Charles R. Larson - US grants

The present study seeks to provide answers to questions regarding the neural control of the larynx during phonation in monkeys. Anatomical and physiological evidence indicates two descending pathways that may be important in phonation, converge at the periaqueductal gray(PG) of the midbrain. Projection from the anterior cingulate gyrus (CG) to the PG are known to be important for phonation, whereas projections from the motor cortex influence laryngeal muscles but have not been shown to affect phonation. Pilot data utilized microstimulation of the motor cortex and wide-field stimulation of the PG. Stimulation of the PG elicited phonation, and of the motor cortex affected laryngeal muscle activity. Simultaneous stimulation of the two structures sometimes interacted but the site and mechanisms of this interaction are unknown. I propose to study these mechanisms of laryngeal control by the method of chronic single unit recording in awake monkeys. Monkeys will be prepared for chronic single unit recording using standard aseptic surgical techniques. A recording chamber will be placed so as to allow recording of single PG neurons. Chronic stimulation electrodes will be implanted in the CG and laryngeal motor cortex. Chronic EMG electrodes will be implanted in the laryngeal muscles. In the first study the CG will be stimulated to elicit phonation. Temporal correlations between CG stimulation and PG unit activity will be sought. The motor cortex will then be stimualted to assess any changes in PG or EMG activity or acoustical properties of phonation. The second study will involve training monkeys to vocalize and PG unit activity will be recorded during such vocalizations. Temporal and spatial (pitch and intensity) correlations between phonation, PG activity and laryngeal EMG will attempt to determine in what ways the PG units are involved in phonation. Data from this study will contribute to a better understanding of the nature of neural control over features of phonation such as pitch and intensity control. It is also hoped that these data may eventually lead to improved theories on the etiology of neurogenic voices disorders such as spastic dysphonia.

All understanding of neural mechanisms controlling the larynx ad voice is an important health objective for the treatment and prevention of disorders affecting voice and speech. The present proposal will attempt to improve our understanding of the role of auditory feedback on voice pitch control. Normal adults, children, trained singers and adult stutterers will serve as subjects. Subjects will vocalize and receive their own voice through earphones as a source of feedback. The pitch and spectral content of the subject's voice will be experimentally manipulated to learn which aspects of the acoustical feedback signal are most important in the control of the voice pitch. Each variable, voice pitch and spectral content will be systematically and independently manipulated. Linear systems analysis utilizing sinusoidal modulation of voice pitch will be done in order to develop a transfer function of the system controlling voice pitch. Subjects will perform various vocal tasks to learn under which vocal conditions auditory feedback is most important. By learning how and under what conditions altered auditory feedback changes vocal output, we will learn how normal vocal output depends on auditory feedback. Comparison of the responses of normal adults with children will provide information on development on neural mechanisms related to control of voice pitch. Comparisons of responses of normal adults with trained singers will provide information on the limits of control of voice pitch in well trained singers. Comparisons of responses from normal adults with stutterers will provide information that may be important for the understanding of the etiology or treatment stuttering. We wish to test the hypotheses that (1) normal vocalization relies to some extent on auditory feedback, (2) control of voice pitch depends on feedback pitch of the auditory signal, (3) the magnitude of a pitch change in the subject's voice feedback influences the magnitude of a change in vocal output, (4) the more similar the spectral characteristics of the feedback are to the speaker's own voice, the stronger the effect of feedback will be, (5) under certain demanding vocal tasks, auditory feedback is more important than simpler tasks, (6) different subject groups rely more heavily on feedback for the control of voice of than others and (7) susceptibility to feedback interruption may be related to training, development or stuttering. Experiments on mechanical stimulation of laryngeal structures will be conducted in order to learn the most effective means of activating mechanical sensory receptors that reflexively modify laryngeal muscles. Eventually, knowledge from these experiments will be used to test models of neural dysfunction involving sensation in voice disordered patients.

DESCRIPTION (provided by applicant): Voice disorders are among the most prevalent disorders affecting people with communication disabilities. People afflicted with these disorders have difficulty communicating with others, the disorders may adversely affect their careers, and the people often become socially isolated. There is little we can do to prevent these disorders without a solid understanding of their cause. Part of the reason for this lack of understanding is because of the lack of basic knowledge of normal control mechanisms of the voice. It is assumed that sensory feedback may be involved in control of the voice, but there is little hard evidence to support this claim. The overall goal of this research project is to understand the function of sensory feedback in the control of voice fundamental frequency (F0) and intensity. People use their voice for a variety of functions such as speech, singing and emotional expression. To fully understand how voice F0 and intensity are controlled, we must study them in different tasks, because it is known from research in other motor systems that the importance of sensory feedback varies according to the demands of the task. Auditory and kinesthetic feedback from the larynx will be studied as subjects are engaged in different vocal tasks. The overall hypothesis of the proposal is that the magnitude of pitch and loudness shift reflexes depend on the presence of laryngeal kinesthetic feedback and vary according to the importance of sensory feedback for accuracy of F0 and intensity control in specific tasks. By testing vocal reflexes as people are using their voice in different tasks, we will learn how sensory feedback is modulated in the tasks. It is hypothesized that auditory reflex magnitudes will increase in tasks that require skilled use of the voice, both in frequency and intensity of phonation. The tasks to be tested include pitch matching, loudness regulation, speech and singing a musical scale. It is also hypothesized that kinesthetic and auditory feedback interact in their control of the voice. This interaction was shown in pilot studies in which the pitch-shift reflex dramatically increased in magnitude when the vocal folds were anesthetized or when vibratory stimuli were applied to the larynx. Altering kinesthetic feedback from the vocal folds and simultaneously testing auditory reflexes will provide important information on brain mechanisms that govern interaction between these two sources of feedback.

DESCRIPTION (provided by applicant): The goal of this proposal is to train pre- and postdoctoral students as well as AuD-PhD students to conduct translational research in communication disorders. Normal communication relies on the healthy functioning of several inter-related processes, including hearing and perception, cognition, motor planning and execution. Most communication disorders similarly reflect disruption of multiple components of these processes. This translational research training program aims to foster trainees'understanding of communication disorders from a broad perspective;to consider how all aspects of communication- sensory processing, linguistic and cognitive factors, and motor processes-interact in normal and disordered functioning and how our latest understanding of normal processes helps to design treatment processes. The proposed training program, led by 15 NIH-funded faculty members from the Department of Communication Sciences and Disorders, will combine traditional courses in our Ph.D. program, such as experimental design and methods and doctoral seminars, with new components such as case-based presentations and a translational seminar. The latter two experiences, taught by a rotating group of faculty throughout the academic year, will involve extensive discussion of both normal and disordered communication processes, allowing trainees with a background in basic or applied research to explore ways to extend their research to the solution of clinical problems. Trainees will be taught how to develop and assess new treatment procedures and treatments. Based on knowledge and experiences gained from participation in the presentations and seminars, trainees will write an NRSA research proposal, focused on translation of basic research to the understanding of communication disorders. Research ethics will be emphasized throughout. This program will produce young investigators who are not only skilled in basic and clinical research, but who also know how to design experiments to solve problems related to that disorder. Pre-doctoral trainees will be recruited nationally, from the CSD Department, and the Northwestern University Interdepartmental Neuroscience Program. Post-doctoral trainees will be recruited nationally from list-servs and advertisements. AuD-PhD trainees will be recruited from our AuD program. All trainees must demonstrate a commitment to translational research. Extensive outreach is planned to recruit under-represented minority trainees. RELEVANCE: There is a dearth of well-trained researchers in the field of CSD, particularly for those capable of translational research. Thus, there is a strong demand for future research investigators who are able to apply our newest knowledge of normal function to development of treatments for clinical problems, which impact the well-being and quality of life of individuals with communication disorders. Well-trained investigators are needed in this field to address increasing demands for services at all age levels.

See instructions): The goal of this proposal is to train pre and postdoctoral students as well as AuD-PhD students to conduct translational research in communication disorders. Normal communication relies on the healthy functioning of several inter-related processes, including hearing and perception, cognition, motor planning and execution. Most communication disorders similarly reflect disruption of multiple components of these processes. This translational research training program aims to foster trainees' understanding of communication disorders from a broad perspective; to consider how all aspects of communication- sensory processing, linguistic and cognitive factors, and motor processes-interact in normal and disordered functioning and how our latest understanding of normal processes helps to design treatment processes. The proposed training program, led by 15 NIH-funded faculty members from the Department of Communication Sciences and Disorders, will combine traditional courses in our Ph.D. program, such as experimental design and methods and doctoral seminars, with new components such as case-based presentations and a translational seminar. The latter two experiences, taught by a rotating group of faculty throughout the academic year, will involve extensive discussion of both normal and disordered communication processes, allowing trainees with a background in basic or applied research to explore ways to extend their research to the solution of clinical problems. Trainees will be taught how to develop and assess new treatment procedures and treatments. Based on knowledge and experiences gained from participation in the presentations and seminars, trainees will write an NRSA research proposal, focused on translation of basic research to the understanding of communication disorders. Research ethics will be emphasized throughout. This program will produce young investigators who are not only skilled in basic and clinical research, but who also know how to design experiments to solve problems related to that disorder. Pre-doctoral trainees will be recruited nationally, from the CSD Department, and the Northwestern University Interdepartmental Neuroscience Program. Post-doctoral trainees will be recruited nationally from list-servs and advertisements. AuD-PhD trainees will be recruited from our AuD program. All trainees must demonstrate a commitment to translational research. Extensive outreach is planned to recruit under- represented minority trainees. RELEVANCE (See instructions): There is a dearth of well-trained researchers in the field of CSD, particularly for those capable of translational research. Thus, there is a strong demand for future research investigators who are able to apply our newest knowledge of normal function to development of treatments for clinical problems, which impact the well-being and quality of life of individuals with communication disorders. Well-trained investigators are needed in this field to address increasing demands for services at all age levels.

PROJECT SUMMARY (See instaictions): The primary purpose of this Research Core Center is to promote advancements in the science and understanding of communication by fostering a collaborative environment among a diverse group of investigators. A key element of this purpose is a shared commitment across the participating Pis to data sharing and standardization of research methodologies across laboratories. An Executive Committee, consisting of the Program Director, Program Co-Director, and each of the three Core Directors, will administer the center operations and make key management and strategic decisions. Core 1 will hire personnel to recruit specific populations of hard-to-reach subjects such as children with autism, young children, adolescents and elderly adults, and to administer routine and standardized screening tests. Core 2 will develop centralized and standardized tools for human subject management and data gathering, and will establish a research participant registry and relational database that will facilitate the secure storage and retrieval of information pertaining to subject groups and screening profiles. Finally, Core 3 will undertake the development and dissemination to research laboratories of broadly applicable tools for the analysis and integration of complex data. The Executive Committee will work with individual staff members and investigators to improve functionality of each core. The Executive Committee will work with individual investigators to make suggestions on how to leverage achievements in data sharing and experimental tool upgrading and standardization towards the establishment of new and innovative cross-laboratory collaborations. It will have regular meetings to discuss problems and strategies for solutions to problems that develop between the constituent cores and for problems within cores that are unable to be resolved within the core itself. The Director will have overall decision-making authority in the event that problems are not resolved by action of the committee. The committee will review applications for employment of staff personnel, will review the performance of staff members and will make decisions on hiring and dismissal. The committee will also evaluate yearly progress in relation to the goals of increasing collaborative research, enhancement of research productivity, strengths and weaknesses of the Center's operations, effective use of facilities and staff, and will review recommendations from Pis for improvement of the Center's operation.

DESCRIPTION: The complexity of human communication disorders requires collaborative research between investigators utilizing a variety of skills and techniques. The proposal seeks funding to provide infrastructure support to researchers at Northwestern University who conduct research on the science and disorders of human communication. Through the establishment of three core facilities, this project will provide support to a group of investigators studying the processes involved in normal and disordered hearing, language processing, and speech production. Core 1 will hire personnel to recruit specific populations of hard-to-reach subjects such as children with autism, small children and older people and to administer routine and standardized screening tests. Core 2 will develop centralized and standardized tools for human subject management and data gathering, and will establish a research participant registry and relational database that will facilitate the secure storage and retrieval of data pertaining to subject groups and screening profiles. Finally, Core 3 will develop, deploy and customize techniques for analysis of fMRI and EEG that can be used by various labs to develop connectivity and graph theoretic models of neural mechanisms underlying normal and disordered communication. The net outcome from the work in the three cores will be an increase in collaborative research among investigators, the development of a database containing screening profiles and results of experimental studies of individuals with a variety of communication disorders, and the development of advanced mathematical tools for investigators using fMRI and EEG techniques for the analysis of neural mechanisms related to normal and disordered communication. The innovative outcome of this project will be the establishment of screening tests and experimental protocols that are most reliable for identifying markers of underlying etiologies of disorders of communication.