@article{Garcia2021,

title = {Implementation of Mobile Audiometry During the COVID‐19 Pandemic},

author = {Alejandro Garcia and Divya A. Chari and Konstantina M. Stankovic and Daniel J. Lee and Elliott D. Kozin and Kevin H. Franck},

doi = {10.1177/01945998211051588},

issn = {1097-6817},

year  = {2022},

date = {2022-09-00},

journal = {Otolaryngol.--head neck surg.},

volume = {167},

number = {3},

pages = {465--468},

publisher = {Wiley},

abstract = {During the COVID‐19 pandemic, the utility of portable audiometry became more apparent as elective procedures were deferred in an effort to limit exposure to health care providers. Herein, we retrospectively evaluated mobile‐based audiometry in the emergency department and outpatient otology and audiology clinics. Air conduction thresholds with mobile audiometry were within 5 dB in 66% of tests (95% CI, 62.8%‐69.09%) and within 10 dB in 84% of tests (95% CI, 81.4%‐86.2%) as compared with conventional audiometry. No significant differences were noted between mobile‐based and conventional audiometry at any frequencies, except 8 kHz (P <. 05). The sensitivity and specificity for screening for hearing loss were 94.3% (95% CI, 91.9%‐96.83%) and 92.3% (95% CI, 90.1%‐94.4%), respectively. While automated threshold audiometry does not replace conventional audiometry, mobile audiometry is a promising screening tool when conventional audiometry is not available.},

keywords = {},

pubstate = {published},

tppubtype = {article}

}

@article{Garcia2021b,

title = {New perspectives in office-based otoendoscopy and endoscopic ear surgery},

author = {Alejandro Garcia and Sarah E. Ridge and Juan M. Garcia and Michael Cohen and Daniel J. Lee},

doi = {10.1016/j.otot.2021.05.002},

issn = {1043-1810},

year  = {2021},

date = {2021-06-00},

journal = {Operative Techniques in Otolaryngology-Head and Neck Surgery},

volume = {32},

number = {2},

pages = {68--78},

publisher = {Elsevier BV},

keywords = {},

pubstate = {published},

tppubtype = {article}

}

@article{Shetty2021,

title = {Clinical and scientific innovations in auditory brainstem implants},

author = {Kunal R. Shetty and Sarah E. Ridge and Vivek Kanumuri and Angela Zhu and M. Christian Brown and Daniel J. Lee},

doi = {10.1016/j.wjorl.2021.02.002},

issn = {2589-1081},

year  = {2021},

date = {2021-04-00},

journal = {World j. otorhinolaryngol.-head neck surg.},

volume = {7},

number = {2},

pages = {109--115},

publisher = {Wiley},

abstract = {The auditory brainstem implant (ABI) was originally developed to provide rehabilitation of retrocochlear deafness caused by neurofibromatosis type 2 (NF2). Recent studies of the ABI have investigated outcomes in non‐NF2 cohorts, such as patients with cochlear nerve aplasia or cochlear ossification and more recently, intractable tinnitus. New technologies that improve the ABI‐neural tissue interface are being explored as means to improve performance and decrease side effects. Innovative discoveries in optogenetics and bioengineering present opportunities to continually evolve this technology into the future, enhancing spatial selectivity of neuronal activation in the cochlear nucleus and preventing side effects through reduction in activation of non‐target neuronal circuitry. These advances will improve surgical planning and ultimately improve patients’ audiological capabilities. ABI research has rapidly increased in the 21st century and applications of this technology are likely to continually evolve. Herein, we aim to characterize ongoing clinical, basic science, and bioengineering advances in ABIs and discuss future directions of this technology.},

keywords = {},

pubstate = {published},

tppubtype = {article}

}

@article{Shetty2021b,

title = {Clinical and scientific innovations in auditory brainstem implants},

author = {Kunal R. Shetty and Sarah E. Ridge and Vivek Kanumuri and Angela Zhu and M. Christian Brown and Daniel J. Lee},

doi = {10.1016/j.wjorl.2021.02.002},

issn = {2589-1081},

year  = {2021},

date = {2021-04-00},

journal = {World j. otorhinolaryngol.-head neck surg.},

volume = {7},

number = {2},

pages = {109--115},

publisher = {Wiley},

abstract = {The auditory brainstem implant (ABI) was originally developed to provide rehabilitation of retrocochlear deafness caused by neurofibromatosis type 2 (NF2). Recent studies of the ABI have investigated outcomes in non‐NF2 cohorts, such as patients with cochlear nerve aplasia or cochlear ossification and more recently, intractable tinnitus. New technologies that improve the ABI‐neural tissue interface are being explored as means to improve performance and decrease side effects. Innovative discoveries in optogenetics and bioengineering present opportunities to continually evolve this technology into the future, enhancing spatial selectivity of neuronal activation in the cochlear nucleus and preventing side effects through reduction in activation of non‐target neuronal circuitry. These advances will improve surgical planning and ultimately improve patients’ audiological capabilities. ABI research has rapidly increased in the 21st century and applications of this technology are likely to continually evolve. Herein, we aim to characterize ongoing clinical, basic science, and bioengineering advances in ABIs and discuss future directions of this technology.},

keywords = {},

pubstate = {published},

tppubtype = {article}

}

@article{Epprecht2021,

title = {Three-dimensional (3D) Printed Vestibular Schwannoma for Facial Nerve Tractography Validation},

author = {Lorenz Epprecht and Ahad Qureshi and Elliott D. Kozin and Stephen McInturff and Aaron Remenschneider and Alexander M. Huber and Merrit Christian Brown and Frederick G. Barker and Katherine L. Reinshagen and Daniel J. Lee},

doi = {10.1097/mao.0000000000003058},

issn = {1537-4505},

year  = {2021},

date = {2021-00-00},

volume = {42},

number = {5},

pages = {e598--e604},

publisher = {Ovid Technologies (Wolters Kluwer Health)},

abstract = {

            Objectives:

            Predicting the course of cranial nerve (CN) VII in the cerebellopontine angle (CPA) on preoperative imaging for vestibular schwannoma (VS) may help guide surgical resection and reduce complications. Diffusion MRI based tractography has been used to identify cranial nerve trajectory, but intraoperative validation of this novel approach is challenging. Currently, validation is based on operative report descriptions of the course of cranial nerves, but yields a simplified picture of the three-dimensional (3D) course of CN VII. In this study, we investigate the accuracy of tractography with detailed patient-specific 3D-printed VS tumors.

          

          

            Design:

            Retrospective case review.

          

          

            Setting:

            Tertiary referral center.

          

          

            Participants:

            Twenty adult VS surgical candidates.

          

          

            Main Outcome Measures:

            We compared tractography with intraoperative 3D course of CN VII. The surgeons were blinded to tractography and drew the intraoperative course of the CN VII on a patient specific 3D-printed tumor model for detailed comparison with tractography.

          

          

            Results:

            Of 20 patients, one was excluded due to subtotal removal and inability to assess CN VII course. In the remaining 19 patients, 84% (16/19) tractography was successful. In 94% of tumors with tractography (15/16), the intraoperative description of CN VII course matched the tractography finding. The maximum distance, however, between tractography and intraoperative course of CN VII was 3.7 mm ± 4.2 mm.

          

          

            Conclusion:

            This study presents a novel approach to CN VII tractography validation in VS. Although descriptions of CN VII intraoperatively match tractography, caution is warranted as quantitative measures suggest a clinically significant distance between tractography and CN VII course.

          },

keywords = {},

pubstate = {published},

tppubtype = {article}

}

@article{Egra-Dagan2021,

title = {Adult Auditory Brainstem Implant Outcomes and Three-Dimensional Electrode Array Position on Computed Tomography},

author = {Dana Egra-Dagan and Isabeau van Beurden and Samuel R. Barber and Christine L. Carter and Mary E. Cunnane and M. Christian Brown and Barbara S. Herrmann and Daniel J. Lee},

doi = {10.1097/aud.0000000000001064},

issn = {1538-4667},

year  = {2021},

date = {2021-00-00},

volume = {42},

number = {6},

pages = {1741--1754},

publisher = {Ovid Technologies (Wolters Kluwer Health)},

abstract = {

            Objectives:

            Factors contributing to auditory brainstem implant (ABI) outcomes are poorly understood. The aims of this study are to (1) characterize ABI electrode array position on postoperative imaging and (2) determine if variability in position is related to perceptual outcomes.

          

          

            Design:

            Retrospective cohort study. Subjects were selected from the adult ABI recipient population at Massachusetts Eye and Ear. Postoperative three-dimensional (3D) computed tomography (CT) reconstruction of the head was used to measure ABI array position in 20 adult ABI recipients (17 with Neurofibromatosis Type 2 (NF2) and three non-NF2 recipients). Three-dimensional electrode array position was determined based on angles from the horizontal using posterior and lateral views and on distances between the proximal array tip superiorly from the basion (D1), laterally (D2P) and posteriorly (D2L) from the midline. Array position was correlated with perceptual data (in 15 of the 20 recipients who used their ABI). Perceptual data included the number of electrodes that provided auditory sensation, location and type of side effects, level of speech perception (from no sound to open-set word recognition of monosyllables) and the amount of charge required for auditory perception.

          

          

            Results:

            Although the 3D orientation of the ABI array exhibited a variety of angles, all arrays were posteriorly tilted from the lateral view and most were medially tilted from the posterior view. ABI position relative to the basion from posterior showed mean distances of 1.71 ± 0.42 and 1.1 ± 0.29 cm for D1 and D2, respectively, and a mean D2 of 1.30 ± 0.45 cm from the lateral view. A strong linear negative correlation was found between the number of active electrodes and the distance of the proximal array tip laterally from the basion (D2P; rs = −0.73, p = 0.006) when measured in the posterior view. Although side effects were experienced in all recipients and varied in type and location across the array, electrodes in the middle part of the array tended to elicit auditory sensations while the proximal and distal tips of the array tended to elicit nonauditory side effects. Arrays with and without low charge thresholds appeared to generally overlap in position. However, the two recipients with the best (open-set) speech perception had low charge thresholds and had arrays that were tilted superiorly in the posterior view.

          

          

            Conclusion:

            ABI recipients with better speech perception appear to share a profile of arrays that are tilted superiorly as compared to recipients with lower speech perception levels. These ABI recipients have a high number of active electrodes (10 or more) and require less electrical charge on individual electrodes to achieve optimal stimulation.

          },

keywords = {},

pubstate = {published},

tppubtype = {article}

}

@article{Tarabichi2019,

title = {Three-Dimensional Surface Reconstruction of the Human Cochlear Nucleus: Implications for Auditory Brain Stem Implant Design},

author = {Osama Tarabichi and Vivek V. Kanumuri and Julian Klug and Nicolas Vachicouras and Maria J. Duarte and Lorenz Epprecht and Elliott D. Kozin and Katherine Reinshagen and Stéphanie P. Lacour and M Christian Brown and Daniel J. Lee},

doi = {10.1055/s-0039-1677863},

issn = {2193-634X},

year  = {2020},

date = {2020-04-00},

journal = {J Neurol Surg B},

volume = {81},

number = {02},

pages = {114--120},

publisher = {Georg Thieme Verlag KG},

abstract = {Abstract

          Objective The auditory brain stem implant (ABI) is a neuroprosthesis placed on the surface of the cochlear nucleus (CN) to provide hearing sensations in children and adults who are not candidates for cochlear implantation. Contemporary ABI arrays are stiff and do not conform to the curved brain stem surface. Recent advancements in microfabrication techniques have enabled the development of flexible surface arrays, but these have only been applied in animal models. Herein, we measure the surface curvature of the human CN and adjoining regions to assist in the design and placement of next-generation conformable clinical ABI arrays. Three-dimensional (3D) reconstructions from ultrahigh T1-weighted brain magnetic resonance imaging (MRI) sequences and histologic reconstructions based on postmortem adult human brain stem specimens were used.

          Design This is a retrospective review of radiologic data and postmortem histologic axial sections.

          Setting This is set at the tertiary referral center.

          Participants Data were acquired from healthy adults.

          Main Outcome Measures The main outcome measures are principal curvature values (Kmin and Kmax) and global radius of curvature.

          Results The CN was successfully extracted and rendered as a 3D surface in all cases. Significant curvatures of the CN in both histologic and radiographic reconstructions were found with global radius of curvature ranging from 2.08 to 8.5 mm. In addition, local curvature analysis revealed that the surface is highly complex.

          Conclusion Detailed rendering of the human CN is feasible using histology and 3D MRI reconstruction and highlights complex surface topography that is not recapitulated by contemporary stiff ABI arrays.},

keywords = {},

pubstate = {published},

tppubtype = {article}

}

@article{Zhu2020,

title = {Concepts in Neural Stimulation},

author = {Angela Zhu and Ahad A. Qureshi and Elliott D. Kozin and Daniel J. Lee},

doi = {10.1016/j.otc.2019.09.002},

issn = {0030-6665},

year  = {2020},

date = {2020-02-00},

journal = {Otolaryngologic Clinics of North America},

volume = {53},

number = {1},

pages = {31--43},

publisher = {Elsevier BV},

keywords = {},

pubstate = {published},

tppubtype = {article}

}

@article{Epprecht2020,

title = {Human Cochlear Nucleus on 7 Tesla Diffusion Tensor Imaging: Insights Into Micro-anatomy and Function for Auditory Brainstem Implant Surgery},

author = {Lorenz Epprecht and Ahad Qureshi and Elliott D. Kozin and Nicolas Vachicouras and Alexander M. Huber and Ron Kikinis and Nikos Makris and M. Christian Brown and Katherine L. Reinshagen and Daniel J. Lee},

doi = {10.1097/mao.0000000000002565},

issn = {1537-4505},

year  = {2020},

date = {2020-00-00},

volume = {41},

number = {4},

pages = {e484--e493},

publisher = {Ovid Technologies (Wolters Kluwer Health)},

abstract = {

            Objective:

            The cochlear nucleus (CN) is the target of the auditory brainstem implant (ABI). Most ABI candidates have Neurofibromatosis Type 2 (NF2) and distorted brainstem anatomy from bilateral vestibular schwannomas. The CN is difficult to characterize as routine structural MRI does not resolve detailed anatomy. We hypothesize that diffusion tensor imaging (DTI) enables both in vivo localization and quantitative measurements of CN morphology.

          

          

            Study Design:

            We analyzed 7 Tesla (T) DTI images of 100 subjects (200 CN) and relevant anatomic structures using an MRI brainstem atlas with submillimetric (50 μm) resolution.

          

          

            Setting:

            Tertiary referral center.

          

          

            Patients:

            Young healthy normal hearing adults.

          

          

            Intervention:

            Diagnostic.

          

          

            Main Outcome Measures:

            Diffusion scalar measures such as fractional anisotropy (FA), mean diffusivity (MD), mode of anisotropy (Mode), principal eigenvectors of the CN, and the adjacent inferior cerebellar peduncle (ICP).

          

          

            Results:

            The CN had a lamellar structure and ventral-dorsal fiber orientation and could be localized lateral to the inferior cerebellar peduncle (ICP). This fiber orientation was orthogonal to tracts of the adjacent ICP where the fibers run mainly caudal-rostrally. The CN had lower FA compared to the medial aspect of the ICP (0.44 ± 0.09 vs. 0.64 ± 0.08, p < 0.001).

          

          

            Conclusions:

            7T DTI enables characterization of human CN morphology and neuronal substructure. An ABI array insertion vector directed more caudally would better correspond to the main fiber axis of CN. State-of-the-art DTI has implications for ABI preoperative planning and future image guidance-assisted placement of the electrode array.

          },

keywords = {},

pubstate = {published},

tppubtype = {article}

}

@article{Epprecht2019,

title = {Super-resolution Diffusion Tensor Imaging for Delineating the Facial Nerve in Patients with Vestibular Schwannoma},

author = {Lorenz Epprecht and Elliott D. Kozin and Marco Piccirelli and Vivek V. Kanumuri and Osama Tarabichi and Aaron Remenschneider and Frederick G. Barker and Michael J. McKenna and Alexander M. Huber and Marybeth E. Cunnane and Katherine L. Reinshagen and Daniel J. Lee},

doi = {10.1055/s-0039-1677864},

issn = {2193-634X},

year  = {2019},

date = {2019-12-00},

journal = {J Neurol Surg B},

volume = {80},

number = {06},

pages = {648--654},

publisher = {Georg Thieme Verlag KG},

abstract = {

            Objectives Predicting the course of cranial nerves (CNs) VII and VIII in the cerebellopontine angle on preoperative imaging for vestibular schwannoma (VS) may help guide surgical resection and reduce complications. Diffusion magnetic resonance imaging dMRI is commonly used for this purpose, but is limited by its resolution. We investigate the use of super-resolution reconstruction (SRR), where several different dMRIs are combined into one dataset. We hypothesize that SRR improves the visualization of the CN VII and VIII.

            Design Retrospective case review.

            Setting Tertiary referral center. SRR was performed on the basis of axial and parasagittal single-shot epiplanar diffusion tensor imaging on a 3.0-tesla MRI scanner.

            Participants Seventeen adult patients with suspected neoplasms of the lateral skull base.

            Main Outcome Measures We assessed separability of the two distinct nerves on fractional anisotropy (FA) maps, the tractography of the nerves through the cerebrospinal fluid (CSF), and FA in the CSF as a measure of noise.

            Results SRR increases separability of the CN VII and VIII (16/17 vs. 0/17, p = 0.008). Mean FA of CSF surrounding the nerves is significantly lower in SRRs (0.07 ± 0.02 vs. 0.13 ± 0.03 [axial images]/0.14 ± 0.05 [parasagittal images], p = 0.00003/p = 0.00005). Combined scanning times (parasagittal and axial) used for SRR were shorter (8 minute 25 seconds) than a comparable high-resolution scan (15 minute 17 seconds).

            Conclusion SRR improves the resolution of CN VII and VIII. The technique can be readily applied in the clinical setting, improving surgical counseling and planning in patients with VS.},

keywords = {},

pubstate = {published},

tppubtype = {article}

}

@article{Meng2019,

title = {Increasing the expression level of ChR2 enhances the optogenetic excitability of cochlear neurons},

author = {Xiankai Meng and Swetha Murali and Yen-Fu Cheng and Jingrong Lu and Ariel E. Hight and Vivek V. Kanumuri and M. Christian Brown and Jeffrey R. Holt and Daniel J. Lee and Albert S.B. Edge},

doi = {10.1152/jn.00828.2018},

issn = {1522-1598},

year  = {2019},

date = {2019-11-01},

journal = {Journal of Neurophysiology},

volume = {122},

number = {5},

pages = {1962--1974},

publisher = {American Physiological Society},

abstract = { Optogenetics comprise a promising alternative to electrical stimulation for characterization of neural circuits and for the next generation of neural prostheses. Optogenetic stimulation relies on expression of photosensitive microbial proteins in animal cells to initiate a flow of ions into the cells in response to visible light. Here, we generated a novel transgenic mouse model in which we studied the optogenetic activation of spiral ganglion neurons, the primary afferent neurons of the auditory system, and showed a strong optogenetic response, with a similar amplitude as the acoustically evoked response. A twofold increase in the level of channelrhodopsin expression significantly increased the photosensitivity at both the single cell and organismal levels but also partially compromised the native electrophysiological properties of the neurons. The importance of channelrhodopsin expression level to optogenetic stimulation, revealed by these quantitative measurements, will be significant for the characterization of neural circuitry and for the use of optogenetics in neural prostheses.  NEW & NOTEWORTHY This study reveals a dose-response relationship between channelrhodopsin expression and optogenetic excitation. Both single cell and organismal responses depend on the expression level of the heterologous protein. Expression level of the opsin is thus an important variable in determining the outcome of an optogenetic experiment. These results are key to the implementation of neural prostheses based on optogenetics, such as next generation cochlear implants, which would use light to elicit a neural response to sound. },

keywords = {},

pubstate = {published},

tppubtype = {article}

}

@article{Vachicouras2019,

title = {Microstructured thin-film electrode technology enables proof of concept of scalable, soft auditory brainstem implants},

author = {Nicolas Vachicouras and Osama Tarabichi and Vivek V. Kanumuri and Christina M. Tringides and Jennifer Macron and Florian Fallegger and Yohann Thenaisie and Lorenz Epprecht and Stephen McInturff and Ahad A. Qureshi and Valentina Paggi and Martin W. Kuklinski and M. Christian Brown and Daniel J. Lee and Stéphanie P. Lacour},

doi = {10.1126/scitranslmed.aax9487},

issn = {1946-6242},

year  = {2019},

date = {2019-10-16},

journal = {Sci. Transl. Med.},

volume = {11},

number = {514},

publisher = {American Association for the Advancement of Science (AAAS)},

abstract = {Engineered conformability in auditory brainstem implant electrode arrays improves the electrode-brainstem interface in mice and in human cadavers.},

keywords = {},

pubstate = {published},

tppubtype = {article}

}

@article{Guex2019,

title = {Auditory brainstem stimulation with a conformable microfabricated array elicits responses with tonotopically organized components},

author = {Amélie A. Guex and Ariel Edward Hight and Shreya Narasimhan and Nicolas Vachicouras and Daniel J. Lee and Stéphanie P. Lacour and M. Christian Brown},

doi = {10.1016/j.heares.2019.02.010},

issn = {0378-5955},

year  = {2019},

date = {2019-06-00},

journal = {Hearing Research},

volume = {377},

pages = {339--352},

publisher = {Elsevier BV},

keywords = {},

pubstate = {published},

tppubtype = {article}

}

@article{Smith2019,

title = {Initial Experience with 3‐Dimensional Exoscope‐Assisted Transmastoid and Lateral Skull Base Surgery},

author = {Sullivan Smith and Elliott D. Kozin and Vivek V. Kanumuri and Samuel R. Barber and Douglas Backous and João Flávio Nogueira and Daniel J. Lee},

doi = {10.1177/0194599818816965},

issn = {1097-6817},

year  = {2019},

date = {2019-02-00},

journal = {Otolaryngol.--head neck surg.},

volume = {160},

number = {2},

pages = {364--367},

publisher = {Wiley},

abstract = {Extracorporeal video microscopes, or “exoscopes,” provide high‐definition views of the operative field and are alternatives to the operating microscope or loupes for large‐corridor surgical approaches. In this proof‐of‐concept study, we aim to determine the feasibility of 3‐dimensional exoscopes as alternatives to operating microscopes in otology and neurotology, espeically in conjunction with endoscopes. Eleven consecutive cases were performed using 3‐dimensional exoscopes in place of, or as adjuncts to, the operating microscope. The exoscope was the sole visualization tool in 7 cases, with 4 including the use of an endoscope or microscope. There were no perioperative complications. Potential subjective advantages include superior ergonomics, compact size, and an equal visual experience for surgeons and observers. Limitations include low lighting in small surgical corridors and pixilation at high magnification. Exoscopes are potentially viable alternatives to the microscope in otologic and neurotologic surgery.},

keywords = {},

pubstate = {published},

tppubtype = {article}

}

@article{Wong2019,

title = {Auditory Brainstem Implants: Recent Progress and Future Perspectives},

author = {Kevin Wong and Elliott D. Kozin and Vivek V. Kanumuri and Nicolas Vachicouras and Jonathan Miller and Stéphanie Lacour and M. Christian Brown and Daniel J. Lee},

doi = {10.3389/fnins.2019.00010},

issn = {1662-453X},

year  = {2019},

date = {2019-01-29},

journal = {Front. Neurosci.},

volume = {13},

publisher = {Frontiers Media SA},

keywords = {},

pubstate = {published},

tppubtype = {article}

}

@article{pmid30017876,

title = {Ancestral Adeno-Associated Virus Vector Delivery of Opsins to Spiral Ganglion Neurons: Implications for Optogenetic Cochlear Implants},

author = {Maria J Duarte and Vivek V Kanumuri and Lukas D Landegger and Osama Tarabichi and Sumi Sinha and Xiankai Meng and Ariel Edward Hight and Elliott D Kozin and Konstantina M Stankovic and M Christian Brown and Daniel J Lee},

doi = {10.1016/j.ymthe.2018.05.023},

issn = {1525-0024},

year  = {2018},

date = {2018-08-01},

journal = {Mol Ther},

volume = {26},

number = {8},

pages = {1931--1939},

abstract = {Optogenetics is a transformative technology based on light-sensitive microbial proteins, known as opsins, that enable precise modulation of neuronal activity with pulsed radiant energy. Optogenetics has been proposed as a means to improve auditory implant outcomes by reducing channel interaction and increasing electrode density, but the introduction of opsins into cochlear spiral ganglion neurons (SGNs) in vivo has been challenging. Here we test opsin delivery using a synthetically developed ancestral adeno-associated virus (AAV) vector called Anc80L65. Wild-type C57BL/6 mouse pups were injected via the round window of cochlea with Anc80L65 carrying opsin Chronos under the control of a CAG promoter. Following an incubation of 6-22 weeks, pulsed blue light was delivered to cochlear SGNs via a cochleosotomy approach and flexible optical fiber. Optically evoked auditory brainstem responses (oABRs) and multiunit activity in inferior colliculus (IC) were observed. Post-experiment cochlear histology demonstrated opsin expression in SGNs (mean = 74%), with an even distribution of opsin along the cochlear basal/apical gradient. This study is the first to describe robust SGN transduction, opsin expression, and optically evoked auditory electrophysiology in neonatal mice. Ultimately, this work may provide the basis for a new generation of cochlear implant based on light.},

keywords = {},

pubstate = {published},

tppubtype = {article}

}

@article{Tarabichi2017,

title = {Diffusion Tensor Imaging of Central Auditory Pathways in Patients with Sensorineural Hearing Loss: A Systematic Review},

author = {Osama Tarabichi and Elliott D. Kozin and Vivek V. Kanumuri and Samuel Barber and Satra Ghosh and Kevin R. Sitek and Katherine Reinshagen and Barbara Herrmann and Aaron K. Remenschneider and Daniel J. Lee},

doi = {10.1177/0194599817739838},

issn = {1097-6817},

year  = {2018},

date = {2018-03-00},

journal = {Otolaryngol.--head neck surg.},

volume = {158},

number = {3},

pages = {432--442},

publisher = {Wiley},

abstract = {ObjectiveThe radiologic evaluation of patients with hearing loss includes computed tomography and magnetic resonance imaging (MRI) to highlight temporal bone and cochlear nerve anatomy. The central auditory pathways are often not studied for routine clinical evaluation. Diffusion tensor imaging (DTI) is an emerging MRI‐based modality that can reveal microstructural changes in white matter. In this systematic review, we summarize the value of DTI in the detection of structural changes of the central auditory pathways in patients with sensorineural hearing loss.Data SourcesPubMed, Embase, and Cochrane.Review MethodsWe used the Preferred Reporting Items for Systematic Reviews and Meta‐Analysis statement checklist for study design. All studies that included at least 1 sensorineural hearing loss patient with DTI outcome data were included.ResultsAfter inclusion and exclusion criteria were met, 20 articles were analyzed. Patients with bilateral hearing loss comprised 60.8% of all subjects. Patients with unilateral or progressive hearing loss and tinnitus made up the remaining studies. The auditory cortex and inferior colliculus (IC) were the most commonly studied regions using DTI, and most cases were found to have changes in diffusion metrics, such as fractional anisotropy, compared to normal hearing controls. Detectable changes in other auditory regions were reported, but there was a higher degree of variability.ConclusionWhite matter changes based on DTI metrics can be seen in patients with sensorineural hearing loss, but studies are few in number with modest sample sizes. Further standardization of DTI using a prospective study design with larger sample sizes is needed.},

keywords = {},

pubstate = {published},

tppubtype = {article}

}

@article{Noij2018,

title = {Audiometric and cVEMP Thresholds Show Little Correlation With Symptoms in Superior Semicircular Canal Dehiscence Syndrome},

author = {Kimberley S. Noij and Kevin Wong and Maria J. Duarte and Salwa Masud and Nicholas A. Dewyer and Barbara S. Herrmann and John J. Guinan and Elliott D. Kozin and David H. Jung and Steven D. Rauch and Daniel J. Lee},

doi = {10.1097/mao.0000000000001910},

issn = {1537-4505},

year  = {2018},

date = {2018-00-00},

volume = {39},

number = {9},

pages = {1153--1162},

publisher = {Ovid Technologies (Wolters Kluwer Health)},

abstract = {

            Objective:

            Evaluate the relationship between objective audiometric and vestibular tests and patient symptoms in superior canal dehiscence (SCD) syndrome.

          

          

            Study Design:

            Retrospective chart review.

          

          

            Setting:

            Tertiary care center.

          

          

            Patients:

            Ninety-eight patients with SCD, preoperative threshold audiograms, cervical vestibular evoked myogenic potential (cVEMP) thresholds, and computed tomography (CT) imaging were included. Clinical reports were reviewed for self-reported SCD symptoms. Twenty-five patients completed the Hearing Handicap Inventory (HHI), Dizziness Handicap Inventory (DHI), Autophony Index (AI), and the 36-item Short Form Survey (SF-36).

          

          

            Main Outcome Measures:

            Correlations between preoperative low-frequency air-bone gap (ABG), cVEMP thresholds, and symptoms (including HHI, DHI, AI, and SF-36). Symptoms included hearing loss, aural fullness, autophony, hyperacusis, tinnitus, vertigo, imbalance and sound-, pressure and exercise provoked dizziness. Secondary outcome measure: Correlations between changes of objective and subjective measures before and after surgery.

          

          

            Results:

            Patients who reported hearing loss had larger ABGs at 250 Hz than patients without subjective hearing loss (p = 0.001). ABGs and cVEMP thresholds did not correlate with any other symptom. No significant correlation was found between ABG or cVEMP threshold and the HHI, DHI, AI or Health Utility Value (derived from the SF-36 quality of life score). Following SCD surgery, ABG decreased (p < 0.001), cVEMP thresholds increased (p < 0.001) and overall symptoms, handicap scores and quality-of-life improved; however, there was no significant relationship between these measures.

          

          

            Conclusion:

            While threshold audiometry and cVEMP are important tools to diagnose SCD and monitor surgical outcomes, these measures showed no significant correlation with vestibular and most auditory symptoms or their severity.

          },

keywords = {},

pubstate = {published},

tppubtype = {article}

}

@article{pmid28700445,

title = {Auditory Brainstem Implant Array Position Varies Widely Among Adult and Pediatric Patients and Is Associated With Perception},

author = {Samuel R Barber and Elliott D Kozin and Aaron K Remenschneider and Sidharth V Puram and Max Smith and Barbara S Herrmann and Mary E Cunnane and M Christian Brown and Daniel J Lee},

doi = {10.1097/AUD.0000000000000448},

issn = {1538-4667},

year  = {2017},

date = {2017-01-01},

journal = {Ear Hear},

volume = {38},

number = {6},

pages = {e343--e351},

abstract = {OBJECTIVES: The auditory brainstem implant (ABI) provides sound awareness to patients who are ineligible for cochlear implantation. Auditory performance varies widely among similar ABI cohorts. We hypothesize that differences in electrode array position contribute to this variance. Herein, we classify ABI array position based on postoperative imaging and investigate the relationship between position and perception.nnDESIGN: Retrospective review of pediatric and adult ABI users with postoperative computed tomography. To standardize views across subjects, true axial reformatted series of scans were created using the McRae line. Using multiplanar reconstructions, basion and electrode array tip coordinates and array angles from vertical were measured. From a lateral view, array angles (V) were classified into types I to IV, and from posterior view, array angles (T) were classified into types A to D. Array position was further categorized by measuring distance vertical from basion (D1) and lateral from midline (D2). Differences between array classifications were compared with audiometric thresholds, number of active electrodes, and pitch ranking.nnRESULTS: Pediatric (n = 4, 2 with revisions) and adult (n = 7) ABI subjects were included in this study. Subjects had a wide variety of ABI array angles, but most were aimed superiorly and posteriorly (type II, n = 7) from lateral view and upright or medially tilted from posterior view (type A, n = 6). Mean pediatric distances were 8 to 42% smaller than adults for D1 and D2. In subjects with perceptual data, electrical thresholds and the number of active electrodes differed among classification types.nnCONCLUSIONS: In this first study to classify ABI electrode array orientation, array position varied widely. This variability may explain differences in auditory performance.},

keywords = {},

pubstate = {published},

tppubtype = {article}

}

@article{pmid25598479,

title = {Superior temporal resolution of Chronos versus channelrhodopsin-2 in an optogenetic model of the auditory brainstem implant},

author = {Ariel Edward Hight and Elliott D Kozin and Keith Darrow and Ashton Lehmann and Edward Boyden and M Christian Brown and Daniel J Lee},

doi = {10.1016/j.heares.2015.01.004},

issn = {1878-5891},

year  = {2015},

date = {2015-04-01},

journal = {Hear Res},

volume = {322},

pages = {235--241},

abstract = {Contemporary auditory brainstem implant (ABI) performance is limited by reliance on electrical neurostimulation with its accompanying channel cross talk and current spread to non-auditory neurons. A new generation ABI based on optogenetic technology may ameliorate limitations fundamental to electrical stimulation. The most widely studied opsin is channelrhodopsin-2 (ChR2); however, its relatively slow kinetic properties may prevent the encoding of auditory information at high stimulation rates. In the present study, we compare the temporal resolution of light-evoked responses of ChR2 to a recently developed fast opsin, Chronos, to ChR2 in a murine ABI model. Viral mediated gene transfer via a posterolateral craniotomy was used to express Chronos or ChR2 in the cochlear nucleus (CN). Following a four to eight week incubation period, blue light (473 nm) was delivered via an optical fiber placed directly on the surface of the infected CN, and neural activity was recorded in the contralateral inferior colliculus (IC). Both ChR2 and Chronos evoked sustained responses to all stimuli, even at high pulse rates. In addition, optical stimulation evoked excitatory responses throughout the tonotopic axis of the IC. Synchrony of the light-evoked response to stimulus rates of 14-448 pulses/s was higher in Chronos compared to ChR2 mice (p < 0.05 at 56, 168, and 224 pulses/s). Our results demonstrate that Chronos has the ability to drive the auditory system at higher stimulation rates than ChR2 and may be a more ideal opsin for manipulation of auditory pathways in future optogenetic-based neuroprostheses. This article is part of a Special Issue entitled "Lasker Award".},

keywords = {},

pubstate = {published},

tppubtype = {article}

}

@article{pmid25481416,

title = {Optogenetic stimulation of the cochlear nucleus using channelrhodopsin-2 evokes activity in the central auditory pathways},

author = {Keith N Darrow and Michaël C C Slama and Elliott D Kozin and Maryanna Owoc and Kenneth Hancock and Judith Kempfle and Albert Edge and Stephanie Lacour and Edward Boyden and Daniel Polley and M Christian Brown and Daniel J Lee},

doi = {10.1016/j.brainres.2014.11.044},

issn = {1872-6240},

year  = {2015},

date = {2015-03-01},

journal = {Brain Res},

volume = {1599},

pages = {44--56},

abstract = {Optogenetics has become an important research tool and is being considered as the basis for several neural prostheses. However, few studies have applied optogenetics to the auditory brainstem. This study explored whether optical activation of the cochlear nucleus (CN) elicited responses in neurons in higher centers of the auditory pathway and whether it elicited an evoked response. Viral-mediated gene transfer was used to express channelrhodopsin-2 (ChR2) in the mouse CN. Blue light was delivered via an optical fiber placed near the surface of the infected CN and recordings were made in higher-level centers. Optical stimulation evoked excitatory multiunit spiking activity throughout the tonotopic axis of the central nucleus of the inferior colliculus (IC) and the auditory cortex (Actx). The pattern and magnitude of IC activity elicited by optical stimulation was comparable to that obtained with a 50dB SPL acoustic click. This broad pattern of activity was consistent with histological confirmation of green fluorescent protein (GFP) label of cell bodies and axons throughout the CN. Increasing pulse rates up to 320Hz did not significantly affect threshold or bandwidth of the IC responses, but rates higher than 50Hz resulted in desynchronized activity. Optical stimulation also evoked an auditory brainstem response, which had a simpler waveform than the response to acoustic stimulation. Control cases showed no responses to optical stimulation. These data suggest that optogenetic control of central auditory neurons is feasible, but opsins with faster channel kinetics may be necessary to convey information at rates typical of many auditory signals.},

keywords = {},

pubstate = {published},

tppubtype = {article}

}

@article{pmid26207184,

title = {Conducting polymer electrodes for auditory brainstem implants},

author = {Amélie A Guex and Nicolas Vachicouras and Ariel E Hight and M Christian Brown and Daniel J Lee and Stéphanie P Lacour},

doi = {10.1039/c5tb00099h},

issn = {2050-750X},

year  = {2015},

date = {2015-01-01},

journal = {J Mater Chem B},

volume = {3},

number = {25},

pages = {5021--5027},

abstract = {The auditory brainstem implant (ABI) restores hearing in patients with damaged auditory nerves. One of the main ideas to improve the efficacy of ABIs is to increase spatial specificity of stimulation, in order to minimize extra-auditory side-effects and to maximize the tonotopy of stimulation. This study reports on the development of a microfabricated conformable electrode array with small (100 m diameter) electrode sites. The latter are coated with a conducting polymer, PEDOT:PSS, to offer high charge injection properties and to safely stimulate the auditory system with small stimulation sites. We report on the design and fabrication of the polymer implant, and characterize the coatings in physiological conditions in vitro and under mechanical deformation. We characterize the coating electrochemically and during bending tests. We present a proof of principle experiment where the auditory system is efficiently activated by the flexible polymeric interface in a rat model. These results demonstrate the potential of using conducting polymer coatings on small electrode sites for electrochemically safe and efficient stimulation of the central auditory system.},

keywords = {},

pubstate = {published},

tppubtype = {article}

}

@article{pmid25650555,

title = {Direct visualization of the murine dorsal cochlear nucleus for optogenetic stimulation of the auditory pathway},

author = {Elliott D Kozin and Keith N Darrow and Ariel E Hight and Ashton E Lehmann and Alyson B Kaplan and M Christian Brown and Daniel J Lee},

doi = {10.3791/52426},

issn = {1940-087X},

year  = {2015},

date = {2015-01-01},

journal = {J Vis Exp},

number = {95},

pages = {52426},

abstract = {Investigation into the use of virus-mediated gene transfer to arrest or reverse hearing loss has largely been relegated to the peripheral auditory system. Few studies have examined gene transfer to the central auditory system. The dorsal cochlear nucleus (DCN) of the brainstem, which contains second order neurons of the auditory pathway, is a potential site for gene transfer. In this protocol, a technique for direct and maximal exposure of the murine DCN via a posterior fossa approach is demonstrated. This approach allows for either acute or survival surgery. Following direct visualization of the DCN, a host of experiments are possible, including injection of opsins into the cochlear nucleus and subsequent stimulation by an optical fiber coupled to a blue light laser. Other neurophysiology experiments, such as electrical stimulation and neural injector tracings are also feasible. The level of visualization and the duration of stimulation achievable make this approach applicable to a wide range of experiments.},

keywords = {},

pubstate = {published},

tppubtype = {article}

}

@article{pmid25437141,

title = {Auditory brainstem implant: electrophysiologic responses and subject perception},

author = {Barbara S Herrmann and M Christian Brown and Donald K Eddington and Kenneth E Hancock and Daniel J Lee},

doi = {10.1097/AUD.0000000000000126},

issn = {1538-4667},

year  = {2015},

date = {2015-01-01},

journal = {Ear Hear},

volume = {36},

number = {3},

pages = {368--376},

abstract = {OBJECTIVES: The primary aim of this study was to compare the perceptual sensation produced by bipolar electrical stimulation of auditory brainstem implant (ABI) electrodes with the morphology of electrically evoked responses elicited by the same bipolar stimulus in the same unanesthetized, postsurgical state. Secondary aims were to (1) examine the relationships between sensations elicited by the bipolar stimulation used for evoked potential recording and the sensations elicited by the monopolar pulse-train stimulation used by the implant processor, and (2) examine the relationships between evoked potential morphology (elicited by bipolar stimulation) to the sensations elicited by monopolar stimulation.nnDESIGN: Electrically evoked early-latency and middle-latency responses to bipolar, biphasic low-rate pulses were recorded postoperatively in four adults with ABIs. Before recording, the perceptual sensations elicited by these bipolar stimuli were obtained and categorized as (1) auditory sensations only, (2) mixed sensations (both auditory and nonauditory), (3) side effect (nonauditory sensations), or (4) no sensation. In addition, the sensations elicited by monopolar higher-rate pulse-train stimuli similar to that used in processor programming were measured for all electrodes in the ABI array and classified using the same categories. Comparisons were made between evoked response morphology, bipolar stimulation sensation, and monopolar stimulation sensation.nnRESULTS: Sensations were classified for 33 bipolar pairs as follows: 21 pairs were auditory, 6 were mixed, 5 were side effect, and 1 was no sensation. When these sensations were compared with the electrically evoked response morphology for these signals, P3 of the electrically evoked auditory brainstem response (eABR) and the presence of a middle-latency positive wave, usually between 15 and 25 msec (electrical early middle-latency response [eMLR]), were only present when the perceptual sensation had an auditory component (either auditory or mixed pairs). The presence of other waves in the early-latency response such as N1 or P2 or a positive wave after 4 msec did not distinguish between only auditory or only nonauditory sensations. For monopolar stimulation, 42 were classified as auditory, 16 were mixed, and 26 were classified as side effect or no sensation. When bipolar sensations were compared with monopolar sensations for the 21 bipolar pairs categorized as auditory, 7 pairs had monopolar sensations of auditory for both electrodes, 9 pairs had only one electrode with a monopolar sensation of auditory, with the remainder having neither electrode as auditory. Of 6 bipolar pairs categorized as mixed, 3 had monopolar auditory sensations for one of the electrodes. When monopolar stimulation was compared with evoked potential morphology elicited by bipolar stimulation, P3 and the eMLR were more likely to be present when one or both of the electrodes in the bipolar pair elicited an auditory or mixed sensation with monopolar stimulation and were less likely to occur when neither of the electrodes had an auditory monopolar sensation. Again, other eABR waves did not distinguish between auditory and nonauditory sensations.nnCONCLUSIONS: ABI electrodes that are associated with auditory sensations elicited by bipolar stimulation are more likely to elicit evoked responses with a P3 wave or a middle-latency wave. P3 of the eABR and M15-25 of the eMLR are less likely to be present if neither electrode of the bipolar pair evoked an auditory sensation with monopolar stimulation.},

keywords = {},

pubstate = {published},

tppubtype = {article}

}

@article{pmid24508368,

title = {Auditory responses to electric and infrared neural stimulation of the rat cochlear nucleus},

author = {Rohit U Verma and Amélie A Guex and Kenneth E Hancock and Nedim Durakovic and Colette M McKay and Michaël C C Slama and M Christian Brown and Daniel J Lee},

doi = {10.1016/j.heares.2014.01.008},

issn = {1878-5891},

year  = {2014},

date = {2014-04-01},

journal = {Hear Res},

volume = {310},

pages = {69--75},

abstract = {In an effort to improve the auditory brainstem implant, a prosthesis in which user outcomes are modest, we applied electric and infrared neural stimulation (INS) to the cochlear nucleus in a rat animal model. Electric stimulation evoked regions of neural activation in the inferior colliculus and short-latency, multipeaked auditory brainstem responses (ABRs). Pulsed INS, delivered to the surface of the cochlear nucleus via an optical fiber, evoked broad neural activation in the inferior colliculus. Strongest responses were recorded when the fiber was placed at lateral positions on the cochlear nucleus, close to the temporal bone. INS-evoked ABRs were multipeaked but longer in latency than those for electric stimulation; they resembled the responses to acoustic stimulation. After deafening, responses to electric stimulation persisted, whereas those to INS disappeared, consistent with a reported "optophonic" effect, a laser-induced acoustic artifact. Thus, for deaf individuals who use the auditory brainstem implant, INS alone did not appear promising as a new approach.},

keywords = {},

pubstate = {published},

tppubtype = {article}

}

@article{pmid23728891,

title = {Identification of inputs to olivocochlear neurons using transneuronal labeling with pseudorabies virus (PRV)},

author = {M Christian Brown and Sudeep Mukerji and Marie Drottar and Alanna M Windsor and Daniel J Lee},

doi = {10.1007/s10162-013-0400-5},

issn = {1438-7573},

year  = {2013},

date = {2013-10-01},

journal = {J Assoc Res Otolaryngol},

volume = {14},

number = {5},

pages = {703--717},

abstract = {Olivocochlear (OC) neurons respond to sound and provide descending input that controls processing in the cochlea. The identities of neurons in the pathways providing inputs to OC neurons are incompletely understood. To explore these pathways, the retrograde transneuronal tracer pseudorabies virus (Bartha strain, expressing green fluorescent protein) was used to label OC neurons and their inputs in guinea pigs. Labeling of OC neurons began 1 day after injection into the cochlea. On day 2 (and for longer survival times), transneuronal labeling spread to the cochlear nucleus, inferior colliculus, and other brainstem areas. There was a correlation between the numbers of these transneuronally labeled neurons and the number of labeled medial (M) OC neurons, suggesting that the spread of labeling proceeds mainly via synapses on MOC neurons. In the cochlear nucleus, the transneuronally labeled neurons were multipolar cells including the subtype known as planar cells. In the central nucleus of the inferior colliculus, transneuronally labeled neurons were of two principal types: neurons with disc-shaped dendritic fields and neurons with dendrites in a stellate pattern. Transneuronal labeling was also observed in pyramidal cells in the auditory cortex and in centers not typically associated with the auditory pathway such as the pontine reticular formation, subcoerulean nucleus, and the pontine dorsal raphe. These data provide information on the identity of neurons providing input to OC neurons, which are located in auditory as well as non-auditory centers.},

keywords = {},

pubstate = {published},

tppubtype = {article}

}

@article{pmid23165747,

title = {Tensor tympani motoneurons receive mostly excitatory synaptic inputs},

author = {Thane E Benson and Daniel J Lee and M Christian Brown},

doi = {10.1002/ar.22620},

issn = {1932-8494},

year  = {2013},

date = {2013-01-01},

journal = {Anat Rec (Hoboken)},

volume = {296},

number = {1},

pages = {133--145},

abstract = {The tensor tympani is a middle ear muscle that contracts in two different situations: in response to sound or during voluntary movements. To gain insight into the inputs and neural regulation of the tensor tympani, we examined the ultrastructure of synaptic terminals on labeled tensor tympani motoneurons (TTMNs) using transmission electron microscopy. Our sample of six TTMNs received 79 synaptic terminals that formed 126 synpases. Two types of synapses are associated with round vesicles and form asymmetric junctions (excitatory morphology). One of these types has vesicles that are large and round (Lg Rnd) and the other has vesicles that are smaller and round (Sm Rnd) and also contains at least one dense core vesicle. A third synapse type has inhibitory morphology because it forms symmetric synapses with pleomorphic vesicles (Pleo). These synaptic terminals can be associated with TTMN spines. Two other types of synapse are found on TTMNs but they are uncommon. Synaptic terminals of all types form multiple synapses but those from a single terminal are always the same type. Terminals with Lg Rnd vesicles formed the most synpases per terminal (avg. 2.73). Together, the synaptic terminals with Lg Rnd and Sm Rnd vesicles account for 62% of the terminals on TTMNs, and they likely represent the pathways driving the contractions in response to sound or during voluntary movements. Having a high proportion of excitatory inputs, the TTMN innervation is like that of stapedius motoneurons but proportionately different from other types of motoneurons.},

keywords = {},

pubstate = {published},

tppubtype = {article}

}

@article{pmid19397898,

title = {A morphologic study of Fluorogold labeled tensor tympani motoneurons in mice},

author = {Sudeep Mukerji and M Christian Brown and Daniel J Lee},

doi = {10.1016/j.brainres.2009.04.035},

issn = {1872-6240},

year  = {2009},

date = {2009-06-01},

journal = {Brain Res},

volume = {1278},

pages = {59--65},

abstract = {The tensor tympani is one of two middle ear muscles that regulates the transmission of sound through the middle ear. Contraction of the tensor tympani in response to both auditory and non-auditory stimulation is mediated by the tensor tympani motoneurons (TTMNs). There are interesting differences among species in the acoustic thresholds for contraction of the middle ear muscles, which may be a reflection of underlying anatomical differences such as the number of TTMNs. However anatomical data for mice are lacking, even though the mouse is becoming the most common animal model for auditory and neuroscience research. We investigated the number and morphology of TTMNs in mice using Fluorogold, a retrograde neuronal tracer. After injections of Fluorogold into the tensor tympani muscle, a column of labeled TTMNs was identified ventro-lateral to the ipsilateral trigeminal nucleus. The labeled TTMNs were classified according to their morphological characteristics into three subtypes: "octopus-like", "fusiform" and "stellate", suggesting underlying differences in function. All three subtypes formed sparsely branched and radiating dendrites, some longer than 600 microm. Dendrites were longest and most numerous in the dorso-medial direction. In 18 cases, the mean number of mouse TTMNs was 51; the largest numbers were 70, 74 and 90 (n=3 injections). The mean size of mouse TTMNs was 13.0 microm (minor axis) and 23.5 microm (major axis). Compared with studies of TTMNs in larger species (cats and rats), mouse TTMNs are both fewer in number and smaller in size.},

keywords = {},

pubstate = {published},

tppubtype = {article}

}

@article{pmid18563488,

title = {Diverse synaptic terminals on rat stapedius motoneurons},

author = {Daniel J Lee and Thane E Benson and M Christian Brown},

doi = {10.1007/s10162-008-0125-z},

issn = {1525-3961},

year  = {2008},

date = {2008-09-01},

journal = {J Assoc Res Otolaryngol},

volume = {9},

number = {3},

pages = {321--333},

abstract = {Stapedius motoneurons (SMN) mediate the contraction of the stapedius muscle, which protects the inner ear from injury and reduces the masking effects of background noise. A variety of inputs to SMNs are known to exist, but their terminal ultrastructure has not been investigated. We characterized the synaptic terminals on retrogradely labeled SMNs found just ventromedial to the facial motor nucleus. About 80% of the terminals contained round synaptic vesicles. One type (Sm Rnd) had small, round vesicles filling the terminal with occasional dense core vesicles and formed an asymmetric synapse. Sm Rnd terminals were small with lengths of apposition to the SMN less than 3 microm. Partial reconstructions from serial sections demonstrated that these terminals formed up to three synapses per terminal. Another terminal type (Lg Rnd) had large, round vesicles and asymmetric synapses. Most Lg Rnd terminals were small but some were extensive, e.g., abutting the SMN for up to 10 microm. One of these terminals formed at least seven synapses. Another terminal type (Pleo) had pleomorphic vesicles and symmetric active zones that, in some cases, were invaginated by spines from the SMN. A fourth uncommon terminal type (Het Rnd) had round vesicles of heterogeneous sizes and asymmetric synapses. A fifth rare terminal type (Cist) had large, round vesicles and an accompanying subsurface cistern in the SMN. These were generally the same kinds of terminals found on other motoneurons, but the high proportion of round vesicle synapses indicate that SMNs receive mostly excitatory inputs.},

keywords = {},

pubstate = {published},

tppubtype = {article}

}

@article{pmid16550576,

title = {Central auditory pathways mediating the rat middle ear muscle reflexes},

author = {Daniel J Lee and Ronald K de Venecia and John J Guinan and M Christian Brown},

doi = {10.1002/ar.a.20296},

issn = {1552-4884},

year  = {2006},

date = {2006-04-01},

journal = {Anat Rec A Discov Mol Cell Evol Biol},

volume = {288},

number = {4},

pages = {358--369},

abstract = {The middle ear muscle (MEM) reflexes function to protect the inner ear from intense acoustic stimuli and to reduce acoustic masking. Sound presented to the same side or to the opposite side activates the MEM reflex on both sides. The ascending limbs of these pathways must be the auditory nerve fibers originating in the cochlea and terminating in the cochlear nucleus, the first relay station for all ascending auditory information. The descending limbs project from the motoneurons in the brainstem to the MEMs on both sides, causing their contraction. Although the ascending and descending pathways are well described, the cochlear nucleus interneurons that mediate these reflex pathways have not been identified. In order to localize the MEM reflex interneurons, we developed a physiologically based reflex assay in the rat that can be used to determine the integrity of the reflex pathways after experimental manipulations. This assay monitored the change in tone levels and distortion product otoacoustic emissions within the ear canal in one ear during the presentation of a reflex-eliciting sound stimulus in the contralateral ear. Preliminary findings using surgical transection and focal lesioning of the auditory brainstem to interrupt the MEM reflexes suggest that MEM reflex interneurons are located in the ventral cochlear nucleus.},

keywords = {},

pubstate = {published},

tppubtype = {article}

}