Impact of muscle biopsy on the clinical decision-making process in patients with suspected idiopathic inflammatory myopathy.

BACKGROUND: The significance of muscle biopsy as a diagnostic tool in idiopathic inflammatory myopathies (IIM) remains elusive. We aimed to determine the diagnostic weight that has been given to muscle biopsy in patients with suspected IIM, particularly in terms of clinical diagnosis and therapeutic decisions. MATERIAL AND METHODS: In this retrospective multicentric study, we analyzed muscle biopsy results of adult patients with suspected IIM referred to a tertiary center between January 1, 2007, and October 31, 2021. Information regarding referral department, suspected diagnosis, biopsy site, demographic, clinical, laboratory data, and imaging results were extracted. Statistical analyses included the level of agreement between suspected and histological diagnosis and calculation of diagnostic performance (positive and negative predictive values, positive and negative likelihood ratios, sensitivity, and specificity of muscle biopsy in relation to clinical diagnosis and/or treatment initiation). Performance was tested in different strata based on clinical pre-test probability. RESULTS: Among 758 muscle biopsies, IIM was histologically compatible in 357/758 (47.1%) cases. Proportion of IIM was higher if there was a solid clinical pre-test probability (64.3% vs. 42.4% vs. 48% for high, medium and low pre-test probability). Sensitivity and specificity of muscle biopsy were highest (82%) when the diagnosis by the clinician was used as outcome scenario. Negative predictive value was only moderate (between 63% and 80%) and lowest if autoantibodies were positive (35%). CONCLUSION: In patients with clinically suspected IIM, approximately 50% of biopsies revealed features indicative of IIM. Diagnostic performance of muscle biopsy was moderate to high depending on clinical pre-test probability.

Phase Locking of Auditory Nerve Fibers: The Role of Lowpass Filtering by Hair Cells.

Phase locking of auditory-nerve-fiber (ANF) responses to the temporal fine structure of acoustic stimuli, a hallmark of the auditory system's temporal precision, is important for many aspects of hearing. Previous work has shown that phase-locked period histograms are often well described by exponential transfer functions relating instantaneous stimulus pressure to instantaneous spike rate, with no observed clipping of the histograms. The operating points and slopes of these functions change with stimulus level. The mechanism underlying this apparent gain control is unclear but is distinct from mechanical compression, is independent of refractoriness and spike-rate adaptation, and is apparently instantaneous. Here we show that these findings can be accounted for by a model consisting of a static Boltzmann transducer function yielding a clipped output, followed by a lowpass filter and a static exponential transfer function. Using responses to tones of ANFs from cats of both sexes, we show that, for a given ANF, the period histograms obtained at all stimulus levels for a given stimulus frequency can be described using one set of level-independent model parameters. The model also accounts for changes in the maximum and minimum instantaneous spike rates with changes in stimulus level. Notably, the estimated cutoff frequency is lower for low- than for high-spontaneous-rate ANFs, implying a synapse-specific contribution to lowpass filtering. These findings advance our understanding of ANF phase locking by highlighting the role of peripheral filtering mechanisms in shaping responses of individual ANFs.SIGNIFICANCE STATEMENT Phase locking of auditory-nerve-fiber responses to the temporal fine structure of acoustic stimuli is important for many aspects of hearing. Period histograms typically retain an approximately sinusoidal shape across stimulus levels, with the peripheral auditory system operating as though its overall transfer function is an exponential function whose slope decreases with increasing stimulus level. This apparent gain control can be accounted for by a static saturating transducer function followed by a lowpass filter. In addition to attenuating the AC component, the filter approximately recovers the sinusoidal waveform of the stimulus. The estimated cutoff frequency varies with spontaneous rate, revealing a synaptic contribution to lowpass filtering. These findings highlight the significant impact of peripheral filtering mechanisms on phase locking.

Phase Locking of Auditory-Nerve Fibers Reveals Stereotyped Distortions and an Exponential Transfer Function with a Level-Dependent Slope.

Phase locking of auditory-nerve-fiber (ANF) responses to the fine structure of acoustic stimuli is a hallmark of the auditory system's temporal precision and is important for many aspects of hearing. Period histograms from phase-locked ANF responses to low-frequency tones exhibit spike-rate and temporal asymmetries, but otherwise retain an approximately sinusoidal shape as stimulus level increases, even beyond the level at which the mean spike rate saturates. This is intriguing because apical cochlear mechanical vibrations show little compression, and mechanoelectrical transduction in the receptor cells is thought to obey a static sigmoidal nonlinearity, which might be expected to produce peak clipping at moderate and high stimulus levels. Here we analyze phase-locked responses of ANFs from cats of both sexes. We show that the lack of peak clipping is due neither to ANF refractoriness nor to spike-rate adaptation on time scales longer than the stimulus period. We demonstrate that the relationship between instantaneous pressure and instantaneous rate is well described by an exponential function whose slope decreases with increasing stimulus level. Relatively stereotyped harmonic distortions in the input to the exponential can account for the temporal asymmetry of the period histograms, including peak splitting. We show that the model accounts for published membrane-potential waveforms when assuming a power-of-three, but not a power-of-one, relationship to exocytosis. Finally, we demonstrate the relationship between the exponential transfer functions and the sigmoidal pseudotransducer functions obtained in the literature by plotting the maxima and minima of the voltage responses against the maxima and minima of the stimuli.SIGNIFICANCE STATEMENT Phase locking of auditory-nerve-fiber responses to the temporal fine structure of acoustic stimuli is important for many aspects of hearing, but the mechanisms underlying phase locking are not fully understood. Intriguingly, period histograms retain an approximately sinusoidal shape across sound levels, even when the mean rate has saturated. We find that neither refractoriness nor spike-rate adaptation is responsible for this behavior. Instead, the peripheral auditory system operates as though it contains an exponential transfer function whose slope changes with stimulus level. The underlying mechanism is distinct from the comparatively weak cochlear mechanical compression in the cochlear apex, and likely resides in the receptor cells.

Absolute auditory threshold: testing the absolute.

The mechanisms underlying the detection of sounds in quiet, one of the simplest tasks for auditory systems, are debated. Several models proposed to explain the threshold for sounds in quiet and its dependence on sound parameters include a minimum sound intensity ('hard threshold'), below which sound has no effect on the ear. Also, many models are based on the assumption that threshold is mediated by integration of a neural response proportional to sound intensity. Here, we test these ideas. Using an adaptive forced choice procedure, we obtained thresholds of 95 normal-hearing human ears for 18 tones (3.125 kHz carrier) in quiet, each with a different temporal amplitude envelope. Grand-mean thresholds and standard deviations were well described by a probabilistic model according to which sensory events are generated by a Poisson point process with a low rate in the absence, and higher, time-varying rates in the presence, of stimulation. The subject actively evaluates the process and bases the decision on the number of events observed. The sound-driven rate of events is proportional to the temporal amplitude envelope of the bandpass-filtered sound raised to an exponent. We find no evidence for a hard threshold: When the model is extended to include such a threshold, the fit does not improve. Furthermore, we find an exponent of 3, consistent with our previous studies and further challenging models that are based on the assumption of the integration of a neural response that, at threshold sound levels, is directly proportional to sound amplitude or intensity.

Spike timing in auditory-nerve fibers during spontaneous activity and phase locking.

In vertebrates, all acoustic information transmitted from the inner ear to the central auditory system is relayed by primary auditory afferents (auditory-nerve fibers; ANFs). These neurons are also the most peripheral elements to use action potentials (spikes) to encode the acoustic information. Here, we review what is known about the spiking of ANFs during spontaneous activity, when spike timing might be regarded as largely random, and during stimulation by low-frequency sounds, when spikes are phase locked to the stimulus waveform, a phenomenon generally considered a hallmark of temporal precision and speed in the auditory system. We focus on mammals, in which each ANF is driven by a single ribbon synapse in a single receptor cell, but also cover relevant research on ANFs of vertebrates from other classes. For spontaneous activity, we highlight several spike-history effects in interspike interval distributions, hazard-rate functions, serial interval correlations, and spike-count statistics. We also review models that have attempted to account for these properties. For phase locking, we focus on the responses to low-frequency tones, rather than to low-frequency components of broadband signals such as noise or clicks. We critically review the measures commonly used to quantify phase locking and urge caution when interpreting such measures with respect to spike-timing precision. We also review the dependence of phase locking on stimulus amplitude and frequency. Finally, we identify some open questions.

A model of synaptic vesicle-pool depletion and replenishment can account for the interspike interval distributions and nonrenewal properties of spontaneous spike trains of auditory-nerve fibers.

In mammalian auditory systems, the spiking characteristics of each primary afferent (type I auditory-nerve fiber; ANF) are mainly determined by a single ribbon synapse in a single receptor cell (inner hair cell; IHC). ANF spike trains therefore provide a window into the operation of these synapses and cells. It was demonstrated previously (Heil et al., 2007) that the distribution of interspike intervals (ISIs) of cat ANFs during spontaneous activity can be modeled as resulting from refractoriness operating on a non-Poisson stochastic point process of excitation (transmitter release events from the IHC). Here, we investigate nonrenewal properties of these cat-ANF spontaneous spike trains, manifest as negative serial ISI correlations and reduced spike-count variability over short timescales. A previously discussed excitatory process, the constrained failure of events from a homogeneous Poisson point process, can account for these properties, but does not offer a parsimonious explanation for certain trends in the data. We then investigate a three-parameter model of vesicle-pool depletion and replenishment and find that it accounts for all experimental observations, including the ISI distributions, with only the release probability varying between spike trains. The maximum number of units (single vesicles or groups of simultaneously released vesicles) in the readily releasable pool and their replenishment time constant can be assumed to be constant (∼4 and 13.5 ms, respectively). We suggest that the organization of the IHC ribbon synapses not only enables sustained release of neurotransmitter but also imposes temporal regularity on the release process, particularly when operating at high rates.

Averaging auditory evoked magnetoencephalographic and electroencephalographic responses: a critical discussion.

In the analysis of data from magnetoencephalography (MEG) and electroencephalography (EEG), it is common practice to arithmetically average event-related magnetic fields (ERFs) or event-related electric potentials (ERPs) across single trials and subsequently across subjects to obtain the so-called grand mean. Comparisons of grand means, e.g. between conditions, are then often performed by subtraction. These operations, and their statistical evaluation with parametric tests such as ANOVA, tacitly rely on the assumption that the data follow the additive model, have a normal distribution, and have a homogeneous variance. This may be true for single trials, but these conditions are rarely met when ERFs/ERPs are compared between subjects, meaning that the additive model is seldom the correct model for computing grand mean waveforms. Here, we summarize some of our recent work and present new evidence, from auditory-evoked MEG and EEG results, that the non-normal distributions and the heteroscedasticity observed instead result because ERFs/ERPs follow a mixed model with additive and multiplicative components. For peak amplitudes, such as the auditory M100 and N100, the multiplicative component dominates. These findings emphasize that the common practice of simply subtracting arithmetic means of auditory-evoked ERFs or ERPs is problematic without prior adequate transformation of the data. Application of the area sinus hyperbolicus (asinh) transform to data following the mixed model transforms them into the requested additive model with its normal distribution and homogeneous variance. We therefore advise checking the data for compliance with the additive model and using the asinh transform if required.

Basic response properties of auditory nerve fibers: a review.

All acoustic information from the periphery is encoded in the timing and rates of spikes in the population of spiral ganglion neurons projecting to the central auditory system. Considerable progress has been made in characterizing the physiological properties of type-I and type-II primary auditory afferents and understanding the basic properties of type-I afferents in response to sounds. Here, we review some of these properties, with emphasis placed on issues such as the stochastic nature of spike timing during spontaneous and driven activity, frequency tuning curves, spike-rate-versus-level functions, dynamic-range and spike-rate adaptation, and phase locking to stimulus fine structure and temporal envelope. We also review effects of acoustic trauma on some of these response properties.

Systemic correlates of cutaneous manifestations of lupus erythematosus.

BACKGROUND: We aimed to investigate the prevalence of skin disease among patients with systemic lupus erythematosus (SLE) and determine whether LE skin disease had clinical or serologic correlates with SLE. METHODS: We reviewed records of 335 patients with SLE (seen at Mayo Clinic, Rochester, Minnesota, USA) and abstracted skin manifestations, fulfilled mucocutaneous SLE criteria, and clinical and serologic parameters. RESULTS: Of the 231 patients with skin manifestations, 57 (24.7%) had LE-specific conditions, 102 (44.2%) had LE-nonspecific conditions, and 72 (31.2%) had both. LE skin disease was associated with photosensitivity, anti-Smith antibodies, and anti-U1RNP antibodies (all P < 0.001). Patients without LE skin disease more commonly had elevated C-reactive protein levels (P = 0.01). Patients meeting 2-4 mucocutaneous American College of Rheumatology criteria less commonly had cytopenia (P = 0.004) or anti-double-stranded DNA antibodies (P = 0.004). No significant associations were observed for systemic involvement (renal, hematologic, neurologic, and arthritis) when comparing patients with or without LE skin involvement. LE skin involvement was not significantly associated with internal SLE disease flare, number of medications, or overall survival. CONCLUSIONS: LE skin disease commonly occurs in patients with SLE. The presence of LE skin disease had no mitigating impact on the severity of SLE sequelae, disease flares, number of medications, or overall survival.

Why longer song elements are easier to detect: threshold level-duration functions in the Great Tit and comparison with human data.

Our study estimates detection thresholds for tones of different durations and frequencies in Great Tits (Parus major) with operant procedures. We employ signals covering the duration and frequency range of communication signals of this species (40-1,010 ms; 2, 4, 6.3 kHz), and we measure threshold level-duration (TLD) function (relating threshold level to signal duration) in silence as well as under behaviorally relevant environmental noise conditions (urban noise, woodland noise). Detection thresholds decreased with increasing signal duration. Thresholds at any given duration were a function of signal frequency and were elevated in background noise, but the shape of Great Tit TLD functions was independent of signal frequency and background condition. To enable comparisons of our Great Tit data to those from other species, TLD functions were first fitted with a traditional leaky-integrator model. We then applied a probabilistic model to interpret the trade-off between signal amplitude and duration at threshold. Great Tit TLD functions exhibit features that are similar across species. The current results, however, cannot explain why Great Tits in noisy urban environments produce shorter song elements or faster songs than those in quieter woodland environments, as detection thresholds are lower for longer elements also under noisy conditions.

A probabilistic model of absolute auditory thresholds and its possible physiological basis.

Detection thresholds for auditory stimuli, specified in terms of their -amplitude or level, depend on the stimulus temporal envelope and decrease with increasing stimulus duration. The neural mechanisms underlying these fundamental across-species observations are not fully understood. Here, we present a "continuous look" model, according to which the stimulus gives rise to stochastic neural detection events whose probability of occurrence is proportional to the 3rd power of the low-pass filtered, time-varying stimulus amplitude. Threshold is reached when a criterion number of events have occurred (probability summation). No long-term integration is required. We apply the model to an extensive set of thresholds measured in humans for tones of different envelopes and durations and find it to fit well. Subtle differences at long durations may be due to limited attention resources. We confirm the probabilistic nature of the detection events by analyses of simple reaction times and verify the exponent of 3 by validating model predictions for binaural thresholds from monaural thresholds. The exponent originates in the auditory periphery, possibly in the intrinsic Ca(2+) cooperativity of the Ca(2+) sensor involved in exocytosis from inner hair cells. It results in growth of the spike rate of auditory-nerve fibers (ANFs) with the 3rd power of the stimulus amplitude before saturating (Heil et al., J Neurosci 31:15424-15437, 2011), rather than with its square (i.e., with stimulus intensity), as is commonly assumed. Our work therefore suggests a link between detection thresholds and a key biochemical reaction in the receptor cells.

How to define thresholds for level and interaural-level-difference discrimination: Insights from scedasticities and distributions.

Sensitivity to changes in the stimulus level at one or at both ears and to changes in the interaural level difference (ILD) between the two ears has been studied widely. Several different definitions of threshold and, for one of them, two different ways of averaging single-listener thresholds have been used (i.e., arithmetically and geometrically), but it is unclear which definition and which way of averaging is most suitable. Here, we addressed this issue by examining which of the differently defined thresholds yielded the highest degree of homoscedasticity (homogeneity of the variance). We also examined how closely the differently defined thresholds followed the normal distribution. We measured thresholds from a large number of human listeners as a function of stimulus duration in six experimental conditions, using an adaptive two-alternative forced-choice paradigm. Thresholds defined as the logarithm of the ratio of the intensities or amplitudes of the target and the reference stimulus (i.e., as the difference in their levels or ILDs; the most commonly used definition) were clearly heteroscedastic. Log-transformation of these latter thresholds, as sometimes performed, did not result in homoscedasticity. Thresholds defined as the logarithm of the Weber fraction for stimulus intensity and thresholds defined as the logarithm of the Weber fraction for stimulus amplitude (the most rarely used definition) were consistent with homoscedasticity, but the latter were closer to the ideal case. Thresholds defined as the logarithm of the Weber fraction for stimulus amplitude also followed the normal distribution most closely. The discrimination thresholds should therefore be expressed as the logarithm of the Weber fraction for stimulus amplitude and be averaged arithmetically across listeners. Other implications are discussed, and the obtained differences between the thresholds in different conditions are compared to the literature.

Validation of a Three-Dimensional Computed Tomography Reconstruction Tool for Aortic Valve Calcium Quantification.

Background: Aortic valve calcification correlates with the severity of aortic valve stenosis and a high calcium score is associated with conduction disturbances and paravalvular leakage after transcatheter aortic valve replacement. The 3mensio Structural Heart is a semiautomated software package to facilitate aortic root analysis by multislice computed tomography.The aim of the contemporary study is to validate a semiautomated calcium quantification scoring tool with a conventional manual calcium quantification tool. Methods: Fifty randomly selected patients who underwent multislice computed tomography for preprocedural planning were retrospectively selected to compare the semiautomated aortic valve Agatston calcium score by 3mensio with the manually obtained score using IntelliSpace Portal as standard reference. Results: Patients had a mean age of 76.7 ± 7.4 years and 60% were male. The median Agatston score was 3390 [interquartile range 1877-4509] with 3mensio and 3434 [interquartile range 1839-4620] with IntelliSpace.The mean difference was -0.18 [95% confidence interval (CI) -53.8 to 53.4]. The intraclass correlation coefficient between the Agatston scores using IntelliSpace and 3mensio showed an excellent correlation of 0.995 [95% CI 0.992-0.997], p ≤ 0.001. The interobserver and intraobserver variability was 0.993 ([95% CI 0.961-0.998], p ≤ 0.001) and 0.995([95%CI 0.981-0.999], p = <0.001), respectively. Conclusions: The semiautomated calcium quantification module in 3mensio Structural Heart highly correlated with a conventional manual calcium scoring tool.

An improved model for the rate-level functions of auditory-nerve fibers.

Acoustic information is conveyed to the brain by the spike patterns in auditory-nerve fibers (ANFs). In mammals, each ANF is excited via a single ribbon synapse in a single inner hair cell (IHC), and the spike patterns therefore also provide valuable information about those intriguing synapses. Here we reexamine and model a key property of ANFs, the dependence of their spike rates on the sound pressure level of acoustic stimuli (rate-level functions). We build upon the seminal model of Sachs and Abbas (1974), which provides good fits to experimental data but has limited utility for defining physiological mechanisms. We present an improved, physiologically plausible model according to which the spike rate follows a Hill equation and spontaneous activity and its experimentally observed tight correlation with ANF sensitivity are emergent properties. We apply it to 156 cat ANF rate-level functions using frequencies where the mechanics are linear and find that a single Hill coefficient of 3 can account for the population of functions. We also demonstrate a tight correspondence between ANF rate-level functions and the Ca(2+) dependence of exocytosis from IHCs, and derive estimates of the effective intracellular Ca(2+) concentrations at the individual active zones of IHCs. We argue that the Hill coefficient might reflect the intrinsic, biochemical Ca(2+) cooperativity of the Ca(2+) sensor involved in exocytosis from the IHC. The model also links ANF properties with properties of psychophysical absolute thresholds.

COVID-19 as a putative trigger of anti-MDA5-associated dermatomyositis with acute respiratory distress syndrome (ARDS) requiring lung transplantation, a case report.

BACKGROUND: Autoimmune disease following COVID-19 has been studied intensely since the beginning of the pandemic. Growing evidence indicates that SARS-CoV-2 infection, by virtue of molecular mimicry can lead to an antigen-mediated cross-reaction promoting the development of a plethora of autoimmune spectrum diseases involving lungs and extrapulmonary tissues alike. In both COVID-19 and autoimmune disease, the immune self-tolerance breaks, leading to an overreaction of the immune system with production of a variety of autoantibodies, sharing similarities in clinical manifestation, laboratory, imaging, and pathology findings. Anti-Melanoma Differentiation-Associated gene 5 dermatomyositis (anti-MDA5 DM) comprises a rare subtype of systemic inflammatory myopathies associated with characteristic cutaneous features and life-threatening rapidly progressive interstitial lung disease (RP-ILD). The production of anti-MDA5 autoantibodies was proposed to be triggered by viral infections. CASE PRESENTATION: A 20-year-old male patient with polyarthritis, fatigue and exertional dyspnea was referred to our department. An elevated anti-MDA5 autoantibody titer, myositis on MRI, ground glass opacifications on lung CT and histological features of Wong-type dermatomyositis were confirmed, suggesting the diagnosis of an anti-MDA5 DM. Amid further diagnostic procedures, a serologic proof of a recent SARS-CoV-2 infection emerged. Subsequently, the patient deteriorated into a fulminant respiratory failure and an urgent lung transplantation was performed, leading to remission ever since (i.e. 12 months as of now). CONCLUSIONS: We report a unique case of a patient with a new-onset anti-MDA5 DM with fulminant ARDS emerging in a post-infectious stage of COVID-19, who underwent a successful lung transplantation and achieved remission. Given the high mortality of anti-MDA5 DM associated RP-ILD, we would like to highlight that the timely recognition of this condition and urgent therapy initiation are of utmost importance.

Comparing and modeling absolute auditory thresholds in an alternative-forced-choice and a yes-no procedure.

Detecting sounds in quiet is arguably the simplest task performed by an auditory system, but the underlying mechanisms are still a matter of debate. Threshold stimulus levels depend not only on the physical properties of the sounds to be detected but also on the experimental procedure used to measure them. Here, thresholds of human subjects were measured for sounds consisting of different numbers of bursts using both an alternative-forced-choice and a yes-no procedure in the same experimental sessions. Thresholds measured with the yes-no procedure were typically higher than thresholds measured with the alternative-forced choice procedure. The difference between the two thresholds decreased as stimulus duration increased. It also varied between subjects and varied with the probability of false alarms in the yes-no procedure. It is shown that a previously proposed model of detection (Heil et al., Hear Res 2017) can account for these findings better than other models. It can also account for the shapes of the psychometric functions. The model is consistent with basic concepts of signal detection theory but is based on a decision variable that follows Poisson statistics. It also differs from other models of detection with respect to the transformation of the stimulus into the decision variable. The findings in this study further support the model.

A simplified physiological model of rate-level functions of auditory-nerve fibers.

Several approaches have been used to describe the rate-level functions of auditory-nerve fibers (ANFs). One approach uses descriptive models that can be fitted easily to data. Another derives rate-level functions from comprehensive physiological models of auditory peripheral processing. Here, we seek to identify the minimal set of components needed to provide a physiologically plausible account of rate-level functions. Our model consists of a first-order Boltzmann mechanoelectrical transducer function relating the instantaneous stimulus pressure to an instantaneous output, followed by a lowpass filter that eliminates the AC component, followed by an exponential synaptic transfer function relating the DC component to the mean spike rate. This is perhaps the simplest physiologically plausible model capable of accounting for rate-level functions under the assumption that the model parameters for a given ANF and stimulus frequency are level-independent. We find that the model typically accounts well for rate-level functions from cat ANFs for all stimulus frequencies. More complicated model variants having saturating synaptic transfer functions do not perform significantly better, implying the system operates far away from synaptic saturation. Rate saturation in the model is caused by saturation of the DC component of the filter output (e.g., the receptor potential), which in turn is due to the saturation of the transducer function. The maximum mean spike rate is approximately constant across ANFs, such that the slope parameter of the exponential synaptic transfer function decreases with increasing spontaneous rate. If the synaptic parameters for a given ANF are assumed to be constant across stimulus frequencies, then frequency- and level-dependent input nonlinearities are derived that are qualitatively similar to those reported in the literature. Contrary to assumptions in the literature, such nonlinearities are obtained even for ANFs having high spontaneous rates. Finally, spike-rate adaptation is examined and found to be accounted for by a decrease in the slope parameter of the synaptic transfer function over time following stimulus onset.

Towards a unifying basis of auditory thresholds: Thresholds for multicomponent stimuli.

Sounds consisting of multiple simultaneous or consecutive components can be detected by listeners when the stimulus levels of the components are lower than those needed to detect the individual components alone. The mechanisms underlying such spectral, spectrotemporal, temporal, or across-ear integration are not completely understood. Here, we report threshold measurements from human subjects for multicomponent stimuli (tone complexes, tone sequences, diotic or dichotic tones) and for their individual sinusoidal components in quiet. We examine whether the data are compatible with the detection model developed by Heil, Matysiak, and Neubauer (HMN model) to account for temporal integration (Heil et al. 2017), and we compare its performance to that of the statistical summation model (Green 1958), the model commonly used to account for spectral and spectrotemporal integration. In addition, we compare the performance of both models with respect to previously published thresholds for sequences of identical tones and for diotic tones. The HMN model is similar to the statistical summation model but is based on the assumption that the decision variable is a number of sensory events generated by the components via independent Poisson point processes. The rate of events is low without stimulation and increases with stimulation. The increase is proportional to the time-varying amplitude envelope of the bandpass-filtered component(s) raised to an exponent of 3. For an ideal observer, the decision variable is the sum of the events from all channels carrying information, for as long as they carry information. We find that the HMN model provides a better account of the thresholds for multicomponent stimuli than the statistical summation model, and it offers a unifying account of spectral, spectrotemporal, temporal, and across-ear integration at threshold.