Учебники / Hearing - From Sensory Processing to Perception Kollmeier 2007

reexamine this question by recording in the IC and the auditory nerve of the guinea pig. The changes in ITD sensitivity that we measure in the IC appear to be consistent with the picture of phase changes that we have measured in the guinea pig auditory nerve.

2Methods

Details of the methods have been previously published (see McAlpine and Palmer 2002; Palmer et al. 1986). Briefly, recordings were made in the right IC of pigmented guinea pigs anesthetized with urethane and Hypnorm (Janssen, High Wycombe, UK). A premedication of atropine sulfate reduced bronchial secretions. The animals were placed inside a sound attenuating room in a stereotaxic frame in which hollow plastic speculae replaced the ear bars to allow sound presentation and direct visualization of the tympanic membrane.

Single-fiber recordings were obtained by introduction of micropipettes filled with 2.7 M KCl into the auditory nerve under direct visual guidance, through a posterior craniotomy, after retraction of the cerebellum using a spatula. The bulla was vented and a silver wire electrode was placed on the round window of the cochlea and the threshold of the cochlear action potential was monitored periodically.

For IC recordings the bullae on both sides were vented. A craniotomy was performed over the IC, the dura reflected and recordings made from single, well-isolated neurons, with glass-insulated tungsten electrodes (Bullock et al. 1988) advanced through the intact cortex by a piezoelectric motor (Burleigh Inchworm IW-700/710).

Extracellular action potentials were amplified (Axoprobe 1A, Axon Instruments, Foster City, CA), filtered between 300 Hz and 2 kHz, discriminated using a level-crossing detector (SD1, Tucker-Davis Technologies, Alachua, FL), and time stamped with a resolution of 1 s.

All experiments were performed in accordance with the United Kingdom Animal (Scientific Procedures) Act of 1986.

2.1Stimulus Generation

Stimuli were delivered to each ear through sealed acoustic systems comprising custom-modified tweeters (Radioshack 40-1377; M. Ravicz, Eaton Peabody Laboratory, Boston, MA), which fitted into the hollow speculum. The output was calibrated a few millimeters from the tympanic membrane using a microphone fitted with a calibrated probe tube.

Stimuli were digitally synthesized (System II, Tucker-Davis Technologies) at between 100 kHz and 200 kHz sampling rates and were output through a waveform reconstruction filter set at 1/4 the sampling rate (135 dB/octave

elliptic: Kemo 1608/500/01 modules supported by custom electronics). Stimuli were of 50 ms duration, switched on and off simultaneously in the two ears with cosine-squared gates with 2 ms rise/fall times (10% to 90%). When a neuron was isolated the lowest threshold and frequency at that threshold (characteristic frequency: CF) were obtained audio-visually. Frequency response areas, rate-level functions and peristimulus response histograms (PSTHs) were obtained using pure tones to enable neurons to be characterized (see Shackleton et al. 2003 for details).

ITDs were obtained by delaying, or advancing, the fine structure of the signal to the ipsilateral ear while keeping the signal to the contralateral ear fixed. Coarse noise ITD functions (spike response vs ITD of the broadband noise) were obtained at 30 dB above noise response threshold to allow classification. Positive values of ITD are defined as contralateral leading.

ITD functions to tones at different ILDs were obtained by fixing the contralateral level at 20 dB above threshold, and varying the ipsilateral level from threshold to 40 dB above threshold in steps of 10 dB. For consistency with the definition of ITDs, positive values of ILD are defined as contralateral more intense (note that this choice results in the unfortunate effect of increasing ipsilateral level corresponding to decreasing ILD). In three early experiments we used 30 dB suprathreshold for the contralateral level and from threshold to 60 dB above threshold for the ipsilateral level, in 15-dB steps. The signals were set at CF and at a selection of frequencies in steps of 0.25 octaves away from CF. Spikes were counted if they occurred between 10 and 80 ms after the stimulus onset. ITD functions were measured over ±0.5 cycles in 0.02-cycle steps using 10 repeats at a repetition rate of 5 per second. Best Phase (BP), vector strength and Rayleigh coefficient were calculated from the ITD functions using a modification of the method of Goldberg and Brown (1969).

Phase-locking in auditory nerve fibers was obtained by computation from the period histograms constructed from isointensity frequency response curves measured in 1/8 octave steps from near threshold in 10-dB steps with up to 10 repetitions at each frequency and level combination.

3Results

3.1Effect of ILD on ITD Sensitivity in IC

ITD functions were recorded from 72 well isolated IC neurons (CFs 56–1300 Hz, but mostly below 700 Hz) of which noise ITD functions were obtained for 54 and full data sets for 50. Of the 54, 54% were peak type units, 20% were trough and 19% were intermediate (see, for example, McAlpine et al. 1996). Initially we measured ITD functions to CF tones and subsequently as time permitted, or as the data dictated, we used frequencies above and below CF. The design of this protocol was based upon the shifts in auditory nerve phase

-0.5 octaves re CF

At CF

+0.5 octaves re CF

Interaural Phase difference (cycles)

Fig. 1 ITD functions at different stimulus frequencies and ILDs (key). At 0.5 octave below CF, the best phase hardly changes at all with ILD. In this neuron, at CF and 0.5 octave above CF, the best phase moved ipsilaterally with increasing ILD as shown by the symbols and arrows above the ITD curves

locking (Anderson et al. 1971) that indicated that the largest shifts occurred at up to an octave away from CF. An example of the responses of a single IC neuron tested at three different frequencies and five different ILDs is shown in Fig. 1. The arrows indicate that as the ILD is increased to favour the contralateral ear there is a progressive change in the best phase for CF and half an octave above CF, but no change at half an octave below CF.

We use the term “null frequency” to describe the frequency at which no change in phase with ILD occurred and in this case it was −0.5 octaves. Contrary to the widely held view of the existing auditory nerve data we found the null to occur at the CF in less than a third of the neurons for which we had sufficient data (14/50). Equally often the null occurred below (15/50) and less often, above CF (8/50). The remaining (13/50) neurons for which we had sufficient data showed phase changes, but these were erratic or parallel and no null could be attributed. The changes in best phase were maximally about 0.2 cycles.

In the majority (33/37) of the units with an identifiable null frequency, best phase moved more ipsilaterally with increasing ILD (as shown by the arrows in Fig. 1) for frequencies above the null frequency, whereas below the null frequency the best phase moved contralaterally with increasing ILD. In two units with the null above CF the best phase moved ipsilaterally below the null. The remaining two units showed clear, but inconsistent, phase shifts. The phase shifts were unrelated to the type of delay sensitivity (peak, trough, intermediate). Even with this limited sample it was clear that null frequencies could be found as frequently above, at, and below CF across the whole range of CFs.

3.2Effect of Sound Level on Auditory Nerve Phase Locking

We measured the level dependency of phase locking in 183 auditory nerve fibers (CFs 0.071–3.227 kHz). These auditory nerve data are consistent in almost all respects with those previously published, but highlight some previously unremarked aspects of those reports.

To facilitate comparison, our early protocol in the auditory nerve replicated as closely as possible that used in the IC. We supplemented these data with isointensity plots covering three or more octaves in 1/8 octave steps. These latter data gave a better definition of the null and so in later experiments we gathered only isointensity plots with as many repeats as possible. Following earlier studies, best phase was obtained from period histograms, unwrapped, and the slope of the plot of best phase against frequency at the highest level used to estimate the cochlear delay, which was then subtracted from all data for that neuron to give the phase changes. An example of the phase changes with level for an auditory nerve fiber for which stability was sufficient to run both protocols is shown in Fig. 2. It is clear that the data from the isointensity plots although noisier give the same phase as using more repeats. Equally clear is the fact that there is a null frequency which in this case occurs well below CF

Fig. 2 Best phase of phase locking in an auditory nerve fiber (CF 222 Hz) as a function of sound level and frequency. The vertical line indicates CF. The arrows highlight the phase change as ipsilateral level increases. The large symbols are from 50 repeats at steps of 0.5 octaves from CF. The smaller symbols are from 5 repeats at 1/8 octave steps. The legend gives the level in dB SPL

(−0.5 octaves). Ninety six fibers yielded data that allowed a null frequency to be determined. The null frequency was at CF in 41 fibers, above CF in 36 fibers and below CF in 19. In all fibers, above the null, there was an increasing phase lead as level increased (as shown by the arrows in Fig. 2), and an increasing phase lag below the null. Nulls at and above the CF could occur at all CFs, but nulls below CF only occurred in lower CF fibers. There was no clear CF at which the null moved from below to above CF.

4Discussion

The direction of changes in ITD sensitivity that we see in the IC are consistent, in general, with the direction of the changes in phase locking that we find in the auditory nerve. Initially, the changes in ITD sensitivity with ILD appeared to be inconsistent with earlier reports of the changes at the input to the coincidence detector due to the level dependency of phase locking at frequencies away from CF in the auditory nerve. However, careful rereading of even the earliest reports (e.g. Anderson et al. 1971) revealed that null frequencies in the nerve could occur well away from the CF, as we had found in the IC data. Our own auditory nerve fiber data confirmed that this was the case and showed that null frequencies could occur at CF, or above, across all of the phase-locking range, but only below CF for CFs below 1 kHz. Existing basilar membrane data suggest that the level dependency of phase locking reflects non-linearities in the mechanics of the cochlea (e.g. Ruggero and Rich 1987), but most of these mechanical measurements are from relatively high-frequency positions along the cochlea where the null frequency occurs at CF. Those from the low-frequency part of the basilar

membrane (Cooper and Rhode 1995; Zinn et al. 2000) suggest complicated mechanics in which the effect of the cochlear amplifier may even be expansive instead of compressive producing attenuation rather than amplification. The phase of the mechanical responses in these studies is difficult to reconcile with our auditory nerve data which looks much more like that at more basal locations. We, like others (Kuwada and Yin 1983) found IC cells whose ITD sensitivity did not change with ILD or in which the changes were erratic. While some of the effects may reflect the complicated apical mechanics, we cannot rule out the possibility that, in these instances, effects along the pathway from the auditory nerve (such as reconvergence and inhibitory modulation) might also be contributing.

References

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Comment by Gleich

One issue related to your finding that the “cross-over” point of the phase vs frequency functions obtained at different levels is not at the best frequency (BF) is the accuracy of the audio-visual determination of BF.

Fibers originating from a given cochlear location have the same BF and the same cochlear response latency that in turn should be reflected in the slopes of the phase vs frequency functions.

Consequently, if the audio-visually determined BFs correctly represent cochlear location, one would predict that the slopes of the phase vs frequency functions at a given BF are the same for fibers with the “cross-over” points below, at and above the BF. Alternatively, steeper slopes (equivalent to longer cochlear delays) in cells with “cross-over” points below and shallower slopes (shorter cochlear delays) in cells with “cross-over” points above the audiovisually determined BF would suggest some error in BF determination.

In addition to audiovisually determined BFs you might consider deriving the frequency dependent discharge rate from the data used to construct the phase vs frequency functions and compare the response peaks with audiovisually determined BFs.

Reply

The estimation of characteristic frequency (CF) is obviously important for the points we are making in this chapter. Certainly, for low-CF fibers the tuning curve is relatively broad and errors could occur. The relationship of cochlear delay to CF is of course correct, but we are dealing here with minor perturbations imposed on this very steep phase slope so it is not completely obvious what the relationship of the major slope to the null frequency should be. We

plotted the cochlear delays derived from the slopes at the highest sound level. With a perfect place frequency map of the cochlea these delays alone could be used to derive characteristic frequencies. However, these data are noisy and the estimates would likely be little better than our audio visual estimates. Comparison of the delays for two fibers from the same cochlea gave cochlear delays that differed by the amount predicted from the difference in audiovisually estimated CFs.

While the relationships we report in the chapter are with respect to the audio-visually derived CFs, we have also extracted CFs from the iso-level functions. It is a moot point whether these are a better estimate, as CF changes with sound level, and the iso-level curves near threshold are noisy. We took the lowest level at which an unambiguous peak was present, but since this was often not at absolute threshold the CF estimate will still be approximate. However, when we calculated the proportions of fibers with null frequencies above, below and at CF using the iso-level function derived CF it was no different from that using audio-visual CFs.

Comment by Greenberg

Some of the variability observed in the phase plots as a function of auditory- nerve-fiber characteristic frequency may be correlated with fiber spontaneous discharge rate. Spontaneous rate is correlated with threshold sensitivity (Liberman and Kiang 1978; Geisler et al. 1985 and phase-locking precision (Greenberg 1986) and thus may affect the phase/CF function as well. It would be interesting to partition your data into low (<10 spikes/s) and high spontaneous rate fiber populations to ascertain if there’s a significant difference in the phase behavior.

A separate issue is the method by which a fiber characteristic frequency is determined. Sinusoidal signals may not always be the most precise stimuli to use, particularly for CFs below <1500 Hz (where significant phase locking is observed). One alternative is to use a two-component signal whose frequencies are arithmetically centered around the nominal unit CF. By moving the two-tone signal through the center of the unit’s response area in fine frequency steps and examining the relatively synchrony patterns associated with each component, it may be possible to derive a more accurate method for estimating CF than the conventional discharge-rate approach (see Greenberg et al. 1986 for a description).

References

Geisler CD, Deng L, Greenberg S (1985) Thresholds for primary auditory fibers using statistically defined criteria. J Acoust Soc Am 77:1102–1109

Greenberg S (1986) Possible role of low and medium spontaneous rate cochlear nerve fibers in the encoding of waveform periodicity. In: Moore B, Patterson R (eds) Auditory frequency selectivity. Plenum, New York, pp 241–248

Greenberg S, Geisler CD, Deng L (1986) Frequency selectivity of single cochlear nerve fibers based on the temporal response patterns to two-tone signals. J Acoust Soc Am 79:1010–1019 Liberman MC, Kiang NY-S (1978) Acoustic trauma in cats: cochlear pathology and auditory-

nerve activity. Acta Oto-Laryngol Suppl Stockh 358:1–63

Reply

An interesting suggestion , but we have plotted the difference between the null frequency and the CF (from the iso-level function) against the spontaneous rate and found no dependence on spontaneous discharge rate.

We are certainly aware of the importance of the accurate determination of the CF. Unfortunately, from the present data set there are only two estimates readily available: the audio-visual estimate, which can be subject to error, and the CF from the iso-level function (see previous reply), which is also not necessarily a good estimate of CF. Taking either of these CF estimates did not change the conclusions we drew from our data.