John Oghalai - Academia.edu (original) (raw)

Papers by John Oghalai

BMJ open, 2015

Aetiological assessment of 71 probands whose clinical presentation suggested a genetic syndrome o... more Aetiological assessment of 71 probands whose clinical presentation suggested a genetic syndrome or auditory neuropathy. Sanger sequencing was performed on DNA isolated from peripheral blood or lymphoblastoid cell lines. Genes were selected for sequencing based on each patient's clinical presentation and suspected diagnosis. Observed DNA sequence variations were assessed for pathogenicity by review of the scientific literature, and mutation and polymorphism databases, through the use of in silico tools including sorting intolerant from tolerant (SIFT) and polymorphism phenotyping (PolyPhen), and according to the recommendations of the American College of Medical Genetics and Genomics for the interpretation of DNA sequence variations. Novel DNA sequence variations were sought in controls. DNA sequencing of the coding and near-coding regions of genes relevant to each patient's clinical presentation revealed 37 sequence variations of known or uncertain pathogenicity in 9 genes f...

Biomedical Optics Express, 2015

We demonstrate a miniature, tunable, minimally invasive endoscope for diagnosis of the auditory s... more We demonstrate a miniature, tunable, minimally invasive endoscope for diagnosis of the auditory system. The probe is designed to sharply image anatomical details of the middle ear without the need for physically adjusting the position of the distal end of the endoscope. This is achieved through the addition of an electrowetted, tunable, electronically-controlled lens to the optical train. Morphological imaging is enabled by scanning light emanating from an optical coherence tomography system. System performance was demonstrated by imaging part of the ossicular chain and wall of the middle ear cavity of a normal mouse. During the experiment, we electronically moved the plane of best focus from the incudo-stapedial joint to the stapedial artery. Repositioning the object plane allowed us to image anatomical details of the middle ear beyond the depth of field of a static optical system. We also demonstrated for the first time to our best knowledge, that an optical system with an electrowetted, tunable lens may be successfully employed to measure sound-induced vibrations within the auditory system by measuring the vibratory amplitude of the tympanic membrane in a normal mouse in response to pure tone stimuli.

Frontiers in cellular neuroscience, 2015

Sensorineural hearing loss is most commonly caused by the death of hair cells in the organ of Cor... more Sensorineural hearing loss is most commonly caused by the death of hair cells in the organ of Corti, and once lost, mammalian hair cells do not regenerate. In contrast, other vertebrates such as birds can regenerate hair cells by stimulating division and differentiation of neighboring supporting cells. We currently know little of the genetic networks which become active in supporting cells when hair cells die and that are activated in experimental models of hair cell regeneration. Several studies have shown that neonatal mammalian cochlear supporting cells are able to trans-differentiate into hair cells when cultured in conditions in which the Notch signaling pathway is blocked. We now show that the ability of cochlear supporting cells to trans-differentiate declines precipitously after birth, such that supporting cells from six-day-old mouse cochlea are entirely unresponsive to a blockade of the Notch pathway. We show that this trend is seen regardless of whether the Notch pathway ...

International journal of pediatric otorhinolaryngology, 2011

To examine middle ear volume in patients with aural atresia and investigate the role of middle ea... more To examine middle ear volume in patients with aural atresia and investigate the role of middle ear volume as an adjunct measure in determining surgical candidacy. We performed a retrospective review of children with aural atresia in a tertiary academic pediatric otolaryngology practice. High resolution multiplanar CT scans of the temporal bones were analyzed for middle ear volume and staged according to existing clinical grading scales. Atretic ears were compared to the nonatretic ears of the same patient as well as to ears of a control population. The average age of patients at the time CT was performed was 4.7 years (range <0.1-13.8 years). The average middle ear volume of the atretic ears was 0.34 cc compared to an average of 0.51 cc for the nonatretic ears. The mean ratio of the atretic to nonatretic volume was 0.67. In patients who underwent serial scans, no statistically significant difference in rates of growth existed between atretic and nonatretic ears. Finally, measures...

The Laryngoscope, Jan 12, 2014

The tectorial membrane (TM) connects to the stereociliary bundles of outer hair cells (OHCs). Her... more The tectorial membrane (TM) connects to the stereociliary bundles of outer hair cells (OHCs). Herein, we summarize key experimental data and modeling analyses that describe how biophysical alterations to these connections underlie hearing loss. The heterozygous C1509G mutation in alpha tectorin produces partial congenital hearing loss that progresses in humans. We engineered this mutation in mice, and histology revealed that

The Laryngoscope, 2002

To evaluate hearing preservation and facial nerve (FN) outcome in the middle fossa (MF) approach ... more To evaluate hearing preservation and facial nerve (FN) outcome in the middle fossa (MF) approach for acoustic neuromas with a cerebellopontine angle (CPA) component >10 mm. Retrospective review of 193 patients. Patients were grouped according to tumor size: intracanalicular tumors (IC; 64), 1 to 9 mm CPA extension (42), and 10 to 18 mm CPA extension (47). Additionally, a group of 40 patients (tumor size 10-18 mm CPA extension) who had undergone a translabyrinthine (TL) approach was studied to assess comparative FN outcome. Hearing and FN function were measured 1 year postoperatively. We defined the success at functional hearing preservation as AAO-HNS class B or better and good FN outcome as House-Brackmann grade II or better. For IC tumors and those with up to 9-mm CPA extension, there was no significant difference in the rate of functional hearing preservation (62.2% vs. 63.1%, P =.931) and good FN outcome (93.7% vs. 97.6%, P =.358). For tumors of 10- to 18-mm CPA extension, th...

PloS one, 2013

The outer hair cell (OHC) motor protein prestin is necessary for electromotility, which drives co... more The outer hair cell (OHC) motor protein prestin is necessary for electromotility, which drives cochlear amplification and produces exquisitely sharp frequency tuning. Tecta(C1509G) transgenic mice have hearing loss, and surprisingly have increased OHC prestin levels. We hypothesized, therefore, that prestin up-regulation may represent a generalized response to compensate for a state of hearing loss. In the present study, we sought to determine the effects of noise-induced hearing loss on prestin expression. After noise exposure, we performed cytocochleograms and observed OHC loss only in the basal region of the cochlea. Next, we patch clamped OHCs from the apical turn (9-12 kHz region), where no OHCs were lost, in noise-exposed and age-matched control mice. The non-linear capacitance was significantly higher in noise-exposed mice, consistent with higher functional prestin levels. We then measured prestin protein and mRNA levels in whole-cochlea specimens. Both Western blot and qPCR ...

Optics letters, 2014

Phase-sensitive optical coherence tomography (PhOCT) offers exquisite sensitivity to mechanical v... more Phase-sensitive optical coherence tomography (PhOCT) offers exquisite sensitivity to mechanical vibration in biological tissues. There is growing interest in using PhOCT for imaging the nanometer scale vibrations of the ear in animal models of hearing disorders. Swept-source-based systems offer fast acquisition speeds, suppression of common mode noise via balanced detection, and good signal roll-off. However, achieving high phase stability is difficult due to nonlinear laser sweeps and trigger jitter in a typical swept laser source. Here, we report on the initial application of a Vernier-tuned distributed Bragg reflector (VT-DBR) swept laser as the source for a fiber-based PhOCT system. The VT-DBR swept laser is electronically tuned and precisely controls sweeps without mechanical movement, resulting in highly linear sweeps with high wavelength stability and repeatability. We experimentally measured a phase sensitivity of 0.4 pm standard deviation, within a factor of less than 2 of ...

Proceedings of the National Academy of Sciences of the United States of America, Jan 3, 2015

Sound is encoded within the auditory portion of the inner ear, the cochlea, after propagating dow... more Sound is encoded within the auditory portion of the inner ear, the cochlea, after propagating down its length as a traveling wave. For over half a century, vibratory measurements to study cochlear traveling waves have been made using invasive approaches such as laser Doppler vibrometry. Although these studies have provided critical information regarding the nonlinear processes within the living cochlea that increase the amplitude of vibration and sharpen frequency tuning, the data have typically been limited to point measurements of basilar membrane vibration. In addition, opening the cochlea may alter its function and affect the findings. Here we describe volumetric optical coherence tomography vibrometry, a technique that overcomes these limitations by providing depth-resolved displacement measurements at 200 kHz inside a 3D volume of tissue with picometer sensitivity. We studied the mouse cochlea by imaging noninvasively through the surrounding bone to measure sound-induced vibra...

JAMA otolaryngology-- head & neck surgery, Jan 8, 2014

The irregular and complex osteology of the bony skull base houses the intrapetrous internal carot... more The irregular and complex osteology of the bony skull base houses the intrapetrous internal carotid artery (ICA), which represents a potential obstacle to the complete extirpation of benign skull base lesions. This 2-part study 1) investigated the cadaveric basis for the mobilization of the intrapetrous ICA and 2) correlated the cadaveric anatomic findings with the authors&amp;amp;amp;amp;amp;#39; clinical experience. We conclude that the ICA can be mobilized relatively safely. The degree of mobility achieved directly relates to the surgical approach and exposure. Limited mobility is achieved when an anterior petrosal approach is used with various neurosurgical procedures. Conversely, transcochlear and infratemporal approaches allow for optimal ICA translation. The safety of ICA mobilization is documented by the low complication rate in our series.

Cochlear outer hair cells (OHCs) are polarized epithelial cells that have mechanoelectrical trans... more Cochlear outer hair cells (OHCs) are polarized epithelial cells that have mechanoelectrical transduction channels within their apical stereocilia and produce electromotile force along their lateral wall. Phase shifts, or time delays, in the transmembrane voltage occurring at different axial locations along the cell may contribute to our understanding of how these cells operate at auditory frequencies. We developed a method to optically measure the phase of the OHC transmembrane potential using the voltage-sensitive dye (VSD) di-8-ANEPPS. The exit aperture of a fibre-optic light source was driven in two dimensions so that a 24 microm spot of excitation light could be positioned along the length of the OHC. We used the whole-cell patch-clamp technique in the current-clamp mode to stimulate the OHC at the base. The photometric response and the voltage response were monitored with a photodetector and patch-clamp amplifier, respectively. The photometric response was used to measure the regional changes in the membrane potential in response to maintained (dc) and sinusoidal (ac) current stimuli applied at the base of the cell. We used a neutral density filter to lower the excitation light intensity and reduce phototoxicity. A sensitive detector and lock-in amplifier were used to measure the small ac VSD signal. This permitted measurements of the ac photometric response below the noise floor of the static fluorescence. The amplitude and phase components of the photometric response were recorded for stimuli up to 800 Hz. VSD data at 400-800 Hz show the presence of a small phase delay between the stimulus voltage at the base of the cell and the local membrane potential measured along the lateral wall. Results are consistent with the hypothesis that OHCs exhibit inhomogeneous membrane potentials that vary with position in analogy with the voltage in nerve axons.

Jaro-journal of The Association for Research in Otolaryngology, 2007

The BETA2/NeuroD1 null mouse has cochlear dysplasia. Its cochlear duct is shorter than normal, th... more The BETA2/NeuroD1 null mouse has cochlear dysplasia. Its cochlear duct is shorter than normal, there is a lack of spiral ganglion neurons, and there is hair cell disorganization. We measured vertical movements of the tectorial membrane at acoustic frequencies in excised cochleae in response to mechanical stimulation of the stapes using laser doppler vibrometry. While tuning curve sharpness was similar

Otology & Neurotology, 2004

Close Window. Close Window. Thank you for choosing to subscribe to the eTOC for Otology &... more Close Window. Close Window. Thank you for choosing to subscribe to the eTOC for Otology &amp;amp; Neurotology. Enter your Email address: Wolters Kluwer Health may email you for journal alerts and information, but is committed to ...

Otology & Neurotology, 2012

Objective: The benefits of cochlear implantation for children with developmental delays (DD) ofte... more Objective: The benefits of cochlear implantation for children with developmental delays (DD) often are unclear. We compared cognition, adaptive behavior, familial stress, and communication in children with and without DD. Study Design: Retrospective review. Setting: Two tertiary care pediatric hospitals. Patients: Two hundred four children who underwent cochlear implantation assessed before and more than 1 year after implantation. Main Outcome Measures: The Mullen Scales of Early Learning (MSEL), Vineland Adaptive Behavior Scales (VABS), Parental Stress Index, and Preschool Language Scale. Results: We developed a specific definition of DD for hearingimpaired children based upon Diagnostic and Statistical Manual of Mental Disorders, Fourth Edition, criteria for mental retardation; 60 children met the criteria for DD, and 144 children did not. Before implantation, multiple linear regression demonstrated that children with DD had lower scores in every domain of the MSEL and VABS (p G 0.05), but no differences in any domains of the Parental Stress Index and Preschool Language Scale (p 9 0.1) compared with children without DD. After implantation, children without DD demonstrated significant improvements in intelligence as measured by the MSEL and ageappropriate improvements in adaptive behavior as evaluated by the VABS, and their familial stress levels were not increased after cochlear implantation. In contrast, children with DD underwent implantation at a later age and demonstrated less comprehensive developmental improvements after cochlear implantation and higher stress levels. However, when the age differences were taken into account using multiple linear regression analyses, the differences between the 2 cohorts were reduced. Conclusion: These data indicate that our definition of DD is a reliable method of stratifying deaf children. Although children with DD have a normal developmental rate of adaptive behavior after cochlear implantation, their developmental rate of intelligence is lower, and they have higher stress levels than children without DD. However, our data suggest that if children with DD could be implanted as early as children without DD, their intelligence and stress outcomes would be improved.

Biomed. Opt. Express, 2013

Sound transduction within the auditory portion of the inner ear, the cochlea, is a complex nonlin... more Sound transduction within the auditory portion of the inner ear, the cochlea, is a complex nonlinear process. The study of cochlear mechanics in large rodents has provided important insights into cochlear function. However, technological and experimental limitations have restricted studies in mice due to their smaller cochlea. These challenges are important to overcome because of the wide variety of transgenic mouse strains with hearing loss mutations that are available for study. To accomplish this goal, we used spectral domain optical coherence tomography to visualize and measure sound-induced vibrations of intracochlear tissues. We present, to our knowledge, the first vibration measurements from the apex of an unopened mouse cochlea.

Journal of Neurophysiology, 2014

The tonotopic map of the mammalian cochlea is commonly thought to be determined by the passive me... more The tonotopic map of the mammalian cochlea is commonly thought to be determined by the passive mechanical properties of the basilar membrane. The other tissues and cells that make up the organ of Corti also have passive mechanical properties; however, their roles are less well understood. In addition, active forces produced by outer hair cells (OHCs) enhance the vibration of the basilar membrane, termed cochlear amplification. Here, we studied how these biomechanical components interact using optical coherence tomography, which permits vibratory measurements within tissue. We measured not only classical basilar membrane tuning curves, but also vibratory responses from the rest of the organ of Corti within the mouse cochlear apex in vivo. As expected, basilar membrane tuning was sharp in live mice and broad in dead mice. Interestingly, the vibratory response of the region lateral to the OHCs, the &amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;quot;lateral compartment,&amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;quot; demonstrated frequency-dependent phase differences relative to the basilar membrane. This was sharply tuned in both live and dead mice. We then measured basilar membrane and lateral compartment vibration in transgenic mice with targeted alterations in cochlear mechanics. Prestin(499/499), Prestin(-/-), and Tecta(C1509G/C1509G) mice demonstrated no cochlear amplification but maintained the lateral compartment phase difference. In contrast, Sfswap(Tg/Tg) mice maintained cochlear amplification but did not demonstrate the lateral compartment phase difference. These data indicate that the organ of Corti has complex micromechanical vibratory characteristics, with passive, yet sharply tuned, vibratory characteristics associated with the supporting cells. These characteristics may tune OHC force generation to produce the sharp frequency selectivity of mammalian hearing.

BMC Medical Genetics, 2005

Background: Cochlear outer hair cells change their length in response to variations in membrane p... more Background: Cochlear outer hair cells change their length in response to variations in membrane potential. This capability, called electromotility, is believed to enable the sensitivity and frequency selectivity of the mammalian cochlea. Prestin is a transmembrane protein required for electromotility. Homozygous prestin knockout mice are profoundly hearing impaired. In humans, a single nucleotide change in SLC26A5, encoding prestin, has been reported in association with hearing loss. This DNA sequence variation, IVS2-2A>G, occurs in the exon 3 splice acceptor site and is expected to abolish splicing of exon 3.