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The earliest research performed in the Department was basic auditory physiology, but today our research interests include a broad range of areas of inquiry related to the anatomy, physiology, and disease processes of the ear, vestibular (balance) system, and head and neck.
Saumil N. Merchant, M.D.,
Michael E. Ravicz, M.S.,
John J. Rosowski, Ph.D.
Eaton-Peabody Laboratory of Auditory Physiology
Tel: 617-573-3503 Fax: 617-573-3939
The goal of this research is to improve knowledge of sound transmission in various pathologic conditions affecting the human middle ear, and to apply this information to improve postoperative hearing results after surgical procedures (tympanoplasty and mastoidectomy) for chronic otitis media.
Physiologic, anatomic, and audiologic data are obtained from studies on temporal bones with normal, diseased, or surgically modified middle ears. Physiologic studies consist of acoustico-mechanical measurements (e.g., oval and round window pressures, stapes footplate motion, middle ear input impedance) made on fresh temporal bones. These measurements are complemented by light microscopic and audiometric studies from subjects with normal and pathologic middle ears. Such physiologic, anatomic, and audiologic data are then coupled with quantitative signal processing analyses in order to allow us to explain signal transmission in the human middle ear in terms of the physical properties of the structures involved. Such knowledge is applied to better understand how the diseased middle ear works and to modify current surgical techniques of tympanoplasty and mastoidectomy in order to optimize postoperative hearing results.
Significance: Chronic otitis media is a common ear disorder that is frequently seen in clinical practice. It results in infection in the middle ear and mastoid, and conductive hearing loss. Therapy is usually surgical and involves a variety of procedures which are collectively termed tympanoplasty and mastoidectomy. Such procedures are quite successful in eradicating infection, but postoperative hearing results often are disappointing. This is especially true in severely diseased ears where the eardrum and middle ear ossicles have been destroyed. One of the reasons for failure to consistently achieve good hearing results is our inability at present to precisely correlate structural features of an ear to audiometric data in order to explain conductive hearing loss. This research project seeks to apply quantitative signal processing analyses to enable us to explain sound transmission in diseased and reconstructed ears in terms of the physical properties of the structures involved. Such knowledge can aid otologic surgeons in improving their techniques of tympanoplasty and mastoidectomy in order to optimize postoperative hearing results.
Rosowski JJ, Merchant SN. A mechanical and acoustical analysis of middle-ear reconstruction. Am J Otol 1995;16:486-497.
Rosowski JJ, Merchant SN, Ravicz ME. Middle-ear mechanics of type IV and type V tympanoplasty. I. Model analysis and predictions. Am J Otol 1995;16:555-564.
Merchant SN, Rosowski JJ, Ravicz ME. Middle-ear mechanics of type IV and type V tympanoplasty. II. Clinical analysis and surgical implications. Am J Otol 1995;16:565-575.
Merchant SN, Ravicz ME, Rosowski JJ. Acoustic input impedance of the stapes and cochlea in human temporal bones. Hear Res 1996;97:30-45.
Merchant SN, Ravicz ME, Rosowski JJ. Experimental investigation of the mechanics of type IV tympanoplasty. Ann Otol Rhinol Laryngol 1997;106:49-60.
Merchant SN, Ravicz ME, Puria S, Voss SE, Whittemore KR, Peake WT, Rosowski JJ. Analysis of middle-ear mechanics and application to diseased and reconstructed ears. Am J Otol 1997;18:139-154.
Sharon G. Kujawa, Ph.D.,
Chris Halpin, Ph.D.,
Barbara S. Herrmann, Ph.D.
Tel: 617-573-3266 Fax: 617-573-3023
In recent years, research and technical advancements in the basic biology and genetics of hearing have been rapid and the implications for clinical care, far reaching. More than ever, we are in a position to take these advancements and integrate them into our clinical activities with the goal of providing better quality care. Such advancements are greatly facilitated through ongoing collaborations among scientists and clinicians. The Infirmary provides an excellent environment for such collaborations.
We are interested in the hearing function of the very young. Our development of an infant hearing screener based on the recording of brainstem auditory evoked potentials, contributed significantly to the implementation of nation-wide programs for early identification of handicapping hearing loss. Infants with such hearing losses are now routinely identified before they ever leave the newborn nursery.
We are also interested in the hearing function of our seniors. By the age of 75, more than half of us will have a hearing loss significant enough to interfere with our communication with others. Some of us, however, will develop a more severe hearing loss than others. We are actively studying factors that may shape susceptibility to hearing loss as we age and as we are exposed to noise or other agents that damage our hearing.
The ultimate goal of our research is to improve hearing outcomes for our patients. With more than 25 audiologists on staff and a large and varied clinical caseload, we have the ideal environment for audiologic studies in many different areas. Our extensive clinical database has been used to improve diagnostic criteria for tumor detection, refine tests of speech ntelligibility, and develop better techniques for hearing aid fitting.
Our research is basic and applied, with the ultimate goal of improving hearing outcomes for our patients. Currently we are involved in a number of research projects as primary or collaborating investigators.
Learn more about these projects.
Donald K. Eddington, Ph.D.
Ph.D. Joseph Tierney, M.S.
Cochlear Implant Research Laboratory
Tel: 617-573-3767
Most people who suffer profound hearing impairment have lost the ability to translate the acoustic energy of sound into the electrical signals carried to the brain by the auditory nerve. Cochlear implants are electronic devices that are designed to bypass the external and middle ears and excite the auditory nerve directly. These devices include a microphone connected to a belt-worn package of electronics (called a sound processor) that translates acoustic signals to electrical stimuli. By directing electrical stimuli to auditory nerve fibers using an array of electrodes implanted in the deaf patient's cochlea (inner ear), patterns of nerve activity occur that the brain interprets as sound.
The goal of these devices is to elicit patterns of nerve activity that mimic those of a normal ear for a wide range of sounds. Such a system would not only enable postlingually deafened individuals with a suitable number of remaining nerve fibers to spontaneously recognize all types of sound (including speech), but would also provide the input required for many children deafened at a young age to acquire speech communication. While this goal has not yet been completely realized, the hearing provided by today's devices enables a few to communicate without lip-reading and most to communicate fluently when the sound is combined with lip reading.
Work in the Cochlear Implant Research Laboratory focuses on the fundamental mechanisms nderlying the sound sensations produced by electrical stimulation of the auditory system. For example, results from computer models of electric current flow in the implanted cochlea and from models of how these flows excite nerve fibers are combined with the results from a wide variety of tests (e.g., threshold, discrimination and speech recognition) conducted in implanted human subjects to provide a rational basis for the design of new and refined sound processing schemes.
Based on these fundamental studies, we are developing and testing new sound processing schemes that, in the laboratory, provide significant improvements in speech reception for some subjects. These new sound processing techniques will be field tested using a programmable, wearable sound processor that we are developing together with investigators from Duke University, the University of Geneva, and Draper Laboratory.
Eddington DK. Speech recognition in deaf subjects with multichannel, intracochlear electrodes. Ann N Y Acad Sci 1983; 405:241-258.
Wilson BS, Finley CC, Lawson DT, Wolford RD, Eddington DK, Rabinowitz WM. Better speech recognition with cochlear implants. Nature 1991; 352:236-238.
Rubinstein, JT. Axon termination conditions for electrical stimulation. IEEE Trans Biomed Eng 1993; 40:654-663.
Eddington DK, Girzon G. An electroanatomical model of intracochlear electrical stimulation, I: formulation, solution and predictions. Hear Res 1994 (submitted).
Eddington DK, Girzon G, Cuneo PA. An electroanatomical model of intracochlear electrical stimulation, II: tests of model predictions. Hear Res 1994 (submitted).
Steven D. Rauch, M.D., in collaboration with
Conrad Wall III, Ph.D.
Kurt J. Bloch, M.D. (MGH)
Richard A. Moscicki, M.D. (Asst. Prof. in Immunology, VP for Medical Research, Genzyme Corp.)
Rauch Laboratory (Inner Ear Immunobiology and Biochemistry)
Jenks Vestibular Laboratory
Bloch Immunology Laboratory (MGH)
Tel: 617-573-3644 Fax: 617-573-3939
E-mail: earsdr@warren.med.harvard.edu
Research time is divided among three projects that relate to each other by addressing issues of pathology and diagnosis of the combined disorders of hearing and balance, Meniere's disease, immune-mediated inner ear disease, and perilymphatic fistula. Meniere's disease is a disorder of unknown cause that produces progressive nerve deafness and attacks of vertigo. Immune-mediated ear disease is a family of conditions in which the immune system seems to attack or otherwise damage the inner ear, resulting in rapidly progressive hearing loss and occasional balance problems. Perilymphatic fistula (PLF) is a condition in which inner ear fluid (perilymph) leaks through an abnormal communication between the inner ear and middle ear, causing progressive or sudden loss and vertigo. The mechanisms that cause these conditions and the actual pathologic processes that damage or destroy normal hearing and balance are poorly understood. Furthermore, the clinical presentations of these entities overlap, leading to considerable difficulty in differential diagnosis in some cases. The individual research projects explore the underlying disease mechanisms and improve diagnosis and treatment of these three conditions.
The Meniere's disease project is designed to test the hypothesis that a subset of Meniere's disease cases are due to immune-mediated mechanism in which patients develop antibodies against their own inner ear tissues. We will test blood samples from patients meeting strict diagnostic criteria for Meniere's disease to look for evidence of these antibodies. Antibody test results will be correlated with clinical features of the disease, such as duration of symptoms, hearing loss pattern, and vertigo pattern, to attempt to characterize the subset of patients with immune-mediated Meniere's disease.
The immune-mediated inner ear disease project is identifying patients with a particular pattern of rapidly progressive nerve deafness and testing their blood for the same antibodies mentioned above. Preliminary results suggest that a high percentage of patients with a positive antibody test can regain hearing by high-dose steroid treatment. Consenting patients meeting strict entry criteria are being treated with either steroids or placebo medication in the hope of eventually determining the success of steroid treatment and the predictive value of the antibody test. Efforts to identify and purify the inner ear antigen that is the target of the circulating antibodies are ongoing.
The perilymphatic fistula project is developing diagnostic protocols to unequivocally differentiate this disorder from the others mentioned. Specifically, patients suspected of PLF will be evaluated by innovative vestibular tests and middle ear fiberoptic endoscopy. They will then have the ear explored surgically and middle ear fluid samples taken for biochemical assay to confirm the presence or absence of perilymph. Eventual correlation of pre-operative diagnostic studies and intra-operative fluid biochemistry will enable us to determine the optimum work-up for diagnosis of PLF. At the same time, animal experiments are testing the ability of the vestibular testing protocol to differentiate between PLF and Meniere's disease.
Considered individually, each of these research projects will yield valuable information about the disorders studied. Taken together, they represent a multifaceted approach to understanding the basic disease mechanisms, diagnosis, and treatment of three of the most common disorders affecting both hearing and balance.
Rauch SD, Merchant SN, Thedinger BA. Meniere's syndrome and endolymphatic hydrops: a double-blind temporal bone study. Ann Otol Rhinol Larvnaol 1989; 98:873-883.
Rauch SD, San Martin J, and Moscicki RA. Bovine temporal bones as a source of inner ear antigen. Ann Otol Rhinol Laryugol 1992; 101:688-690.
Wall CW, Rauch SD. Perilymph fistula pathophysiology. Otolaryngol Head Neck Surg 1994 (in press).
Moscicki RA, San Martin JE, Quintero CH, Rauch SD, Nadol JB Jr, Bloch KJ. Specificity of serum antibodies to a 68 kD inner ear antigen in disease associated with hearing loss and responsivity to corticosteroid therapy. JAMA, 1994 (submitted).
James B. Kobler, Ph.D.
Harris Peyton Mosher Laryngological Research Laboratory
Tel: 617-573-3830 Fax: 617-720-4408
We are studying the functional anatomy of muscles of the head and neck, their special adaptations, and their control by the brain. Many of these muscles are small and under delicate control for functions such as speech and swallowing. Some of the tenets of motor control theory developed through research on the more widely studied limb muscles must be re-examined or extended for cranial muscles. Many cranial muscles, for example, have few proprioceptors, a small ratio of muscle fibers to motor neurons and complex synergies with other muscles. My work with Dr. John Guinan of the Eaton- Peabody Laboratory on the stapedius muscle of the middle ear showed that for this muscle there are also differences in CNS control mechanisms. Some of these differences may be more general features of the motor control of other cranial muscles such as those of the larynx and pharynx.
To take advantage of our clinical setting, we are focusing on muscles of particular surgical or pathological significance in Otolaryngology. One muscle we are currently investigating is the cricopharyngeus, which acts as a sphincter between the airway and the esophagus. Dysfunction of this muscle is implicated in both swallowing difficulties and in reflux of gastric fluids into the airway. We are studying the innervation and control of this muscle from the brainstem using neurophysiological and neuroanatomical tracing methods.
Another muscle of current interest is the striated muscle of the upper esophagus. Recently it has been shown that, unlike spinal motor neurons, the motor neurons supplying some of the cranial muscles contain neuropeptides and other potential modulators of synaptic transmission. The striated muscle of the esophagus receives nerve endings that stain for an enzyme found in neurons that use nitric oxide as a neurotransmitter. We are investigating the esophageal endplates anatomically and pharmacologically, in conjunction with groups at Beth Israel and Boston City Hospitals. Knowing more about the neuromuscular junctions of the muscles of the head and neck may help us better understand how these muscles respond to nerve injuries and to drugs.
One spin-off of basic neurophysiological studies of cranial neuromuscular systems in animal models is the development of methods that can be applied to assess muscle function clinically. For example, in conjunction with clinicians Dr. Robert Hillman of the Voice Laboratory and Dr. Gregory Randolph of the ENT surgical staff, we are currently developing applications of electromyography for monitoring the function of the vagus nerve during surgery. We also hope to develop and evaluate these methods for clinical diagnosis of laryngeal nerve paralysis and for research on human motor voice disorders.
Kobler JB, Vacher SR, Guinan JJ Jr. The recruitment order of stapedius motoneurons in the acoustic reflex varies with sound laterality. Brain Res 1987; 425:372-375.
Kobler JB, Guinan JJ Jr, Vacher SR, Norris BE. Acoustic-reflex frequency selectivity in single stapedius motoneurons of the cat. J Neurophysiol 1992; 68:807-817.
Kobler JB, Datta S, Goyal R, Benecchi EJ. Innervation of the larynx, pharynx, and upper esophageal sphincter of the rat. J Comp Neurol 1994 (in press).
William W. Montgomery, M.D. Stuart K. Montgomery Ann McLean-Muse, Ph.D. Anna Choi, M.S. Voice and Speech Laboratory Tel: 617-573-3669 Fax: 617-573-3188
The production of sound, or voice, by the larynx is the foundation of normal human speech. Voice is produced when airflow from the lungs drives the two vocal cords in the larynx into vibration. In addition, the vocal cords assist in closing off and protecting the lower airway during swallowing. It is not uncommon for damage to occur to the nerves that control laryngeal muscles, and/or to the structures of the larynx, as a result of trauma (e.g., car accident) or secondary to head and neck surgery. In such cases the vocal cords may not move properly and the affected individual can be left with debilitating voice, speech, and/or swallowing difficulties. This project has focused on developing a standardized system to treat unilateral vocal cord immobility by medializing the affected vocal cord.
The Montgomery Thyroplasty Implant System consists of a medialization implant, measuring devices, and surgical instruments. This system offers several advantages over other medialization approaches including: 1) prefabrication eliminates the need to fashion an implant at the time of surgery, 2) measuring devices allow for easy predetermination of implant size, 3) device design allows for easy implantation , and 4) removal and revision can be accomplished without damage to laryngeal structures.
Results from more than 176 patients at MEEI in whom the implant has already been used indicate that this approach offers an effective method for treating unilateral vocal cord immobility. A multi-center clinical trial of the implant system is currently underway.
Montgomery WW, Blaugrund SM, Varvares MA. Thyroplasty: a new approach. Ann Otol Rhinol Laryngol 1993;102:571-579.
Montgomery WW, Montgomery SK. Montgomery® Thyroplasty Implant System. Ann Otol Rhinol Laryngol 1997;106(9):Suppl. 170:1-16.
This new project is part of the Neural Prosthesis Research Center that is currently funded by the W.M. Keck Foundation to develop prosthetic devices which will assist individuals who have severe hearing, vision, balance, or speech deficits.
The production of sound, or voice, by the larynx is the foundation of normal human speech. Each year, thousands of people in the United States alone, lose the ability to produce voice and speech because of conditions which render the larynx non-functional (e.g., laryngeal cancer). For many of these individuals, the only viable option is to use a hand held electrolarynx (EL). Unfortunately, currently available EL devices produce speech that is unnatural (non-human) sounding, has reduced loudness and intelligibility, and draws undesirable attention to the user. In addition, fine control over the timing of vocal fold vibration (e.g., rapid adjustments in pitch and voice onset and offset) that is provided by laryngeal innervation is lost. Thus, the long-term goal of this project is to provide patients who have lost laryngeal function with a substantially improved EL-based communication system that more closely approximates normal voice and speech production.
The system that we are pursuing is based on the development and integration of three rimary modular components which are specifically designed to remedy the major deficits in EL speech: (1) an improved EL voicing source module, (2) a signal processing module to enhance alaryngeal speech, and (3) a control module that uses physiological signals to modulate the voicing source. Because of the modular nature of this system, it will be possible to apply advances in the development of individual components to improving the communication functioning of patients as such advances are accomplished, thus avoiding the need to delay implementation until the entire system has been fully developed. This should enable us to have an ongoing positive impact on the communication function of alaryngeal speakers.
Hillman RE, Walsh MJ, Wolf GT, Fisher SG, Hong WK, Department of Veterans Affairs Laryngeal Cancer Study Group. Functional Outcomes Following Treatment for Advanced Laryngeal Cancer; Part I-Voice Preservation in Advanced Laryngeal Cancer; Part II-Laryngectomy Rehabilitation: The State of the Art in the VA System. Ann Otol Rhinol Laryngol, in press.
Voice and Speech Laboratory
Tel: 617-573-3557 Fax: 617-573-3068
The larynx has the most complex three-dimensional motion of any organ or system in the human body. This is reflected by the extremely complex neural processing, which comprises the innervation of the small volume of intrinsic musculature. Abnormalities of vocal fold motion can lead to airway obstruction, vocal problems, and swallowing difficulties. Re-establishing these vital and important functions in patients who have sustained deficits and injuries often presents as a difficult surgical challenge.
This research has focused on the physiologic function of a variety of diseased states such as vocal fold paralysis. This work has led to the design of innovative surgical procedures which provide optimal functional rehabilitation. These investigations have included cadaver dissections and stroboscopic analyses of vocal fold vibration, and have resulted in a number of successful clinical trials.
Most notable has been the design of a new operation to treat vocal fold paralysis ( adduction arytnopexy), which is done under local anesthesia and allows for stretching, "tuning", and aligning the paralyzed vocal cord, while simultaneously conversing with the patient. This, in turn, facilitates the optimal postoperative voice result and improved swallowing. The authors have recently received the Casselberry Award of the American Laryngological Association for this work.
Zeitels SM, Hillman RE, Bunting GW, Vaughan TL. Reinke's edema: phonatory mechanisms and management strategies. Ann Otol Rhinol Laryngol 1997;106:533-543.
Zeitels SM, Hochman IL, Hillman RE. Adduction arytenopexy: a new procedure for paralytic dysphonia and its implications for medialization laryngoplasty. Ann Otol Rhinol Laryngol, in press.
Joseph B. Nadol, Jr., M.D.
Electron Microscopy Laboratory
Tel: 617-573-3652 Fax: 617-573-3939
Microscopic examination of the human inner ear, both normal and pathological, can be significantly enhanced by the resolving power of electron microscopy. Post-mortem human inner ear tissue, in which fixation can be achieved in a sufficiently short period of time, is prepared for electron microscopy using aldehyde fixation, microdissection, decalcification, plastic embedding, and microtomy.
Electron microscopy has contributed new knowledge concerning the normal and pathologic anatomy of the inner ear. Certain aspects of the anatomy of the human organ of Corti are distinctly different from that seen in animals. For example, radial fibers innervating the inner hair cell rarely branch in animals, but commonly do so at the base of inner hair cells in the human. Likewise, multiple synaptic contacts between the inner hair cell and radial fibers are common in the human, but rare in the animal. At the base of outer hair cells in the animal, there are two varieties of synapses: afferent and efferent. However, in the human a third synaptic relationship has been described in our laboratory. Such "reciprocal" synapses have the morphologic characteristics of both afferent and efferent components between the same outer hair cell and neuron. Such reciprocal synapses have been described in other neural systems, but never before in the normal organ of Corti.
Immunostaining for synaptophysin, a structural protein of synaptic vesicles, has demonstrated small, apparently efferent, fibers in the supranuclear region of outer hair cells. Transmission electron microscopy demonstrates a synaptic relationship between these fibers and hair cells, and, also, with supporting cells. Such supranuclear synapses may have an entirely different function than synapses at the neural pole of outer hair cells.
Transmission electron microscopy of pathologic human material has provided evidence for progressive denervation of hair cells as a degenerative phenomenon in presbycusis, Meniere's disease, and Usher's syndrome. In some cases such retrograde neural degeneration may explain otherwise poor correlation between audiometry and histopathology of the organ of Corti and spiral ganglion by light microscopy. We will direct future research to include continued collection of pathologic human material with particular attention to submicroscopic pathology in the organ of Corti and spiral ganglion in the human.
Nadol JB Jr. Incidence of reciprocal synapses on outer hair cells of the organ of Corti. Ann Otol Rhinol Laryngol 1984; 93:247-250.
Nadol JB Jr. Application of electron microscopy to human otopathology. Acta Otolaryngol (Stockh) 1988; 105:411-419.
Nadol JB Jr. Synaptic morphology of inner and outer hair cells of the human organ of Corti. J Electron Microsc Tech 1990; 15: 187-196.
Nadol JB Jr, Cho YB, Burgess BJ, Adams JC. The localization of synaptophysin in the organ of Corti of the human as shown by immunoelectron microsconv. Acta Otolarvngol (Stockh) 1993; 113:312-317.
Robert S. Kimura, Ph.D.
ENT Electron Microscopy Laboratory
Tel: 617-573-3592
The objective of our research is to find both the cause(s) of and a cure for Meniere's disease. The pathology (endolymphatic hydrops) and clinical symptoms (dizziness, tinnitus, and hearing loss) of this disease are well known, however many treatments are not effective due to its unknown etiology. Our approach is to develop an animal model with similar pathology for this disease and to control the disease process using various experimental procedures. We have such an animal model in the guinea pig, which develops endolymphatic hydrops by ablation of the endolymphatic sac, an inner ear fluid regulation site. However, in some other species the same procedure will not produce endolymphatic hydrops. We are in the process of determining morphometrical and enzyme activity differences in the endolymphatic sacs among these different species; this will provide us with a clue to the etiology of endolymphatic hydrops. Malfunction of the endolymphatic sac elevates calcium ions in endolymph which may be a cause for hearing loss. We will inject calcium chloride into the inner ear and determine whether it will cause endolymphatic hydrops and/or damage to the hearing organ.
One theory is that the clinical symptoms of Meniere's are thought to occur from an increase in endolymphatic pressure as manifested by endolymphatic hydrops or a rupture of the distended membrane. The vestibular symptoms are normally lacking in the guinea pig model, but may be initiated by applying intermittent increased pressure with the aid of a hyperbaric pressure chamber. Another theory is that the symptoms have a vascular origin. Our recent finding in the gerbil indicates that the animals experience dizziness after interfering with blood drainage from the inner ear at the endolymphatic sac and their ears show vestibular sense organ damage.
We will attempt to control endolymphatic hydrops by various methods. We will use a hormone-regulating drug to control over-secretion of endolymph from the strict vascularis and vestibular dark cells. A calcium antagonist will be used to control calcium ions and reduce endolymphatic hydrops. Patients afflicted with Meniere's disease are sensitive to atmospheric pressure changes. Hydropic animals will be placed in the hyperbaric chamber to decrease endolymph pressure in an attempt to control endolymphatic hydrops. We will provide a ventilation tube or make a hole in the tympanic membrane of the hydropic animal's ears to minimize endolymphatic pressure.
Kimura RS, Trehey JA, Hutta J. Degeneration of vestibular sensory cells caused by ablation of the vestibular aqueduct in the gerbil ear. Ann Otol Rhinol Larvngol 1994 (in press).
Rox Anderson, M.D.
Ilan Hochman, M.D.
Massachusetts Eye and Ear Infirmary
Massachusetts General Hospital
Wellman Laboratories of Photomedicine
Laryngo-tracheal aspiration is a pervasive problem that accompanies a variety of medical and surgical illnesses, and is commonly encountered in acute care as well as chronic care facilities. Chronic aspiration results from sensory and/or motor disturbances of the laryngo-pharynx and larynx. It may occur during swallowing, from salivary soilage, and from extra-esophageal reflux into the tracheobronchial tree. The morbidity of chronic aspiration is profound because it deprives individuals of a fundamental human instinct, eating. Chronic aspiration also results in an extraordinary financial burden to the health care system primarily from the management of recurrent pneumonias and gradual pulmonary deterioration. Since an ideal solution to chronic laryngotracheal aspiration has not been developed, an endoscopic reversible supraglottic [laryngeal] closure procedure has been designed that employs a retro-caudal advancement epiglottic flap to partially obliterate the laryngeal introitus.
This project has been recently funded by the Center For Innovative Minimally Invasive Therapy [CIMIT] of the Massachusetts General Hospital. A patented bivalved supraglottiscope and a super pulse carbon dioxide laser will be used to perform the surgery. The project will be done in two phases. First an in vitro laboratory trial will be done to assess and optimize welding of supraglottic tissues in a mammalian larynx. Based on these findings, an in vivo trial in the canine will be done to assess healing and long-term stability of the closure procedure.
One goal of this project has been to optimize a thermal welding technique for fusion of supraglottic laryngeal tissues. Tensile strength is being measured as a function of tissue welding temperature and apposition pressure in vitro. A second goal has been to build a prototype welding device for supraglottic tissue welding in vivo. The final goal has been to transfer this information to perform a minimally-invasive, endoscopic, supraglottic closure in the in vivo canine model. This study has yielded encouraging results thus far and we are currently developing an instrumental delivery system to determine the feasibility of a clinical study.
Zeitels SM, Vaughan CW, Domanowski G, et al. Laser epiglottectomy: indications and technique. Otolaryngol Head Neck Surg 1990;103:337-343.
Zeitels SM, Vaughan CW. The adjustable supraglottiscope. Otolaryngol Head Neck Surg 1990;103:487-492.
Zeitels SM, Koufman JA, Davis RK, Vaughan CW. Endoscopic treatment of supraglottic and hypopharynx cancer. Laryngoscope 1994;104:71-78.
John J. Guinan, Jr., Ph.D.
Eaton-Peabody Laboratory
Tel: 617-573-4236
We are interested in understanding the function and mechanisms of the feedback pathways by which the brain controls the auditory periphery. In particular, we are studying the "medial efferents," nerve fibers which originate in the brainstem and terminate in the cochlea. Activity in these nerves can change the mechanics of the cochlea and reduce its output. Our work also includes studying the two middle ear muscles, the stapedius, and the tensor tympani. Contractions of these muscles reduce transmission through the middle ear. Middle ear muscles and medial efferents do some similar functions, but they are activated under different circumstances.
In animal studies directed toward understanding the mechanisms by which the medial efferents produce their effects, we activate these nerves and measure changes in cochlear potentials, auditory-nerve firing, and "otoacoustic emissions." Otoacoustic emissions can be monitored non-invasively in humans and can demonstrate the effects of medial efferents activity. By combining a variety of techniques, we hope to understand both the function of medial efferents in hearing and the mechanisms by which medial efferents accomplish this function. Because medial efferents act at a known place in the cochlea and change many aspects of cochlear function, they have been an important tool in understanding cochlear mechanisms. Such studies are important both for understanding hearing and because many clinical problems occur in the cochlea.
We also study the acoustically evoked middle ear reflexes. Our past work emphasized the stapedius motor-control system and has shown that, in the cat, there is considerable complexity and organization in this system. The stapedius motor control system is different in important respects from most well-studied motor control systems and may provide new insights into motor control issues. We are currently studying the interactions of the stapedius and the tensor tympani muscles. We know that the middle-ear transmission changes when these muscles are activated separately, but we do not know what happens when these muscles are activated together. We are also studying the interaction of the middle-ear muscles and medial efferents. Knowledge of the effects of these reflexes acting in concert is essential for understanding signal processing by the peripheral auditory system and central control of the auditory periphery.
Guinan JJ Jr, Gifford ML. Effects of electrical stimulation of efferent olivocochlear neurons on cat auditory nerve fibers, III: tuning curves and threshold at CF. Hear Res 1988; 37:29-46.
Vacher SR, Guinan JJ Jr, Kobler JB. Intracellularly labeled stapedius-motoneuron cell bodies in the cat are spatially organized according to their physiologic responses. J Comp Neurol 1989; 289:401-415.
Guinan JJ Jr. Changes in stimulus frequency otoacoustic emissions produced by two-tone suppression and efferent stimulation in cats. In: Dallos P. Geisler CD. Matthews JW, Steele CR, eds. The mechanics and biophysics of hearing. Springer-Verlag, 1990; 170-177.
Kobler JB, Guinan JJ Jr, Vacher SR, Norris BE. Acoustic-reflex frequency selectivity in single stapedius motoneurons of the cat. J Neurophysiol 1392; 68:807-817.
McCue MP, Guinan JJ Jr. Influence of efferent stimulation on acoustically-responsive vestibular afferents in the cat. J Neurosci 1994 (in press).
Conrad Wall, III, Ph.D.
Jenks Vestibular Diagnostic Laboratory
Tel: 617-573-4153 Fax: 617-573-4154
E-mail: cwall@space.mit.edu
The inner ear contains the organs of hearing; the cochlea; and the vestibular system, the organs that sense angular and linear accelerations. My primary interest is the human vestibular system: how its performance is characterized in normal individuals and how characterization can be used to test patients who complain of dizziness. In basic vestibular research with laboratory models, that response can be recorded directly from the end organs themselves. At present, however, the response in humans cannot be directly recorded and must be measured using reflexes that involve compensatory movements of the eyes or of the body in response to a vestibular stimulus. Thus, my experimental approach is to introduce a stimulus, such as head-over-heels pitch, and to record a response, such as vertical eye movement. One approach is to record the response to a single stimulus alone as described above. Another is to investigate the response to sensory interactions, for example, a motion input and a visual input. I employ both of these techniques. My research interests also include: (1) the effect of weightlessness (as in space travel) upon the vestibular system and (2) development of techniques to detect abnormal fluid leaks between the inner ear and its surroundings. I am currently funded as Principal Investigator to conduct research in these areas by two National Institutes of Health (NIH) grants. A NASA grant is in competitive renewal, has a favorable score, and is awaiting funding which depends on NASA's overall funding level from Congress.
The practical significance of this research is as follows: In terms of testing patients, the standard-of-practice test procedure for vestibular function is to test one of the five vestibular end organs in each of the two inner ears. My ongoing funded NIH research will characterize the response in the other four motion sensors in each inner ear and will enable me to create more thorough clinical vestibular test procedures for the evaluation of these other end organs. In addition, there is no objective, quantitative method of determining inner ear leaks, which can be caused by disease or trauma. The goal of my second NIH-funded research will be to establish this methodology.
Wall C III, Smith TR, Furman JMR. Plasticity of the human otolith-ocular reflex. Acta Otolaryngol (Stockh) 1992; 112:413420.
Wall C III, Harris LR, Lathan CE. Interaction between otoliths and vision revealed by the response to z-axis linear movements. Ann N Y Acad Sci 1992; 656:898-900.
Wall C III, Petropoulos AK. Human vertical eye movement responses to earth horizontal pitch. Acta Otolaryngol (Stockh) 1993; 113:111-118.
Wall C III, Casselbrant ML. System identification of perilymphatic fistula in an animal model. Am J Otol 1992; 13:443-448.
Joe C. Adams, Ph.D.
Laboratory of Otoimmunochemistry
Tel: 617-573-3975 Fax: 617-720-4408
The work in this laboratory focuses on the study of the inner ear as well as the parts of the brain that are involved in hearing. In both cases, the goal is to identify and study the significance of the chemical constituents of individual cells.
Antibodies are the primary means of identifying cell-specific chemicals by identifying locations of chemicals within the tissue using techniques of immunohistochemistry. Once the normal constituents of given cell classes are identified, experiments are performed to determine what conditions affect the cells' chemical contents. In the inner ear, emphasis is placed on the study of cells which control fluid and electrolyte balance. These cells are known to be affected in ear disorders resulting from damage produced by excessive sound, damage to the ear by certain drugs, and damage from disease states such as Meniere's disease. The use of immunostaining to assay for changes in cell constituents due to experimental manipulations is a new approach that is revealing a wealth of new information about the normal functioning and pathological states of the inner ear. To determine the extent to which the results of the experiments, which are done in animals such as guinea pigs, can be applied to human disorders, the same antibody staining techniques that are applied to animal tissue are used on human tissue. The human tissue comes from the Department's Human Temporal Bone Collection, in which there are a great number of specimens of inner ears from donors who willed their remains to the collection. Included in the collection are inner ears from people who had a wide variety of well-documented inner ear disorders.
In brain research, similar techniques are employed. Antibodies are used to identify normal chemical constituents within the auditory portions of the brain. The goal is to identify classes of nerve cells that have characteristic chemical signatures and to learn to associate cell classes identified in this manner with cell classes determined by neuroanatomical and physiological measures. Determination of these associations is done in animals where it is possible to perform physiological and anatomical experiments. In many cases, simply identifying normal constituents reveals a great deal about the cells' functions. Once chemically distinctive nerve cell classes have been established in animal tissue, and other traits such as physiological properties and connections with other cell classes have been established, efforts are made to ascertain whether there are equivalent chemical classes of cells in human brains. Finding corresponding cell classes in animal and human tissue permits inferences to be made about the functional role of given cell classes in human tissue. The relatively stable correspondence of the chemical bases for cell function which exits across species helps to substantiate the inferences made about functions of chemically characterized nerve cells in humans.
The significance of this research rests in the degree to which attempts are successful in establishing appropriate correspondences between animal and human tissue, and in correctly inferring the function of the tissue components in humans. It is not possible to do experiments on human ears or brains, but the immunostaining technique makes it possible to analyze human tissue for a great variety of chemical constituents. This research program aims to explore this technique insofar as possible to learn about the chemical makeup of both human and animal tissue and to explore the nature of changes that occur in pathological states. The technique is one of the few approaches that permit analysis of normal and pathological states in the human ear and brain at cellular and subcellular levels.
Adams JC. Glutamate decarboxylase immunostaining in the human cochlear nucleus. In: Syka J, Masterton RB, eds. Auditory pathway, structure and function. New York, NY: Plenum Press, 1988; 133-139.
Schulte BA, Adams JC. Distribution of immunoreactive Na+, K+-ATPase in the gerbil cochlea. J Histochem 1989;7:127-134.
Adams JC, Mugnaini E. Immunocytochemical evidence for inhibitory and disinhibitory circuits in the superior olive. Hear Res 1990; 49:28 1-298.
M. Christian Brown, Ph.D.
Thane E. Benson, Ph.D.
John R. Iversen, Graduate Student
Eaton-Peabody Laboratory
Tel: 617-573-3875
Email: mcb@epl.meei.harvard.edu
We seek to understand how the ear and brain communicate by studying fibers that send information from one structure to the other: namely, afferent fibers, which carry information from the ear to the brain, and efferent fibers, which carry information from the brain to the ear. Both types of fibers are studied by (1) recording their responses to sound with micropipette recording electrodes and (2) injecting them with neural tracers and tracing their connections in the ear and the brain. By understanding the ways that information is coded under normal conditions, we may be able to design better coding schemes for use in devices like cochlear implants that replace non-functioning ears.
We also study the responses of neurons in the brain by the use of a new technique involving immediate-early genes. These genes are expressed in auditory parts of the brain when sound is presented. The cells that express these genes can easily be stained using antibodies. This technique permits one measurement of neural activity throughout the brain at the single-cell level and is likely to be very useful in future studies of brain activity.
Brown, M.C. (1999) Auditory System. In: M. Zigmond, F. Bloom, S. Landis, J. Roberts and L. Squire (eds): Fundamental Neuroscience. New York: Academic Press, pp. 791-820.
Brown, M.C., S.G. Kujawa, and M.L. Duca (1998) Single olivocochlear neurons in the guinea pig: I. Binaural facilitation of responses to high-level noise. J. Neurophysiol. 79: 3077-3087.
Brown, M.C., and T.S. Liu (1995) Fos-like immunoreactivity in central auditory neurons of the mouse. J. Comp. Neurol. 357: 85-97.
Michael J. McKenna, M.D. Otopathology Laboratory Harvard Molecular Genetics Laboratory Tel: 617-573-3672 Fax: 617-573-3939
Otosclerosis is a common bone disease which affects the human temporal bone. It is among the most common causes of hearing loss in the general population. Although there is a clearly established genetic predisposition for the development of the disease, the etiology of otosclerosis is unknown.
We have initiated investigation into the molecular basis of inheritance of otosclerosis by evaluating selected candidate genes in affected individuals utilizing single- stranded conformational polymorphism. If this line of investigation is unsuccessful, we will conduct a linkage analysis using DNA from individuals with multiple affected family members. Since 1993, we have been identifying affected individuals and prospective families and collecting blood specimens.
In addition, a continuing investigation of a possible viral role in the initiation of the disease process is being conducted. This line of research was initiated because of mounting evidence for viral etiology in Paget's disease of bone which closely resembles otosclerosis, both clinically and histopathologically. Viral nucleocapsid structures identical to those found in subacute sclerosing panencephalitis have been identified in active otosclerotic lesions by transmission electron microscopy. Immunohistochemistry has substantiated the presence of the measles virus antigens in active lesions. We have developed a process for extracting both DNA and RNA from pathologic human temporal bone sections and are using the polymerase chain reaction technique to identify specific gene sequences. Currently, we are refining this process for use in our ongoing investigation of otosclerosis as well as other pathologic processes.
McKenna MJ, Mills BG, Galey FR, Linthicum FH. Filamentous structures morphologically similar to viral nucleocapsids in otosclerotic lesions in two patients. Am J Otol 1986; 7:25-28.
McKenna MJ, Mills BG. Immunohistochemical evidence of measles virus antigens in active otosclerosis. Otolaryngol Head Neck Surg 1989; 101:415-421.
McKenna MJ, Gadre AK, Rask-Anderson H. Ultrastructural characterization of otospongiotic lesions in re-embedded celloidin sections. Acta Otolarvngol (Stockh) 1990; 109:397-405.
McKenna MJ, Adams JC. Immunohistochemical demonstration of measles fusion and phosphor protein antigens in active otosclerosis. In: Immunobiology in otology, rhinology, and laryugology. McCabe BF, Veldman JE, Mogi G, eds. Amsterdam, the Netherlands: Kugler Publications 1992; 101-107.
James T. Heaton, Ph.D.,
James B. Kobler, Ph.D.
Harris Peyton Mosher Laryngological Research Laboratory
W.M. Keck Foundation Neural Prosthesis Research Center
Tel: 617-573-3830 Fax: 617-573-4060
E-mail: james_heaton@meei.harvard.edu
In the Mosher Laryngological Research Laboratory we study the neurophysiology and anatomy of the larynx with the goal of better understanding both normal and diseased laryngeal function. In collaboration with researchers and clinicians in the Voice and Speech Laboratory, we have the opportunity to apply basic research to specific voice disorders.
As part of the Keck Neural Prosthesis Research Center, our recent efforts have focused on the development of a neuromotor interface for the control of artificial voice sources. Each year in the United States alone, thousands of individuals lose their larynx to disease or injury and depend on artificial voice sources in order to speak. In most cases, the laryngeal nerves and the neuromotor signals that the nerves transmit are healthy at the time of laryngectomy. We believe that by tapping into these residual laryngeal neuromotor signals we can provide improved control of prosthetic speech aids.
We have considered two basic approaches for extracting residual neural control signals from laryngeal nerves cut during laryngectomy. The first approach is to transpose laryngeal nerves into "host" muscle tissue at the time of laryngectomy so that after reinnervation these muscles will sustain and naturally amplify laryngeal nerve signals. Our recent animal experiments have demonstrated that laryngeal nerves will readily innervate strap muscles of the neck. Since these muscles are otherwise rendered useless during laryngectomy, they make ideal targets for reinnervation by laryngeal nerves. In our experiments, electrodes placed on the skin surface overlying the laryngeal-innervated strap muscles can detect electromyographic potentials correlated with vocalization. If similar procedures are successful in humans, we will use these signals to control the output of prosthetic voice sources like the electro-larynx (hand held buzzer). We hope to begin human trials of laryngeal nerve transposition within the next year.
Our second approach for extracting neuromotor signals from cut laryngeal nerves is to record directly from the nerves. This is made possible by recently developed implantable "sieve" microelectrode arrays. Axons of a regenerating nerve can be directed to grow through a tiny etched plate containing microscopic holes with independent recording contact points. The bioelectrical activity of individual axons growing through these holes can be detected, multiplexed, and radio-transmitted to a receiver on or near the body surface. We will explore the application of this technology not only for its potential application to prosthetic voice control, but also for the far reaching implications of direct computer-neural interfaces in general.
Although these research projects have a direct application for human voice restoration, they are also designed to advance the basic science of neural regenerative processes. Moreover, we have a continued interest in comparative studies, with experience in human, rodent, bat, and avian vocal production. Our work therefore pertains to functional reinnervation and reanimation in a wide variety of motor systems and animal models.
Heaton JT, Farabaugh SM, Brauth SE. Effect of syringeal denervation in the budgerigar (Melopsittacus undulatus): the role of the syrinx in call production. Neurobiol Learn Memory 1995;64:68-82.
Heaton JT. The role of descending forebrain projections and auditory feedback in budgerigar vocal development [Dissertation]. College Park, MD: University of Maryland, 1997:217 pp.
Kobler JB, Datta S, Goyal RK, Benecchi EJ. Innervation of the larynx, pharynx, and upper esophageal sphincter of the rat. J Comp Neurol 1994;349:129-147.
John J. Rosowski, Ph.D.
William T. Peake, Sc.D.
Saumil N. Merchant, M.D.
Eaton-Peabody Laboratory
Tel: 617-573-3745
Our group measures the mechanics and acoustics of the external and middle ears of normal and diseased human ears, as well as the ears of other terrestrial vertebrates. By measuring the minute forces and motions in different kinds of ears, we can formulate general laws of sound transmission through ears. Our work is grounded in the comparative physiology and anatomy of animal hearing.
All vertebrate hearing follows a general plan in which sound is transmitted to the inner ear by the mechanical and acoustical system of the external ear, tympanic membrane, and ossicles. Each species ear structure is specialized for its specific needs. Elephants have large ears that are sensitive to the very low-frequency sounds they use to communicate over long distances, while bats have minute middle ear structures that are sensitive to the high frequencies used in their echo-locating sonar. The ears of these two species are so different that there is little overlap in their auditory range; bat sounds are inaudible to elephants and vice-versa. Systematic measurements of function in ears with different structures will establish physical laws that relate the anatomy of the external ear and the middle ear to hearing function.
These laws can then be applied to a number of problems, including (1) The improvement of techniques used in the surgical reconstruction of the ear, (2) the determination of the contributions of external and middle ear function to hearing in diseased ears or ears with greatly different structures, (3) predictions of the hearing capabilities of extinct animals whose ears are preserved in the fossil record, and (4) the establishment of correlations between ear structure and animal behavior.
Rosowski JJ. The effects of external- and middle-ear filtering on auditory threshold and noise-induced hearing loss, J Acoust Soc Am 1991; 90:124-135.
Rosowski JJ. Hearing in transitional mammals: predictions from the middle ear anatomy and hearing capabilities of extant mammals. In: DB Webster, AN Popper, RR Fay, eds. The evolutionary biology of hearing. New York, NY: Springer-Verlag, 1991; 625-631.
Peake WT, Rosowski JJ, Lynch TJ III. Middle-ear transmission: acoustic vs. ossicular coupling in cat and human. Hear Res 1992; 57:245-268.
Ravicz ME, Rosowki JJ, Voigt HF. Sound-power collection by the auditory periphery of the Mongolian gerbil Meriones unguiculatus, I: middle-ear input impedance. J Acoust Soc Am 1992; 92:157-177.
Puria S, Rosowski JJ, Peake WT. Middle-ear pressure gain in humans. In: Duifhuis H, Horst JW, van Dijk P, van Netten S, eds. Biophysics of hair cell sensory systems. World Scientific Publishing Co. Pte. Ltd., 1993.
Bertrand Delgutte, Ph.D.
Peter A. Cariani, Ph.D.
Ruth Y. Litowsky, Ph.D.
Eaton-Peabody Laboratory
Information about sound is conveyed from the inner ear to the brain by the auditory nerve. We study how the brain processes this information in order to explain how we perceive sounds. We are also hope to apply this basic knowledge to hearing aids and cochlear prostheses for the profoundly deaf, as well as to the design of high-quality systems for the transmission and reproduction of speech and music.
In our current research, we are recording the activity of single cells in the auditory nerve and brainstem nuclei in response to speech and musical sounds. Recent results suggest that musical pitch may correspond to the most frequent interval between action potentials in the entire auditory nerve. This finding may provide a simple explanation for the "missing fundamental" phenomenon, which has long intrigued experimental psychologists, physiologists, and musicians. This phenomenon refers to listeners hearing a pitch at the fundamental frequency of a voice or musical instrument even when this frequency is not physically present.
We are also investigating how the brain localizes sources of sound. In this work, using virtual reality techniques to provide "natural" acoustic inputs to the ears, we can achieve the precise stimulus control needed to dissect the response properties of nerve cells. A long-term goal of this research is to understand why hearing-impaired listeners have much greater difficulty understanding speech in the presence of competing sounds than do normal-hearing listeners and to apply this knowledge to the design of hearing aids that would be more effective in noisy environments.
Delgutte B, Kiang NYS. Speech coding in the auditory nerve, IV: sounds with consonant-like dynamic characteristics. J Acoust Soc Am 1984; 75:897-907.
Delgutte B. Physiological mechanisms of psychophysical masking: observations from auditory-nerve fibers. J Acoust Soc Am 1990; 75 897-907.
Delgutte B, Cariani PA. Coding of the pitch of harmonic and inharmonic complex tones in the inerspike intervals of auditory nerve fibers. In: Schouten MEH, ed., The processing of speech. Berlin, Germany: Mouton-De Gruyter, 1992; 37-45.
Delgutte B, Litovsky RY, Joris PX, Yin TCT. Relative importance of different acoustic cues to the directional sensitivity of inferior- colliculus neurons. Proc Tenth International Symposium on Hearing, Irsee, Germany, June 1994.
William F. Sewell, Ph.D.
Edmund A. Mroz, Ph.D.
Eaton-Peabody Laboratory
Tel: 617-573-3156
We are working to understand the chemical processes that take place when the ear communicates auditory information to the brain. Neurons within the ear and brain use small molecules, called neurotransmitters, to communicate with other neurons. Most drugs that affect the nervous system do so by interfering with the action of neurotransmitters in the brain. It should be possible to develop drugs that can affect these processes in the inner ear. Such drugs will be useful tools for intervening therapeutically in diseases of the inner ear, as well as for increasing our understanding of the biology of the ear and brain.
One project is to identify the excitatory neurotransmitter released by the sensory cells of the ear. This neurotransmitter does not appear to be one of the known neurotransmitters. We extract the neurotransmitter from sensory cells in the ear and detect its presence in the extract with a bioassay that normally responds to the neurotransmitter released from the sensory cells. The bioassay is used to monitor purification and chemical characterization of the extracted neurotransmitter. We have purified the excitatory chemical, and we are now attempting to deduce the chemical structure of this compound.
Another project is to understand the mechanism by which neurotransmitters released from neurons in the brain alter the way the inner ear responds to sound. One of these neurotransmitters, acetylcholine, may enhance the response of the ear in noisy environments as well as protect the delicate sensory cells of the inner ear from loud sounds. We think the protective function of acetylcholine is produced by a different molecular mechanism than the auditory enhancement function and are working to identify the chemical processes that might be involved in protection. This work is likely to lead to a better understanding of how loud sounds destroy the inner ear and, thereby, to developing strategies for preventing and treating acoustic trauma.
There are a number of other neurotransmitters in neurons of the brain which might be released into the inner ear. However, almost nothing is known of the effects they might have on the ear. We are working to determine the effects of these other neurotransmitters on inner ear function. This project will increase our basic understanding of these neurotransmitters and may provide findings that can be used to enhance our understanding and treatment of pathological situations in the ear.
Sewell WF, Mroz EA. Neuroactive substances in inner ear extracts. J Neurosci 1987; 7: 2645-2475.
Starr PA, Sewell WF. Neurotransrnitter release and its blockade by glutamate-receptor antagonists. Hear Res 1991; 52:23-42.
Sewell WF, Starr PA. Effects of calcitonin gene-related peptide and efferent nerve stimulation on afferent transmission in the lateral line organ. J Neurophysiol 1991; 65:1158-1169.
Davis RL. Sewell WF. Neurite reaeneration from single primary-auditory neurons in vitro. Hear Res 1992; 58:107-121.
Joseph B. Nadol, Jr., M.D.,
Saumil N. Merchant, M.D.
Tel: 617-573-3711 / 800-822-1327
TDD: 617-573-3888 Fax: 617-573-3838
Microscopic study of the anatomy and pathology of the human temporal bone is a scientific endeavor that is critical to our understanding of disease processes affecting the hearing and balance systems. Such study is essential for progress in diagnosis, therapy, and prevention of disorders affecting these organs. In addition to traditional light microscopic examination, a variety of new and innovative techniques are now available to study these tissues including immunohistochemistry, electron microscopy, computer-aided imaging, and molecular genetic research techniques. The National Temporal Bone Registry was established by the National Institute on Deafness and Other Communication Disorders (NIDCD) on September 30, 1992, via a contract awarded to the Infirmary. The Registry is meant to serve as a national resource for researchers and the public to promote and facilitate human temporal bone research. Fifteen active and eleven inactive temporal bone laboratories in the United States work in collaboration with the Registry and constitute its peripheral network.
The Registry's missions and activities are:
It maintains and regularly updates a computerized database of all human temporal bone
collections in the United States. At present, the database contains detailed information on
over 12,000 temporal bone specimens.
It maintains a 24-hour toll-free telephone, TDD, fax
service, and an internet web page (www.tbregistry.org) to respond to inquiries from the public
and the scientific community about human temporal bone research.
It develops and disseminates information about temporal bone donation and related research by
a variety of mechanisms. For example, it publishes a semi-annual newsletter which has a
circulation of over 12,000.
It develops and holds periodic professional educational courses and workshops to train
investigators in the field of human otopathology research.
It identifies human temporal bone collections in the nation that are at risk of being
discarded or lost, and develops strategies to conserve them.
It maintains a national temporal bone donor program. Under this program, patients with ear
disease can pledge their temporal bones for scientific study after death. Over 6,000 pledges
are currently on file. The donor program is an extremely valuable resource to clinicians in
understanding and improving their knowledge of ear disorders.
The Registry maintains a national temporal bone acquisition network to procure temporal bone
tissue from registered donors.
The current state-of-the-art technology in voice assessment relies heavily on subjective (perceptual) judgments about voice quality and vocal function. The availability of objective measures should improve diagnostic and treatment procedures by providing quantitative information about how specific underlying mechanisms are functioning (or malfunctioning). Such measures will also allow for the unbiased assessment of methods used to treat voice disorders (e.g., efficacy of laryngeal surgical procedures). This latter application is particularly critical given the increasing pressures to provide objective outcome data to support the efficacy of treatments.
Hyperfunctional disorders are the most common types of voice disorders and fall into two general categories: (1) organic disorders such as vocal cord nodules and (2) disorders with no apparent organic pathology. In this latter case, the larynx may be producing a voice that sounds disordered, but there are no visible growths in the larynx and the specific cause of the problem is not evident. Our work in this area includes studies ranging from (1) how normal voice is produced, (2) computer modeling of how normal and disordered vocal cords function, (3) the use of objective measures to describe the mechanisms which underlie vocal hyperfunction, and (4) clinical efficacy studies of the various voice therapy techniques that are used to treat vocal hyperfunction.
Even though hyperfunctional disorders are very common, there is a paucity of objective data about the mechanisms which underlie vocal hyperfunction as well as a lack of information concerning the actual role of hyperfunction in the development of voice disorders. The information gained from our work should lead to new insights concerning the etiology of vocal hyperfunction and to improvements in clinical methods used to diagnose and treat these disorders.
Hillman RE, Holmberg EB, Perkell JS, Walsh M, Vaughan C. Objective assessment of vocal hyperfunction: an experimental framework and preliminary results. J Speech Hear Res 1989; 32:373-392. Holmberg EB, Hillman RE, Perkell JS, Gress C. Relationships between intra-speaker variation in aerodynamic measures of voice production and variation in SPL across repeated recordings. J Speech Hear Res 1994; 37.
Saumil N. Merchant, M.D.,
Joseph B. Nadol, Jr., M.D.
Otopathology Laboratory
Tel: 617-573-3651 Fax: 617-573-3939
The Otopathology Laboratory was established in 1961 by Harold F. Schuknecht, M.D. for the purpose of elaborating the morphologic and physiologic alterations occurring in disorders of hearing and balance. The material under study consists of the temporal bones acquired post mortem from human subjects with clinically documented, naturally occurring diseases of the audiovestibular system and the temporal bones of lower mammalian species with experimentally induced alterations designed to alter audiovestibular function. The objectives of these studies is to describe and quantify the pathologic changes and to correlate them with the clinical manifestations for the purpose of providing information on the cause, prevention, and treatment of ear diseases.
Generally the temporal bones are prepared for light microscopic examination by a process consisting of decalcification, embedding in celloidin, serial sectioning, staining, and mounting on glass slides. The human collection prepared in this manner numbers 1600 temporal bones from 700 subjects and continues to grow. Other methods in use for both human and animal temporal bones includes surface preparations, electron microscopy, immunostaining, and molecular biologic techniques.
A series of more than 100 otolaryngologists appointed to 1- or 2-year research fellowships have greatly enhanced the scientific productivity of the laboratory. Studies performed in this laboratory have resulted in over 150 original journal articles, 16 chapters and 3 books which represent a large contribution to knowledge on the pathophysiology of the audiovestibular system. These reports provide new knowledge on Meniere's disease, otosclerosis, Paget's disease, noise trauma, otitis media, acoustic tumors, positional vertigo, deafness of aging, disequilibrium of aging, and numerous other developmental, infectious, traumatic, and neoplastic diseases. Experimental studies that have provided insight into the pathophysiology of the audiovestibular system include: frequency localization in the cochlea; morphologic changes associated with induced endolymphatic hydrops; deafness and disequilibrium caused by ototoxic drugs; biologic adaptability of the middle ear to the implantation of tissues, metals and plastic; noise-induced deafness; fluid mechanics of the inner ear; reparative responses of the inner ear to surgical trauma; and numerous anatomic studies on the microscopic anatomy of the sensory and neural structures.
Edmund Mroz, Ph.D.
Eaton-Peabody Laboratory
Tel: 617-573-4232
Many diseases of the inner ear arise from defects in the management of fluids in special compartments. This research examines how the sensory cells of the inner ear regulate their mineral composition, volume, and acidity. For the inner ear to function properly, its cells must have the proper combination of the minerals potassium, sodium, magnesium, and calcium. The volumes of the cells and their acidity (pH) must also be controlled. In the inner ear, the processes that regulate these properties of cells face some unique challenges: the fluids bathing some inner-ear cells have unusual mineral compositions, and stimulation of the ear by sound may significantly stress these regulatory processes. It is possible that some types of hearing loss due to loud noise or to drugs may result from problems with this regulation. Understanding these regulatory processes may thus help to prevent or to minimize some forms of hearing loss.
A combination of techniques, including video microscopy, fluorescence microscopy, and electron probe analysis, is used to investigate these regulatory processes. In some experiments, we analyze hair cells after they have been isolated from other cells of the inner ear. These experiments allow detailed study of the regulatory processes and how the processes are influenced by the composition of the fluids bathing the cells and by drugs. Work thus far has shown the importance of a sodium/potassium "pump" in regulating hair-cell composition and has led us to hypothesize that some forms of hearing loss may be due to problems in regulating hair-cell sodium.
In other experiments, hair cells are examined microscopically in relatively intact inner ears. This type of experiment allows us to investigate the stresses placed upon these regulatory processes by sound stimulation and how the various cell types in the inner ear may work together to deal with these stresses.
M. Charles Liberman, Ph.D.
Eaton-Peabody Laboratory
Tel: 617-573-4233
The normal inner ear is interconnected with the brain by means of nerve fibers: some carry sensory information about sounds in the environment from the ear to the brain, while others feed control signals from the brain back to the ear. These sensory (afferent) and feedback ( efferent) pathways are each composed of two fundamentally different kinds of nerve fibers. Little is known about why so many different kinds of nerve fibers are needed and what role each plays in the overall process of hearing. Our research aims to answer these basic questions.
Currently, we are investigating one of the feedback pathways which may act to minimize the masking effects of background noise. Understanding the normal mechanisms underlying such anti-masking effects should help us understand why noisy backgrounds present such problems for the hearing impaired and why most hearing aids perform badly in noisy environments.
We know that overexposure to loud sounds can damage the inner ear, leading to hearing loss. Sometimes the damage is temporary, and sometimes it is permanent. Our research aims to understand how this damage takes place, which structures are most vulnerable, and which types of damage are reversible and which are irreversible. It has long been known that some individuals are much more susceptible to noise damage than others. One of the major goals of our current research is to understand the basis for these differences. Ultimately, we hope that strategies can be developed for identifying those most at risk as well as for minimizing the permanent effects of noise exposure.
Darlene R. Ketten, Ph.D.
Cochlear Implant Research Laboratory
Three-Dimensional Head and Neck Imaging
Tel: 617-573-4083 Fax: 617-720-4408
E-mail: eolunix!drk@eddie.mit.edu
In our work, we seek to understand how structural changes in the ear relate to differences in hearing abilities. By comparing ears from ultra- and infrasonic animals as well as normal and hearing impaired humans, we determine how structural differences--whether brought about by evolution or disease--affect the frequency ranges detected. The results also provide a better understanding of how each middle and inner ear component contributes to hearing ranges and acuity as well as insights into alternative sound transduction mechanisms that may eventually assist in treating some types of hearing impairment. Our current research focus is on basilar membrane construction and spiral ganglion cell distributions. These components are fundamental to the resonance and sensitivity characteristics of any ear.
Three-dimensional computerized models of the middle and inner ear of each ear specimen are produced from histological thin sections and/or computerized tomographic (CT and MRI) images. Because modern biomedical imaging techniques are used in this research, an additional but important benefit of the work has been the development of far better techniques for imaging inner ear pathologies in our patients. The effectiveness of each new scan technique is verified by comparing scan results with the histology of the same bones. The majority of human specimens are post-mortem donations from the temporal bone bank. Non-human species include both conventional land mammal ears (e.g., cat, rat, bovine, etc.) and several exotic species obtained through donations from zoos and aquaria.
Work with live human ears is done in conjunction with the Cochlear Implant Research Program. We use in vivo CT images are used to analyze the ears of cochlear implant patients both pre- and post-operatively. Using pre-operative scans, we determine which ear is better for implantation and to quantify any pathologies that may affect the success of the implant. Three-dimensional analyses of post-operative patient scans provide not only new anatomical data, but also measurements of individual electrode placement, which may affect the success of the implant.
Michael P. Joseph, M.D.
Simmons Lessell, M.D.
Joseph F. Rizzo, III, M.D.
Departments of Ophthalmology and Otolaryngology
Tel: 617-573-3192 Fax: 617-573-3939
Loss of vision can result from head injury. In some cases, there is no injury to the orbit nd the visual loss is thought to be due to injury to the optic nerve in its bony canal. Though there is no standard treatment of patients with this injury, we have treated these patients with corticosteroids and surgical decompression of the optic canal. Our series is the largest carefully documented series.
We have organized two international meetings to discuss this clinical problem. We also have organized an international, multicenter, prospective, and randomized study to compare treatments. Patients will be randomly selected to receive either corticosteroids alone or to receive corticosteroids coupled with a surgical opening of the optic canal.
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