The upper frequency limit for the use of phase locking to code temporal fine structure in humans:A compilation of viewpoints

The relative importance of neural temporal and place coding in auditory perception is still a matter of much debate. The current article is a compilation of viewpoints from leading auditory psychophysicists and physiologists regarding the upper frequency limit for the use of neural phase locking to code temporal fine structure in humans. While phase locking is used for binaural processing up to about 1500 Hz, there is disagreement regarding the use of monaural phase-locking information at higher frequencies. Estimates of the general upper limit proposed by the contributors range from 1500 to 10000 Hz. The arguments depend on whether or not phase locking is needed to explain psychophysical discrimination performance at frequencies above 1500 Hz, and whether or not the phase-locked neural representation is sufficiently robust at these frequencies to provide useable information. The contributors suggest key experiments that may help to resolve this issue, and experimental findings that may cause them to change their minds. This issue is of crucial importance to our understanding of the neural basis of auditory perception in general, and of pitch perception in particular

Assessment of fundamental cochlear limits of frequency resolution and phase-locking in humans and animal models

Frequency selectivity and neural phase-locking are two primary properties of the peripheral auditory system and are fundamental to hearing. These properties are reflected in neural signals as a place-rate and time code and are quantified by means of responses from single auditory nerve fibers (AN fibers). Because of practical issues, the limits of both properties are poorly characterized in humans and widely differing values are assumed in the interpretation of non-electrophysiological results. Recent otoacoustic and behavioral measurements suggest that frequency selectivity is higher in humans than in laboratory animals (Shera et al., 2002), but this is disputed based on comparisons of behavioral and electrophysiological measurements across species (Ruggero and Temchin, 2005). Neural phase-locking declines with frequency and becomes undetectable at an upper frequency limit which differs between species. Some studies suggest that phase-locking in human extends to much higher frequencies than that found in common laboratory animals such as cat. In this thesis we investigate the use of mass potentials to electrophysiologically quantify these properties in humans.A minimally invasive transtympanic protocol was developed to record stimulus-evoked mass-potentials from the cochlear promontory or from the niche of the round window in monkey (macaque) and human. This involved a custom made ear mold with openings for the transtympanic needle electrode and for acoustic stimulation (ER-2 earphone, in situ calibrated with an ER-7 microphone). To obtain frequency selectivity a notched-noise forward masking paradigm (Oxenham and Shera, 2003) was combined with the recording of compound action potentials (CAP). For neural phase-locking, we developed a method based on forward masking to disambiguate phase-locked contributions of receptor and neural origin (neurophonic). Both methods were first developed, assessed and validated at the round window in cat and thereafter applied in monkey and human.Frequency selectivity. We found that the empirical method that was first developed and assessed in cat was a suitable means to examine frequency tuning for a number of reasons. a) Masking of CAP responses behaved as expected from the physiology of single AN-fibers. b) Masking tuning curves were equivalent to tuning curve of single AN-fibers. c) The sharpness of masking tuning curves, quantified as a Q10-factor, closely followed the lower boundary of single AN-fibers and was only slightly higher at high frequencies. CAP-tuning was dependent on probe level consistent with cochlear physiology. The CAP responses behaved similar in human and monkey, but the responses and signal-to-noise ratios were much smaller and therefore higher stimulus levels (>30 dB) were needed in human and monkey. We found that CAP tuning in human was on average 1.6 times sharper than in cat and chinchilla and 1.35 times sharper than in monkey (macaque).Neural phase-locking. We found that potentials near the round window have a considerable neural phase-lockedcontribution that can be isolated and quantified with the present method. Moreover, the neural component was in many ways similar to that measured on the auditory nerve. The only noteworthy differences with the latter were a typically larger magnitude and a smaller time lag for the neural component at the round window. The frequency limit obtained in cat was 4.7 kHz, which is very similar to the limit reported for individual AN-fibers (~ 5 kHz). We found in many respects similarities between the measurements in human, monkey and those at the round window in cat, with similar temporal and spectral properties. The most notable difference in human and monkey compared to cat was a much smaller magnitude (-30 dB) and also signal-to-noise(floor) ratio (-20 dB) for the neurophonic. The upper detectable frequency limits of neural phase-locking obtained from stimulus evoked potentials was 3.3 kHz in human and 4.0 kHz in monkey (macaque).Frequency selectivity and neural phase-locking can be characterized from mass potentials with a minimally invasive technique from awake, normal hearing subjects. We found evidence that a) humans have sharper frequency tuning than commonly studied animals, consistent with previous reports (Shera et al., 2002; Oxenham and Shera, 2003) and; b) humans have an upper frequency limit of phase-locking that is not higher than in cat (5 kHz), and likely is somewhat lower.List of abbreviations xi Abstract xiii Chapter 1. General Introduction 1 Chapter 2. Auditory nerve frequency tuning measured with forward-masked compound action potentials 23 Chapter 3. Electrophysiological evidence for sharp cochlear tuning in humans 59 Chapter 4. Upper frequency limit of phase-locking in stimulus evoked potentials 73 Chapter 5. Upper frequency limit of phase-locking in human and monkey 121 Chapter 6. General Discussion 143 References 153 Summary/samenvatting 159 Bibliography 167nrpages: 169status: publishe

High-resolution frequency tuning but not temporal coding in the human cochlea

Frequency tuning and phase-locking are two fundamental properties generated in the cochlea, enabling but also limiting the coding of sounds by the auditory nerve (AN). In humans, these limits are unknown, but high resolution has been postulated for both properties. Electrophysiological recordings from the AN of normal-hearing volunteers indicate that human frequency tuning, but not phase-locking, exceeds the resolution observed in animal models.status: publishe

High-resolution frequency tuning but not temporal coding in the human cochlea.

Frequency tuning and phase-locking are two fundamental properties generated in the cochlea, enabling but also limiting the coding of sounds by the auditory nerve (AN). In humans, these limits are unknown, but high resolution has been postulated for both properties. Electrophysiological recordings from the AN of normal-hearing volunteers indicate that human frequency tuning, but not phase-locking, exceeds the resolution observed in animal models

Assessment of the Limits of Neural Phase-Locking Using Mass Potentials

Artículo de publicación ISIIn the diverse mechanosensory systems that animals evolved, the waveform of stimuli can be encoded by phase locking in spike trains of primary afferents. Coding of the fine structure of sounds via phase locking is thought to be critical for hearing. The upper frequency limit of phase locking varies across species and is unknown in humans. We applied a method developed previously, which is based on neural adaptation evoked by forward masking, to analyze mass potentials recorded on the cochlea and auditory nerve in the cat. The method allows us to separate neural phase locking from receptor potentials. We find that the frequency limit of neural phase locking obtained from mass potentials was very similar to that reported for individual auditory nerve fibers. The results suggest that this is a promising approach to examine neural phase locking in humans with normal or impaired hearing or in other species for which direct recordings from primary afferents are not feasible

Assessment of Ipsilateral Efferent Effects in Human via ECochG

Development of electrophysiological means to assess the medial olivocochlear (MOC) system in humans is important to further our understanding of the function of that system and for the refinement and validation of psychoacoustical and otoacoustic emission methods which are thought to probe the MOC. Based on measurements in anesthetized animals it has been hypothesized that the MOC-reflex (MOCR) can enhance the response to signals in noise, and several lines of evidence support such a role in humans. A difficulty in these studies is the isolation of efferent effects. Efferent activation can be triggered by acoustic stimulation of the contralateral or ipsilateral ear, but ipsilateral stimulation is thought to be more effective. However, ipsilateral stimulation complicates interpretation of effects since these sounds can affect the perception of other ipsilateral sounds by mechanisms not involving olivocochlear efferents. We assessed the ipsilaterally evoked MOCR in human using a transtympanic procedure to record mass-potentials from the cochlear promontory or the niche of the round window. Averaged compound action potential (CAP) responses to masked probe tones of 4 kHz with and without a precursor (designed to activate the MOCR but not the stapedius reflex) were extracted with a polarity alternating paradigm. The masker was either a simultaneous narrow band noise masker or a short (20-ms) tonal ON- or OFF-frequency forward masker. The subjects were screened for normal hearing (audiogram, tympanogram, threshold stapedius reflex) and psychoacoustically tested for the presence of a precursor effect. We observed a clear reduction of CAP amplitude by the precursor, for different masking conditions. Even without an MOCR, this is expected because the precursor will affect the response to subsequent stimuli via neural adaptation. To determine whether the precursor also activated the efferent system, we measured the CAP over a range of masker levels, with or without precursor, and for different types of masker. The results show CAP reduction consistent with the type of gain reduction caused by the MOCR. These results generally support psychoacoustical paradigms designed to probe the efferent system as indeed activating the MOCR system, but not all observations are consistent with this mechanism.status: publishe

Auditory nerve frequency tuning measured with forward-masked compound action potentials

Frequency selectivity is a fundamental cochlear property. Recent studies using otoacoustic emissions and psychophysical forward masking suggest that frequency selectivity is sharper in human than in common laboratory species. This has been disputed based on reports using compound action potentials (CAPs), which reflect activity in the auditory nerve and can be measured in humans. Comparative data of CAPs, obtained with a variety of simultaneous masking protocols, have been interpreted to indicate similarity of frequency tuning across mammals and even birds. Unfortunately, there are several issues with the available CAP measurements which hamper a straightforward comparison across species. We investigate sharpness of CAP tuning in cat and chinchilla using a forward masking notched-noise paradigm- which is less confounded by cochlear nonlinearities than simultaneousmasking paradigms and similar to what was used in the psychophysical study reporting sharper tuning in humans. Our parametr

Assessment of Ipsilateral Efferent Effects in Human via ECochG

Development of electrophysiological means to assess the medial olivocochlear (MOC) system in humans is important to further our understanding of the function of that system and for the refinement and validation of psychoacoustical and otoacoustic emission methods which are thought to probe the MOC. Based on measurements in anesthetized animals it has been hypothesized that the MOC-reflex (MOCR) can enhance the response to signals in noise, and several lines of evidence support such a role in humans. A difficulty in these studies is the isolation of efferent effects. Efferent activation can be triggered by acoustic stimulation of the contralateral or ipsilateral ear, but ipsilateral stimulation is thought to be more effective. However, ipsilateral stimulation complicates interpretation of effects since these sounds can affect the perception of other ipsilateral sounds by mechanisms not involving olivocochlear efferents. We assessed the ipsilaterally evoked MOCR in human using a transtympanic procedure to record mass-potentials from the cochlear promontory or the niche of the round window. Averaged compound action potential (CAP) responses to masked probe tones of 4 kHz with and without a precursor (designed to activate the MOCR but not the stapedius reflex) were extracted with a polarity alternating paradigm. The masker was either a simultaneous narrow band noise masker or a short (20-ms) tonal ON- or OFF-frequency forward masker. The subjects were screened for normal hearing (audiogram, tympanogram, threshold stapedius reflex) and psychoacoustically tested for the presence of a precursor effect. We observed a clear reduction of CAP amplitude by the precursor, for different masking conditions. Even without an MOCR, this is expected because the precursor will affect the response to subsequent stimuli via neural adaptation. To determine whether the precursor also activated the efferent system, we measured the CAP over a range of masker levels, with or without precursor, and for different types of masker. The results show CAP reduction consistent with the type of gain reduction caused by the MOCR. These results generally support psychoacoustical paradigms designed to probe the efferent system as indeed activating the MOCR system, but not all observations are consistent with this mechanism