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About the Authors:
Andrew J. K. Phillips
Roles Conceptualization, Formal analysis, Funding acquisition, Investigation, Methodology, Software, Visualization, Writing - original draft, Writing - review & editing
* E-mail: [email protected]
Affiliation: Division of Sleep Medicine, Departments of Medicine and Neurology, Harvard Medical School, and Division of Sleep and Circadian Disorders, Brigham and Women's Hospital, Boston, MA, United States of America
Elizabeth B. Klerman
Contributed equally to this work with: Elizabeth B. Klerman, James P. Butler
Roles Conceptualization, Funding acquisition, Methodology, Supervision, Writing - review & editing
Affiliation: Division of Sleep Medicine, Departments of Medicine and Neurology, Harvard Medical School, and Division of Sleep and Circadian Disorders, Brigham and Women's Hospital, Boston, MA, United States of America
ORCID http://orcid.org/0000-0002-7402-3171
James P. Butler
Contributed equally to this work with: Elizabeth B. Klerman, James P. Butler
Roles Conceptualization, Formal analysis, Methodology, Writing - review & editing
Affiliations Division of Pulmonary and Critical Care Medicine, Brigham and Women’s Hospital, and Department of Medicine, Harvard Medical School, Boston, MA, United States of America, Department of Environmental Health, Harvard T.H. Chan School of Public Health, Boston, MA, United States of AmericaAbstract
Sleep loss causes profound cognitive impairments and increases the concentrations of adenosine and adenosine A1 receptors in specific regions of the brain. Time courses for performance impairment and recovery differ between acute and chronic sleep loss, but the physiological basis for these time courses is unknown. Adenosine has been implicated in pathways that generate sleepiness and cognitive impairments, but existing mathematical models of sleep and cognitive performance do not explicitly include adenosine. Here, we developed a novel receptor-ligand model of the adenosine system to test the hypothesis that changes in both adenosine and A1 receptor concentrations can capture changes in cognitive performance during acute sleep deprivation (one prolonged wake episode), chronic sleep restriction (multiple nights with insufficient sleep), and subsequent recovery. Parameter values were estimated using biochemical data and reaction time performance on the psychomotor vigilance test (PVT). The model closely fit group-average PVT data during acute sleep deprivation, chronic sleep restriction, and recovery. We tested the model’s ability to reproduce timing and duration of sleep in a separate experiment where individuals were permitted to sleep for up to 14 hours per day for 28 days. The model accurately reproduced these...