Brain morphology associated with obstructive sleep apnea.

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.

[1]  J. Spreer,et al.  Thalamic gray matter changes in unilateral Parkinsonian resting tremor: a voxel-based morphometric analysis of 3-dimensional magnetic resonance imaging , 2002, Neuroscience Letters.

[2]  Arthur W. Toga,et al.  A Probabilistic Atlas of the Human Brain: Theory and Rationale for Its Development The International Consortium for Brain Mapping (ICBM) , 1995, NeuroImage.

[3]  T. Hayakawa,et al.  Changes in cerebral oxygenation and hemodynamics during obstructive sleep apneas. , 1996, Chest.

[4]  G. Bonsignore,et al.  Thyroarytenoid muscle activity in sleep apneas. , 1993, Journal of applied physiology.

[5]  L O Lutherer,et al.  Stimulating fastigial nucleus pressor region elicits patterned respiratory responses. , 1986, The American journal of physiology.

[6]  J. Baron,et al.  In Vivo Mapping of Gray Matter Loss with Voxel-Based Morphometry in Mild Alzheimer's Disease , 2001, NeuroImage.

[7]  R Bandler,et al.  Lateralized and widespread brain activation during transient blood pressure elevation revealed by magnetic resonance imaging , 2000, The Journal of comparative neurology.

[8]  D. Gozal,et al.  Developmental differences in cortical and hippocampal vulnerability to intermittent hypoxia in the rat , 2001, Neuroscience Letters.

[9]  Y. Inoue,et al.  Cerebral metabolic impairment in patients with obstructive sleep apnoea: an independent association of obstructive sleep apnoea with white matter change , 2001, Journal of neurology, neurosurgery, and psychiatry.

[10]  D. Gozal,et al.  Behavioral and Anatomical Correlates of Chronic Episodic Hypoxia during Sleep in the Rat , 2001, The Journal of Neuroscience.

[11]  E. Sforza,et al.  Pulmonary hypertension, hypoxemia, and hypercapnia in obstructive sleep apnea patients. , 1989, Chest.

[12]  E. Tolosa,et al.  Cerebellar Cortex Delayed Maturation in Sudden Infant Death Syndrome , 1997, Journal of neuropathology and experimental neurology.

[13]  R. Harper,et al.  Cardiac and respiratory correlations with unit discharge in human amygdala and hippocampus. , 1989, Electroencephalography and clinical neurophysiology.

[14]  F. Cirignotta,et al.  Pathogenic aspects of snoring and obstructive apnea syndrome. , 1988, Schweizerische medizinische Wochenschrift.

[15]  C. Barnes,et al.  Bilateral lesions of the fastigial nucleus prevent the recovery of blood pressure following hypotension induced by hemorrhage or administration of endotoxin , 1983, Brain Research.

[16]  Karl J. Friston,et al.  Statistical parametric maps in functional imaging: A general linear approach , 1994 .

[17]  O. Mathew Upper airway negative-pressure effects on respiratory activity of upper airway muscles. , 1984, Journal of applied physiology: respiratory, environmental and exercise physiology.

[18]  Karl J. Friston,et al.  Voxel-Based Morphometry—The Methods , 2000, NeuroImage.

[19]  K. Franklin,et al.  Impairment of cerebral perfusion during obstructive sleep apneas. , 1994, American journal of respiratory and critical care medicine.

[20]  R. Druga,et al.  Control of breathing and brain activation in human subjects seen by functional magnetic resonance imaging. , 1999, Physiological research.

[21]  H. Kinney,et al.  Decreased Serotonergic Receptor Binding in Rhombic Lip‐Derived Regions of the Medulla Oblongata in the Sudden Infant Death Syndrome , 2000, Journal of neuropathology and experimental neurology.

[22]  J. Snyder,et al.  Global Ischemia in Dogs: Cerebrovascular CO2 Reactivity and Autoregulation , 1975, Stroke.

[23]  Karl J. Friston,et al.  Cortical grey matter and benzodiazepine receptors in malformations of cortical development. A voxel-based comparison of structural and functional imaging data. , 1997, Brain : a journal of neurology.

[24]  Karl J. Friston,et al.  Voxel-Based Morphometry of Herpes Simplex Encephalitis , 2001, NeuroImage.

[25]  J. Cervós-Navarro,et al.  Selective vulnerability in brain hypoxia. , 1991, Critical reviews in neurobiology.

[26]  H. Kinney,et al.  Brainstem Tegmental Necrosis and Olivary Hypoplasia: A Lethal Entity Associated with Congenital Apnea , 1996, Journal of neuropathology and experimental neurology.

[27]  K. Murphy,et al.  Evidence for reflex upper airway dilator muscle activation by sudden negative airway pressure in man. , 1991, The Journal of physiology.

[28]  A. Saykin,et al.  Functional MRI localisation of central nervous system regions associated with volitional inspiration in humans , 1999, The Journal of physiology.

[29]  R. Harper,et al.  Relationships between Hippocampal Activity and Breathing Patterns , 1998, Neuroscience & Biobehavioral Reviews.

[30]  M. Montuori,et al.  Feasibility of a high‐temperature bolometer based on Bi2Sr2CaCu2O8+x superconducting films , 1993 .

[31]  K. Alberti,et al.  Hormonal and metabolic profiles in subjects with obstructive sleep apnea syndrome and the acute effects of nasal continuous positive airway pressure (CPAP) treatment. , 1995, Sleep.

[32]  D. Gozal,et al.  Obstructive sleep apnea and the prefrontal cortex: towards a comprehensive model linking nocturnal upper airway obstruction to daytime cognitive and behavioral deficits , 2002, Journal of sleep research.

[33]  M. Molliver,et al.  The Olivocerebellar Projection Mediates Ibogaine-Induced Degeneration of Purkinje Cells: A Model of Indirect, Trans-Synaptic Excitotoxicity , 1997, The Journal of Neuroscience.

[34]  A. Clerk,et al.  Comparison of the severity of sleep-disordered breathing in Asian and Caucasian patients seen at a sleep disorders center. , 1998, Respiratory medicine.

[35]  J B Poline,et al.  Neural substrates for the perception of acutely induced dyspnea. , 2001, American journal of respiratory and critical care medicine.

[36]  R. Andersen,et al.  Intention-related activity in the posterior parietal cortex: a review , 2000, Vision Research.

[37]  J. Ficker,et al.  [Changes in regional CNS perfusion in obstructive sleep apnea syndrome: initial SPECT studies with injected nocturnal 99mTc-HMPAO]. , 1997, Pneumologie.

[38]  C Guilleminault,et al.  Obstructive sleep apnea and related disorders. , 1996, Neurologic clinics.

[39]  T. Samorajski How the Human Brain Responds to Aging , 1976, Journal of the American Geriatrics Society.

[40]  Karl J. Friston,et al.  A Voxel-Based Morphometric Study of Ageing in 465 Normal Adult Human Brains , 2001, NeuroImage.

[41]  Florent Haiss,et al.  Why do Purkinje cells die so easily after global brain ischemia? Aldolase C, EAAT4, and the cerebellar contribution to posthypoxic myoclonus. , 2002, Advances in neurology.

[42]  S. Chokroverty,et al.  Autonomic dysfunction and sleep apnea in olivopontocerebellar degeneration. , 1984, Archives of neurology.

[43]  D. Frazier,et al.  Respiratory-related neurons of the fastigial nucleus in response to chemical and mechanical challenges. , 1997, Journal of applied physiology.

[44]  W C Eckelman,et al.  Opioid receptor imaging with positron emission tomography and [(18)F]cyclofoxy in long-term, methadone-treated former heroin addicts. , 2000, The Journal of pharmacology and experimental therapeutics.

[45]  Richard S. J. Frackowiak,et al.  Human cerebral activity with increasing inspiratory force: a study using positron emission tomography. , 1996, Journal of applied physiology.

[46]  Peter Sörös,et al.  Axonal polyneuropathy in obstructive sleep apnoea , 2001, Journal of neurology, neurosurgery, and psychiatry.

[47]  K. Waters,et al.  Sleep-disordered breathing in children with myelomeningocele. , 1998, The Journal of pediatrics.

[48]  M. Lawrence,et al.  Stuttering: a brief review. , 1998, American family physician.

[49]  T. McHugh,et al.  Subtle Developmental Abnormalities in the Inferior Olive: An Indicator of Prenatal Brainstem Injury in the Sudden Infant Death Syndrome , 2002, Journal of neuropathology and experimental neurology.

[50]  K J Friston,et al.  Detecting bilateral abnormalities with voxel‐based morphometry , 2000, Human brain mapping.

[51]  D. Mathalon,et al.  A quantitative magnetic resonance imaging study of changes in brain morphology from infancy to late adulthood. , 1994, Archives of neurology.

[52]  Karl J. Friston,et al.  Multisubject fMRI Studies and Conjunction Analyses , 1999, NeuroImage.

[53]  R. Harper,et al.  Cardiac and respiratory relationships with neural discharge in the anterior cingulate cortex during sleep-waking states , 1986, Experimental Neurology.

[54]  G. Poe,et al.  Hippocampal reflected optical patterns during sleep and waking states in the freely behaving cat , 1994, The Journal of neuroscience : the official journal of the Society for Neuroscience.