Otoacoustic Emission Measurements Research Articles

Auditory brainstem responses in the bat Carollia perspicillata: threshold calculation and relation to audiograms based on otoacoustic emission measurement.

An objective method to evaluate auditory brainstem-evoked responses (ABR) based on the root-mean-square (rms) amplitude of the measured signal and bootstrapping procedures was used to determine threshold curves (see Lv et al. in Med Eng Phys 29:191-198, 2007; Linnenschmidt and Wiegrebe in Hear Res 373:85-95, 2019). The rms values and their significance for threshold determination depended strongly on the filtering of the signal. Using the minimum threshold values obtained at three different low-frequency filter corner frequencies (30, 100, 300Hz), ABR threshold curves were calculated. The course of the ABR thresholds was comparable to that of published DPOAE (distortion-product otoacoustic emission) thresholds based on a - 10dB SPL threshold criterion for the 2f1-f2 emission (Schlenther et al. in J Assoc Res Otolaryngol 15:695-705, 2014, frequency range 10-90kHz). For frequencies between 20 and 80kHz, which is the most sensitive part of the bat's audiogram, median thresholds ranged between 10 and 28dB SPL, and the DPOAE thresholds ranged between 10 and 23dB SPL. At frequencies below 20kHz (5-20kHz) and above 80kHz (80-120kHz), ABR thresholds increased by 20dB/octave and 45dB/octave, respectively. We conclude that the combination of objective threshold determination and multiple filtering of the signal gives reliable ABR thresholds comparable to cochlear threshold curves.

Variable-rate frequency sweeps and their application to the measurement of otoacoustic emissions.

Swept tones allow the efficient measurement of otoacoustic emissions (OAEs) with fine frequency resolution. Although previous studies have explored the influence of different sweep parameters on the measured OAE, none have directly considered their effects on the measurement noise floor. The present study demonstrates that parameters such as sweep type (e.g., linear or logarithmic), sweep rate, and analysis bandwidth affect the measurement noise and can be manipulated to control the noise floor in individual subjects. Although responses to discrete-tone stimuli can be averaged until the uncertainty of the measurement meets a specified criterion at each frequency, linear or logarithmic sweeps offer no such flexibility. However, measurements of the power spectral density of the ambient noise can be used to construct variable-rate sweeps that yield a prescribed (e.g., constant) noise floor across frequency; in effect, they implement a form of frequency-dependent averaging. The use of noise-compensating frequency sweeps is illustrated by the measurement of distortion-product OAEs at low frequencies, where the ear-canal noise is known to vary significantly.

Verification results of objective newborn hearing screening

Sufficient hearing is the cornerstone of the development of children's complex sensory perception, sound recognition, speech development and optimal communication skills. Hearing screening of newborns is necessary to detect congenital hearing disorders. Compulsory objective hearing screening in Hungary is a significant improvement in early diagnosis. The Audiological Department of Otorhinolaryngology, Head and Neck Surgery Clinic at Semmelweis University serves as a verification center for children identified via the compulsory objective newborn hearing screening and necessitates more detailed assessment. The goal of this study was to summarize the verification results of the year 2018. Case history, ENT examination, electric response measurement, impedance tests, otoacoustic emission measurement, surdopedagogical examination, and genetic examination are the basics of the diagnosis and the therapy as well. Altogether 261 newborns were examined in 2018 and 164 were subjected to audiological tests during the analyzed seven-month period. Normal hearing was detected in both ears in 77% of the cases, while hearing loss has been verified in 37 patients (23% of cases). Permanent hearing loss has been diagnosed in 19 cases, 4 unilateral and 15 bilateral. Hearing loss of sensorineural origin was confirmed in 17, conductive in 2 children. Temporary hearing loss caused by otitis media with effusion was found in further 18 children which healed spontaneously in most cases. Organized neonatal objective hearing examination has been established in Hungary in 2015. As a result, we can diagnose and provide care for children with hearing loss at the earliest stage. The National Newborn Hearing Screening Registry ensures a well-coordinated and smooth process. Orv Hetil. 2019; 160(47): 1850-1855.

Effect of chronic suppurative otitis media on distortion product otoacoustic emission input-output functions in conventional and ultra-high frequencies.

Detection and valid measurements of distortion product otoacoustic emissions are not influenced by cochlear status alone, but also by middle-ear status. There is a need to understand the use of ultra-high frequency distortion product otoacoustic emissions in cases of abnormal distortion product otoacoustic emission findings for conventional frequencies related to the middle-ear condition. The present study investigated distortion product otoacoustic emission input-output functions in conventional and ultra-high frequencies in: 37 adults with chronic suppurative otitis media (clinical group) and 37 adults with normal hearing sensitivity (control group). There were significant reductions in distortion product otoacoustic emission amplitude and mean signal-to-noise ratio in the clinical group compared to the control group, especially for conventional frequencies. There was a significant reduction in the rate of ears with measurable distortion product otoacoustic emissions in the clinical group, especially for conventional frequencies. The effect of chronic suppurative otitis media was more pronounced in the conventional frequency range compared to the smaller effect seen in the ultra-high frequency range.

Efficacy of 2 Different Intratympanic Steroid Regimen on Prevention of Cisplatin Ototoxicity: An Experimental Study

Ototoxicity is the general name of cochlear and vestibular organ injury resulting from encountering various therapeutic agents and chemical substances. Cisplatin is commonly used in the treatment of many cancers. In this study, the efficacy of intratympanic steroids was compared for preventing cisplatin ototoxicity. In this study, 32 (64 ears) rats were used by separating into 4 groups. Cisplatin was administered intraperitoneally to the first group (n = 8). Methylprednisolone and then cisplatin were administered intratympanically to the second group (n = 8). On the third group (n = 8), dexamethasone and then cisplatin were administered intratympanically. To the fourth group (n = 8), 0.9% NaCl and then cisplatin were given intratympanically. Otoacoustic emission (OAE) measurements and auditory brainstem responses (ABRs) tests were performed on all groups before and 72 hours after the procedure. Pretreatment of ABR-IV values were 4.29 ± 0.19 milliseconds in group 2 and 4.27 ± 0.16 milliseconds in group 3, whereas posttreatment ABR-IV values were 4.95 ± 0.35 milliseconds in group 2 and 4.65 ± 0.26 milliseconds in group 3. The ABR-IV values were measured significantly shorter in the rats given dexamethasone and methylprednisolone, according to control and cisplatin groups (P < .001). Pretreatment of ABR I-IV interval values were 2.98 ± 0.34 milliseconds and 3.03 ± 0.42 milliseconds in group 1 and group 4, respectively, and ABR I-IV interval values in group 1 and group 4 posttreatment were 3.49 ± 0.39 milliseconds and 3.5 ± 0.39 milliseconds in group 1 and group 4, respectively. Auditory brainstem responses I-IV interval was significantly longer in the cisplatin and control group than in the rats given dexamethasone and methylprednisolone (P < .001). After cisplatin treatment, OAE amplitudes decreased significantly in group 1 and group 4 for all frequencies, while OAE values were protected in methylprednisolone and dexamethasone group (P < .001). In conclusion, it has been shown that both agents have protective effects on cisplatin ototoxicity, with dexamethasone slightly more than methylprednisolone.

Assessment of the Effectiveness of Quercetin on Cisplatin-Induced Ototoxicity in Rats.

This study aimed to evaluate the effect of quercetin on cochlear function and morphology, and its possible protective effect against acute cisplatin-induced ototoxicity in rats. This prospective and controlled animal study was conducted on Wistar albino rats divided into four groups. Otoacoustic emission measures were performed three days after the first infiltration in Group 1 (saline), 2 (cisplatin), and 3 (quercetin). This interval was five days for Group 4 (cisplatin+quercetin). At the end of the study, the rats were decapitated with deep anesthesia, and histological changes in the cochleas were observed by light microscopy. Group 2 (cisplatin) revealed significant differences between the first and second measures in all frequencies. When compared to other group, the difference of the changes in Group 2 statistically significantly decreased, especially in higher frequencies. Morphologically, there were no acute changes in Group 1 and Group 3. Outer hair cell loss and the degeneration of stria vascularis and spiral ganglion were observed in both Groups 2 and 4; the damages in the latter were lesser. Quercetin does not have negative effect on cochlea, and it has protective effect on cisplatin-induced ototoxicity.

Efficacy of adrenomedullin on cisplatin ototoxicity in rats

Purpose: The aim of this study was to evaluate the efficacy of adrenomedullin on damage associated with cisplatin ototoxicity created in an experimental animal model.Materials and Methods: A total of 32 Wistar Albino rats were separated into 4 groups of 8. To the rats in Group 1 (control), 1% acetic acid was administered intraperitoneally and intratympanically, to Group 2, cisplatin (10mg/kg/2 days) + intratympanic acetic acid, to Group 3, cisplatin + intraperitoneal adrenomedullin (12 µg/kg) and to Group 4, cisplatin +0.1- 0.3ml intratympanic adrenomedullin (12 µg/kg). The drugs were administered on the first 5 days and signal-to-noise ratio (SNR) measurements of the auditory brainstem response (ABR) and distortion product otoacoustic emissions (DPOAE) were made on days 0, 5 and 15. The rats were sacrificed and serum and ear tissue samples were taken for histopathological examination and examination of oxidative stress levels.Results: A statistically significant difference was determined in the cisplatin+intratympanic adrenomedullin group in the Auditory brain-stem response (ABR) measurements on days 0, 5 and 15 . In the Distortion product-evoked otoacoustic emission (DPOAE) measurements, the between-day differences at 16000 frequency in the cisplatin + intraperitoneal adrenomedullin group were accepted as statistically significantConclusion: Adrenomedullin, which is a strong vasodilator and antioxidant, was found to have a protective effect against cisplatin ototoxicity in the cochlea.

Auditory and Histopathological Effects of Topical Mercurochrome Treatment in Rats with Tympanic Membrane Perforation.

Topical treatment is first choice in the treatment of uncomplicated chronic otitis media. It was intended to assess auditory and histopathological safety of ototopical use of mercurochrome solution in rats with induced tympanic membrane perforation. The study was conducted on 21 female Wistar-Albino rats which were randomly assigned into 3 groups. In all rats, perforation was performed at right tympanic membrane. Distortion product otoacoustic emissions (DPOAEs) measurements were performed at frequencies of 2000, 3000 and 4000 Hz (with L1/L2: 70 /70 dB at 2f1-f2 frequency; f2/f1 ratio: 1:22) before recovery from anesthesia and signal-to-noise ratio (SNR) were recorded. Normal saline, 2% mercurochrome and gentamicin were given to group 1, 2 and 3 twice daily over a week, respectively. Rats were sacrificed after DPOAE measurements on day 14. Right temporal bone specimens were examined under light microscope after processing. Based on DPOAE results, there was no significant difference among groups before treatment. On day 14, significant differences were found in DPOAE measurements at 3000 and 4000 Hz, and in mean SNR values in 2% mercurochrome and gentamicin groups when compared to normal saline group while no significant difference was detected at 2000 Hz among groups. In addition, significant degeneration was detected in Corti organs, spiral ganglions and stria vascularis in groups 2 and 3. In this study, it was observed that mercurochrome use in external otitis and otitis media with tympanic membrane perforation could cause ototoxicity and concluded that the solution should be used cautiously.

Protective Effect of Melatonin on Cisplatin-induced Ototoxicity in Rats.

Cisplatin is a highly effective chemotherapeutic agent that is used to treat solid tumors; however, its severe side effects remain a limitation. In particular, the high incidence of cisplatin-induced ototoxicity has attracted interest. Melatonin has been shown to decrease the toxic effects of cisplatin due to its antioxidant activity, and could increase the efficacy of cancer chemotherapy. The aim of this study was to determine the effect of melatonin against ototoxicity in rats treated with cisplatin. Rats were randomly divided into four groups (saline, melatonin, cisplatin+saline, and melatonin+cisplatin). Distortion-product otoacoustic emission (DPOAE) measurements were carried out on days 1 and 8. There was a decrease in DPOAE amplitudes in the animals that received cisplatin (10 mg/kg); however, the group treated with cisplatin+melatonin presented DPOAE amplitudes comparable to those of the control groups. Melatonin can be used as an adjuvant tumor treatment due to its ability to decrease cisplatin-induced ototoxicity.

Protective and therapeutic effects of milrinone on acoustic trauma in rat cochlea.

The aim of this study was to investigate the potential protective and therapeutic effects of milrinone, a specific phosphodiesterase (PDE) III inhibitor, on acoustic trauma-induced cochlear injury and apoptosis. A total number of 30 healthy Wistar albino rats were evenly divided into five groups as follows: group 1 was assigned as control group; group 2 and 3 were assigned as low-dosage groups (0.25mg/kg) in which milrinone was administered 1h before acoustic trauma (AT) and 2h after AT, respectively; group 4 and 5 were assigned as high-dosage groups (0.50mg/kg) in which the drug was administered 1h before AT and 2h after AT, respectively. Except control group, all treatment groups received a single dosage of milrinone for 5days. Distortion product otoacoustic emissions (DPOAE) measurements were recorded before AT as well as at second and fifth post-traumatic days. At the end of fifth day, all rats were sacrificed and the cochlea of the rats was removed for histopathological evaluation. In addition, the groups were compared in terms of apoptotic index via caspase-3 staining. In terms of signal-to-noise ratio (SNR), there was no statistically significant difference among the groups following AT (p > 0.05). After 5days of milrinone treatment, the best SNR values were found in group 5, though all groups did not statistically differ (p > 0.05). In histopathological evaluation, vacuolization, inflammation, and edema scores in all treatment groups were statistically lower than those of the control group (p < 0.05). In group 2 and 4 where the drug was administered before AT, the inflammation and apoptosis index was lower than those of group 3 and 5 where the drug was administered after AT (p < 0.0001). We reveal that milrinone has a protective effect on cochlear damage in the experimental acoustic model of rats. This protective effect was more apparent following the pre-traumatic milrinone administration, and is associated with its effect on decreasing inflammation and apoptosis. Based on DPOAE measurements following AT, especially in the group 5 (high-dosage group), milrinone may also have a therapeutic effect.

Prenatal masculinization of the auditory system in infants: The MIREC-ID study

Sex differences in inner-ear function are detectable in infants, notably through the measurement of otoacoustic emissions (OAEs). Prevailing theories posit that prenatal exposure to high levels of androgens in boys may weaken OAEs, and that this phenomenon may predominantly affect the right ear/left hemisphere (Geschwind-Galaburda (GG) hypothesis). Yet, actual tests of these models have been difficult to implement in humans. Here we examined the relationship between markers of fetal androgen exposure collected at birth (anogenital distances (AGD); penile length/width, areolar/scrotal/vulvar pigmentation) and at 6 months of age (2nd to 4th digit ratio (2D:4D)) with two types of OAEs, click-evoked OAEs (CEOAEs) and distortion-product OAEs (DPOAEs) (n = 49; 25 boys; 24 girls). We found that, in boys, scrotal pigmentation was inversely associated with the amplitude and reproducibility of CEOAEs in the right ear at 4 kHz, with trends also present in the same ear for mean CEOAE amplitude and CEOAE amplitude at 2 kHz. Penile length was inversely associated with the mean amplitude of DPOAEs in both the right and left ears, as well as with DPOAE amplitude in the right ear at 2 kHz and the reproducibility of CEOAEs in the left ear at 2.8 kHz. Finally, AGD-scrotum in boys was positively associated in boys with the amplitude of DPOAEs in the left ear at 2.8 kHz. Unexpectedly, there were no sex differences in the amplitude or reproducibility of OAEs, nor, in girls, any associations between androgenic markers and auditory function. Nonetheless, these findings, reported for the first time in a sample of human infants, support both the prenatal-androgen-exposure and GG models as explanations for the masculinization of auditory function in male infants.

SENS-401 Effectively Reduces Severe Acoustic Trauma-Induced Hearing Loss in Male Rats With Twice Daily Administration Delayed up to 96 hours.

SENS-401 (R-azasetron besylate) is effective against severe acoustic trauma-induced hearing loss. SENS-401 has calcineurin inhibiting properties and attenuates cisplatin-induced hearing loss in a rat model. Cisplatin-induced and acoustic trauma-induced hearing loss share common apoptotic pathways. The dose-response relationship of SENS-401 (6.6 mg/kg BID, 13.2 mg/kg BID, 26.4 mg/kg QD) and treatment time-window (13.2 mg/kg BID starting 24, 72, and 96 h posttrauma) versus placebo for 28 days were evaluated in a male rat model of severe acoustic trauma-induced hearing loss (120 dB SPL, 2 h) using auditory brainstem response (ABR) and distortion product otoacoustic emissions (DPOAE) measures followed by cochlear outer hair cell (OHC) counting with myosin-VIIa immunolabeling. All SENS-401 doses improved ABR threshold shift and recovery, reaching statistical significance (p < 0.05) for ABR threshold recoveries after 28-days treatment. DPOAE amplitude loss and recovery improved markedly for 13.2 mg/kg BID SENS-401, reaching significance after 14 days (p < 0.05). Significant improvements in ABR threshold shifts/recovery and DPOAE amplitude loss occurred with up to 96-hours delay in initiating SENS-401 (p < 0.05), and in DPOAE amplitude recovery with up to 72-hours delay (p < 0.05). Significantly more surviving OHCs were present after SENS-401 treatment compared with placebo after 24 to 96-hours delay posttrauma, with up to 5.3-fold more cells in the basal cochlea turn. In vivo data support the otoprotective potential of twice daily oral SENS-401. Improvements in hearing loss recovery make SENS-401 a promising clinical candidate for acoustic trauma-induced hearing loss, including when treatment is not initiated immediately.

The Effect of Endoscopic Endonasal Transsphenoidal Skull Base Surgery on Cochlear Function.

Endoscopic transsphenoidal skull base surgery (ETSS) has become a standard approach in the treatment of sellar and clival lesions, such as pituitary adenoma and chordoma. Due to the close proximity of the clivus and the sella turcica to the inner ear, it is thought that bone drilling in the surgery may have effects on hearing. The aim of this study was to assess the effect of bone drilling in ETSS procedure on cochlear function. This study was performed on 18 patients who underwent ETSS procedure between December 2016 and May 2017. The study was designed as a prospective study. All of the data were prospectively collected. These included demographic data, date of surgery, type of surgery, preoperative pure-tone audiometry, and preoperative and postoperative distortion product otoacoustic emission (DPOAE) measurements. Of the DPOAE measurements of the patients who were operated for pituitary adenoma, there was a statistically significant difference between the signal-to-noise ratio (SNR) measurements at 0.5, 1, 2 and 4 kHz ( p < 0.05). Additionally, there were no significant differences in preoperative and postoperative SNR measurements of six patients who were selected for clivus chordoma. When the preoperative and postoperative tonal audiometric tests of the patients were compared, no statistically significant difference was found ( p > 0.05). In conclusion, it is found that bone drilling in ETSS procedure has a negative effect on cochlear function in the early period. This is the first study to evaluate the degree of noise-induced cochlear damage in patients who were gone under ETSS procedure.

Effects of anesthetic drugs on otoacoustic emissions: Experimental study

Aim: Otoacoustic emission measurements are generally performed under sedation for children and experimental animals. In the literature it is stated that due to systemic effects of medications used with the aim of sedation, there are variations in cochlear perfusion and as a result, otoacoustic emission (OAE) measurements are affected. Our study aims to investigate this interaction.Material and Methods: The study was completed using 15 healthy adult Wistar Albino rats. The rats were divided into three groups based on anesthetic agent used; group midazolam (M), group ketamine (K) and group dexmedetomidine (D). After OAE measurements were performed in Groups M and D, noradrenalin was administered, OAE measurements were repeated and these were defined as group MN and Group DN. During the study, the hemodynamic data and OAE measurement results were recorded. Results were assessed for statistical significance.Results: The mean arterial pressure in Group M and Group D was 66±16 mmHg, while in Group K, Group DN and Group MN it was 134±16. The mean HR in Group M and Group D was 196±20 beats/min, while in Group K, Group DN and Group MN it was 170±40 beats/min. In Group M and D, there was a correlation with mean arterial pressure only at 2 and 4 kHz, while in the noradrenalin group there was a direct correlation identified for mean arterial pressure only at 6 kHz.Discussion: Though it is frequently emphasized in the literature that in addition to direct pharmacological effects of anesthetic agents, they may affect OAE results due to hemodynamic changes, in our study we conclude there is no significant interaction in clinical terms.Keywords: Sedation; otoacoustic emission measurements; cochlear hypoperfusion.

Effects of Forward- and Emitted-Pressure Calibrations on the Variability of Otoacoustic Emission Measurements Across Repeated Probe Fits.

The stimuli used to evoke otoacoustic emissions (OAEs) are typically calibrated based on the total SPL measured at the probe microphone. However, due to the acoustics of the ear-canal space (i.e., standing-wave interference), this method can underestimate the stimulus pressure reaching the tympanic membrane at certain frequencies. To mitigate this effect, stimulus calibrations based on forward pressure level (FPL) can be applied. Furthermore, the influence of ear-canal acoustics on measured OAE levels can be compensated by expressing them in emitted pressure level (EPL). To date, studies have used artificial shallow versus deep probe fits to assess the effects of calibration method on changes in probe insertion. In an attempt to better simulate a clinical setting, the combined effects of FPL calibration of stimulus level and EPL compensation of OAE level on response variability during routine (noncontrived) probe fittings were examined. The distortion component of the distortion-product OAE (DPOAE) and the stimulus-frequency OAE (SFOAE) were recorded at low and moderate stimulus levels in 20 normal-hearing young-adult subjects across a five-octave range. In each subject, three different calibration approaches were compared: (1) the conventional SPL-based stimulus calibration with OAE levels expressed in SPL; (2) FPL stimulus calibration with OAEs expressed in SPL; and (3) FPL stimulus calibration with OAEs expressed in EPL. Test and retest measurements were obtained during the same session and, in a subset of subjects, several months after the initial test. The effects of these different procedures on the inter- and intra-subject variability of OAE levels were assessed across frequency and level. There were no significant differences in the inter-subject variability of OAE levels across the three calibration approaches. However, there was a significant effect on OAE intra-subject variability. The FPL/EPL approach resulted in the overall lowest test-rest differences in DPOAE level for frequencies above 4 kHz, where standing-wave interference is strongest. The benefit was modest, ranging on average from 0.5 to 2 dB and was strongest at the lower stimulus level. SFOAE level variability did not show significant differences among the three procedures, perhaps due to insufficient signal-to-noise ratio and nonoptimized stimulus levels. Correlations were found between the short-term replicability of DPOAEs and the benefit derived from the FPL/EPL procedure: the more variable the DPOAE, the stronger the benefit conferred by the advanced calibration methods. Stimulus and response calibration procedures designed to mitigate the effects of standing-wave interference on both the stimulus and the OAE enhance the repeatability of OAE measurements and reduce their dependence on probe position, even when probe shifts are small. Modest but significant improvements in short-term test-retest repeatability were observed in the mid- to high-frequency region when using combined FPL/EPL procedures. The authors posit that the benefit will be greater in a more heterogeneous group of subjects and when different testers participate in the fitting and refitting of subjects, which is a common practice in the audiology clinic. The impact of calibration approach on OAE inter-subject variability was not significant, possibly due to a homogeneous subject population and because factors other than probe position are at play.

Abnormalities of Otoacoustic Emissions in Myasthenia Gravis: Association With Serological and Electrophysiological Features.

Objective: To investigate whether otoacoustic emissions (OAEs) are impaired in patients with myasthenia gravis (MG) and whether such dysfunction is associated with serological and electrophysiological features of MG.Methods: We tested 15 patients with MG (30 ears) and 10 healthy age- and sex-matched subjects (20 ears) for transiently evoked OAE (TEOAE) and distortion product OAE (DPOAE).Results: Compared with controls, MG patients revealed a significant reduction in the amplitude of TEOAEs (p < 0.05) and DPOAEs at higher frequencies between 2,026 and 4,053 Hz (p < 0.05). In the subgroup analysis, TEOAE and DPOAE amplitudes were significantly lower in the acetylcholine receptor (AChR) antibody-positive group (p < 0.05) as well as in the repetitive nerve stimulation (RNS)-positive (p < 0.05) group. In particular, the OAE alteration significantly correlated with anti-AChR antibody titers. No significant difference of the OAEs was found between thymomatous and non-thymomatous MG or between purely ocular and generalized MG.Conclusions: Our study confirms that OAEs reveal subclinical dysfunction of the cholinergic neurotransmission of cochlear outer hair cells and correlate well with electrophysiological and serological characteristics of MG patients. Our findings imply that the measurement of OAEs might increase the diagnostic accuracy and help to monitor the severity of MG.

Use of non-invasive measures to predict cochlear synapse counts

Cochlear synaptopathy, the loss of synaptic connections between inner hair cells (IHCs) and auditory nerve fibers, has been documented in animal models of aging, noise, and ototoxic drug exposure, three common causes of acquired sensorineural hearing loss in humans. In each of these models, synaptopathy begins prior to changes in threshold sensitivity or loss of hair cells; thus, this underlying injury can be hidden behind a normal threshold audiogram. Since cochlear synaptic loss cannot be directly confirmed in living humans, non-invasive assays will be required for diagnosis. In animals with normal auditory thresholds, the amplitude of wave 1 of the auditory brainstem response (ABR) is highly correlated with synapse counts. However, synaptopathy can also co-occur with threshold elevation, complicating the use of the ABR alone as a diagnostic measure. Using an age-graded series of mice and a partial least squares regression approach to model structure-function relationships, this study shows that the combination of a small number of ABR and distortion product otoacoustic emission (DPOAE) measurements can predict synaptic ribbon counts at various cochlear frequencies to within 1–2 synapses per IHC of their true value. In contrast, the model, trained using the age-graded series of mice, overpredicted synapse counts in a small sample of young noise-exposed mice, perhaps due to differences in the underlying pattern of damage between aging and noise-exposed mice. These results provide partial validation of a noninvasive approach to identify synaptic/neuronal loss in humans using ABRs and DPOAEs.

The effect of resveratrol on the histologic characteristics of the cochlea in diabetic rats.

The aim of this study was to investigate changes in the cochlea and the potential dose-dependent effects of resveratrol (RSV) against diabetes mellitus (DM) ototoxicity. Animal model. Twenty-four male Wistar albino rats were divided into four groups. Baseline distortion product otoacoustic emission (DPOAE) measurements were evaluated. Group I was the control group, group II was made diabetic with single-dose streptozotocin, and groups III and IV were rendered diabetic as group II and administered 10 and 20 mg RSV, respectively, intraperitoneally for 4 weeks. All animals were sacrificed after repeated DPOAE measurement. Apoptosis was investigated using caspase-3, Bax (Bcl-associated X protein), and TUNEL (terminal deoxynucleotidyl transferase dUTP nick end labeling) staining. The DPOAE values in the diabetic group were found to be significantly lower compared with the other groups at 5,714 Hz and 8,000 Hz (P < .05). No significant difference in otoacoustic emission was detected in the comparison of the RSV doses (P > .05). The histopathologic investigation using caspase-3, Bax, and TUNEL staining showed that the mean rank of the diabetic group was significantly higher compared with the RSV10, RSV20, and control groups (DM > RSV10 > RSV20 > control) (P < .05). These results imply that RSV administration offered statistically significant protection for the cochleas of rats against diabetes. This protective effect improved histologically with higher doses. NA Laryngoscope, 129:E1-E6, 2019.

Could the Use of Acoustic Reflexes Prior to Administering Distortion Product Otoacoustic Emissions (DPOAEs) Affect the Results of DPOAEs?

The purpose of this study is to investigate whether acoustic reflex threshold testing before administration of distortion product otoacoustic emissions can affect the results of the distortion product otoacoustic emissions testing using an automated protocol. Fifteen young adults with normal hearing ranging in age from 19 to 25 years participated in the study. All participants had clear external ear canals and normal Jerger Type A tympanograms and had passed a hearing screening. Testing was performed using the Interacoustics Titan acoustic reflex threshold and distortion product otoacoustic emissions protocol. Participants underwent baseline distortion product otoacoustic emissions. A paired-samples t test was conducted for both the right and left ears to assess within-group differences between baseline distortion product otoacoustic emissions and repeated distortion product otoacoustic emissions measures. No significant differences were found in distortion product otoacoustic emission measures following administration of acoustic reflexes. The use of a protocol when using an automated system that includes both acoustic reflexes and distortion product otoacoustic emissions is important. Overall, presentation of acoustic reflexes prior to measuring distortion product otoacoustic emission did not affect distortion product otoacoustic emission results; therefore, test sequence can be modified as needed.

Using Thresholds in Noise to Identify Hidden Hearing Loss in Humans.

Recent animal studies suggest that noise-induced synaptopathy may underlie a phenomenon that has been labeled hidden hearing loss (HHL). Noise exposure preferentially damages low spontaneous-rate auditory nerve fibers, which are involved in the processing of moderate- to high-level sounds and are more resistant to masking by background noise. Therefore, the effect of synaptopathy may be more evident in suprathreshold measures of auditory function, especially in the presence of background noise. The purpose of this study was to develop a statistical model for estimating HHL in humans using thresholds in noise as the outcome variable and measures that reflect the integrity of sites along the auditory pathway as explanatory variables. Our working hypothesis is that HHL is evident in the portion of the variance observed in thresholds in noise that is not dependent on thresholds in quiet, because this residual variance retains statistical dependence on other measures of suprathreshold function. Study participants included 13 adults with normal hearing (≤15 dB HL) and 20 adults with normal hearing at 1 kHz and sensorineural hearing loss at 4 kHz (>15 dB HL). Thresholds in noise were measured, and the residual of the correlation between thresholds in noise and thresholds in quiet, which we refer to as thresholds-in-noise residual, was used as the outcome measure for the model. Explanatory measures were as follows: (1) auditory brainstem response (ABR) waves I and V amplitudes; (2) electrocochleographic action potential and summating potential amplitudes; (3) distortion product otoacoustic emissions level; and (4) categorical loudness scaling. All measurements were made at two frequencies (1 and 4 kHz). ABR and electrocochleographic measurements were made at 80 and 100 dB peak equivalent sound pressure level, while wider ranges of levels were tested during distortion product otoacoustic emission and categorical loudness scaling measurements. A model relating the thresholds-in-noise residual and the explanatory measures was created using multiple linear regression analysis. Predictions of thresholds-in-noise residual using the model accounted for 61% (p < 0.01) and 48% (p < 0.01) of the variance in the measured thresholds-in-noise residual at 1 and 4 kHz, respectively. Measures of thresholds in noise, the summating potential to action potential ratio, and ABR waves I and V amplitudes may be useful for the prediction of HHL in humans. With further development, our approach of quantifying HHL by the variance that remains in suprathreshold measures of auditory function after removing the variance due to thresholds in quiet, together with our statistical modeling, may provide a quantifiable and verifiable estimate of HHL in humans with normal hearing and with hearing loss. The current results are consistent with the view that inner hair cell and auditory nerve pathology may underlie suprathreshold auditory performance.