, both administered at doses ineffective when applied alone. These observations establish the combined application of a class of modulators used at low concentrations and of the UIC2 antibody as a novel, specific, and effective way of blocking Pgp function in vivo.

ATP Binding Cassette Transporter, Subfamily B, Mem↗