NEUROSCIENCES TECHNOLOGY DEVELOPMENT

Release Date:  March 27, 1998

PA NUMBER:  PA-98-050

P.T.

National Center for Research Resources
National Institute on Aging
National Institute of Child Health and Human Development
National Institute on Deafness and Other Communication Disorders
National Institute of Dental Research
National Institute on Drug Abuse
National Institute of Mental Health
National Institute of Neurological Disorders and Stroke

Application Receipt Dates:  June 1, October 1, and February 1

This Program Announcement supersedes PA-98-012  "Neurosciences Technology
Development."

PURPOSE

The purpose of this Program Announcement (PA) is to encourage submission of new
research project grant (R01) and exploratory/developmental research grant (R21)
applications to develop innovative technologies, methodologies, or
instrumentation for the study of the biology of the brain.  Research is solicited
that will explore new approaches, test imaginative new ideas, and challenge
existing paradigms in technologies to study the development, structure, function,
and aging of the brain in both human and animal models.  Also solicited is
research that will develop significant enhancements to existing technologies
important to neuroscience, and research that will translate a scientific concept
into the basis for a future technology that may advance understanding of
important neuroscience research problems.  It is emphasized that the research
solicited can include tools and approaches that relate to any and all aspects of
neuroscience.

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 is related to several of the
priority areas. 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 non-profit and for-profit
organizations, public and private, such as universities, colleges, hospitals,
laboratories, units of state and local governments, and eligible agencies of the
Federal government. Racial/ethnic minority individuals, women, and persons with
disabilities are encouraged to apply.

MECHANISM OF SUPPORT

Support of this activity will be through the National Institutes of Health (NIH)
research project grants (R01) and the exploratory/developmental research grants
(R21) mechanisms. Indirect costs will be provided.

RESEARCH OBJECTIVES

Background

In biomedicine, new tools and approaches often make possible quantum advances in
research on health and disease, and sometimes shift the manner in which such
research is undertaken, and results interpreted. Conversely, the complexity of
living systems represent interesting challenges to scientific/technology
researchers, providing ample opportunity for the limits of that science to be
tested and expanded.

One of the most complex systems in biomedicine is the brain. Despite this,
neuroscience is rapidly advancing, with important discoveries coming to light
almost daily. These discoveries will improve understanding of normal development
and aging of the brain and offer promise to the millions suffering from brain
disorders of all types.  This program announcement seeks to enable neuroscience
research by soliciting research and development of novel tools and approaches for
the study of the development, structure, function, and aging of the brain. 
Significant enhancements of existing technologies are also solicited, as is
translational research. Research solicited under this program announcement is not
limited to any particular type of technology, level of analysis, or approach.
Multidisciplinary teams of researchers are encouraged to apply.

Research Topics

The research topics identified here represent examples of technologies that are
appropriate for this solicitation. These examples are not a complete list of the
technology development sought for the neurosciences area; they are intended as
a guide for determining the appropriateness of a research topic.

Recently, several new technologies from microscopic to tomographic approaches
have enabled significant progress in this area. However, these imaging approaches
are in early stages of development.  It is an opportune time to capitalize on
these beginnings. Investigators are encouraged to engage other sophisticated and
sensitive image acquisition and analysis methodologies, and to develop
appropriate strategies for integrating the large amounts of data that are derived
from such imaging systems. Similar opportunities exist for developing other
neuroscience research tools that will be useful for the study of the nervous
system and/or for clinical assessment of neurological conditions.

This solicitation is intended to include any novel or emerging technology
suitable for studying the brain, including:
o  magnetic resonance imaging (including fMRI)
o  microscopic imaging (including multiphoton laser techniques)
o  physiological tracer imaging
o  image processing/manipulation/fusion
o  modeling/simulation
o  database access/analysis
o  structural imaging of brain related proteins
o  magnetoencephalography (MEG)
o  photoacoustic and ultrasonic imaging
o  function monitoring of the brain

Since such imaging approaches must ultimately be linked to the development,
structure, function, or aging of the brain, various existing and new technologies
must be developed or enhanced in ways that permit mapping onto imaging results
/databases. These technologies include:
o  electrophysiological recording
o  mass spectrometry
o  cartography
o  virtual reality/environments
o  visualization

The special requirements imposed on studies of the brain suggest general thrusts
for methodological and technical developments.  These include:
o  hierarchical brain modeling (simulation)
o  multiscale (time/space) data acquisition and integration
o  development of reporter/indicator molecules
o  novel detectors/sensors
o  nanotechnology devices
o  unique data visualization
o  bioinformatics
Increasing the speed of data processing, ultimately to the level of real time,
is urgently required.

Under these general areas, applications are solicited for specific technological
innovations and enhancements such as:
o  creation and delivery of new labels and dyes
o  federated data bases and search engines
o  optical and higher field electrical imaging
o  technology for high resolution EEG and MEG analysis
o  higher temporal/space resolution
o  larger field- of- view cameras
o  more efficient/effective microscopies for use in the living brain
o  non-invasive (or non-destructive) stimulators (e.g. transcranial magnetic
stimulation)
o  techniques that bridge interfaces (e.g. dyes that work with MR, confocal, and
other modalities)
o  image analysis tools (e.g. intelligent segmentation and registration tools)
o  functional optical imaging using new infrared techniques
o  real-time, bedside monitoring of brain function in neonates and adults
o  innovations for chronic electrophysiological recording and stimulation at the
microscopic level
o  innovations for chronic monitoring of neurotransmitters at the microscopic
level
o  innovations for chronic monitoring of gene expression in selected areas of the
brain
o  virtual or augmented visualization.

It is stressed that the examples given above are not meant to be exhaustive.
Applications for any technology with the potential to enable more
efficient/effective research in the neurosciences area are encouraged.

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 are provided that inclusion is inappropriate with
respect to the health of the subjects or the purpose of the research.  This
policy results from the NIH Revitalization Act of 1993 (Section 492B of  Public
Law 103-43).

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 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 also may provide additional relevant information
concerning the policy.

APPLICATION PROCEDURES

Applications are to be submitted on the grant application form PHS 398 (rev.
5/95) and prepared according to the instructions provided.  Application kits are
available at most institutional offices of sponsored research and may be obtained
from the Division of Extramural Outreach and Information Resources, National
Institutes of Health, 6701 Rockledge Drive, MSC 7910, Bethesda, MD 20892-7910,
telephone 301/435-0714, email: asknih@od.nih.gov.

C.  SPECIFIC INSTRUCTIONS

1.  Face Page of the application:

Item 2,  Check the box marked þYESþ and type the number and title of this program
announcement.

Item 7a, DIRECT COSTS REQUESTED FOR PROPOSED PERIOD OF SUPPORT:

For R21 applications only, direct costs are limited to a maximum of $75,000 per
year for a maximum of two years. The award is non-renewable and may not be used
to supplement an ongoing project.

Item 8a, DIRECT COSTS REQUESTED FOR PROPOSED PERIOD OF SUPPORT:

For R21 applications only, direct costs requested for the proposed period may not
exceed $150,000.

2.  Description:

As part of the description, identify concisely the technology or methodology to
be developed, its innovative nature, its relationship to presently available
capabilities, and its expected impact on brain research.

Research Plan:

Item a, SPECIFIC AIMS:

The instructions for this section suggest that the applicant state þthe
hypotheses to be tested.þ  Since the goal of this program announcement is to
develop innovative technologies, hypothesis testing per se may not be the driving
force in developing such a proposal and, therefore, may not be applicable.
Furthermore for R21 grant applications, preliminary data are not required, but
when available, should be included. For both the R01 and R21 mechanisms, research
that develops new technologies does require the application of principles of
fields such as engineering, materials science, physics, mathematics, and computer
science. Clear statements of these underlying principles within this section are
essential.

Item b, BACKGROUND SIGNIFICANCE:

Elaborate on the innovative nature of the proposed research. Clarify how the
technology development proposed in this project is a significant improvement over
existing approaches. Explain the potential of the proposed technology for having
a broad impact on neuroscience research or on improved human health. Clearly
identify how the project, if successful, would result in new capabilities for
research, and how these capabilities would differ from existing technologies.

Items aþd:  (for R21 applications only)

Do not exceed a total of ten pages for Items a-d in the Research Plan. Tables and
figures are included in the page limitation. Applications that exceed the page
limitation or NIH requirements for type size and margins (refer to PHS 398
application for details) will be returned to the applicant without further
consideration.

The ten-page limitation does not include Items e-I (Human Subjects, Vertebrate
Animals, Literature Cited, Consortia, and Consultants/Collaborators).

10. Appendix (for R21 applications only)

Color illustrations or original photographs may be included in an Appendix. These
are allowed only if there are copies of black and white figures appearing in the
body of the application. No other appendix material is permitted.

Applications not following the above instructions will be returned to the
applicant without review.

Use the mailing label in the application kit to mail the original and five copies
of the application to:

CENTER FOR SCIENTIFIC REVIEW (formerly 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 assigned on the basis of established PHS referral
guidelines.  Applications not adhering to application instructions described
above and those applications that are incomplete will be returned to the
applicant without review.

Initial review groups convened by the Center for Scientific Review (CSR) in
accordance with NIH peer review procedures will evaluate applications that are
responsive to the program announcement for scientific and technical merit. As
part of the initial merit review, all applications will receive a written
critique and may undergo a process in which only those applications deemed to
have the highest scientific merit, generally the top half of the applications,
will be discussed, assigned a priority score, and receive a second level review
by the appropriate National Advisory Council.

Review Criteria for R01 Applications

The goals of NIH-supported research are to advance our understanding of
biological systems, improve the control of disease, and enhance health.  In the
written review, comments on the following aspects of the application will be made
in order to judge the likelihood that the proposed research will have a
substantial impact on the pursuit of these goals.  Each of these criteria will
be addressed and considered in the assignment of the overall score.

Significance.  Does the study focus on the development of an important
technology? If the technological aims of the project are achieved, will it have
a significant impact in advancing neuroscience?

Approach.  Are the experimental and engineering approaches adequately developed,
well integrated, and appropriate to the aims of the project? Does the applicant
acknowledge potential problem areas and consider alternative tactics?

Innovation.  Does the project propose new technological approaches or explore new
research paradigms in engineering, instrumentation, physical sciences,
mathematics, or computer science as applied to neuroscience or challenge existing
paradigms in these fields?

Investigator.  Are the principal investigator and other researchers appropriately
trained and well suited to carry out this work? Is the work proposed appropriate
to the experience level of the principal investigator and other researchers?

Environment.  Does the scientific and technological environment in which the work
will be done contribute to the probability of success? Do the proposed
experiments take advantage of unique features of the scientific environment or
employ useful collaborative arrangements? Is there evidence of institutional
support?

Review Criteria for R21 Applications

o  Does the proposed project have potential for developing ground-breaking
technology or methodology that may lead to significant expansion of biomedical
research horizons or a paradigm shift in research or improved human health?

o  Degree of innovation: does the project challenge existing paradigms or develop
new methodologies or technologies?

o  Does the project have potential for broad impact on biomedical research?

o  Are the conceptual framework, design, methods, and analyses adequately
developed, well integrated, and appropriate to the aims of the project?  Does the
applicant acknowledge potential problem areas and consider alternative tactics?

o  Is the investigator appropriately trained and well suited to carry out this
work?

o  Are the available and requested resources adequate to conduct the proposed
work?

Investigators should be aware that NIH urges applicants to give added attention,
where feasible and appropriate, to the inclusion of minorities and women in study
populations. If minorities and/or women are not included in a given study
involving human subjects, a clear rationale for their exclusion must be provided.

The initial review group will also examine the adequacy of the proposed means for
protecting against or minimizing potential adverse effects upon humans, animals,
or the environment.

In addition to review of the merit of the application, the review committee will
also examine the appropriateness of the requested budget.

AWARD CRITERIA

The award of grants is contingent on the receipt of applications of high
scientific merit, relevance to the missions of the participating NIH institutes
and centers, and the availability of appropriated funds.

INQUIRIES

Inquiries are encouraged.  The opportunity to clarify any issues or questions
from potential applicants is welcome.

Direct inquiries regarding programmatic issues to:

Dr. Richard DuBois
Biomedical Technology
National Center for Research Resources
6705 Rockledge Drive Room 6160, MSC 7965
Bethesda, MD  20892-7965
Telephone:  (301) 435-0755
FAX:  (301) 480-3659
Email:  richardd@ep.ncrr.nih.gov

Dr. Deborah Henken
Center for Research for Mothers and Children
National Institute for Child Health and Human Development
6100 Executive Boulevard, Room 4B01, MSC 7510
Bethesda, MD  20892-7510
Telephone:  (301) 496-5541
FAX:  (301) 402-4083
Email:  dh50g@nih.gov

Dr. Norman Braveman
Division of Extramural Research
National Institute of Dental Research
45 Center Drive, Room 4AN24
Bethesda, MD  20892-6401
Telephone:  (301) 594-2089
FAX:  (301) 480-8318
Email:  BravemanN@de45.nidr.nih.gov

Dr. Thomas Aigner
Division of Basic Research
National Institute on Drug Abuse
5600 Fishers Lane, Room 10A-19
Rockville, MD  20857
Telephone:  (301) 443-6975
FAX:  (301) 594-6443
Email:  ta17r@nih.gov

Dr. Michael Huerta
Division of Basic and Clinical Neuroscience Research
National Institute of Mental Health
Parklawn Building, Room 11-103
Rockville, MD  20857
Telephone:  (301) 443-3563
FAX:  (301) 443-1731
Email:  mhuerta@helix.nih.gov

Dr. William Heetderks
Division of Stroke, Trauma, and Neurodegenerative Disorders
National Institute for Neurological Disorders and Stroke
Federal Building, Room 8A13
Bethesda, MD  20892-9155
Telephone:  (301) 496-1447
FAX:  (301) 402-1501
Email:  Heet@NIH.GOV

Dr. Bradley Wise
Neuroscience and Neuropsychology of Aging Program
National Institute on Aging
7201 Wisconsin Avenue, Suite 3C307, MSC9205
Bethesda, MD  20892-9205
Telephone:  (301) 496-9350
FAX:  (301) 496-1494
Email:  w86y@nih.gov

Dr. Lynn Huerta
Division of Human Communication
National Institute on Deafness and Other Communication Disorders
6120 Executive Boulevard, Room 400-C, MSC 7180
Bethesda, MD  20892-7180
Telephone:  (301) 402-3458
FAX:  (301) 402-6251
Email:  lh99s@nih.gov

Direct inquiries regarding fiscal matters to:

Ms. Judith Musgrave
Office of Grants Management
National Center for Research Resources
6705 Rockledge Drive, Room 6086, MSC 7965
Bethesda, MD  20892-7965
Telephone:  (301) 435-0844
Email:  judithm@ep.ncrr.nih.gov

Mr. E. Douglas Shawver
Grants Management Branch
National Institute for Child Health and Human Development
6100 Executive Boulevard, Room 8A17, MSC 7510
Bethesda, MD  20892-7510
Telephone:  (301) 496-1303
Email:  Shawver@hd01.nichd.nih.gov

Mr. Martin Rubinstein
Grants Management Officer
National Institute of Dental Research
45 Center Drive
Bethesda, MD  20892-6401
Telephone:  (301) 594-2089
Email:  RubinsteinM@de45.nidr.nih.gov

Mr. Gary Fleming, JD
Grants Management Branch
National Institute on Drug Abuse
5600 Fishers Lane, Room 8A-54
Rockville, MD  20857
Telephone:  (301) 443-6710
Email:  gf6s@nih.gov

Ms. Diana Trunnell
Grants Management Branch
National Institute of Mental Health
Parklawn Building, Room 7C-08
Rockville, MD  20857
Telephone:  (301) 443-2805
Email:  Diana Trunnell@nih.gov

Ms. Brenda Kibler
Grants Management Specialist
National Institute for Neurological Disorders and Stroke
Federal Building, Room 1004
Bethesda, MD  20892
Telephone:  (301) 496-9231
Email:  bk29j@nih.gov

Mr. Joseph Ellis
Grants Management Officer
National Institute on Aging
7201 Wisconsin Avenue, Suite 2N212, MSC9205
Bethesda, MD  20892-9205
Telephone:  (301) 496-1472
Email:  ellisj@exmur.nia.nih.gov

Ms. Sharon Hunt
Grants Management Officer
National Institute on Deafness and Other Communication Disorders
6120 Executive Boulevard, Room 400-B, MSC 7180
Bethesda, MD  20892-7180
Telephone:  (301) 402-0909
Email:  sh79f@nih.gov

AUTHORITY AND REGULATIONS

This program is described in the Catalog of Federal Domestic Assistance No.
93.371.  Awards are made under authorization of the Public Health Service Act,
Title III, 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.  This program is not subject to the 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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