Growth Hormone and the Auditory Pathway: Neuromodulation and Neuroregeneration.

Growth hormone (GH) plays an important role in auditory development during the embryonic stage. Exogenous agents such as sound, noise, drugs or trauma, can induce the release of this hormone to perform a protective function and stimulate other mediators that protect the auditory pathway. In addition, GH deficiency conditions hearing loss or central auditory processing disorders. There are promising animal studies that reflect a possible regenerative role when exogenous GH is used in hearing impairments, demonstrated in in vivo and in vitro studies, and also, even a few studies show beneficial effects in humans presented and substantiated in the main text, although they should not exaggerate the main conclusions.

Auditory processing and neuropsychological profiles of children with functional hearing loss.

OBJECTIVES: This paper compares structured history, auditory processing abilities and neuropsychological findings of children with functional hearing loss (FHL) to those with suspected auditory processing disorder without FHL (control). The main aim was to evaluate the value of a holistic assessment protocol for FHL used in a routine pediatric audiology clinic. The protocol incorporated a commercially available test battery for auditory processing disorder (APD), non-verbal intelligence (NVIQ) and tools to screen for common co-existing neurodevelopmental conditions such as attention deficit hyperactivity disorder (ADHD), language impairment (LI) and developmental coordination disorder (DCD). The outcome of such holistic assessment was expected to help in understanding the nature of FHL and to provide individualized support to mitigate their difficulties. METHODS: This retrospective study compared two groups, 40 children (M = 17, F = 23) in each group between seven and sixteen years of age, one group with a history of FHL and the other with suspected APD without FHL (control). The groups were matched against age, gender, hand use, diagnosis of APD or non-APD (31 with APD and 9 without APD in each group) and non-verbal intelligence. All the children were healthy English speaking children attending mainstream schools with no middle or inner ear abnormalities. Structured history was obtained from parents regarding different nonacademic and academic concerns. The SCAN-3:C and SCAN-3:A test batteries were used to assess auditory processing abilities; Lucid Ability test for NVIQ; Children's Communication Checklist-2 (CCC-2) for language ability; Swanson Nolan and Pelham-IV Rating Scale (SNAP-IV) for ADHD; and the manual dexterity components of the Movement Assessment Battery for Children-2 (MABC-2) as a screening tool for DCD. RESULTS: About 60% of children in both the groups had concerns regarding listening in noisy background. In the history, poor attention was reported in 45% of children in the FHL group compared to 82.5% in the control group (p < 0.01). Hyperacusis was present in 35% of children in the FHL group and in 62% of children in the control group (p < 0.05). Concerns about overall academic abilities were present in 59% of children in the FHL group and 75% of the controls (p > 0.05). Only 15% of children in the FHL group had concerns with numeracy skills in contrast to 41% of the controls (p < 0.05). Significantly fewer (p < 0.01) children in the FHL group (41%) received additional support at school than the controls (75%). Fewer children performed poorly in Filtered Words (FW) test of the SCAN-3 batteries, 30% in the FHL group and 17.5% in the control group, in contrast to Auditory Figure Ground 0 (AFG0), 85% in FHL and 80% in the control group. The number of children performing poorly in AFG0 was significantly higher compared to all the other SCAN-3 tests in FHL (P < 0.05), in contrast to FW and Competing Sentences (CS) only in the control group (p < 0.05). The control group had higher prevalence of atypical ear advantage (AEA) in left directed Competing Words (CW) (32.5%) and Time Compressed Sentences (TCS) (32.5%) compared to FW (7.5%). In contrast, FHL group had higher prevalence of AEA in AFG0 (48.7%) compared to CS (21%). High proportions of children in both the groups had LI (80% in FHL and 82.5% in the control group), with significantly lower (p < 0.05) levels of ADHD symptoms in the FHL group (39.5%) compared to the control group (72.5%). Impaired manual dexterity was present in 30.7% of children in FHL group and 47.5% in the controls. CONCLUSIONS: The prevalences of APD and language impairment are high compared to ADHD symptoms in children with FHL, and holistic assessment is recommended. Despite some similarities in the auditory and neuropsychological profiles between children with FHL and those with suspected APD without FHL some differences were noted. The results suggest that children with FHL have genuine difficulties that need to be identified and addressed. Future research is required to identify the neural pathways which could explain the similarities and dissimilarities between the two groups.

Pure-Tone-Spondee Threshold Relationships in Functional Hearing Loss: A Test of Loudness Contribution.

Purpose: The purpose of this article is to examine explanations for pure-tone average-spondee threshold differences in functional hearing loss. Method: Loudness magnitude estimation functions were obtained from 24 participants for pure tones (0.5 and 1.0 kHz), vowels, spondees, and speech-shaped noise as a function of level (20-90 dB SPL). Participants listened monaurally through earphones. Loudness predictions were obtained for the same stimuli by using a computational, dynamic loudness model. Results: When evaluated at the same SPL, speech-shaped noise was judged louder than vowels/spondees, which were judged louder than tones. Equal-loudness levels were inferred from fitted loudness functions for the group. For the clinical application, the 2.1-dB difference between spondees and tones at equal loudness became a 12.1-dB difference when the stimuli were converted from SPL to HL. Conclusions: Nearly all of the pure-tone average-spondee threshold differences in functional hearing loss are attributable to references for calibration for 0 dB HL for tones and speech, which are based on detection and recognition, respectively. The recognition threshold for spondees is roughly 9 dB higher than the speech detection threshold; persons feigning a loss, who base loss magnitude on loudness, do not consider this difference. Furthermore, the dynamic loudness model was more accurate than the static model.

Inside implant criteria or not? - Detection of non-organic hearing loss during cochlear implant assessment.

OBJECTIVES: The diagnosis of non-organic hearing loss (NOHL) is a difficult but important issue during the assessment process for cochlear implantation (CI). We aim to identify the key factors in identifying patients with NOHL during CI assessment and present our local screening protocol for NOHL. METHODS: A retrospective review of patients referred to the Yorkshire Auditory Implant Service (YAIS) between 2003 and 2015 who were subsequently diagnosed with NOHL during the assessment. Patient demographic data, audiological and functional assessments were assessed. RESULTS: Thirty-two patients were included in the study. Mean age was 43 years (range 14-82 years). Male to female ratio was 1:1.7. Indicators of possible NOHL included a sudden deterioration in hearing (n = 21; 66%), mismatches in observed behaviour and either pure-tone audiogram (PTA) (n = 27; 84%) or functional testing (n = 20; 80%) and stapedial reflexes below reported audiological thresholds (n = 12; 46%). A mismatch in functional hearing and PTA was seen in 72% of patients. Patients with suspected NOHL were referred for further objective testing. All 23 patients who underwent objective testing had better hearing levels compared to reported hearing thresholds thus placing them outside of implant criteria. Five candidates were found to have normal hearing thresholds. DISCUSSION: NOHL can present a significant challenge to the implant team, particularly in the subgroup with a pre-existing organic hearing loss with non-organic overlay. We discuss the common features in this cohort of patients. CONCLUSIONS: To facilitate the identification of patients with NOHL, the YAIS has developed a screening protocol.

Load-induced inattentional deafness.

High perceptual load in a task is known to reduce the visual perception of unattended items (e.g., Lavie, Beck, & Konstantinou, 2014). However, it remains an open question whether perceptual load in one modality (e.g., vision) can affect the detection of stimuli in another modality (e.g., hearing). We report four experiments that establish that high visual perceptual load leads to reduced detection sensitivity in hearing. Participants were requested to detect a tone that was presented during performance of a visual search task of either low or high perceptual load (varied through item similarity). The findings revealed that auditory detection sensitivity was consistently reduced with higher load, and that this effect persisted even when the auditory detection response was made first (before the search response) and when the auditory stimulus was highly expected (50 % present). These findings demonstrate a phenomenon of load-induced deafness and provide evidence for shared attentional capacity across vision and hearing.

Epigenome-wide DNA methylation in hearing ability: new mechanisms for an old problem.

Epigenetic regulation of gene expression has been shown to change over time and may be associated with environmental exposures in common complex traits. Age-related hearing impairment is a complex disorder, known to be heritable, with heritability estimates of 57-70%. Epigenetic regulation might explain the observed difference in age of onset and magnitude of hearing impairment with age. Epigenetic epidemiology studies using unrelated samples can be limited in their ability to detect small effects, and recent epigenetic findings in twins underscore the power of this well matched study design. We investigated the association between venous blood DNA methylation epigenome-wide and hearing ability. Pure-tone audiometry (PTA) and Illumina HumanMethylation array data were obtained from female twin volunteers enrolled in the TwinsUK register. Two study groups were explored: first, an epigenome-wide association scan (EWAS) was performed in a discovery sample (n=115 subjects, age range: 47-83 years, Illumina 27 k array), then replication of the top ten associated probes from the discovery EWAS was attempted in a second unrelated sample (n=203, age range: 41-86 years, Illumina 450 k array). Finally, a set of monozygotic (MZ) twin pairs (n = 21 pairs) within the discovery sample (Illumina 27 k array) was investigated in more detail in an MZ discordance analysis. Hearing ability was strongly associated with DNA methylation levels in the promoter regions of several genes, including TCF25 (cg01161216, p = 6.6 × 10(-6)), FGFR1 (cg15791248, p = 5.7 × 10(-5) and POLE (cg18877514, p= 6.3 × 10(-5)). Replication of these results in a second sample confirmed the presence of differential methylation at TCF25 (p(replication)=6 × 10(-5)) and POLE (p(replication) =0.016). In the MZ discordance analysis, twins' intrapair difference in hearing ability correlated with DNA methylation differences at ACP6 (cg01377755, r= -0.75, p=1.2 × 10(-4)) and MEF2D (cg08156349, r= -0.75, p=1.4 × 10(-4)). Examination of gene expression in skin, suggests an influence of differential methylation on expression, which may account for the variation in hearing ability with age.

Nonorganic hearing loss in children: audiometry, clinical characteristics, biographical history and recovery of hearing thresholds.

OBJECTIVES: The term "nonorganic hearing loss" (NOHL) (pseudohypacusis, functional or psychogenic hearing loss) describes a hearing loss without a detectable corresponding pathology in the auditory system. It is characterized by a discrepancy between elevated pure tone audiometry thresholds and normal speech discrimination. The recommended audiological management of NOHL in children comprises history taking, diagnosis, and counseling. According to the literature, prognosis depends on the severity of the patient's school and/or personal problems. Routine referral to a child psychiatrist is discussed as being controversial. METHODS: The clinical history of 34 children with NOHL was retrospectively evaluated. In 15 children, follow up audiometry was performed. Results of biographical history, subjective and objective audiometry, additional speech and language assessment, psychological investigations and follow up audiometry are presented and discussed. RESULTS: The prevalence of NOHL was 1.8% in children with suspected hearing loss. Mean age at diagnosis was 10.8 years. Girls were twice as often affected as boys. Patient history showed a high prevalence of emotional and school problems. Pre-existing organic hearing loss can be worsened by nonorganic causes. Children with a fast recovery of hearing thresholds (n=6) showed a high rate (4/6) of family, social and emotional problems. In children with continuous threshold elevation (n=9), biographical history showed no recognizable or obvious family, social or emotional problems; learning disability (4/9) was the most frequently presented characteristic. CONCLUSIONS: Due to advances in objective audiometry, the diagnosis of NOHL is less challenging than management and counseling. Considering the high frequency of personal and school problems, a multidisciplinary setting is helpful. On the basis of our results, drawing conclusions from hearing threshold recovery on the severity of underlying psychic problems seems inappropriate. As a consequence, a referral to a child psychiatrist can be generally recommended.

Pure tone auditory thresholds can change according to duration of interrupted tones in patients with psychogenic hearing loss.

CONCLUSION: Pure tone auditory thresholds can change according to duration of interrupted tones in patients with mild to severe psychogenic hearing loss (PHL). OBJECTIVES: To examine how the duration of stimulus tones affects the hearing thresholds of patients with PHL. METHODS: Twelve patients with PHL (21 ears) were enrolled in this study. We initially measured their hearing thresholds using interrupted tones with a duration of 2 s and equal length of on-time and off-time, 225 ± 35 ms, respectively. After a 10 min interval, we measured their hearing thresholds using the same interrupted tones conditions lasting 5 s. The average threshold gains (2 s thresholds minus 5 s thresholds) were compared to those of 15 control subjects with normal hearing (25 ears), 15 patients with cochlear hearing loss (23 ears), and 4 patients with retrocochlear lesions (4 ears). Patients with profound PHL (4 patients, 6 ears) were analyzed separately. RESULTS: The average threshold gain of PHL patients (excluding profound PHL patients) at all frequencies was 18.3 dB, which was significantly larger than that of other groups: 0.3 dB (profound PHL patients), 3.8 dB (controls with normal hearing), 3.0 dB (patients with cochlear hearing loss), and 3.2 dB (patients with retrocochlear lesions).

Non-organic hearing loss: new and confirmed findings.

Although non-organic hearing losses are relatively rare, it is important to identify suspicious findings early to be able to administer specific tests, such as objective measurements and specific counseling. In this retrospective study, we searched for findings that were specific ti or typical for non-organic hearing losses. Patient records from a 6 year period (2003-2008) from the University ENT Department of Bern, Switzerland, were reviewed. In this period, 40 subjects were diagnosed with a non-organic hearing loss (22 children, ages 7-16, mean 10.6 years; 18 adults, ages 19-57, mean 39.7 years; 25 females and 15 males). Pure tone audiograms in children and adults showed predominantly sensorineural and frequency-independent hearing losses, mostly in the range of 40-60 dB. In all cases, objective measurements (otoacoustic emissions and/or auditory-evoked potentials) indicated normal or substantially better hearing thresholds than those found in pure tone audiometry. In nine subjects (22.5%; 2 children, 7 adults), hearing aids had been fitted before the first presentation at our center. Six children (27%) had a history of middle ear problems with a transient hearing loss and 11 (50%) knew a person with a hearing loss. Two new and hitherto unreported findings emerged from the analysis: it was observed that a small air-bone gap of 5-20 dB was typical for non-organic hearing losses and that speech audiometry might show considerably poorer results than expected from pure tone audiometry.

Pseudohypacusis: the most frequent etiology of sudden hearing loss in children.

Sudden hearing loss is a rare pathology in children. Several factors may be responsible for it although the exact etiology remains frequently undiagnosed. Among them, pseudohypacusis has been reported. However, the extent to which this pathology contributes to sudden hearing loss in children is unknown. This study evaluates the incidence of pseudohypacusis in children presented with sudden hearing loss. The medical records of 48 children presented to our department because of sudden hearing loss from 2002 to 2007 were reviewed. Diagnostic process included both subjective and objective audiological tests while organic hearing losses were further subjected to proper evaluation and treatment. 26 cases (54%) of pseudohypacusis and 22 cases (46%) of organic sudden hearing loss were diagnosed. In the pseudohypacustic group, girls outnumbered boys (16:10) and their mean age was 10.5 years. Pseudohypacusis represents the most frequent etiology of sudden hearing loss in children. Its detection is relatively simple using conventional audiological tests though in some cases even experienced clinicians may come to incorrect diagnosis.

[N100m findings of auditory-evoked fields in patients with psychogenic hearing impairment].

We recorded the auditory-evoked fields in five patients with psychogenic hearing impairment and ten healthy controls. The maximum N100m peak amplitude and latency were measured under 1000 and 2000-Hz tone burst stimuli in each ear. The mean N100m amplitude in the patients was smaller than that in the controls. Especially, regardless of the side of stimulation, the mean amplitude in the left-hemisphere was significantly smaller in the patients than in the controls, except for the 2000-Hz stimulus condition in the left ear. There was no significant difference in the latency of the N100m peak between patients and controls. We attribute the findings of attenuation of the N100m amplitude to the peculiar auditory perception in patients with psychogenic hearing impairment. Concerning the cause of this finding, we suggest two possible mechanisms: inhibitory auditory processing and attention deficit.

A clinical analysis of psychogenic sudden deafness.

OBJECTIVE: Sudden deafness, in most cases, has no apparent cause. In some cases viral infection, vascular occlusion, or a cochlear membrane rupture may be responsible for the sudden loss of hearing. In this study, we analyzed etiology, audiologic, psychiatric, and clinical aspects of psychogenic sudden deafness through a retrospective chart review. Patients included were thought to have sudden deafness as a result of psychogenic causes and/or stresses. STUDY DESIGN AND SETTING: We reviewed the records of 277 patients who had been admitted to the Department of Otolaryngology, Kangbuk Samsung Hospital, from January 1997 to July 2003, with the initial diagnosis of idiopathic sudden hearing loss. RESULTS: In the medical history of 9 patients, there was an association between sudden onset of hearing loss and psychogenic events. There were 4 patients who had a preexisting mental health condition. A psychiatrist provided the classification of psychogenic sudden deafness for 7 patients (2.5%) who had organic causes ruled out. These patients showed discrepancy between pure tone audiometry and ABR. There were 2 males and 5 females; 4 patients were in their 10's, 1 in his 20's, and 2 in their 40's. Three patients had bilateral hearing loss and 4 had unilateral loss. The hearing test scores revealed: 4 patients with severe to profound hearing loss at 71 dB or higher, 2 patients with moderately severe hearing loss ranging from 56 to 70 dB, and 1 patient with moderate hearing loss from 41 to 56 dB. Hearing was restored in all patients, partially or completely, by treatment with steroid injections and psychotherapy. CONCLUSIONS: A total of 2.5% of sudden onset hearing loss cases in our study were a result of psychogenic causes. We observed distinctive features for audiologic measures, psychiatric findings, and clinical characteristics. The recovery rate and prognosis were better in patients who had accurate audiometry and were under the care of a psychiatrist. EBM RATING: C-4.

Diagnostic tools in pseudohypacusis in children.

Pseudohypacusis is the term used for a non-organic or functional hearing loss. The mainstay of diagnosis is a lack of consistency in audiological testing. It is usually easier to diagnose in children than in adults, as children are less able to reproduce consistently erroneous results on repeated testing. Nevertheless, the diagnosis is often missed in children, probably due to a lack of awareness of the condition. In a previous study from our department, we highlighted the usefulness of speech audiometry in establishing the diagnosis. However, with the advent of otoacoustic emissions testing, we have changed the emphasis of our testing protocol. Using otoacoustic emissions, the diagnosis of pseudohypacusis can be established quickly and easily.

King-Kopetzky syndrome in the light of an ecological conceptual framework.

The principal symptom of subjects suffering from King-Kopetzky syndrome is a perceived difficulty in recognizing and understanding speech in noisy backgrounds. For some patients, minor disturbances in auditory function, e.g. a deteriorated signal-to-noise ratio for speech, can be demonstrated; for others, all measurements of hearing are normal. A conceptual framework developed for the analysis of communication disorders is applied to King-Kopetzky syndrome in the present article. The usefulness of the framework is evaluated, and an extended system for the analysis of King-Kopetzky syndrome patients is suggested. It is emphasized that changes in demands resulting from external conditions and altered perception and evaluation of the conditions may generate the symptoms. A change in the subjects' desired self-image (preferendum) and a change in social role, new, unfamiliar vocabulary, as well as minor dysfunctions in peripheral and central auditory processing, might generate the characteristic features of the syndrome. The framework is related to the current literature, and arguments for the usefulness of the framework in the planning of support and rehabilitation are presented. Several new questions are generated for further analysis of King-Kopetzky syndrome.

Diminished auditory mismatch fields in dyslexic adults.

Electroencephalographic studies have demonstrated smaller auditory responses to infrequent deviances of speech and nonspeech sounds in dyslexic than normal-reading subjects. We used a whole-scalp neuromagnetometer to study selectively reactivity of the auditory cortices to sound deviances in 8 dyslexic and 11 normal-reading adults. Within a monotonous sequence of 50-millisecond 1000 Hz binaural tones, tones of 920 and 1080 Hz occurred with 7% probability each. Magnetic mismatch fields, elicited by the stimulus deviances, were diminished in the left hemisphere of the dyslexic subjects. The results indicate deficient change detection in the left auditory cortex of right-handed dyslexic adults.

Time trends analysis of hearing loss: an alternative approach to evaluating hearing loss prevention programs.

Two general approaches for evaluating the performance of hearing loss prevention programs (HLPPs) are described in the literature: (1) a comparison of the rate of hearing loss in an HLPP with a reference population and (2) a comparison of audiometric variability or annual incidence of hearing loss with an established set of criteria that rank HLPP performance on a graded scale. This article discusses a third method, time trends analysis, which assesses patterns in hearing loss over time. Patterns may reflect program improvement (decreased hearing loss incidence over time), deterioration (a pattern of increased incidence), or stasis (unchanged incidence). To demonstrate this method, a time trends analysis was conducted on a population of 44,547 industrial workers. Subjects were divided into 11 subgroups based on year of enrollment in the HLPP (1980-1990) and followed retrospectively for 3 years to determine the incidence of hearing loss. Hazard ratios (HRs) were estimated for each subgroup by gender using the Cox Proportional Hazards model and adjusting for age, race, and hearing threshold at enrollment in the HLPP. For women, plots of adjusted HRs against enrollment years produced a statistically significant (p < 0.05) quadratic trend of an initial increase in hearing loss, followed by decreasing incidence over time. For men, there was a statistically significant linear trend of decreasing hearing loss over time. The downward trend, particularly during the late 1980s, indicates improved HLPP performance during the latter portion of the decade. Time trends analysis can be a valuable tool for assessing HLPP performance for those with access to follow-up data and ability to work with statistical models.

The role of a family history in King Kopetzky Syndrome (obscure auditory dysfunction).

King Kopetzky Syndrome (KKS) is a common condition in which individuals with normal audiograms complain of hearing difficulties, particularly in noisy places. Several studies have shown many patients with KKS to have a family history of hearing problems. In 82 consecutive patients with KKS and normal middle ear function, we compared the performance of those with and without a family history of hearing impairment on a number of sensitized tests. Those with a family history were more likely to have notches on Audioscan testing (p < 0.005) and these notches were broader than those found in patients with no family history (p < 0.05). There was also a tendency for those with a family history to be more likely to have notches on DPOAEs (p < 0.07), and the reproducibility of the TOAEs was poorer in those with a family history. Psychological testing showed males with a family history to have higher scores on free-floating anxiety (p < 0.01) and obsessionality (p < 0.05).

Masking-level differences in older adults: the effect of the level of the masking noise.

In Experiment 1, masking-level differences (MLDs) for a 500-Hz tone at five masker levels were obtained from younger and older adults. For both age groups, there were no reliable increases in MLD once the spectrum level of the masker exceeded 27 dB SPL. MLDs were larger for younger than for older adults over the range of masker levels tested. In Experiment 2, the levels of both the signal and the masker in one ear were attenuated by either 15 or 30 dB relative to their level in the other ear, which was fixed at a spectrum level of 47 dB SPL. MLDs for both age groups declined with increasing IAA and age-related differences were observed in all conditions. The findings of these experiments indicate that (1) age-related differences in MLDs exist even when the level of the masker is sufficiently high that older adults achieve their plateau performance, and (2) older listeners are not disadvantaged more than younger listeners by interaural differences in the level of the input.

[Functional hearing loss in children who were not aware of their hearing loss].

We investigated one hundred and fourteen ears of 60 children (8 males, 52 females, aged from 6 to 13 years) with diagnoses of functional hearing loss (FHL), and were not aware of their own hearing loss. Forty nine (81.7%) of 60 cases examined were detected by school screening tests, 6 (10.0%) were referred to our hospital because their families noticed poor hearing responses, and 5 (8.3%) were enrolled because they complained of otalgia or discomfort in the ear. Forty (66.7%) showed only pure tone threshold loss without complications, and the remaining 20 associated nonorganic disorders. In addition, our investigation found 11 cases (18.3%) with nonorganic otalgia, 5 (8.3%) with functional visual disturbance, 1 (1.7%) with enuresis nocturna who refused to attend school, 1 with tinnitus, 1 with vertigo, and 1 with tic. Moreover, 11 (18.3%) of the 60 cases were suspected of being in conflict with school and/or home. The Type V Békésy pattern, which is frequently observed in FHL and it has clinical utility to distinguish FHL from other types of organic hearing loss, was detected in 44 ears (38.6%). Fifty two (45.6%) of 114 ears showed normal pure-tone thresholds during the clinical course. Sixteen (14.0%) ears needed more than 1 year for thresholds to normalize. These findings suggest that some FHL cases without awareness of their hearing loss resemble psychogenic hearing loss. In such cases, otolaryngologists should carefully check the patient's individual circumstances, and when appropriate, refer patients for psychiatric consultation.

[Studies of the evaluation of cochlea function with distortion product otoacoustic emission].

Distortion product otoacoustic emission (DPOAE) is one of the acoustic responses derived from the inner ears and it has very sharp frequency specificities. The purpose of this study is to investigate the utility of DPOAE as a method for evaluating human cochlea functions. The whole subjects of this study were 414 ears with inner ear hearing loss, 278 ears with normal hearing, 113 ears of neonates, 62 ears of the patients who were administered cisplatin, and 15 ears with functional hearing loss. At first, 5 studies described below were performed to examine the characters and reliability of DPOAE as a clinical test: 1) The average DPOAE-gram of normal hearing ears. 2) The comparison between DPOAE levels and hearing levels. 3) The reproducibility of DPOAE on the different examinations in the same subjects. 4) The influences of respiratory noises on DPOAE levels. 5) The detection of fine cochlea damages using DPOAE which can not be detected by pure tone audiometry. Then the following 2 clinical studies were performed: 6) The utility of DPOAE in neonates and children. 7) The utility of DPOAE in functional deafness cases. From these studies, the following characters of DPOAE were confirmed. Since DPOAE levels have correlations with hearing levels at the same frequencies, normal hearing could be determined by the DPOAE level. DPOAE is useful for following chronological changes in hearing because of its reproducibility in a same subject at different times. The early and fine damages on the cochlea that could not be detected by conventional pure tone audiometry might be detected by DPOAE in some cases. Considering these results, it was concluded that DPOAE could be a new objective hearing test which would help the conventional examinations. Especially in infants who can't be examined with pure tone audiometry, DPOAE is thought to be a very useful examination.