Obstructive sleep apnea (OSA) is a very common disease with major health consequences. The fundamental problem leading to OSA is a failure of the neural control of the upper airway muscles during sleep in those anatomically predisposed. Some progress has been made in the understanding of the mechanisms underlying OSA by performing multi-unit electromyography recordings on upper airway dilator muscles such as the genioglossus (GG). Although these studies have been useful in establishing the importance of these muscles in protecting upper airway patency, and the potential stimuli of importance, we still have a relatively cursory understanding of apnea pathogenesis. Using a newer technique in this area, we are now actively recording single motor units (SMUs) in order to establish the characteristics of the various components contributing to overall genioglossus activity. We have characterized six different SMU patterns of genioglossus firing, some with activity predominantly during inspiration, some with constant activity throughout the respiratory cycle, and some with various combinations. Of note these various SMUs appear to have different response characteristics from standpoint of their activity, for example in going from wakefulness to sleep. Similarly, the response of these various SMUs to standard respiratory stimuli appears to be quite different. Specifically, the change in behavior of SMUs in the transitions from wakefulness to sleep is predicated on the discharge pattern during prior wakefulness. We have also observed major differences in SMUs in OSA patients compared to controls and during REM sleep. Also, certain types of motor units appear to be critically involved in the development of upper airway collapse. Based on animal and human data, we are in the process of developing a working neurobiological model to understand the major pathways regulating GG activity, and how these may be dysfunctional in OSA. We therefore strongly believe that the detailed characterization of SMUs in normal subjects and OSA patients and how SMU behavior changes from wakefulness to NREM and REM sleep will lead to major advances in our understanding of apnea pathogenesis. Ultimately, the development of this working model of upper airway motor control, and the characterization of the muscle control abnormalities in OSA will facilitate the identification of therapeutic targets for the treatment of OSA.

Public Health Relevance

. Obstructive sleep apnea is a highly prevalent and debilitating disease with well established consequences to the brain and cardiovascular system. Current understanding of why sleep apnea occurs is incomplete, although the control of upper airway dilator muscles such as the genioglossus are thought to be important. Single motor unit technology allows scientists to understand the various different groups of neurons that are controlling the muscle and to draw inferences regarding how these neurons are being controlled;such studies will be critical for new treatments for this condition to emerge, such as drug treatment of sleep apnea.

Agency
National Institute of Health (NIH)
Institute
National Heart, Lung, and Blood Institute (NHLBI)
Type
Research Project (R01)
Project #
5R01HL085188-04
Application #
8096742
Study Section
Special Emphasis Panel (ZRG1-RES-B (03))
Program Officer
Laposky, Aaron D
Project Start
2008-09-15
Project End
2013-05-31
Budget Start
2011-06-01
Budget End
2013-05-31
Support Year
4
Fiscal Year
2011
Total Cost
$387,855
Indirect Cost
Name
Brigham and Women's Hospital
Department
Type
DUNS #
030811269
City
Boston
State
MA
Country
United States
Zip Code
02115
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