A unifying basis of auditory thresholds based on temporal summation

Peter Heil*† and Heinrich Neubauer*‡
*Leibniz Institute of Neurobiology, Brenneckestrasse 6, 39118 Magdeburg, Germany; and ‡Institute of Experimental Audiology and Medical Physics, Otto-von-Guericke University, 39118 Magdeburg, Germany Edited by A. James Hudspeth, The Rockefeller University, New York, NY, and approved March 13, 2003 (received for review December 30, 2002)

Thresholds of auditory-nerve (AN) fibers and auditory neurons are commonly specified in terms of sound pressure only, implying that they are independent of time. At the perceptual level, however, the sound pressure required for detection decreases with increasing stimulus duration, suggesting that the auditory system integrates sound over time. The quantity commonly believed to be integrated is sound intensity, implying that the auditory system would have an energy threshold. However, leaky integrators of intensity with time constants of hundreds of milliseconds are required to fit the data. Such time constants are unknown in physiology and are also incompatible with the high temporal resolution of the auditory system, creating the resolution–integration paradox. Here we demonstrate that cortical and perceptual responses are based on integration of the pressure envelope of the sound, as we have previously shown for AN fibers, rather than on intensity. The functions relating the pressure envelope integration thresholds and time for AN fibers, cortical neurons, and perception in the same species (cat), as well as for perception in many different vertebrate species, are remarkably similar. They are well described by a power law that resolves the resolution–integration paradox. The data argue for the integrator to be located in the first synapse in the auditory pathway and we discuss its mode of operation.

he detection of sounds constitutes a prerequisite for their further analysis by the auditory system, and a thorough understanding of the system’s operation requires knowledge of how threshold is determined. Surprisingly, confusion still exists as to how auditory thresholds are best defined and by which process they are reached. In physiological and audiological studies of the auditory system, thresholds are routinely specified in terms of the sound pressure level (SPL) of the signal needed to evoke a response. This practice, exemplified by tuning curves and audiograms, implies that thresholds of auditory neurons are sufficiently characterized by that pressure and are independent of stimulus duration (1). However, at the perceptual level, the threshold SPL decreases as stimulus duration increases in every species examined (2–23). Such a trading relationship between a sound’s amplitude, or a related parameter, and its duration is consistent with the notion that the auditory system summates or integrates sound over time. It is commonly believed that the physical quantity of sound ultimately integrated by the auditory system is sound intensity, I(t) (2–11, 13–15, 17–19, 21–29). I(t) is the sound power transmitted per unit area and, for pure tones, is proportional to the square of the peak pressure or the pressure envelope, P(t) (30). Sound power integrated over time yields acoustic energy (30), and so the common interpretation of the perceptual data implies that the auditory system has a threshold that is best specified in terms of the sound’s acoustic energy density, and not its pressure. Notably, the energy of threshold stimuli is also not constant but, in contrast to threshold SPL, generally increases with increasing stimulus duration. Only for very short durations has the reverse been suspected (21). This time dependence of the energy of threshold stimuli has been attributed to leaky integration of I(t), combined with spectral spread of energy and limited spectral integration at short durations. However, the physiological foundations of this interwww.pnas.org cgi doi 10.1073 pnas.1030017100

T

Methods
Electrophysiology. As detailed (35, 39), spikes generated by single AN fibers and single AI neurons were recorded in a soundattenuating chamber from 10 adult barbiturate-anaesthetized cats. AN fibers and AI neurons respond preferentially at sound onset (34–39), where I(t) and P(t) both increase dynamically, but differently, because I(t) P(t)2. To exploit these differences, we stimulated each neuron with tones at its characteristic frequency (CF; the frequency to which a neuron is most sensitive) while varying P(t). The latter was achieved by employing different onset functions and systematically varying both the time to the steady-state SPL (onset time) and the SPL. Onset functions were either linear, i.e., P(t) increased linearly with time, t, during the onset time, tr, to the maximum, Pmax: P(t) Pmax t/tr, with onset times of 1, 5, 10, 50, and 100 ms; or cosine-squared (cos2), i.e., P(t) Pmax sin2( /2 t/tr), with onset times of 1.7, 4.2, 8.5, 17, 42, 85, and 170 ms. The SPL was increased from low to high values (usually 0–90 dB SPL during steady-state) in 5- or 10-dB steps. For each combination of parameters, the stimulus was repeated

This paper was submitted directly (Track II) to the PNAS office. Abbreviations: AI, primary auditory cortex; AN, auditory nerve; CF, characteristic frequency; IHC inner hair cell; SPL, sound pressure level.
†To

whom correspondence should be addressed. E-mail: peter.heil@ifn-magdeburg.de.

PNAS

May 13, 2003

vol. 100

no. 10

6151– 6156

NEUROSCIENCE

pretation are unclear. Very long time constants, up to hundreds of milliseconds, are needed to describe the increase in threshold energy with increasing duration (for summaries, see refs. 18 and 22). Such long time constants contrast with the short membrane time constants of neurons in the auditory periphery (28, 29, 31, 32) and are also difficult to reconcile with the high temporal resolution of the auditory system. Several ideas have been proposed to resolve this resolution–integration paradox (6, 7, 18, 32, 33). Here we develop a unifying description of auditory thresholds at the physiological and perceptual levels, disclose the parameter that is really traded for stimulus duration, and aid the identification of the processes by which thresholds are reached. We exploit the stimulus-dependent timing of the first spike of auditory neurons to derive their thresholds. Our approach is based on the rationale that the first spike following the onset of a stimulus is triggered when the stimulus reaches the neuron’s threshold and occurs with some fixed ‘‘transmission delay’’ thereafter. In this way, we have previously shown that thresholds of auditory nerve (AN) fibers and primary (AI) and other auditory cortical neurons are not specified in terms of fixed pressures (34–38). In fact, the instantaneous values of P(t), and hence also of I(t), at which the first spike was triggered decreased as first-spike latency increased, a trading relationship consistent with temporal summation. Here we first examine whether thresholds of AI neurons, as well as perceptual thresholds, are largely determined by integrating I(t), and thus whether they are specified in terms of acoustic energy or, as is the case for AN fibers (38), by integrating P(t). Second, and equally important, we examine the characteristics of the time dependence of these thresholds.

whose latencies behave similarly (38. 2 described this time dependence satisfactorily for a fraction of AI neurons.1030017100 . The mean residuals (solid line. AI thresholds result from temporal integration of the pressure envelope of a sound rather than its intensity. L Lmin. For humans (right ear) and cats (binaural). 8.57 ms for q 2. Fixed pressure envelope integration thresholds (q 1) explained the data of most fibers 6152 www. first passed a Schmitt-trigger level were stored with a 10. after conventional amplification and filtering. plotted against integration time. for 11 human subjects (four tested twice) and five cats were measured as detailed (18. 1a. Additional late discharges. 10. (a) Mean first spike latency. The carrier frequency was 3. depending on which was most effective.and multiple-burst stimuli differing in duration and envelope characteristics (Fig. T.20–50 times. The ipsilateral ear was used for AN fibers. 1b plots. Lmin. we initially explained firstspike timing by assuming that threshold. 2 with q 1). The analysis window always commenced with stimulus onset and usually terminated shortly after stimulus offset (10 ms for AN fibers) to allow for transmission delays. The geometric mean was 0. and the contralateral. is constant and equal to the temporal integral. The instances at which the recorded spikes. plotted against SPL for different onset times and onset functions [linear or cos2 increase in P(t) with time.25 kHz for cats. 2. were excluded from the analysis.org cgi doi 10. The distribution of q obtained from 89 AN fibers was narrow and centered on 1. The shortest stimulus (stimulus 1) was composed only of onset and offset portions of 4. if present. q: L Psychoacoustics and Perception. 1a illustrates that for each onset function. indicating that it is also necessary to assume a time dependence of AI thresholds. the measured latencies against those predicted by Eq. 1. 2a). right ordinate) reveal systematic deviations of the data from the model.51 Pa s. These deviations could be well explained by time-dependent thresholds and an extension of Eq. namely a power law Heil and Neubauer Refinement of Previous Models. Following training (at least four complete sets of 24 thresholds in humans and 10 in cats). and Pc 27. Fig. was 12. Lmin.125 kHz for humans and 6. (c) Individual thresholds (key as in a) for the AI neuron. 2 when q 1. 1b.5-dB steps in cats. 12. Fig. (b) Mean latencies (key as in a) plotted against those predicted by a pressure envelope integration threshold that increases linearly with integration time. Pc (in Pa) can be viewed as a system-inherent pressure-like force that adds linearly to the external sound pressure. not explain the data of AI neurons. All subjects were tested with a set of single. finally approaching a neuron-specific minimum. 1 shows the data for one representative neuron.21 ms for q 1 and 12. respectively. right ordinate). and an onset–offset series (stimuli 1 and 15–20) was created by varying onset and offset times. well. and distribution of the optimal q obtained from 32 neurons tested with different onset functions (black dots. and not 2.1073 pnas. of P(t) raised to some power. Lower). and not of I(t).1 Pa. Upper) than for integration of I(t) (q 2. L generally decreased as the SPL of the stimulus tones increased and their onset times decreased. used to derive threshold. 1. Fit parameters were Lmin 12. 39).791–1. by using a simple up–down method with decreasing step size. for the same neuron as in Fig. Tones had durations of 200 ms (AN) or 400 ms (AI) and were presented at 2 Hz (AN) or 1 Hz (AI) through sound-delivery tubes sealed into the external meati. ipsilateral.054. right ordinate) reveal only small. Dallas). Despite the rather close match. L Lmin (Eq.914 with an error interval of 0. Data are from a single cat AI neuron (except frequency distribution in d) tested at its CF of 22 kHz. and 14). L T L L min 0 Lmin P t qdt T0 Pc L Lmin [2] Compared with Eq. The first spike following each stimulus onset was used to calculate mean latency. and q are free parameters.16 ms each [P(t) of cos2 function]. An important step toward the aims of the present study was to derive thresholds of AI neurons from the stimulus dependence of their mean first-spike latency. We obtained a grand mean for all subjects from the individual mean threshold SPLs by minimizing the sum of the total variance across subjects without altering the mean SPL across all subjects and stimuli.06 ms. this approach resulted not only in better fits but also in an even narrower distribution of q around 1 (38). The scatter of individual thresholds and the systematic differences between mean thresholds obtained with different rise functions are smaller for integration of P(t) (q 1. 19) and kindly provided by G. Gerken (University of Texas. suggesting that AN fibers reach threshold by temporal integration of P(t). mean threshold for a subject was based on 12 such thresholds for each of the 24 stimuli in humans (10 in cats). In our study of AN fibers (38). 1. the only free parameter of the fits. Fig. the residuals (Fig. solid line. Multipleburst stimuli were composed of stimulus 1 repeated to form stimuli that differed either in number of bursts (multiple-burst series: stimuli 1–5) or in interburst interval (interval series: stimuli 3 and 21–24). The responses of most AI neurons consisted of 1–3 spikes tightly locked to stimulus onset. Threshold was the average of six transitions using 2-dB steps in humans and 2. L.s precision for offline analysis. (d) Costs (purple symbols) and proportion of data points for which Lmin L (green triangles) as a function of the exponent q of P(t). A fixed integration threshold could T 0 Lmin P t qdt Tconst. thresholds were determined for all 24 stimuli and 10 stimuli (1–5. see key]. 6. or both ears were used for AI neurons.pnas. [1] where T. Lmin. but systematic deviations of the data from that model. Eq. T0 1. A single-burst series (stimuli 6–14) was created by adding a constant amplitude plateau in the middle of the stimulus. Results and Discussion Background. from stimulus onset to the trigger time of the first spike. These suggest that a slight modification of Eq. but systematic deviations of the data from that model were evident in some fibers. Detection thresholds (in dB SPL) Fig. M. the constant transmission delay (34–37).

3 and 21–24.32 and 33. (a) Pressure envelopes of the stimuli for which detection thresholds were obtained. a fact that will become apparent later (Figs. For both exponents. the optimal values of the exponent q of P(t) were narrowly distributed around 1.org). This novel approach only postulates that thresholds to those CF tones of different onset function. 2.16 ms. We will then turn to the time dependence of the thresholds defined in this way. [3] 0 would provide an even better description. which approximates to the observed differences in threshold SPLs for such stimuli in humans and cats (arrows). and interval series (yellow squares).e. It imposes no a priori constraints on thresholds for different values of L Lmin. Fig. multiple-burst stimuli. right ordinate). calculated with a specific impedence of 414 Pa s m 1. [Reproduced and modified with permission from Gerken et al. 5. Fig. Heil and Neubauer www. Perceptual Thresholds Are also Largely Determined by Temporal Integration of P(t). The optimal exponent q of P(t) for a given AI neuron was obtained by minimizing a cost function that depended on q and Lmin. onset– offset series (green triangles). with the issue of whether P(t) or I(t) is integrated to reach threshold. The same symbols are used in b–d and f. single-burst series (blue circles). Inset shows the upper half of P(t) for eight consecutive bursts (red line) and for a single burst of the same duration but of a 6-dB-lower amplitude (blue area). black dots. stimuli 1–5.e. T(L Lmin) T1. 1d shows that the cost function (purple) of the example neuron is W-shaped with its global minimum near q 1. Abscissa duration.pnas.] (b) Grand means of threshold SPL plotted against stimulus duration for human subjects (right ordinate) and cats (left ordinate). and rectangular (gray) threshold stimuli with durations of 8.g. including the value of m in the right-hand term of Eq. 6 –14. Stimulus duration excludes interburst intervals. rendering temporal integration of I(t) rather implausible. Multiple-burst series (red circles). 1 and 15–20. (c and d) Thresholds of humans (right ordinates) and cats (left ordinates) expressed as temporal integrals of I(t) (i. green triangles). thresholds vary with integration time. which is published as supporting information on the PNAS web site. 2 and 3). both at the AI neuronal and the perceptual level. 100 no. These findings demonstrate that AI neurons. The human data from b for single-burst stimuli. threshold may be constant (as in Eq. When L Lmin 1 ms. 1d. Envelopes of multiple-burst (red). ( f) Threshold SPL plotted against stimulus duration for theoretical rectangular stimuli (gray squares). 3. The exponent m corresponds to Lmin in the slope of the increase in T(L Lmin) with L double-log scales. and not I(t). evaluated at a point L Lmin The presentation of the data analysis will first deal with the value of q in the middle term of Eqs.. 2–3). respectively. The cost function was defined such that its minimum was obtained when the spread of thresholds at any given integration time and systematic differences between the thresholds obtained with linear and cos2 onset functions were minimal (Fig.Fig. Straight red and black lines are power law fits for red and gray symbols. and not 2 (Fig.28 ms are depicted. Thus. the proportion of stimuli for which the measured latency L was shorter than the estimated Lmin increased steadily from near zero for q 1 to 20% for q 2 (Fig. Eqs. AI Thresholds Are Largely Determined by Temporal Integration of P(t). single-burst (blue). and the scaling factor k defines the curve’s vertical position. Perceptual thresholds result from temporal integration of the pressure envelope of a sound rather than its intensity. To also distinguish between integration of P(t) and of I(t) at the perceptual level. 1–3. Further. 275 ms. like AN fibers (38). we next reanalyzed perceptual thresholds for both cats and humans tested with a large set of PNAS May 13. an issue that will be dealt with later. 10 6153 . (18) (Copyright 1990. as energy densities. onset time.. i. c) and as temporal integrals of P(t) (d) plotted against stimulus duration. The temporal integrals of P(t) for such stimuli are nearly identical.. 2 comprises the first two terms of a Taylor series approxi0. 2 and 3 are intimately related. mation of the power law. 2003 vol. The variances unexplained (1 r2) by power laws between the respective threshold quantity and duration are given. NEUROSCIENCE T L L min L Lmin P t qdt k L Lmin m. and the solid curved line was calculated from the latter for stimuli with cos2 onset and offset times of 4. and interval series are replotted. and SPL that elicit responses with identical L Lmin should be identical. Across the AI sample. reach threshold by temporal integration of P(t). those of Eqs. (e) Geometric mean and range of the ratios of unexplained variances for integration of P(t) to integration of I(t) of individual subjects. 1d. because the right-hand term of Eq. 1c shows that when the thresholds (obtained from best fits) to all tones for this neuron are plotted against integration time. Acoustical Society of America). the vertical scatter of the data points is appreciably smaller for q 1 (Upper) than for q 2 (Lower). 1) or may form any function of L Lmin (e.

contrary to what would be expected from a temporal integrator of I(t). Further. threshold SPLs increase more rapidly the shorter the stimulus duration becomes. Hence. The closer alignment of thresholds for q 1 compared with q 2 was expected from the 6-dB difference between threshold SPLs for single.org cgi doi 10.e. 4.1030017100 perceptual pressure envelope integration thresholds increase almost linearly with stimulus duration on double-log scales for both cats and humans. Threshold SPL did not differ for stimuli that were temporal mirror images (stimuli 19 and 20) or for multiple-burst stimuli differing in interburst interval (stimuli 3 and 21–24) (the five yellow squares representing the threshold SPLs for these stimuli in Fig. a much closer alignment of the thresholds for stimuli in the different series was obtained by plotting the temporal integral of P(t) (in Pa s. This curved shape could suggest an exponential function with a long time constant. replaces the term L Eq. 2f ). The SPL corresponding to the peak amplitude of threshold stimuli decreased with an increasing number of bursts (stimuli 1–5 in Fig. For the porpoise. 1c). and fish (8–14. ts. However. This was similarly true for the grand mean data (unexplained variances given in Fig. particularly because m and k are the only two free parameters. also at this level. 2d and 3c reveal that P t 1dt m k ts [4] 0 provides an excellent descriptor of the data that leaves remarkably little unexplained variance (0. Lines connect thresholds derived from tones of different SPLs but of the same onset function and onset time.1073 pnas. increased as the number of bursts. an order of magnitude (Fig. and stimulus onset–offset times increased. plateau duration. 4 was smaller for each subject than that given by the equivalent power law relating threshold energy and duration by. We also reanalyzed available perceptual thresholds from other studies of temporal summation in various mammals. 17) and replotted the data (Fig. and onset–offset series diverged as duration increased (Fig. plateau duration (stimuli 1 and 6–14). without any correction of onset– offset versus plateau duration. birds. These trading relationships between threshold SPL and stimulus duration are all consistent with thresholds reached by temporal summation.84% and 1. 2f (blue circles). The adequacy of this power law may be obscured in the conventional plot of threshold SPL versus log duration. 2 b and f ). Thus. and onset–offset times for a single burst without plateau (stimuli 1 and 15–18) (Fig.and multiple-burst stimuli of longer durations (Fig. single-burst. 2e). 2a). it matches the finding on AI neurons (Fig. the temporal integral of I(t) (in W s m 2). Threshold SPL for stimuli in the multiple-burst.Fig. These theoretical threshold SPLs fall on Heil and Neubauer . or by SPL only. The energy density of threshold stimuli. and blue triangles). Consequently. 2b).and multiple-burst tones that differed in duration and envelope characteristics (refs. 3 and T(ts) T1 for ts 1 ms. 2 b–f ) show clearly that. The unexplained variance in Eq. threshold SPL is not an invariant function of stimulus duration. we calculated the threshold SPLs for theoretical stimuli with rectangular P(t) that had durations and temporal integrals of P(t) identical to those of the single-burst threshold stimuli by dividing the temporal integral of P(t) of each stimulus by its duration (gray squares in Fig. as illustrated with high resolution for the grand mean human data in Fig. it results from the concomitant increase in the proportion of onset and offset times with respect to the entire duration of the tone. and field sparrow. particularly when only single-burst stimuli with fixed onset and offset times are used.11% of the grand means for humans and for cats. like neuronal. the power law T ts ts The Time Dependence of Pressure Envelope Integration Thresholds Is Well Described by a Power Law. parakeet. on average.. green. i. again. Figs. Shown are plots of thresholds for 5 AN fibers (a) and 5 AI neurons (b) with different CFs (different colors). which would predict an increase in threshold SPL with increasing interburst intervals because leakage would continue during these intervals and its net effect would increase with time (18). integration of P(t) provides a much better fit to the data than integration of I(t). It is apparent that in each species the dependence of pressure envelope integration thresholds on stimulus duration can be well described by Eq. 2a). This shows that threshold energy is also not an invariant function of stimulus duration. and as stated above. For such stimuli. again with pronounced divergence of the thresholds between the series (Fig. Comparison of the pressure envelope integration thresholds for neuronal (a and b) and perceptual (c and d) measurements. The duration Lmin of of the threshold stimulus. Fig. The latter result is inconsistent with the leaky integration hypothesis. (d) Analogous functions for mean perceptual thresholds for a range of vertebrate species. as for the calculation of energy densities.pnas. single. 2 c and d) and again emphasizes that integration of P(t) provides a much better explanation for threshold than of I(t). Fig. 2d). In contrast. The results (Fig. 3. respectively). 2b Inset). calculated from published data (8 –14. thresholds are much better defined by the temporal integral of P(t) than that of I(t). 17–19). 3d). 2c). To illustrate this. Lines connect thresholds obtained with stimuli of different series (see Fig. (c) Analogous functions for perceptual thresholds for two cats (purple and black circles) and three humans (red. 2a). 6154 www. 18 and 19. 2 b–d and f fall on top of one another). perceptual. absolute thresholds could not be determined from the original articles and thus the position on the ordinate is arbitrary.

06 for cats.. a factor of 2. together with the compelling evidence that each IHC is innervated by 10–30 AN fibers of different spontaneous rates and thresholds (47.g. These observations agree well with the short. R (in s 1) 0 can be interpreted as a mean rate of individual events. because the proportion of onset and offset times also does not change with duration.32 ms (blue) and perceptual tests of cats (yellow). just below the IHC. 4) obtained from AI neurons for integration times 8.e. and blue symbols in Fig.4-ms (46). and P [ ts P(t)dt]/ts is the mean amplitude of P(t) during ts. 17). symbols show geometric means in bins of 0. i. These are also the most sensitive neurons. (a) Histograms of values for m (Eq. because sensitivity increases.. Also. i. (1 m) 1. the integration of P(t) over the observed long time scales cannot have been accomplished at. For the other species (8–14. the integrator is most likely peripheral to the site of spike generation in the AN fibers. 4. This potential almost instantaneously follows the fine structure of the stimulus at low frequencies and the pressure envelope. yellow bars). Pa s).e. possibly point processes. c const (1/k) .e. which could readily account for the range of AN fiber sensitivities. (b) Sensitivity increases. as well as from the plausible idea that a certain number of individual events may be necessary to reach threshold.09 for humans and 0.76 0. The peripheral boundary for the location of the integrator is marked by the membrane potential of the sensory receptors. but for some neurons the values match those for perception (Fig. AI neurons. 33) do not seem necessary to explain the present data. are closely matched (Fig. m derived from perceptual tests matches that of the most sensitive neurons. 44). which is published as supporting information on the PNAS web site).33 0. The power law (Eq. at higher frequencies. This interpretation results from the units of R. R.44). 4b). 41–44). 48). black. ranging from 0. relative to that for the rectangular stimuli. and. the higher (lower) the mean rate of these events. from efferent fibers of the lateral olivocochlear system (49).. 5. with additional specification of that time. is not equivalent to the temporal integration of a continuously changing quantity.. IHC membrane time constants. The exponent m of Eq. as m increases by 32 5 dB per m (Fig.15 0.e. 4a. latency increases with decreasing SPL until an upper limit is reached that is caused. 3 a–d). a mean m of 0. Detection thresholds are likely mediated by the most sensitive neurons. i. the level of the receptor potential. and so to pinpoint the underlying mechanism of temporal summation. Deviations from the power law can be observed for short integration times in some AI neurons (purple.64 0. This excludes a fixed pressure threshold. the inner hair cells (IHCs). including that distal dendrite with its additional synaptic inputs. [5] of the pressure envelope integration thresholds with stimulus duration. or peripheral to.’’ which is likely mediated by fast inhibition (43. PNAS May 13. we obtained very similar values. T1 decreases. a straight line (black line through gray squares in Fig. r2 0. 2003 vol. This synaptic region is structurally diverse. This general interpretation of this trading law does not require any assumptions about the necessary number of events or about their distribution (homogeneous or inhomogeneous) over time.69 0. and corroborates our previous conclusions (34–38). Eq. 3b) and for long integration times in some AN fibers (purple symbols in Fig. In AN fibers. which is published as supporting information on the PNAS web site). namely the cat. blue bars). Threshold SPLs measured for multiple-burst stimuli fall on a line (red line through red circles and yellow squares in Fig. 18. Thus. For cat AI neurons. To identify the parameter really traded for stimulus duration. the slope of the increase The Location of the Integrator. The present analyses thus show that both neuronal and perceptual thresholds are better measured in units of pressure multiplied by time (e. than in units of pressure only or in units of energy. and its value determined. Because the functions relating the pressure envelope integration threshold to integration time or stimulus duration for AN fibers. thus disenabling pinna gain). The yellow ellipse shows the mean 1 SD of T1 and m for perceptual data of cats. without any slow changes of its DC component when P(t) is constant (45). 3 c–d). latency decreases with increasing SPL for low SPLs but for higher SPLs remains relatively constant (40) or even increases with further increments in SPL (36. 100 no.09 dB per decade of duration). for which m 1 and the integral T(ts) ts. 5. In cats. 1. and perception in the same species. after weighting them with the number of individuals. 2f ) with a slope of 20(m 1) (here. 3a). The Possible Nature of the Processes Leading to Threshold. 3a) and are readily explained as follows. This ‘‘paradoxical latency shift. by the fiber’s spontaneous activity (38. as m increases. P(t). Such an accumulation process of individual events. 7. as described by Eq. 2f ) of similar slope ( 5. The line is elevated by 6. 32. Thus. 4b).67 to 0. averaged 0. Fig.10 dB per decade of duration). T1 Heil and Neubauer Here R c (P) . multiplied with duration ts yields a constant R ts const. i. and stimuli tested. stimulation of mostly one ear only and near the tympanum. 39). converts to the steep increase of pressure envelope integration thresholds for short integration times.. 3b) and AN fibers (Fig. because the peak amplitudes of multiple-burst stimuli are twice as high as their mean amplitudes and hence as the peak amplitudes of equivalent rectangular stimuli. and more central processes (6.79. the shorter (longer) the time needed to accumulate the necessary number. the values of m were more widely distributed (Fig. This limits the possible location of the integrator to the first synapse in the auditory pathway. the observation that the sensitivity of AN fibers of similar CF in the same individual can differ by several orders of magnitude (Fig.decreases. perceptual sensitivity is 20 dB better than that of the most sensitive neurons (Fig.1 width. between the IHC and the distal dendrite of a single AN fiber. but this is readily explained by the conditions used for neuronal recording (anesthesia. 4. 6. because there are systematic relationships between morphological and physiological properties (47–50). In some neurons of the central auditory pathway. and regression (dashed blue line) obtained from individual AI neurons (n 57. 4 with L Lmin instead of ts) can also well describe the functions relating the pressure envelope integration thresholds to the integration time of cat AI neurons (Fig. This upper limit produces roughly constant latencies to low-SPL stimuli and consequently results in a nearly vertical drop of threshold estimates for such stimuli. The Slope m of the Time Dependence of Pressure Envelope Integration Thresholds.75 (Table 1. The values of m are all 1. frequencies. 4 was reformulated such that this parameter. at least over the time range corresponding to the durations tested for perception in that species (Fig. 4a.22 dB. 10 6155 NEUROSCIENCE . argues against an integrator identical for all afferent fibers of a given IHC (38).

443–460. 5. P. D. N.. R. J. Soc. S. when P is low. D. Soc.. (1993) Hearing Res. R. M. 52). Viemeister. Physiol. Acoust. J. M. J. R. Neurosci. & Thaller. Acoust. 42. A 162. Benda. 6. New York). Covey. & Kemp. ts. Neurophysiol. 9. 77. M. (2000) Hearing Res. 2. for which. Burger. A. 21. & Hutchison-Clutter. M. 10434–10448. MA). H. & Liberman.. Tel Aviv). J. B. 20. R.. 54. or five subevents. Nachtigall. 189–203. S. 25. the probability of each of those occurring being proportional to P. Cortex 8. 18. 1046–1060. F. the duration. Heil. A. 46. 147–163. J. (2001) J. 90. Gerken. 56. B. Dodge. Jr. M. J. Comp. & Powers. Feigenbaum. (Univ. J. 148. Irvine for helpful comments on the manuscript and collaboration in the recording of electrophysiological data. A.. ¨ 34. Physiol. V. 1058–1064. & Orman. Comp. Heil. D. L. A. W. M. D. and G. Physiol. W.1073 pnas. (1983) Hearing Res. (1990) J. Altman. Michelsen. W. 57. the state of Sachsen¨ Anhalt. 78. Watson. Klump. H. R. M. 208–221. 1065–1072. J. & Harker. M. Plomp. eds.. 21. (2001) Eur. Otolaryngol. Thus. M. F. 5 also provides a hint to the nature of the integrator. R. Fay. R. Comp. 88. Numbers between three and five have been reported for peripheral and central synapses in squid. 1421–1427. Neher. (2000) J.. 99. 37. D. 371. Acoust. Neurol. & Maier.. D. R. Heil. Soc. (2001) J. T. S. Garner. (1991) J. & Coombs. (1959) J. 301. S. 59. Herz. pp. and three anonymous reviewers for helpful comments on earlier versions of the manuscript. M. B. V. Recio. A 178. Am. 43–54.. 3456–3470. & Gengel. 71... (1996) J. J. & Park.. Salvi. The probability of the occurrence of the individual events. 31. (1986) J. 362–376.Eq. Acoust. Ehret. 12. Hurley. 79. G. & Ruggero. Grothe. eds. (London) 193. Neurophysiol. Because R P . 3623–3631. Comp. A. Acoust. 32. H. (Springer. R. 49. Heil. 23. Am. 523–531. E. G. 2616–2641. R. (1947) J. G.H. Schmidt. M. N. E. R. G. Physiol. A. 35. 3073–3076. 318–385. Halvorsen. (1980) J. Brosch. T. Cambridge. 563–572. D. M. E. E. R. R. C. 7. (1986) in Sensorineural Hearing Loss. New York). & Wakefield. B. (1946) Proc. Tougaard. G. pp. & Fay. R. 802–806. (1991) J. Heil. N. Hughes. 10. Khan. S. W. Syrlykke. (London) 381. J. Barruel. Fay.. L. A. (2001) J. & Moser. N. Heidelberg). (1985) in Time Resolution in the Auditory System. Fastl. (1988) in Animal Sonar: Processes and Performance. 36. & Kohlrausch.1030017100 Heil and Neubauer .org cgi doi 10. G. P. 953–957. Phillips. & Neubauer. R. (1969) J.. 889–893. 55. R. 1058–1060. Clock. S. 11. & Casseday. D. 52. 41. pp. 4. Puschel. & Irvine. it seems meaningful to search for events that are mediated by three. & Feng.. 37–50. Soc. R. 53. (1990) J. Comp. A. Am. E. frog. P. 51. London Ser. J. (Springer. P. 2. 39. Assoc. IOS. Am. 29). Sullivan. Henderson. A 183. A. J. A. C. Neurosci. J. & Moore. Ronacher. 954–965. 767–778. 65. This work was supported by the Bundesministerium fur Bildung und Forschung. B. 2438–2454. A. 753–768. M. K. 681–690. pp. D. Am. A 186. T. (1990) J. 44. R. 779–785. Saunders.. Soc. K. A. 19. P. B. L. Gollisch. Soc. M. 5. J. Acoust. Pujol. M.. Bhat. (Plenum. J. Bollmann. 31. (Springer. of Iowa. C. 15. F. 989–997. (1998) Cereb. J. over which the events need to be accumulated is short when P is high. (2001) in Computational Models of the Auditory System. & Michelsen. (1990) J. R. Acoust. 14. Am. & Popper. Temchin. P. 486–490. R. Acoust. & Herz. M. Michelsen. Am. R. M. A. G. Am. 8. (1984) J. D. 153–195. (1996) in The Cochlea. Green. (1976) J. & Housley.. 125–141. (1982) Science 216. R. A. J. Zucker. M. (1997) J. (1985) in Time Resolution in the Auditory System. A. Am. ed. four... eds. Irwin. L. & Borst. Costalupes. Webster. Am. H. O‘Connor. E. W. One candidate for such events is exocytosis at the IHC–AN fiber synapse. W. Physiol. Fay. indicating high temporal resolution. & Charlton. N. 43. Raybould. F. (1981) Audiology 20. 1882–1884. 46. 48. eds. Krahe. Am. (1997) J. 27. Gerken for helpful comments on the manuscript and access to his perceptual data. C. Buser. R. E. & Tanner. four to five Ca2 -binding steps are necessary. 84. A. Iowa City). Narayan. Dau. R. 22. Meddis. Comp. J.. E. eds. M. Am. Acoust. & Imbert. and rat (54–58). 24. 58. F. 94–100. & Maloney. Neurosci. 38. C. H. Conversely. Klug.. Gervais d’Aldin. P. in mouse (53). A. C. 757–763. Jagger. P. (1992) Audition (MIT Press. 69–92. A. five (Table 1). Zwislocki. J. J. D. P. 11. 10. Clark. Nouvian. 51. 43. Schneggenburger. 32. 88. Comp. Heidelberg). Acoust. proportional to P . (1967) J. Amsterdam). Beutner. (1976) J. & Irvine. W. Bauer E.. & Hennig. Galazyuk. 59–82. (1992) in The Evolutionary Biology of Hearing. 45. 22. eds. (1996) J. consistent with available data (51. Glattke. Acoust. 17. (1986) J. & Irvine. Soc. O. S. Hajalilou. & Hanani. (NATO Advanced Study Institute. (1998) Science 282. 808–815. (1988) J. D. 68. R. Kros. (1960) J. N. C. (1982) J. Dooling. M. (2000) Science 289. B. (Springer. W. T. S. 1033–1047. Popper. 977–986. Soc. A. Soc. (2001) Neuron 29. Salvi. & Sutter.. 26. pp. Sakmann. Neurophysiol. and grants from the Deutsche Forschungsgemeinschaft to P. 122–140. 195–203. V. 7404–7415. L. P. 29. R. ref. M... & Bohne. M. Gollisch. C. RC147. & Rahamimoff. 106. W. Florentine. J. Soc. P. 107–123. Acoust. 33. A. A. Greenberg. 48. Collins. in contrast to proposed relatively short maximum integration times ( 200 ms.. Soc.. G. 9. & Bouman. 1239–1241. Soc. M. Neurosci.. Psychol. (1994) Hearing Res. Soc. M. L. ts increases and the temporal resolution decreases. 104. 28. Am. 229–263. J. Am. 858 – 865. 3. B. Calculating from m for the perceptual data yields values between three and 1. Res. G.. can be viewed as a conditional probability that results from the interaction of subevents. M. (1983) Hearing Res. Acoust. (1996) NeuroReport 7. 6156 www. Acoust. Hinchcliffe.. S. (2002) J. Am. Eybalin. 16. T. Green. Soc. S. 77. P.. A. 40. 419–432. T. 367–374. 3d) reveals no obvious deviations from Eq. pp. Dallos. (Freund. (2000) Nature 406.. 50. 13. Johnson. S. Brown. Liberman. & Pierce. D. (1991) in Presynaptic Regulation of Neurotransmitter Release: A Handbook. Neurosci. Neurol.pnas. L. deBoer. 234–243. Birdsall. Tougaard. R. P. Am. E. S. Our reanalysis of the perceptual data (Fig. Yang. N. 749–758. & Hamernik. Dodds. A. M. W. Soc. K. N. 141–158. 14. Acoust. We thank J.. & Puel. W. 669–677. New York). P. D. 47. & Gerken. H. H. pp. B 133. V. Schutze. 21. (1957) J. R. S. S. M. (1999) J. Au. Ruel. Soc. H. Neurophysiol. ed. R. Physiol. R. Larsen. Giraudi. H. G. P. T. A. R. & Slaney. F. Liberman. 125–134.. R. T. Heil... Eq. Soc. Solecki. 5 reveals that there is no real resolution–integration paradox. S. 29. Merchan-Perez. C. 619–640. (1996) J.-L. L. Voets. (1988) J. 30. 19. pp. (1998) J. & Buus. & Neher. G. Acoust. J. (1968) J. S. Augustine.