Altered resting-state brain activity in obstructive sleep apnea.

STUDY OBJECTIVES Structural and functional brain changes may contribute to neural dysfunction in patients with obstructive sleep apnea (OSA). However, the effect of OSA on resting-state brain activity has not been established. The objective of this study was to investigate alterations in resting-state functional connectivity (rsFC) of the common brain networks in patients with OSA and their relationships with changes in gray matter volume (GMV) in the corresponding brain regions. DESIGNS Resting-state functional and structural MRI data were acquired from patients with OSA and healthy controls. Seven brain networks were identified by independent component analysis. The rsFC in each network was compared between groups and the GMV of brain regions with significant differences in rsFC was also compared. SETTING University hospital. PATIENTS AND PARTICIPANTS Twenty-four male patients with untreated OSA and 21 matched healthy controls. INTERVENTIONS N/A. MEASUREMENTS AND RESULTS OSA specifically affected the cognitive and sensorimotor-related brain networks but not the visual and auditory networks. The medial prefrontal cortex and left dorsolateral prefrontal cortex (DLPFC) showed decreased rsFC and GMV in patients with OSA, suggesting structural and functional deficits. The right DLPFC and left precentral gyrus showed decreased rsFC and unchanged GMV, suggesting a functional deficit. The right posterior cingulate cortex demonstrated increased rsFC and unchanged GMV, suggesting functional compensation. In patients with OSA, the rsFC of the right DLPFC was negatively correlated with the apnea-hypopnea index. CONCLUSIONS OSA specifically affects resting-state functional connectivity in cognitive and sensorimotor-related brain networks, which may be related to the impaired cognitive and motor functions in these patients.

[1]  Jennifer D. Davis,et al.  Neuropsychological sequelae of obstructive sleep apnea-hypopnea syndrome: A critical review , 2004, Journal of the International Neuropsychological Society.

[2]  M. Schluchter,et al.  Relation of measures of sleep-disordered breathing to neuropsychological functioning. , 2001, American journal of respiratory and critical care medicine.

[3]  Jeffry R Alger,et al.  Brain morphology associated with obstructive sleep apnea. , 2002, American journal of respiratory and critical care medicine.

[4]  B. Desgranges,et al.  A combined neuropsychological and brain imaging study of obstructive sleep apnea , 2009, Journal of sleep research.

[5]  Tianzi Jiang,et al.  The Neuronal Correlates of Digits Backward Are Revealed by Voxel-Based Morphometry and Resting-State Functional Connectivity Analyses , 2012, PloS one.

[6]  F. Barkhof,et al.  Resting state networks change in clinically isolated syndrome. , 2010, Brain : a journal of neurology.

[7]  Stephen M. Smith,et al.  Investigations into resting-state connectivity using independent component analysis , 2005, Philosophical Transactions of the Royal Society B: Biological Sciences.

[8]  S. Hong,et al.  Reduced cerebral blood flow during wakefulness in obstructive sleep apnea-hypopnea syndrome. , 2007, Sleep.

[9]  Michael W. L. Chee,et al.  Sleep deprivation reduces default mode network connectivity and anti-correlation during rest and task performance , 2012, NeuroImage.

[10]  S. Petersen,et al.  Development of distinct control networks through segregation and integration , 2007, Proceedings of the National Academy of Sciences.

[11]  R. Harper,et al.  Neural alterations associated with anxiety symptoms in obstructive sleep apnea syndrome , 2009, Depression and anxiety.

[12]  Franco Cauda,et al.  Different functions in the cingulate cortex, a meta-analytic connectivity modeling study , 2011, NeuroImage.

[13]  C. Stern,et al.  Functional imaging of working memory in obstructive sleep-disordered breathing. , 2005, Journal of applied physiology.

[14]  M. Raichle,et al.  Cortical network functional connectivity in the descent to sleep , 2009, Proceedings of the National Academy of Sciences.

[15]  C. Guilleminault,et al.  EEG arousals: scoring rules and examples: a preliminary report from the Sleep Disorders Atlas Task Force of the American Sleep Disorders Association. , 1992, Sleep.

[16]  M. Greicius.  Resting-state functional connectivity in neuropsychiatric disorders , 2008, Current opinion in neurology.

[17]  David Gozal,et al.  The scoring of respiratory events in sleep: reliability and validity. , 2007, Journal of clinical sleep medicine : JCSM : official publication of the American Academy of Sleep Medicine.

[18]  G. Shulman,et al.  Medial prefrontal cortex and self-referential mental activity: Relation to a default mode of brain function , 2001, Proceedings of the National Academy of Sciences of the United States of America.

[19]  F. Esposito,et al.  Distributed changes in default-mode resting-state connectivity in multiple sclerosis , 2011, Multiple sclerosis.

[20]  S. Rombouts,et al.  Consistent resting-state networks across healthy subjects , 2006, Proceedings of the National Academy of Sciences.

[21]  Daniel L. Schacter,et al.  Default network activity, coupled with the frontoparietal control network, supports goal-directed cognition , 2010, NeuroImage.

[22]  T. Young,et al.  The occurrence of sleep-disordered breathing among middle-aged adults. , 1993, The New England journal of medicine.

[23]  O. Algın,et al.  Neurochemical-structural changes evaluation of brain in patients with obstructive sleep apnea syndrome. , 2012, European journal of radiology.

[24]  S. Ancoli-Israel,et al.  Relationship between obstructive sleep apnea severity and brain activation during a sustained attention task. , 2009, Sleep.

[25]  J. Montplaisir,et al.  Cognitive deficits associated with sleep apnea syndrome: a proposed neuropsychological test battery. , 2000, Sleep.

[26]  J. Pekar,et al.  A method for making group inferences from functional MRI data using independent component analysis , 2001, Human brain mapping.

[27]  M. Czisch,et al.  Increased sleep pressure reduces resting state functional connectivity , 2010, Magnetic Resonance Materials in Physics, Biology and Medicine.

[28]  Kannan Ramar,et al.  Updates on definition, consequences, and management of obstructive sleep apnea. , 2011, Mayo Clinic proceedings.

[29]  M. Johns,et al.  A new method for measuring daytime sleepiness: the Epworth sleepiness scale. , 1991, Sleep.

[30]  D. Schacter,et al.  The Brain's Default Network , 2008, Annals of the New York Academy of Sciences.

[31]  Rajesh Kumar,et al.  Brain structural changes in obstructive sleep apnea. , 2008, Sleep.

[32]  M. Greicius,et al.  Default-mode network activity distinguishes Alzheimer's disease from healthy aging: Evidence from functional MRI , 2004, Proc. Natl. Acad. Sci. USA.

[33]  Jeffry R Alger,et al.  Neural alterations and depressive symptoms in obstructive sleep apnea patients. , 2008, Sleep.

[34]  Qiyong Gong,et al.  Cerebral and functional adaptation with chronic hypoxia exposure: A multi-modal MRI study , 2010, Brain Research.

[35]  Yufeng Zang,et al.  Subject order-independent group ICA (SOI-GICA) for functional MRI data analysis , 2010, NeuroImage.

[36]  Terrence J. Sejnowski,et al.  An Information-Maximization Approach to Blind Separation and Blind Deconvolution , 1995, Neural Computation.

[37]  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.

[38]  E. Verstraeten.  Neurocognitive effects of obstructive sleep apnea syndrome , 2007, Current neurology and neuroscience reports.

[39]  Seung-Schik Yoo,et al.  The Unrested Resting Brain: Sleep Deprivation Alters Activity within the Default-mode Network , 2010, Journal of Cognitive Neuroscience.

[40]  J. Svaldi,et al.  Obstructive sleep apnea syndrome: autobiographical memory predicts the course of depressive affect after nCPAP therapy. , 2003, Scandinavian journal of psychology.

[41]  Justin L. Vincent,et al.  Distinct brain networks for adaptive and stable task control in humans , 2007, Proceedings of the National Academy of Sciences.

[42]  Xi Zhang,et al.  A functional MRI evaluation of frontal dysfunction in patients with severe obstructive sleep apnea. , 2011, Sleep medicine.

[43]  Kyungmo Park,et al.  Intrinsic brain connectivity in fibromyalgia is associated with chronic pain intensity. , 2010, Arthritis and rheumatism.

[44]  L. Sweet,et al.  Default Network Response to a Working Memory Challenge after Withdrawal of Continuous Positive Airway Pressure Treatment for Obstructive Sleep Apnea , 2010, Brain Imaging and Behavior.

[45]  Biyu J. He,et al.  Breakdown of Functional Connectivity in Frontoparietal Networks Underlies Behavioral Deficits in Spatial Neglect , 2007, Neuron.

[46]  C. F. Beckmann,et al.  Tensorial extensions of independent component analysis for multisubject FMRI analysis , 2005, NeuroImage.

[47]  Zhijun Zhang,et al.  Specifically Progressive Deficits of Brain Functional Marker in Amnestic Type Mild Cognitive Impairment , 2011, PloS one.

[48]  Gregory G. Brown,et al.  Sleep deprivation-induced reduction in cortical functional response to serial subtraction. , 1999, Neuroreport.

[49]  Teresa Paiva,et al.  Task positive and default mode networks during a parametric working memory task in obstructive sleep apnea patients and healthy controls. , 2011, Sleep.

[50]  P Eusebi,et al.  A 1H magnetic resonance spectroscopy study in patients with obstructive sleep apnea , 2008, European journal of neurology.

[51]  Andrea Falini,et al.  Obstructive sleep apnea: brain structural changes and neurocognitive function before and after treatment. , 2011, American journal of respiratory and critical care medicine.