This Article Full Text Full Text (PDF) Online Data Supplement Alert me when this article is cited Alert me if a correction is posted Services Similar articles in this journal Similar articles in PubMed Alert me to new issues of the journal Download to citation manager Citing Articles Citing Articles via HighWire Citing Articles via Google Scholar Google Scholar Articles by Macey, P. M. Articles by Harper, R. M. Search for Related Content PubMed PubMed Citation Articles by Macey, P. M. Articles by Harper, R. M.

Brain Morphology Associated with Obstructive Sleep Apnea

Department of Neurobiology and the Brain Research Institute; Department of Radiological Sciences; and School of Nursing, University of California at Los Angeles, Los Angeles, California

Correspondence and requests for reprints should be addressed to Ronald M. Harper, Ph.D., Department of Neurobiology, University of California at Los Angeles, 10833 Le Conte Avenue, Los Angeles, CA 90095-1763. E-mail: rharper{at}ucla.edu

Obstructive sleep apnea (OSA) is characterized by repeated occurrences of hypoxic, hypercapnic, and transient blood pressure elevation episodes that may damage or alter neural structures. Underdeveloped structures or pre-existing damage in brain areas may also contribute to the genesis of the syndrome. Brain morphology in 21 patients with OSA and in 21 control subjects was assessed using high-resolution T1-weighted magnetic resonance imaging. Three-dimensional brain images were obtained with voxels of approximately 1 mm³. Images were spatially normalized and segmented into gray matter, white matter, and cerebrospinal fluid. For each segment, regional volumetric differences were determined relative to age, handedness, and group (patients with OSA versus control subjects), using voxel-based morphometry, with OSA effects weighted by disease severity. A significant age effect on total gray matter was found in control subjects but not in patients with OSA. Diminished regional and often unilateral gray matter loss was apparent in multiple sites of the brain in patients with OSA, including the frontal and parietal cortex, temporal lobe, anterior cingulate, hippocampus, and cerebellum. Unilateral loss in well-perfused structures suggests onset of neural deficits early in the OSA syndrome. The gray matter loss occurs within sites involved in motor regulation of the upper airway as well as in areas contributing to cognitive function.

Key Words: neuroanatomy • magnetic resonance imaging • hypoxia • ischemia

This article has been cited by other articles:

				I. C. Burckhardt, D. Gozal, E. Dayyat, Y. Cheng, R. C. Li, A. D. Goldbart, and B. W. Row Green Tea Catechin Polyphenols Attenuate Behavioral and Oxidative Responses to Intermittent Hypoxia Am. J. Respir. Crit. Care Med., May 15, 2008; 177(10): 1135 - 1141. [Abstract] [Full Text] [PDF]

				P.J. Wrigley, S.M. Gustin, P.M. Macey, P.G. Nash, S.C. Gandevia, V.G. Macefield, P.J. Siddall, and L.A. Henderson Anatomical Changes in Human Motor Cortex and Motor Pathways following Complete Thoracic Spinal Cord Injury Cereb Cortex, May 14, 2008; (2008) bhn072v1. [Abstract] [Full Text] [PDF]

				A. C. Halbower, S. L. Ishman, and B. M. McGinley Childhood Obstructive Sleep-Disordered Breathing: A Clinical Update and Discussion of Technological Innovations and Challenges Chest, December 1, 2007; 132(6): 2030 - 2041. [Abstract] [Full Text] [PDF]

				Y. Zhu, P. Fenik, G. Zhan, E. Mazza, M. Kelz, G. Aston-Jones, and S. C. Veasey Selective Loss of Catecholaminergic Wake Active Neurons in a Murine Sleep Apnea Model J. Neurosci., September 12, 2007; 27(37): 10060 - 10071. [Abstract] [Full Text] [PDF]

				R. M. Douglas, N. Miyasaka, K. Takahashi, A. Latuszek-Barrantes, G. G. Haddad, and H. P. Hetherington Chronic intermittent but not constant hypoxia decreases NAA/Cr ratios in neonatal mouse hippocampus and thalamus Am J Physiol Regulatory Integrative Comp Physiol, March 1, 2007; 292(3): R1254 - R1259. [Abstract] [Full Text] [PDF]

				C. Sveller, R. S. Briellmann, M. M. Saling, L. Lillywhite, D. F. Abbott, R.A.J. Masterton, and G. D. Jackson Relationship between language lateralization and handedness in left-hemispheric partial epilepsy Neurology, November 28, 2006; 67(10): 1813 - 1817. [Abstract] [Full Text] [PDF]

				D. M. Rector, C. A. Richard, and R. M. Harper Cerebellar fastigial nuclei activity during blood pressure challenges J Appl Physiol, August 1, 2006; 101(2): 549 - 555. [Abstract] [Full Text] [PDF]

				L. C. Johnson, T. L. Richards, K. H. Archbold, and C. A. Landis Functional magnetic resonance imaging in nursing research. Biol Res Nurs, July 1, 2006; 8(1): 43 - 54. [Abstract] [PDF]

				R. L. Horner and T. D. Bradley Update in sleep and control of ventilation 2005. Am. J. Respir. Crit. Care Med., April 15, 2006; 173(8): 827 - 832. [Full Text] [PDF]

				K. Hashimoto, T. Ono, E.-i. Honda, K. Maeda, H. Shinagawa, S. Tsuiki, S. Hiyama, T. Kurabayashi, and K. Ohyama Effects of mandibular advancement on brain activation during inspiratory loading in healthy subjects: a functional magnetic resonance imaging study J Appl Physiol, February 1, 2006; 100(2): 579 - 586. [Abstract] [Full Text] [PDF]

				F. J. O'Donoghue, R. S. Briellmann, P. D. Rochford, G. S. Pell, and R. J. Pierce OSA Brain Morphology Differences: Magnitude of Loss Approximates Age-related Effects Am. J. Respir. Crit. Care Med., October 15, 2005; 172(8): 1057 - 1058. [Full Text] [PDF]

				P. M. Macey and R. M. Harper OSA Brain Morphology Differences: Magnitude of Loss Approximates Age-related Effects Am. J. Respir. Crit. Care Med., October 15, 2005; 172(8): 1056 - 1057. [Full Text] [PDF]

				C. J. Dobbin, D. Bartlett, K. Melehan, R. R. Grunstein, and P. T. P. Bye The Effect of Infective Exacerbations on Sleep and Neurobehavioral Function in Cystic Fibrosis Am. J. Respir. Crit. Care Med., July 1, 2005; 172(1): 99 - 104. [Abstract] [Full Text] [PDF]

				D. Gozal and L. Kheirandish Sleepiness and Neurodegeneration in Sleep-disordered Breathing: Convergence of Signaling Cascades Am. J. Respir. Crit. Care Med., June 15, 2005; 171(12): 1325 - 1327. [Full Text] [PDF]

				R. J. Thomas, B. R. Rosen, C. E. Stern, J. W. Weiss, and K. K. Kwong Functional imaging of working memory in obstructive sleep-disordered breathing J Appl Physiol, June 1, 2005; 98(6): 2226 - 2234. [Abstract] [Full Text] [PDF]

				F. J. O'Donoghue, R. S. Briellmann, P. D. Rochford, D. F. Abbott, G. S. Pell, C. H. P. Chan, N. Tarquinio, G. D. Jackson, and R. J. Pierce Cerebral Structural Changes in Severe Obstructive Sleep Apnea Am. J. Respir. Crit. Care Med., May 15, 2005; 171(10): 1185 - 1190. [Abstract] [Full Text] [PDF]

				E.-K. Pae, J. Wu, D. Nguyen, R. Monti, and R. M. Harper Geniohyoid muscle properties and myosin heavy chain composition are altered after short-term intermittent hypoxic exposure J Appl Physiol, March 1, 2005; 98(3): 889 - 894. [Abstract] [Full Text] [PDF]

				P. M. Macey, M. A. Woo, K. E. Macey, T. G. Keens, M. M. Saeed, J. R. Alger, and R. M. Harper Hypoxia reveals posterior thalamic, cerebellar, midbrain, and limbic deficits in congenital central hypoventilation syndrome J Appl Physiol, March 1, 2005; 98(3): 958 - 969. [Abstract] [Full Text] [PDF]

				K. E. Macey, P. M. Macey, M. A. Woo, R. K. Harper, J. R. Alger, T. G. Keens, and R. M. Harper fMRI signal changes in response to forced expiratory loading in congenital central hypoventilation syndrome J Appl Physiol, November 1, 2004; 97(5): 1897 - 1907. [Abstract] [Full Text] [PDF]

				G. E. Meadows, D. M. O'Driscoll, A. K. Simonds, M. J. Morrell, and D. R. Corfield Cerebral blood flow response to isocapnic hypoxia during slow-wave sleep and wakefulness J Appl Physiol, October 1, 2004; 97(4): 1343 - 1348. [Abstract] [Full Text] [PDF]

				J. L. Feldman and W. A. Janczewski Slip of the Tongue Am. J. Respir. Crit. Care Med., September 15, 2004; 170(6): 581 - 582. [Full Text] [PDF]

				R. M. Harper Impaired Arousals and Sudden Infant Death Syndrome: Preexisting Neural Injury? Am. J. Respir. Crit. Care Med., December 1, 2003; 168(11): 1262 - 1263. [Full Text] [PDF]

				J. Harbison, G. J. Gibson, D. Birchall, I. Zammit-Maempel, and G. A. Ford White matter disease and sleep-disordered breathing after acute stroke Neurology, October 14, 2003; 61(7): 959 - 963. [Abstract] [Full Text] [PDF]

				M. A. Woo, P. M. Macey, G. C. Fonarow, M. A. Hamilton, and R. M. Harper Regional brain gray matter loss in heart failure J Appl Physiol, August 1, 2003; 95(2): 677 - 684. [Abstract] [Full Text] [PDF]

				B. W. Row, R. Liu, W. Xu, L. Kheirandish, and D. Gozal Intermittent Hypoxia Is Associated with Oxidative Stress and Spatial Learning Deficits in the Rat Am. J. Respir. Crit. Care Med., June 1, 2003; 167(11): 1548 - 1553. [Abstract] [Full Text] [PDF]

				R. M. Harper, P. M. Macey, L. A. Henderson, M. A. Woo, K. E. Macey, R. C. Frysinger, J. R. Alger, K. P. Nguyen, and F. L. Yan-Go fMRI responses to cold pressor challenges in control and obstructive sleep apnea subjects J Appl Physiol, April 1, 2003; 94(4): 1583 - 1595. [Abstract] [Full Text] [PDF]

				L. A. Henderson, M. A. Woo, P. M. Macey, K. E. Macey, R. C. Frysinger, J. R. Alger, F. Yan-Go, and R. M. Harper Neural responses during Valsalva maneuvers in obstructive sleep apnea syndrome J Appl Physiol, March 1, 2003; 94(3): 1063 - 1074. [Abstract] [Full Text] [PDF]

				M. J. Tobin Sleep-Disordered Breathing, Control of Breathing, Respiratory Muscles, and Pulmonary Function Testing in AJRCCM 2002 Am. J. Respir. Crit. Care Med., February 1, 2003; 167(3): 306 - 318. [Full Text] [PDF]

				D. Gozal The Brain in Sleep-disordered Breathing: Is It the Chicken or Is It the Egg? Am. J. Respir. Crit. Care Med., November 15, 2002; 166(10): 1305 - 1306. [Full Text] [PDF]