Research Updates in Otolaryngology

Spring 2009 

Under the direction of Anil Lalwani, MD, department chairman, and Mario Svirsky, PhD, vice chair for research, the Department of Otolaryngology has an impressive portfolio of research funding from both internal and external sources.

Project Highlights

Matthew B. Fitzgerald, PhD has obtained a $927,000 grant from the National Institutes of Health. Because bilateral cochlear implants are known to improve the patient’s ability both to understand speech and localize sound, implanting devices in both ears has become increasingly common practice. Yet to date, the fi tting of the two implants is performed largely independently, with no method for programming them — other than minor loudness adjustments — so they work together in optimal fashion. Working from the hypothesis that pitch- and loudness-matching procedures across the two implants will enhance speech perception and localization abilities, he and Dr. Svirsky are investigating diff erent methods for optimizing the fi tting of bilateral cochlear implants with the goal of achieving significant improvement in patient outcomes.

Robert Machold, PhD, has received a pilot grant from the Alzheimer’s Association. The cognitive decline and dementia observed in patients suff ering from Alzheimer’s disease is widely thought to be caused by dysfunction of the system of nerve cells in the brain that use the chemical acetylcholine to transmit information from one nerve to another. Dr. Robert Machold, in collaboration with Dr. Bernardo Rudy of the Department of Physiology and Neuroscience, is testing this hypothesis using advanced genetic techniques. Dr. Machold has engineered mice that lack the ability to produce the acetylcholine neurotransmitter in specific brain regions that are known to be aff ected in Alzheimer’s disease. He and Dr. Rudy are currently identifying the resultant changes in brain circuitry, as well as the cognitive and behavioral abnormalities that manifest themselves over the lifespan of the mice.

Daniel Jethanamest, MD, has received funding from the Centralized Otolaryngology Research Efforts (CORE) Grant Program, American Academy of Otolaryngology - Head and Neck Surgery. Animal research suggests that the correspondence between acoustic frequency and populations of neurons stimulated in response to that frequency is not fixed, but rather dependent on sound intensity. In other words, frequency mapping in the mammal ear depends on the intensity of the input a. Dr. Jethanamest, in collaboration with Dr. Elad Sagi and Dr. Mario Svirsky, will investigate whether this intensity dependence actually takes place in humans. Results will be very important for the development of new cochlear implants, as current versions of these devices make the assumption that the frequency map is not intensity-dependent. Dr. Jethanamest’s project will investigate the eff ects this intensity-dependent shift may have in speech perception by cochlear implant users.

Pamela Roehm, MD, PhD, has received a 5-year, $993,000 grant from the National Institute for Deafness and Communicative Disorders at the National Institutes of Health for a project, “Mechanism of Neurotrophin Latency Response in a HSV1 Vestibular Neuritis Model.” The grant will fund her studies of herpes simplex virus type 1 infection in vestibular ganglion cells. Herpes simplex virus type 1 is the same virus that causes cold sores, and affects over 80% of the US population by adulthood. Infection with the virus typically occurs during early childhood and causes flu-like symptoms. After the initial infection, it can remain in a latently infected state in nerve cells. Later, the virus can become reactivated due to a variety of stimuli, including stress, ultraviolet light, and other infections, and cause cold sores and other symptoms.

There is evidence that reactivation of this virus causes a number of diverse diseases in the head and neck, including Bell’s palsy, vestibular neuritis, and sudden sensorineural hearing loss. Vestibular neuritis is a common syndrome of sudden spinning vertigo which lasts days to a week, followed by a gradual recovery of balance function. Some patients never fully recover their balance after vestibular neuritis due to incomplete central (brain) compensation for the damage to the peripheral vestibular system by the process. Dr. Roehm will study the processes of reactivation of latent herpes simplex virus in vestibular ganglion cells as a model of the acute process that occurs during vestibular neuritis. In particular, she will examine the role of neurotrophins, which are proteins critical in neuron development, survival, and recovery from injury, in the maintenance of latent infections of these neurons. Once these mechanisms of latent infection maintenance are known, small molecules will be screened to assess their effi cacy in prevention of herpes simplex virus type 1 reactivation.

Chin-Tuan Tan, PhD, has received funding from Deafness Research Foundation. Dr. Tan, an electrical engineer, has extensive experience examining the types of distortion that are common in cell phones. He has developed a mathematical model to predict how sound quality may suffer from diff erent types of distortions that may be introduced by cell phone microphones and speakers. The patent he obtained for the mathematical model has been purchased by Nokia due to the strong likelihood that it might be helpful to design the next generation of cell phones. Now Dr. Tan, in collaboration with Dr. Mario Svirsky and Dr. Brian Moore (Dr. Tan’s former mentor) has obtained funding from the Deafness Research Foundation to extend the model to the perception of distorted speech and music by hearing-impaired listeners. The final models developed should be useful to manufacturers of assistive listening devices in assessing the perceptual eff ects of the distortion generated by those devices, and should ultimately lead to improved hearing aids and cell telephones.

Kevin Wang, MD, has also received funding from the Centralized Otolaryngology Research Efforts (CORE) Grant Program (sponsored by Xoran Technologies), American Academy of Otolaryngology - Head and Neck Surgery. Dr. Wang is using a new CT scanner, the flat-panel CT, to evaluate and hopefully improve outcomes for bilateral cochlear implant patients. He is collaborating with Drs. Roland, Fitzgerald, and Svirsky. By comparing the exact placement of the electrodes in each ear, and then adjusting their frequency maps, he hopes to ‘match’ the perception of sound in each ear and ultimately improve the patient’s hearing experience.