Gu JW, Halpin CF, Nam E-C, Levine RA, Melcher JR. Tinnitus, diminished sound-level tolerance, and elevated auditory activity in humans with clinically normal hearing sensitivity. J Neurophysiol 104: 3361-3370, 2010. First published September 29, 2010 doi:10.1152/jn.00226.2010. Phantom sensations and sensory hypersensitivity are disordered perceptions that characterize a variety of intractable conditions involving the somatosensory, visual, and auditory modalities. We report physiological correlates of two perceptual abnormalities in the auditory domain: tinnitus, the phantom perception of sound, and hyperacusis, a decreased tolerance of sound based on loudness. Here, subjects with and without tinnitus, all with clinically normal hearing thresholds, underwent 1) behavioral testing to assess sound-level tolerance and 2) functional MRI to measure soundevoked activation of central auditory centers. Despite receiving identical sound stimulation levels, subjects with diminished sound-level tolerance (i.e., hyperacusis) showed elevated activation in the auditory midbrain, thalamus, and primary auditory cortex compared with subjects with normal tolerance. Primary auditory cortex, but not subcortical centers, showed elevated activation specifically related to tinnitus. The results directly link hyperacusis and tinnitus to hyperactivity within the central auditory system. We hypothesize that the tinnitus-related elevations in cortical activation may reflect undue attention drawn to the auditory domain, an interpretation consistent with the lack of tinnitus-related effects subcortically where activation is less potently modulated by attentional state. The data strengthen, at a mechanistic level, analogies drawn previously between tinnitus/ hyperacusis and other, nonauditory disordered perceptions thought to arise from neural hyperactivity such as chronic neuropathic pain and photophobia.

Objective This study compares measurements of ear-canal reflectance (ECR) to other objective measurements of middle-ear function including, audiometry, umbo velocity (VU), and tympanometry in a population of strictly defined normal hearing ears. Design Data were prospectively gathered from 58 ears of 29 normal hearing subjects, 16 female and 13 male, aged 22–64 years. Subjects met all of the following criteria to be considered as having normal hearing. (1) No history of significant middle-ear disease. (2) No history of otologic surgery. (3) Normal tympanic membrane (TM) on otoscopy. (4) Pure-tone audiometric thresholds of 20 dB HL or better for 0.25 – 8 kHz. (5) Air-bone gaps no greater than 15 dB at 0.25 kHz and 10 dB for 0.5 – 4 kHz. (6) Normal, type-A peaked tympanograms. (7) All subjects had two “normal” ears (as defined by these criteria). Measurements included pure-tone audiometry for 0.25 – 8 kHz, standard 226 Hz tympanometry, Ear canal reflectance(ECR) for 0.2 – 6 kHz at 60 dB SPL using the Mimosa Acoustics HearID system, and Umbo Velocity (VU ) for 0.3 – 6 kHz at 70–90 dB SPL using the HLV-1000 laser Doppler vibrometer (Polytec Inc). Results Mean power reflectance (|ECR|2) was near 1.0 at 0.2– 0.3 kHz, decreased to a broad minimum of 0.3 to 0.4 between 1 and 4 kHz, and then sharply increased to almost 0.8 by 6 kHz. The mean pressure reflectance phase angle (∠ECR) plotted on a linear frequency scale showed a group delay of approximately 0.1 ms for 0.2 – 6 kHz. Small significant differences were observed in |ECR|2 at the lowest frequencies between right and left ears, and between males and females at 4 kHz. |ECR|2 decreased with age, but reached significance only at 1 kHz. Our ECR measurements were generally similar to previous published reports. Highly significant negative correlations were found between |ECR|2 and VU for frequencies below 1 kHz. Significant correlations were also found between the tympanometrically determined peak total compliance and |ECR|2 and The results suggest that middle-ear compliance VU at frequencies below 1 kHz. contributes significantly to the measured power reflectance and umbo velocity at frequencies below 1 kHz, but not at higher frequencies. Conclusions This study has established a database of objective measurements of middle ear function (ear-canal reflectance, umbo velocity, tympanometry) in a population of strictly defined normal hearing ears. The data will promote our understanding of normal middle ear function, and will serve as a control for comparison to similar measurements made in pathological ears.

Objectives-Patients with large vestibular aqueduct syndrome (LVAS) often demonstrate an airbone gap at the low frequencies on audiometric testing. The mechanism causing such a gap has not been well elucidated. We investigated middle ear sound transmission in patients with LVAS, and present a hypothesis to explain the air-bone gap.Methods-Observations were made on 8 ears from 5 individuals with LVAS. The diagnosis of LVAS was made by computed tomography in all cases. Investigations included standard audiometry and measurements of umbo velocity by laser Doppler vibrometry (LDV) in all cases, as well as tympanometry, acoustic reflex testing, vestibular evoked myogenic potential (VEMP) testing, distortion product otoacoustic emission (DPOAE) testing, and middle ear exploration in some ears.Results-One ear with LVAS had anacusis. The other 7 ears demonstrated air-bone gaps at the low frequencies, with mean gaps of 51 dB at 250 Hz, 31 dB at 500 Hz, and 12 dB at 1,000 Hz. In these 7 ears with air-bone gaps, LDV showed the umbo velocity to be normal or high normal in all 7; tympanometry was normal in all 6 ears tested; acoustic reflexes were present in 3 of the 4 ears tested; VEMP responses were present in all 3 ears tested; DPOAEs were present in 1 of the 2 ears tested, and exploratory tympanotomy in 1 case showed a normal middle ear. The above data suggest that an air-bone gap in LVAS is not due to disease in the middle ear. The data are consistent with the hypothesis that a large vestibular aqueduct introduces a third mobile window into the inner ear, which can produce an air-bone gap by 1) shunting air-conducted sound away from the cochlea, thus elevating air conduction thresholds, and 2) increasing the difference in impedance between the scala vestibuli side and the scala tympani side of the cochlear partition during bone conduction testing, thus improving thresholds for bone-conducted sound.Conclusions-We conclude that LVAS can present with an air-bone gap that can mimic middle ear disease. Diagnostic testing using acoustic reflexes, VEMPs, DPOAEs, and LDV can help to identify a non-middle ear source for such a gap, thereby avoiding negative middle ear exploration. A large vestibular aqueduct may act as a third mobile window in the inner ear, resulting in an airbone gap at low frequencies.

Objective The goal of the present study was to investigate the clinical utility of measurements of ear-canal reflectance (ECR) in a population of patients with conductive hearing loss in the presence of an intact, healthy tympanic membrane (TM) and an aerated middle ear. We also sought to compare the diagnostic accuracy of umbo velocity (VU) measurements and measurements of ECR in the same group of patients. Design This prospective study comprised 31 adult patients with conductive hearing loss, of which 14 had surgically-confirmed stapes fixation due to otosclerosis, 6 had surgically-confirmed ossicular discontinuity, and 11 had CT- and VEMP-confirmed superior semicircular canal dehiscence (SCD). Measurements on all 31 ears included pure-tone audiometry for 0.25 – 8 kHz, ECR for 0.2 – 6 kHz using the Mimosa Acoustics HearID system, and VU for 0.3 – 6 kHz using the HLV-1000 laser Doppler vibrometer (Polytec Inc). We analyzed power reflectance |ECR|2 as well as the absorbance level = 10×log10(1−|ECR|2). All measurements were made prior to any surgical intervention. The VU and ECR data were plotted against normative data obtained in a companion study of 58 strictly defined normal ears (Rosowski et al. 2011). Results Small increases in |ECR|2 at low-to-mid frequencies (400–1000 Hz) were observed in cases with stapes fixation, while narrow-band decreases were seen for both SCD and ossicular discontinuity. The SCD and ossicular discontinuity differed in that the SCD had smaller decreases at mid-frequency (~1000 Hz), while ossicular discontinuity had larger decreases at lower frequencies (500–800 Hz). SCD tended to have less air-bone gap at high frequencies (1–4 kHz) compared to stapes fixation and ossicular discontinuity. The |ECR|2 measurements, in conjunction with audiometry, could successfully separate 28 of the 31 cases into the three pathologies. By comparison, VU measurements, in conjunction with audiometry, could successfully separate various pathologies in 29 of 31 cases. Conclusions The combination of |ECR|2 with audiometry showed clinical utility in the differential diagnosis of conductive hearing loss in the presence of an intact TM and an aerated middle ear, and appears to be of similar sensitivity and specificity to measurements of VU plus audiometry. Additional research is needed to expand upon these promising preliminary results.

This article describes an observer-based technique for assessing auditory capacities of infants from 3 to 12 months of age. This technique, referred to as the Observer-based Psychoacoustic Procedure (OPP), combines features of the Forced-choice Preferential Looking technique developed by Teller (1979) and of Visual Reinforcement Audiometry (Moore ; Thompson, & Thompson, 1975). The rationale behind the procedure and the specific techniques used in its application are detailed here. Psychometric functions and thresholds for pure-tone detection and frequency discrimination obtained with OPP are also presented. The results for 6-month-olds are compared with results from previous studies employing a visually reinforced head-turn procedure. 627

The ability of 3-, 6-, and 12-month-old infants to detect pure tones in quiet was tested at frequencies ranging from 250–8000 Hz. Stimuli were presented monaurally via headphone. Signal trials consisted of ten repetitions of a 500-ms tone burst, with 10-ms rise-fall time and 500 ms between bursts; no-signal trials were 10-s intervals of quiet. The infant's response to a tone was judged by an observer, who, blind to trial type, decided whether or not a tone had been presented on each trial, based on the infant's behavior. Comparison of infant thresholds, determined using an adaptive rule, to those of adults tested under similar conditions showed a progressive improvement in threshold from 3–12 months. Three-month-olds' threshold were relatively poorer at 250 and at 8000 Hz compared to adults. The 6- and 12-month-olds' thresholds were somewhat closer to those of adults at 4000 and at 8000 Hz than at lower frequencies. Maturation of absolute sensitivity, of frequency resolution, and of nonsensory processing may all contribute to these age-related changes. [Work supported by NIH.]

We report a novel locus responsible for postlingual progressive sensorineural hearing loss (designated DFNA9) that maps to chromosome 14q12-13. A large kindred with autosomal dominant transmission of non-syndromic hearing loss was clinically studied. Hearing in affected individuals deteriorated at approximately 20 years of age and progressed to anacusis in the fifth decade. A random genome-wide search using polymorphic short tandem repeats demonstrated linkage with D14S121 (maximum two point LOD score = 6.19, theta = 0). Haplotype analysis of recombination events defined a 9 cM disease interval, between D14S252 and D14S49.

Objectives/Hypothesis Otosclerosis is a disease of abnormal bone remodeling in the otic capsule. Although several drugs that inhibit bone remodeling, including sodium fluoride and first generation bisphosphonates, have been tried, there remains no clearly effective treatment for otosclerosis-related sensorineural hearing loss (SNHL). Over the past several years, third generation bisphosphonates, with more powerful anti-resorptive properties and increased bone affinity, have been developed and have demonstrated effectiveness in the treatment of osteoporosis and other metabolic bone diseases. We hypothesized that newer generation bisphosphonates, such as risedronate and zoledronate, would be effective in slowing the progression of SNHL in patients with otosclerosis. Study design Retrospective review Setting Tertiary referral center, ambulatory care Interventions Risedronate or zoledronate administration Main outcome measures Bone conduction pure tone threshold averages (PTA) and word recognition (WR) scores were examined for each ear before and after bisphosphonate treatment. Criteria for significant change were defined as greater than 10 decibels in PTA or between 4 to 18% in WR based on binomial variance. Results All 10 patients had audiometric progression of SNHL in the pre-treatment monitoring interval and 12 ears met criteria for significant progression. All 10 patients (19 ears) showed at least no significant progression of SNHL (i.e. stabilization) at an average follow up of 13 months. Two patients (3 ears) showed improvement by defined audiometric criteria. There were no major complications. Conclusion Treatment with zoledronate or risedronate stabilized progressive SNHL related to otosclerosis in this small group of patients. Further evaluation of third generation bisphosphonate treatments is warranted.