Digital music exposure reliably induces temporary threshold shift in normal-hearing human subjects

Abstract

Objectives: One of the challenges for evaluating new otoprotective agents for potential benefit in human populations is the availability of an established clinical paradigm with real-world relevance. These studies were explicitly designed to develop a real-world digital music exposure that reliably induces temporary threshold shift (TTS) in normal-hearing human subjects.

Design: Thirty-three subjects participated in studies that measured effects of digital music player use on hearing. Subjects selected either rock or pop music, which was then presented at 93 to 95 (n = 10), 98 to 100 (n = 11), or 100 to 102 (n = 12) dBA in-ear exposure level for a period of 4 hr. Audiograms and distortion product otoacoustic emissions (DPOAEs) were measured before and after music exposure. Postmusic tests were initiated 15 min, 1 hr 15 min, 2 hr 15 min, and 3 hr 15 min after the exposure ended. Additional tests were conducted the following day and 1 week later.

Results: Changes in thresholds after the lowest-level exposure were difficult to distinguish from test-retest variability; however, TTS was reliably detected after higher levels of sound exposure. Changes in audiometric thresholds had a "notch" configuration, with the largest changes observed at 4 kHz (mean = 6.3 ± 3.9 dB; range = 0-14 dB). Recovery was largely complete within the first 4 hr postexposure, and all subjects showed complete recovery of both thresholds and DPOAE measures when tested 1 week postexposure.

Conclusions: These data provide insight into the variability of TTS induced by music-player use in a healthy, normal-hearing, young adult population, with music playlist, level, and duration carefully controlled. These data confirm the likelihood of temporary changes in auditory function after digital music-player use. Such data are essential for the development of a human clinical trial protocol that provides a highly powered design for evaluating novel therapeutics in human clinical trials. Care must be taken to fully inform potential subjects in future TTS studies, including protective agent evaluations, that some noise exposures have resulted in neural degeneration in animal models, even when both audiometric thresholds and DPOAE levels returned to pre-exposure values.

Figures

Figure 1

Songs were assembled into two four-hour playlists (“Rock” and “Pop”) and levels were sampled with ER6I earphones inserted into Type 4157 Artificial Ear Simulators (Brüel & Kjær). Spectral data were sampled at 0.001 ms intervals using the PULSE system (version 12.5, Brüel & Kjær, Denmark). These virtually continuous data samples entered a multi-buffer that maintained a running average of sound levels for the previous 64 sec (sum of 1/3-octave bands from 20 Hz to 20 kHz), with data exported at 1 sec intervals. Thus, for each 4-hour playlist, approximately 14,400 time-level samples were collected. Right and left ear levels are averaged here.

Figure 2

Average threshold sensitivity was ~5 dB HL (2A). Thresholds did not significantly differ as a function of ear (right versus left, see 2B). Male subjects had significantly (p

Figure 3

Thresholds were re-measured 15 min post-music; change from pre-music baseline is shown (3A). In the 10 subjects that participated in DAP1 (Rock: 94.4±0.9 dB-A; Pop: 94.5±0.7 dB-A coupler level), no reliable changes in thresholds were observed after music player use. In the 11 subjects that participated in DAP2 (Rock: 99.8±0.6 dB-A; Pop: 99.6±0.7 dB-A), discrete changes in threshold sensitivity at a small number of frequencies were detected, including 3 and 4 kHz. In the 12 subjects that participated in DAP3 (Rock: 100.5±0.6 dB-A; Pop: 100.3±0.6 dB-A), there was a broader pattern of change, with more robust TTS at 3 and 4 kHz. TTS was also reliably detected at 2 and 6 kHz. All subjects showed complete recovery of function; data from subjects in the DAP3 study are shown (3B). The time course of recovery included rapid return to baseline over the first several hours, with thresholds at 2, 3, and 6 kHz largely recovered by 135–195 min post-music. Thresholds at 4 kHz were within 2 dB of pre-music baseline the following day, and no deficits in any subject were evident during final tests conducted one week later. Data are mean +/− S.E.M. to illustrate confidence intervals with respect to the true mean for the population sampled.

Figure 4

Changes in threshold measured 15 min post-music for the 12 subjects (24 ears) in the DAP3 study (Rock: 100.5±0.6 dB-A; Pop: 100.3±0.6 dB-A) are shown (4A). Across 12 subjects that participated in DAP3 (Rock: 100.5±0.6 dB-A; Pop: 100.3±0.6 dB-A), there was significant individual variability, with changes in the most affected frequency region (i.e., 2–4 kHz) ranging from −5 (5 dB better than baseline) to 14 dB (14 dB worse than baseline) across ears. The most affected frequency was 4 kHz, and there was a statistically significant relationship between pre-music threshold at 4 kHz and change in threshold at 4 kHz (4B); the individual data points are plotted for each ear, and points at which there were two ears with identical data points are marked with a circle around the symbol. No reliable differences were detected when right ears were compared to left ears (4C), or when males were compared to females (4D). Three subjects selected the Rock Music playlist in DAP1, and two subjects per study selected the Rock Music playlist in the DAP2 and DAP3 studies. TTS measured in the two individuals that selected Rock Music (subjects 84 and 91) was generally consistent with TTS measured in the other ten subjects (4E). Data in figures 4C–4E are mean +/− S.D., to illustrate population variability.

Figure 5

Distortion product otoacoustic emission (DPOAE) amplitude was assessed before and after music exposure for subjects in the DAP1, DAP2, and DAP3 studies; pre-music baseline and 15 min-post music retest is shown for subjects in the DAP3 study at 3 kHz (5A), 4 kHz (5C), and 6 kHz (5E). All subjects showed complete recovery of function; pre-music baseline and 1 week post music retest is shown for subjects in the DAP3 study at 3 kHz (5B), 4 kHz (5D), and 6 kHz (5F). In the 10 subjects that participated in DAP1 (Rock: 94.4±0.9 dB-A; Pop: 94.5±0.7 dB-A coupler level), no reliable changes in OAE amplitude as a consequence of music exposure were detected (not shown). In the 11 subjects that participated in DAP2 (Rock: 99.8±0.6 dB-A; Pop: 99.6±0.7 dB-A), discrete changes at a small number of frequencies were observed, including 3 and 4 kHz (not shown). Data in figures 5A–5E are mean +/− S.D., to illustrate population variability.