VESTIBULAR REFLEXES DURING NATURAL MOTION

NIH GUIDE, Volume 22, Number 11, March 19, 1993



PA NUMBER:  PA-93-066



P.T. 34



Keywords:

  Electrophysiology 

  Physiology, Human 

  Sensory System 



National Institute on Deafness and Other Communication Disorders

National Eye Institute



PURPOSE



The National Institute on Deafness and Other Communication Disorders

(NIDCD) and the National Eye Institute (NEI) invite applications for

the support of basic and applied studies seeking to characterize the

vestibular reflexes that maintain binocular fixation on visual targets

during locomotion and other volitional movements of the head and body.

The NIDCD and the NEI share an interest in this area.  The

vestibulo-ocular reflex (VOR) is, at present, the most direct and

accessible probe of vestibular function.  This initiative seeks to

establish the fundamental knowledge base that will lead to the

development of clinical test protocols for assessing the vestibular

system in vivo during natural motion.



HEALTHY PEOPLE 2000



The Public Health Service (PHS) is committed to achieving the health

promotion and disease prevention objectives of "Healthy People 2000,"

a PHS-led national activity for setting priority areas.  This Program

Announcement (PA), Vestibular Reflexes During Natural Motion, is

related to the priority area of physical activity fitness,

unintentional injuries, occupational health and safety and clinical

prevention services.  Potential applicants may obtain a copy of

"Healthy People 2000" (Full Report:  Stock No. 017-001-00474-0) or

"Healthy People 2000" (Summary Report:  Stock No. 017-001-00473-1)

through the Superintendent of Documents, Government Printing Office,

Washington, DC 20402-9325 (telephone 202-783-3238).



ELIGIBILITY REQUIREMENTS



Applications may be submitted by domestic and foreign for-profit and

non-profit organizations, public and private, such as universities,

colleges, hospitals, laboratories, units of State and local

governments, and eligible agencies of the Federal government.  Domestic

applications may include international components.  Applications from

minority individuals and women are encouraged.



MECHANISM OF SUPPORT



The mechanism of support for this program will be the National

Institutes of Health (NIH) individual research project grant (R01).



RESEARCH OBJECTIVES



Background



The VOR is driven by two types of head accelerations, angular, sensed

by the labyrinthine semicircular canals, and linear, sensed by the

otolithic organs.  It is a rapid and robust reflex system that usually

operates synergistically with the slower visual following reflexes to

maintain a stable image on the retina over the broad range of

trajectories, velocities and frequencies of head motion performed

during daily living.  By illustration, when subjects fixate on a target

while walking, their VORs must produce compensatory eye movements to

stabilize gaze in the face of linear and rotational (pitch) head motion

in the vertical plane.  The predominant frequencies of these natural

head movements greatly exceed the frequencies assessed during

conventional tests of vestibular function.



Oscillopsia, the illusory movement of the stationary world caused by

slippage of images on the retina during head movement, results from an

inability of the vestibular gaze-stabilizing reflexes to compensate for

head movement.  It is a well-recognized symptom of low VOR gain

associated with marked bilateral vestibular disease.  Patients with

oscillopsia are typically symptomatic during the head motion that

accompanies locomotion.  The face validity of assessing the vestibular

reflexes during locomotion with vision fixed or during combined eye and

head movements is apparent, since the vestibular system stabilizes gaze

during active movement of the head, eyes, and body.  Yet, most studies

of the VOR have been performed with passive stimuli, by rotating

subjects in the horizontal plane with both the head and body fixed.

Furthermore, it has been estimated that as many as 50 percent of

patients whose complaints suggest a high likelihood of vestibular

pathology have normal vestibular test findings.  Some of these

undiagnosed patients would likely be identified by testing the system

under its operational state of free motion.  Study of the vestibular

system in its operational state will enhance the understanding of this

system in both health and disease.



Scope



This initiative seeks to establish the fundamental knowledge base that

will ultimately lead to the development and expansion of much-needed

clinical test protocols for assessing the image-stabilizing vestibular

reflexes during locomotion and other volitional movements, such as gait

transitions.  Specifically, the goal of this project is to determine

how the VOR generates compensatory eye movements to maintain binocular

fixation on visual targets during the linear, angular and complex head

motion associated with daily living.  Such an approach to the

evaluation of the balance-disordered patient will likely enhance the

diagnostic efficiency of vestibular testing.



Human and/or animal studies of the biophysical dynamics and underlying

neural mechanisms of the VOR are sought.



Research studies may include, but are not limited to, the topics listed

below:



o  role of the vestibular system in the control of gaze stability

during stance versus gait;



o  development of animal models for the study of the VOR during natural

motion;



o  development of computational models relating the VOR during natural

motion to its neural substrates;



o  role of the vestibulo-collic reflexes and head stabilization in gaze

stability during motion;



o  coding and integration of vestibular, visual and proprioceptive

signals in response to coacting linear and angular acceleration forces;



o  effects of vestibular system abnormalities on the VOR during natural

motion.



STUDY POPULATIONS



SPECIAL INSTRUCTIONS TO APPLICANTS REGARDING IMPLEMENTATION OF NIH

POLICIES CONCERNING INCLUSION OF WOMEN AND MINORITIES IN CLINICAL

RESEARCH STUDY POPULATIONS



NIH policy is that applicants for NIH clinical research grants and

cooperative agreements are required to include minorities and women in

study populations so that research findings can be of benefit to all

persons at risk of the disease, disorder or condition under study;

special emphasis must be placed on the need for inclusion of minorities

and women in studies of diseases, disorders and conditions which

disproportionately affect them.  This policy is intended to apply to

males and females of all ages.  If women or minorities are excluded or

inadequately represented in clinical research, particularly in proposed

population-based studies, a clear compelling rationale must be

provided.



The composition of the proposed study population must be described in

terms of gender and racial/ethnic group.  In addition, gender and

racial/ethnic issues must be addressed in developing a research design

and sample size appropriate for the scientific objectives of the study.

This information must be included in the form PHS 398 in Sections 1-4

of the Research Plan AND summarized in Section 5, Human Subjects.

Applicants are urged to assess carefully the feasibility of including

the broadest possible representation of minority groups.  However, NIH

recognizes that it may not be feasible or appropriate in all research

projects to include representation of the full array of United States

racial/ethnic minority populations (i.e., Native Americans [including

American Indians or Alaskan Natives], Asian/Pacific Islanders, Blacks,

Hispanics).  The rationale for studies on single minority population

groups should be provided.



For the purpose of this policy, clinical research is defined as human

biomedical and behavioral studies of etiology, epidemiology, prevention

(and preventive strategies), diagnosis, or treatment of diseases,

disorders or conditions, including but not limited to clinical trials.



The usual NIH policies concerning research on human subjects also

apply.  Basic research or clinical studies in which human tissues

cannot be identified or linked to individuals are excluded.  However,

every effort should be made to include human tissues from women and

racial/ethnic minorities when it is important to apply the results of

the study broadly, and this should be addressed by applicants.



For foreign awards, the policy on inclusion of women applies fully;

since the definition of minority differs in other countries, the

applicant must discuss the relevance of research involving foreign

population groups to the United States' populations, including

minorities.



If the required information is not contained within the application,

the application will be returned.



Peer reviewers will address specifically whether the research plan in

the application conforms to these policies.  If the representation of

women or minorities in a study design is inadequate to answer the

scientific questions(s) addressed AND the justification for the

selected study population is inadequate, it will be considered a

scientific weakness or deficiency in the study design and reflected in

assigning the priority score to the application.



All applications for clinical research submitted to NIH are required to

address these policies.  NIH funding components will not award grants

or cooperative agreements that do not comply with these policies.



APPLICATION PROCEDURES



Applications are to be submitted on the grant application form PHS 398

(rev. 9/91) and will be accepted at the standard application deadlines

as indicated in the application kit.  The receipt dates for

applications for AIDS-related research are found in the PHS 398

instructions.



Application kits are available at most institutional offices of

sponsored research and may be obtained from the Office of Grants

Inquiries, Division of Research Grants, National Institutes of Health,

Westwood Building, Room 449, Bethesda, MD 20892, telephone

301-496-7441.  The title and number of the announcement must be typed

in Section 2a on the face page of the application.



The completed original application and five legible copies must be sent

or delivered to:



Division of Research Grants

National Institutes of Health

Westwood Building, Room 240

Bethesda, MD  20892**



Applicants from institutions that have a General Clinical Research

Center (GCRC) funded by the NIH National Center for Research Resources

(NCRR) may wish to identify the GCRC as a resource for conducting the

proposed research.  If so, a letter of agreement from either the GCRC

program director or Principal Investigator should be included with the

application.



REVIEW PROCEDURES



Applications will be assigned on the basis of established PHS referral

guidelines.  Applications will be reviewed for scientific and technical

merit by study sections of the Division of Research Grants, NIH, in

accordance with the standard NIH peer review procedures.  Following

scientific-technical review, the applications will receive a

second-level review by the appropriate national advisory council.



AWARD CRITERIA



Applications will compete for available funds with all other approved

applications.  The following will be considered in making funding

decisions:



o  Quality of the proposed project as determined by peer review

o  Availability of funds

o  Program balance among research areas of the announcement



INQUIRIES



Written and telephone inquiries concerning this PA are encouraged.  The

opportunity to clarify any issues or questions from potential

applicants is welcome.



Direct inquiries regarding programmatic issues to:



Daniel A. Sklare, Ph.D.

Division of Communication Sciences and Disorders

National Institute on Deafness and Other Communication Disorders

Executive Plaza South, Room 400-B

6120 Executive Boulevard

Rockville, MD  20892

Telephone:  (301) 402-3461

FAX:  (301) 402-6251



Michael D. Oberdorfer, Ph.D.

Strabismus, Amblyopia and Visual Processing Branch

National Eye Institute

Building 31, Room 6A-47

Bethesda, MD 20892

Telephone:  (301) 496-5301

FAX:  (301) 402-0528



Direct inquiries regarding fiscal matters to:



Sharon Hunt

Division of Extramural Activities

National Institute on Deafness and Other Communication Disorders

Executive Plaza South, Room 400-B

6120 Executive Boulevard

Rockville, MD  20892

Telephone:  (301) 402-0909



Carolyn E. Grimes

Extramural and Collaborative Program

National Eye Institute

Building 31, Room 6A48

Bethesda, MD  20892

Telephone:  (301) 496-5884



AUTHORITY AND REGULATIONS



This program is described in the Catalog of Federal Domestic Assistance

No. 93.173 and No. 93.867.  Awards are made under authorization of the

Public Health Service Act, Title IV, Part A (Public Law 78-410, as

amended by Public Law 99-158, 42 USC 241 and 285) and administered

under PHS grants policies and Federal Regulations 42 CFR 52 and 45 CFR

Part 74.  This program is not subject to the intergovernmental review

requirements of Executive Order 12372 or Health Systems Agency review.



.

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