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Mechanistic insight is achieved only when experiments are employed to test formal or computational models. Furthermore, in analogy to lesion studies, phantom perception may serve as a vehicle to understand the fundamental processing principles underlying healthy auditory perception. With a special focus on tinnitus-as the prime example of auditory phantom perception-we review recent work at the intersection of artificial intelligence, psychology and neuroscience. In particular, we discuss why everyone with tinnitus suffers from (at least hidden) hearing loss, but not everyone with hearing loss suffers from tinnitus. We argue that intrinsic neural noise is generated and amplified along the auditory pathway as a compensatory mechanism to restore normal hearing based on adaptive stochastic resonance. The neural noise increase can then be misinterpreted as auditory input and perceived as tinnitus. This mechanism can be formalized in the Bayesian brain framework, where the percept (posterior) assimilates a prior prediction (brain's expectations) and likelihood (bottom-up neural signal). A higher mean and lower variance (i.e. enhanced precision) of the likelihood shifts the posterior, evincing a misinterpretation of sensory evidence, which may be further confounded by plastic changes in the brain that underwrite prior predictions. Hence, two fundamental processing principles provide the most explanatory power for the emergence of auditory phantom perceptions: predictive coding as a top-down and adaptive stochastic resonance as a complementary bottom-up mechanism. We conclude that both principles also play a crucial role in healthy auditory perception. Finally, in the context of neuroscience-inspired artificial intelligence, both processing principles may serve to improve contemporary machine learning techniques.

This diagnostic study assesses the performance of the Apple Watch Noise application in comparison with a class 1 sound level meter.

Use of artificial intelligence (AI) is a burgeoning field in otolaryngology and the communication sciences. A virtual symposium on the topic was convened from Duke University on October 26, 2020, and was attended by more than 170 participants worldwide. This review presents summaries of all but one of the talks presented during the symposium; recordings of all the talks, along with the discussions for the talks, are available at https://www.youtube.com/watch?v=ktfewrXvEFg and https://www.youtube.com/watch?v=-gQ5qX2v3rg . Each of the summaries is about 2500 words in length and each summary includes two figures. This level of detail far exceeds the brief summaries presented in traditional reviews and thus provides a more-informed glimpse into the power and diversity of current AI applications in otolaryngology and the communication sciences and how to harness that power for future applications.

While noninvasive brain stimulation is convenient and cost effective, its utility is limited by the substantial distance between scalp electrodes and their intended neural targets in the head. The tympanic membrane, or eardrum, is a thin flap of skin deep in an orifice of the head that may serve as a port for improved efficiency of noninvasive stimulation. Here we chose the cochlea as a target because it resides in the densest bone of the skull and is adjacent to many deep-brain-stimulation structures. We also tested the hypothesis that noninvasive electric stimulation of the cochlea may restore neural activities that are missing in acoustic stimulation. We placed an electrode in the ear canal or on the tympanic membrane in 25 human adults (10 females) and compared their stimulation efficiency by characterizing the electrically-evoked auditory sensation. Relative to ear canal stimulation, tympanic membrane stimulation was four times more likely to produce an auditory percept, required eight times lower electric current to reach the threshold and produced two-to-four times more linear suprathreshold responses. We further measured tinnitus suppression in 14 of the 25 subjects who had chronic tinnitus. Compared with ear canal stimulation, tympanic membrane stimulation doubled both the probability (22% vs. 55%) and the amount (-15% vs. -34%) of tinnitus suppression. These findings extended previous work comparing evoked perception and tinnitus suppression between electrodes placed in the ear canal and on the scalp. Together, the previous and present results suggest that the efficiency of conventional scalp-based noninvasive electric stimulation can be improved by at least one order of magnitude via tympanic membrane stimulation. This increased efficiency is most likely due to the shortened distance between the electrode placed on the tympanic membrane and the targeted cochlea. The present findings have implications for the management of tinnitus by offering a potential alternative to interventions using invasive electrical stimulation such as cochlear implantation, or other non-invasive transcranial electrical stimulation methods.

ObjectivesElectric stimulation is used to treat a number of neurologic disorders such as epilepsy and depression. However, delivering the required current to far-field neural targets is often ineffective because of current spread through low-impedance pathways. Here, the specific aims are to develop an empirical measure for current passing through the human head and to optimize stimulation strategies for targeting deeper structures, including the auditory nerve, by utilizing the cochlear implant (CI).Materials and methodsOutward input/output (I/O) functions were obtained by CI stimulation and recording scalp potentials in five CI subjects. Conversely, inward I/O functions were obtained by noninvasive transcranial electric stimulation (tES) and recording intracochlear potentials using the onboard recording capability of the CI.ResultsI/O measures indicate substantial current spread, with a maximum of 2.2% gain recorded at the inner ear target during tES (mastoid-to-mastoid electrode configuration). Similarly, CI stimulation produced a maximum of 1.1% gain at the scalp electrode nearest the CI return electrode. Gain varied with electrode montage according to a point source model that accounted for distances between the stimulating and recording electrodes. Within the same electrode montages, current gain patterns varied across subjects suggesting the importance of tissue properties, geometry, and electrode positioning.ConclusionThese results provide a novel objective measure of electric stimulation in the human head, which can help to optimize stimulation parameters that improve neural excitation of deep structures by reducing the influence of current spread.Conflict of interestThe authors declare that the research was conducted in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest.

Wenhui Mao and coauthors discuss possible implications of the COVID-19 pandemic for health aspirations in low- and middle-income countries.

Electrophysiological studies show that nicotine enhances neural responses to characteristic frequency stimuli. Previous behavioral studies partially corroborate these findings in young adults, showing that nicotine selectively enhances auditory processing in difficult listening conditions. The present work extended previous work to include both young and older adults and assessed the nicotine effect on sound frequency and intensity discrimination. Hypotheses were that nicotine improves auditory performance and that the degree of improvement is inversely proportional to baseline performance. Young (19-23 years old) normal-hearing nonsmokers and elderly (61-80) nonsmokers with normal hearing between 500 and 2000 Hz received nicotine gum (6 mg) or placebo gum in a single-blind, randomized crossover design. Participants performed three experiments (frequency discrimination, frequency modulation identification, and intensity discrimination) before and after treatment. The perceptual differences were analyzed between pre- and post-treatment, as well as between post-treatment nicotine and placebo conditions as a function of pre-treatment baseline performance. Compared to pre-treatment performance, nicotine significantly improved frequency discrimination. Compared to placebo, nicotine significantly improved performance for intensity discrimination, and the improvement was more pronounced in the elderly with lower baseline performance. Nicotine had no effect on frequency modulation identification. Nicotine effects are task-dependent, reflecting possible interplays of subjects, tasks and neural mechanisms.

Tinnitus is a sound heard by 15% of the general population in the absence of any external sound. Because external sounds can sometimes mask tinnitus, tinnitus is assumed to affect the perception of external sounds, leading to hypotheses such as "tinnitus filling in the temporal gap" in animal models and "tinnitus inducing hearing difficulty" in human subjects. Here we compared performance in temporal, spectral, intensive, masking and speech-in-noise perception tasks between 45 human listeners with chronic tinnitus (18 females and 27 males with a range of ages and degrees of hearing loss) and 27 young, normal-hearing listeners without tinnitus (11 females and 16 males). After controlling for age, hearing loss, and stimulus variables, we discovered that, contradictory to the widely held assumption, tinnitus does not interfere with the perception of external sounds in 32 of the 36 measures. We interpret the present result to reflect a bottom-up pathway for the external sound and a separate top-down pathway for tinnitus. We propose that these two perceptual pathways can be independently modulated by attention, which leads to the asymmetrical interaction between external and internal sounds, and several other puzzling tinnitus phenomena such as discrepancy in loudness between tinnitus rating and matching. The present results suggest not only a need for new theories involving attention and central noise in animal tinnitus models but also a shift in focus from treating tinnitus to managing its comorbid conditions when addressing complaints about hearing difficulty in individuals with tinnitus.SIGNIFICANCE STATEMENT Tinnitus, or ringing in the ears, is a neurologic disorder that affects 15% of the general population. Here we discovered an asymmetrical relationship between tinnitus and external sounds: although external sounds have been widely used to cover up tinnitus, tinnitus does not impair, and sometimes even improves, the perception of external sounds. This counterintuitive discovery contradicts the general belief held by scientists, clinicians, and even individuals with tinnitus themselves, who often report hearing difficulty, especially in noise. We attribute the counterintuitive discovery to two independent pathways: the bottom-up perception of external sounds and the top-down perception of tinnitus. Clinically, the present work suggests a shift in focus from treating tinnitus itself to treating its comorbid conditions and secondary effects.

RATIONALE: Electrophysiological studies show that systemic nicotine narrows frequency receptive fields and increases gain in neural responses to characteristic frequency stimuli. We postulated that nicotine enhances related auditory processing in humans. OBJECTIVES: The main hypothesis was that nicotine improves auditory performance. A secondary hypothesis was that the degree of nicotine-induced improvement depends on the individuals baseline performance. METHODS: Young (18-27 years old), normal-hearing nonsmokers received nicotine (Nicorette gum, 6mg) or placebo gum in a single-blind, randomized, crossover design. Subjects performed four experiments involving tone-in-noise detection, temporal gap detection, spectral ripple discrimination, and selective auditory attention before and after treatment. The perceptual differences between posttreatment nicotine and placebo conditions were measured and analyzed as a function of the pre-treatment baseline performance. RESULTS: Nicotine significantly improved performance in the more difficult tasks of tone-in-noise detection and selective attention (effect size = - 0.3) but had no effect on relatively easier tasks of temporal gap detection and spectral ripple discrimination. The two tasks showing significant nicotine effects further showed no baseline-dependent improvement. CONCLUSIONS: Nicotine improves auditory performance in difficult listening situations. The present results support future investigation of nicotine effects in clinical populations with auditory processing deficits or reduced cholinergic activation.

ObjectivesElectro-acoustic stimulation (EAS) enhances speech and music perception in cochlear-implant (CI) users who have residual low-frequency acoustic hearing. For CI users who do not have low-frequency acoustic hearing, tactile stimulation may be used in a similar fashion as residual low-frequency acoustic hearing to enhance CI performance. Previous studies showed that electro-tactile stimulation (ETS) enhanced speech recognition in noise and tonal language perception for CI listeners. Here, we examined the effect of ETS on melody recognition in both musician and nonmusician CI users.DesignNine musician and eight nonmusician CI users were tested in a melody recognition task with or without rhythmic cues in three testing conditions: CI only (E), tactile only (T), and combined CI and tactile stimulation (ETS).ResultsOverall, the combined electrical and tactile stimulation enhanced the melody recognition performance in CI users by 9% points. Two additional findings were observed. First, musician CI users outperformed nonmusicians CI users in melody recognition, but the size of the enhancement effect was similar between the two groups. Second, the ETS enhancement was significantly higher with nonrhythmic melodies than rhythmic melodies in both groups.ConclusionsThese findings suggest that, independent of musical experience, the size of the ETS enhancement depends on integration efficiency between tactile and auditory stimulation, and that the mechanism of the ETS enhancement is improved electric pitch perception. The present study supports the hypothesis that tactile stimulation can be used to improve pitch perception in CI users.

BackgroundDeep brain stimulation (DBS) can be an effective therapy for tics and comorbidities in select cases of severe, treatment-refractory Tourette syndrome (TS). Clinical responses remain variable across patients, which may be attributed to differences in the location of the neuroanatomical regions being stimulated. We evaluated active contact locations and regions of stimulation across a large cohort of patients with TS in an effort to guide future targeting.MethodsWe collected retrospective clinical data and imaging from 13 international sites on 123 patients. We assessed the effects of DBS over time in 110 patients who were implanted in the centromedial (CM) thalamus (n=51), globus pallidus internus (GPi) (n=47), nucleus accumbens/anterior limb of the internal capsule (n=4) or a combination of targets (n=8). Contact locations (n=70 patients) and volumes of tissue activated (n=63 patients) were coregistered to create probabilistic stimulation atlases.ResultsTics and obsessive-compulsive behaviour (OCB) significantly improved over time (p0.05). The median time was 13 months to reach a 40% improvement in tics, and there were no significant differences across targets (p=0.84), presence of OCB (p=0.09) or age at implantation (p=0.08). Active contacts were generally clustered near the target nuclei, with some variability that may reflect differences in targeting protocols, lead models and contact configurations. There were regions within and surrounding GPi and CM thalamus that improved tics for some patients but were ineffective for others. Regions within, superior or medial to GPi were associated with a greater improvement in OCB than regions inferior to GPi.ConclusionThe results collectively indicate that DBS may improve tics and OCB, the effects may develop over several months, and stimulation locations relative to structural anatomy alone may not predict response. This study was the first to visualise and evaluate the regions of stimulation across a large cohort of patients with TS to generate new hypotheses about potential targets for improving tics and comorbidities.

Noninvasive transcranial or minimally invasive transtympanic electric stimulation may offer a desirable treatment option for tinnitus because it can activate the deafferented auditory nerve fibers while posing little to no risk to hearing. Here, we built a flexible research interface to generate and control accurately charge-balanced current stimulation as well as a head-mounted instrument capable of holding a transtympanic electrode steady for hours. We then investigated the short-term effect of a limited set of electric stimulation parameters on tinnitus in 10 adults with chronic tinnitus. The preliminary results showed that 63% of conditions of electric stimulation produced some degree of tinnitus reduction, with total disappearance of tinnitus in six subjects in response to at least one condition. The present study also found significant side effects such as visual, tactile, and even pain sensations during electric stimulation. In addition to masking and residual inhibition, neuroplasticity is likely involved in the observed tinnitus reduction. To translate the present electric stimulation into a safe and effective tinnitus treatment option, we need to optimize stimulation parameters that activate the deafferented auditory nerve fibers and reliably suppress tinnitus, with minimal side effects and tolerable sensations. Noninvasive or minimally invasive electric stimulation can be integrated with sound therapy, invasive cochlear implants, or other forms of coordinated stimulation to provide a systematic strategy for tinnitus treatment or even a cure.

Noninvasive transcranial electric stimulation is increasingly being used as an advantageous therapy alternative that may activate deep tissues while avoiding drug side-effects. However, not only is there limited evidence for activation of deep tissues by transcranial electric stimulation, its evoked human sensation is understudied and often dismissed as a placebo or secondary effect. By systematically characterizing the human sensation evoked by transcranial alternating-current stimulation, we observed not only stimulus frequency and electrode position dependencies specific for auditory and visual sensation but also a broader presence of somatic sensation ranging from touch and vibration to pain and pressure. We found generally monotonic input-output functions at suprathreshold levels, and often multiple types of sensation occurring simultaneously in response to the same electric stimulation. We further used a recording circuit embedded in a cochlear implant to directly and objectively measure the amount of transcranial electric stimulation reaching the auditory nerve, a deep intercranial target located in the densest bone of the skull. We found an optimal configuration using an ear canal electrode and low-frequency (

As the only medical device used in the treatment for deafness, the cochlear implant has benefited to more than half a million individuals worldwide. However, the device has limited penetration due to its high cost, especially in low- and middle-income countries. China alone has 27.8 million deaf people, but less than 100,000 of them have received a cochlear implant. The Nurotron Venus device was developed to address the need for an affordable yet safe and effective cochlear implant. The present study describes the design, development, and evaluation of the Nurotron intracochlear electrode array. The standard array is 22 mm in length from the round window marker to the apical tip of the carrier and has 24 electrodes, with a surface area of 0.32 mm2 and center-to-center spacing of 0.85 mm. The Nurotron array has been tested to meet the mechanical, chemical, and electrical requirements specified by the ISO Standard 14708-07. Human temporal bone and clinical trial results showed that the Nurotron array is easy to insert (7.8/10 rating with 10 indicating the highest ease of use) and has a low complication rate (12.5%) of severe insertion trauma while achieving high device stability and reliability (6 array failures in 43,000 patient years of experience). As a critical component, the Nurotron array has contributed to the high level of Nurotron implant speech performance, equivalent to that produced by other existing devices. The Nurotron device has benefited 10,000 deaf people and helped reduce the unit cost from US$25,000 in 2011 to US$4,620 in 2017 through the Chinese Government Tender Program. New, slim, and micromachined electrodes are being developed to further improve performance and accessibility.

Here I identify two gaps in cochlear implants that have been limiting their performance and acceptance. First, cochlear implant performance has remained largely unchanged, despite the number of publications tripling per decade in the last 30 years. Little has been done so far to address a fundamental limitation in the electrode-to-neuron interface, with the electrode size being a thousand times larger than the neuron diameter while the number of electrodes being a thousand times less. Both the small number and the large size of electrodes produce broad spatial activation and poor frequency resolution that limit current cochlear implant performance. Second, a similarly rapid growth in cochlear implant volume has not produced an expected decrease in unit price in the same period. The high cost contributes to low market penetration rate, which is about 20% in developed countries and less than 1% in developing countries. I will discuss changes needed in both research strategy and business practice to close the gap between prosthetic and normal hearing as well as that between haves and have-nots.

For cochlear implant users, combined electro-acoustic stimulation (EAS) significantly improves the performance. However, there are many more users who do not have any functional residual acoustic hearing at low frequencies. Because tactile sensation also operates in the same low frequencies (

ObjectiveTo record envelope following responses (EFRs) to monaural amplitude-modulated broadband noise carriers in which amplitude modulation (AM) depth was slowly changed over time and to compare these objective electrophysiological measures to subjective behavioral thresholds in young normal hearing and older subjects.DesignParticipantsthree groups of subjects included a young normal-hearing group (YNH 18 to 28 years; pure-tone average = 5 dB HL), a first older group ("O1"; 41 to 62 years; pure-tone average = 19 dB HL), and a second older group ("O2"; 67 to 82 years; pure-tone average = 35 dB HL). Electrophysiology: In condition 1, the AM depth (41 Hz) of a white noise carrier, was continuously varied from 2% to 100% (5%/s). EFRs were analyzed as a function of the AM depth. In condition 2, auditory steady-state responses were recorded to fixed AM depths (100%, 75%, 50%, and 25%) at a rate of 41 Hz. Psychophysics: A 3 AFC (alternative forced choice) procedure was used to track the AM depth needed to detect AM at 41 Hz (AM detection). The minimum AM depth capable of eliciting a statistically detectable EFR was defined as the physiological AM detection threshold.ResultsAcross all ages, the fixed AM depth auditory steady-state response and swept AM EFR yielded similar response amplitudes. Statistically significant correlations (r = 0.48) were observed between behavioral and physiological AM detection thresholds. Older subjects had slightly higher (not significant) behavioral AM detection thresholds than younger subjects. AM detection thresholds did not correlate with age. All groups showed a sigmoidal EFR amplitude versus AM depth function but the shape of the function differed across groups. The O2 group reached EFR amplitude plateau levels at lower modulation depths than the normal-hearing group and had a narrower neural dynamic range. In the young normal-hearing group, the EFR phase did not differ with AM depth, whereas in the older group, EFR phase showed a consistent decrease with increasing AM depth. The degree of phase change (or phase slope) was significantly correlated to the pure-tone threshold at 4 kHz.ConclusionsEFRs can be recorded using either the swept modulation depth or the discrete AM depth techniques. Sweep recordings may provide additional valuable information at suprathreshold intensities including the plateau level, slope, and dynamic range. Older subjects had a reduced neural dynamic range compared with younger subjects suggesting that aging affects the ability of the auditory system to encode subtle differences in the depth of AM. The phase-slope differences are likely related to differences in low and high-frequency contributions to EFR. The behavioral-physiological AM depth threshold relationship was significant but likely too weak to be clinically useful in the present individual subjects who did not suffer from apparent temporal processing deficits.

ConclusionThis study described objective and subjective evaluations of the Nurotron® Venus™ Cochlear Implant System and indicated that this system produced a satisfactory performance.ObjectiveTo observe the performance of the Nurotron® Venus™ cochlear implant (CI) system via electrophysiological and psychophysical evaluations.MethodsA 26-electrode CI system was specially designed. The performance of MRI in animal and cadaveric head experiments, EABR in cats experiment, the correlation between ESRT and C level, and psychophysics evaluations in clinical trials were observed.ResultsIn the animal and cadaveric head experiments, magnet dislocation could not be prevented in the 1.5 T MRI without removal of the internal magnet. The EABR was clearly elicited in cat experiment. In the clinical trial, the ESRT was strongly correlated with C level (p

PURPOSE OF REVIEW: Electric stimulation is a potent means of neuromodulation that has been used to restore hearing and minimize tremor, but its application on tinnitus symptoms has been limited. We examine recent evidence to identify the knowledge gaps in the use of electric stimulation for tinnitus treatment. RECENT FINDINGS: Recent studies using electric stimulation to suppress tinnitus in humans are categorized according to their points of attacks. First, noninvasive, direct current stimulation uses an active electrode in the ear canal, tympanic membrane, or temporal scalp. Second, inner ear stimulation uses charge-balanced biphasic stimulation by placing an active electrode on the promontory or round window, or a cochlear implant array in the cochlea. Third, intraneural implants can provide targeted stimulation of specific sites along the auditory pathway. Although these studies demonstrated some success in tinnitus suppression, none established a link between tinnitus suppression efficacy and tinnitus-generating mechanisms. SUMMARY: Electric stimulation provides a unique opportunity to suppress tinnitus. Challenges include matching electric stimulation sites and patterns to tinnitus locus and type, meeting the oftentimes-contradictory demands between tinnitus suppression and other indications, such as speech understanding, and justifying the costs and risks of electric stimulation for tinnitus symptoms.

Long-term loudness perception of a sound has been presumed to depend on the spatial distribution of activated auditory nerve fibers as well as their temporal firing pattern. The relative contributions of those two factors were investigated by measuring loudness adaptation to sinusoidally amplitude-modulated 12-kHz tones. The tones had a total duration of 180 s and were either unmodulated or 100%-modulated at one of three frequencies (4, 20, or 100 Hz), and additionally varied in modulation depth from 0% to 100% at the 4-Hz frequency only. Every 30 s, normal-hearing subjects estimated the loudness of one of the stimuli played at 15 dB above threshold in random order. Without any amplitude modulation, the loudness of the unmodulated tone after 180 s was only 20% of the loudness at the onset of the stimulus. Amplitude modulation systematically reduced the amount of loudness adaptation, with the 100%-modulated stimuli, regardless of modulation frequency, maintaining on average 55%-80% of the loudness at onset after 180 s. Because the present low-frequency amplitude modulation produced minimal changes in long-term spectral cues affecting the spatial distribution of excitation produced by a 12-kHz pure tone, the present result indicates that neural synchronization is critical to maintaining loudness perception over time.

Although the cochlear implant has been widely acknowledged as the most successful neural prosthesis, only a fraction of hearing-impaired people who can potentially benefit from a cochlear implant have actually received one due to its limited awareness, accessibility, and affordability. To help overcome these limitations, a 26-electrode cochlear implant has been developed to receive China's Food and Drug Administration (CFDA) approval in 2011 and Conformité Européenne (CE) Marking in 2012. The present article describes design philosophy, system specification, and technical verification of the Nurotron device, which includes advanced digital signal processing and 4 current sources with multiple amplitude resolutions that not only are compatible with perceptual capability but also allow interleaved or simultaneous stimulation. The article also presents 3-year longitudinal evaluation data from 60 human subjects who have received the Nurotron device. The objective measures show that electrode impedance decreased within the first month of device use, but was stable until a slight increase at the end of two years. The subjective loudness measures show that electric stimulation threshold was stable while the maximal comfort level increased over the 3 years. Mandarin sentence recognition increased from the pre-surgical 0%-correct score to a plateau of about 80% correct with 6-month use of the device. Both indirect and direct comparisons indicate indistinguishable performance differences between the Nurotron system and other commercially available devices. The present 26-electrode cochlear implant has already helped to lower the price of cochlear implantation in China and will likely contribute to increased cochlear implant access and success in the rest of the world. This article is part of a Special Issue entitled .

Cochlear implant (CI) listeners have difficulty understanding speech in complex listening environments. This deficit is thought to be largely due to peripheral encoding problems arising from current spread, which results in wide peripheral filters. In normal hearing (NH) listeners, central processing contributes to segregation of speech from competing sounds. We tested the hypothesis that basic central processing abilities are retained in post-lingually deaf CI listeners, but processing is hampered by degraded input from the periphery. In eight CI listeners, we measured auditory nerve compound action potentials to characterize peripheral filters. Then, we measured psychophysical detection thresholds in the presence of multi-electrode maskers placed either inside (peripheral masking) or outside (central masking) the peripheral filter. This was intended to distinguish peripheral from central contributions to signal detection. Introduction of temporal asynchrony between the signal and masker improved signal detection in both peripheral and central masking conditions for all CI listeners. Randomly varying components of the masker created spectral-variance cues, which seemed to benefit only two out of eight CI listeners. Contrastingly, the spectral-variance cues improved signal detection in all five NH listeners who listened to our CI simulation. Together these results indicate that widened peripheral filters significantly hamper central processing of spectral-variance cues but not of temporal cues in post-lingually deaf CI listeners. As indicated by two CI listeners in our study, however, post-lingually deaf CI listeners may retain some central processing abilities similar to NH listeners.

Contemporary cochlear implants with multiple electrode stimulation can produce good speech perception but poor music perception. Hindered by the lack of a gold standard to quantify electric pitch, relatively little is known about the nature and extent of the electric pitch abnormalities and their impact on cochlear implant performance. Here we overcame this obstacle by comparing acoustic and electric pitch perception in 3 unilateral cochlear-implant subjects who had functionally usable acoustic hearing throughout the audiometric frequency range in the non-implant ear. First, to establish a baseline, we measured and found slightly impaired pure tone frequency discrimination and nearly perfect melody recognition in all 3 subjects acoustic ear. Second, using pure tones in the acoustic ear to match electric pitch induced by an intra-cochlear electrode, we found that the frequency-electrode function was not only 1-2 octaves lower, but also 2 times more compressed in frequency range than the normal cochlear frequency-place function. Third, we derived frequency difference limens in electric pitch and found that the equivalent electric frequency discrimination was 24 times worse than normal-hearing controls. These 3 abnormalities are likely a result of a combination of broad electric field, distant intra-cochlear electrode placement, and non-uniform spiral ganglion cell distribution and survival, all of which are inherent to the electrode-nerve interface in contemporary cochlear implants. Previous studies emphasized on the mean shape of the frequency-electrode function, but the present study indicates that the large variance of this function, reflecting poor electric pitch discriminability, is the main factor limiting contemporary cochlear implant performance.

Recent evidence suggests that late auditory evoked potentials (LAEP) provide a useful objective metric of performance in cochlear implant (CI) subjects. However, the CI produces a large electrical artifact that contaminates LAEP recordings and confounds their interpretation. Independent component analysis (ICA) has been used in combination with multi-channel recordings to effectively remove the artifact. The applicability of the ICA approach is limited when only single channel data are needed or available, as is often the case in both clinical and research settings. Here we developed a single-channel, high sample rate (125 kHz), and high bandwidth (0-100 kHz) acquisition system to reduce the CI stimulation artifact. We identified two different artifacts in the recording: 1) a high frequency artifact reflecting the stimulation pulse rate, and 2) a direct current (DC, or pedestal) artifact that showed a non-linear time varying relationship to pulse amplitude. This relationship was well described by a bivariate polynomial. The high frequency artifact was completely attenuated by a 35 Hz low-pass filter for all subjects (n = 22). The DC artifact could be caused by an impedance mismatch. For 27% of subjects tested, no DC artifact was observed when electrode impedances were balanced to within 1 kΩ. For the remaining 73% of subjects, the pulse amplitude was used to estimate and then attenuate the DC artifact. Where measurements of pulse amplitude were not available (as with standard low sample rate systems), the DC artifact could be estimated from the stimulus envelope. The present artifact removal approach allows accurate measurement of LAEPs from CI subjects from single channel recordings, increasing their feasibility and utility as an accessible objective measure of CI function.

Recent evidence suggests that late auditory evoked potentials (LAEP) provide a useful objective metric of performance in cochlear implant (CI) subjects. However, the CI produces a large electrical artifact that contaminates LAEP recordings and confounds their interpretation. Independent component analysis (ICA) has been used in combination with multi-channel recordings to effectively remove the artifact. The applicability of the ICA approach is limited when only single channel data are needed or available, as is often the case in both clinical and research settings. Here we developed a single-channel, high sample rate (125 kHz), and high bandwidth (0-100 kHz) acquisition system to reduce the CI stimulation artifact. We identified two different artifacts in the recording: 1) a high frequency artifact reflecting the stimulation pulse rate, and 2) a direct current (DC, or pedestal) artifact that showed a non-linear time varying relationship to pulse amplitude. This relationship was well described by a bivariate polynomial. The high frequency artifact was completely attenuated by a 35 Hz low-pass filter for all subjects (n = 22). The DC artifact could be caused by an impedance mismatch. For 27% of subjects tested, no DC artifact was observed when electrode impedances were balanced to within 1 kΩ. For the remaining 73% of subjects, the pulse amplitude was used to estimate and then attenuate the DC artifact. Where measurements of pulse amplitude were not available (as with standard low sample rate systems), the DC artifact could be estimated from the stimulus envelope. The present artifact removal approach allows accurate measurement of LAEPs from CI subjects from single channel recordings, increasing their feasibility and utility as an accessible objective measure of CI function.

Abnormal auditory adaptation is a standard clinical tool for diagnosing auditory nerve disorders due to acoustic neuromas. In the present study we investigated auditory adaptation in auditory neuropathy owing to disordered function of inner hair cell ribbon synapses (temperature-sensitive auditory neuropathy) or auditory nerve fibres. Subjects were tested when afebrile for (i) psychophysical loudness adaptation to comfortably-loud sustained tones; and (ii) physiological adaptation of auditory brainstem responses to clicks as a function of their position in brief 20-click stimulus trains (#1, 2, 3 … 20). Results were compared with normal hearing listeners and other forms of hearing impairment. Subjects with ribbon synapse disorder had abnormally increased magnitude of loudness adaptation to both low (250 Hz) and high (8000 Hz) frequency tones. Subjects with auditory nerve disorders had normal loudness adaptation to low frequency tones; all but one had abnormal adaptation to high frequency tones. Adaptation was both more rapid and of greater magnitude in ribbon synapse than in auditory nerve disorders. Auditory brainstem response measures of adaptation in ribbon synapse disorder showed Wave V to the first click in the train to be abnormal both in latency and amplitude, and these abnormalities increased in magnitude or Wave V was absent to subsequent clicks. In contrast, auditory brainstem responses in four of the five subjects with neural disorders were absent to every click in the train. The fifth subject had normal latency and abnormally reduced amplitude of Wave V to the first click and abnormal or absent responses to subsequent clicks. Thus, dysfunction of both synaptic transmission and auditory neural function can be associated with abnormal loudness adaptation and the magnitude of the adaptation is significantly greater with ribbon synapse than neural disorders.

Tinnitus is a phantom sensation of sound in the absence of external stimulation. However, external stimulation, particularly electric stimulation via a cochlear implant, has been shown to suppress tinnitus. Different from traditional methods of delivering speech sounds or high-rate (>2000 Hz) stimulation, the present study found a unique unilaterally-deafened cochlear implant subject whose tinnitus was completely suppressed by a low-rate (

ObjectivesAuditory cortical N100s were examined in ten auditory neuropathy (AN) subjects as objective measures of impaired hearing.MethodsLatencies and amplitudes of N100 in AN to increases of frequency (4-50%) or intensity (4-8 dB) of low (250 Hz) or high (4000 Hz) frequency tones were compared with results from normal-hearing controls. The sites of auditory nerve dysfunction were pre-synaptic (n=3) due to otoferlin mutations causing temperature sensitive deafness, post-synaptic (n=4) affecting other cranial and/or peripheral neuropathies, and undefined (n=3).ResultsAN consistently had N100s only to the largest changes of frequency or intensity whereas controls consistently had N100s to all but the smallest frequency and intensity changes. N100 latency in AN was significantly delayed compared to controls, more so for 250 than for 4000 Hz and more so for changes of intensity compared to frequency. N100 amplitudes to frequency change were significantly reduced in ANs compared to controls, except for pre-synaptic AN in whom amplitudes were greater than controls. N100 latency to frequency change of 250 but not of 4000 Hz was significantly related to speech perception scores.ConclusionsAs a group, AN subjects' N100 potentials were abnormally delayed and smaller, particularly for low frequency. The extent of these abnormalities differed between pre- and post-synaptic forms of the disorder.SignificanceAbnormalities of auditory cortical N100 in AN reflect disorders of both temporal processing (low frequency) and neural adaptation (high frequency). Auditory N100 latency to the low frequency provides an objective measure of the degree of impaired speech perception in AN.

ObjectiveAuditory temporal processes in quiet are impaired in auditory neuropathy (AN) similar to normal hearing subjects tested in noise. N100 latencies were measured from AN subjects at several tone intensities in quiet and noise for comparison with a group of normal hearing individuals.MethodsSubjects were tested with brief 100 ms tones (1.0 kHz, 100-40 dB SPL) in quiet and in continuous noise (90 dB SPL). N100 latency and amplitude were analyzed as a function of signal intensity and audibility.ResultsN100 latency in AN in quiet was delayed and amplitude was reduced compared to the normal group; the extent of latency delay was related to psychoacoustic measures of gap detection threshold and speech recognition scores, but not to audibility. Noise in normal hearing subjects was accompanied by N100 latency delays and amplitude reductions paralleling those found in AN tested in quiet. Additional N100 latency delays and amplitude reductions occurred in AN with noise.ConclusionsN100 latency to tones and performance on auditory temporal tasks were related in AN subjects. Noise masking in normal hearing subjects affected N100 latency to resemble AN in quiet.SignificanceN100 latency to tones may serve as an objective measure of the efficiency of auditory temporal processes.

ObjectivesTo examine auditory cortical potentials in normal-hearing subjects to intensity increments in a continuous pure tone at low, mid, and high frequency.MethodsElectrical scalp potentials were recorded in response to randomly occurring 100 ms intensity increments of continuous 250, 1000, and 4000 Hz tones every 1.4 s. The magnitude of intensity change varied between 0, 2, 4, 6, and 8 dB above the 80 dB SPL continuous tone.ResultsPotentials included N100, P200, and a slow negative (SN) wave. N100 latencies were delayed whereas amplitudes were not affected for 250 Hz compared to 1000 and 4000 Hz. Functions relating the magnitude of the intensity change and N100 latency/amplitude did not differ in their slope among the three frequencies. No consistent relationship between intensity increment and SN was observed. Cortical dipole sources for N100 did not differ in location or orientation between the three frequencies.ConclusionsThe relationship between intensity increments and N100 latency/amplitude did not differ between tonal frequencies. A cortical tonotopic arrangement was not observed for intensity increments. Our results are in contrast to prior studies of brain activities to brief frequency changes showing cortical tonotopic organization.SignificanceThese results suggest that intensity and frequency discrimination employ distinct central processes.

ObjectiveWe examined auditory cortical potentials in normal hearing subjects to spectral changes in continuous low and high frequency pure tones.MethodsCortical potentials were recorded to increments of frequency from continuous 250 or 4000Hz tones. The magnitude of change was random and varied from 0% to 50% above the base frequency.ResultsPotentials consisted of N100, P200 and a slow negative wave (SN). N100 amplitude, latency and dipole magnitude with frequency increments were significantly greater for low compared to high frequencies. Dipole amplitudes were greater in the right than left hemisphere for both base frequencies. The SN amplitude to frequency changes between 4% and 50% was not significantly related to the magnitude of spectral change.ConclusionsModulation of N100 amplitude and latency elicited by spectral change is more pronounced with low compared to high frequencies.SignificanceThese data provide electrophysiological evidence that central processing of spectral changes in the cortex differs for low and high frequencies. Some of these differences may be related to both temporal- and spectral-based coding at the auditory periphery. Central representation of frequency change may be related to the different temporal windows of integration across frequencies.

Perceptual consequences of disrupted auditory nerve activity were systematically studied in 21 subjects who had been clinically diagnosed with auditory neuropathy (AN), a recently defined disorder characterized by normal outer hair cell function but disrupted auditory nerve function. Neurological and electrophysical evidence suggests that disrupted auditory nerve activity is due to desynchronized or reduced neural activity or both. Psychophysical measures showed that the disrupted neural activity has minimal effects on intensity-related perception, such as loudness discrimination, pitch discrimination at high frequencies, and sound localization using interaural level differences. In contrast, the disrupted neural activity significantly impairs timing related perception, such as pitch discrimination at low frequencies, temporal integration, gap detection, temporal modulation detection, backward and forward masking, signal detection in noise, binaural beats, and sound localization using interaural time differences. These perceptual consequences are the opposite of what is typically observed in cochlear-impaired subjects who have impaired intensity perception but relatively normal temporal processing after taking their impaired intensity perception into account. These differences in perceptual consequences between auditory neuropathy and cochlear damage suggest the use of different neural codes in auditory perception: a suboptimal spike count code for intensity processing, a synchronized spike code for temporal processing, and a duplex code for frequency processing. We also proposed two underlying physiological models based on desynchronized and reduced discharge in the auditory nerve to successfully account for the observed neurological and behavioral data. These methods and measures cannot differentiate between these two AN models, but future studies using electric stimulation of the auditory nerve via a cochlear implant might. These results not only show the unique contribution of neural synchrony to sensory perception but also provide guidance for translational research in terms of better diagnosis and management of human communication disorders.

ObjectiveTo study objectively auditory temporal processing in a group of normal hearing subjects and in a group of hearing-impaired individuals with auditory neuropathy (AN) using electrophysiological and psychoacoustic methods.MethodsScalp recorded evoked potentials were measured to brief silent intervals (gaps) varying between 2 and 50ms embedded in continuous noise. Latencies and amplitudes of N100 and P200 were measured and analyzed in two conditions: (1) active, when using a button in response to gaps; (2) passive, listening, but not responding.ResultsIn normal subjects evoked potentials (N100/P200 components) were recorded in response to gaps as short as 5ms in both active and passive conditions. Gap evoked potentials in AN subjects appeared only with prolonged gap durations (10-50ms). There was a close association between gap detection thresholds measured psychoacoustically and electrophysiologically in both normals and in AN subjects.ConclusionsAuditory cortical potentials can provide objective measures of auditory temporal processes.SignificanceThe combination of electrophysiological and psychoacoustic methods converged to provide useful objective measures for studying auditory cortical temporal processing in normals and hearing-impaired individuals. The procedure used may also provide objective measures of temporal processing for evaluating special populations such as children who may not be able to provide subjective responses.

We have studied 72 members belonging to a large kindred with a hearing disorder inherited in an autosomal dominant pattern. We used audiological, physiological, and psychoacoustic measures to characterize the hearing disorders. The initial phenotypic features of the hearing loss are of an auditory neuropathy (AN) with abnormal auditory nerve and brainstem responses (ABRs) and normal outer hair cell functions [otoacoustic emissions (OAEs) and cochlear microphonics (CMs)]. Psychoacoustic studies revealed profound abnormalities of auditory temporal processes (gap detection, amplitude modulation detection, speech discrimination) and frequency processes (difference limens) beyond that seen in hearing impairment accompanying cochlear sensory disorders. The hearing loss progresses over 10-20 years to also involve outer hair cells, producing a profound sensorineural hearing loss with absent ABRs and OAEs. Affected family members do not have evidence of other cranial or peripheral neuropathies. There was a marked improvement of auditory functions in three affected family members studied after cochlear implantation with return of electrically evoked auditory brainstem responses (EABRs), auditory temporal processes, and speech recognition. These findings are compatible with a distal auditory nerve disorder affecting one or all of the components in the auditory periphery including terminal auditory nerve dendrites, inner hair cells, and the synapses between inner hair cells and auditory nerve. There is relative sparing of auditory ganglion cells and their axons.

We studied a family with hereditary sensory motor neuropathy and deafness accompanying a missense mutation in the MPZ gene. Pathological examination of the cochlea in one of the family members revealed marked loss of auditory ganglion cells and central and peripheral auditory nerve fibres within the cochlea. The inner hair cells were of normal number with preserved morphology. The outer hair cells were normal in number except for a 30% reduction in just the apical turn. Examination of the sural nerve and the auditory nerve adjacent to the brainstem showed marked loss of fibres with evidence of incomplete remyelination of some of the remaining fibres. Studies of auditory function in surviving family members using electrophysiological and psychoacoustic methods provided evidence that the hearing deficits in this form of auditory neuropathy were probably related to a decrease of auditory nerve input accompanying axonal disease. Altered synchrony of discharge of the remaining fibres was a possible additional contributing factor.

Auditory neuropathy affects the normal synchronous activity in the auditory nerve, without affecting the amplification function in the inner ear. Patients with auditory neuropathy often complain that they can hear sounds, but cannot understand speech. Here we report psychophysical tests indicating that these patients' poor speech recognition is due to a severe impairment in their temporal processing abilities. We also simulate this temporal processing impairment in normally hearing listeners and produce similar speech recognition deficits. This study demonstrates the importance of neural synchrony for auditory perceptions including speech recognition in humans. The results should contribute to better diagnosis and treatment of auditory neuropathy.