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1.  Mastoid cavity dimensions and shape: method of measurement and virtual fitting of implantable devices 
Audiology & neuro-otology  2009;14(5):308-314.
Temporal bone implants can be used to electrically stimulate the auditory nerve, to amplify sound, to deliver drugs to the inner ear and potentially for other future applications. The implants require storage space and access to the middle or inner ears. The most acceptable space is the cavity created by a canal wall up mastoidectomy and commonly access is gained through the facial recess. Detailed knowledge of the available space for implantation and pathways to access the middle and inner ears is necessary for the design of implants and successful implantation. Based on temporal bone CT scans a method for 3D reconstruction of a virtual canal wall up mastoidectomy space is described. Using Amira® software the area to be removed during such surgery is marked on axial CT slices and a 3D model of that space is created. The average volume of 31 reconstructed models is 12.6 cm3 with standard deviation of 3.69 cm3, ranging from 7.97 cm3 to 23.25 cm3. Critical distances were measured directly from the models and their averages were calculated: height 3.69cm, depth 2.43cm, length above the external auditory canal (EAC) 4.45cm and length posterior to EAC 3.16cm. These linear measurements did not correlate well with the computed volumes. The shape of the models was variable to a significant extent making the prediction of successful implantation for a given design based on linear and volumetric measurements unreliable. Hence, to assure successful implantation, preoperative assessment should include virtual fitting of an implant to the intended storage space. The above mentioned 3D models were exported from Amira® to a Solidworks application where virtual fitting was preformed. Our results are compared to other temporal bone implant virtual fitting studies. Virtual fitting has been suggested for other human applications.
PMCID: PMC2712579  PMID: 19372649
Mastoid dimension; mastoid size measurement method; implantable device
2.  Mastoid Cavity Dimensions and Shape: Method of Measurement and Virtual Fitting of Implantable Devices 
Audiology & Neuro-Otology  2009;14(5):308-314.
Temporal bone implants can be used to electrically stimulate the auditory nerve, to amplify sound, to deliver drugs to the inner ear and potentially for other future applications. The implants require storage space and access to the middle or inner ears. The most acceptable space is the cavity created by a canal wall up mastoidectomy. Detailed knowledge of the available space for implantation and pathways to access the middle and inner ears is necessary for the design of implants and successful implantation. Based on temporal bone CT scans a method for three-dimensional reconstruction of a virtual canal wall up mastoidectomy space is described. Using Amira® software the area to be removed during such surgery is marked on axial CT slices, and a three-dimensional model of that space is created. The average volume of 31 reconstructed models is 12.6 cm3 with standard deviation of 3.69 cm3, ranging from 7.97 to 23.25 cm3. Critical distances were measured directly from the model and their averages were calculated: height 3.69 cm, depth 2.43 cm, length above the external auditory canal (EAC) 4.45 cm and length posterior to EAC 3.16 cm. These linear measurements did not correlate well with volume measurements. The shape of the models was variable to a significant extent making the prediction of successful implantation for a given design based on linear and volumetric measurement unreliable. Hence, to assure successful implantation, preoperative assessment should include a virtual fitting of an implant into the intended storage space. The above-mentioned three-dimensional models were exported from Amira to a Solidworks application where virtual fitting was performed. Our results are compared to other temporal bone implant virtual fitting studies. Virtual fitting has been suggested for other human applications.
PMCID: PMC2712579  PMID: 19372649
Mastoid dimension; Mastoid size measurement method; Implantable device
3.  Long-Term Speech and Language Outcomes in Prelingually Deaf Children, Adolescents and Young Adults Who Received Cochlear Implants in Childhood 
Audiology & neuro-otology  2013;18(5):289-296.
This study investigated long-term speech and language outcomes in 51 prelingually deaf children, adolescents, and young adults who received cochlear implants (CIs) prior to 7 years of age and used their implants for at least 7 years. Average speech perception scores were similar to those found in prior research with other samples of experienced CI users. Mean language test scores were lower than norm-referenced scores from nationally representative normal-hearing, typically-developing samples, although a majority of the CI users scored within one standard deviation of the normative mean or higher on the Peabody Picture Vocabulary Test, Fourth Edition (63%) and Clinical Evaluation of Language Fundamentals, Fourth Edition (69%). Speech perception scores were negatively associated with a meningitic etiology of hearing loss, older age at implantation, poorer pre-implant unaided pure tone average thresholds, lower family income, and the use of Total Communication. Users of CIs for 15 years or more were more likely to have these characteristics and were more likely to score lower on measures of speech perception compared to users of CIs for 14 years or less. The aggregation of these risk factors in the > 15 years of CI use subgroup accounts for their lower speech perception scores and may stem from more conservative CI candidacy criteria in use at the beginning of pediatric cochlear implantation.
PMCID: PMC3895537  PMID: 23988907
cochlear implant; deafness; language; speech perception; children; prelingual hearing loss
4.  Time-Frequency Analysis of Transient-Evoked Otoacoustic Emissions in Children exposed to Carboplatin Chemotherapy 
Audiology & neuro-otology  2012;18(2):71-82.
The aims of this study were to characterize and quantify time-frequency changes in transient-evoked otoacoustic emissions (TEOAEs) recorded in children diagnosed with retinoblastoma who were receiving carboplatin chemotherapy. A signal processing technique, the wavelet transform (WT), was used to analyze TEOAE waveforms in narrow-band frequency components. Ten children (aged 3–72 months) diagnosed with unilateral or bilateral retinoblastoma were enrolled in the study. TEOAEs were acquired from the children with linear sequences of 70 dB peSPL clicks. After WT analysis, TEOAE energy, latency, and normalized energy in the narrow-band frequency components were compared before and during carboplatin (average dose 1693 mg/m2) chemotherapy treatment. On a group basis, no significant differences (p>0.05) in pre- and post-carboplatin TEOAE energy, latency, or normalized energy were observed. There were decreases in normalized energy on an individual basis in 10/18 ears in the sample. Exposure to carboplatin chemotherapy did not cause significant changes in TEOAE energy, latency, and normalized energy during treatment. However, long-term monitoring of hearing with measurements of TEOAEs is warranted given the risks of delayed hearing loss in some children receiving carboplatin chemotherapy.
PMCID: PMC3777667  PMID: 23147804
Carboplatin; Children; Cochlea; Ototoxicity; TEOAE; Wavelet
5.  Cortical Encoding of Pitch Contour Changes in Cochlear Implant Users: A Mismatch Negativity Study 
Audiology & neuro-otology  2013;18(5):10.1159/000351802.
A better understanding of melodic pitch perception in cochlear implants (CIs) may guide signal processing and/or rehabilitation techniques to improve CI patients' music perception and appreciation. In this study, the mismatch negativity (MMN) in response to infrequent changes in five-tone pitch contours was obtained in CI users and normal hearing (NH) listeners. Melodic contour identification (MCI) was also measured. Results showed that MCI performance was poorer in CI subjects than in NH subjects; The MMNs were missing in all CI subjects for the 1-semitone contours. The MMNs with the 5-semitone contours were observed in a smaller proportion of CI subjects than in NH subjects. Results suggest that encoding of pitch contour changes in CI users appears to be degraded, most likely due to the limited pitch cues provided by the CI and deafness-related compromise of brain substrates.
PMCID: PMC3823678  PMID: 23920129
cochlear implant; music perception; pitch contour; mismatch negativity; electrophysiology
6.  Hypoxia-Inducible Factor and Vascular Endothelial Growth Factor Pathway for the Study of Hypoxia in a New Model of Otitis Media with Effusion 
Audiology & neuro-otology  2012;17(6):349-356.
The hypoxia-inducible factor and vascular endothelial growth factor (HIF-VEGF) pathway in hypoxic conditions of the middle ear due to dysfunction of the eustachian tube is still unknown, but it is considered as one pathogenetic mechanism in otitis media. This study was designed to investigate the possible involvement of the HIF-VEFG pathway in otitis media with effusion induced by dysfunction of the eustachian tube. We adopted a soft palate approach to obstruct the orifice of the eustachian tube to establish otitis media in a rat model. Auditory evoked brainstem response and tympanometry were used as hearing function tests, hypoxia-related factors were examined by reverse transcriptase polymerase chain reaction (RT-PCR). The expression of hypoxia-related proteins was detected by Western blot and immunostaining. The model of otitis media with effusion was successfully induced by cauterizing the orifice of the eustachian tube. RT-PCR showed up-regulation of hypoxia-related factors in cauterized ears. Western blot and immunostaining showed that the expression of hypoxia-related proteins in cauterized ears was increased. Hypoxia-induced vascular proliferation and an increase in permeability may be one pathogenetic mechanism of otitis media due to dysfunction of the eustachian tube.
PMCID: PMC3637049  PMID: 22907120
Animal model; Dysfunction; Eustachian tube; Hypoxia-inducible factor-1 α; Vascular endothelial growth factor
7.  Effects of Lower Frequency-to-Electrode Allocations on Speech and Pitch Perception with the Hybrid Short-Electrode Cochlear Implant 
Audiology & neuro-otology  2012;17(6):357-372.
Because some users of a Hybrid short-electrode cochlear implant (CI) lose their low-frequency residual hearing after receiving the CI, we tested whether increasing the CI speech processor frequency allocation range to include lower frequencies improves speech perception in these individuals. A secondary goal was to see if pitch perception changed after experience with the new CI frequency allocation. Three subjects who had lost all residual hearing in the implanted ear were recruited to use an experimental CI frequency allocation with a lower frequency cutoff than their current clinical frequency allocation. Speech and pitch perception results were collected at multiple time points throughout the study. In general, subjects showed little or no improvement for speech recognition with the experimental allocation when the CI was worn with a hearing aid in the contralateral ear. However, all three subjects showed changes in pitch perception that followed the changes in frequency allocations over time, consistent with previous studies showing that pitch perception changes upon provision of a CI.
PMCID: PMC3519932  PMID: 22907151
short-electrode; Hybrid; electro-acoustic stimulation; cochlear implant; pitch; speech perception; plasticity
8.  The Effect of Superior Semicircular Canal Dehiscence on Intracochlear Sound Pressures 
Audiology & neuro-otology  2012;17(5):338-348.
Semicircular canal dehiscence (SCD) is a pathological opening in the bony wall of the inner ear that can result in conductive hearing loss. The hearing loss is variable across patients, and the precise mechanism and source of variability are not fully understood. Simultaneous measurements of basal intracochlear sound pressures in scala vestibuli (SV) and scala tympani (ST) enable quantification of the differential pressure across the cochlear partition, the stimulus that excites the cochlear partition. We used intracochlear sound pressure measurements in cadaveric preparations to study the effects of SCD size. Sound-induced pressures in SV and ST, as well as stapes velocity and ear-canal pressure were measured simultaneously for various sizes of SCD followed by SCD patching. Our results showed that at low frequencies (<600 Hz), SCD decreased the pressure in both SV and ST, as well as differential pressure, and these effects became more pronounced as dehiscence size was increased. Near 100 Hz, SV decreased about 10 dB for a 0.5 mm dehiscence and 20 dB for a 2 mm dehiscence, while ST decreased about 8 dB for a 0.5 mm dehiscence and 18 dB for a 2mm dehiscence. Differential pressure decreased about 10 dB for a 0.5 mm dehiscence and about 20 dB for a 2 mm dehiscense at 100 Hz. In some ears, for frequencies above 1 kHz, the smallest pinpoint dehiscence had bigger effects on the differential pressure (10 dB decrease) than larger dehiscenses (less than 10 dB decrease), suggesting larger hearing losses in this frequency range. These effects due to SCD were reversible by patching the dehiscence. We also showed that under certain circumstances such as SCD, stapes velocity is not related to how the ear can transduce sound across the cochlear partition because it is not directly related to the differential pressure, emphasizing that certain pathologies cannot be fully assessed by measurements such as stapes velocity.
PMCID: PMC3541532  PMID: 22814034
superior semicircular canal dehiscence; cochlear pressure; SCD; scala vestibuli; scala tympani; cochlea; differential pressure
9.  The Role of Vascular Endothelial Growth Factors and Fibroblast Growth Factors in Angiogenesis during Otitis Media 
Audiology & Neurotology  2011;17(3):148-154.
The middle ear response to otitis media includes transformation and hyperplasia of the mucosal epithelium and subepithelial connective tissue. Significant neovascularization is also noted, which occurs both to support the hypertrophied mucosa and to mediate the increased trafficking of leukocytes. We investigated the role of two known potent angiogenic growth factor families, the fibroblast growth factors (FGFs) and vascular endothelial growth factors (VEGFs), in middle ear mucosal angiogenesis. DNA microarrays were used to evaluate the expression of FGFs and VEGFs, as well as their receptors and unique signaling proteins, in the middle ears of mice undergoing a complete course of acute bacterial otitis media. In addition, a member of each family was introduced to the middle ear submucosal compartment of the normal middle ears of guinea pigs, by a continuous-release osmotic minipump system over 1 week. During the course of bacterial otitis media, a significant regulation of a number of genes important for angiogenesis was identified. Histologic evaluation of middle ear mucosa following micropump infusion of both FGF1 and VEGF-A showed significant angiogenesis at the site of infusion in comparison to control saline infusion. These results support a role for FGFs and VEGFs in the neovascularization of the middle ear mucosa during otitis media, and offer a potential avenue for therapeutic intervention.
PMCID: PMC3238030  PMID: 22104377
Angiogenesis; Otitis media; Fibroblast growth factor; Vascular endothelial growth factor
10.  Psychoacoustic Performance and Music and Speech Perception in Prelingually Deafened Children with Cochlear Implants 
Audiology & Neurotology  2012;17(3):189-197.
The number of pediatric cochlear implant (CI) recipients has increased substantially over the past 10 years, and it has become more important to understand the underlying mechanisms of the variable outcomes in this population. In this study, psychoacoustic measures of spectral-ripple and Schroeder-phase discrimination, the Clinical Assessment of Music Perception, and consonant-nucleus-consonant (CNC) word recognition in quiet and spondee reception threshold (SRT) in noise tests have been presented to 11 prelingually deafened CI users, aged 8–16 years with at least 5 years of CI experience. The children's performance was compared to the previously reported results of postlingually deafened adult CI users. The average spectral-ripple threshold (n = 10) was 2.08 ripples/octave. The average Schroeder-phase discrimination was 67.3% for 50 Hz and 56.5% for 200 Hz (n = 9). The Clinical Assessment of Music Perception test showed that the average complex pitch direction discrimination was 2.98 semitones. The mean melody score was at a chance level, and the mean timbre score was 34.1% correct. The mean CNC word recognition score was 68.6%, and the mean SRT in steady noise was −8.5 dB SNR. The children's spectral-ripple resolution, CNC word recognition, and SRT in noise performances were, within statistical bounds, the same as in a population of postlingually deafened adult CI users. However, Schroeder-phase discrimination and music perception were generally poorer than in the adults. It is possible then that this poorer performance seen in the children might be partly accounted for by the delayed maturation in their temporal processing ability, and because of this, the children's performance may have been driven more by their spectral sensitivity.
PMCID: PMC3375765  PMID: 22398954
Cochlear implant; Prelingual hearing loss; Psychophysics; Music; Speech perception
11.  Effects of computer-assisted speech training on Mandarin-speaking hearing-impaired children 
Audiology & neuro-otology  2007;12(5):307-312.
The present study investigated whether moderate amounts of computer-assisted speech training can improve the speech recognition performance of hearing-impaired children. Ten Mandarin-speaking children (3 hearing aid users and 7 cochlear implant users) participated in the study. Training was conducted at home using a personal computer for one half-hour per day, five days per week, for a period of 10 weeks. Results showed significant improvements in subjects’ vowel, consonant, and tone recognition performance after training. The improved performance was largely retained two months after training was completed. These results suggest that moderate amounts of auditory training, using a computer-based auditory rehabilitation tool with minimal supervision, can be effective in improving the speech performance of hearing-impaired children.
PMCID: PMC3580209  PMID: 17536199
12.  What Is the Site of Origin of Cochleovestibular Schwannomas? 
Audiology & Neurotology  2011;17(2):121-125.
The belief that cochleovestibular schwannomas arise from the glial-Schwann cell junction has repeatedly been quoted in the literature, although there is no published evidence that supports this statement. A systematic evaluation of the nerve of origin and the precise location of cochleovestibular schwannomas using our respective archival temporal bone collections was conducted. Forty tumors were within the internal auditory canal (IAC), while 10 were intralabyrinthine neoplasms. Of the 40 IAC schwannomas, 4 arose from the cochlear nerve, and 36 from the vestibular nerve. Twenty-one tumors clearly arose lateral to the glial-Schwann cell junction, while 16 tumors filled at least two thirds of the IAC, with the epicenter of the neoplasm located in the mid part or the lateral part of the IAC. Only 3 schwannomas were located in the medial one third of the IAC in the area of the glial-Schwann cell junction. We concluded that cochleovestibular schwannomas may arise anywhere along the course of the axons of the eighth cranial nerve from the glial-Schwann sheath junction up until their terminations within the auditory and vestibular end organs.
PMCID: PMC3221249  PMID: 21968195
Vestibular schwannoma; Histopathology, temporal bone; Origin; Obersteiner-Redlich zone; Glial-Schwann cell transition zone
13.  The Benefits of Combining Acoustic and Electric Stimulation for the Recognition of Speech, Voice and Melodies 
Audiology & neuro-otology  2007;13(2):105-112.
Fifteen patients fit with a cochlear implant in one ear and a hearing aid in the other ear were presented with tests of speech and melody recognition and voice discrimination under conditions of electric (E) stimulation, acoustic (A) stimulation and combined electric and acoustic stimulation (EAS). When acoustic information was added to electrically stimulated information performance increased by 17–23 percentage points on tests of word and sentence recognition in quiet and sentence recognition in noise. On average, the EAS patients achieved higher scores on CNC words than patients fit with a unilateral cochlear implant. While the best EAS patients did not outperform the best patients fit with a unilateral cochlear implant, proportionally more EAS patients achieved very high scores on tests of speech recognition than unilateral cochlear implant patients.
PMCID: PMC3559130  PMID: 18057874
Cochlear implant; Low-frequency hearing; Electric and acoustic stimulation
14.  Interaural Stacked Auditory Brainstem Response Measures for Detecting Small Unilateral Acoustic Tumors 
Audiology & Neurotology  2011;17(1):54-68.
The Stacked auditory brainstem response (SABR) was developed and investigated as a screening tool for small (≤1 cm) unilateral acoustic tumors (vestibular schwannomas) that were missed by standard clinical auditory brainstem response (ABR) measures [Don et al.: Am J Otol 1997;18:608–621; Audiol Neurotol 2005;10:274–290]. While the SABR measure provided much greater sensitivity than the standard ABR measures for small tumor detection, we believed that the large intersubject variability of the SABR measure compromised both the sensitivity and specificity of the measure. However, as we demonstrate in this paper, the variability between ears of a given individual is small. Thus, we introduced an interaural SABR (ISABR) amplitude difference measure to improve the sensitivity and specificity of the SABR amplitude measure to detect small unilateral acoustic tumors. Its main advantages are two-fold. First, it is somewhat immune to variables that affect the absolute SABR amplitudes because it is a relative measure. Second, it is better at assessing tumor patients with very large and non-tumor patients with very small absolute SABR amplitudes. We believe that the ISABR is a useful addition to ABR measures aimed at detecting the presence of unilateral acoustic tumors.
PMCID: PMC3169358  PMID: 21829011
Interaural Stacked auditory brainstem responses; Acoustic tumor; Vestibular schwannoma; Derived-band auditory brainstem responses; High-pass masking
15.  Infection-Mediated Vasoactive Peptides Modulate Cochlear Uptake of Fluorescent Gentamicin 
Audiology & Neurotology  2010;16(6):347-358.
Inflammatory mediators released during bacterial infection include vasoactive peptides such as histamine and serotonin, and their serum levels are frequently elevated. These peptides also modulate the vascular permeability of endothelial cells lining the blood-brain and blood-labyrinth barriers (BLB). These peptides may also modulate the permeability of the BLB to ototoxic aminoglycoside antibiotics prescribed to resolve bacterial sepsis. To test this hypothesis, we compared the effect of histamine and serotonin on the cochlear distribution of fluorescently conjugated gentamicin (GTTR) in control animals at 0.5, 1 and 3 h after injection of GTTR. The intensity of GTTR fluorescence was attenuated at 1 h in the histamine group compared to control mice, and more intense 3 h after injection (p < 0.05). In the serotonin group, the intensity of GTTR fluorescence was attenuated at 0.5 and 1 h (p < 0.05) and was increased at 3 h compared to control animals, where GTTR intensities peaked at 1 h and then plateaued or was slightly decreased at 3 h. This biphasic pattern of modulation was statistically significant in the apical turn of the cochlea. No difference in the intensity of GTTR fluorescence was observed in kidney proximal tubules. Systemic increases in serum levels of vasoactive peptides can modulate cochlear uptake of gentamicin, likely via permeability changes in the BLB. Conditions that influence serum levels of vasoactive peptides may potentiate aminoglycoside ototoxicity.
PMCID: PMC3023003  PMID: 21196726
Ototoxicity; Aminoglycosides; Gentamicin; Histamine; Serotonin; Blood-labyrinth barrier
16.  Distribution of Dexamethasone and Preservation of Inner Ear Function following Intratympanic Delivery of a Gel-Based Formulation 
Audiology & Neurotology  2010;16(5):323-335.
Intratympanic (IT) delivery of drugs to the ear is increasingly used for both clinical and research purposes. One limitation of IT delivery is that drugs are rapidly lost from the middle ear by a number of processes, so that prolonged delivery of drug is technically difficult. In the present study, the delivery characteristics of a poloxamer hydrogel formulation containing dexamethasone (dex) were evaluated. The gel is liquid at room temperature, allowing IT injection, but transitions to a gel at body temperature, providing a prolonged residence time in the middle ear. A 50-μl volume of control or dex-containing gel (dex-gel) was injected through the tympanic membrane of guinea pigs. Cochlear function was assessed with cochlear action potential and acoustic emission thresholds measured immediately, 6 or 24 h after IT gel injection. After 6- or 24-hour treatment with dex-gel, perilymph drug gradients along the cochlea were assessed by taking samples sequentially from the apex, and endolymph was sampled from the basal turn. Control gel injections caused small changes in sound field calibrations and functional measures for low-frequency stimuli, consistent with an induced conductive loss. Within 24 h, responses returned to normal. Twenty-four hours after dex-gel injection, low-frequency changes remained as the dex-gel was retained better in the middle ear, but there was no indication of high-frequency loss. While perilymph sample data showed that dex gradients were substantially lower than after single injections of dex solution, quantitative analysis of this result suggests that some dex may have entered the perilymph through the thin bone in the apical region of the cochlea. Endolymph levels of dex remained lower than those in the perilymph. This study confirms that a poloxamer hydrogel-based dex formulation provides an effective method for a prolonged delivery, providing a more uniform distribution of drug in the inner ear.
PMCID: PMC3023000  PMID: 21178339
Cochlea; Perilymph; Round window; Intratympanic drug delivery; Dexamethasone
17.  Factors Associated with Incomplete Insertion of Electrodes in Cochlear Implant Surgery: A Histopathologic Study 
Audiology & Neurotology  2010;16(2):69-81.
Atraumatic and complete insertion of the electrode array is a stated objective of cochlear implant surgery. However, it is known that obstructions within the cochlea such as new bone formation, cochlear otosclerosis, temporal bone fracture, and cochlear anomalies may limit the depth of insertion of the electrode array. In addition, even among patients without obvious clinical or radiographic indicators of obstruction, incomplete insertion may occur. The current study is a histopathologic evaluation of possible sources of resistance to insertion of the electrode array using the temporal bone collection of the Massachusetts Eye and Ear Infirmary.
Forty temporal bones from patients who in life had undergone cochlear implantation were evaluated. Temporal bones were removed at autopsy and fixed and prepared for histologic study by standard techniques. Specimens were then serially sectioned and reconstructed by 2-dimensional methods. Two electrode metrics were determined for each bone: the inserted length (IL: the distance measured from the cochleostomy site to the apical tip of the electrode) and the active electrode length (AEL: the distance between the most basal and most apical electrodes on the electrode array). The ratio of these two metrics (IL/AEL) was used to split the temporal bones into two groups: those with incomplete insertion (n = 27, IL/AEL <1.0) and those with complete insertion (n = 13, IL/AEL ≥1.0). Seven possible histopathologic indicators of resistance to insertion of the electrode due to contact with the basilar membrane, osseous spiral lamina and/or spiral ligament were evaluated by analysis of serial sections from the temporal bones along the course of the electrode tracks.
Obvious obstruction by abnormal intracochlear bone or soft tissue accounted for only 6 (22%) of the 27 partial insertions. Of the remaining 21 bones with incomplete insertions and 13 bones with complete insertions, dissection of the spiral ligament to the lateral cochlear wall was the only histopathologic indicator of insertion resistance identified with significantly higher frequency in the partial-insertion bones than in the complete-insertion bones (p = 0.003). An observed trend for the percentage of complete insertions to decrease with the number of times the electrode penetrated the basilar membrane did not reach significance. In the bones without an obvious obstruction, the most frequently observed indicator of insertion resistance was dissection of the spiral ligament (with no contact of the lateral cochlear wall) identified in 67% (14/21) of partial-insertion bones and in 92% (12/13) of complete-insertion bones.
These results are consistent with the view that (1) electrode contact with cochlear structures resulting in observable trauma to the basilar membrane, osseous spiral lamina and/or spiral ligament does not necessarily impact the likelihood of complete insertion of the electrode array and (2) once contact trauma to the spiral ligament reaches the point of dissection to the cochlear wall, the likelihood of incomplete insertion increases dramatically.
PMCID: PMC2948664  PMID: 20571258
Cochlear implant; Causes of incomplete electrode insertion; Histopathology of the human temporal bone
18.  Effect of Stimulation Rate on Cochlear Implant Users’ Phoneme, Word and Sentence Recognition in Quiet and in Noise 
Audiology & Neurotology  2010;16(2):113-123.
High stimulation rates in cochlear implants (CI) offer better temporal sampling, can induce stochastic-like firing of auditory neurons and can increase the electric dynamic range, all of which could improve CI speech performance. While commercial CI have employed increasingly high stimulation rates, no clear or consistent advantage has been shown for high rates. In this study, speech recognition was acutely measured with experimental processors in 7 CI subjects (Clarion CII users). The stimulation rate varied between (approx.) 600 and 4800 pulses per second per electrode (ppse) and the number of active electrodes varied between 4 and 16. Vowel, consonant, consonant-nucleus-consonant word and IEEE sentence recognition was acutely measured in quiet and in steady noise (+10 dB signal-to-noise ratio). Subjective quality ratings were obtained for each of the experimental processors in quiet and in noise. Except for a small difference for vowel recognition in quiet, there were no significant differences in performance among the experimental stimulation rates for any of the speech measures. There was also a small but significant increase in subjective quality rating as stimulation rates increased from 1200 to 2400 ppse in noise. Consistent with previous studies, performance significantly improved as the number of electrodes was increased from 4 to 8, but no significant difference showed between 8, 12 and 16 electrodes. Altogether, there was little-to-no advantage of high stimulation rates in quiet or in noise, at least for the present speech tests and conditions.
PMCID: PMC2948665  PMID: 20639631
Cochlear implant; Stimulation rate; Speech recognition; Speech processing
19.  Depth of Electrode Insertion and Postoperative Performance in Humans with Cochlear Implants: A Histopathologic Study 
Audiology & Neurotology  2010;15(5):323-331.
The depth of electrode insertion of a multichannel cochlear implant has been suggested as a clinical variable that may correlate with word recognition using the implant. The current study evaluates this relationship using the human temporal bone collection at the Massachusetts Eye and Ear Infirmary. Twenty-seven temporal bones of subjects with cochlear implants were studied. Temporal bones were removed at autopsy, fixed and prepared for histological study by standard techniques. Specimens were then serially sectioned, and reconstructed by two-dimensional methods. Three measures of length were made from each subject's reconstruction: (1) depth of insertion (DI) of the cochlear implant electrode array, from the round window to the array's apical tip; (2) inserted length (IL) from the cochleostomy to the apical tip of the array, and (3) cochlear duct length (CDL) from the round window to the helicotrema. The active electrode length (AEL) was defined as the distance between the most apical and most basal electrodes of the array. Stepwise regression was used to identify whether subsets of six metrics associated with insertion depth (DI, DI/AEL, DI/CDL, IL, IL/AEL and IL/CDL), duration of deafness, sound-processing strategy, potential for central impairment and age at implantation accounted for significant across-subject variance in the last recorded NU-6 word score measured during each subject's life. Age at implantation and potential for central impairment account for significant percentages of the across-subject variance in NU-6 word scores for the 27 subjects studied. None of the insertion metrics accounted for significant performance variance, even when the variance associated with the other variables was controlled. These results, together with those of previous studies, are consistent with a relatively weak association between electrode insertion depth and speech reception.
PMCID: PMC2919426  PMID: 20203481
Cochlear implant; Word recognition; Depth of electrode insertion
20.  Stimulus Rate and Subcortical Auditory Processing of Speech 
Audiology & Neurotology  2010;15(5):332-342.
Many sounds in the environment, including speech, are temporally dynamic. The auditory brainstem is exquisitely sensitive to temporal features of the incoming acoustic stream, and by varying the speed of presentation of these auditory signals it is possible to investigate the precision with which temporal cues are represented at a subcortical level. Therefore, to determine the effects of stimulation rate on the auditory brainstem response (ABR), we recorded evoked responses to both a click and a consonant-vowel speech syllable (/da/) presented at three rates (15.4, 10.9 and 6.9 Hz). We hypothesized that stimulus rate affects the onset to speech-evoked responses to a greater extent than click-evoked responses and that subcomponents of the speech-ABR are distinctively affected. While the click response was invariant with changes in stimulus rate, timing of the onset response to /da/ varied systematically, increasing in peak latency as presentation rate increased. Contrasts between the click- and speech-evoked onset responses likely reflect acoustic differences, where the speech stimulus onset is more gradual, has more delineated spectral information, and is more susceptible to backward masking by the subsequent formant transition. The frequency-following response (FFR) was also rate dependent, with response magnitude of the higher frequencies (>400 Hz), but not the frequencies corresponding to the fundamental frequency, diminishing with increasing rate. The selective impact of rate on high-frequency components of the FFR implicates the involvement of distinct underlying neural mechanisms for high- versus low-frequency components of the response. Furthermore, the different rate sensitivities of the speech-evoked onset response and subcomponents of the FFR support the involvement of different neural streams for these two responses. Taken together, these differential effects of rate on the ABR components likely reflect distinct aspects of auditory function such that varying rate of presentation of complex stimuli may be expected to elicit unique patterns of abnormality, depending on the clinical population.
PMCID: PMC2919427  PMID: 20215743
Stimulation rate; Auditory brainstem response; Frequency-following response; Subcortical auditory structures; Brainstem
21.  Round Window Membrane Implantation with an Active Middle Ear Implant: A Study of the Effects on the Performance of Round Window Exposure and Transducer Tip Diameter in Human Cadaveric Temporal Bones 
Audiology & Neurotology  2010;15(5):291-302.
To assess the importance of 2 variables, transducer tip diameter and resection of the round window (RW) niche, affecting the optimization of the mechanical stimulation of the RW membrane with an active middle ear implant (AMEI). Materials and Methods: Ten temporal bones were prepared with combined atticotomy and facial recess approach to expose the RW. An AMEI stimulated the RW with 2 ball tip diameters (0.5 and 1.0 mm) before and after the resection of the bony rim of the RW niche. The RW drive performance, assessed by stapes velocities using laser Doppler velocimetry, was analyzed in 3 frequency ranges: low (0.25–1 kHz), medium (1–3 kHz) and high (3–8 kHz).
Driving the RW produced mean peak stapes velocities (HEV) of 0.305 and 0.255 mm/s/V at 3.03 kHz, respectively, for the 1- and 0.5-mm tips, with the RW niche intact. Niche drilling increased the HEV to 0.73 and 0.832 mm/s/V for the 1- and 0.5-mm tips, respectively. The tip diameter produced no difference in output at low and medium frequencies; however, the 0.5-mm tip was 5 and 6 dB better than the 1-mm tip at high frequencies before and after niche drilling, respectively. Drilling the niche significantly improved the output by 4 dB at high frequencies for the 1-mm tip, and by 6 and 10 dB in the medium- and high-frequency ranges for the 0.5-mm tip.
The AMEI was able to successfully drive the RW membrane in cadaveric temporal bones using a classical facial recess approach. Stimulation of the RW membrane with an AMEI without drilling the niche is sufficient for successful hearing outputs. However, the resection of the bony rim of the RW niche significantly improved the RW stimulation at medium and higher frequencies. Drilling the niche enhances the exposure of the RW membrane and facilitates positioning the implant tip.
PMCID: PMC3202919  PMID: 20150727
Round window; Active middle ear implant; Laser Doppler velocimetry; Temporal bone
22.  Change in Cochlear Response in an Animal Model of Otitis Media with Effusion 
Audiology & Neurotology  2009;15(3):155-167.
Our previous studies confirm that middle ear mobility is reduced in the presence of otitis media with effusion (OME). Variations in middle ear function may result in changes in cochlear response in OME ears. With the long-term goal of evaluating cochlear function in OME ears, the aim of this study was to measure the displacement of the basilar membrane (BM) in guinea pig ears with OME. Vibrations of the BM at the apex and basal turn were measured in an in vitro preparation extracted 3 and 14 days after injection of lipopolysaccharide in the middle ear of guinea pigs. The results show that the displacement sensitivity of the BM at the apex and the basal turn to sound pressure in the ear canal was reduced up to 25 dB at their characteristic frequencies, respectively. Cochlear gain with respect to umbo movement was also changed in ears with OME in both groups. This study provides data for analysis of the change of BM vibration in a guinea pig OME model.
PMCID: PMC2853584  PMID: 19776565
Otitis media with effusion; Basilar membrane; Cochlear response
23.  Expression and localization of K+ channels KCNQ2 and KCNQ3 in the mammalian cochlea 
Audiology & neuro-otology  2008;14(2):98-105.
KCNQ1 and KCNQ4 voltage-gated potassium channel subunits play key roles in hearing. Other members of the KCNQ family also encode slow, low voltage-activated K+ M currents. We have previously reported the presence of M-like K+ currents in sensory hair cells, and expression of Kcnq family genes in the cochlea. Here, we describe Kcnq2/3 gene expression and distribution of M channel subunits KCNQ2 and 3 in the cochlea. By using RT-PCR, we found expression of Kcnq2 in modiolus and organ of Corti, while Kcnq3 expression was also detected in the cochlear lateral wall. Five alternative splice variants of the Kcnq2 gene, one of which has not been reported previously, were identified in the rat cochlea. KCNQ2 and KCNQ3 immunoreactivities were observed in spiral ganglion auditory neurons. In addition, the unmyelinated parts of the nerve fibers innervating hair cells and synaptic regions under hair cells showed KCNQ2 immunoreactivity. KCNQ3 immunoreactivity was also prominent in spiral ganglion satellite cells. These findings suggest that cochlear M channels play important roles in regulation of cellular excitability and maintenance of cochlear K+ homeostasis in the auditory system.
PMCID: PMC3030994  PMID: 18827480
Alternative splicing; Cochlea; Gene expression; Immunohistochemistry; Voltage-gated K+ channel KCNQ2; Voltage-gated K+ channel KCNQ3
24.  Hybrid 10 Clinical Trial 
Audiology & neuro-otology  2009;14(Suppl 1):32-38.
Acoustic plus electric (electric-acoustic) speech processing has been successful in highlighting the important role of articulation information in consonant recognition in those adults that have profound high-frequency hearing loss at frequencies greater than 1500 Hz and less than 60% discrimination scores. Eighty-seven subjects were enrolled in an adult Hybrid multicenter Food and Drug Administration clinical trial. Immediate hearing preservation was accomplished in 85/87 subjects. Over time (3 months to 5 years), some hearing preservation was maintained in 91% of the group. Combined electric-acoustic processing enabled most of this group of volunteers to gain improved speech understanding, compared to their preoperative hearing, with bilateral hearing aids. Most have preservation of low-frequency acoustic hearing within 15 dB of their preoperative pure tone levels. Those with greater losses (> 30 dB) also benefited from the combination of electric-acoustic speech processing. Postoperatively, in the electric-acoustic processing condition, loss of low-frequency hearing did not correlate with improvements in speech perception scores in quiet. Sixteen subjects were identified as poor performers in that they did not achieve a significant improvement through electric-acoustic processing. A multiple regression analysis determined that 91% of the variance in the poorly performing group can be explained by the preoperative speech recognition score and duration of deafness. Signal-to-noise ratios for speech understanding in noise improved more than 9 dB in some individuals in the electric-acoustic processing condition. The relation between speech understanding in noise thresholds and residual low-frequency acoustic hearing is significant (r = 0.62; p < 0.05). The data suggest that, in general, the advantages gained for speech recognition in noise by preserving residual hearing exist, unless the hearing loss approaches profound levels. Preservation of residual low-frequency hearing should be considered when expanding candidate selection criteria for standard cochlear implants. Duration of profound high-frequency hearing loss appears to be an important variable when determining selection criteria for the Hybrid implant.
PMCID: PMC3010181  PMID: 19390173
Short electrode; Electric-acoustic stimulation; Sensorineural; Hearing loss; Hearing preservation
25.  Principles of Local Drug Delivery to the Inner Ear 
Audiology & Neurotology  2009;14(6):350-360.
As more and more substances have been shown in preclinical studies to be capable of preventing damage to the inner ear from exposure to noise, ototoxic drugs, ischemia, infection, inflammation, mechanical trauma and other insults, it is becoming very important to develop feasible and safe methods for the targeted delivery of drugs to specific regions in the inner ear. Recently developed methods for sampling perilymph from the cochlea have overcome major technical problems that have distorted previous pharmacokinetic studies of the ear. These measurements show that drug distribution in perilymph is dominated by passive diffusion, resulting in large gradients along the cochlea when drugs are applied intratympanically. Therefore, in order to direct drugs to specific regions of the ear, a variety of delivery strategies are required. To target drugs to the basal cochlear turn and vestibular system while minimizing exposure of the apical cochlear turns, single one-shot intratympanic applications are effective. To increase the amount of drug reaching the apical cochlear turns, repeated intratympanic injections or controlled-release drug delivery systems, such as biodegradable biopolymers or catheters and pumps, are more effective. However, if the applied substance does not easily pass through the round window membrane, or if a more widespread distribution of drug in the ear is required, then intralabyrinthine injections of the substance may be required. Intralabyrinthine injection procedures, which are currently in development in animals, have not yet been proven safe enough for human use.
PMCID: PMC2820328  PMID: 19923805
Animal; Cochlea; Perilymph; Controlled release; Inner ear; Human; Local drug delivery; Pharmacokinetics

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