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Failure to obtain comodulation masking release with frequency-modulated maskers.

These experiments were intended to determine whether comodulation masking release (CMR) occurs for maskers that are modulated in frequency rather than in amplitude. In experiment I, thresholds for a sinusoidal signal were measured in the presence of two continuous sinusoidal maskers: one was centered at the signal frequency (1.0 kHz), and the other was positioned at flanking frequencies ranging from 0.5 to 2.0 kHz. The two maskers were frequency modulated (FM) by the same low-pass-noise modulator (correlated condition) or by independent noise modulators (uncorrelated condition). Thresholds were the same for the correlated and uncorrelated maskers, i.e., no CMR occurred. This was also true when the flanking band was presented in the ear opposite to that containing the signal and the on-frequency masking band. In experiment II, 25-Hz-wide noise maskers were used. The on-frequency band was sinusoidally frequency modulated, while the off-frequency band either had the same FM or no FM. Thresholds were similar for the two conditions, again indicating that no CMR occurred. The results suggest that, unlike amplitude modulation, correlated FM of the masker in different frequency bands does not give rise to a release from masking.

Acoustic Stimulation↗

Responses to amplitude-modulated tones in the auditory nerve of the cat.

Sinusoidally amplitude-modulated (AM) tones are frequently used in psychophysical and physiological studies, yet a comprehensive study on the coding of AM tones in the auditory nerve is lacking. AM responses of single auditory-nerve fibers of the cat are studied, systematically varying modulation depth, frequency, and sound level. Synchrony-level functions were nonmonotonic with maximum values that were inversely correlated with spontaneous rate (SR). In most fibers, envelope phase-locking showed a positive gain. Modulation transfer functions were uniformly low pass. Their corner frequency increased with characteristic frequency (CF), but changed little for CFs above 10 kHz. The highest modulation frequencies to which phase locking occurred were more than 0.8 oct lower than the highest frequencies to which phase locking to pure tones occurs. Cumulative, or unwrapped, phase increased linearly with modulation frequency: The slope was inversely related to CF, and slightly higher than group delays reported for pure tones. High SR, low CF fibers showed the poorest envelope phase locking. In some low CF fibers, phase locking increased at high levels, associated with "peak-splitting" phenomena. Changes in average rate due to modulation were small, and could be enhancement or suppression.

Acoustics↗

Discrimination and identification of modulation rate using a noise carrier.

Modulation-rate perception was measured for three tasks: a fixed-standard, forced-choice discrimination task with a 500-ms interstimulus interval; a random-standard, forced-choice discrimination task with an 8-s interstimulus interval; and an identification task. Thresholds were obtained for modulation rates from 14-224 Hz using noise carriers bandpass filtered from 500-4000 Hz, 500-1600 Hz, 1700-2800 Hz, and 2900-4000 Hz. The four bands yielded similar results except for modulation rates greater than 100 Hz, where the 500- to 1600-Hz thresholds were higher. Fixed-standard discrimination thresholds were about 3 Hz for modulation rates up to 66 Hz. The increase of thresholds for modulation rates above 66 Hz could be due to temporal resolution limits with a time constant of about 2-3 ms. For modulation rates above 100 Hz, critical-band filtering may further decrease sensitivity for the 500- to 1600-Hz noise band. Resolution in the random-standard discrimination task was similar to that for the identification task. Thresholds were elevated relative to fixed-standard thresholds except at the extremes of the stimulus range. In the random-standard discrimination task, a pronounced criterion bias was present for stimuli near the extremes of the range. Durlach and Braida's model [N. I. Durlach and L. D. Braida, J. Acoust. Soc. Am. 46, 372-383 (1969)] describes the data well and provides quantitative measures for our data in good agreement with those for intensity perception.

Adult↗

Speech enhancement based on physiological and psychoacoustical models of modulation perception and binaural interaction.

A novel approach for analyzing and filtering speech is described and evaluated which utilizes the "modulation spectrogram," i.e., the two-dimensional representation of modulation frequencies versus center frequency as a function of time. This approach is based on physiological findings of a tonotopical organization of modulation frequencies perpendicular to carrier frequencies as well as psychoacoustical findings of "modulation tuning curves." In addition, an interaction is assumed between the representation of modulation frequencies and the representation of auditory space as described by physiological and psychological models of binaural hearing. A noise-reduction algorithm based on this approach was implemented and tested which enhances or suppresses each combination of modulation frequency and center frequency according to its phase and intensity relation between the two input signals (i.e., both stereo channels of a dummy-head recording). When tested in several situations with interfering speakers and background noise both in anechoic and reverberant environment, the algorithm provided a small but a very robust increase in speech intelligibility which corresponds to approximately 2 dB in signal-to-noise ratio. Possible applications of this algorithm are noise reduction in adverse acoustical situations, digital hearing aids, processing schemes and preprocessing for speech recognition.

Adult↗

The critical modulation frequency and its relationship to auditory filtering at low frequencies.

If the thresholds for detecting sinusoidal amplitude or frequency modulation of a sinusoidal carrier with frequency fc are expressed in terms of the respective modulation indices, m and beta, the ratio beta/m decreases as the modulation frequency increases, and approaches an asymptotic value of unity. The modulation frequency at which the ratio first becomes unity is called the critical modulation frequency (CMF). It has been suggested that the CMF is reached when the spectral sidebands in the stimulus first become detectable and that the CMF corresponds to half the value of the critical bandwidth (CB) at fc. In this paper it is demonstrated that the CMF is confounded as a measure of frequency selectivity at low frequencies, since, for modulation frequencies around the CMF, the sideband that is most detectable changes with fc. For values of fc above 250 Hz, the lower sideband is most detectable. For values of fc below 200 Hz, the upper sideband is most detectable. These findings can account for the fact that the CMF flattens off at low carrier frequencies, reaching an asymptotic value of about 40 Hz, whereas the auditory filter bandwidth continues to decrease down to very low center frequencies.

Acoustic Stimulation↗

Further evidence against an across-frequency mechanism specific to the detection of frequency modulation (FM) incoherence between resolved frequency components.

Previously, Carlyon [J. Acoust. Soc. Am. 89, 329-340 (1991)] argued that there exists no across-frequency mechanism specific to the detection of frequency modulation (FM) incoherence, defined as a difference in FM phase, between pairs of resolved frequency components. Experiments are described which attempted to reconcile this conclusion with the results of two recent studies. Wilson et al. [J. Acoust. Soc. Am. 88, 1333-1338 (1990)] reported that the detection of FM imposed on a target component was impaired by the presence of an FM "interfering tone," and that the size of the effect depended on the FM coherence between interferer and target. Experiment 1 replicated their findings but showed, by using low-pass and wideband noise, that its dependence on FM coherence was consistent with the detection of combination tones and of beating between the interferer and target. Cohen and Chen [J. Acoust. Soc. Am. 92, 766-722 (1992)] reported that the detection threshold for an FM signal was higher when it was masked by two components modulated coherently with it than when the masker and signal modulations were incoherent. Experiment 2 showed that, when the masker consisted of eight components, thresholds were largely determined by the modulation coherence between the signal and the masker component closest to it in frequency. Experiment 3 presented evidence that Cohen and Chen's findings were influenced by harmonicity between the masker and signal, even in conditions which attempted to control it. Experiment 4 replicated another of Cohen and Chen's findings, that when the masker modulation was held constant and the signal FM depth varied, some listeners' thresholds reached a maximum when the masker and signal FM depths were equal. By manipulating the frequency ratio between masker and signal, it was shown that this finding, too, could be attributed to harmonicity between the signal and one of the masker components. Finally, experiment 5 replicated Carlyon's (1991) findings at a higher sensation level and with a different pattern of modulation than used previously.

Acoustic Stimulation↗

Effect of temporal modulation reduction on spectral contrasts in speech.

In this paper the effect of temporal modulation reduction on spectral contrasts is investigated. First, a spectral modulation transfer function (SMTF) is presented as a method to measure the transfer of spectral ripples (sinusoidal periods/oct) in the short-time spectral envelope by comparing the spectral modulation depth of original and processed speech fragments. Measuring the SMTF for speech subjected to uniform reduction of the temporal modulation depth (i.e., modulation-frequency-independent reduction) in 24 1/4-oct bands showed an almost equal uniform reduction of the spectral modulations. Furthermore, the SMTF was used to measure the reduction of spectral contrasts associated with low-pass and high-pass temporal-envelope filtering [Drullman et al., J. Acoust. Soc. Am.95, 1053-1064 and 2670-2680 (1994a, b)]. For a perceptual evaluation, sentences were processed to reduce spectral contrasts and the speech-reception threshold (SRT) in noise was measured with ten normal-hearing subjects. Comparison of the results with those obtained previously after temporal-envelope filtering revealed that the SRT-effect of temporal high-pass filtering can be completely accounted for by the associated reduction of spectral contrasts. However, this relationship cannot be demonstrated conclusively in the case of temporal low-pass filtering.

Adolescent↗

The effects of frequency region and bandwidth on the temporal modulation transfer function.

Temporal resolution was examined as a function of frequency region and listening region. The first experiment demonstrated that amplitude- and frequency-modulated tones are not appropriate stimuli to study temporal resolution as a functional of frequency region, due to the availability of other cues in addition to temporal ones. In the other experiments, thresholds for detection of sinusoidal amplitude modulation of a noise band were measured as a function of frequency region, bandwidth, and level of surrounding notched noise masker. Temporal modulation transfer functions (TMTFs) measured in low- and high-frequency regions did not differ in sensitivity or in cutoff frequency, suggesting that initial "critical band" filtering did not affect temporal resolution. When the upper cutoff frequency of the noise was held constant, TMTF sensitivity increased with noise bandwidth, while the cutoff frequency of the TMTF did not show measurable change. These results are consistent with the predictions of an envelope detector model if peripheral filtering in the lower-frequency range is assumed to be approximately twice as wide as that estimated by measuring thresholds for a tone in notched noise. Restricting the listening region with notched noise increased thresholds for low modulation frequencies but not for high. This is consistent with other data showing that upward spread of excitation may increase the effective modulation depth, but only for low modulation frequencies.

Audiometry, Pure-Tone↗

Binaural modulation detection interference.

The ability to detect amplitude modulation (AM) of a tonal probe can be disrupted by the presence of modulated masking tones. Two experiments examined whether a disparity in the interaural parameters of the probe and masker can reduce the amount of interference. In the first experiment, the effects of interaural time and intensity differences were studied in separate sets of conditions. With low-frequency carriers, the detection of 10-Hz probe modulation in the presence of 10-Hz masker modulation was not significantly affected by interaural time differences. With higher-frequency carriers, dichotic stimuli were generated through combinations of diotic, dichotic, or monotic probe and masker presentations in which the probe and masker did not share a common interaural intensity difference. In these conditions, the amount of interference was affected by the interaural configuration. However, monotic level differences between the probe and masker may have contributed to the effect of interaural configuration. In the second experiment, the probe and masker were presented through separate speakers in an enclosed listening environment. Spatial separation between the sources for the probe and masker led to a small reduction in the amount of interference. When the masker modulation rate was varied with the probe AM rate fixed at 10 Hz, the extent of tuning in the modulation domain in the sound-field conditions was similar to that obtained with diotic stimulus presentation over headphones.

Analysis of Variance↗

Modeling interaural-delay sensitivity to frequency modulation at high frequencies.

Interaural-delay sensitivity to high-frequency (> or = 3 kHz) sinusoidal-frequency-modulated (SFM) tones is examined for rates from 25 to 800 Hz and depths of -12 to 18 dB. Comparison is made to thresholds obtained for sinusoidal-amplitude-modulated (SAM) tones for the same observers and modulation rates. Both SAM and SFM threshold-by-rate functions are U-shaped with optimum sensitivity to SFM tones occurring at higher rates (fm = 200-400 Hz) compared to those for SAM tones (fm = 100-200 Hz). Effects of modulation depth were examined for rates from 50 to 300 Hz. In all cases thresholds improved considerably with increasing modulation depth. It is also shown that a hybrid dichotic signal composed of an SFM tone presented to one ear and an SAM tone to the other, can perceptually fuse and be lateralized, with the contingency that both stimuli have equal modulation rates but not necessarily equal carrier frequencies. Using bandpass noise to restrict off-frequency listening, it was shown that for this stimulus, observers can use information from filters either below or above the carrier frequency. Consistent with FM-to-AM conversion from cochlear bandpass filtering, several important differences between the SAM- and SFM-tone data can be predicted from a nonstationary stochastic model of binaural interaction whose parameters are uniquely determined from the SAM-tone data.

Auditory Perception↗

Intensity discrimination and detection of amplitude modulation.

Thresholds for detection of low-rate sinusoidal amplitude modulation and for detection of intensity increments were measured over a wide range of levels in an examination of the relationship between these fundamental aspects of intensity processing. As expected, thresholds measured with a continuous 1-kHz tone decrease with increasing carrier/pedestal level. For levels between 6 and 85 dB SPL the data are well described by 10 log delta I/I = 0.44.(20 log m) + D(fm), where delta I/I is the Weber fraction for increment detection, m is the modulation index at threshold, and D(fm) depends on modulation rate (fm). The relationship between the psychometric functions for modulation and increment detection is also consistent with this equation. The data indicate a clear relationship between modulation and increment detection and thus provide an important additional consideration for models of modulation processing. No existing models provide an adequate account of this relationship.

Auditory Perception↗

Within-channel cues in comodulation masking release (CMR): experiments and model predictions using a modulation-filterbank model.

Experiments and model calculations were performed to study the influence of within-channel cues versus across-channel cues in comodulation masking release (CMR). A class of CMR experiments is considered that are characterized by a single (unmodulated or modulated) bandpass noise masker with variable bandwidth centered at the signal frequency. A modulation-filterbank model suggested by Dau et al. [J. Acoust. Soc. Am. 102, 2892-2905 (1997)] was employed to quantitatively predict the experimental data. Effects of varying masker bandwidth, center frequency, modulator bandwidth, modulator type, and signal duration on CMR were examined. In addition, the effect of band limiting the noise before or after modulation was shown to influence the CMR in the same way as a systematic variation of the modulation depth. It is demonstrated that a single-channel analysis, which analyzes only the information from one peripheral channel, quantitatively accounts for the CMR in most cases, indicating that an across-channel process is generally not necessary for simulating results from this class of CMR experiments. True across-channel processes may be found in another class of CMR experiments.

Adult↗

Neuroactive steroid interactions with voltage-dependent anion channels: lack of relationship to GABA(A) receptor modulation and anesthesia.

Neuroactive steroids modulate the function of gamma-aminobutyric acid type A (GABA(A)) receptors in brain; this is the presumed basis of their action as anesthetics. In a previous study using the neuroactive steroid analog, (3alpha,5beta)-6-azi-3-hydroxypregnan-20-one (6-AziP), as a photoaffinity-labeling reagent, we showed that voltage-dependent anion channel-1 (VDAC-1) was the predominant protein labeled in brain. Antisera to VDAC-1 were shown to coimmunoprecipitate GABA(A) receptors, suggesting a functional relationship between steroid binding to VDAC-1 and modulation of GABA(A) receptor function. This study examines the contribution of steroid binding to VDAC proteins to modulation of GABA(A) receptor function and anesthesia. Photolabeling of 35-kDa protein with [(3)H]6-AziP was reduced 85% in brain membranes prepared from VDAC-1-deficient mice but was unaffected by deficiency of VDAC-3. The photolabeled 35-kDa protein in membranes from VDAC-1-deficient mice was identified by two-dimensional electrophoresis and electrospray ionization-tandem mass spectrometry as VDAC-2. The absence of VDAC-1 or VDAC-3 had no effect on the ability of neuroactive steroids to modulate GABA(A) receptor function as evidenced by radioligand ([(35)S] t-butylbicyclophosphorothionate) binding or by electrophysiological studies. Electrophysiological studies also showed that neuroactive steroids modulate GABA(A) receptor function normally in VDAC-2-deficient fibroblasts transfected with alpha(1)beta(2)gamma(2) GABA(A) receptor subunits. Finally, the neuroactive steroid pregnanolone [(3alpha,5beta)-3-hydroxypregnan-20-one] produced anesthesia (loss of righting reflex) in VDAC-1- and VDAC-3-deficient mice, and there was no difference in the recovery time between the VDAC-deficient mice and wild-type controls. These data indicate that neuroactive steroid binding to VDAC-1, -2, or -3 is unlikely to mediate GABA(A) receptor modulation or anesthesia.

Anesthesia↗

Distinct sites for inverse modulation of N-methyl-D-aspartate receptors by sulfated steroids.

Steroid sulfation occurs in nervous tissue and endogenous sulfated steroids can act as positive or negative modulators of N-methyl-D-aspartate (NMDA) receptor function. In the current study, structure-activity relationships for sulfated steroids were examined in voltage-clamped chick spinal cord and rat hippocampal neurons in culture and in Xenopus laevis oocytes expressing NR1(100) and NR2A subunits. The ability of pregnenolone sulfate (a positive modulator) and epipregnanolone sulfate (a negative modulator) to compete with each another, as well as with other known classes of NMDA receptor modulators, was examined. The results show that steroid positive and negative modulators act at specific, extracellularly directed sites that are distinct from one another and from the spermine, redox, glycine, Mg2+, MK-801, and arachidonic acid sites. Sulfated steroids are effective as modulators of ongoing glutamate-mediated synaptic transmission, which is consistent with their possible role as endogenous neuromodulators in the CNS.

Animals↗

Identification of essential residues involved in the allosteric modulation of the human A(3) adenosine receptor.

We examined the effects on allosteric modulation and ligand binding of the mutation of amino acid residues of the human A(3) adenosine receptor (A(3)AR) that are hypothesized to be near one of three loci: the putative sodium binding site, the putative ligand binding site, and the DRY motif in transmembrane helical domain 3. The effects of three heterocyclic allosteric modulators [the imidazoquinoline 2-cyclopentyl-4-phenylamino-1H-imidazo[4,5-c]quinoline (DU124183), the pyridinylisoquinoline 4-methoxy-N-[7-methyl-3-(2-pyridinyl)-1-isoquinolinyl]benzamide (VUF5455), and the amiloride analog 5-(N,N-hexamethylene)-amiloride] on the dissociation of the agonist radioligand, N(6)- (4-amino-3-[(125)I]iodobenzyl)-5'-N-methylcarboxamidoadenosine, were compared at wild-type (WT) and mutant A(3)ARs. The F182A(5.43) and N274A(7.45) mutations eliminated the allosteric effects of all three modulators but had little effect on agonist binding. The N30A(1.50) and D58N(2.50) mutations abolished the allosteric effects of DU124183 and VUF5455, but not HMA, whereas the D107N(3.49) mutation abolished the effects of DU124183, but not HMA or VUF5455. The T94A(3.36), H95A(3.37), K152A(EL2), W243A(6.48), L244A(6.49), and S247A(6.52) mutations did not influence allosteric effects of the modulators. Sodium ions (100 mM), which modulate agonist binding at a variety of receptors, caused an approximately 80% inhibition of agonist binding in WT A(3)ARs but did not show any effect on D58N(2.50), D107N(3.49), and F182A(5.43) mutant receptors. In contrast, NaCl induced a modest increase of agonist binding in N30A(1.50) and N274A(7.45) mutant receptors. NaCl decreased the dissociation rate of the antagonist radioligand [(3)H]8-ethyl-4-methyl-2-phenyl-(8R)-4,5,7,8-tetrahydro-1H-imidazo[2.1-i]purin-5-one (PSB-11) at the WT A(3)ARs, but not the D58N(2.50) mutant receptor. The results were interpreted using a rhodopsin-based molecular model of the A(3)AR to suggest multiple binding modes of the allosteric modulators.

Adenosine↗

Organization of tn2610 containing two transposition modules.

Transposon Tn2610, found in a conjugative plasmid from an Escherichia coli isolate recovered at a hospital in Chiba, Japan, in 1975, was completely sequenced. Tn2610 is 23,883 bp long and is bracketed by two transposition modules, a Tn1721-like module and a Tn21-derived module, which correspond, respectively, to the long inverted repeats IRa and IRb previously described for this transposon. Although both tnpA genes are intact, only that in the Tn21-derived module (IRb) functions in the transposition, while that in the Tn1721-derived module (IRa) cannot recognize the 38-bp imperfect repeat at the end of the IRb element. Both tnpR and res are present in IRa, while the tnpR gene of IRb is interrupted by the insertion of an IS26 insertion element. The intervening region, between the res site of the Tn1721 module and IS26, carries multiple integron-associated resistance genes within a Tn21 backbone, including a region identical to that found in the genome of Salmonella enterica serovar Typhimurium DT104. These findings suggest that Tn2610 originated from Tn1721 and Tn21, with extensive recombination events with other elements which have resulted in a complex mosaic structure.

Base Sequence↗

Essentiality of a newly identified carbohydrate-binding module for the function of CelB (BH0603) from the alkaliphilic bacterium Bacillus halodurans.

CelB (BH0603) from Bacillus halodurans is a modular glycoside hydrolase with a family 5 catalytic module, an immunoglobulin-like module, and module PfamB of unknown function. The recombinant PfamB module bound to Avicel and was essential for CelB hydrolytic function. We propose that module PfamB be designated a new carbohydrate-binding module.

Alkalies↗

Characterization of a cellulase containing a family 30 carbohydrate-binding module (CBM) derived from Clostridium thermocellum CelJ: importance of the CBM to cellulose hydrolysis.

Clostridium thermocellum CelJ is a modular enzyme containing a family 30 carbohydrate-binding module (CBM) and a family 9 catalytic module at its N-terminal moiety. To investigate the functions of the CBM and the catalytic module, truncated derivatives of CelJ were constructed and characterized. Isothermal titration calorimetric studies showed that the association constants (K(a)) of the CBM polypeptide (CBM30) for the binding of cellopentaose and cellohexaose were 1.2 x 10(4) and 6.4 x 10(4) M(-1), respectively, and that the binding of CBM30 to these ligands is enthalpically driven. Qualitative analyses showed that CBM30 had strong affinity for cellulose and beta-1,3-1,4-mixed glucan such as barley beta-glucan and lichenan. Analyses of the hydrolytic action of the enzyme comprising the CBM and the catalytic module showed that the enzyme is a processive endoglucanse with strong activity towards carboxymethylcellulose, barley beta-glucan and lichenan. By contrast, the catalytic module polypeptide devoid of the CBM showed negligible activity toward these substrates. These observations suggest that the CBM is extremely important not only because it mediates the binding of the enzyme to the substrates but also because it participates in the catalytic function of the enzyme or contributes to maintaining the correct tertiary structure of the family 9 catalytic module for expressing enzyme activity.

Bacterial Proteins↗