Robert V Harrison

The Hospital for Sick Children, and University of Toronto · Otolaryngology - Head and Neck Surgery

Congenital cytomegalovirus (CMV) infection is a significant cause of neonatal hearing loss. However, at the cochlear level, the anatomical lesions and pathophysiological mechanisms that underlie hearing loss are still not clearly understood. In murine models of CMV infection, we have observed early damage to the capillary networks in stria vascular...

Introduction Ultrasonic bone removal devices (UBD) are capable of cutting through bony tissue without injury to adjacent soft tissue. The feasibility and safety of using this technology for removal of bone from an intact ossicular chain (as might be required for otosclerosis or congenital fixation) was investigated in an animal model. Methods This...

Objective(s) To create and validate a synthetic simulator for teaching tracheostomy and laryngotracheal reconstruction (LTR) using anterior costal cartilage and thyroid ala cartilage grafts. Methods A late adolescent/adult neck and airway simulator was constructed based on CT scans from a cadaver and a live patient. Images were segmented to create...

We present a new hypothesis for the pathogenesis of auditory neuropathy spectrum disorder (ANSD) in at risk neonates involving depletion of riboflavin. The association between neonatal hyperbilirubinemia and ANSD is well recognized, yet causation has not been proven. The risk of ANSD does not correlate clearly with severity of hyperbilirubinemia an...

Objectives/hypothesis: To evaluate the validity of a live porcine model for surgical training in tracheostomy and open-airway surgery. Study design: Prospective observational study. Methods: Eleven expert otolaryngologists-head and neck surgeons rated a live porcine model's realism/anatomical accuracy (face validity) and perceived effectivenes...

Background: Inherited defects in adenosine deaminase (ADA) cause severe immune deficiency, which can be corrected by ADA enzyme replacement therapy (ERT). Additionally, ADA-deficient patients suffer from hearing impairment. We hypothesized that ADA-deficient (–/–) mice also exhibit hearing abnormalities and that ERT from an early age will improve t...

Sensory brain regions show neuroplastic changes following deficits or experimental augmentation of peripheral input during a neonatal period. We have previously shown reorganization of cortical tonotopic maps after neonatal cochlear lesions or exposure to an enhanced acoustic environment. Such experiments probe the cortex and show reorganization, b...

Background: Cochlear nerve aplasia (CNA) may present with features of auditory neuropathy spectrum disorder (ANSD), having detectable otoacoustic emissions (OAE) but profound hearing loss. We propose that some children with CNA have a distinct form of afferent ANSD in which efferent cochlear nerve function can be detected using contralateral suppr...

The lizard is a useful model for study of the biophysics of peripheral auditory function, not least because it has a hearing organ that is relatively simple compared to the mammalian cochlea. To fully understand inner ear mechanisms, an accurate and detailed description of anatomy is required. To that end we describe morphology and arrangement of h...

Cytomegalovirus (CMV) infection is one of the most common causes of congenital hearing loss in children. We have used a murine model of CMV infection to reveal functional and structural cochlear pathogenesis. The cerebral cortex of Balb/c mice (Mus musculus) was inoculated with 2000 pfu (plaque forming units) of murine CMV on postnatal day 3. At 6...

The Canadian Hearing and Auditory Research Translation (CHART) group is a newly formed taskforce to develop collaborative research initiatives. Initial discussions centered on diagnostic improvements for middle ear disease, auditory neuropathy spectrum disorder, tinnitus and presbycusis. Central to these discussions was the widely held view that th...

Conclusion With age, in a mouse model, degenerative changes to the capillaries of the stria vascularis are observed. These range from a narrowing of vessel lumen to complete degeneration of strial vessels. Other vascular beds in the cochlea are relatively unchanged with age. Strial capillaries at the cochlear base are significantly more affected th...

Auditory brain areas undergo reorganization resulting from abnormal sensory input during early postnatal development. This is evident from studies at the cortical level but it remains unclear whether there is reorganization in the auditory midbrain in a species similar to the human, that is, with early hearing onset. We have explored midbrain plast...

We discuss issues related to cochlear implantation in children with auditory neuropathy spectrum disorder (ANSD). We describe the varied nature of this disease category including the numerous potential causes of auditory neuropathy. The most prevalent etiology for infants with ANSD is associated with prolonged neonatal intensive care unit (NICU) st...

Many causes of age-related hearing loss have been proposed including degenerative changes to cochlear vasculature. This is the basis for the concept of strial presbyacusis. However a close relationship between auditory threshold changes and local vascular degeneration has not been clearly demonstrated. Here we quantify structural properties of stri...

The aim of this study was to characterize changes in the vascular architecture along the cochlear length in an animal model of CMV. We expected to detect vascular degeneration along the cochlea that correlates with an increase of the thresholds of auditory brainstem responses (ABR) and distortion products otoacustic emissions (DPOAEs) measurements....

Objectives/hypothesis: To investigate the timing and degree of angiogenesis following anterior costal cartilage graft laryngotracheoplasty in an animal model. Study design: Randomized controlled animal model. Methods: Twelve pigs were included in this study. Three control pigs were perfused with intravascular methyl methacrylate, and overlying...

We describe in detail a reliable experimental protocol for c-fos immuno-labeling of patterns of neural activation in the chinchilla (chinchilla laniger). We report on resting-level neural activity in inferior colliculus (IC) of auditory midbrain, and on tonotopic bands present following 90 minutes of pure-tone sound stimulation. Neurons activated b...

An emerging environmental health issue relates to potential ill-effects of wind turbine noise. There have been numerous suggestions that the low-frequency acoustic components in wind turbine signals can cause symptoms associated with vestibular system disorders, namely vertigo, nausea, and nystagmus. This constellation of symptoms has been labeled...

The dynamics of cochlear excitotoxicity can be monitored from effects on the contralateral ear. After unilateral mechanical ablation of the cochlea (in a mouse model) we observed immediate elevations in auditory brainstem evoked response (ABR) thresholds in the contralateral ear. Threshold elevations peaked at 2-3 hrs post ablation, and returned to...

Background The two ears are linked with a neural pathway such that stimulation of one ear has a modulating effect on the contralateral cochlea. This is mediated by cochlear afferent neurons connecting with olivo-cochlear efferents. The monitoring of this pathway is easily achieved by measuring contralateral suppression of otoacoustic emissions, and...

Structure and function of central synapses are profoundly influenced by experience during developmental sensitive periods. Sensory synapses, which are the indispensable interface for the developing brain to interact with its environment, are particularly plastic. In the auditory system, moderate forms of unilateral hearing loss during development a...

Newborn hearing screening is an established healthcare standard in many countries and testing is feasible using otoacoustic emission (OAE) recording. It is well documented that OAEs can be suppressed by acoustic stimulation of the ear contralateral to the test ear. In clinical otoacoustic emission testing carried out in a sound attenuating booth, a...

Objectives: Mediated by the medial olivocochlear system (MOCS), distortion product otoacoustic emission (DPOAE) levels are reduced by presentation of contralateral acoustic stimuli. Such acoustic signals can also evoke a middle ear muscle reflex (MEMR) that also attenuates recorded DPOAE levels. Our aim is to clearly differentiate these two inhibi...

Subglottic stenosis can result from endotracheal tube injury. The mechanism by which this occurs, however, is not well understood. The purpose of this study was to examine the role of angiogenesis, hypoxia and ischemia in subglottic mucosal injury following endotracheal intubation. Six Yorkshire piglets were randomized to either a control group (N=...

Closed-field stimulation of one ear, at high sound intensity, will activate both ears because of bone/soft tissue transmission of the acoustic signal across the skull. In human psychophysics and in clinical audiometry a knowledge of interaural attenuation values is important, particularly when assessing asymmetrical hearing loss or in studies of mo...

Conclusion: In the neonatal chinchilla, the degree of contralateral distortion product otoacoustic emission (DPOAE) suppression and the latency and time constants of suppression are immature for 40-60 days. This suggests that olivocochlear efferent innervation of outer hair cells is not fully mature at birth in this animal model, and this may also...

Auriculo-condylar syndrome (ACS) is a rare condition affecting first branchial arch structures. The types of hearing loss and temporal bone findings in ACS have not been reported. We describe a 14-year-old male with constricted pinnae, mandibular dysostosis, glossoptosis, a high-arched palate, hearing loss, and cholesteatoma. Computed tomography im...

The mammalian ear has an extraordinary capacity to detect very low-level acoustic signals from the environment. Sound pressures as low as a few μ Pa (-10 dB SPL) can activate cochlear hair cells. To achieve this sensitivity, biological noise has to be minimized including that generated by cardiovascular pulsation. Generally, cardiac pressure change...

Introduction. Previous work has shown a strong association between alterations in cochlear vasculature, aging, and the development of presbycusis. The important role of vascular endothelial growth factor (VEGF) and its receptors Flt-1 and Flk-1 in angiogenesis suggests a potential role for involvement in this process. The aim of this study was to c...

Increasingly, our acoustic environment is filled with amplified sound sources (e.g., MP3 players, video game stations, and sports/entertainment venues). There is serious concern and also some controversy about the risks of acoustic trauma in children. This overview provides some basic information on the physiological mechanisms that lead to noise i...

Presbycusis is the most common degenerative otologic condition. New research is pointing toward vascular changes within the cochlea with age. Vascular endothelial growth factor (VEGF) and its receptors, Flt-1 and Flk-1, are important regulators of angiogenesis. The aim of this study was to characterize the hearing, VEGF expression, and vasculature...

Conductive hearing loss (CHL) lowers resting neural activity patterns in the auditory periphery. Such reductions of peripheral auditory activity may influence the developing central brain during early postnatal years when the system is still highly plastic. A common cause of CHL in young children is otitis media; if chronic and/or episodic there ma...

The ability of marine mammals to adapt to an underwater acoustic environment is a remarkable evolutionary achievement. Of particular interest is how the middle and inner ear structures are modified relative to those of terrestrial mammals. For the large whale species there are very few anatomical descriptions of the ear, in part because of the larg...

Histological comparison of the cochlea from WT and DIP/WISH-deficient mice using scanning electron microscopy. There were no obvious differences in cochlear structure and hair cell morphology between WT and DIP/WISH KO. Scale bars indicate 100 μm (apex), 20 μm (mid-turn) and 50 μm (base).

DIP (diaphanous interacting protein)/WISH (WASP interacting SH3 protein) is a protein involved in cytoskeletal signaling which regulates actin cytoskeleton dynamics and/or microtubules mainly through the activity of Rho-related proteins. Although it is well established that: 1) spine-head volumes change dynamically and reflect the strength of the s...

Early postnatal exposure to an abnormal acoustic environment has been shown to significantly influence the behaviour of neurons in the auditory cortex. In the present study, we ask if sustained neonatal exposure to an FM sweep affects the development of responses to tonal and FM stimuli in chinchilla auditory cortex. Newborn chinchilla pups were ex...

2527 May-Hegglin Anomaly was originally defined as patients with macrothrombocytopenia. It is now recognized that the phenotypes of May-Hegglin Anomaly and the related syndromes described by Epstein, Fechtner and Sebastian overlap comprising macrothrombocytopenia, neutrophil inclusions, deafness, cataract formation and nephritis. These disorders ar...

Books Reviews - Imaging the Brain with Optical Methods. 2010. Edited by Anna W. Roe. Published by Springer. 267 pages. C$190 approx. - Volume 37 Issue 5 - Robert V. Harrison

The objective of this study was to evaluate the critical time period between the onset of sensorineural hearing loss and cochlear implantation with respect to normal voice production in children with post-meningitic hearing loss. Acoustic measures of voice production were obtained from ten paediatric cochlear implant recipients with post-meningitic...

To measure acoustic voice outcomes in children with bilateral cochlear implants and to compare these with established norms, as well as to determine whether these acoustic measures were influenced by duration of cochlear implant use, age at implantation, and overall "time in sound." Cross-sectional study. Pediatric tertiary care cochlear implant ce...

Responses to cortical neurons to frequency-modulated (FM) stimuli have been described in various adult animal models. Here, we ask whether FM coding at the cortical level is innate or if it is influenced by postnatal environmental experience. We report on the FM response properties of neurons in core auditory cortex of newborn (P3), 1-month-old (P2...

1) To apply perceptual and acoustic voice assessments to children treated for juvenile-onset recurrent respiratory papillomatosis (JORRP); 2) to compare voice outcomes following treatment for JORRP using microdebrider versus carbon dioxide (CO(2)) laser. Prospective cohort study. This study was conducted at a tertiary pediatric academic center (Mar...

OBJECTIVES: 1) To apply perceptual and acoustic voice assessments to children treated for juvenile-onset recurrent respiratory papillomatosis (JORRP); 2) to compare voice outcomes following treatment for JORRP using microdebrider versus carbon dioxide (CO 2) laser. STUDY DESIGN: Prospective cohort study. SETTING: This study was conducted at a terti...

We have found a reorganization of tonotopic maps (based on neuron response thresholds) in primary auditory cortex of the adult chinchilla after amikacin-induced basal cochlear lesions. We find an over-representation of a frequency that corresponds to the border area of the cochlear lesion. The reorganization observed is similar in extent to that pr...

Micro-computed tomography (micro-CT) is an X-ray imaging technique that can produce detailed 3D images of cerebral vasculature. This paper describes the development of a novel method for using micro-CT to measure cerebral blood volume (CBV) in the mouse brain. As an application of the methodology, we test the hypotheses that differences in CBV exis...

Frequency-modulated (FM) stimuli have been used to explore the behavior of neurons in the auditory cortex of several animal models; however, the properties of FM-sensitive auditory cortical neurons in the chinchilla are still unknown. Single-unit responses to FM stimulation were obtained from the auditory cortex of anesthetized adult chinchillas (C...

Electrophysiologic responses used to predict behavioural stimulation levels in implant users are typically evoked with a single-pulse stimulus versus higher-rate pulse trains of longer duration. Unfortunately, electrophysiologic measures tend to overestimate behavioural responses. It may be possible to improve the predictive ability of evoked poten...

Discrepancies between electrophysiological and behavioral thresholds in cochlear implant users might be due to differences in stimuli such as the duration and rate of the electrical pulse train. In the present study, we asked: Is there an effect of stimulus duration on electrophysiological responses of the auditory brainstem, thalamo-cortex, and be...

Electrophysiological thresholds do not accurately predict behavioral thresholds in pediatric cochlear implant users possibly due to differences in rate and duration of pulse presentation. We asked: (1) Is there an effect of rate of stimulus presentation on the electrophysiological responses of the auditory brainstem and thalamo-cortex? and (2) can...

Tissue organization in Drosophila is regulated by the core planar cell polarity (PCP) proteins Frizzled, Dishevelled, Prickle, Van Gogh and Flamingo. Core PCP proteins are conserved in mammals and function in mammalian tissue organization. Recent studies have identified another group of Drosophila PCP proteins, consisting of the protocadherins Fat...

A review of the problems of noise-induced hearing loss in children, especially related to recreational music and the use of personal entertainment devices. The pathophysiology of noise-induced hearing loss and its associated problems (eg, tinnitus) are discussed. The evidence for an increase in noise-induced hearing loss in children and young peopl...

Otoacoustic emissions generated by outer hair cells (OHCs) are influenced by stimulation of the contralateral ear via a neural pathway involving the olivo-cochlear efferent system. This is often referred to as a contralateral 'suppression reflex', but we suggest that such a term is inappropriate since distortion product otoacoustic emissions (DPOAE...

The role of apical versus basal cochlear implant electrode stimulation on central auditory development was examined. We hypothesized that, in children with early onset deafness, auditory development evoked by basal electrode stimulation would differ from that evoked more apically. Responses of the auditory nerve and brainstem, evoked by an apical a...

Objective: To describe temporal bone findings on computed tomography (CT) imaging in GJB2-related hearing loss (HL). We asked whether evaluation of the temporal bone is required in individuals with biallelic GJB2 mutations. Study design: Randomized, blinded, controlled, prospective measurement. Methods: Blood from 264 pediatric cochlear implan...

Patterns of neural activity generated at peripheral sensory organs are influential in the development, maintenance, and plastic change to central brain areas. This chapter explores these mechanisms in the auditory system, specifically in the context of cochleotopic (tonotopic) projections up to cortex. It briefly reviews a series of studies in whic...

Characterization of the vocal profile of profoundly deaf children using an objective voice analysis was carried out in a university-based pediatric otolaryngology clinic. 21 persons ages 3.5 to 18 years were assessed. From each sustained phonation of the vowel /a/ the following acoustic variables were extracted: fundamental frequency (F0), jitter p...

To determine the relationship between ethnicity and mutations in the GJB2 and GJB6 genes in multi-cultural patients enrolled in a Canadian paediatric Cochlear Implant Program. Blood was analyzed from 65 paediatric cochlear implant users by direct sequencing of the coding region and intron/exon boundaries of the GBJ2 gene. Individuals heterozygous f...

It is reasonable to suppose that the pattern of sensorineural damage along the length of the cochlea depends on the etiology of a hearing loss (HL). In GJB2-related deafness, we hypothesize that gap junction deficits are uniformly distributed and will result in similar damage along the length of the cochlea as compared with non-GJB2 subjects. We as...

Central auditory responses to electrical stimulation from a cochlear implant were studied in 75 pre-lingually deafened children and 11 adults. Electrically evoked auditory brainstem response (EABR) latencies significantly decreased with duration of cochlear implant use and were not significantly affected by the age at implant activation. Significan...

Single-unit responses to tone pip stimuli were isolated from numerous microelectrode penetrations of core primary auditory cortex (AI) and a dorsocaudal (DC) belt region in the ketamine-anesthetized chinchilla (laniger). Results are reported at postnatal day 3 (P3), P15, P30, and from adult animals. The AI core could be distinguished from the DC be...