Michael P. Gorga, Ph.D. - US grants

The overall theme of this research program is to describe cochlear nonlinearities in humans with normal hearing and with hearing loss. Cochlear nonlinearities are evident in many measures, all of which change as a consequence of damage to the peripheral auditory system. It is not possible to directly assess cochlear status in humans, but indirect acoustical and electrophysiological measures can be used to assess nonlinear behavior in responses that describe cochlear function. It also is possible to test the hypothesis that different measures reflect the influences from common underlying mechanisms. Studies included in this proposal will (1) increase our knowledge of underlying processes responsible for the relationship between sensitivity loss and otoacoustic emission generation, (2) lead to a better understanding of the consequences of damage to nonlinear mechanisms with respect to response latencies, (3) describe the changes in suprathreshold function following cochlear damage, and (4) lead to better diagnostic tests that identify the sensory cell population underlying hearing loss in humans. It is hypothesized that all of the phenomena to be studied as part of this research program may reflect different manifestations of a single underlying mechanism associated with cochlear nonlinearities. This unified interpretation will be evaluated with multiple correlational analyses and by manipulation of a simple cochlear model that has anatomical correlates. The melding of both basic and clinical studies will lead to advancements in knowledge of auditory function in humans with normal hearing and with hearing loss, leading to improvements in how hearing loss is identified, quantified and remediated. These improvements, being based on objective measures of threshold and suprathreshold function, will be especially helpful in the diagnosis and treatment of hearing loss in infants, young children, and patients with developmental delay.

[unreadable] DESCRIPTION (provided by applicant): This application requests continued funding for a period of 3 years to support translational research lectures, a special interdisciplinary session, and the presentation of student/resident research at the annual meeting of the American Auditory Society (AAS). These functions were funded by NIH conference grants in 2002 and 2003, and both were highly successful. The AAS was founded in 1974 as a multi-disciplinary association whose mission is to foster dissemination of knowledge and exchange of information about hearing and balance among professionals in Otolaryngology, Hearing Science, Audiology and Industry. Since 1999, we have held our own stand-alone annual conference. The attendance at these meetings has steadily increased from less than 180 in 1999 to over 275 in 2003. The meetings represent a unique opportunity to share the latest applied, clinical research in otolaryngology, audiology and prosthetic development in a small meeting venue. [unreadable] [unreadable] While there are excellent meetings for basic research, fewer opportunities exist for the presentation of rigorous clinical research, and there is no single venue in which basic and applied research are integrated. The purpose of the translational research lectures is to facilitate the transfer of basic research findings into clinical application. The purpose of the special session is to provide a focused interdisciplinary session on one topic of current interest to the disciplines represented in the AAS. The purpose of the Mentored Student/Resident Research Poster Session is to promote the future of research in our disciplines through recognition and mentorship of doctoral students in Audiology and residents engaged in research in Otolaryngology. There has been a decline in the number of Ph.D. [unreadable] Audiology graduates, and increasingly fewer of those graduates enter academic or research careers. Research by clinician scientists in Otolaryngology has also declined in recent years, although trends are changing. We propose a poster-session venue designed to showcase and support Ph.D.-student and resident research, and to encourage individual interaction with noted scientists and mentors in Audiology, Otolaryngology, Hearing Science and Bioengineering. [unreadable] [unreadable] The invited speakers and student/resident poster session provide unique opportunities for basic scientific research to be presented in a format that will encourage its application to clinical practice and will promote future research in Hearing Science, Audiology, and Otolaryngology. Our approach also provides an opportunity for interdisciplinary discussion and cross fertilization, which should foster more productive, applied research endeavors. [unreadable] [unreadable]

DESCRIPTION (provided by applicant): The goal of this research program is to use noninvasive techniques to gain a better understanding of cochlear nonlinearity in humans with normal hearing and with hearing loss. This objective will be approached through a combination of acoustical (middle-ear transfer functions, distortion product otoacoustic emissions, DPOAE), electrophysiological (auditory brainstem response, ABR), and behavioral measurements. The variability in DPOAE measurements will be studied by evaluating the influences of behavioral threshold, middle-ear forward and reverse energy transmission, contributions from the reflection source, and contributions resulting from basal spread of the inter-modulation source on the variability in response levels in humans. Studies of the nonlinearity at the cochlear apex and base will focus on comparisons of compression, response growth, tuning and cochlear amplification for low- and high-frequency cochlear regions. The extent to which behavioral simultaneous masking can be attributed to mechanical suppression in the cochlea will be studied by comparing simultaneous masking and DPOAE suppression in the same subjects. Behavioral and mechanical measurements will be compared in terms of masking/suppression growth, tuning, and cochlear-amplifier gain. The relation between mechanical and neural (ABR) estimates of response growth, tuning and cochlear-amplifier gain will be explored, including measurements in both normal and impaired ears. Here, ABR measurements will make in a simultaneous masking paradigm in much the same way as DPOAE suppression measurements are made, extending the range of stimulus levels over which cochlear processes can be examined. A physically based model of cochlear mechanics will be used to simulate mechanical, neural, and behavioral measurements related to cochlear function, with particular attention to nonlinear processes. The plan of study should increase our knowledge of human cochlear processes and has the potential to lead to the development of better diagnostic strategies for patients with heating loss, especially infants, young children and patients with developmental disabilities who may be unable to provide voluntary responses to sound. The research program combines studies that increase our understanding of underlying process with more clinically oriented efforts that should help to increase the translational nature of the work.

The extent to which research programs involving human subjects are productive depends, in large part, on the ability to efficiently recruit subjects to participate in studies. In general, the widest impact of research involving humans is achieved when participants represent both genders and majority and minority populations. Individual research programs in communication sciences and disorders may have specialized subject needs, including subjects with hearing loss, infants, children, users of either hearing aids or cochlear implants, or children with normal speech and language. Independent efforts by individual research programs to recruit subjects meeting both general and specific needs would be time-consuming, inefficient, and less successful relative to what can be achieved with a more centralized recruitment function. As in the previous cycle, the goals for the continuation of the Human Research Subjects Core (HRSC) are to support the research process by providing access to a large pool of individuals who are interested in participating in research. Through concerted and broadly based recruitment efforts, the HRSC provides access to subjects meeting both general and specific requirements, and, thus, provides benefit to virtually every research program at BTNRH that involves humans as subjects. It will continue and expand minority-recruitment efforts that would be difficult, if not impossible, for individual programs. It will continue to provide additional services related to the preparation of IRB and NIH grant applications, and IRB annual reports and NIH progress reports. It will continue to provide additional layers of security for patient/subject confidentiality and evaluations of the subjectconsent process. It will expand the clinical information contained in the HRSC database by including speech, language, and vocabulary scores from standardized clinical tests. Most importantly, the HRSC is expected to have a positive impact on both the quality and quantity of the human-research studies at BTNRH.

DESCRIPTION (provided by applicant): This application requests continued funding to support translational-research lectures, interdisciplinary special-session presentations, and presentations of student-resident research at the annual meeting of the American Auditory Society (AAS). NIH conference grants have supported these activities for the past 5 years with great success. As a result of this support, the AAS has provided a forum for basic-research scientists to present their work to a clinical audience, thus increasing the translational value of fundamental research findings. The NIH conference grant has also provided support for special interdisciplinary sessions that bring together audiologists, otolaryngologists, hearing scientists and representatives from industry (the four constituencies that make up the membership of the AAS) on a focused topic of broad interest. This session fosters interactions among these disciplines, enhancing opportunities for scientific transfer into the clinic, including the development of improved technologies and intervention strategies. Finally, the NIH conference-grant support has enabled the AAS to encourage the next generation of clinical researchers by providing a forum for students and resident physicians to present their research, and to receive feedback and constructive criticism from senior members of both the basic-science and clinical-research communities. The present application requests support that will allow the AAS to continue these highly successful activities. There is a critical need to translate basic research findings to the care of patients with hearing and balance problems through clinical research efforts. Unfortunately, there is a shortage of individuals embarking on careers in which clinical research is an important component. In an effort to facilitate the transfer from laboratory to bedside, this conference grant supports presentations of basic research findings to a clinical audience. It also encourages students, postdoctoral fellows and residents in training interested in clinical research through a travel-scholarship program that allows them to present their research to more seasoned basic and applied researchers. In this way, the grant fosters translational efforts and provides a nurturing environment for individuals interested in clinical research at the earliest stages of their careers.

HUMAN RESEARCH SUBJECTS CORE Subject recruitment influences research productivity and the pace of research. There are, however, barriers to efficient subject recruitment. In general, few contacted individuals participate in research, with even lower participation among minority communities. Regulatory changes result in additional barriers to subject recruitment. Ensuring compliance with regulations related to human research detracts from time engaged in research. The overarching goal of the Human Research Subjects Core (HRSC), to increase productivity and the pace of research for programs that involve human subjects, is achieved through three mechanisms: (1) increase subject-recruitment efficiency, with special attention to minority-subject recruitment, (2) assist investigators with quality-assurance evaluations, ensure compliance with regulations, and provide a secure environment in which consent/assent/HlPAA forms are stored, and (3) assist investigators in the preparation of IRB and NIH progress reports, IRB applications, and enrollment forms for NIH applications. These services are designed to increase productivity by allowing PIs to focus more on research while assuring that they are in compliance with regulations governing the use of human subjects. With the assistance of the HRSC, 70% of contacted individuals now participate as research subjects. Minority representation in research studies now approximates their representation in our catchment area. Many mechanisms have been put into place that alleviate administrative burdens and ensure compliance. New to the coming cycle, HRSC staff will (1) provide audiometric, tympanometric, and speech-language testing for individuals in the database for whom information is not available, (2) provide these services to research programs that do not have staff qualified to perform these evaluations, and (3) provide consentprocess evaluations by having the HRSC Coordinator observe the consenting of subjects for IRB-approved protocols. The combination of HRSC services will increase both productivity and the pace of research for NIDCD-funded programs that involve humans as subjects.

The proposed Core Center for Communication Disorders (CCCD) differs from our generic Core Center of the previous two cycles in that it has a research base that includes faculty members at the University of Nebraska - Lincoln (UNL) and Creighton University Medical Center (CUMC) as well as the Boys Town National Research Hospital (BTNRH). Geographic expansion of the base was not necessary to qualify for the current level of funding or to provide a sufficient number of users for any given core, but it will allow us to develop a more dynamic, growth-oriented Core Center. Our goal is to achieve further expansion that would include grants from the University of Nebraska Medical Center (UNMC) and the University of Nebraska at Omaha (UNO) as well as CUMC and UNL as part of the future research base. The larger, multi-institutional center will require greater care in the allocation of center resources than was necessary when the Core Center and the BTNRH research program were synonymous with one another and the same individual served as director of both. Under Approach, we outline the distinctions to be made between allocation of resources for members of the research base and the potential base, the governance structure of the CCCD that will monitor core performance and budgets, and the processes that will be used to make adjustments where necessary. Our prior experience suggests that the ongoing cores of the CCCD will play a significant role in increasing efficiency and collaboration within the research base. We can achieve further increases in both efficiency and collaboration by reaching out to the larger group of programs in the potential research base. This will benefit the programs in the current base at least as much as it will benefit the new programs because it will broaden the scope of the programs conducting research related to communication disorders. The growth of communication disorders research at BTNRH and the neighboring institutions is dependent on the Core Center running smoothly. We have the necessary experience and ties among institutions to develop administrative procedures that will insure success.

DESCRIPTION (provided by applicant): The Core Center for Communication Disorders (CCCD) will increase the efficiency of qualifying investigators and promote collaboration among a wide range of research programs at the Boys Town National Research Hospital (BTNRH) and neighboring academic institutions by providing Core support in three areas. The Laboratory Computing and Biostatistics Core (LCBC), under the direction of Stephen Neely, will continue to support research programs by: 1) providing troubleshooting and software development that enables research productivity; 2) developing and maintaining useful software packages that benefit multiple laboratories; and 3) providing expert assistance in the use of research hardware and software. With the addition of a biostatistics resource, the LCBC will provide essential services to all CCCD research programs. The new Research Synergy Core (RSC), under the direction of Barbara Morley and Mary Pat Moeller, will facilitate interactions within a large group of investigators at BTNRH and neighboring institutions by: 1) fostering scientific collaboration through a multifaceted, interdisciplinary program of research and information sharing; 2) fostering the integration of new ideas and research technologies by establishing affinity groups; and 3) reducing barriers to collaboration by identifying opportunities for resource sharing and other forms of interdependence across laboratories and institutions. The Human Research Subjects Core (HRSC), under the direction of Michael Gorga, will continue to support research with human subjects by: 1) increasing the efficiency, with which potential subjects are recruited, including minority subjects, by maintaining and expanding a database of individuals who have expressed an interest in participating in research; 2) assisting investigators in assuring that they are in compliance with local and national regulations; and 3) assisting investigators in the preparation of IRB protocols, IRB and NIH progress reports and in the proper storage and handling of consent forms and related documents. The current CCCD user base includes nine R01grants, but there are more than 20 additional investigators at BTNRH and neighboring institutions with a history of NIH funding and an interest in communication disorders research that can provide the critical mass necessary for increased efficiency and effective collaborations.

DESCRIPTION (provided by applicant): The Short-Term Research Training Program for AuD Students at the Boys Town National Research Hospital (BTNRH) will provide 3-month, full-time hands-on translational research experiences in the hearing sciences to five predoctoral AuD students per year. AuD student will be involved in all aspects of a research project, working in one of 13 BTNRH laboratories currently conducting translational research related to audiology. Most of the 13 laboratory directors have extramural support, mainly from the NIDCD in the form of R01 and R03 grants. Students will work with BTNRH faculty mentors who have extensive experience working in a clinically oriented, multidisciplinary research environment. The experience will include (1) experimental design, (2) subject recruitment, scheduling and consenting (assuming the research project involve humans), (3) data collection and analysis, (4) preparation of a poster describing their work, and (5) if appropriate, preparation of a manuscript. Prior to research participation, students will complete the CITI training course related to research involving human as participants. In addition, they will participate in a course on responsible conduct in research which will meet over the course of their traineeship. Students will attend colloquia and journal groups, and will be exposed to a wide range of laboratories, in addition to the one in which they have primary interest. They will benefit from support services, including cores devoted to laboratory computing and statistical analyses, subject recruitment, and a new core, the Synergy Core, which supports colloquia and other presentations by speakers from outside BTNRH. T35 trainees also will benefit from the presence of postdoctoral fellows who work in many of the laboratories in which predoctoral AuD students will be trained. Postdoctoral fellows, many of whom will go on to academic careers, will benefit by participating with faculty mentors in the training of students. T35 trainees will benefit from the experience of BTNRH faculty who have mentored postdoctoral fellows (as part of the T32 grant), provided research training to AuD and PhD students at the University of Nebraska - Lincoln, and mentored AuD trainees who participated in the first cycle of the T35 program. T35 trainees will be recruited from AuD programs nationally, with special efforts to identify and recruit trainees from under-represented populations. Several measures will be used to assess program success including (1) exit questionnaires completed by each trainee, (2) a survey questionnaire sent to AuD program directors who are asked to provide an assessment of the impact of the T35 traineeship on their students, (3) the number of T35 trainees who go on to the PhD in preparation for a career in research, (4) the number of AuDs who work in positions in which research is emphasized, (5) the number of trainees who present their work at the national meeting of the American Auditory Society (AAS), and (6) the number of publications on which trainees are either first authors or co-authors. PUBLIC HEALTH RELEVANCE: The purpose of this training program is to prepare AuD students so that they can become active participants in translational research. The overarching goal is prepare these students in a way that enables them to become active partners in the process by which laboratory discoveries are moved into clinical practices related to serving patients with hearing loss. The importance of this training is magnified by the progress being made in basic and translational science, the need to translate these discoveries into clinical practice, and the number of individuals with hearing loss in the United States (numbering approximately 30 million) who require clinical services, which will be provided mainly by audiologists.