Full Text PA-96-009

CENTRAL AUDITORY SYSTEM PLASTICITY IN ADULTS

NIH GUIDE, Volume 24, Number 41, December 1, 1995

PA NUMBER:  PA-96-009

P.T. 34

Keywords: 
  Hearing 


National Institute on Deafness and Other Communication Disorders

PURPOSE

The National Institute on Deafness and Other Communication Disorders
(NIDCD) invites applications for the support of research on central
auditory system plasticity in adults.  Such studies may lead to a
better understanding of normal brain function and development as well
as an explanation of the recovery of auditory function sometimes seen
following injury to the auditory system.  In addition, these studies
have the potential to reveal how auditory learning occurs, including
that often seen following cochlear implantation.  Findings from these
studies may also guide the development of therapies for recovery of
function following brain injuries, diseases, and disorders that
affect auditory perception.

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 PA,
Central Auditory System Plasticity in Adults, is related to the
priority area of diabetes and chronic disabling conditions.
Potential applicants may obtain a copy of "Healthy People 2000" (Full
Report:  Stock No. 017-001-00474-0 or Summary Report:  Stock No.
017-001-00473-1) through the Superintendent of Documents, Government
Printing Office, Washington, DC 20402-9325 (telephone 202-512-1800).

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. Foreign
institutions are not eligible for First Independent Research Support
and Transition (FIRST) (R29) awards.  Applications from minority
individuals, women, and individuals with disabilities are encouraged.

MECHANISM OF SUPPORT

The support mechanism for grants in this area will be the individual
investigator-initiated research project grant (R01) and the FIRST
(R29) award.

RESEARCH OBJECTIVES

Background

Change in synaptic strength has long been invoked as a possible
mechanism underlying learning and memory throughout the lifespan.
While it has also been recognized that major features of functional
organization of neural structures, such as representation of the body
surface in somatosensory cortex, are modifiable during specific
periods of development, these maps were considered to be "hard-wired"
in adults and incapable of change.  Over the last decade, however,
studies of several sensory- and motor-related regions of neocortex
have revealed that such maps undergo significant reorganization in
response to injury and learning in adults.  Despite the potential
significance that such research holds for understanding a host of
basic and clinical issues regarding auditory function, few studies of
plasticity have been carried out in the mature auditory system.  This
program announcement (PA) encourages research on plasticity in the
adult auditory system at any level(s) of biological organization,
from the level of the molecule to behavior, and at any processing
station(s), from the cochlea to higher-order areas of auditory
cortex, and beyond.

Changes in the organization of representations of the periphery at
the cortical level have been demonstrated following cochlear damage,
retinal damage, limb amputation, and disruption of sensory
innervation of the skin in adults.  Following such peripheral
perturbations, regions of cortex that are deprived of normal input do
not become "silent," but typically respond to the remaining (usually
adjacent) sensory inputs that are still intact.  This often results
in a shrinkage or elimination of the representation of the perturbed
periphery and an enlargement of the representation of the intact
periphery.  Although most investigations of this type have examined
changes in neocortex, subcortical structures have also been studied
using these experimental approaches.

The effects of learning on sensory cortex have been documented in the
auditory system.  For example, frequency receptive fields of neurons
in the adult primary auditory cortex can be modified to that of a
conditioned stimulus using classical conditioning paradigms.  These
changes have been shown to develop rapidly, are highly specific, can
last indefinitely, and occur for different learning paradigms.
Subcortical plasticity in the adult animal is also seen in changes in
the receptive fields of midbrain neurons during sound localization
tasks.

While it is accepted that the central nervous system remains plastic
throughout the lifespan, the mechanisms underlying this plasticity
are unclear.  The time course for these changes is variable, and may
be due to the growth of axons and the formation of new connections
over long distances or due to alterations in synaptic strength and
the "unmasking" or activation of subthreshold pathways.  The
involvement of different forms of synaptic change, such as short- and
long-term depression and potentiation, appears to vary for different
brain regions.  This suggests that, although the brain has a variety
of means of modifying synapses, all regions do not achieve these
modifications in the same way.  The molecular mechanisms underlying
the various forms of synaptic change also vary across brain regions.
There are many possible explanations for these differences, but it is
clear that understanding the implications of adult plasticity for
auditory function would be best served by examining this specifically
in the auditory system.

The roles of drug and nondrug therapies for the recovery of function
following peripheral or central injury or disease and their
relationships to plastic changes in the central nervous system are
under investigation.  For example, the ability of nerve growth
factors to enhance functional brain recovery following stroke is
being studied in humans.  The role of physical therapy in the
recovery of motor function and observed changes in motor cortical
regions is also being examined.  Studies of such therapies offer
great promise for improving and speeding recovery from brain and
sensory and motor system diseases and disorders, but have thus far
received little attention in the auditory system.

Research Goals and Scope

Current research related to central auditory plasticity in adults is
yielding exciting insights into the nature of this phenomenon, and
promises to improve understanding of the auditory system.  Research
on adult plasticity of the auditory system is, however, still in its
infancy, and many areas need to be explored.  Fulfilling the ultimate
hope that this phenomenon will be harnessed to improve the lives of
those with hearing impairment depends upon a sophisticated
understanding of plasticity of the adult auditory system.  The
purpose of this PA is to encourage applications for research on
topics such as, but not limited to, the following:

o  determination of the limits (e.g., time course, neural distance,
effects of training) of central auditory nervous system plasticity
following damage to the auditory system;

o  determination of the limits (e.g., time course, neural distance,
effects of training) of central auditory nervous system plasticity
induced by auditory training and deprivation;

o  elucidation of the relationship between central auditory nervous
system plasticity and functional recovery following damage to the
auditory system;

o  comparison of the nature and extent of plasticity occurring at
different processing stations of the central auditory nervous system;

o  identification and characterization of the various forms of
synaptic change (e.g., long- and short-term potentiation and
depression) involved in central auditory nervous system plasticity;

o  identification and characterization of candidate neurochemical
mechanisms for central auditory nervous system plasticity; and

o  development of new or improvement of existing therapies (both drug
and nondrug) for the recovery of function following damage to the
auditory system or for the enhancement of plasticity in the intact
auditory system.

INCLUSION OF WOMEN AND MINORITIES IN RESEARCH INVOLVING HUMAN
SUBJECTS

It is the policy of the NIH that women and members of minority groups
and their subpopulations must be included in all NIH supported
biomedical and behavioral research projects involving human subjects,
unless a clear and compelling rationale and justification is provided
that inclusion is inappropriate with respect to the health of the
subjects or the purpose of the research.  This new policy results
from the NIH Revitalization Act of 1993 (Section 492B of Public Law
103-43) and supersedes and strengthens the previous policies
(Concerning the Inclusion of Women in Study Populations, and
Concerning the Inclusion of Minorities in Study Populations), which
have been in effect since 1990.  The new policy contains some
provisions that are substantially different from the 1990 policies.

All investigators proposing research involving human subjects should
read the "NIH Guidelines for Inclusion of Women and Minorities as
Subjects in Clinical Research," which have been published in the
Federal Register of March 28, 1994 (FR 59 14508- 14513) and reprinted
in the NIH Guide for Grants and Contracts, Volume 23, Number 11,
March 18, 1994.

Investigators also may obtain copies of the policy from the program
staff listed under INQUIRIES.  Program staff may also provide
additional relevant information concerning the policy.

APPLICATION PROCEDURES

The research grant application form PHS 398 (rev. 5/95) is to be used
in applying for these grants.  These forms are available at most
institutional offices of sponsored research and may be obtained from
the Office of Grants Information, Division of Research Grants,
National Institutes of Health, 6701 Rockledge Drive, Room 3032, MSC
7762, Bethesda, MD 20892-7762, telephone 301/435-0714, email:
girg@drgpo.drg.nih.gov.

The completed original and five legible copies must be sent or
delivered to:

DIVISION OF RESEARCH GRANTS
NATIONAL INSTITUTES OF HEALTH
6701 ROCKLEDGE DRIVE, ROOM 1040 - MSC 7710
BETHESDA, MD  20892-7710
BETHESDA, MD  20817 (for express/courier service)

REVIEW CONSIDERATIONS

Applications will be evaluated for scientific and technical merit by
an appropriate peer review group convened in accordance with NIH peer
review procedures.  As part of the initial merit review, all
applications will receive a written critique and undergo a process in
which only those applications deemed to have the highest scientific
merit, generally the top half of applications under review, will be
discussed, assigned a priority score, and receive a second level
review by the appropriate national advisory council or board.

The review criteria are:  scientific, technical, or medical
significance and originality of proposed research; appropriateness
and adequacy of the experimental approach and methodology proposed to
carry out the research; qualifications and research experience of the
Principal Investigator and staff, particularly, but not exclusively,
in the area of the proposed research; availability of the resources
necessary to perform the research; appropriateness of the proposed
budget and duration in relation to the proposed research; and
adequacy of plans to include both genders and minorities and their
subgroups as appropriate for the scientific goals of the research.
Plans for the recruitment and retention of subjects will also be
evaluated.

AWARD CRITERIA

Applications will compete for available funds with all other
applications assigned to that Institute or Center.  The following
will be considered in making funding decisions: quality of the
proposed project as determined by peer review; availability of funds;
and program priorities among research areas of the program
announcement.

INQUIRIES

Written, telephone, and email inquiries concerning this PA are
encouraged; the opportunity to clarify any issues or questions from
potential applicants is welcome.

Direct inquiries regarding scientific content to:

Lynn E. Huerta, Ph.D.
Division of Human Communication
National Institute on Deafness and Other Communication Disorders
Executive Plaza South, Room 400-C
6120 Executive Boulevard MSC 7180
Bethesda, MD  20892-7180
Telephone:  (301) 402-3458
FAX:  (301) 402-6251
Email:  Lynn_Huerta@nih.gov

Direct inquiries regarding fiscal matters to:

Sharon Hunt
Grants Management Office
National Institute on Deafness and Other Communication Disorders
6120 Executive Boulevard, Room 400-B, MSC 7180
Bethesda, MD  20892-7180
Telephone:  (301) 402-0909
FAX:  (301) 402-1758
Email:  Sharon_Hunt@nih.gov

AUTHORITY AND REGULATIONS

This program is described in the Catalog of Federal Domestic
Assistance No. 93.173. 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 intergovernmental review
requirements of Executive Order 12372 or Health Systems Agency
review.

The PHS strongly encourages all grant and contract recipients to
provide a smoke-free workplace and promote the non-use of all tobacco
products.  In addition, Public Law 103- 227, the Pro-Children Act of
1994, prohibits smoking in certain facilities (or in some cases, any
portion of a facility) in which regular or routine education,
library, day care, health care or early childhood development
services are provided to children.  This is consistent with the PHS
mission to protect and advance the physical and mental health of the
American people.

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