title: Affective brain areas and sleep-disordered breathing.
abstract: The neural damage accompanying the hypoxia, reduced perfusion, and other consequences of sleep-disordered breathing, found in obstructive sleep apnea, heart failure, and congenital central hypoventilation syndrome (CCHS), appears in areas that serve multiple functions, including emotional drives to breathe, and involve systems that serve affective, cardiovascular, and breathing roles. The damage, assessed with structural magnetic resonance imaging (MRI) procedures, shows tissue loss or water content and diffusion changes indicative of injury, and impaired axonal integrity between structures; damage is preferentially unilateral. Functional MRI responses in affected areas also are time- or amplitude-distorted to ventilatory or autonomic challenges. Among the structures injured are the insular, cingulate, and ventral medial prefrontal cortices, as well as cerebellar deep nuclei and cortex, anterior hypothalamus, caudal raphé, ventrolateral medulla, portions of the basal ganglia and, in CCHS, the locus coeruleus. Caudal raphé and locus coeruleus injury have the potential to modify serotonergic and adrenergic modulation of upper airway and arousal characteristics, as well as affective drive to breathe. Since both axons and gray matter show injury, the consequences to function, especially to autonomic, cognitive, and mood regulation, are major. Several of the affected rostral sites mediate aspects of dyspnea, especially in CCHS, while others participate in initiation of inspiration after central breathing pauses, and the medullary injury can impair baroreflex and breathing control. The ancillary injury associated with sleep-disordered breathing to central structures can elicit multiple other distortions in cardiovascular, cognitive, and emotional functions in addition to effects on breathing regulation.
authors.affiliation: Department of Neurobiology, David Geffen School of Medicine at UCLA, University of California at Los Angeles, Los Angeles, CA, USA; Brain Research Institute, University of California at Los Angeles, Los Angeles, CA, USA. Electronic address: rharper@ucla.edu.
authors.forename: Ronald M
authors.initials: RM
authors.lastname: Harper
authors.affiliation: Department of Neurobiology, David Geffen School of Medicine at UCLA, University of California at Los Angeles, Los Angeles, CA, USA; Brain Research Institute, University of California at Los Angeles, Los Angeles, CA, USA.
authors.forename: Rajesh
authors.initials: R
authors.lastname: Kumar
authors.affiliation: Brain Research Institute, University of California at Los Angeles, Los Angeles, CA, USA; UCLA School of Nursing, University of California at Los Angeles, Los Angeles, CA, USA.
authors.forename: Paul M
authors.initials: PM
authors.lastname: Macey
authors.affiliation: UCLA School of Nursing, University of California at Los Angeles, Los Angeles, CA, USA.
authors.forename: Mary A
authors.initials: MA
authors.lastname: Woo
authors.affiliation: UCLA School of Nursing, University of California at Los Angeles, Los Angeles, CA, USA.
authors.forename: Jennifer A
authors.initials: JA
authors.lastname: Ogren
mesh_terms: D000818:Animals; D001921:Brain / Q000473:pathology*; D006801:Humans; D012891:Sleep Apnea Syndromes / Q000150:complications / Q000473:pathology*
keywords: brainstem; congenital central hypoventilation syndrome; heart failure; hypothalamus; magnetic resonance imaging; medulla; obstructive sleep apnea
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