The contributors have taken a number of different approaches to the questions, from a focus on the underlying neural representations to a focus on perceptual
performance, and including comparative results from animal and human studies, and computational modeling. As described by several contributors, phase locking can be used for binaural processing in humans up to about 1500 Hz. In the binaural case we can say with some assurance that phase-locking information is used up to this frequency because no other cues are available. However, there is clearly some disagreement about the general upper limit, which includes monaural TFS processing, with values of ~1500 Hz (Oxenham, Joris and Verschooten), 3000-4000 Hz (Shamma), and 8000-10000 Hz (Moore, Heinz) proposed by the contributors. The question posed by Joris and Verschooten is why should, and how can, the limit for monaural TFS coding be greater than that for binaural TFS coding? Proponents of a high upper limit need neurophysiological evidence that these high frequencies are represented by phase locking in humans, and that this temporal information is processed in the (preferably human) auditory brain.
The range of frequencies under debate, from 1500 to 10000 Hz, is highly significant for human hearing. This range includes the range of maximum threshold sensitivity, and is of vital importance for speech perception. If phase locking is not used to code frequencies above 1500 Hz, then we are left with some difficult questions. In particular, why is pure tone frequency discrimination, measured in terms of a relative difference limen, so good for frequencies up to 4000-5000 Hz? Indeed, as described by Moore and by Heinz, the relative difference limen continues to increase up to about 8000 Hz. If phase locking is not used up to 8000 Hz, how can place information give such good performance and why can the
auditory system not get the same benefit from place information at frequencies above 8000 Hz? Proponents of a low upper limit need evidence that place coding can account for the high fidelity of frequency coding up to 4000-5000 Hz, for the drop off in fidelity at higher frequencies, and for performance on tasks such as the TFS1 test for high harmonic
frequencies. As Oxenham suggests, it is possible that there are central constraints that limit performance at high frequencies, perhaps because of the lack of everyday exposure to these stimuli. If this is the case, and the deterioration in discrimination performance does not reflect a change in mechanism, should we consider the possibility that frequency discrimination, and perhaps pitch perception in general, is dependent on place coding at all frequencies?
The contributors suggest a number of experiments that may help to resolve the question of the upper frequency limit. Moore, Heinz, Shamma, and Joris and Verschooten, all suggest that recordings from the human auditory nerve would help to determine the maximum frequency for peripheral phase locking. Joris and Verschooten provide recent evidence from human neurophonic recordings that suggests an upper limit in the auditory nerve below 5000 Hz, consistent with that of other mammals. However, Moore questions the assumptions behind this derivation. Direct recordings from the human auditory nerve (preferably single fiber) may be the only way to settle this issue conclusively. Furthermore, Heinz argues that the neurophonic data of Verschooten et al. (2018) are in fact consistent with a high upper limit, of perhaps 10000 Hz. The argument rests on whether phase locking at these high rates can be extracted from the noise floor, as suggested by Heinz and
disputed by Shamma and by Joris and Verschooten. Shamma suggests that information regarding the upper limit may also be obtained by studying the electrical properties of human inner hair cells in vitro.
Even if the peripheral frequency limit can be determined, the existence of a
temporal representation in the auditory nerve does not imply that the information is used by higher centers. Animal experiments that demonstrate the use of monaural TFS
information (Oxenham) would help to confirm that such information can be utilized in humans, and perhaps suggest an upper frequency limit. Alternatively, electrophysiological binaural recordings in humans may provide evidence of a higher upper limit than expected based on behavioral studies (Joris and Verschooten). Such studies may not give a definitive answer, but they will provide further fuel to a debate that is enriched (or perhaps cursed) by strong arguments from all viewpoints.
Acknowledgments
BCJM was supported by the Engineering and Physical Sciences Research Council (UK), grant number RG78536. AJO was supported by the National Institutes of Health (Grant R01
DC005216). MGH was supported by the National Institutes of Health (Grant R01 DC009838). SS was supported by National Institutes of Health grants and by an ERC Advanced Grant (Neume). PXJ and EVE were supported by grants from the Fund for Scientific Research – Flanders and Research Fund KU Leuven. CJP was supported by the Biotechnology and Biological Sciences Research Council (UK), grant number BB/M007423/1, and by the National Institute for Health Research Manchester Biomedical Research Centre. We thank the Editor and two anonymous reviewers for constructive comments on an earlier version of this manuscript.
References
Alves-Pinto, A., Lopez-Poveda, E.A., 2005. Detection of high-frequency spectral notches as a function of level. J. Acoust. Soc. Am. 118, 2458–2469.
Attneave, F., Olson, R.K., 1971. Pitch as a medium: A new approach to psychophysical scaling. Am. J. Psychol. 84, 147-166.
Attwell, D., Laughlin, S.B., 2001. An energy budget for signaling in the grey matter of the brain. J. Cereb. Blood Flow Metab. Off. J. Int. Soc. Cereb. Blood Flow Metab. 21, 1133–1145. https://doi.org/10.1097/00004647-200110000-00001
Bernstein, L.R., Trahiotis, C., 1996. The normalized correlation: accounting for binaural detection across center frequency. J. Acoust. Soc. Am. 100, 3774–3784.
Blackburn, C.C., Sachs, M.B., 1989. Classification of unit types in the anteroventral cochlear nucleus: PST histograms and regularity analysis. J. Neurophysiol. 62, 1303–1329. Brand, A., Behrend, O., Marquardt, T., McAlpine, D., Grothe, B., 2002. Precise inhibition is
essential for microsecond interaural time difference coding. Nature 417, 543-547. Brughera, A., Dunai, L., Hartmann, W.M., 2013. Human interaural time difference thresholds
for sine tones: the high-frequency limit. J. Acoust. Soc. Am. 133, 2839-2855. Carlyon, R. P., Moore, B. C. J., 1984. Intensity discrimination: a severe departure from
Weber's Law. J. Acoust. Soc. Am. 76, 1369-1376.
Carr, C.E., Konishi, M., 1990. A circuit for detection of interaural time differences in the brain stem of the barn owl. J. Neurosci. 10, 3227-3246.
Cedolin, L., Delgutte, B., 2005. Pitch of complex tones: rate-place and interspike interval representations in the auditory nerve. J. Neurophysiol. 94, 347–362.
Cohen, M.R., Kohn, A., 2011. Measuring and interpreting neuronal correlations. Nat. Neurosci. 14, 811-819.
Devore, S., Delgutte, B., 2010. Effects of reverberation on the directional sensitivity of auditory neurons across the tonotopic axis: influences of interaural time and level differences. J. Neurosci. 30, 7826–7837. https://doi.org/30/23/7826 [pii]
10.1523/JNEUROSCI.5517-09.2010
Eggermont, J.J., 1977. Compound action potential tuning curves in normal and pathological human ears. J. Acoust. Soc. Am. 62, 1247–1251.
Evans, E.F., 1972. The frequency response and other properties of single fibres in the guinea-pig cochlear nerve. J. Physiol. 226, 263-287.
Florentine, M., 1983. Intensity discrimination as a function of level and frequency and its relation to high-frequency hearing. J. Acoust. Soc. Am. 74, 1375-1379.
Füllgrabe, C., Moore, B. C. J., Stone, M. A., 2015. Age-group differences in speech
identification despite matched audiometrically normal hearing: Contributions from auditory temporal processing and cognition. Front. Aging Neurosci. 6, Article 347, 1- 25.
Füllgrabe, C., Harland, A. J., Sek, A. P., Moore, B. C. J., 2017. Development of a method for determining binaural sensitivity to temporal fine structure. Int. J. Audiol. 56, 926- 935.
Glasberg, B. R., Moore, B. C. J., 1990. Derivation of auditory filter shapes from notched-noise data. Hear. Res. 47, 103-138.
Harrison, R.V., Aran, J.M., Erre, J.P., 1981. AP tuning curves from normal and pathological human and guinea pig cochleas. J. Acoust. Soc. Am. 69, 1374–85.
Hartmann, W.M., Macaulay, E.J., 2014. Anatomical limits on interaural time differences: an ecological perspective. Front. Neurosci. 8, 34.
https://doi.org/10.3389/fnins.2014.00034
Heffner, R.S., Koay, G., Heffner, H.E., 2001. Sound localization in a new-world frugivorous bat, Artibeus jamaicensis: acuity, use of binaural cues, and relationship to vision. J. Acoust. Soc. Am. 109, 412–421.
Heinz, M.G., Colburn, H.S., Carney, L.H., 2001. Evaluating auditory performance limits: I. one-parameter discrimination using a computational model for the auditory nerve. Neural Comput. 13, 2273-2316.
Henry, K.R., 1995. Auditory nerve neurophonic recorded from the round window of the Mongolian gerbil. Hear. Res. 90, 176–84.
Hopkins, K., Moore, B. C. J., 2007. Moderate cochlear hearing loss leads to a reduced ability to use temporal fine structure information. J. Acoust. Soc. Am. 122, 1055-1068. Jackson, H. M., Moore, B. C. J., 2014. The role of excitation-pattern and temporal-fine-
structure cues in the discrimination of harmonic and frequency-shifted complex tones. J. Acoust. Soc. Am. 135, 1356-1570.
Jackson, L.L., Heffner, H.E., Heffner, R.S., 1996. Species differences in the upper limit of binaural phase discrimination. Assoc. Res. Otolaryngol. Abs. 19, 63.
Johnson, D.H., 1974. The response of single auditory-nerve fibers in the cat to single tones: synchrony and average discharge rate. Ph.D. dissertation, M.I.T.
Johnson, D.H., 1980. The relationship between spike rate and synchrony in responses of auditory-nerve fibers to single tones. J. Acoust. Soc. Am. 68, 1115–1122.
Joris, P.X., 2003. Interaural time sensitivity dominated by cochlea-induced envelope patterns. J. Neurosci. 23, 6345–50. https://doi.org/23/15/6345 [pii]
Joris, P.X., Carney, L.H., Smith, P.H., Yin, T.C., 1994a. Enhancement of neural synchronization in the anteroventral cochlear nucleus. I. Responses to tones at the characteristic frequency. J. Neurophysiol. 71, 1022–36.
Joris, P.X., Smith, P.H., Yin, T.C., 1994b. Enhancement of neural synchronization in the anteroventral cochlear nucleus. II. Responses in the tuning curve tail. J.
Neurophysiol. 71, 1037–51.
Joris, P.X., Verschooten, E., 2013. On the limit of neural phase locking to fine structure in humans. Adv. Exp. Med. Biol. 787, 101–108. https://doi.org/10.1007/978-1-4614- 1590-9_12
Kale, S., 2011. Temporal coding in auditory-nerve fibers following noise-induced hearing loss. PhD dissertation, Purdue University, West Lafayette, IN, USA.
Kale, S., Heinz, M.G., 2010. Envelope coding in auditory nerve fibers following noise-induced hearing loss. J. Assoc. Res. Otolaryngol. 11, 657–673.
Kale, S., Heinz, M.G., 2012. Temporal fine structure coding at high frequencies following noise-induced hearing loss. Assoc. Res. Otolaryngol. Abs. 35, 364.
Kidd, R.C., Weiss, T.F., 1990. Mechanisms that degrade timing information in the cochlea. Hear. Res. 49, 181–207.
Konishi, M., 1973. How the owl tracks its prey: Experiments with trained barn owls reveal how their acute sense of hearing enables them to catch prey in the dark. Am. Sci. 61, 414–424.
Köppl, C., 1997. Phase locking to high frequencies in the auditory nerve and cochlear nucleus magnocellularis of the barn owl, Tyto alba. J. Neurosci. 17, 3312-3321.
Kuwada, S., Yin, T.C.T., 1983. Binaural interaction in low-frequency neurons in inferior colliculus of the cat. I. Effects of long interaural delays, intensity, and repetition rate on interaural delay function. J. Neurophysiol. 50, 981–999.
Lau, B.K., Mehta, A.H., Oxenham, A.J., 2017. Superoptimal perceptual integration suggests a place-based representation of pitch at high frequencies. J. Neurosci. 37, 9013-9021. Loeb, G.E., White, M.W., Merzenich, M.M., 1983. Spatial cross correlation: A proposed
mechanism for acoustic pitch perception. Biol. Cybern. 47, 149-163.
Manley, G.A., Gleich, O., 1992. Evolution and specialization of function in the avian auditory periphery. In The evolutionary biology of hearing (pp. 561-580). Springer, New York, NY.
Marmel, F., Linley, D., Carlyon, R. P., Gockel, H. E., Hopkins, K., Plack, C. J., 2013. Subcortical neural synchrony and absolute thresholds predict frequency discrimination
independently. J. Assoc. Res. Otolaryngol. 14, 757-766.
Marmel, F., Plack, C. J., Hopkins, K., Carlyon, R. P., Gockel, H. E., Moore, B. C. J., 2015. The role of excitation-pattern cues in the detection of frequency shifts in bandpass- filtered complex tones. J. Acoust. Soc. Am. 137, 2687-2697.
McAlpine, D., Jiang, D., Palmer, A.R., 1995. Interaural delay sensitivity and the classification of low best-frequency binaural responses in the inferior colliculus of the guinea pig. Hear. Res. 97, 136-152.
McAlpine, D., Jiang, D., Palmer, A.R., 2001. A neural code for low frequency sound localization in mammals. Nat. Neurosci. 4, 396-401.
Micheyl, C., Delhommeau, K., Perrot, X., Oxenham, A.J., 2006. Influence of musical and psychoacoustical training on pitch discrimination. Hear. Res. 219, 36–47.
Micheyl, C., Xiao, L., Oxenham, A.J., 2012. Characterizing the dependence of pure-tone frequency difference limens on frequency, duration, and level. Hear. Res. 292, 1-13. Micheyl, C., Schrater, P.R., Oxenham, A.J., 2013. Auditory frequency and intensity
discrimination explained using a cortical population rate code. PLoS Comput. Biol. 9, e1003336
Mohan, H., Verhoog, M.B., Doreswamy, K.K., Eyal, G., Aardse, R., Lodder, B.N., Goriounova, N.A., Asamoah, B., B. Brakspear, A.C., Groot, C., van der Sluis, S., 2015. Dendritic and axonal architecture of individual pyramidal neurons across layers of adult human neocortex. Cereb. Cort. 25, 4839-4853.
Møller, A.R., 1983. Frequency selectivity of phase-locking of complex sounds in the auditory nerve of the rat. Hear. Res. 11, 267-284.
Møller, A.R., Jho, H.D., 1989. Response from the exposed intracranial human auditory nerve to low-frequency tones: basic characteristics. Hear. Res. 38, 163–175.
Moore, B.C.J., 1973. Frequency difference limens for short-duration tones. J. Acoust. Soc. Am. 54, 610-619.
Moore, B.C.J., 2008. The role of temporal fine structure processing in pitch perception, masking, and speech perception for normal-hearing and hearing-impaired people. J. Assoc. Res. Otolaryngol. 9, 399-406.
Moore, B.C.J., 2014. Auditory Processing of Temporal Fine Structure: Effects of Age and Hearing Loss, World Scientific, Singapore.
Moore, B.C.J., Ernst, S. M., 2012. Frequency difference limens at high frequencies: Evidence for a transition from a temporal to a place code. J. Acoust. Soc. Am. 132, 1542-1547. Moore, B.C.J., Gockel, H., 2011. Resolvability of components in complex tones and
Moore, B.C.J., Moore, G. A., 2003. Discrimination of the fundamental frequency of complex tones with fixed and shifting spectral envelopes by normally hearing and hearing- impaired subjects. Hear. Res. 182, 153-163.
Moore, B.C.J., Sek, A., 1995. Effects of carrier frequency, modulation rate, and modulation waveform on the detection of modulation and the discrimination of modulation type (amplitude modulation versus frequency modulation). J. Acoust. Soc. Am. 97, 2468- 2478.
Moore, B.C.J., Sek, A., 2009a. Development of a fast method for determining sensitivity to temporal fine structure. Int. J. Audiol. 48, 161-171.
Moore, B.C.J., Sek, A., 2009b. Sensitivity of the human auditory system to temporal fine structure at high frequencies. J. Acoust. Soc. Am. 125, 3186-3193.
Moore, B.C.J., Sek, A., 2011. Effect of level on the discrimination of harmonic and frequency- shifted complex tones at high frequencies. J. Acoust. Soc. Am. 129, 3206-3212. Oxenham, A.J., 2018. How we hear: The perception and neural coding of sound. Annu. Rev.
Psychol. 69, 27-50.
Oxenham, A.J., Micheyl, C., Keebler, M.V., 2009. Can temporal fine structure represent the fundamental frequency of unresolved harmonics? J. Acoust. Soc. Am. 125, 2189- 2199.
Oxenham, A.J., Micheyl, C., Keebler, M.V., Loper, A., Santurette, S., 2011. Pitch perception beyond the traditional existence region of pitch. Proc. Nat. Acad. Sci. 108, 7629- 7634.
Oxenham, A.J., Shera, C. A., 2003. Estimates of human cochlear tuning at low levels using forward and simultaneous masking. J. Assoc. Res. Otolaryngol. 4, 541-554.
Palmer, A.R., Russell, I.J., 1986. Phase-locking in the cochlear nerve of the guinea-pig and its relation to the receptor potential of inner hair-cells. Hear. Res. 24, 1–15.
Reale, R.A., Brugge, J.F., 1990. Auditory cortical neurons are sensitive to static and continuously changing interaural phase cues. J. Neurophysiol. 64, 1247–1260.
Recio-Spinoso, A., Temchin, A.N., van Dijk, P., Fan, Y.-H., Ruggero, M.A., 2005. Wiener-kernel analysis of responses to noise of chinchilla auditory-nerve fibers. J. Neurophysiol. 93, 3615–3634. https://doi.org/10.1152/jn.00882.2004
Rhode, W.S., Smith, P.H., 1986. Encoding timing and intensity in the ventral cochlear nucleus of the cat. J. Neurophysiol. 56, 261–286.
Rose, J.E., Brugge, J.F., Anderson, D.J., Hind, J.E., 1967. Phase-locked response to low- frequency tones in single auditory nerve fibers of the squirrel monkey. J. Neurophysiol. 30, 769–793.
Rose, J.E., Gross, N.B., Geisler, C.D., Hind, J.E., 1966. Some neural mechanisms in the inferior colliculus of the cat which may be relevant to localization of a sound source. J. Neurophysiol. 29, 288–314.
Rose, M. M., Moore, B. C. J., 2005. The relationship between stream segregation and frequency discrimination in normally hearing and hearing-impaired subjects. Hear. Res. 204, 16-28.
Sayles, M., Heinz, M.G., 2017. Afferent coding and efferent control in the normal and impaired cochlea, in: Manley, G.A., Gummer, A.W., Popper, A.N., Fay, R.R. (Eds.), Understanding the cochlea. Springer, Cham Switzerland, pp. 215–252.
Scott, B.H., Malone, B.J., Semple, M.N., 2007. Effect of behavioral context on representation of a spatial cue in core auditory cortex of awake macaques. J. Neurosci. Off. J. Soc. Neurosci. 27, 6489–6499. https://doi.org/10.1523/JNEUROSCI.0016-07.2007
Semal, C., Demany, L., 1990. The upper limit of "musical" pitch. Music Percepn. 8, 165-176. Semal, C., Demany, L., 2006. Individual differences in the sensitivity to pitch direction. J.
Acoust. Soc. Am. 120, 3907-3915.
Shamma, S., Klein, D., 2000. The case of the missing pitch templates: How harmonic
templates emerge in the early auditory system. J. Acoust. Soc. Am. 107, 2631-2644. Siebert, W.M., 1970. Frequency discrimination in auditory system - Place or periodicity
mechanisms? Proc. IEEE 58, 723–730.
Suga, N., O'Neill, W.E., Manabe, T., 1978. Cortical neurons sensitive to combinations of information-bearing elements of biosonar signals in the mustache bat. Science 200, 778-781.
Sumner, C.J., Palmer, A.R., 2012. Auditory nerve fibre responses in the ferret. Eur. J. Neurosci. 36, 2428-2439.
Sumner, C.J., Wells, T.T., Bergevin, C., Sollini, J., Kreft, H.A., Palmer, A.R., Oxenham, A.J., Shera, C.A., 2018. Mammalian behavior and physiology converge to confirm sharper cochlear tuning in humans. Proc. Natl. Acad. Sci. USA. 115, 11322-11326.
Taberner, A.M., Liberman, M.C., 2005. Response properties of single auditory nerve fibers in the mouse. J. Neurophysiol. 93, 557-569.
Teich, M.C., Khanna, S.M., Guiney, P.C., 1993. Spectral characteristics and synchrony in primary auditory-nerve fibers in response to pure-tone acoustic stimuli. J. Stat. Phys. 70, 257–279.
Temchin, A.N., Recio-Spinoso, A., van Dijk, P., Ruggero, M.A., 2005. Wiener kernels of chinchilla auditory-nerve fibers: verification using responses to tones, clicks, and noise and comparison with basilar-membrane vibrations. J. Neurophysiol. 93, 3635– 3648.
Trahiotis, C., Stern, R.M., 1994. Across-frequency interaction in lateralization of complex binaural stimuli. J. Acoust. Soc. Am. 96, 3804–3806.
Verschooten, E., Desloovere, C., Joris, P.X., 2018. High-resolution frequency tuning but not temporal coding in the human cochlea. PLOS Biol. 16, e2005164.
https://doi.org/10.1371/journal.pbio.2005164
Verschooten, E., Joris, P.X., 2014. Estimation of neural phase locking from stimulus-evoked potentials. J. Assoc. Res. Otolaryngol. 15, 767–787. https://doi.org/10.1007/s10162- 014-0465-9
Verschooten, E., Robles, L., Joris, P.X., 2015. Assessment of the limits of neural phase- locking using mass potentials. J. Neurosci. 35, 2255–2268.
https://doi.org/10.1523/JNEUROSCI.2979-14.2015
Wakeford, O.S., Robinson, D.E., 1974. Lateralization of tonal stimuli by the cat. J. Acoust.