Adjunctive Dexamethasone for Tuberculous Meningitis in HIV-Positive Adults.

BACKGROUND: Adjunctive glucocorticoids are widely used to treat human immunodeficiency virus (HIV)-associated tuberculous meningitis despite limited data supporting their safety and efficacy. METHODS: We conducted a double-blind, randomized, placebo-controlled trial involving HIV-positive adults (≥18 years of age) with tuberculous meningitis in Vietnam and Indonesia. Participants were randomly assigned to receive a 6-to-8-week tapering course of either dexamethasone or placebo in addition to 12 months of antituberculosis chemotherapy. The primary end point was death from any cause during the 12 months after randomization. RESULTS: A total of 520 adults were randomly assigned to receive either dexamethasone (263 participants) or placebo (257 participants). The median age was 36 years; 255 of 520 participants (49.0%) had never received antiretroviral therapy, and 251 of 484 participants (51.9%) with available data had a baseline CD4 count of 50 cells per cubic millimeter or less. Six participants withdrew from the trial, and five were lost to follow-up. During the 12 months of follow-up, death occurred in 116 of 263 participants (44.1%) in the dexamethasone group and in 126 of 257 participants (49.0%) in the placebo group (hazard ratio, 0.85; 95% confidence interval, 0.66 to 1.10; P = 0.22). Prespecified analyses did not reveal a subgroup that clearly benefited from dexamethasone. The incidence of secondary end-point events, including cases of immune reconstitution inflammatory syndrome during the first 6 months, was similar in the two trial groups. The numbers of participants with at least one serious adverse event were similar in the dexamethasone group (192 of 263 participants [73.0%]) and the placebo group (194 of 257 participants [75.5%]) (P = 0.52). CONCLUSIONS: Among HIV-positive adults with tuberculous meningitis, adjunctive dexamethasone, as compared with placebo, did not confer a benefit with respect to survival or any secondary end point. (Funded by the Wellcome Trust; ACT HIV ClinicalTrials.gov number, NCT03092817.).

Real-time estimation of eye gaze by in-ear electrodes.

Cognitive control of a hearing aid is the topic for several ongoing studies. The relevance of these studies should be seen in the light of inadequate steering of current hearing aids. While most studies are concerned with auditory attention tracking from the electroencephalogram (EEG), a complimentary approach may be to use visual attention tracking to steer the devices. Visual attention may be characterized by gaze direction, which can be obtained by electrooculography (EOG). EOG may be recorded from electrodes placed in the ear canal, termed EarEOG. To test the comparison of conventional EOG and EarEOG recordings, we conducted two experiments with six subjects. In the first experiment, the subjects were instructed to follow a moving dot on the screen moving in large saccades. In the second experiment, there were five large targets, and within each target, the dot had minor movements. When comparing conventional EOG and EarEOG, correlations of 0.9 and 0.91 with standard deviations of 0.02 were obtained for the two experiments respectively. To assess the feasibility of using EarEOG in real-time, correlation between EarEOG and the timecourse of the dot position was performed. When both signals were filtered with the same real-time applicable filter, correlations of 0.83 and 0.85 with standard deviations of 0.09 and 0.05 were found respectively to the two experiments. In conclusion, this study provides motivational aspects of using EarEOG to estimate eye gaze, as well as it identifies important future challenges in real-time applications to steer external devices such as a hearing aid.

Quantitative analysis of protease recognition by inhibitors in plasma using microscale thermophoresis.

High abundance proteins like protease inhibitors of plasma display a multitude of interactions in natural environments. Quantitative analysis of such interactions in vivo is essential to study diseases, but have not been forthcoming, as most methods cannot be directly applied in a complex biological environment. Here, we report a quantitative microscale thermophoresis assay capable of deciphering functional deviations from in vitro inhibition data by combining concentration and affinity measurements. We obtained stable measurement signals for the substrate-like interaction of the disease relevant inhibitor α-1-antitrypsin (AAT) Z-variant with catalytically inactive elastase. The signal differentiates between healthy and sick AAT-deficient individuals suggesting that affinity between AAT and elastase is strongly modulated by so-far overlooked additional binding partners from the plasma.

Autoprocessing of neutrophil elastase near its active site reduces the efficiency of natural and synthetic elastase inhibitors.

An imbalance between neutrophil-derived proteases and extracellular inhibitors is widely regarded as an important pathogenic mechanism for lung injury. Despite intense efforts over the last three decades, attempts to develop small-molecule inhibitors for neutrophil elastase have failed in the clinic. Here we discover an intrinsic self-cleaving property of mouse neutrophil elastase that interferes with the action of elastase inhibitors. We show that conversion of the single-chain (sc) into a two-chain (tc) neutrophil elastase by self-cleavage near its S1 pocket altered substrate activity and impaired both inhibition by endogenous α-1-antitrypsin and synthetic small molecules. Our data indicate that autoconversion of neutrophil elastase decreases the inhibitory efficacy of natural α-1-antitrypsin and small-molecule inhibitors, while retaining its pathological potential in an experimental mouse model. The so-far overlooked occurrence and properties of a naturally occurring tc-form of neutrophil elastase necessitates the redesign of small-molecule inhibitors that target the sc-form as well as the tc-form of neutrophil elastase.

Reconciling frequency selectivity and phase effects in masking.

The effects of auditory frequency selectivity and phase response on masking were studied using harmonic tone complex maskers with a 100-Hz fundamental frequency. Positive and negative Schroeder-phase complexes (m+ and m-), were used as maskers and the signal was a long-duration sinusoid. In the first experiment, thresholds for signal frequencies of 1 and 4 kHz were measured as a function of masker bandwidth and number of components. A large difference in thresholds between the m+ and m- complexes was found only when masker components were presented ipsilateral to the signal over a frequency range wider than the traditional critical band, regardless of the absolute number of components. In the second experiment, frequency selectivity was measured in harmonic tone complexes with fixed or random phases as well as in noise, using a variant of the notched-noise method with a fixed masker level. The data showed that frequency selectivity is not affected by masker type, indicating that the wide listening bandwidth suggested by the first experiment cannot be ascribed to broader effective filters in complex-tone maskers than in noise maskers. The third experiment employed a novel method of measuring frequency selectivity, which has the advantage that the overall level at the input and the output of the auditory filter remains roughly constant across all conditions. The auditory filter bandwidth measured using this method was wider than that measured in the second experiment, but may still be an underestimate, due to the effects of off-frequency listening. The data were modeled using a single-channel model with various initial filters. The main findings from the simulations were: (1) the magnitude response of the Gammatone filter is too narrow to account for the phase effects observed in the data; (2) none of the other filters currently used in auditory models can account for both frequency selectivity and phase effects in masking; (3) the Gammachirp filter can be made to provide a good account of the data by altering its phase response. The final conclusion suggests that masker phase effects can be accounted for with a single-channel model, while still remaining consistent with measures of frequency selectivity: effects that appear to involve broadband processing do not necessarily require across-channel mechanisms.

Modeling temporal and compressive properties of the normal and impaired auditory system.

Three modifications of a psychoacoustically and physiologically motivated processing model [Dau et al., J. Acoust. Soc. Am. 102 (1997a) 2892-2905] are presented and tested. The modifications aim at simulating sensorineural hearing loss and incorporate a level-dependent peripheral compression whose properties are affected by hearing impairment. Model 1 realizes this difference by introducing for impaired listeners an instantaneous level-dependent expansion prior to the adaptation stage of the model. Model 2 and Model 3 realize a level-dependent compression with time constants of 5 and 15 ms, respectively, for normal hearing and a reduced compression for impaired hearing. In Model 2, the compression occurs after the envelope extraction stage, while in Model 3, envelope extraction follows compression. All models account to a similar extent for the recruitment phenomenon measured with narrow-band stimuli and for forward-masking data of normal-hearing and hearing-impaired subjects using a 20-ms, 2-kHz tone signal and a 1-kHz-wide bandpass noise masker centered at 2 kHz. A clear difference between the different models occurs for the processing of temporally fluctuating stimuli. A modulation-rate-independent increase in modulation-response level for simulating impaired hearing is only predicted by Model 1 while the other two models realize a modulation-rate-dependent increase. Hence, the predictions of Model 2 and Model 3 are in conflict with the results of modulation-matching experiments reported in the literature. It is concluded that key properties of sensorineural hearing loss (altered loudness perception, reduced dynamic range, normal temporal properties but prolonged forward-masking effects) can effectively be modeled by incorporating a fast-acting expansion within the current processing model prior to the nonlinear adaptation stage. Based on these findings, a model of both normal and impaired hearing is proposed which incorporates a fast-acting compressive nonlinearity, representing the cochlear nonlinearity (which is reduced in impaired listeners), followed by an instantaneous expansion and the nonlinear adaptation stage which represent aspects of the retro-cochlear information processing in the auditory system.

Modulation detection interference: effects of concurrent and sequential streaming.

The presence of amplitude fluctuations in one frequency region can interfere with our ability to detect similar fluctuations in another (remote) frequency region. This effect is known as modulation detection interference (MDI). Gating the interfering and target sounds asynchronously is known to lead to a reduction in MDI, presumably because the two sounds become perceptually segregated. The first experiment examined the relative effects of carrier and modulator gating asynchrony in producing a release from MDI. The target carrier was a 900-ms, 4.3-kHz sinusoid, modulated in amplitude by a 500-ms, 16-Hz sinusoid, with 200-ms unmodulated fringes preceding and following the modulation. The interferer (masker) was a 1-kHz sinusoid, modulated by a narrowband noise with a 16-Hz bandwidth, centered around 16 Hz. Extending the masker carrier for 200 ms before and after the signal carrier reduced MDI, regardless of whether the target and masker modulators were gated synchronously or were gated with onset and offset asynchronies of 200 ms. Similarly, when the carriers were gated synchronously, asynchronous gating of the modulators did not produce a release from MDI. The second experiment measured MDI with a synchronous target and masker and investigated the effect of adding a series of precursor tones, which were designed to promote the forming of a perceptual stream with the masker, thereby leaving the target perceptually isolated. Four modulated or unmodulated precursor tones presented at the masker frequency were sufficient to completely eliminate MDI. The results support the idea that MDI is due to a perceptual grouping of the masker and target, and show that conditions promoting sufficient perceptual segregation of the masker and target can lead to a total elimination of MDI.

Towards a measure of auditory-filter phase response.

This study investigates how the phase curvature of the auditory filters varies with center frequency (CF) and level. Harmonic tone complex maskers were used, with component phases adjusted using a variant of an equation proposed by Schroeder [IEEE Trans. Inf. Theory 16, 85-89 (1970)]. In experiment 1, the phase curvature of the masker was varied systematically and sinusoidal signal thresholds were measured at frequencies from 125 to 8000 Hz. At all signal frequencies, threshold differences of 20 dB or more were observed between the most effective and least effective masker phase curvature. In experiment 2, the effect of overall masker level on masker phase effects was studied using signal frequencies of 250, 1000, and 4000 Hz. The results were used to estimate the phase curvature of the auditory filters. The estimated relative phase curvature decreases dramatically with decreasing CF below 1000 Hz. At frequencies above 1000 Hz, relative auditory-filter phase curvature increases only slowly with increasing CF, or may remain constant. The phase curvature of the auditory filters seems to be broadly independent of overall level. Most aspects of the data are in qualitative agreement with peripheral physiological findings from other mammals, which suggests that the phase responses observed here are of peripheral origin. However, in contrast to the data reported in a cat auditory-nerve study [Carney et al., J. Acoust. Soc. Am. 105, 2384-2391 (1999)], no reversal in the sign of the phase curvature was observed at very low frequencies. Overall, the results provide a framework for mapping out the phase curvature of the auditory filters and provide constraints on future models of peripheral filtering in the human auditory system.

Characterizing frequency selectivity for envelope fluctuations.

Three experimental paradigms were used to specify the auditory system's frequency selectivity for amplitude modulation (AM). In the first experiment, masked-threshold patterns were obtained for signal-modulation frequencies of 4, 16, 64, and 256 Hz in the presence of a half-octave-wide modulation masker, both applied to the same noise carrier with a bandwidth ranging from 1 to 4 kHz. In the second experiment, psychophysical tuning curves (PTCs) were obtained for signal-modulation frequencies of 16 and 64 Hz imposed on a noise carrier as in the first experiment. In the third experiment, masked thresholds for signal-modulation frequencies of 8, 16, 32, and 64 Hz were obtained according to the "classical" band-widening paradigm, where the bandwidth of the modulation masker ranged from 1/8 to 4 octaves, geometrically centered on the signal frequency. The first two experiments allowed a direct derivation of the shape of the modulation filters while the latter paradigm only provided an indirect estimate of the filter bandwidth. Thresholds from the experiments were predicted on the basis of an envelope power-spectrum model (EPSM) which integrates the envelope power of the modulation masker in the passband of a modulation filter tuned to the signal-modulation frequency. The Q-value of second-order bandpass modulation filters was fitted to the masking patterns from the first experiment using a least-squares algorithm. Q-values of about 1 for frequencies up to 64 Hz suggest an even weaker selectivity for modulation than assumed in earlier studies. The same model also accounted reasonably well for the shape of the temporal modulation transfer function (TMTF) obtained for carrier bandwidths in the range from 1 to 6000 Hz. Peripheral filtering and effects of peripheral compression were also investigated using a multi-channel version of the model. Waveform compression did not influence the simulated results. Peripheral bandpass filtering only influenced thresholds for high modulation frequencies when signal information was strongly attenuated by the transfer function of the peripheral filters.

The influence of carrier level and frequency on modulation and beat-detection thresholds for sinusoidal carriers

This paper is concerned with modulation and beat detection for sinusoidal carriers. In the first experiment, temporal modulation transfer functions (TMTFs) were measured for carrier frequencies between 1 and 10 kHz. Modulation rates covered the range from 10 Hz to about the rate equaling the critical bandwidth at the carrier frequency. In experiment 2, TMTFs for three carrier frequencies were obtained as a function of the carrier level. In the final experiment, thresholds for the detection of either the lower or the upper modulation sideband (beat detection) were measured for "carrier" frequencies of 5 and 10 kHz, using the same range of modulation rates as in experiment 1. The TMTFs for carrier frequencies of 2 kHz and higher remained flat up to a modulation rate of about 100-130 Hz and had similar values across carrier frequencies. For higher rates, modulation thresholds initially increased and then decreased rapidly, reflecting the subjects' ability to resolve the sidebands spectrally. Detection thresholds generally improved with increasing carrier level, but large variations in the exact level dependence were observed, across subjects as well as across carrier frequencies. For beat rates up to about 70 Hz (at 5 kHz) and 100 Hz (at 10 kHz), beat detection thresholds were the same for the upper and the lower sidebands and were about 6 dB higher than the level per sideband at the modulation-detection threshold. At higher rates the threshold for both sidebands increased, but the increase was larger for the lower sideband. This reflects an asymmetry in masking with more masking towards lower frequencies. Only at rates well beyond the maximum of the TMTF did detection for the lower sideband start to be better than that for the upper sideband. The asymmetry at intermediate frequency separations can be explained by assuming that detection always takes place in filters centered above the stimulus spectrum. The shape of the TMTF and the beat-detection data reflects a limitation in resolving fast amplitude variations, which must occur central to the inner-ear filtering. Its characteristic resembles that of a first-order low-pass filter with a cutoff frequency of about 150 Hz.

On the role of envelope fluctuation processing in spectral masking.

This study examines the role of temporal cues in spectral masking, such as beats and intrinsic envelope fluctuations. Predictions from the modulation-filterbank model developed by Dau et al. [J. Acoust. Soc. Am. 102, 2906-2919 (1997)] are compared to average masking patterns from Moore et al. [J. Acoust. Soc. Am. 104, 1023-1038 (1998)]. In these experiments, tones and narrow-band noises have been used as the signal and the masker, so that all four signal-masker combinations are considered. In addition, model predictions are compared with new experimental data in conditions of notched-noise masking, where the masker consisted of two narrow-band noises whose bandwidth and frequency separation were varied systematically. The model uses a peripheral filtering stage with linear and symmetric Gammatone filters, an adaptation stage that includes a static compressive nonlinearity for stationary input stumuli and a higher sensitivity for envelope fluctuation, and a modulation filterbank that analyzes the output for each peripheral channel. For low and medium masker levels, the model accounts very well for the masking patterns in all signal-masker conditions, as well as for the notched-noise conditions. In contrast, predictions from a version of the model that acts like an energy detector account for only some of the notched-noise data, and generally do not account for the shape of the masking patterns. For a high masker level, the simulations suggest the use of asymmetric filters, with a steeper high-frequency slope than is used in the linear model, consistent with results from previous studies. In addition, several nonlinear effects become apparent at this masker level, which cannot be accounted for by the current model.

Auditory brainstem responses with optimized chirp signals compensating basilar-membrane dispersion.

This study examines auditory brainstem responses (ABR) elicited by rising frequency chirps. The time course of frequency change for the chirp theoretically produces simultaneous displacement maxima by compensating for travel-time differences along the cochlear partition. This broadband chirp was derived on the basis of a linear cochlea model [de Boer, "Auditory physics. Physical principles in hearing theory I," Phys. Rep. 62, 87-174 (1980)]. Responses elicited by the broadband chirp show a larger wave-V amplitude than do click-evoked responses for most stimulation levels tested. This result is in contrast to the general hypothesis that the ABR is an electrophysiological event most effectively evoked by the onset or offset of an acoustic stimulus, and unaffected by further stimulation. The use of this rising frequency chirp enables the inclusion of activity from lower frequency regions, whereas with a click, synchrony is decreased in accordance with decreasing traveling velocity in the apical region. The use of a temporally reversed (falling) chirp leads to a further decrease in synchrony as reflected in ABR responses that are smaller than those from a click. These results are compatible with earlier experimental results from recordings of compound action potentials (CAP) [Shore and Nuttall, "High synchrony compound action potentials evoked by rising frequency-swept tonebursts," J. Acoust. Soc. Am. 78, 1286-1295 (1985)] reflecting activity at the level of the auditory nerve. Since the ABR components considered here presumably reflect neural response from the brainstem, the effect of an optimized synchronization at the peripheral level can also be observed at the brainstem level. The rising chirp may therefore be of clinical use in assessing the integrity of the entire peripheral organ and not just its basal end.

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.

Intrinsic envelope fluctuations and modulation-detection thresholds for narrow-band noise carriers.

A model is presented which calculates the intrinsic envelope power of a bandpass noise carrier within the passband of a hypothetical modulation filter tuned to a specific modulation frequency. Model predictions are compared to experimentally obtained amplitude modulation (AM) detection thresholds. In experiment 1, thresholds for modulation rates of 5, 25, and 100 Hz imposed on a bandpass Gaussian noise carrier with a fixed upper cutoff frequency of 6 kHz and a bandwidth in the range from 1 to 6000 Hz were obtained. In experiment 2, three noises with different spectra of the intrinsic fluctuations served as the carrier: Gaussian noise, multiplied noise, and low-noise noise. In each case, the carrier was spectrally centered at 5 kHz and had a bandwidth of 50 Hz. The AM detection thresholds were obtained for modulation frequencies of 10, 20, 30, 50, 70, and 100 Hz. The intrinsic envelope power of the carrier at the output of the modulation filter tuned to the signal modulation frequency appears to provide a good estimate for AM detection threshold. The results are compared with predictions on the basis of the more complex auditory processing model by Dau et al.

Masking patterns for sinusoidal and narrow-band noise maskers.

The masking patterns produced by narrow-band maskers can show distinct irregularities. These experiments attempted to clarify the relative importance of factors contributing to these irregularities. A three-alternative adaptive forced-choice method with feedback was used, to promote use of the optimal detection cues. The masker and signal were either a sinusoid or a band of noise that was 80 Hz wide, giving four possible combinations of masker and signal type. In experiment 1, masking patterns were measured for maskers centered at 1 kHz, for all combinations of masker and signal type (tone or noise). The masking patterns showed irregularities (dips or "shoulders") above the masker frequency, and the irregularities were larger for the sinusoidal than for the noise masker. Experiment 2 was similar to experiment 1, except that low-pass noise was added to mask combination products. For the noise masker, the low-pass noise slightly increased thresholds, and largely eliminated the irregularities in the patterns, but for the tone masker, the irregularities persisted. Experiment 3 used a noise signal with tone and noise maskers centered at 250, 1000, and 4000 Hz. The tone masker produced less masking than the noise masker for masker-signal frequency separations of 150-250 Hz, regardless of masker frequency. Experiment 4 used an additional masker tone to introduce beats similar to those produced by the interaction of the signal and (main) masker, and to mask combination products. This largely eliminated the dips in the masking patterns for both the noise and tone maskers. Experiment 5 used an additional pair of high-frequency tones to introduce beats, with similar results. We conclude that temporal fluctuations (beats) have a strong influence on the masking patterns for sinusoidal maskers, for masker-signal frequency separations up to a few hundred Hz. Beats may also have some influence on the masking patterns for noise maskers. The detection of combination products also plays a role.

Modeling auditory processing of amplitude modulation. I. Detection and masking with narrow-band carriers.

This paper presents a quantitative model for describing data from modulation-detection and modulation-masking experiments, which extends the model of the "effective" signal processing of the auditory system described in Dau et al. [J. Acoust. Soc. Am. 99, 3615-3622 (1996)]. The new element in the present model is a modulation filterbank, which exhibits two domains with different scaling. In the range 0-10 Hz, the modulation filters have a constant bandwidth of 5 Hz. Between 10 Hz and 1000 Hz a logarithmic scaling with a constant Q value of 2 was assumed. To preclude spectral effects in temporal processing, measurements and corresponding simulations were performed with stochastic narrow-band noise carriers at a high center frequency (5 kHz). For conditions in which the modulation rate (fmod) was smaller than half the bandwidth of the carrier (delta f), the model accounts for the low-pass characteristic in the threshold functions [e.g., Viemeister, J. Acoust. Soc. Am. 66, 1364-1380 (1979)]. In conditions with fmod > delta f/2, the model can account for the high-pass characteristic in the threshold function. In a further experiment, a classical masking paradigm for investigating frequency selectivity was adopted and translated to the modulation-frequency domain. Masked thresholds for sinusoidal test modulation in the presence of a competing modulation masker were measured and simulated as a function of the test modulation rate. In all cases, the model describes the experimental data to within a few dB. It is proposed that the typical low-pass characteristic of the temporal modulation transfer function observed with wide-band noise carriers is not due to "sluggishness" in the auditory system, but can instead be understood in terms of the interaction between modulation filters and the inherent fluctuations in the carrier.

Modeling auditory processing of amplitude modulation. II. Spectral and temporal integration.

A multi-channel model, describing the effects of spectral and temporal integration in amplitude-modulation detection for a stochastic noise carrier, is proposed and validated. The model is based on the modulation filterbank concept which was established in the accompanying paper [Dau et al., J. Acoust. Soc. Am. 102, 2892-2905 (1997)] for modulation perception in narrow-band conditions (single-channel model). To integrate information across frequency, the detection process of the model linearly combines the channel outputs. To integrate information across time, a kind of "multiple-look" strategy, is realized within the detection stage of the model. Both data from the literature and new data are used to validate the model. The model predictions agree with the results of Eddins [J. Acoust. Soc. Am. 93, 470-479 (1993)] that the "time constants" associated with the temporal modulation transfer functions (TMTF) derived for narrow-band stimuli do not vary with carrier frequency region and that they decrease monotonically with increasing stimulus bandwidth. The model is able to predict masking patterns in the modulation-frequency domain, as observed experimentally by Houtgast [J. Acoust. Soc. Am. 85, 1676-1680 (1989)]. The model also accounts for the finding by Sheft and Yost [J. Acoust. Soc. Am. 88, 796-805 (1990)] that the long "effective" integration time constants derived from the data are two orders of magnitude larger than the time constants derived from the cutoff frequency of the TMTF. Finally, the temporal-summation properties of the model allow the prediction of data in a specific temporal paradigm used earlier by Viemeister and Wakefield [J. Acoust. Soc. Am. 90, 858-865 (1991)]. The combination of the modulation filterbank concept and the optimal decision algorithm proposed here appears to present a powerful strategy for describing modulation-detection phenomena in narrow-band and broadband conditions.

A quantitative model of the "effective" signal processing in the auditory system. I. Model structure.

This paper describes a quantitative model for signal processing in the auditory system. The model combines a series of preprocessing stages with an optimal detector as the decision device. The present paper gives a description of the various preprocessing stages and of the implementation of the optimal detector. The output of the preprocessing stages is a time-varying activity pattern to which "internal noise" is added. In the decision process, a stored temporal representation of the signal to be detected (template) is compared with the actual activity pattern. The comparison amounts to calculating the correlation between the two temporal patterns and is comparable to a "matched filtering" process. The detector itself derives the template at the beginning of each simulated threshold measurement from a suprathreshold value of the stimulus. The model allows one to estimate thresholds with the same signals and psychophysical procedures as those used in actual experiments. In the accompanying paper [Dau et al., J. Acoust. Soc. Am. 99, 3623-3631 (1996)] data obtained for human observers are compared with the optimal-detector model for various masking conditions.

A quantitative model of the "effective" signal processing in the auditory system. II. Simulations and measurements.

This and the accompanying paper [Dau et al., J. Acoust. Soc. Am. 99, 3615-3622 (1996)] describe a quantitative model for signal processing in the auditory system. The model combines several stages of preprocessing with a decision device that has the properties of an optimal detector. The present paper compares model predictions for a variety of experimental conditions with the performance of human observers. Simulated and psychophysically determined thresholds were estimated with a three-interval forced-choice adaptive procedure. All model parameters were kept constant for all simulations discussed in this paper. For frozen-noise maskers, the effects of the following stimulus parameters were examined: signal frequency, signal phase, temporal position and duration of the signal within the masker under conditions of simultaneous masking, masker level, and masker duration under conditions of forward masking, and backward masking. The influence of signal phase and the temporal position of the signal, including positions at masker onset, was determined for a random-noise masker and compared with corresponding results obtained for a frozen noise. The model describes all the experimental data with an accuracy of a few dB with the following exceptions: forward-masked thresholds obtained with brief maskers are too high and the change in threshold with a change in signal duration is too small. Both discrepancies have their origin in the adaptation stages in the preprocessing part of the model. On the basis of the wide range of simulated conditions we conclude that the present model is a successful approach to describing the detection process in the human auditory system.