My research focuses on the neurobiology of sleep, with long-range goals aimed at understanding the causes and consequences of sleep disorders (e.g. sleep apnea syndrome, narcolepsy) and developing improved diagnostic and therapeutic options for these clinical disorders. I conduct basic animal investigations to identify and characterize the neural networks responsible for modifying the regulation of autonomic behaviors in differing sleep/wake states. These studies also aim to identify specific derangements of the nervous system that may lead to clinical disorders such as narcolepsy or sleep apnea syndrome and their manifestations and consequences. In collaboration with Miodrag Radulovacki, I have developed a rodent model of sleep-disordered breathing and am using this model to test putative drug treatments for sleep apnea. This approach already has led to promising findings in three separate drug trials in patients with sleep apnea syndrome. We are now leading a multi-site randomized controlled trial of dronabinol in obstructive sleep apnea. This is the largest RCT of a drug treatment for sleep apnea ever conducted and the first sponsored for the NIH. In collaboration with Irina Topchiy and Michael Ragozzino, I also am developing this model to conduct innovative research into the central mechanisms by which sleep-related breathing disorder produces impaired cognition.
In collaboration with Bharati Prasad and Jonathan Waxman, my research also focuses on sleepiness, in particular drowsy driving – a major public health hazard. The Center has developed and is validating a novel, realistic driving simulator for controlled research studies of drowsy driving. This simulator is being used to study driving behavior in healthy normal sleepers, sleep deprived individuals and patients with narcolepsy or sleep apnea. These studies aim to define the relationships between driving performance and standard measures of sleepiness, as they may vary across clinical disorders. We also are developing physiological monitoring methods suitable to predict driving performance failures in real time. In particular, we are testing pupillometry as a tool for predicting driving performance. These studies may lead to new monitoring devices suitable for over-the-road deployment.
- 2013 Inaugural Katherine M. Minnich Endowed Professor
- 2010 University of Illinois Inventor of the Year Award
- 1990 Veterans Administration Outstanding Performance Award
- 1989 - 1992 Chicago Lung Association Career Investigator Award
- 1979 - 1982 Surdna Foundation Fellowship
- 1978 BSEE Summa Cum Laude
- Fink, AM, I Topchiy, M Ragozzino, D Amodeo, JA Waxman, M Radulovacki, DW Carley. Brown Norway and Zucker Lean Rats Demonstrate Circadian Variation in Ventilation and Sleep Apnea. Sleep, In Press.
- Topchiy, I, DA Amodeo, ME Ragozzino, JA Waxman, M Radulovacki, DW Carley. Acute exacerbation of sleep apnea by hyperoxia impairs cognitive flexibility in Brown-Norway rats. Sleep, 37:715-721, 2014.
- Waxman, JA, D Graupe, DW Carley. Realtime prediction of disordered breathing events in people with obstructive sleep apnea. Sleep and Breathing, In Press.
- Calik, MW, M Radulovacki, DW Carley. A method of nodose ganglia injection in Sprague-Dawley rat. J Vis Exp, In Press.
- Weaver, TE, MW Calik, SS Farabi, AM Fink, MT Galang-Boquiren, MK Kapella, B Prasad, DW Carley. Innovative treatments for obstructive sleep apnea. Nature and Science of Sleep, In Press.
- Calik, MW, DW Carley. Cannabinoid type 1 and type 2 receptor antagonists prevent attenuation of serotonin-induced reflex apneas by dronabinol in Sprague-Dawley rats. PLOS ONE, In Press.
- Farabi, SS, DW Carley, D Smith, L Quinn,. Impact of exercise on diurnal and nocturnal markers of glycemic variability and oxidative stress in obese individuals with type 2 diabetes or impaired glucose tolerance. Diabetes and Vascular Disease Research, In Press.
- Farabi, SS, B Prasad, L Quinn, DW Carley. Impact of dronabinol on quantitative electroencephalogram (qEEG) measures of sleep in obstructive sleep apnea syndrome. J Clin Sleep Med, 10:49-56, 2014.
- Calik, MW, M Radulovacki, DW Carley. Intranodose ganglion injections of dronabinol attenuate serotonin-induced apnea in Sprague-Dawley rat. Resp Physiol Neurobiol, 190:20-24, 2014.
- Prasad, B, MG Radulovacki, DW Carley. Proof of concept trial of dronabinol in obstructive sleep apnea. Frontiers in Psychiatry, 4:1. doi:10.3389/fpsyt.2013.00001.
- Prasad, B, DW Carley, JA Krishnan, TE Weaver, FM Weaver. Effects of positive airway pressure treatment on clinical measures of hypertension and type 2 diabetes. J Clin Sleep Med, 8:481-487, 2012.
- Prasad, B, YK Choi, TE Weaver, DW Carley. Pupillometric assessment of sleepiness in narcolepsy. Frontiers in Psychiatry, 2:35. 2011. doi: 10.3389/fpsyt.2011.00035.
- Kapella, MC, JJ Herdegen, ML Perlis, JL Shaver, JL Larson, JA Law, DW Carley. Cognitive behavioral therapy for insomnia co-morbid with COPD is feasible with preliminary evidence of positive sleep and fatigue effects. Int J COPD 6:625-635, 2011.
- Topchiy, I, M Radulovacki, J Waxman, DW Carley. Impact of the vagal feedback on cardiorespiratory coupling in anesthetized rats. Resp Physiol Neurobiol 175:375-382, 2011.
- Topchiy, I, J Waxman, M Radulovacki, DW Carley. Functional topography of respiratory, cardiovascular and pontine-wave responses to glutamate microstimulation of the pedunculopontine tegmentum of the rat. Resp Physiol Neurobiol 173:64-70, 2010.
- Prasad, B, M Radulovacki, CS Olopade, JJ Herdegen, T Logan, DW Carley. Prospective trial of efficacy and safety of ondansetron and fluoxetine in patients with obstructive sleep apnea syndrome. Sleep, 33:982-989, 2010.
- Waxman, JA, D Graupe, DW Carley. Automated prediction of apnea and hypopnea using a LAMSTAR artificial neural network. Am J Resp Crit Care Med 181:727-733, 2009.
- Mahmood, K, N Akhter, K Eldeirawi, E Önal, JW Christman, DW Carley, JJ Herdegen. Prevalence of type 2 diabetes in patients with obstructive sleep apnea in a multi-ethnic sample. J Clin Sleep Med, 5:215-221, 2009.
- Bojic, T, J Saponjic, M Radulovacki, DW Carley and A Kalauzi. Monotone signal segments analysis as a novel method of breath detection and breath-to-breath interval analysis in rat. Resp Physiol Neurobiol, 161:273-280, 2008.
- Carley, DW and M Radulovacki. Pharmacology of vagal afferent influences on disordered breathing during sleep. Resp Physiol Neurobiol, 164:197-203, 2008.
- Carley, DW, C Olopade, GS Ruigt and M Radulovacki. Efficacy of mirtazapine in obstructive sleep apnea syndrome. Sleep, 30:35-41, 2007.
- Radulovacki, M, S Pavlovic, J Saponjic and DW Carley. Modulation of reflex and sleep related apnea by pedunculopontine tegmental and intertrigeminal neurons. Resp Physiol Neurobiol, 143:293-306, 2004.
- Saponjic, J, M Radulovacki, DW Carley. Respiratory pattern modulation by the pedunculopontine tegmental nucleus. Respiratory Physiology and Neurobiology, 138:223-237, 2003.
Neurobiology of Sleep Apnea in Aging
David W. Carley, Principal Investigator (5R01AG016303-11)
Respiratory pattern generation and motor output integration are strongly influenced by behavioral state. In extreme cases, the respiratory dysrhythmia permitted or provoked during rapid eye movement (REM) sleep appears to be a pathogenic factor for sleep-related breathing disorders such as sleep apnea syndrome. The neuronal networks and synaptic mechanisms that render autonomic outputs more labile during REM sleep remain poorly defined, but during the previous funding cycle we developed key evidence supporting a respiratory modulating function of the pedunculopontine tegmental (PPT) nucleus – an important region for REM sleep homeostasis and sensorimotor integration. Specifically, PPT stimulation produced respiratory dysrhythmia in sleeping and anesthetized animals and PPT lesions reduced apnea expression during REM sleep. Within the PPT, serotonin blunted glutamate-induced respiratory perturbation. Narcolepsy results from a loss of hypothalamic orexinergic neurons that provide excitatory inputs to PPT as well as to brainstem serotonergic neurons. REM sleep control is aberrant in narcolepsy and PPT dysfunction has been implicated. Moreover, the prevalence of sleep apnea is greatly increased among patients with narcolepsy. During years 11 to 13 of this program, we will pursue 3 specific aims to establish the importance of orexinergic modulation of respiratory integration, and the state-dependent role of the PPT in these effects. Aim 1 will quantify impairments to: respiratory chemoreflexes, respiratory short term potentiation (STP) and respiratory long term facilitation (LTF) during wakefulness and sleep in animals that spontaneously exhibit apnea during sleep; and will quantify the impact of orexin signaling on chemoreflexes, STP, LTF and apnea frequency. Aim 2 parallels an experiment of nature (narcolepsy), using pharmacologic blockade of orexin receptors and paired-pulse acoustic stimulation in conscious rats to determine if PPT-mediated gating of autonomic responses is impaired in the absence of orexin signaling. Aim 3 will further probe the specific role of the PPT in orexinergic regulation of respiratory, cardiovascular and skeletal motor outputs in anesthetized rats using a combination of systemic and local pharmacological manipulations of orexin activity. Similar targeted manipulations will be conducted in the raphe nuclei, an important source of serotonergic inputs to PPT. By extending the progress of the previous funding cycle, these aims will provide important insights regarding the state-dependent mechanisms by which the PPT modulates respiratory pattern in health and disease.
Physiological Predictors of Driving Performance
David W. Carley, Principal Investigator (Funded by a grant from Joseph A. Piscopo)
Drowsy driving is now recognized as a major public health and safety problem, with drowsiness conferring a relative risk similar to that of alcohol intoxication. As highlighted in the 1998 report from the National Highway Traffic Safety Administration Expert Report, insufficient sleep is an epidemic in the United States and restricting sleep by even 1 – 2 hours per night can lead to significant chronic sleepiness. Even without chronic sleepiness, almost every driver is intermittently faced with drowsiness while driving. Drowsiness-related crashes tend to occur late at night or in midafternoon; are likely to be serious; often involve a single vehicle leaving the roadway or not attempting to avoid a crash; are most common on high speed roadways and when the driver is alone in the vehicle.
Several factors increase the risks for drowsy-driving crashes including especially: sleep loss (acute or chronic); patterns that involve regular late-night or long-distance driving, driving alone and driving long periods without breaks; use of sedating medications; untreated or insufficiently treated sleep disorders such as narcolepsy or sleep apnea; and most especially alcohol consumption. These risk factors are even more dangerous when combined. For example, even small amounts of alcohol resulting in blood alcohol levels far below the legal limit can undermine driving performance and increase crashes when combined with mild sleep loss.
These factors highlight the need for research and development in several areas. One critical area is crash prevention in both commercial and noncommercial driving. There are some in-vehicle systems intended to measure sleepiness or behaviors associated with sleepiness during driving: brain wave monitors, eye-blink monitors, monitors of steering variance or lane drift all are being explored. However, a portable system (that could also be deployed within a vehicle) to reliably characterize drowsiness prior to driving (e.g. at a rest stop) would be tremendously valuable to establish “duty readiness”; whereas after a crash it could serve to better assess the real contributions of drowsiness in motor vehicle accidents.
Pupillometry has been suggested to provide an objective physiological basis to assess sleepiness or drowsiness. The “pupillary unrest index” (PUI) is the most commonly employed pupillometric measure of sleepiness, but its validity has been tested only under controlled, dimly lit, steady state conditions. To be of real practical value in driving safety assessment, pupillometric measures of sleepiness and/or driving performance must be established for shorter, more “real time” assessments in natural light conditions.
This pilot study is collecting collect key preliminary data necessary to establish the feasibility of this approach and to gain an initial assessment of the best methods for analyzing pupil dynamics to estimate sleepiness and driving readiness. These data will then be leveraged to support an NIH R01 or SBIR/STTR application to more rigorously develop the approach toward a validated commercially viable tool. Specifically, in the pilot study we will: employ a state-of-the-art VisionTrak pupillometer capable of providing real time pupil diameter assessment and point of gaze analysis with automatic calibration; test subjects using well standardized measures of sleep quality (PSQI, FOSQ), sleep history (diary), immediate sleepiness (VAS), and psychomotor vigilance (PVT); assess PUI under standard conditions; analyze papillary dynamics during the PVT test and during both rural and urban simulated driving using the CNSHR driving simulator. For this pilot study, we will test: 10 healthy normal sleepers; 10 adults subjects with narcolepsy under routine clinical treatment conditions; 10 adult subjects with newly diagnosed and never treated narcolepsy. For this pilot study, we will not objectively assess nocturnal sleep by PSG or daytime sleepiness by MSLT.
Prediction of Physiological Events in People with Sleep Disordered Breathing
Jonathan Waxman, Principal Investigator (5F31HL097403-03)
Sleep-disordered breathing (SDB) refers to a spectrum of disorders characterized by abnormal respiratory patterns or levels of ventilation during sleep. The most common is obstructive sleep apnea (OSA). People with OSA experience repetitive apnea (cessation of breathing) and hypopnea (marked decrease in tidal volume) during sleep in association with airway compromise and excessive daytime sleepiness (EDS). An arousal, or brief, often unnoticed, disruption of sleep is commonly associated with apnea. People with OSA also exhibit cognitive dysfunction, including impairment to memory, attention, and executive function. OSA- associated EDS and cognitive dysfunction are thought to significantly contribute to automobile accidents and workplace injuries. The first aim of this research is to predict the onset of nocturnal apnea, hypopnea, and arousal. Our proposal to accomplish this aim represents an entirely new approach to improving the effectiveness and tolerability of SBD therapy. The most common therapy is continuous positive airway pressure (CPAP), which is difficult for many patients to tolerate. Existing auto-adjusting PAP may be more tolerable but relies on detection of disordered breathing events and does not appear to improve quality of life compared with conventional CPAP. Predicting these events could lead to more effective titration of PAP levels and improved outcomes. Other therapies, such as the electrical stimulation of various cranial nerves or pharyngeal muscles, could also be improved by predicting disordered breathing. The second aim is to predict the onset of unintended daytime sleep while subjects undergo maintenance of wakefulness tests, which assess one's ability to resist sleep in a soporific condition. The third aim is to predict performance lapses during driving simulations. Accomplishing aims two and three could lead to the development of warning devices for at-risk individuals. Our novel prediction algorithms track the interactions between several physiological systems and reveal the most important predictors. The fourth aim is to contrast the key predictors between OSA, acutely sleep-deprived, and control subjects, and between men and women. By doing so, we expect to gain insight into the underlying pathophysiology of SDB and EDS, and will investigate sex differences in OSA and sleep deprivation. OSA is a major public health problem whose effects on society are comparable to those of smoking. The capability to predict its adverse consequences will be an invaluable tool to improve the quality of life of people with SDB, reduce the associated costs, and improve public health.
Mechanisms of Cognitive Impairment in Sleep Apnea Syndrome: Feasibility Studies in a Novel Animal Model
Irina Topchiy, Michael Ragozzino, David W. Carley Principal Investigators (Chancellor’s Discovery Award)
Sleep related breathing disorder (SRBD), especially obstructive sleep apnea (OSA), afflicts at least 3% of the US population1 and is associated with various cognitive impairments – especially in the areas of executive function, learning and memory2. However, the mechanisms underlying cognitive dysfunction in OSA have proven difficult to identify by human studies3, 4.
Respiratory neurophysiologists have identified spontaneous SRBD in various animals, and we demonstrated that Wistar-Kyoto rats express only rare sleep-apneas, but Brown-Norway rats exhibit more than 20 apneas/hour during sleep – corresponding to moderate OSA severity5, 6. Cognitive scientists have developed tools for assessing numerous aspects of cognition in rats7-9 and have demonstrated that various sleep disturbances can impair cognition10, 11. However, collaborations of cognitive scientists with respiratory neurophysiologists have been rare and no studies of cognitive function have been conducted in animal models of spontaneous SRBD.
This project initiates such a collaboration to test the feasibility of an innovative animal approach to determine the mechanisms of cognitive impairment in SRBD. Specifically, we are testing the hypotheses that rats with SRBD (Brown-Norway) exhibit domain-specific cognitive impairment with respect to control (Wistar-Kyoto) rats, and that disrupted sleep processes in SRBD correlate with impaired cognitive performance. These findings would provide a strong rationale for future externally funded investigations of the neural mechanisms by which apnea leads to cognitive impairment.
1. Pagel JF. Obstructive sleep apnea (OSA) in primary care: evidence-based practice. J Am Board Fam Med 2007;20(4):392-8.
2. Greenberg GD, Watson RK, Deptula D. Neuropsychological dysfunction in sleep apnea. Sleep 1987;10(3):254-62.
3. Tsai JC. Neurological and neurobehavioral sequelae of obstructive sleep apnea. NeuroRehabilitation;26(1):85-94.
4. Veasey S. Insight from animal models into the cognitive consequences of adult sleep-disordered breathing. ILAR J 2009;50(3):307-11.
5. Carley DW, Berecek K, Videnovic A, Radulovacki M. Sleep-disordered respiration in phenotypically normotensive, genetically hypertensive rats. Am J Respir Crit Care Med 2000;162(4 Pt 1):1474-9.
6. Carley DW, Trbovic S, Radulovacki M. Sleep apnea in normal and REM sleep-deprived normotensive Wistar-Kyoto and spontaneously hypertensive (SHR) rats. Physiol Behav 1996;59(4-5):827-31.
7. McCool MF, Patel S, Talati R, Ragozzino ME. Differential involvement of M1-type and M4-type muscarinic cholinergic receptors in the dorsomedial striatum in task switching. Neurobiol Learn Mem 2008;89(2):114-24.
8. Palencia CA, Ragozzino ME. The influence of NMDA receptors in the dorsomedial striatum on response reversal learning. Neurobiol Learn Mem 2004;82(2):81-9.
9. Ragozzino ME, Kim J, Hassert D, Minniti N, Kiang C. The contribution of the rat prelimbic-infralimbic areas to different forms of task switching. Behav Neurosci 2003;117(5):1054-65.
10. Saha S, Datta S. Two-way active avoidance training-specific increases in phosphorylated cAMP response element-binding protein in the dorsal hippocampus, amygdala, and hypothalamus. Eur J Neurosci 2005;21(12):3403-14.
11. Datta S, Mavanji V, Ulloor J, Patterson EH. Activation of phasic pontine-wave generator prevents rapid eye movement sleep deprivation-induced learning impairment in the rat: a mechanism for sleep-dependent plasticity. J Neurosci 2004;24(6):1416-27.
Pharmacotherapy of Apnea by Cannabimimetic Enhancement -- The PACE Clinical Trial
David W. Carley, Principal Investigator (1UM1HL112856)
Sleep related breathing disorders (SRBD), especially obstructive sleep apnea (OSA), represent an important
health problem, conferring substantial cognitive/behavioral symptoms and increased risk of motor vehicle accident, hypertension, myocardial infarction, stroke, diabetes and death on at least 3% of the US population. Identifying novel treatments for OSA would be of great public health significance, because fully effective and acceptable OSA treatments are lacking. A critical need remains for NIH supported, mechanistically driven proof-of-concept clinical studies to evaluate novel therapeutic strategies. Despite basic research advances regarding the pathogenesis of OSA, generally effective drug treatments have not been identified. Based on our animal and preliminary human data, we propose to test the innovative hypothesis that cannabimimetic drugs are both effective in reducing sleep apnea severity and disease modifying in protecting against cardiovascular and neurological sequelae of OSA.
Project 1 will be a randomized, placebo-controlled parallel groups proof-of-concept clinical trial of dronabinol in patients with OSA. Subjects will be randomized to receive either placebo or dronabinol for a period of 6 weeks. The overarching goal will be to establish the safety, tolerability and therapeutic efficacy of dronabinol in OSA, with co-primary efficacy endpoints including: reduced in apnea/hypopnea index (AHI) and improved subjective and objective daytime alertness at the end of treatment. Secondary endpoints will include improved oxygenation, sleep quality, blood pressure control and time-on-treatments effects.
Project 2 will employ anesthetized and chronically instrumented conscious behaving animals to directly test the mechanisms of dronabinol action schematized in figure 1. For example, we will characterize dronabinol’s dose-dependent inhibition of afferent vagal reflexes elicited by pharmacological and mechanical stimuli. We will use CB1 and CB2 antagonists to confirm the receptor targets for reduced apnea propensity and we will establish the CNS versus vagal-reflex impact of dronabinol on upper airway muscle activity during sleep. We will test the hypothesis that cannabimimetics lower blood pressure by reducing sympathetic activity.
Taken together, these projects will provide critical evidence regarding the potential efficacy and mechanisms of action for cannabimimetic treatment of OSA. By providing a path toward the first viable OSA pharmacotherapeutic, the proposed studies could have a tremendous impact on clinical practice.
Oral Appliance and Pharmacologic Agents in Treatment of Sleep Apnea: A Pilot Clinical Study
Therese Galang, Bharati Prasad, David W. Carley, Principal Investigators (Chancellor’s Discovery Award)
Obstructive sleep apnea (OSA) is a common sleep disorder characterized by intermittent and repetitive obstruction of the upper airway during sleep resulting from collapse of the surrounding structures. OSA is a public health problem of great importance with a worldwide prevalence estimated at 3-7% in men and 2-5% in women. The occurrence of OSA has been linked to serious long-term adverse health consequences such as hypertension, metabolic dysfunction, cardiovascular disease, neurocognitive deficits and motor vehicle accidents. Unfortunately, there is no cure for OSA and effective, well-tolerated treatment options are lacking. We propose a new multidisciplinary approach to develop novel OSA therapeutic strategies, with a potentially great impact on pubic health.
Current OSA treatments are mechanical – intended to support the airway opening. According to the American Academy of Sleep Medicine (AASM), the gold standard treatment for OSA is continuous positive airway pressure (CPAP). Unfortunately, CPAP’s potentially high level of efficacy often is not achieved due to poor patient compliance. AASM practice parameters recommend the use of an oral appliance (OA) as a treatment alternative for patients with moderate to severe OSA who are unable to tolerate CPAP, and also as a primary treatment for mild to moderate sleep apnea. OA alone is viewed to have only partial efficacy for patients with moderate to severe OSA. Much of the research to develop OA devices and to establish their efficacy has been conducted by dentists. Pulmonologists and pharmacologists have sought pharmacotherapies, but generally effective drugs treatments remain to be identified for OSA. Co-I Prasad and Co-PI Carley recently demonstrated a drug treatment with efficacy similar to OA in human subjects with OSA. We will establish a new multidisciplinary collaboration blending the expertise and conceptual frameworks of sleep medicine, orthodontics, and neuropharmacology with a long-term goal to develop new combination therapies for OSA. The project proposed for this Discovery Award represents a natural and essential starting point for this program.
We broadly hypothesize that mandibular repositioning achieved by OA, coupled with pharmacologic augmentation will provide synergistic effects toward a more effective OSA treatment. In particular, we hypothesize that augmentation of OA by pharmacotherapy with ondansetron and fluoxetine will improve OA efficacy in patients with moderate to severe sleep apnea. Specifically, the proposed project will: 1) establish the feasibility and acceptability of combined treatment by OA+pharmacotherapy, providing initial estimates of adherence for OA alone and OA+pharmacotherapy; 2) generate appropriate estimates of the treatment effect sizes for OA and OA+pharmacotherapy in patients with moderate to severe OSA; and 3) differentiate these effect sizes according to respiratory event frequency (apnea-hypopnea index), daytime sleepiness (Epworth Sleepiness Scale), and functional capacity (Functional Outcomes of Sleep Questionnaire) using well validated outcome measures.
The National Institutes of Health (NIH) has shown keen interest in funding newer effective treatment options for OSA and achieving the abovementioned objectives will provide strong support for externally funded investigations aimed to rigorously assess the long-term efficacy of this combination regimen. The current research plan of the National Center for Sleep Disorders Research of the NIH identifies current OSA treatment options as suboptimal and views the research workforce addressing sleep science as inadequate. Through this pilot study we will collect key preliminary data necessary to support larger scale studies and we will establish our collaborative team and disseminate our preliminary findings through at least two national presentations. Based on the successful results of this pilot study, we anticipate submitting a competitive R01 application to the NIH in 2013.
The Biobehavioral Effects of Disturbed Sleep Consortium
Sleep-Dependent Determinants of Biobehavioral Function
David W. Carley, Principal Investigator (1R13HL112617)
The broad goal of this application is to create and nurture the early development of an interdisciplinary team that will broaden the research scope and accelerate the pace of discovery into the impact of sleep on alertness and cognitive/motor performance. A related goal will be to enable development of new analytical methods to deepen insight into the basic mechanisms linking sleep to alertness and cognitive/motor function. The potential impact of defining these poorly understood mechanisms is great. Less than one-quarter of the population routinely achieves an optimal amount of sleep. Insufficient or disordered sleep reduces quality of life and worker and student performance; impairs mood, judgment, alertness, and cognitive/motor performance; and increases the risk of accidents. Further, the prevalence and consequences of insufficient or poor sleep differ among men and women, different races/ethnicities, and across age groups. Defining how sleep influences alertness and cognitive/motor performance, and how this may differ among key subgroups or between individuals, is of great significance to the promotion of optimal health and well-being. At UIC, we have an ideal opportunity to address this unmet research need by building a cohesive research team representing: nursing and sleep sciences; psychological and physiological sciences; biological and social sciences; and mathematics and engineering. Specifically, we will accomplish the following: AIM 1 is to institute the team and develop shared terminology around key research concepts and methods. The initial vehicle will be a dedicated research retreat. Two key focus areas illustrate the need for and benefits of interdisciplinary formation: 1) bridging basic animal science to human investigation and 2) developing new mathematical and imaging methods to understand group differences and to predict individual variations in the impact of sleep on daytime function. AIM 2 is to develop a shared conceptual framework representing cutting edge thinking spanning the represented disciplines. A central activity to achieve this goal will be bi-weekly seminars structured to facilitate sharing key research findings and interpretive concepts in a highly interactive and supportive environment. Consultants also will support this team effort. AIM 3 is to develop a specific and practical team research agenda. During a second research retreat the team will outline the shape and scope of a realistic research agenda. During year 2, working subgroups will draft and continue to refine sections of the research agenda, prior to team approval and final review by and endorsement by campus administration. Accomplishing these specific aims will strongly position the team to enter its developmental stage, during which multiple research project grants will be submitted. We anticipate the generation of multiple R21, R01 or P01 applications from the team. The team's innovative focus on bridging animal to human investigation, to exploring the basis for group and individual differences in the relationships between sleep, alertness and behavior, and to developing novel mathematical and imaging methods will serve as a model to other teams. PUBLIC HEALTH RELEVANCE: The proposed activities will create and nurture the early development of a new interdisciplinary team. The long- term aim of this team will be to elucidate the basic mechanisms linking sleep, alertness and cognitive/motor performance. Our team will encompass numerous traditional disciplines that do not historically collaborate actively, enabling us to bridge animal investigation to human behavior and to develop new mathematical models, analytical methods and imaging tools to understand how the impact of sleep on alertness and cognitive/motor performance may differ according developmental status, age, gender, race/ethnicity and health status, and even to predict differences between individuals.