Objective:This study aims to analyze the threshold changes in distortion product otoacoustic emissions（DPOAE） and auditory brainstem response（ABR） in adult Otof-/- mice before and after gene therapy, evaluating its effectiveness and exploring methods for assessing hearing recovery post-treatment. Methods:At the age of 4 weeks, adult Otof-/- mice received an inner ear injection of a therapeutic agent containing intein-mediated recombination of the OTOF gene, delivered via dual AAV vectors through the round window membrane（RWM）. Immunofluorescence staining assessed the proportion of inner ear hair cells with restored otoferlin expression and the number of synapses.Statistical analysis was performed to compare the DPOAE and ABR thresholds before and after the treatment. Results:AAV-PHP. eB demonstrates high transduction efficiency in inner ear hair cells. The therapeutic regimen corrected hearing loss in adult Otof-/- mice without impacting auditory function in wild-type mice. The changes in DPOAE and ABR thresholds after gene therapy are significantly correlated at 16 kHz. Post-treatment,a slight increase in DPOAE was observeds,followed by a recovery trend at 2 months post-treatment. Conclusion:Gene therapy significantly restored hearing in adult Otof-/- mice, though the surgical delivery may cause transient hearing damage. Precise and gentle surgical techniques are essential to maximize gene therapy's efficacy.
Mice ; Animals ; Otoacoustic Emissions, Spontaneous/physiology* ; Hearing/physiology* ; Ear, Inner ; Hearing Loss/therapy* ; Genetic Therapy ; Auditory Threshold/physiology* ; Evoked Potentials, Auditory, Brain Stem/physiology* ; Membrane Proteins

The qualitative, quantitative, and localization analysis of hearing loss is one of the important contents of forensic clinical research and identification. Pure-tone audiometry is the "gold standard" for hearing loss assessment, but it is affected by the subjective cooperation of the assessed person. Due to the complexity of the auditory pathway and the diversity of hearing loss, the assessment of hearing loss requires the combination of various subjective and objective audiometric techniques, along with comprehensive evaluation based on the case situation, clinical symptoms, and other examinations to ensure the scientificity, accuracy and reliability of forensic hearing impairment assessment. Objective audiometry includes acoustic impedance, otoacoustic emission, and various auditory evoked potentials. The frequency-specific auditory brainstem response (ABR), 40 Hz auditory event related potential, and auditory steady-state response are commonly used for objective hearing threshold assessment. The combined application of acoustic impedance, otoacoustic emission and ABR can be used to locate hearing loss and determine whether it is located in the middle ear, cochlea, or posterior cochlea. This article reviews the application value of objective audiometry techniques in hearing threshold assessment and hearing loss localization, aiming to provide reference for forensic identification of hearing loss.
Humans ; Reproducibility of Results ; Auditory Threshold/physiology* ; Evoked Potentials, Auditory, Brain Stem/physiology* ; Hearing Loss/diagnosis* ; Audiometry, Pure-Tone/methods* ; Clinical Medicine

Objective: To study the protective effects of metformin on noise-induced hearing loss (NIHL) and its differential protein omics expression profile. Methods: In January 2021, 39 male Wistar rats were randomly divided into control group, noise exposure group and metformin+noise exposure group, with 13 rats in each group. Rats in the noise exposure group and metformin+noise exposure group were continuously exposed to octave noise with sound pressure level of 120 dB (A) and center frequency of 8 kHz for 4 h. Rats in the metformin+noise exposure group were treated with 200 mg/kg/d metformin 3 d before noise exposure for a total of 7 d. Auditory brainstem response (ABR) was used to test the changes of hearing thresholds before noise exposure and 1, 4, 7 d after noise exposure in the right ear of rats in each group. Tandem mass tag (TMT) quantitative proteomics was used to identify and analyze the differentially expressed protein in the inner ear of rats in each group, and it was verified by immunofluorescence staining with frozen sections. Results: The click-ABR thresholds of right ear in the noise exposure group and metformin+noise exposure group were significantly higher than those in the control group 1, 4, 7 d after noise exposure (P<0.05) . The click-ABR threshold of right ear in the metformin+noise exposure group were significantly lower than that in the noise exposure group (P<0.05) . Compared with the noise exposure group, 1035 up-regulated proteins and 1145 down-regulated proteins were differentially expressed in the metformin+noise exposure group. GO enrichment analysis showed that the significantly differentially expressed proteins were mainly involved in binding, molecular function regulation, signal transduction, and other functions. Enrichment analysis of KEGG pathway revealed that the pathways for significant enrichment of differentially expressed proteins included phosphatidylinositol 3-kinase-protein kinase B (PI3K-Akt) signaling pathway, focal adhesion, diabetic cardiomyopathy, mitogen, and mitogen-activated protein kinase (MAPK) signaling pathway. Immunofluorescence experiments showed that compared with the noise exposure group, the fluorescence intensity of insulin-like growth factor 1 receptor (IGF1R) in the metformin+noise exposure group was increased, and the fluorescence intensity of eukaryotic translation initiation factor 4E binding protein 1 (eIF4EBP1) was decreased. Conclusion: Noise exposure can lead to an increase in rat hearing threshold, and metformin can improve noise-induced hearing threshold abnormalities through multiple pathways and biological processes.
Animals ; Auditory Threshold/physiology* ; Cochlea ; Ear, Inner ; Evoked Potentials, Auditory, Brain Stem/physiology* ; Hearing Loss, Noise-Induced/prevention & control* ; Male ; Metformin/pharmacology* ; Phosphatidylinositol 3-Kinases/metabolism* ; Rats ; Rats, Wistar

High level noise can damage cochlear hair cells, auditory nerve and synaptic connections between cochlear hair cells and auditory nerve, resulting in noise-induced hearing loss (NIHL). Recent studies have shown that animal cochleae have circadian rhythm, which makes them different in sensitivity to noise throughout the day. Cochlear circadian rhythm has a certain relationship with brain-derived neurotrophic factor and glucocorticoids, which affects the degree of hearing loss after exposure to noise. In this review, we summarize the research progress of the regulation of cochlear sensitivity to noise by circadian rhythm and prospect the future research direction.
Animals ; Auditory Threshold ; Circadian Rhythm ; Cochlea ; Evoked Potentials, Auditory, Brain Stem/physiology* ; Hair Cells, Auditory ; Hearing Loss, Noise-Induced ; Noise/adverse effects*

OBJECTIVES: To explore the relationship between the frequency characteristics and response threshold of auditory steady-state response (ASSR), auditory brainstem response (ABR) and 40 Hz auditory event related potential (40 Hz AERP), and their application values in forensic medicine. METHODS: Thirty volunteers with normal hearing (60 ears) were selected to perform pure tone audiometry (PTA) threshold and ASSR, ABR and 40 Hz AERP response threshold tests in the standard sound insulation shielding room, and the results were statistically analyzed by SPSS 22.0 software. RESULTS: At 0.5 kHz and 1.0 kHz frequencies, the correlation between 40 Hz AERP response threshold and PTA threshold was good, which was better than that of ASSR and ABR response threshold. At 2.0 kHz and 4.0 kHz frequencies, the correlation between ASSR and ABR response thresholds and PTA threshold was good, which was better than that of 40 Hz AERP response threshold. CONCLUSIONS To evaluate the hearing at 0.5 kHz and 1.0 kHz frequencies, it is recommended to use 40 Hz AERP and ASSR to comprehensively assess the PTA threshold of the subjects. To evaluate the hearing at 2.0 kHz and 4.0 kHz frequencies, ABR and ASSR are recommended to assess the PTA threshold of subjects comprehensively. The combination of ASSR, ABR and 40 Hz AERP can improve the accuracy of hearing function evaluation.
Acoustic Stimulation/methods* ; Audiometry, Evoked Response ; Audiometry, Pure-Tone ; Auditory Threshold/physiology* ; Evoked Potentials, Auditory, Brain Stem/physiology* ; Forensic Medicine ; Hearing/physiology* ; Humans

OBJECTIVES: To explore the characters and the relationship among latency response, amplitude and sound stimulus intensity of auditory long latency response（ALR）, and to investigate the significance of ALR applied in auditory threshold prediction. METHODS: Total 46 subjects （92 ears） with normal hearing were tested by ALR. The ALR waves of the subjects were elicited by 5 sound stimulus intensity according to the order of 70, 50, 30, 20 and 10 dB nHL. By making N₁ wave and P₂ wave, the values of 3 observed indexes （the latencies of N₁ wave and P₂ wave and N₁-P₂ amplitude） were obtained, and the variation trend of the observed indexes were statistically analyzed. The differences in the frequency of the indexes were observed. RESULTS: The rate of ALR waves from 46 subjects （92 ears） with normal hearing was 100%. The latencies of N₁ wave and P₂ wave delayed gradually and N₁-P₂ amplitude declined with sound stimulus intensity descending. CONCLUSIONS In suitable conditions, ALR is a stable technology for hearing thresholds prediction. The relation between sound stimulus intensity and latency of N₁ wave, latency of P₂ wave and N₁-P₂ amplitude of ALR plays an important part in auditory thresholds assessment.
Acoustic Stimulation ; Auditory Threshold/physiology* ; Evoked Potentials, Auditory ; Evoked Potentials, Auditory, Brain Stem/physiology* ; Female ; Hearing ; Humans ; Male ; Noise ; Reaction Time

OBJECTIVE: To observe the change of auditory brainstem response (ABR) in hearing deprivation rat model induced by bilateral cochlears ablation at different time points. METHOD: Forty SD rats were randomly divided into four experiment groups including 2-week group, 4-week group, 6-week group, 8-week group and four control groups with 5 rats (n = 10) in each group. Then bilateral cochlears ablation was applied to experiment groups. The threshold value of ABR was measured at different time and latent period of each wave was compared. RESULT: The threshold of ABR in experiment group was elevated significantly. The latent period of each wave was pro longed significantly (P < 0.01). In experiment group, the threshold value of ABR in 2-week and 4-week group was significantly greater than that in 6-week group and 8-week group (P < 0.01). CONCLUSION Bilateral cochlears ablation surgery could elevate the threshold of ABR and latent period of each wave prolonged. The effect of hearing deprivation became apparent after surgery for 4 weeks.
Animals ; Auditory Threshold ; Cochlea ; physiopathology ; surgery ; Disease Models, Animal ; Evoked Potentials, Auditory, Brain Stem ; physiology ; Hearing Loss ; Male ; Rats ; Rats, Sprague-Dawley

OBJECTIVE: To evaluate the electrophysiological characteristics of electrically evoked auditory brainstem responses (EABR) and its application in cochlear implantation, especially in evaluating acoustic nerve survival. METHOD: An auditory evoked potential instrument was used to record responses and Cochlear Nucleus 24CA implants were used to generate electrical stimulation. We measured EABR in 23 patients with cochlear implants and compared EABR with behavioral measures and neural response telemetry (NRT). RESULT: EABR III-V waveforms were recognized in all of the 23 patients. The characteristics and origins of EABR waveforms were similar to those of ABR. The average EABR threshold was (172.61 +/- 14.61) CL. At 20 CL above threshold, the average latencies of Wave III, V were (2.93 +/- 0.18)ms, (4.80 +/- 0.28)ms which were 1-2 ms shorter than ABR latencies. But III-V intervals remained at (1.86 +/- 0.18)ms. EABR thresholds were strongly correlated with behavioral performance and NRT thresholds, while EABR input-output function is correlated with behavioral dynamic range (DR). CONCLUSION EABR is such an effective method to objectively evaluate the function of auditory pathway which can estimate residual spiral ganglion cell count. This is consistent with the foreign study leading to the conclusion that DR reflects spiral ganglion cell survival.
Auditory Threshold ; Child ; Child, Preschool ; Cochlear Implantation ; Cochlear Nerve ; physiopathology ; Deafness ; physiopathology ; surgery ; Evoked Potentials, Auditory, Brain Stem ; physiology ; Female ; Humans ; Infant ; Male

OBJECTIVE: Analysis of normal young people multiple stimuli ASSR (m-ASSR), single stimuli ASSR (s-ASSR), C-ABR, PTA threshold, exploratory investigation of relevance of hearing test combination thresholds (C-ABR combines with 0.5, 1.0 kHz s-ASSR) predict behavioral thresholds, using a within-subjects design. METHOD: Forty-three normal hearing adults (86 ears) were treated with pure tone audiometry (PTA), m-ASSR, 0.5, 1.0 kHz s-ASSR, C-ABR. Data were analyzed by SPSS 18.0 for bivariate correlation analysis. RESULT: There was significant correlation between thresholds of hearing test combination and PTA,and the correlation coefficient (r) were 0.803, 0.650, 0.649, 0.734 at 0.5, 1.0, 2.0 and 4.0 kHz; while the correlation coefficient (r) between thresholds of m-ASSR and PTA were 0.48, 0.64, 0.57, 0.64. CONCLUSION There is significant correlation between thresholds of hearing test combination and PTA, hearing test combination can be more accurate, more reliable assessment of adults with normal hearing threshold level.
Acoustic Stimulation ; Adolescent ; Adult ; Audiometry, Pure-Tone ; Auditory Threshold ; physiology ; Evoked Potentials, Auditory, Brain Stem ; physiology ; Female ; Humans ; Male ; Young Adult

OBJECTIVE: Using the neural response telemetry (NRT) software to investigate whether a difference exists in ECAP properties depending on the region of the cochlea that is stimulated and measured. METHOD: Twenty seven Nucleus CI24R (CA) cochlear implant users participated in this study. ECAPs were recorded intraoperatively using the NRT software. No. 1, 4, 8, 11, 17, 22 electrodes were tested for each patient. ECAP amplitude, threshold and slope were measured using amplitude growth sequences. RESULT: Apical recordings showed on average higher ECAP amplitudes, lower ECAP thresholds and steeper slopes of the ECAP amplitude growth function. CONCLUSION Considerable variability exists in ECAPs due to the region of the cochlea that is stimulated and measured.
Auditory Threshold ; Child ; Child, Preschool ; Cochlear Implants ; Cochlear Nerve ; physiology ; Electric Stimulation ; Electrodes ; Evoked Potentials ; Female ; Humans ; Infant ; Male