Sleep Disorders Research Advisory Board Meeting Minutes

December 6, 2005

The 23rd meeting of the Sleep Disorders Research Advisory Board (SDRAB) was convened at 8:45 on Tuesday, December 6, 2005, in Room D of the Natcher Conference Center on the National Institutes of Health (NIH) campus in Bethesda, MD. Dr. Rafael Pelayo presided as Chair.


Opening Comments
Report of the Director NCSDR
NIH State-of-the-Science Conference - Dr. William Riley
The Synaptic Homeostasis Hypothesis - Dr. Giulio Tononi
Public Reports
Presentation: Sleep Apnea - Ms. Elizabeth Johns
Other Business
Final Discussion

NCSDR Home Page

Sleep Disorders Research Advisory Board Page


Dr. Rafael Pelayo (Chair)
Ms. M. Elizabeth Johns
Dr. Kathryn Lee
Dr. Gina Poe
Dr. Susan Redline (via conference call)
Dr. Howard Roffwarg
Dr. Michael Smolensky
Dr. Lorraine Wearley
Dr. Phyllis Zee


Ms. Sheila Connolly
Ms. Julianne Hill
Dr. Michael Sateia


Dr. Carl Hunt, SDRAB Executive Secretary
Dr. Merrill Mitler
Dr. William Riley
Dr. Marian Willinger


Dr. Harold Gordon
Dr. Lindsey Grandison (for Dr. Ellen Witt)
Dr. Nancy Pearson
Dr. Thomas Raslear
Dr. Roger Rosa
Dr. Michael Twery


Mr. Al Golden, NHLBI
Dr. Dante Picchioni, Walter Reed Army Institute of Research and NIDCD
Ms. Sue Rogus, NHLBI
Ms. Ellen Sommer, NHLBI


Dr. Charles Atwood, American College of Chest Physicians
Dr. Robert Bassner, American Thoracic Society
Mr. Scott Brawley, National Sleep Foundation
Mr. Darrell Drobnich, National Sleep Foundation
Mr. Richard Gelula, National Sleep Foundation
Dr. Edward Grandi, American Sleep Apnea Association
Dr. Mary Ann Greco, SRI International
Ms. Sarah Hanson, Institute of Medicine
Dr. Eveline Honig, Narcolepsy Network
Mr. Robert Hoover, Sunrise Medical/DeVilbiss
Ms. Jennifer Markkanen, American Academy of Sleep Medicine
Ms. Kelsey Spoon, Restless Legs Syndrome Foundation
Ms. Kristen Thorson, American Fibromyalgia Syndrome Association


Dr. Giulio Tononi, University of Wisconsin

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OPENING COMMENTS - Drs. Carl E. Hunt and Rafael Pelayo

Dr. Hunt welcomed the Board members and other participants to the meeting, including those joining by live Webcast. He called attention to the NIH Conflict of Interest and Ethics rules for NIH Advisory Committee members in the Board meeting materials. Dr. Pelayo also welcomed the participants and asked them to introduce themselves. He thanked the Board for the opportunity to serve as Chair.

The Minutes from the June 9, 2005, SDRAB meeting were adopted unanimously.

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New Members: Dr. Hunt welcomed new members of the SDRAB. The two new Board members representing the scientific community are Dr. Harold Roffwarg, Professor of Psychiatry and Human Behavior, University of Mississippi Medical Center, and Director of its Division of Sleep Medicine; and Dr. Phyllis Zee, Professor of Neurobiology and Physiology, Northwestern University Medical School, and Director of its Sleep Disorders Center. The third new Board member, who could not attend the meeting, is Ms. Julianne Hill, a public member on behalf of insomnia and a freelance writer/producer

Dr. Hunt provided updates on the following topics:

Funding for Sleep Research: NIH funding for sleep research increased steadily from 1996 to 2005. In FY 2004, this increase reached 158 percent, compared to increases of 223 percent and 130 percent for NHLBI and total NIH research grant funding since 1996, respectively. This increase for sleep research since 1996 is projected to reach 164 percent for 2005; however, a flat or slight decrease in the NIH budget is anticipated for 2006. The challenge is to continue to increase the growth of sleep research in light of these budgetary constraints. Current funding opportunities include:

- Research on Sleep and Sleep Disorders, PA-05-046, is sponsored by SRCC member ICs and uses the R01 or R21 mechanisms. Its purpose is to advance biomedical knowledge, improve understanding of neurobiology or sleep functions, enhance timely diagnosis and treatment, and evaluate public health education and intervention programs.

- Mechanisms Linking Short Sleep Duration and Risk of Obesity or Overweight, RFA-HL-06-003, is designed to stimulate studies on cause-and-effect relationships and mechanisms to explain associations between short sleep duration and increased risk of obesity or overweight due to altered metabolism, appetite, or inflammation. Approximately $2 million is set aside to fund 3-4 new R01 grants in FY 2006. The application deadline is January 25, 2006.

- 2006 NIH Director's Pioneer Award, RFA-RM-06-005, a key component of the NIH Roadmap for Medical Research, will support exceptionally creative individual scientists who take innovative approaches to major challenges in biomedical research. The application deadline is February 27, 2006. Five to 10 new Pioneer Awards will be made in September 2006, with up to $2.5 million in direct costs over 5 years.

- Workshop on Neuroimaging in Sleep Research. This workshop will be held March 29-30, 2006, during National Sleep Awareness Week (NSAW). The three sessions will address (1) what has been done in sleep biology and sleep deprivation, (2) the questions we need to answer with neuroimaging, and (3) the future for neuroimaging in sleep and sleep disorders.

Education Activities: Dr. Hunt mentioned the following education activities:

- The Diseases and Conditions Index (DCI) is part of the new NHLBI Web Health Index for patients and the public. DCI sleep topic updates have received input from the Trans-NIH SRCC members and external reviewers. The links to sleep disorders topics in the DCI are accessible at h DCI updates on sleep apnea and restless legs syndrome are now available, and updates on insomnia and narcolepsy are in development. These Web resources will replace previous hard-copy brochures and will be updated on an as-needed basis. Board members are asked to consider additional sleep topics that should be added.

- "Your Guide to Healthy Sleep" is a new booklet for patients and the public that provides comprehensive sleep information across the age span, including an overview of sleep apnea, insomnia, narcolepsy, and restless legs syndrome. A shorter version is the fact sheet titled "In Brief - Your Guide to Healthy Sleep." Release is scheduled for 2006.

- The Professor Garfield Foundation was established by Paws, Inc. (creator of Garfield; NHLBI sleep partner) and Ball State University. The Foundation developed a Web site for grades K-8 to support classroom learning on sleep with resources for children, parents, and teachers. The site is available at

"Insight" Supplement on Sleep: Sleep was the topic of the October 27, 2005, issue of the "Insight" supplement to the journal Nature. The supplement includes six articles: role of the brain in sleep and hypothalamic regulation of sleep and circadian rhythms; functions of mammalian sleep; sleep-dependent memory consolidation; memory sources of dreaming; insights from studying human sleep disorders; and memory sources of dreaming. Sponsors of this project include NHLBI/NCSDR, the National Institute of Mental Health (NIMH), the National Institute on Neurological Disorders and Stroke, and the Office of Research on Women's Health. The "Insight" material is available electronically via the Nature website at Hard copies of the "Insight" supplement are available on request.

NCSDR Brochure: Released in mid-2005. Briefly describes the role of the NCSDR, SRCC, SDRAB, and their sleep-related research programs. Relevant Web site addresses are included.

Sleep Database: An analysis to identify existing databases with data pertaining to sleep and sleep disorders for biomedical researchers. The end product will be an annotated selection of resources, including data on accessibility, cohort size, and summary tabulations. The report will be available in spring 2006 in HTML and PDF formats.

Web Site Redesign: The NCSDR Web site is being redesigned to make it more user-friendly, and to include more comprehensive current information and resources, a site-specific search engine, and integration with the NHLBI Web domain.

Electronic Receipt of NIH Grant Applications: NIH is in the process of converting from paper to electronic submission of grant applications. It will require electronic submission for all grant applications by May 2007; deadlines are June 1, 2006 for R21s, October 2006 for R01s, and January 2007 for P01s. Researchers can obtain additional information at

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Dr. Riley summarized the results of the SOS Conference on Manifestations and Management of Chronic Insomnia in Adults, which was held June 13-15, 2005, in Bethesda. The SOS Conference was sponsored by the NIMH, the Office of Medical Applications of Research (OMAR), NCSDR, and eight co-sponsors. The SOS Panel was charged with answering five questions:

1) How is chronic insomnia defined, diagnosed, and classified, and what is known about its etiology?
2) What are the prevalence, natural history, incidence, and risk factors for chronic insomnia?
3) What are the consequences, morbidities, comorbidities, and public health burden associated with insomnia?
4) What treatments are used for the management of chronic insomnia, and what is the evidence regarding their safety, efficacy, and effectiveness?
5) What are important future directions for insomnia-related research?

The panel's Final Statement addresses each of the five questions; key points include the following:

- Favors the term "comorbid insomnia" over "secondary insomnia." Closely follows the Research Data Center's criteria for chronic insomnia.

- Supports cognitive-behavioral therapy and the use of benzodiazepine receptor agonists. Expresses concern about the safety and efficacy of antidepressants and over-the-counter (OTC) medications.

- Recommends research on the following topics: development of validated instruments; genetic and neural mechanisms; longitudinal observational studies; the impact of insomnia on quality of life; the costs of illness and cost-effectiveness of treatments; long-term outcome data (particularly after treatment discontinuation); large-scale, multisite comparative treatment trials; OTCs and alternative remedies; efficacy trials in subpopulations (such as children and postmenopausal women); and clinical decision-making.

The SOS conference results have been disseminated via the OMAR Web site and news releases. The Final Statement is available at The Agency for Health Research and Quality (AHRQ) published an Evidence Report/Technology Assessment available at

The Journal of Clinical Sleep Medicine published a special issue with abstracts and the Final Statement (Vol. 1, No. 4, 2005); Sleep published the Final Statement with editorials (Vol. 28, No. 9, 2005); and Medscape provides an online Continuing Medical Education (CME) Clinical Update on Insomnia and Sleep Health available at In addition, the National Sleep Foundation (NSF) plans to disseminate the report to clinicians.

In light of the SOS Conference recommendations, the Board discussed enhancing research funding focusing on insomnia. One possibility is to release a request for applications (RFAs) that is co-sponsored by multiple relevant ICSs. It was also noted that the final SOS Statement not only identifies new potential areas of research, but also includes substantial focus on clinical practice and improving patient outcomes.

The Board discussed their important role in advising NHLBI/NIH and in advocating for high priority research initiatives. A motion was approved unanimously to recommend a plan for implementing recommendations from the SOS conference on insomnia:

The Sleep Disorders Research Advisory Board commends the Trans-NIH Sleep Research Coordinating Committee (SRCC) for its role in organizing the Insomnia State-of-the-Science Conference on "Manifestations and Management of Chronic Insomnia in Adults." The Board urges the Trans-NIH SRCC to review and prioritize recommendations from the Conference Statement and the 2003 National Sleep Disorders Research Plan and implement steps to stimulate new insomnia research and dissemination initiatives to address high priority gaps in knowledge.

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Dr. Merrill Mitler introduced Dr. Giulio Tononi, a recent recipient of the NIH Director's Pioneer Award.

Dr. Tononi discussed the synaptic homeostasis hypothesis about the significance of slow wave activity (SWA) during non-REM sleep. He noted that every neuron in the cerebral cortex oscillates between an up-state (when it fires) and a down-state (when it is silent). In humans, oscillations can be recorded as EEG slow waves, in which every neuron goes up and down. The longer one is awake, the bigger the slow waves, which leads to synaptic downscaling. Active learning leads to increases in synaptic strength, but strengthening circuits in the brain comes at a price in terms of energy, space, and saturation. The alteration between up and down states during sleep leads to synaptic depression, or downscaling. This leads to smaller slow waves during the night, resulting in savings in energy and space and increases in signal/noise. At waking, the brain is capable of functioning, and we can learn again. Thus, downscaling is tied to the beneficial effects of sleep on performance.

Evidence for the hypothesis is found in molecular correlates. Being awake involves markers associated with increased expression of genes related to synaptic potentiation. Studies in animal models (such as the fruit fly Drosophila) focus on the consequences of sleep and sleep deprivation at the cellular and molecular level. These studies have found striking differences in the expression of certain genes between sleep and waking and identified molecular markers. For example, one study found that sleep was associated with increased expression of genes related to synaptic depression. A consequence of the homeostasis hypothesis is that inducing plasticity in one region of the brain (e.g., by a learning task) induces sleep potentiation, increases slow wave homeostasis, and leads to performance benefits.

Dr. Tononi said that the hypothesis can lead to research to answer questions such as whether other learning tasks produce local increase of slow wave homeostasis during subsequence sleep. Research can show structural changes after sleep, such as weaker synapses and evoked potentials. Sleep deprivation should lead to symptoms of synaptic overload (e.g., brain areas that cannot function optimally). If the hypothesis is correct, it could lead to specific ideas about how to achieve good sleep. For example, drugs could be developed to increase sleep by promoting SWA, leading to downscaling.

In response to questions, Dr. Tononi made the following points. Aging is associated with decreases in SWA and generally weaker synapses; a promising area for research is to determine if there is also a decrease in plasticity. There is evidence that REM sleep causes synaptic potentiation, but further research is needed to determine whether deprivation of REM sleep would strengthen upscaling or downscaling. Drugs and Transcranial Magnetic Stimulation could be used to study whether learning is enhanced by increased SWA associated with sleep changes and synaptic activity.

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Ms. Kelsey Spoon, Restless Legs Syndrome (RLS) Foundation

Ms. Spoon listed a number of recent activities. It presented its first RLS Science Award to Dr. Ron Krall at the 2005 annual Society for Neuroscience meeting. It will partner with GlaxoSmithKline to develop a video-"Understanding and Improving Symptoms of RLS"-for cable channel release in 2006. Its latest Medical Bulletin contains the first RLS treatment algorithm and will be distributed at the end of 2005. The Foundation will continue to fund a large epidemiology research project; its seed grant program has received 10 letters of intent. It awarded 109 CME certificates at its third annual RLS Symposium at the 2005 meeting of the Associated Professional Sleep Societies (APSS). The third annual National RLS Patient Meeting was held in November, 2005, and included support group leader training for 150 participants. The American Academy of Family Physicians published a CME Bulletin "RLS-Common, Underdiagnosed, and Manageable" as part of its Annual Focus series.

Ms. Kristen Thorson, American Fibromyalgia Syndrome Association, Inc.

Ms. Thorson reported that the Association has funded 28 research projects on fibromyalgia syndrome (FMS), chronic fatigue syndrome, and related disorders since 1994. FMS affects 3-5 percent of the population and has a 26 percent disability rate. Symptoms include disturbed sleep, pain, lethargy, cognitive impairments, exercise intolerance, headache, irritable bowel syndrome, and temporal mandibular disorders. A 2004 study indicated that many patients with FMS have upper airway resistance syndrome (UARS) and that continuous positive airway pressure reduces FMS symptoms, improves sleep, and relieves pain. Pharmaceutical treatment of FMS enhances low-wave sleep. Most patients with UARS and FMS are undiagnosed, and FMS patients should be assessed for sleep disorders.

Mr. Richard Gelula, National Sleep Foundation (NSF)

The 9th National Sleep Awareness Week (NSAW) will be held March 27-April 2, 2006. The theme is "Sleep-As Important as Diet and Exercise-Only Easier." The event will include a 2-day conference on sleep and obesity, including the metabolic effects of sleep apnea. NSAW will also include a Bio-information Conference and the 6th Annual "Night of a Thousand Dreams" Gala on March 28 to honor Dr. James K. Walsh, President of NSF's Board of Directors, and Ms. Theresa Shumart, who helped organize Operation Sleep Community Katrina Relief. NSF conducts outreach through media, sleep centers, the Internet, and coalitions with other organizations. An animated learning program, "Cycles of Sleeping and Waking with the Doze Family," was launched on the NSF Web site in 2005 and is also available as a CD-ROM.

Dr. Charles Atwood, American College of Chest Physicians Sleep Institute (AACP-SI)

The Sleep Institute (AACP-SI) is a new part of the AACP and reflects a commitment to sleep medicine through partnerships and initiatives. Its mission is to promote sleep health and the recognition, diagnosis, and treatment of sleep disorders through leadership education, research, and communication. Ongoing projects include a partnership with the NSF to collaborate on initiatives to provide guidance to physicians, durable medical equipment providers, and patients regarding sleep-disordered breathing. Other goals are to work with the American Sleep Apnea Association (ASAA) on a second annual program related to undiagnosed and insufficient treatment of obstructive sleep apnea. Education activities include an annual Sleep Medicine course each January and a new annual Sleep Board Review course for physicians. An updated version of the CD-ROM on polysomnography will be released in 2006.

Ms. Jennifer Markkanen, American Academy of Sleep Medicine (AASM)

The AASM is coordinating 'Sleep 2006', the 20th Anniversary Meeting on June 17-22, 2006, in Salt Lake City, Utah. AASM recently launched an initiative to increase the number of educational courses and products for the sleep medicine community. These include a course on the Management of a Sleep Disorders Center in San Diego in February, 2006, and a course on insomnia in Tampa, FL, in March. The AASM's Advanced Sleep Medicine Course will be offered in February in La Jolla, CA, in conjunction with the Sleep Research Course offered by the Sleep Research Society (SRS) and the Introduction to Dental Sleep Medicine Course offered by the Academy of Dental Sleep Medicine (ADSM). AASM also offers training for sleep technologists, including a self-study module to prepare for the Board of Registered Polysomnographic Technologists exam.

The Sleep Research Society (SRS) recently announced four recipients of the 2005 J. Christian Gillen, M.D., Research Awards for beginning investigators in sleep research, and one recipient of the 2005 Elliott D. Weitzman, M.D., Research Award. These 1-year awards are $20,000 each. The SRS also supported the Drowsy Driving Act of 2005, which was passed recently in Massachusetts.

Dr. Eveline Honig, Executive Director, Narcolepsy Network (NN)

The NN held a successful 20th annual conference in Boston-"The Boston SLEEP Party" in November, 2005, with more than 230 attendees. The NN's membership has increased at all levels: individual, professional, and sleep centers. New initiatives include a more extensive national sleep awareness screening program during NSAW at shopping malls. Increased public education efforts include plans to approach schools through teachers, school nurses, and guidance counselors.

Dr. Robert Bassner, American Thoracic Society (ATS)

The ATS will conduct courses in May in conjunction with its annual meeting in San Diego, CA. New activities include partnering with organizations to develop sleep education and public awareness of sleep disorders, credentialing polysomnography, and holding advisory panels such as the National Board on Responsible Care.

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Ms. Johns, a public member of the SDRAB, is a social worker who manages a nonprofit organization to help developmentally disabled adults in Oklahoma, and is a sleep apnea advocate. She described her experience as an undiagnosed sleep apnea (OSA) patient. For years she was tired and sleepy; she didn't know that snoring is a symptom of OSA, and her doctor didn't ask if she snored. Ultimately, she found OSA information and support sites on the Internet. After a sleep study and starting on CPAP, symptoms improved dramatically. Other family members have subsequently also been diagnosed with OSA and are also being treated. She has become an "apnea evangelist."

Approximately one-third of clients in her program have symptoms of OSA. However, only a small percentage of people with OSA symptoms are being treated. Snoring should be included in the patient history, and physicians should ask their patients if they snore. Mental health professionals should also ask questions about snoring. Three groups with a particular need for education on OSA are family/caregivers for people with Downs Syndrome; mental health patients, including those with depression; and Native Americans. The Indian Health Service (IHS) has 28 clinics in Oklahoma, but sleep studies are not generally available. There is a need for increased availability of equipment for OSA, and to that research subjects identified as having OSA also receive the necessary treatment.

SDRAB members added that diagnosis and follow-up are problems in the Native American cohort in the Sleep Heart Health Study-a long-term epidemiological observation study that includes many Native Americans in Oklahoma, South Dakota, New Mexico, and Arizona-and in the Wisconsin Sleep Cohort Study. Reimbursement for sleep studies is another concern The SDRAB will pursue additional strategies to translate knowledge into public initiatives, and to increase awareness.

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Institute of Medicine (IOM) Study Update - Dr. Hunt

The IOM Project -Development of Strategies and Recommendations for Enhanced Support of Sleep Medicine and Sleep Research in Academic Health Centers -began in early 2005. The final report will be released in electronic form in April 2006, followed by dissemination and publication in June. A session is being planned for the Sleep 2006 meeting to present the study findings, and the report will be a topic at the next SDRAB meeting in June.

NHLBI Strategic Plan

The NHLBI is embarking on an extensive strategic planning process and seeks the Board's input. The Web site that provides an interface for input is The goal of the Strategic Plan is to develop a scientific working plan or blueprint for the next decade. Planning principles include identifying science directions for which NHLBI is well poised to make a major contribution; evaluating NHLBI operational policies; ensuring that the process is inclusive; engaging intra/extramural staff to take part; implementing the steps; and providing ongoing evaluation.

The planning process has an integrated approach, with input from the following NHLBI divisions that have been charged with identifying proposed research themes:

- The Division of Lung Diseases (DLD) has the majority of NHLBI funding for neurobiology of sleep and circadian rhythms and sleep disordered breathing. The DLD identified six proposed themes, including development and early origins of disease, shared mechanisms of pathogenesis and comorbidity, personalized medicine, and enabling therapeutic trials and translational research. Dr. Redline serves on the DLD's Executive Planning Committee.

- The Division of Heart and Vascular Diseases (DHVD) and Division of Epidemiology and Clinical Applications (DECA) fund research on cardiovascular diseases (CVD), including observational and intervention trials of CVD, obesity, and metabolic syndrome. Sleep topics are integrated in ongoing research. Of their 12 proposed themes, 8 are potentially relevant to sleep, including (1) coronary artery disease, (2) heart failure, (3) arrhythmia, (4) vascular diseases, (5) translational basic research (phase I translation), (6) translational implementation and community research (phase II translation), (7) personalized medicine, and (8) clinical trial design.

- The Division of Blood Diseases and Resources (DBDR) strategic plan may have limited relevance for sleep research. Two themes of potential relevance, however, are the role of inflammation in ischemic disorders caused by blood disorders, and interactions between chronic blood disorders and sleep deprivation and sleep disorders.

The planning process includes three levels: Level 1 to identify research program themes; Level 2 to identify Institute-wide strategic themes and draft the strategic plan; and Level 3 to review, revise, and finalize the strategic plan. Level 1 is now underway. Level 2 will start in fall 2006, and Level 3 will start by winter 2007. The planning effort will be competed by spring 2007.

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The Strategic Research Plan will result in a manageable list of focus areas to help set the future NHLBI research agenda. This planning effort should provide multiple opportunities for the sleep research community to develop collaborative research agendas with other programs within NHLBI.

The National Sleep Disorders Research Plan is very comprehensive, but the most important priorities need reassessment. There was a Board consensus that a subgroup of the Board should review the plan and identify priority areas that should be integrated with the evolving NHLBI strategic research plan" This subcommittee will be appointed by Dr. Pelayo and will be convened in January by conference call.

The Board also agreed that a second subcommittee be appointed to identify educational programs in need of implementation, including enhanced distribution and utilization of the high school biology curriculum related to sleep. This subcommittee will also be appointed in January and will be convened by conference call.


Dr. Pelayo thanked the Board for their contributions and adjourned the meeting at 3 p.m.

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I hereby certify that the foregoing minutes are accurate and complete.

Rafael Pelayo M.D.
Chair, Sleep Disorders Research Advisory Board

Carl E. Hunt, M.D.
Executive Secretary, Sleep Disorders Research Advisory Board

Adoption of the December, 2005 Minutes will be before the the Full Board at its June, 2006 meeting.

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