The first National Sleep Disorders Research Plan was released by the National Institutes of Health (NIH) in 1996. Considerable scientific and clinical growth of the field has occurred since then, necessitating a reassessment and update of research opportunities and recommendations. This 2003 Revised Sleep Disorders Research Plan summarizes the new knowledge acquired since the 1996 Plan and provides an updated and expanded guide for scientific research on sleep and its disorders.

The sections selected for inclusion in this Revised Plan provide a broad perspective on the field of sleep and sleep disorders, and highlight the crosscutting and highly interdisciplinary evolution of this field. Each section provides:

- A brief overview of the topic.
- The major research accomplishments since release of the 1996 National Sleep Disorders Research Plan.
- The research recommendations for the future, including a listing of the two top recommendations followed by a listing of any additional recommendations.

This executive summary presents the Task Force's highest recommendations for future research. All the recommendations highlighted in this Executive Summary are considered relatively equal in importance and are therefore not listed in any prioritized order.

Several specifics of the overall process by the Task Force merit further comment. First, there was considerable discussion on how to address pediatric sleep science since some developmental processes are only encountered in infants and children while others represent a continuum from infancy to old age. Reflecting this continuum, the adult and pediatric sections were combined whenever possible (e.g., insomnia, sleep and breathing). Separate sections focusing only on pediatric science were developed where there was no direct adult relevance.

Second, there was considerable discussion of how sleep and its disorders should be addressed in this document relative to women's health. It was ultimately decided to both create a specific section on sex differences and women's health in sleep to emphasize scientific content unique to women and to include in other sections, wherever appropriate, information as to how a particular disorder or physiologic process might differentially affect women and men. In this way, there would be adequate emphasis of all the diverse ways in which sleep concerns impact on maintenance of health and prevention of disease in women. Similarly, there is a separate section in the 2003 Revised Plan devoted exclusively to racial and ethnic disparities in sleep and health, and relevant content is also included in other sections wherever appropriate.

Progress Since the 1996 National Sleep Disorders Research Plan

The years since release of the original National Sleep Disorders Research Plan in 1996 have been remarkably eventful not only in terms of progress in the sleep sciences, but also in terms of lifestyle and activities of daily life that impact on sleep habits and behaviors. America is increasingly becoming a 24-hour per day society with ever-escalating expectations for around-the-clock services, information and entertainment. After the events of September 11th, 2001, we have also become a much more vigilant society. All of these lifestyle changes are directly impacting not only the number of hours Americans sleep each day but also when during the 24 hours that sleep occurs.

We are now beginning to understand the impact of chronic sleep loss or sleeping at adverse circadian times on our ability to function optimally and on our physical and mental health. How sleep loss, sleep displacement (e.g., shift work, jet lag), and a wide range of sleep disorders affect one's ability to maintain health and healthy functioning in this 24/7 world, however, remains relatively poorly understood. Thus, despite the scientific progress made since 1996 in both clinical and basic science related to sleep and its disorders, there remains the challenge and the need to discover the functions of sleep, to understand and develop better treatments for the many disorders affecting sleep, and to explain the nature of human physiology during wakefulness and the individual stages of sleep. Without progress in these areas, countless millions will continue to suffer the consequences of dysfunction and abuse of this most basic regulatory process. Progress in every area cannot be included in this Executive Summary, but the most important gains in knowledge and understanding will be discussed to provide a context for the research recommendations that follow.

Sleep Neurobiology:
The discovery in 1998-99 of hypocretin/orexin and its role in the development of narcolepsy in animal models and in humans revolutionized our understanding of this debilitating disorder and promises important advances in the diagnosis and therapy of human narcolepsy. Discovery of the neuromodulatory role of hypocretin/orexin also greatly improved our understanding of the basic neurobiologic processes that control sleep and wakefulness. Anatomic areas promoting sleep such as the ventrolateral preoptic (VLPO) area of the hypothalamus have also been characterized. New anatomical and physiological approaches have led to advances in our understanding of the location and interconnections between hypothalamic and brainstem circuits controlling REM, nonREM, and wake states. Factors regulating the activity of these sleep-controlling neurons have been identified. Circuitry and neurotransmitter mechanisms controlling muscle tone across the sleep cycle, of relevance to numerous sleep pathologies, have also been identified.

Circadian Biology:
A growing number of "clock genes" have been identified since 1996 that play a critical role in mammalian circadian timing. In addition, there is clear evidence that non- suprachiasmatic nucleus (SCN) tissues have clock genes and can demonstrate circadian rhythms. Thus, circadian modulation is now established to occur both centrally and peripherally, further emphasizing the importance of circadian chronobiology in the timing of sleep and waking as well as a wide variety of physiologic functions. Now these genetic studies are also being applied to humans, in particular patients with advanced sleep phase syndrome.

Sleep-Disordered Breathing (SDB):
The consequences of SDB (obstructive sleep apnea, sleep apnea) in both adults and children have become increasingly clear over the last few years. In adults, the contribution of sleep apnea to the development of systemic hypertension is becoming more evident and data are accumulating that other adverse cardiovascular outcomes (stroke, congestive heart failure, myocardial infarction) may result from this disorder. In children, there is increasing evidence that sleep apnea may contribute to behavioral problems as well as learning and cognitive deficits. Thus, the diagnosis and treatment of this disorder is important from a variety of perspectives and across all ages.

Pediatrics:
The recognition that having infants sleep supine (on their back) can substantially reduce the incidence of Sudden Infant Death Syndrome (SIDS) is now appreciated as a profoundly important early infant intervention and has saved thousands of lives. Recent research regarding the physiologic, psychological and developmental aspects of sleep in infants, children, and adolescents has contributed to an increased understanding of the unique aspects of sleep and development. The study of pediatric disorders such as Congenital Central Hypoventilation Syndrome and Rett Syndrome has led to a better basic understanding of autonomic regulation and respiratory control. Recent findings regarding the complex relationship between sleep patterns and hormonal changes in adolescence have broadened our understanding of pubertal influences on sleep and circadian biology. The extent of sleep restriction and sleep disturbances among children and adolescents is now recognized to be much greater than previously believed, and the consequent impact on mood, neurobehavioral and academic functioning, safety, and health is considerable. Recognition of the link between sleep disturbances and neurobehavioral disorders in childhood, such as attention deficit hyperactivity disorder (ADHD), has profound public health implications for both the treatment and prevention of psychiatric co-morbidity.

Insomnia:
The high prevalence, risk factors, and consequences of insomnia have been increasingly recognized since 1996. Insomnia has been identified as a risk factor for the onset of subsequent depression, anxiety, and substance use disorders. In addition, the efficacy and durability of behavioral therapies for insomnia have been demonstrated in controlled clinical trials.

Sleep Deprivation:
Although previous studies have demonstrated many of the ill effects of total sleep deprivation, the impact of chronic partial sleep deprivation (restriction) had not been extensively investigated even though it is a much more common phenomenon. However, recent studies indicate that 4 to 6 hours of sleep per night yields a progressive, cumulative deterioration in neurobehavioral function including vigilance, neurocognitive performance, and mood. This reduction in performance is also associated with changes in cerebral activation during cognitive tasks. Physiologic changes (insulin resistance and increased sympathetic activation) appear to occur as well. Both the neurocognitive and physiologic effects of chronic sleep loss suggest there is optimal sleep duration and that there is a cost for failing to achieve it. However, the exact duration of sleep required at different periods of life remains poorly understood, as do the mechanisms driving these neural and metabolic processes.

Sleep Education:
There is now broad recognition of the curriculum inadequacies regarding sleep and its disorders at most medical schools and residency training programs. A Sleep Academic Award Program was established in 1996 to address these educational gaps. This program has led to the development of undergraduate and postgraduate sleep curricula, educational tools, and methods to enhance sleep knowledge. The awardees, working with national professional societies, have also begun to address sleep and fatigue in medical training. There have also been several public health education initiatives, including an effort to establish lifelong healthy sleep habits in school-age children begun in 2001 with Garfield, the "Star Sleeper" as the "spokescat" for healthy sleep. A high school biology curriculum on sleep, sleep disorders, and biological rhythms has also been created, as have programs to combat drowsy driving. Thus, a variety of educational activities have recently been implemented that have substantial potential impact on knowledge and public health behaviors. We need to consolidate and extend the research progress made to date and to translate new knowledge and discoveries into effective therapies and improved lifestyle behaviors for all Americans (as described in the Department of Health and Human Services 'Healthy People 2010' initiative). Sleep-related research must continue across the full spectrum from basic science to clinical investigation to community-based translational programs in order to apply what is known to improve public health and quality of human life.

The scientific areas most important in extending and translating the research gains made to date are summarized in the following paragraphs. The order in which they are listed does not reflect any prioritization; indeed, these individual recommendations are all important and of equivalent high priority.

Research Recommendations

An improved understanding of all aspects of the neurobiology and functions of sleep is needed. These aspects include:

The neurocircuitry whereby the previously described and yet-to-be-identified cellular systems that modulate state are connected to each other and to other neural systems needs to be characterized. In addition, the neuropharmacology and neuromodulators that mediate neural signaling in sleep and wakefulness and their hierarchy in this process need to be better understood. The genetic and p roteomic mechanisms involved in the generation of sleep and wakefulness also need elucidation. Finally, the phylogeny of sleep needs to be further investigated to help define the functions of sleep.

The neurobiologic basis of the two-process sleep system (homeostatic and circadian) needs to be better characterized regarding the anatomical, physiological and functional links between the two systems and the contribution of each to altered sleep quality and timing.

Further research is needed to better understand how developmental maturation from the fetus to the adult influences all of the neurobiologic processes described above. This would include studies addressing how sleep itself influences neural development and how such development affects sleep at the neurobiologic level.

Investigation is needed of the neurobiological function of sleep as a whole and the independent functions of NREM and REM sleep. Without some grasp of the functional role of sleep in the behavior and survival of an organism, it remains very difficult to understand the development, neurobiology, and importance of sleep to physiologic function.

Enhance our understanding of the impact of reduced or restricted sleep on behavior, and neurobiologic and physiologic functions across the age spectrum from childhood through old age. Studies in this area should address:

The neurobiologic processes mediating sleepiness, state instability, and decrements in specific aspects of neurocognitive performance and alertness: this includes identification of brain structures, proteins, and genes that mediate the neural basis of sleepiness and the neurocognitive performance changes resulting from sleep loss. Also, the neurobiologic processes mediating the restoration of stable wakefulness, alertness and performance require further investigation.

A systematic delineation is needed of the processes involved in, the mechanisms underlying, and the developmental aspects of acute and chronic sleep deprivation on non-neural systems. These systems include endocrine, cardiovascular, immune, hematopoietic, renal, gastrointestinal and muscle.

The effects of sleep loss on behaviors that diminish the safety of both the individual and society in general need to be studied. This includes but is not limited to the transportation industry, the armed services, the space industry, health care, law enforcement and at-risk jobs in the construction, manufacturing and service sectors.

Improve our understanding of the processes that lead to specific sleep disorders in children and adults. The following disorders are included in this summary due to both their prevalence and their impact on afflicted patients:

Insomnia (difficulty initiating or maintaining sleep): This should include the development of animal models of insomnia, the study of specific insomnia phenotypes and the application of neurophysiologic, neurochemical, neuroanatomic and functional neuroimaging approaches to the study of insomnia in humans. Understanding why women are at higher risk for insomnia should be a goal as well. Finally, genetic, genomic and proteomic studies are also needed.

Restless Legs Syndrome (RLS) and Periodic Limb Movement Disorder (PLMD): Studies should address the role of altered central dopaminergic mechanisms and abnormal iron metabolism in their pathogenesis. Further development, refinement and validation of animal models of RLS and PLMD are also needed. The use of neuropathologic techniques in the evaluation of brains and spinal cords of affected patients are likely to be useful as well.

Sleep-Disordered breathing (sleep apnea) and disorders of ventilatory control: These studies should address the processes that control both upper airway patency and ventilation itself with a particular focus on the influence of sleep on these biologic processes. The neural connections, neuromodulators and molecular events mediating these state-dependent processes affecting respiration during sleep need to be studied.

Primary disorders leading to hypersomnolence: The neural mechanisms leading to hypersomnolence in conditions such as narcolepsy or primary central nervous system hypersomnolence need to be investigated, and the focus these studies should be how the neurobiologic causes of hypersomnolence differ from or resemble the effects of sleep loss.

An assessment of normal human sleep phenotypes and the normal range of variation in this phenotype in adults and children (including racial and ethnic differences) is needed, not only to establish normative standards but also to serve as a model for recommended sleep behaviors. This assessment should include sleep duration, sleep stage distribution, sleep timing, sleep disruption, sleep quality, and other variables by which sleep and sleepiness can be quantitatively evaluated.

Once normal sleep phenotypes are defined, the associated genotypes should be fully evaluated.

Abnormal sleep phenotypes should subsequently be recognizable and genotyping of these individuals should then be pursued to define the genetic underpinning of abnormal sleep or altered circadian rhythm profiles. The impact of single nucleotide polymorphisms (SNPs) on normal sleep phenotypes should be testable as well.

The phenotype of patients with specific sleep disorders should be carefully defined in order to set the stage for subsequent genetic testing.

Methods to define normal and abnormal phenotypes through questionnaires or simple non-invasive testing should be a goal. Population surveillance and assessment of associated morbidities will then be possible on a large scale.

New treatments for sleep disorders are needed. Adapting these therapies to individual patients using pharmacogenetic and other approaches is an important research priority. The outcomes of such treatments, including complementary and alternative medicine (CAM) therapies, need to be assessed at all levels including adherence, effectiveness, morbidity, quality of life, health care costs, safety, and performance/productivity. Such studies will likely require carefully designed and appropriately powered clinical trials in order to yield evidence-based guidelines for improved management and treatment of sleep disorders and hence substantial public health benefit:

Sleep-Disordered Breathing (Sleep Apnea):
Adult and Pediatric: Continuous positive airway pressure (CPAP) devices have improved substantially and remain an effective form of therapy for adult Sleep-Disordered breathing (SDB). However, they are cumbersome and have achieved only moderate acceptance by patients. Other approaches such as oral appliances and upper airway surgery have relatively limited success rates for more than mild to moderate SDB. Current forms of therapy hence need to be improved and novel new therapies need to be developed. In children, the indications for surgical intervention need to be better defined. In addition, new surgical and non-surgical treatments for SDB in children are needed as well, including those that address major risk factors such as overweight and obesity.

Insomnia:
Although the efficacy and durability of behavioral therapies have been demonstrated for primary insomnia, long-term trials evaluating the efficacy and safety of hypnotic medications have not been conducted and are a high priority. The development of novel pharmacologic and non-pharmacologic therapies, as well as complementary and alternative medicine therapies, for insomnia of all types (including insomnia in high-risk populations) remains a priority as well. Finally, the effectiveness of behavioral, psychological, and popular mind-body approaches and treatments should be evaluated in routine care settings.

Narcolepsy:
The neurobiology of narcolepsy is now better understood and the role of hypocretin well recognized. Exciting possibilities for new research worthy of exploration include therapies involving hypocretin peptide supplementation, the development of hypocretin receptor agonists, cell transplantation, and gene therapy.

Restless Legs Syndrome (RLS):
Without a better understanding of the etiology, pathogenesis, and neurophysiology of RLS, treatment strategies are limited and not effective in all patients. RLS and Periodic Limb Movement Disorder (PLMD) can have profound negative impacts on quality of life including daytime functioning, work performance, and social and family life. Therefore, methods to determine the extent of nocturnal sleep disturbance and daytime sleepiness both in children and adults with RLS can potentially enhance opportunities to develop novel and effective treatments.

The relationship between the processes of sleep and the development and progression of diseases of both neural and non-neural tissues are areas in need of further investigation. How sleep and its disorders contribute to the development of disease processes and alter their natural history is minimally understood. On the other hand, the impact of various diseases on sleep should also be studied. The interaction between sleep and a variety of disease processes hence needs to be studied at the epidemiologic, behavioral, physiologic and basic neurobiologic levels. Examples of these potential interactions include:

Medical Conditions:
Many medical disorders can impair sleep quality and can, in turn, be adversely affected by poor sleep. Common examples include congestive heart failure, pain, and obstructive lung disease. Congestive heart failure, for example, can lead to a cycling respiratory pattern resulting in sleep fragmentation and decrements in both quality of life and performance. The recurrent arousal from sleep secondary to the intermittent hypoxia associated with this respiratory pattern can potentially lead to a progression of heart failure and hence to reduced survival.

Neurological Disorders:
Neurological conditions such as neurodegenerative disorders (Alzheimer's disease, Parkinson's disease), head trauma, encephalitis, stroke and epilepsy are associated with insomnia, somnolence, motor activity during sleep, and/or breathing abnormalities during sleep. Studies should evaluate whether sleep disorders predispose to specific neurological conditions, whether neurological conditions can produce sleep disorders, and whether sleep disorders impair recovery for selected neurological disorders.

Psychiatric, Alcohol and Substance Use Disorders:
The complex relationships and causal pathways linking insomnia and sleep deprivation to these disorders require further investigation. The impact of sleep disturbances on treatment outcomes and recurrence risk is also significant. Specific examples include the risk for subsequent depression among individuals with insomnia, the importance of sleep and dream disturbances in the development of post-traumatic stress disorder, and the role of insomnia and sleep deprivation in increasing risk for relapse to alcoholism and drug addiction.

Pediatric Genetic and Neurodevelopmental Disorders:
Several genetic and neurodevelopmental disorders have associated sleep and/or Sleep-Disordered breathing abnormalities. These include both rare syndromes and more frequent conditions such as ADHD. Specific areas for further investigation include (1) understanding the pathophysiology of autonomic nervous system (ANS) dysregulation in order to better understand maturation of the ANS and the abnormalities that occur in Sleep-Disordered Breathing (SDB); (2) investigating the anatomical contributions of the upper airway to the obstruction found in children with craniofacial malformation in order to better understand etiology of the more common causes of SDB; and (3) understanding how genetic disorders produce primary insomnia, daytime somnolence, or movement disorders during sleep. Rare genetic disorders associated with sleep abnormalities provide unique models that may facilitate exploration of novel pathophysiologic mechanisms and the discovery of new sleep-related genes that may be relevant to other, more common sleep disorders.

The education of health care providers and the public about the role of healthy sleep habits as an important lifestyle behavior and about sleep disorders is important. Current evidence suggests minimal learning opportunities at all levels (undergraduate, post-graduate, and continuing education). The development and implementation of sleep educational programs needs to encompass all relevant health professionals, including physicians, nurses, dentists, pharmacists, nutritionists, psychologists and other mental health practitioners). Furthermore, since many individuals use dietary supplements and other natural products as sleep aids, research findings regarding the effectiveness and safety of such products should be widely disseminated to health care providers and the public. In addition, a rigorous evaluation of the impact of these educational programs is needed to assess their efficacy in changing:

- Professional knowledge, attitudes, skills and behavior
- Clinical practice
- Patient and healthcare provider health and quality of life

Public education programs about healthy sleep and sleep disorders should continue with an emphasis on culturally, ethnically and racially appropriate materials. These efforts should include school-based programs for both elementary and high school students as well as adult educational programs. An assessment of the impact of these programs on knowledge, attitudes and sleep practices of children and adults should be a component of this process.

Recent scientific advances have led to the development of new technologies and methodologies, but these new approaches have not been systematically applied to the sleep sciences. In addition, new methods and approaches not currently available are needed in the sleep field to answer scientific questions and to better diagnose and manage patients. Prominent examples include:

Mechanisms needed to study the neurobiology of a variety of sleep disorders, possibly including the development of relevant human brain banks. Examples include Sleep-Disordered Breathing and Restless Legs Syndrome/Periodic Limb Movement Disorder, sleep disorders for which little is known neuropathologically.

Animal models of normal sleep as well as individual sleep disorders would be highly useful in not only understanding normal sleep physiology, but the pathogenesis of a variety of disorders and their behavioral and physiologic consequences.

Functional neuroimaging techniques (e.g., PET, fMRI, MRS, MEG, NIR, SPECT) are increasingly available to study sleep, sleep deprivation, and sleep disorders-providing insights into the patterns of regional brain activity that characterize both normal and abnormal sleep/wake states. Application of these techniques to the study of sleep and sleepiness should be continued and expanded as further improvements and refinements become available.

Sleep monitoring in rodents, although currently utilized in a few laboratories, needs to be standardized and then made more broadly available so that mouse/rat sleep phenotypes can be easily defined in genetically altered animals.

New methods to measure and quantify the structure of sleep in humans are greatly needed. Such methods should be outcome focused such that what is measured predicts not only the restorative processes of sleep, but also the consequences of disrupting this process. Methods to relatively easily define circadian phase are also needed.

Effective new measures and methods to quantify sleep and other relevant physiological signals (such as respiration) in the home are greatly needed to facilitate both large epidemiologic investigations and the broader evaluation of patients with potential sleep disorders.

Quantifiable, non-invasive, relatively rapid methods to measure sleepiness in children and adults are greatly needed to scientifically understand its causes and consequences, and to predict performance such that the safety of the individual and society can be protected.

Informatics can be directly applied to clinical, neurophysiologic, imaging, and genetic questions as they apply to sleep and its disorders, but are not currently widely utilized in this field. Thus the use of these devices must be expanded.

Women from adolescence to post-menopause are underrepresented in studies of sleep and its disorders. Enhanced efforts are needed to better understand the neurophysiology of sleep and the neuropathology of sleep disorders in women. These efforts should include:

Basic and clinical studies to establish how sex-related differences in sleep and its regulation influence the risk for, and mechanisms of, sleep disorders.

Conduct longitudinal studies in women including both subjective and objective sleep indicators before and during menarche, women of childbearing age including pregnancy and the post-partum period, and women during the menopausal transition.

Study how sleep disturbance in pregnancy affects fetal development and health both acutely and postnatally.

Racial and ethnic minorities have significant health disparities. There is a need for improved data to develop and implement effective prevention, intervention, treatment, and other sleep-related programs and services in racial and ethnic minorities. Elimination of disparities in sleep disorder outcomes should address not only social and environmental factors such as education and access to health care, but also relevant gene-environment interactions. Relevant studies should include:

Identifying the neurophysiological and neuroanatomical correlates and gene-environment interactions contributing to racial and ethnic disparities in prevalence and severity of individual sleep disorders.

Developing effective strategies to reach racial and ethnic minorities in public health education programs for sleep-related conditions.

Research Training

Although clinical activities and opportunities in the sleep field are expanding, a larger and more interdisciplinary scientific work force is needed if we are to fully address the scientific questions discussed above. Attracting new basic and clinical investigators to this field represents a major challenge for the field if we are to meet the expanding research needs and opportunities. Some of the potential barriers include:

The perceived difficulty of defining sleep phenotypes in mice/rats, thereby making molecular and genetic studies more difficult.

The perceived difficulty of studying a "state" in very reduced preparations or cell lines.

The challenges posed to clinical research by the need for objective measurement of sleep-wake physiology and behavior using cumbersome and expensive technology, and the need to control a wide range of factors, limit effective measurement of sleep-wake processes in naturalistic environments.

"Sleep science" does not have Division or Departmental status at most medical centers. As a consequence, designated space, faculty positions, access to graduate students and potential for collaboration are all limited.

Novel strategies to increase the number and scope of sleep investigators need to be identified and implemented. There is an acute need for additional dedicated Sleep Medicine training programs and for investigators in other training programs ( e.g., neurobiology, genetics, aging, pulmonology, neurology, psychiatry, pediatrics and neuropathology) to train sleep scientists. Sleep is a highly interdisciplinary field and successful sleep centers therefore require scientific and clinical expertise from multiple disciplines with a sufficient critical mass of investigators focused on sleep in order to achieve scientific progress. The association between basic sleep investigators and clinical scientists at these sleep centers also promotes translational research that can yield results more immediately applicable to patient care and public health interventions. Due to a lack of a critical mass of sleep investigators at most medical centers, this goal may demand a more regional or national approach than is needed for most other disciplines. This may also require a n iterative process by which integrated, multidisciplinary sleep centers are carefully developed with substantial training programs and the increasing dispersal of well-trained program graduates can then contribute to development of new sleep centers.

In addition to attracting new investigators to the sleep field, there is a need to expand the number of trained scientists from other relevant disciplines electing to focus on sleep-related research. These disciplines include informatics, epidemiology and genetic epidemiology, clinical trials, functional imaging, genetics, and molecular biology. Without collaborators having these specific skills, sleep science will not be able to utilize currently available technologies and methodologies and hence will have diminished potential for progress. Ongoing training and expanded collaborative opportunities are needed, as is a comprehensive plan to attract, train and retain new scientists, and to continue expanding the skills of current investigators.

Conclusion

Considerable progress has been made since release of the original National Sleep Disorders Research Plan in 1996. Resources expended by the National Institutes of Health to study sleep and its disorders have steadily increased (Appendix C). New scientific techniques that facilitate research discovery are being applied to sleep questions. This has led to an improved understanding of normal sleep physiology and the pathogenesis of a variety of sleep disorders. As a result, both access to care for patients with sleep disorders and the quality of care are substantially better. However, many research questions remain unanswered and new questions need to be addressed, therapy for a number of sleep disorders remains suboptimal, and the research workforce addressing sleep science is inadequate. This Revised National Sleep Disorders Research Plan presents a comprehensive summary of focused research, training and education recommendations that addresses these opportunities and needs.