Examining the Profile of Noise-Induced Cochlear Synaptopathy Using iPhone Health App Data and Cochlear and Brainstem Electrophysiological Responses to Fast Clicks Rates

Abstract

Little is known about objective classifying of noise exposure risk levels in personal listening device (PLD) users and electrophysiologic evidence of cochlear synaptopathy at very fast click rates. The aim of the study was to objectively classify noise exposure risk using iPhone Health app and identify signs of cochlear synaptopathy using behavioral and electrophysiologic measures. Thirty normal-hearing females (aged 18–26 years) were grouped based on their iPhone Health app's 6-month listening level and noise exposure data into low-risk and high-risk groups. They were assessed using a questionnaire, extended high-frequency (EHF) audiometry, QuickSIN test, distortion-product otoacoustic emission (DPOAE), and simultaneous recording of electrocochleography (ECochG) and auditory brainstem response (ABR) at three click rates (19.5/s, 97.7/s, 234.4/s). A series of ANOVAs and independent samples t -test were conducted for group comparison. Both groups had within-normal EHF hearing thresholds and DPOAEs. However, the high-risk participants were over twice as likely to suffer from tinnitus, had abnormally large summating potential to action potential amplitude and area ratios at fast rates, and had slightly smaller waves I and V amplitudes. The high-risk group demonstrated a profile of behavioral and objective signs of cochlear synaptopathy based on ECochG and ABR recordings at fast click rates. The findings in this study suggest that the iPhone Health app may be a useful tool for further investigation into cochlear synaptopathy in PLD users.

An estimated 20 million adults in the United States have some sort of nonoccupational, noise-induced auditory symptoms, including noise-induced hearing loss (NIHL), difficulty with speech perception in noise, hyperacusis, or tinnitus, ¹ and as many as 17% of teenagers 12 to 19 years of age are estimated to have NIHL. ² With growing popularity of listening to music through cellphones and other devices, researchers have begun investigating their effects on the human auditory system. Questionnaire data have shown that 86% of young adults usually listen to music through their earphones for approximately 250 hours per year (or 125 hours per 6 months). ³ Studies have found personal listening devices (PLDs) such as cellphones and MP3 players may generate maximum outputs that are above permissible exposure limits (PELs) recommended ^{4 5} established by Occupational Safety and Health Administration (OSHA: 90 dBA for 8 hours), ⁶ National Institute for Occupational Safety and Health 1998 standards (NIOSH: 85 dBA for 8 hours), ⁷ and World Health Organization (WHO: 75 dBA for 8 hours). ⁸ Regardless of the PLD brand and type of coupling, all genres of music at maximum output easily exceed the PELs and are considered hazardous. ⁵ For example, listening to music on an iPod for only 30 minutes at a maximum (100%) volume setting may result in a temporary threshold shift on the audiogram and decreased distortion-product otoacoustic emission (DPOAE) amplitudes for at least a week, ⁹ whereas listening to music using PLDs for 5 or more years has been linked to a permanent threshold shift at extended high frequencies (EHFs; i.e., for frequencies above 8 kHz). ^{10 11}

Recently, researchers have shown that noise exposure in both animal models and in humans can also cause selective damage to the synapses between inner hair cells (IHCs) and type I auditory nerve fibers (ANFs) or “cochlear synaptopathy.” ^{12 13 14 15 16} Histological examination of animal models has shown degeneration of type I ANF preferentially affecting the low-to-medium spontaneous rate ANF (low-SR fibers), decreased synaptic counts in the IHC region, and minimal damage to the outer hair cells (OHCs). ^{17 18 19} Since the damage is in the synapse between IHCs and type I ANFs, signs are often not exhibited on DPOAE testing, and because the affected low-SR fibers have high response thresholds the signs are not always present on the conventional (250–8,000 Hz) audiogram. ¹² However, hearing loss at the EHF can occur due to loss of OHCs at the base of the cochlea, ²⁰ and patients may complain of tinnitus, hyperacusis, and difficulty understanding speech in noise despite having a normal pure-tone audiogram. ^{21 22} For further information about the physiology of cochlear synaptopathy, please review these papers. ^{17 18 20 23 24 ,}

Little is known about the effect of noise exposure via PLDs on IHCs–type I ANF synapses and the risk for cochlear synaptopathy in young adults. Given that studies on animal models with noise exposure have shown histopathologic signs of cochlear synaptopathy, it is important to investigate the possibility of cochlear synaptopathy in humans from noise exposure via PLDs. In addition, with the increasing popularity and accessibility of PLDs for personal music listening in teenagers and young adults, and the documented auditory symptoms and damage from long-term use, it is important to consider PLD usage as a risk factor for cochlear synaptopathy. ^{9 10 11 13} With the release of iOS 13, iPhone users gained a useful resource for monitoring noise exposure levels within the Health app ( https://www.apple.com/ios/health/ ). Apple integrated data about user's daily headphone listening levels (dBA) and exposure duration, and their criteria, are based on the WHO's PELs for music (75 dBA for 8 hours, 78 dBA for 2 hours, 81 dBA for 1 hour, and 84 dBA for 30 minutes), ⁸ which are stricter than PELs by OSHA and NIOSH. The iPhone Health app provides users with icons indicating whether their listening levels are “okay” or “loud” to help them to monitor their noise exposure risk on a daily, weekly, monthly, or yearly basis, or over a specific duration. The information provided within the iPhone Health app can be a useful tool not only to assess risk for noise-induced auditory symptoms but also to objectively classify risk for cochlear synaptopathy based on noise exposure levels and duration of exposure in young adult users of PLDs.

In previous research, high-risk individuals with suspected cochlear synaptopathy have demonstrated normal DPOAEs, and abnormally large summating potential (SP) amplitude with reduced action potential (AP) amplitude of the click electrocochleography (ECochG), resulting in an abnormally large SP/AP ratio, ^{12 13 16} consistent with findings in animal models. ^{15 23} In addition, suprathreshold click auditory brainstem response (ABR) has been measured to assess cochlear synaptopathy in humans, but findings were inconsistent between studies. Some researchers reported significant reductions of the ABR wave I amplitude in groups with high noise exposure risk, ^{21 25} consistent with confirmed cochlear synaptopathy profile in animal models, whereas others did not show a reduction of wave I amplitude. ^{22 26 27 28}

Those inconsistent findings may be related to differences in the study samples, that is, gender, age, noise exposure's level, and duration and susceptibility, ^{29 30 31} and the presence of tinnitus or hearing loss at EHFs. Research has shown that OHC damage due to noise exposure ⁹ and the presence of tinnitus can reduce ABR amplitudes and affect the waves V/I amplitude ratio, ²¹ not allowing for conclusion on whether those ABR findings are due to tinnitus or OHC damage, or cochlear synaptopathy. Those inconsistent findings between studies may also be related to recording parameter differences, such as the type of recording electrodes. Majority of studies were done using an ear canal TipTrode electrode to record ECochG ¹⁶ or/and ABR, ²⁶ and disposable surface electrodes to record ABR in humans, ^{21 27} which yield small and variable response amplitudes than when recording using a tympanic membrane electrode. ³²

Stimulus rate is another factor that could affect response latency and amplitude. Recording at fast click rates (e.g., 50–100 clicks/s) is usually used for neurodiagnostic evaluation to assess neural adaptation, and the recorded response is usually analyzed using the conventional signal averaging procedure. On the other hand, recording at rates faster than 100 clicks/s has been used for site-of-lesion testing and to further assess neural adaptation in both animals ^{33 34} and humans. ^{35 36} However, the recorded responses are overlapped and superimposed, making it difficult to identify and label individual peaks using the conventional signal averaging procedure. ^{37 38} In this case, a special algorithm such as the continuous loop averaging deconvolution (CLAD) mathematical technique is used to deconvolve and unwrap the complex, convoluted individual waves and create an undistorted, averaged response for labeling and analysis. ^{35 36} Further research is needed for simultaneous tympanic membrane recording of ECochG and ABR at fast click stimulus rates to assess neural adaptation and, thus, to increase the sensitivity of ECochG and ABR tests in detecting signs of cochlear synaptopathy in young adults. Previous studies on cochlear synaptopathy in young adults have also lacked an objective measure to classify risk. Researchers have mainly used subjective measures such as the Noise Exposure Questionnaire (NEQ) and self-reports to classify noise exposure, ^{16 39 40} or personal noise dosimeters to objectively classify noise-exposure risk for NIHL and cochlear synaptopathy. ^{41 41} A central limitation in these studies is that dosimeters were used to assess risk for NIHL and not assessing risk of cochlear synaptopathy. Also, dosimeters could not detect noise exposure levels from PLDs. There are currently no known studies that have utilized objective tools for classifying noise exposure risk levels in young adult PLD users, and no studies that have provided electrophysiologic evidence of cochlear synaptopathy at very fast click rates.

The purposes of this study were (1) to utilize the iPhone Health app as a risk analysis tool to objectively classify healthy young adults with normal hearing, who self-report as regular listeners of music using their iPhones, into low-risk and high-risk groups based on their listening sound levels and exposure duration, and (2) to identify signs of cochlear synaptopathy in the high-risk group compared with the low-risk group using both behavioral measures (i.e., noise questionnaire, EHF audiometry, and the Quick Speech-In-Noise [QuickSIN] test) and objective measures (i.e., DPOAE, and ECochG and ABR recordings with slow and fast click rates). The hypothesis is participants that are assigned into a high-risk group based on their iPhone Health app data will demonstrate behavioral and electrophysiologic signs of cochlear synaptopathy, mainly when recording ECochG and ABR at fast click rates.

METHODS

Participants

Thirty healthy female individuals, between the ages of 18 and 26 years, participated voluntarily in this study. All participants were native English speakers. Only females were recruited to reduce documented gender differences in results of audiometric and ABR tests. ^{27 28 43} Inclusion criteria included participants being an owner of an iPhone with the iOS 13 or newer and being a regular listener of music through headphones on their own device. The iPhone Health app was used to track their listening and noise exposure levels. Also, participants listening data were compared with WHO's PELs (i.e., cutoff levels) as an additional measure for grouping (see Table 1 ). Apple Inc. recommendations for tracking headphone listening levels and noise exposure data include usage of Apple Inc. headphones or Beats Inc. (a subsidiary of Apple) headphones for the most accurate measurements. Participants were required to report which type of headphones they utilized for listening to music and were included in the study only if they reported use of Apple or Beats headphones. While some Android devices have similar features to the iPhone Health app, there is a lack of uniform features/apps across different manufacturers of Android devices, and thus Android devices were not included in this study.

Table 1. iPhone Health App Listening Level Classification of Sound Levels (dBA) and Maximum Exposure Time Limit.

Listening sound level (dBA)	Maximum exposure time limit
	Over 7 d	Over 6 mo
75	127 h	3,048 h
80	40 h	960 h
90	4 h	96 h
100	24 min	9.6 h
110	2 min	48 min
120	14 s	5.6 min

Other inclusion criteria included (1) no history of otologic or neurological disorders, and no history of ototoxic medication use; (2) normal otoscopic examination, with clear ear canals and normal tympanic membrane ^{16 26} ; (3) pure tone air-conduction audiometric thresholds of 20 dB HL or better from 250 to 8,000 Hz; and (4) normal middle ear status with Jerger Type A tympanogram (normal static admittance, tympanometric peak pressure, and ear canal volume). ^{44 45} Participants completed the Noise Exposure Questionnaire (NEQ) ³ as a screening tool to ensure no participants had a history of any excessive noise exposure (i.e., occupational, episodic, or recreational) other than through the use of headphones, and no self-reported noise exposure in the 24 hours prior to testing to avoid a possible temporary threshold shift and/or tinnitus. The research protocol for this study was approved by the Institutional Review Board of Missouri State University (IRB-FY2021–45; July 29, 2020). All participants signed informed written consent prior to participation.

Group Classification

Participants were classified into two groups: low-risk ( n  = 15) and high-risk ( n  = 15), based on average noise exposure listening levels and exposure duration over a 6-month period obtained from their iPhone Health app. The choice of using noise exposure data over 6 months was to ensure chronic, permanent effects rather than acute, temporary overexposure with a possible recovery from a short-term overexposure. Participants who were recruited had no prior knowledge of the objective measures taken from their iPhone Health app. At the day of testing, their listening data were taken retrospectively from the prior 6-month period. To identify listening levels (in dBA SPL) and exposure duration in hours, data were accessed via “headphone audio levels” under the iPhone Health app. The steps for viewing and filtering listening data are based on Apple Inc. Web site. ⁴⁶ Table 1 shows the iPhone listening level classifications based on the cutoff levels for determining “OK” versus “Loud” classification within the iPhone Health app according to the WHO's PELs to classify exposure limits. Participants whose iPhone Health app indicated listening levels (in dBA SPL) under the maximum exposure limit were classified as “OK” or low-risk group, and those over the maximum exposure time limit period were automatically classified as “Loud” or high-risk group. Participant's listening data were also compared with WHO's PELs to ensure that those marked “OK” or “Loud” were accurately placed into low- and high-risk groups based on their exposure levels and durations. Fig. 1 shows an example of iPhone Health app listening data due to headphone use over a 6-month period from two participants: one from the low-risk group and one from the high-risk group. The listening data from the low-risk participant showed “OK,” indicating minimal noise exposure (63 dBA SPL). On the other hand, the listening data from the high-risk “Loud” participant revealed “Loud,” indicating excessive noise exposure (100 dBA SPL) that exceeded the cutoff levels.

Figure 1.

iPhone Health app listening data from a low-risk participant and a high-risk participant over a 6-month period. The listening data from the low-risk participant shows “OK,” indicating minimal noise exposure duration and level (63 dBA SPL) due to headphone use. In contrast, listening data from the high-risk participant show “Loud” due to excessive exposure to music (100 dBA SPL) via the iPhone headphone. iPhone Health app provides useful information as a risk analysis tool for objective classification of noise exposure risk.

Procedures

Behavioral Perceptual Measures

Participants were asked about the presence of tinnitus on a basic medical questionnaire. Participants were asked to elaborate on the characteristics of their tinnitus, that is, which ear(s), and occurrence (constant vs. intermittent). To assess perceived difficulties in a variety of listening situations, participants were given an eight-item listening situations self-report (see Appendix A ) to evaluate participant's perception of their abilities to hear/localize sound in specific situations in three categories: speech in quiet (one question), speech in noise (four questions), and sound localization (three questions), using a 10-point scale with 0 being “Not at all” to 10 being “Perfectly.” ¹⁶ Participants' air-conduction hearing thresholds were measured in a sound-booth over conventional frequencies (0.25–8 kHz) using TDH-39 headphones, and EHFs at 9, 10, 12, 14, 16, 18, and 20 kHz using Sennheiser HDA 200 headphones and a GSI AudioStar Pro audiometer. The QuickSIN test was administered monaurally to both ears at 70 dB HL through TDH 39 headphones, with recorded lists 1 and 2 being administered to the right ear and lists 3 and 4 being administered to the left ear using the GSI AudioStar Pro audiometer. ⁴⁷

Appendix A The Eight-Item Listening Situations Self-Report.

The following questions ask about your ability and experience in hearing and listening in different situations.

For each question, put a mark, such as a cross (X), anywhere on the scale that runs from 0 through 10, below each question. Putting a mark at 10 means you would be perfectly able to do or experience what is described in the question. Putting a mark at 0 means you would be unable to do or experience what is described.

We expect that all the questions are relevant to your everyday experience, but if a question describes a situation that does not apply to you, put a cross in the “not applicable” box.

1. You are in a group of about five people, sitting round a table. It is an otherwise quiet place. You can see everyone else in the group. Can you follow the conversation?

   • Not at all 0—1—2—3—4—5—6—7—8—9—10 Perfectly ☐ Not Applicable

2. You are talking with one other person. There is continuous background noise, such as a fan or running water close by. Can you follow what the person says?

   • Not at all 0—1—2—3—4—5—6—7—8—9—10 Perfectly ☐ Not Applicable

3. You are in a group of about five people in a busy restaurant. You CANNOT see everyone else in the group. Can you follow the conversation?

   • Not at all 0—1—2—3—4—5—6—7—8—9—10 Perfectly ☐ Not Applicable

4. You are talking to someone in a place where there are a lot of echoes, such as a church or railway station. Can you follow what the other person says?

   • Not at all 0—1—2—3—4—5—6—7—8—9—10 Perfectly ☐ Not Applicable

5. You are having a conversation with one person in a room where there are many other people talking. Can you follow what the person you are talking to is saying?

   • Not at all 0—1—2—3—4—5—6—7—8—9—10 Perfectly ☐ Not Applicable

6. You are sitting around a table or at a meeting with several people. You can't see everyone. Can you tell where any person is as soon as they start speaking?

   • Not at all 0—1—2—3—4—5—6—7—8—9—10 Perfectly ☐ Not Applicable

7. You are sitting in between two people. One of them starts to speak. Can you tell right away whether it is the person on your left or your right, without having to look?

   • Not at all 0—1—2—3—4—5—6—7—8—9—10 Perfectly ☐ Not Applicable

8. You are in an unfamiliar house. It is quiet. You hear a door slam. Can you tell right away where that sound came from?

   • Not at all 0—1—2—3—4—5—6—7—8—9—10 Perfectly ☐ Not Applicable

Objective Measures Using DPOAEs and Simultaneous Click ECochG and ABR

Distortion-Product Otoacoustic Emissions

DPOAEs were measured from both ears in a quiet room using the GSI Audera system and software (Grason-Stadler, Eden Prairie, Minnesota). DP-grams were elicited with two simultaneously presented “primary” tones (frequencies f ₁ and f ₂ ) at an f ₂ /f ₁ ratio of 1.21, with f ₂ frequencies varied from 1 to 12 kHz (996.1, 1,183.6, 1,418.0, 1,687.5, 2,003.9, 2,378.9, 2,824.2, 3,363.3, 3,996.1, 4,757.8, 5,660.2, 6,726.6, 8,003.9, 9,515.6, and 11,308.6 Hz). DPOAE level (at 2f ₁ –f ₂ ) was measured with L ₁  = 65 dB SPL and L ₂  = 55 dB SPL. Responses were considered present if the signal-to-noise ratio (SNR) was ≥ 6 dB.

Simultaneous Click ECochG and ABR

Stimulus and recording parameters of ECochG and ABR tests are listed in Table 2 . A two-channel Intelligent Hearing System Smart Evoked Potentials (IHS SmartEP) system, version 3.97, was used for simultaneous recording of both suprathreshold click ECochG and ABR using a custom-made extratympanic TM-electrode. ⁴⁸ A TM-electrode recording site provides robust ECochG and ABR responses due to recordings obtained closer to the generator sites resulting in a better SNR ratio and a reduced intersubject variability when compared with surface electrodes or TipTrode recording. ^{32 35q} ECochG responses were recorded using a horizontal montage (contralateral mastoid TM-electrode) and ABRs were recorded with a vertical montage (Fz-TM electrode) and a common ground electrode. Electrode impedances were kept between 2 and 5 kΩ. Click (100 μs) stimuli were presented with alternating polarity at 85 dB nHL. ^{12 36 49} Alternating polarity was used because it is the recommended polarity to record SP response that is independent of stimulus phase, and it eliminates stimulus artifact and cochlear microphonic wave that obscure both the SP and AP response. ⁵⁰

Table 2. Stimulus and Recording Parameters for the Simultaneous Click Electrocochleography (ECochG) and Auditory Brainstem Response (ABR) Recording.

Stimulus and recording parameters	Setting
Two-channel recording using custom-made TM-electrode	Channel A for ECochG and channel B for ABR  • Inverting (−): TM-electrode linked to both channels (A and B)   • Noninverting (+): contralateral mastoid (channel A + ) and high forehead (channel B + )   • Common ground: mid-forehead and the ground end of the TM-electrode lead
Stimulus characteristics	85 dB nHL, alternating 100-μs-duration clicks Three click rates: 19.5/s, 97.7/s, and 234.4/s
Bandpass filter	10–3,000 Hz
Amplification	100,000
Sweeps	2,000 for the 19.5/s and 97.7/s rates 2,500 for the 234.4/s rate
Artifact rejection	30%
Window	50 ms

Prior to recording ECochG and ABR, the TM-electrode was soaked in conduction gel for 15 minutes to ensure good conductivity. Then, it was placed gently into the ear canal close to rest against the tympanic membrane, and an insert earphone with a pediatric size foam insert ear tip was placed into the ear canal for sound delivery. Participants were seated in a comfortable recliner in a sound-booth and were asked to relax and close their eyes for the duration of testing. The recordings were conducted monaurally in a randomized order, that is, the left ear being tested first in half of the participants, and the right ear being tested first in the other half.

The recordings were obtained at three different click rates: a slow rate (19.5/s) and two fast rates (97.7/s and 234.4/s). Two repeatable tracings were recorded for each condition. Each trace was derived from averaging of 2,000 sweeps at the lower rates (19.5/s and 97.7/s) and of 2,500 sweeps at the 234.4/s rate to improve SNR. The two fast rates were chosen to assess neural adaptation of the auditory nerve, without sacrificing the ECochG and ABR morphology at a faster rate (e.g., above 500/s). ³⁷ Research has shown that testing at a fast stimulus rate improves detection of SP wave by separating it from the AP wave. ^{35 36} However, recording at a fast click rate, such as 234.4/s in this study, would result in a sequence of four overlapped (convolved) ECochG (or ABR) individual waves in each recorded trace within a 50-ms window, making it hard to analyze this complex waveform without deconvolving individual waves, that is, using the CLAD technique. Fig. 2 illustrates a representative click ECochG responses at three click rates from a participant in the low-risk group prior to and after deconvolving the response using the CLAD technique. The top panel ( A ) of Fig. 2 illustrates two repeatable traces at each click rate of the non-deconvolved ECochG responses from both ears. At the slow rate, 19.5/s, the SP and AP waves were identifiable and marked in both ears. However, at fast click rates (97.7/s and 234.4/s), the waves were not identifiable and could not be marked because the responses were overlapped (convolved), resulting in a complex response in a 50-ms window. The bottom panel ( B ) of Fig. 2 shows the deconvolved, averaged click ECochG responses after applying the CLAD technique, resulting in identifiable and easily marked SP and AP waves mainly at the two fast click rates. Moreover, as the click rate increased from 19.5/s to 97.7/s to 234.8/s, the SP wave separated from the AP wave and the AP amplitude decreased due to physiological neural adaptation. Therefore, the use of the CLAD technique is beneficial for recording auditory evoked potential at fast stimulation rates to unwrap and deconvolve the complex responses for labeling and analysis.

Figure 2.

Click ECochG responses at three click rates from one of the participants in the low-risk group prior to deconvolution ( A) and after using continuous loop averaging deconvolution (CLAD) technique ( B ). ( A ) Recorded click ECochG non-deconvoluted responses without the use of the CLAD technique. At the slow rate (19.5/s), the SP and AP waves were identifiable and marked in both ears. At fast click rates, the waves were not identifiable and could not be labeled because the responses were overlapped (convoluted), resulting in a complex waveform of approximately four overlapped ECochG responses in a 50-ms window at 234.8/s click rate. ( B ) The deconvolved, averaged click ECochG responses after applying the CLAD technique, resulting in identified and easily marked SP and AP waves mainly at the fast click rates. Moreover, as the click rate increased from 19.5/s to 97.7/s to 234.8/s, the SP wave separated from the AP wave and the AP amplitude decreased due to physiological neural adaptation. Figs. 8 and 9 also show deconvolved, grand averaged click ECochG and ABRs, respectively, after applying CLAD.

ECochG and ABR Response Labeling

Two repeatable traces of ECochG and ABR waves recorded at each rate were deconvolved using CLAD and then averaged. Both ECochG response (base, SP, AP) and ABR waves (I, III, V) were labeled independently by the first and the second authors. The inter-rater reliability of both ECochG and ABR data was judged to be high, with labeling of each ECochG and ABR component being within 0.01 ms for all testing conditions. All labeling was completed using IHS-Smart EP system recommendations for base (lowest point around 0.3–0.5 ms latency where the SP response usually begins), SP response (the highest “peak” among the first deflection in the response), and AP response (the highest “peak” which occurred 0.5–1.5 ms after stimulus onset). The SP amplitude and AP amplitude were labeled from peak to base, and then SP/AP amplitude ratio and SP/AP area ratio were calculated automatically by the IHS-Smart EP system. Click ABR wave I and wave V peak amplitudes were measured from peak to the following largest trough, and the absolute latency was measured from the stimulus onset to the positive peak of each wave.

Statistical Analysis

Descriptive and inferential statistical analyses were conducted to compare results of both groups for behavioral measures (reports of tinnitus, averaged percentage score of each of the three categories of the eight-item listening situations self-report, EHF thresholds, and QuickSIN scores) and objective measures (DPOAE levels, ECochG SP/AP amplitude and area ratios, and ABR waves I and V amplitude and latency measures for the three click rates). Wave III was not included in the statistical analysis because it was small-to-indiscernible at the two fast rates. A two-tailed, independent samples t -test was performed to assess differences between the high- and low-risk groups regarding their listening scores of the eight-item listening situations self-report. To determine group differences in the EHF thresholds, a 2 (group) × 2 (ear) × 3 (frequency range) analyses of variance (NOVA) test was performed for three frequency ranges (9–10 kHz, 12–16 kHz, and 18–20 kHz) instead of individual high frequencies, ^{16 51} to reduce repeated measure analysis with reduced power in the analysis. Another 2 (group) × 2 (ear) ANOVA was performed for QuickSIN scores. Also, a series of ANOVAs with repeated measures and post hoc pairwise comparisons was conducted to compare DPOAE response amplitudes between groups [2 (group) × 2 (ear) × 4 (f ₂ frequency range)], the SP/AP amplitude and area ratios, and ABR wave I and V amplitudes and absolute latencies between groups [2 (group) × 2 (ear) × 3 (click rate)]. All group comparisons and post hoc multiple comparisons with a Bonferroni correction were considered significant at α level of ≤0.05. Analyses were conducted using the JASP stats software, version 0.8.1.2.

RESULTS

iPhone Health App Listening Levels and Exposure Duration as a Risk Analysis Tool

Data from the iPhone Health app (see Table 3 ) showed statistically significant higher levels of exposure in participants in the high-risk group (91.1 dBA SPL) than in the low-risk group (69.1 dBA SPL), [ t (28)  = 15.976, p < 0.001, Cohen's d = 5.833 ], as well as longer exposure duration, 197 versus 76.7 hours, [ t (28)  = 3.049, p < 0.005, Cohen's d = 1.113 ]. The data for the high-risk group exceeded both the iPhone Health app classification of having at least 4 hours of exposure time at 90 dBA over 7 days or 96 hours over 6-month period (see Table 1 ) and WHO PEL recommendation of only 30 minutes of exposure time at 84 dBA listening level; none of the data for the low-risk group exceeded these limits. ³⁰

Table 3. Mean (±Standard Error) of iPhone Health App Listening Levels and Exposure Duration (Hours) Over 6-Month in the High-Risk and Low-Risk Groups ( N  = 15 Per Group) .

	Listening levels (dBA)	Exposure duration (h)
Low-risk group	69.1 ± 1.0	30.9 ± 8.0
High-risk group	91.1 ± 0.9	197.1 ± 38.7

Overall findings from the high-risk participants suggest a profile consistent with cochlear synaptopathy profile. These include normal hallmark features and abnormal hallmark features of cochlear synaptopathy profile.

Normal Hallmark Profile of Cochlear Synaptopathy

Conventional and Extended High-Frequency Pure-Tone Thresholds

Pure-tone audiometric data showed that all participants had normal hearing thresholds for both conventional and EHF. Fig. 3 displays mean pure-tone EHF hearing thresholds between 9 and 20 kHz for both groups, split by ears and grouped by frequency range (9–10 kHz, 12–16 kHz, and 18–20 kHz). The result of the 2 (group) × 2 (ear) × 3 (frequency range) ANOVA with repeated measures revealed no significant difference for ear [ F (1.28) = 3.556, p  = 0.070, η _p²  = 0.113], frequency [ F (2.56) = 2.689, p  = 0.096, η _p²  = 0.088], or group [ F (1.28) = 0.016, p  = 0.899, η _p²  = 0.000]. Also, there was no significant difference for any interaction effects ( p  > 0.05).

Figure 3.

Mean extended high-frequency hearing thresholds from 9 to 20 kHz of both ears in both groups. There is no significant difference in hearing thresholds within the three frequency ranges (9–10, 12–16, and 18–20 kHz) between the high-risk group (dashed line) and the low-risk group (solid line) in both ears.

Distortion-Product Otoacoustic Emissions

Fig. 4 displays the means and standard errors of DPOAE amplitudes for the two groups split by ear. DPOAEs were present in all tested f ₂ frequencies from 1 to 12 kHz for both ears of all participants in the low- and high-risk groups. Results of the 2 (group) × 2 (ear) × 4 (f ₂ frequency range) ANOVA showed no significant main effect of ear, [ F (1.28) = 0.818, p  = 0.052, ηp2  = 0.002, and no group difference, [ F (1.28) = 0.011, p  = 0.916, ηp2  = 0.000, and no significant two-way or three-way interactions ( p  > 0.050). As expected, there was a significant main effect of f ₂ frequency, [ F (3.84) = 47.343, p  < 0.001, η _p²  = 0.628]. Post hoc comparisons with a Bonferroni correction showed that the DPOAE amplitude was smaller in the highest f ₂ frequency range (9–12 kHz) in both groups than for lower f ₂ frequencies (1–5 kHz; p  < 0.005).

Figure 4.

Mean DPOAE response amplitude for the low- and high-risk groups for both ears in four ranges of f ₂ frequencies from 1 to 12 kHz. DPOAE responses were present bilaterally in both groups (low risk: solid line, high risk: dashed line) at all tested f ₂ frequencies grouped by frequency range. The standard errors of the mean and the noise floor levels (thin lines) are shown per ear and group.

Abnormal Hallmark Perceptual and Electrophysiologic Profile of Cochlear Synaptopathy

Tinnitus Perception and the Eight-Item Listening Situations Self-Report

When asked about tinnitus, more than twice as many participants in the high-risk group (12 out of 15) reported having tinnitus than those in the low-risk group (5 out of 15). Of the 12 high-risk participants with tinnitus, 8 characterized their tinnitus as intermittent ringing and 4 as constant multitonal. None of the five participants in the low-risk group reported constant or multitonal tinnitus. This finding may suggest that having ringing or multitonal tinnitus in the presence of normal hearing is a sign that fits into the profile of cochlear synaptopathy.

Participants in the high-risk group had slightly lower overall score (56.9 ± 9.8) than participants in the high-risk group (60.4 ± 8.2) on the eight-item listening self-report (see Appendix A ), as well as a lower score at each of the three categories (speech in quiet, speech in noise, and sound localization) as depicted in Fig. 5 . These results indicate that participants in the high-risk group reported slightly more difficulty (a lower score) in listening situations than participants in the low-risk group (a higher score). However, results of the independent samples t -test revealed no statistically significant difference in the overall score between the two groups for those three listening situations [t(28) =    −   1.050, p = 0.303, d =    −   0.380] .

Figure 5.

Mean (and standard errors) rating percentage for three categories on the eight-item listening situations self-report of the low-risk and high-risk groups. While the findings did not represent a significant difference, the high-risk group (black bars) did have a lower self-rating percentage, i.e., slightly more difficulty in all listening situations, than the low-risk group (gray bars).

QuickSIN Results to Assess Difficulty Hearing Speech in Noise

Ability to hear speech in noise was assessed using the QuickSIN test. Higher scores on the QuickSIN are indicative of a greater difficulty of understanding speech in noise than lower scores. Scores in the range of 0 to 3 dB indicate within normal abilities, whereas scores in the 3 to 7 dB, 7 to 15 dB, or greater than 15 dB SNR range are indicative of mild, moderate, or severe difficulty of speech perception in noise. ⁴⁷ Fig. 6 shows that for both groups, QuickSIN test scores were within normal range (<3 dB SNR), with slightly higher scores, yet more variable, in both ears, mainly the left ear, of the high-risk group as compared with the low-risk group. Results revealed a statistically significant group effect and group × ear interaction effect ( p  < 0.025), but there was no significant main effect for the ear ( p  = 0.961). Post hoc tests with the Bonferroni correction revealed that the significant group × ear interaction effect was related to groups, not ear, as the paired t -test for ear was not significant ( p  = 0.154), mostly due to larger variability in the high-risk group.

Figure 6.

Mean QuickSIN scores for the low- and high-risk groups for both ears. The high-risk group having significantly increased QuickSIN scores, more visible in the left ear, compared with the low-risk group. Results showed no significant ear effect, mostly due to the high variability in the high-risk group. The thin lines represent the standard error of the mean, which also shows larger variability in the high-risk group.

Click ECochG to Assess Inner Hair Cells and Eighth Nerve Function

SP/AP Amplitude Ratio

The SP/AP amplitude ratio was within normal limits in all participants in the low-risk group at all three click rates (0.31, 0.36, and 0.47) in agreement with Kaf et al's findings. ³⁵ On the other hand, about half of the participants (7 of 15) in the high-risk group had abnormally large (e.g., at least 0.05 μV larger) SP amplitude, and thus large SP/AP amplitude ratio at the slow rate, increasing to 12 participants with abnormal ratios at the two fast rates. Fig. 7 depicts the mean SP/AP amplitude ratios for the low- and high-risk groups split by ears, showing differences between the two groups, except in the left ear at the slowest click rate (19.5/s). Table 4 summarizes the 2 (group) × 2 (ear) × 3 (click rate) ANOVA findings of the SP/AP amplitude ratio and area ratio. Results show a significant group effect and rate effect, with no significant main effect of ear or interactions. Post hoc tests with a Bonferroni correction revealed that the SP/AP amplitude ratio increased as the click rate increased from the slowest (19.5/s) to the highest (234.4/s) rate (p  = 0.004) due to neural adaptation at fast rates. The difference between the two groups is due to abnormally large SP/AP amplitude ratio in the high-risk group at the three click rates (19.5/s to 97.7/s and 234.4/s and 97.7/s and 234.4/s).

Figure 7.

Mean SP/AP amplitude ratio of both ears of the low-risk and high-risk groups. High-risk group (gray bars) have significantly larger SP/AP amplitude ratio than the low-risk group (black bars) at the three click rates (19.5, 97.7, 234.4 per second) in both ears, except in the left ear at the slow rate (19.5/s). The standard errors of the mean are shown per ear and group at each click rate.

Table 4. Summary of the 2 (Group) × 2 (Ear) × 3 (Rate) ANOVA of Click SP/AP Amplitude and Area Ratio Findings between the Low-Risk and High-Risk Groups ( N  = 15 Per Group) .

	SP/AP amplitude ratio				SP/AP area ratio
Main effects	F	df	p	η p2	F	df	p	η p2
Rate	6.227	2.56	0.004 a	0.210	5.567	2.56	0.026 b	0.195
Ear	0.179	1.28	0.676	0.006	1.278	1.28	0.291	0.084
Group	6.186	1.28	0.001 a	0.291	4.968	1.28	0.003 a	0.213
Interaction effects
Rate × ear	1.028	2.56	0.433	0.045	1.949	2.56	0.356	0.046
Rate × group	1.674	2.56	0.532	0.014	1.747	2.56	0.292	0.042
Ear × group	2.289	1.28	0.378	0.076	1.696	1.28	0.238	0.049
Rate × ear × group	2.728	2.56	0.210	0.067	1.691	2.56	0.246	0.075

Abbreviations: df, degrees of freedom; F, F statistic; p , significance level; η _p ² , partial eta square.

^aSignificance at < 0.005.

^bSignificance at <0.05.

SP/AP Area Ratio

Fig. 8 depicts the averaged, deconvolved SP/AP area ratio of a participant from the high-risk group showing within normal SP/AP area ratio (≤1.94) at the slow rate (19.5/s). In agreement with the mean data of larger SP/AP amplitude ratio in the high-risk group than the low-risk group, Fig. 8 displays the abnormally large SP/AP area ratio in both ears, more on the right ear, at the two fast rates (97.7/s and 234.4/s). This abnormally large SP/AP area ratio is mainly due to the abnormally large SP amplitude at the two faster rates. Table 3 summarizes the 2 (group) × 2 (ear) × 3 (rate) ANOVA area ratio results between the two groups. Results showed a significant main effect of rate ( p  = 0.026), group effect (p  = 0.003), with no main effect of ear ( p  = 0.291) nor interactions. Post hoc comparisons with a Bonferroni correction revealed that the SP/AP area ratio significantly increased as the click rate increased from the slowest to the highest rate ( p  = 0.014). The SP/AP area ratio was significantly larger in the high-risk group than in the low-risk group at all three click rates ( p  = 0.014 at 19.5/s, p  = 0.001 at 97.7/s, p  = 0.005 at 234.4/s).

Figure 8.

Averaged, deconvolved click ECochG response from both ears shows the SP/AP area ratio from a representative participant from the high-risk group at the three click rates. SP area is shown in yellow, and the AP area is shown in green; SP amplitude and AP amplitude are thin black lines from peak to base. The SP/AP amplitude ratio is measured from baseline to peak of SP and baseline to AP wave as shown on the ECochG response to 19.5/s on the left ear. The significantly large SP amplitude and the relatively small AP of both ears at the two fast rats result in abnormally large SP/AP amplitude and area ratios in the high-risk group. Although the SP/AP area ratio at the slow rate (19.5/s) is within a normal range on both ears (1.31 and 1.59), the area ratio is abnormally large at the two fast rates (97.7/s and 234.4/s), suggesting a profile consistent with cochlear synaptopathy. Note the clear separation between the SP and AP waves at the two faster rates and the smaller AP amplitude with increasing click rate.

Click ABR to Assess Eighth Nerve and Brainstem Neural Function

ABR Amplitude and Latency Findings

Fig. 9 displays grand averaged, deconvolved ABR waveforms from each ear of both groups at the three click rates. Both groups show, as expected, a small decrease in amplitude and a prolongation in latency of all waves as click rate was increased. The results of the 2 (group) × 2 (ear) × 3 (rate) ANOVA revealed no significant main effect of ear nor group, but there was a significant main effect of rate for all three waves ( p  < 0.001) for both amplitude and latency responses. Post hoc comparisons showed a significant difference at all pairwise comparisons of rate ( p  < 0.001) due to a decrease in amplitude and increase in latency as the rate increased from 19.5/s to 97.7/s, 19.5/s to 234.4/s, and 97.7/s to 234.4/s for all three waves. Fig. 9 also shows that the ABR waves I and V were smaller in amplitude for the high-risk group at the two fastest click rates compared with the low-risk group. However, there were no significant differences for waves I or V amplitude and latency between the two groups (see Table 5 ). As shown in Table 5 , the only significant interaction was the rate × group interaction ( p  < 0.046) due to smaller wave I amplitude at the two fast click rates (97.7/s and 234.4/s) for the high-risk group compared with the low-risk group; this finding also supports the importance of recording click ABR at fast click rates. Wave V/I amplitude ratio was not measured in this study because recording click ABR to a tympanic membrane electrode or a TipTrode electrode compared with a mastoid electrode results in recording a large wave I amplitude, but a smaller wave V amplitude. ^{52 53}

Figure 9.

Grand, deconvolved averaged ABR waveforms from the high-risk and low-risk groups are plotted across alternating click rates. The mean traces are superimposed to show the difference in the ABR amplitude and latency responses between the low-risk group (black traces) and high-risk group (gray traces) at the three click rates (19.5/s, 97.7/s, and 234.4/s). Compared with the low-risk group, the high-risk group has relatively smaller waves I and V amplitudes (measured from peak-to-trough) at the two fastest rates (97.7/s and 234.4/s), but no difference in latency response. Similar to ECochG findings, recording click ABR to alternating polarity allows the recording of SP response. It is obvious that the SP response of the ABR is abnormally larger in the high-risk group compared with the low-risk group in both ears at the three click rates. These findings of large SP and relatively smaller ABR waves are consistent with signs of cochlear synaptopathy in the high-risk group. Also, note the noticeable separation of the SP wave from wave I (a.k.a. AP wave) with a relatively consistent SP latency (a receptor potential) as click rate increases, which enhances detection of the SP wave and assesses neural degradation of auditory nerve and brainstem neurons.

Table 5. Summary of the 2 (Group) × 2 (Ear) × 3 (Rate) ANOVA Results for Click ABR Amplitude in μV ( Latency in ms ) Findings between the Low-Risk and High-Risk Groups ( n  = 15 Per Group) .

	F		df	p		η p 2
Main effects	Wave I	Wave V		Wave I	Wave V	Wave I	Wave V
Rate	46.7 (74.9)	67.6 (1.2)	2.56	<0.001 a (<0.001 a )	<0.001 a (<0.001 a )	0.721 (0.732)	0.715 (0.980)
Ear	0.43 (0.02)	5.54 (7.23)	1.28	0.521 (0.736)	0.056 (0.063 )	0.015 (0.005)	0.165 (0.212)
Group	2.37 (0.17)	0.32 (0.01)	1.28	0.137 (0.682)	0.567 (0.980)	0.082 (0.007)	0.010 (0.001)
Interaction effects
Rate × ear	0.11 (0.28)	4.86 (0.92)	2.56	0.812 (0.631)	0.062 (0.423)	0.003 (0.011)	0.147 (0.042)
Rate × group	4.18 (0.13)	1.27 (0.91)	2.56	0.046 b (0.910)	0.293 (0.422)	0.131 (0.006)	0.054 (0.031)
Ear × group	0.43 (0.02)	2.12 (1.23)	1.28	0.521 (0.921)	0.137 (0.298)	0.016 (0.001)	0.071 (0.038)
Rate × ear × group	0.13 (1.03)	2.01 (3.81)	2.56	0.911 (0.337)	0.145 (0.056)	0.001 (0.034)	0.53 (0.126)

Abbreviations: df, degrees of freedom; F, F-statistic; p , significance level; η _p ² , partial eta square.

^aSignificance at <0.005.

^bSignificance at <0.05.

DISCUSSION

The main purpose of this research was to use the iPhone Health app as a tool to objectively classify risk for noise exposure in normal-hearing young adult female listeners to music via their personal iPhones and to identify signs of cochlear synaptopathy using behavioral and physiological tests.

Group Classification Using iPhone Health App

As shown in Table 3 , significant differences in listening level (91.1 vs. 69.1 dBA SPL) and duration exposure (197.1 vs. 76.7 hours) between the two groups were found based on their iPhone Health app data. The listening level and exposure duration of participants in the high-risk group have exceeded all PELs by WHO, ⁸ OSHA, ⁶ and NIOSH ⁷ guidelines. These data indicated that the iPhone Health app is not only an objective measure but a useful tool for assessing risk for cochlear synaptopathy.

Normal Hearing and DPOAE Profile of Cochlear Synaptopathy

Hearing Thresholds at Conventional and Extended High Frequency

The presence of normal conventional (250–8,000 Hz) pure-tone audiometric thresholds in both groups is consistent with previous animal and human findings of a cochlear neural degeneration between IHCs and type I ANFs without cochlear hair cells damage. ^{12 15 16 21 27 54} Given the theory that cochlear synaptopathy results from excessive noise exposure, it is reasonable to consider a potential increase (i.e., hearing loss) in EHF thresholds in those with cochlear synaptopathy. ^{55 56} Guest at el have evaluated EHF thresholds in relation to cochlear synaptopathy and reported increased thresholds at 10 and 14 kHz among high-risk participants but did not report if the EHF threshold shifts were significant. ²² Prior studies have shown statistically significant increases in EHF thresholds at every frequency tested in participants at risk for noise exposure ^{16 51} ; however, in our study, there were no significant differences between groups found, which conflicts with findings of other studies. A possible explanation for the lack of threshold shift in the EHF region in our study is because any exposure to loud recreational noise 24 hours prior to testing was ruled out. In addition, we used an average of EHF range to reduce repeated measures analysis with reduced power in the analysis, while other studies analyzed differences between groups at individual frequencies. ^{16 51} It is important to note that peripheral hearing loss in EHF can contribute to poor speech perception in noise ^{51 57 58 59} and decreased ABR wave I (a.k.a. AP response of the ECochG) amplitude, ⁴³ and in this case such findings are signs of EHF hearing loss but not necessarily signs of cochlear synaptopathy.

Distortion-Product Otoacoustic Emissions

DPOAEs provide an opportunity to evaluate the function of OHCs. ⁶⁰ Previous studies have reported reduced or absent DPOAEs among individuals with OHC damage due to noise exposure. ^{39 40 61} On the other hand, individuals with suspected cochlear synaptopathy are expected to have normal OHC function, and thus normal DPOAE amplitudes, ^{23 27 51 62} also supported by the findings of the current study. While DPOAEs may not be sensitive for detecting those with cochlear synaptopathy with concomitant OHCs damage, DPOAE should be measured as a resource for distinguishing between cochlear pathology and cochlear synaptopathy.

Abnormal Perceptual and Electrophysiologic Profile of Cochlear Synaptopathy

The Eight-Item Listening Situations Self-Report

Many researchers have highlighted that speech in noise difficulties may be a defining symptom of cochlear synaptopathy. ^{16 21 22} In this study, the Eight-Item Listening Situations Self-Report Questionnaire ¹⁶ and the QuickSIN test were used to assess hearing difficulty in noise and in different listening situations combined with the NEQ to rule out exposure to loud occupational noise. Findings of the eight-item listening situation self-report revealed that the high-risk groups perceived slightly more difficulty in all listening situations, but without significant difference between the two groups: speech in quiet (86 vs. 95%), speech in noise (79 vs. 84%), and sound localization (88 vs. 92%) for the high- and low-risk groups, respectively. Liberman et al ¹⁶ reported that their high-risk group experienced significant difficulty only for speech in noise abilities, with no difference between low-risk group for speech in quiet (scores over 95% for both groups) and localization (88% vs 93%) on the same questionnaire. A possible explanation for the lack of difference in speech in noise ability in the current versus Liberman et al ¹⁶ could be attributed to (1) age of participants (18–26 years in this study vs. 18–41), (2) gender (females only in this study vs. both genders with more males in the high-risk group but more females in the low-risk group), (3) group classification method (iPhone Health app in this study vs. self-reports), (4) duration of noise exposure (6 months in this study vs. not specified), and (5) EHF thresholds (within normal with no difference between the two groups in this study vs. elevated threshold at EHF in the high-risk group than the low-risk group). In addition, the lack of significant differences between low- and high-risk groups on the eight-item listening situation self-report may be influenced by the lack of accuracy in reporting and self-recall of noise exposure levels without accounting for exposure duration.

Presence of Tinnitus in the High-Risk Group

The presence of tinnitus is a proposed hallmark sign of cochlear synaptopathy in humans. ^{21 22} The findings of this study did indicate that participants in the high-risk group were over twice as likely to suffer from tinnitus as compared with the low-risk group. Also, four participants in the high-risk group reported having the distinct characteristic of constant multitonal tinnitus. Interestingly, these four participants exhibited increased SP/AP amplitude and area ratios in the presence of normal hearing and normal DPOAEs. There have been no known studies that have discussed the presence of multitonal tinnitus in individuals with possible cochlear synaptopathy. Prior studies have reported tinnitus characteristics from tinnitus pitch and loudness match tests ²¹ and self-described characteristics (e.g., ringing, high pitched whine, shooshing), ⁶³ with no mention of multitonality. However, a recent study ⁶⁴ compared EHF thresholds and tinnitus in normal-hearing adults group with tinnitus (43 ears; mean age = 28.0 ± 4.7 years) and a matched control group (68 ears) using tinnitus pitch matching at several frequencies (0.125, 0.25, 0.5, 1, 2, 4, 8, and 10 kHz). They did note that participant's tinnitus was matched to the 10 kHz as the dominant tinnitus pitch regardless of the EHF thresholds (10–20 kHz mean = 19.7 ± 7.9 dB), which suggests they may have experienced multitonal tinnitus. ⁶⁴ Our finding is that the perception of tinnitus, mainly constant multitonal tinnitus, may be an indicator of cochlear synaptopathy, but further investigation is warranted into the relationship between cochlear synaptopathy and multitonal tinnitus.

QuickSIN Score

Although the scores of the QuickSIN test for both groups were within normal range for signals presented monaurally at 70 dB HL (i.e., <3 dB SNR), statistical analysis indicated a significantly increased (worse) QuickSIN scores in the high-risk group in both ears than those in the low-risk group. Participants in the high-risk group had relatively poorer scores in the left ear (1.8) than in the right ear (1.2), while low-risk participants had similar scores in both ears (i.e., 0.9 and 0.8 for the left and right ears, respectively). This could be partly attributed to a large variability of the QuickSIN score in the high-risk group. Similar results of poorer scores in left ears than scores in right ears were reported in participants with tinnitus and at high risk for cochlear synaptopathy, using QuickSIN test (2.57 vs. 1.54) ⁶⁵ or other speech discrimination in noise tests. ⁵¹

Click ECochG: Abnormal Findings in the High-Risk Group

Based on results of animal and human studies, it is postulated that cochlear synaptopathy occurs as a result of damage to the IHC synapses with ANF, particularly those with low-SR and high thresholds. ^{12 13 14 15 54} This is supported by suprathreshold recording of abnormally robust SP amplitude with decreased or unchanged AP amplitude, creating increased SP/AP amplitude ratio at slow click rates. ^{16 35} At the slow rate, the mean SP/AP amplitude ratio (0.31) in our low-risk group, collapsed by ears, was very close to the value reported for other low-risk groups (<0.356) ^{16 66} and the normative value (0.25), ³⁵ whereas the participants in the high-risk group had abnormally large SP/AP amplitude ratio (0.47) that is consistent with the previous ratio of 0.46 reported by Liberman et al for patients with symptoms consistent with the cochlear synaptopathy profile. ¹⁶ At the two fast click rates, the mean SP/AP amplitude ratios (0.36 and 0.47) for low-risk participants showed comparable values to normative data reported by Kaf et al using the same protocol (TM-electrode recording and the same fast click rates). ³⁵ In contrast, the SP/AP amplitude ratios from the high-risk group recorded at the two fast rates (0.76 and 0.79) were abnormally higher than those from the low-risk group and above the normative values. ³⁵ Overall, the SP/AP amplitude ratio in the high-risk group was twice that of the low-risk group mainly at the two fast click rates. These findings are consistent with the data of Liberman et al ¹⁶ which reported a slow rate between the two groups (0.46 vs. 0.26), ¹⁶ even though there were differences in the protocols. Our findings support the possibility of cochlear synaptopathy in the high-risk group and the need for recording ECochG at fast click rates for individuals at risk for such a pathology.

Assessment of the SP/AP area ratio in conjunction with the SP/AP amplitude ratio is mainly used in the diagnosis of Meniere's disease. ^{67 68} The same approach was included in the current study to improve the likelihood of detection of cochlear synaptopathy by analyzing the SP/AP area ratio between the two groups. To the best of our knowledge, there was only one unpublished data (S. L. C., The University of British Columbia, 2017) that assessed SP/AP area ratio to identify signs of cochlear synaptopathy. In this study, 18 music students (high-risk group) with a history of exposure to loud music were compared with nonmusic students (control group). ⁶⁹ Chang reported no significant differences between the high-risk group and the control group for mean SP/AP area ratios (1.8 vs. 1.5) and mean amplitude ratios (0.25 vs. 0.19), respectively. ⁶⁹ The lack of a difference in Chang's study was attributed to a lack of significant difference in noise exposure history, based on the Noise Exposure Structured Interview (NESI), between both groups. In the current study, the mean SP/AP area ratio was significantly higher in the high-risk group (2.13) compared with the low-risk group (1.74) and to normative upper cutoff of 1.94 (range of 1.02–1.75) at a slow (11.3/s), click rate. ^{66 68} Moreover, at the two fast click rates, the SP/AP area ratio significantly increased for the high-risk group and it was twice that of the low-risk group at the 97.7/s rate (2.95 vs. 1.9), and it was three times higher (8.81 vs. 2.33) at the fastest (234.4/s) click rate. The increase of the SP/AP amplitude and area ratios as click rate increase is due to a physiological degradation of AP (wave I) amplitude in the low-risk group. ³⁵ The abnormal increase in the SP/AP amplitude and area ratios in the high-risk group may be due to abnormal neural desynchronization and a lower number of nerve fibers firing at fast click rates without a change in the SP amplitude, ^{70 71} which is a potential mechanism in cochlear synaptopathy. The overall findings indicate that both SP/AP amplitude and area ratios, mainly at fast click rates, are useful in the diagnosis of cochlear synaptopathy profile in high-risk participants. Further recording of ECochG at fast click rates may help identify the site-of-lesion (presynaptic vs. synaptopathy vs. postsynaptic).

Click ABR: Lack of Abnormal Findings in the High-Risk Group

In addition to click ECochG being the primary measure of choice for studying hair cell and auditory nerve function, click ABRs have also been a popular measure to study auditory function (specifically wave I and wave V/I amplitude ratio) in participants at risk for cochlear synaptopathy. Results of the ABR recordings regarding mainly wave I amplitude were inconclusive in prior studies, with some reporting significant differences, ^{21 26 25 54 72 73 74} while others found no significant differences between controls and participants with suspected cochlear synaptopathy. ^{21 22 27 ,} Similar to our AP amplitude data, our ABR findings revealed reduced mean wave I amplitude for the high-risk participants compared with the low-risk participants (control group) at all three click rates: 19.5/s (0.51 vs. 0.70 µV), 97.7/s (0.34 vs. 0.44 µV), and 234.4/s (0.20 vs. 0.34 µV), but it did not reach statistically significant difference between the two groups. Also, wave V was slightly smaller in the high-risk group than in the low-risk group at all three click rates (0.49, 0.47, 0.29 vs. 0.51, 0.50, 0.36 µV). Despite smaller wave I and wave V amplitudes in the high-risk group, response amplitude and absolute latency of waves I and V did not differ significantly between the two groups at any of the three click rates, which may rule out a lesion proximal to the auditory nerve and may suggest presence of a central compensation mechanism as a result of a neural deficit affecting wave I. ^{21 54} However, our findings of a significant rate × group interaction of wave I along with a relatively small wave I amplitude at the two fast click rates in the high-risk group may support a possible loss of synapses between IHC and type I ANF and abnormal neural dyssynchrony in those participants. This possible conclusion is based on human temporal bone histopathological studies that have shown a correlation between age-related reduction in wave I amplitude and cochlear neuronal degeneration of synaptic ribbons and spiral ganglion cells. ^{75 76}

However, confounding factors such as high-frequency hearing loss, hair cell damage in the basal turn of the cochlea, transducer, and the presence of tinnitus may result in reduction of wave I amplitude. Current data of normal EHF thresholds and normal DPOAEs in the high-risk group suggest that the slight reduction in wave I amplitude in the high-risk group may potentially be an early sign of cochlear synaptopathy and not due to hair cell damage or high-frequency hearing loss. It is also possible that suprathreshold recording of ABR at 85 dB nHL and using E-A-RTONE 3A insert earphones with a flat frequency response up to 4 kHz could result in a reduction of wave I amplitude due to reduced neural contribution from the basal region of the cochlea to the generation of wave I. ⁷⁷ However, these factors could be ruled out since reduction of wave I amplitude was seen only in the high-risk group and not in the low-risk group of our study, and previous studies have reported a similar trend of decreased wave I amplitude in the high-risk group whether recorded with E-A-RTONE 3A ^{16 78 79} or another transducer (ER2 insert earphones) ²⁴ with a broader-frequency response and a higher output above 4 kHz. It is also possible that the presence of tinnitus with normal audiogram may be a contributing factor in the reduction of wave I amplitude in the high-risk group. ²¹ Similar to previous animal and human studies, the current ABR findings are inconclusive and do not provide additional information regarding a possible cochlear synaptopathy profile in the high-risk group. ^{16 27 63} However, recording ABR simultaneously with ECochG could provide valuable diagnostic advantages while not adding any additional recording time or subject preparation. For example, ABR has the potential to provide important neurodiagnostic information up to the level of the inferior colliculus and may help distinguish low-SR versus high-SR ANF lesion when recording ABR at different intensity levels. ^{12 54}

CONCLUSIONS

This is the only known study to assess cochlear synaptopathy by simultaneous recording of ECochG and ABR at a very fast click rate with the CLAD method and using the iPhone Health app as a risk analysis tool for objective classification of noise exposure risk. The high-risk group in our study showed behavioral and electrophysiologic signs of cochlear synaptopathy profile in agreement with previous animals and human findings. These signs included normal pure-tone hearing thresholds and DPOAE response, the presence of tinnitus, multitonal in nature, difficulty hearing in noise, abnormally large SP/AP amplitude, and area ratios due to large SP amplitude and relatively small AP amplitude (ABR wave I amplitude). The presence of normal hearing and normal DPOAEs in the high-risk group ruled out OHC damage and NIHL as a possible cause for tinnitus and difficulty hearing in noise and relatively small AP (wave I) amplitude. Also, the presence of abnormally large SP/AP amplitude and area ratios without significantly affecting ABR wave V at fast click rates support a possibility of damage at the synapses between IHC and type I ANF known as cochlear synaptopathy. These current findings are potential markers for cochlear synaptopathy due to noise exposure in young adults listening to loud music via PLDs. In addition, the presence of abnormal ECochG and ABR findings only in our high-risk group is an indication that the iPhone Health app is a useful objective tool in identifying those at risk for cochlear synaptopathy.

Future studies should consider a longitudinal evaluation of new users of PLDs to monitor their iPhone Health app's listening data over a variety of exposure duration (1 vs. 6 months vs. 1 vs. 2 years) to assess possible onset and progression of signs of cochlear synaptopathy profile in high-risk participants. In addition, examining the combination of shorter duration periods (e.g., 1 day vs. 1 week vs. 2 weeks vs. 3 weeks) and higher cutoff levels (e.g., 90 dBA for the high-risk group) may provide additional valuable insight to determine what damage, OHCs or synaptopathy, may occur when listening to loud music via PLDs for a short duration. Future studies should also consider expansion into different age ranges (e.g., teenagers and middle-aged adults) and including male patients to evaluate any possible gender differences in the cochlear synaptopathy profile. Incorporation of the Apple Watch Series 4 environmental sound exposure levels could provide valuable insight for future studies, as users can import data from both their environment and headphone listening levels, for example, to be evaluated within their iPhone Health app.

The main limitations of this study were the relatively small sample size ( n  = 30 ears in each group), gender limitation (females only), and a narrow age range (18–26 years old). This study also required participants to be iPhone users, and thus others who may be at risk from music listening (such as Android users) or any other sort of noise exposure were not assessed. The iPhone Health app does not evaluate risks due to occupational or recreational noise exposure. Therefore, the use of a questionnaire will be needed to screen for and rule out any participants with other significant sources of noise exposure. Given that there are no known studies that have utilized very fast click rate with CLAD method to assess cochlear synaptopathy, recording ECochG and ABR at fast click rates ≥234.4/s and to high-frequency, tone burst stimuli to distinguish from presynaptic and postsynaptic lesion and to rule out the contribution from cochlear high-frequency region should be considered. Finally, given that millions of children and young adults listen to loud music using PLDs and the known link between noise exposure and risk for not only NIHL but also cochlear synaptopathy, the field may consider an annual audiological assessment for young adults with noise-exposure risk to assess their hearing thresholds at conventional frequencies and EHF, speech in noise ability, and tinnitus evaluation.

Overall, this study is the first of its kind to obtain objective measurements on PLD listening levels and exposure duration particularly with a focus on using these measurements to assess risk for cochlear synaptopathy and provide important contributions to the literature. New technology, like PLDS, that so many of us carry around daily, combined with applications similar to iPhone Health app, can be incredibly useful for insight into hearing health and provide critical information when understanding risks for noise exposure and its consequences of causing NIHL and/or cochlear synaptopathy. In addition, recording ECochG at fast click rates with CLAD method increases the likelihood of detecting abnormal neural dyssynchrony due to cochlear synaptopathy.

Funding Statement

Funding/Acknowledgments The authors would like to thank all participants for their voluntary participation in this study. We also acknowledge the tremendous support from the RStat Institute at MSU in guiding data analysis. This study was supported by the Graduate Research Project Fund, the Graduate College, Missouri State University. Findings from this study were accepted for presentation at the American Academy of Audiology Conference in St. Louis, MO (March 30 to April 2, 2022).