Brainstem changes associated with increased muscle sympathetic drive in obstructive sleep apnoea

• Published in: NeuroImage (Orlando, Fla.) Vol. 103; pp. 258 - 266
• Main Authors: Lundblad, Linda C., Fatouleh, Rania H., Hammam, Elie, McKenzie, David K., Macefield, Vaughan G., Henderson, Luke A.
• Format: Journal Article
• Language: English
• Published: Amsterdam Elsevier Inc 01-12-2014; Elsevier; Elsevier Limited
• Subjects: Adult; Anatomy & physiology; Apnea; Biological and medical sciences; Blood pressure; Brain stem; Brain Stem - physiopathology; Electrodes; Female; Functional magnetic resonance imaging; Fundamental and applied biological sciences. Psychology; Genioglossus muscle; Humans; Hypertension; Image Interpretation, Computer-Assisted; Magnetic Resonance Imaging; Male; Medulla oblongata; Mesencephalon; Morbidity; Morphometry; Muscle, Skeletal - innervation; Muscle, Skeletal - physiopathology; NMR; Nuclear magnetic resonance; Peripheral nervous system. Autonomic nervous system. Neuromuscular transmission. Ganglionic transmission. Electric organ; Physiology; Pons; Respiration; Scanners; Sleep; Sleep apnea; Sleep Apnea, Obstructive - physiopathology; Sleep disorders; Sleep. Vigilance; Spinal cord; Studies; Substantia grisea; Sympathetic Nervous System - physiopathology; Vertebrates: nervous system and sense organs; Australia; Canada; Montreal Quebec Canada; United States > US; Sleep; Autonomic nervous system; Brain stem; Central nervous system; Muscle; Sympathetic nervous system; Encephalon
• ISSN: 1053-8119; 1095-9572
• DOI: 10.1016/j.neuroimage.2014.09.031

Obstructive sleep apnoea (OSA) is associated with significantly increased bursts of muscle sympathetic nerve activity (MSNA), leading to hypertension and increased cardiovascular morbidity. The underlying mechanism responsible for this sympathoexcitation is unknown. The aim of this investigation was to determine brainstem sites that contribute to this increased on-going muscle vasoconstrictor drive. We measured regional grey matter volume using voxel-based morphometry of T1-weighted anatomical images in 20 subjects with OSA and 19 healthy age-matched controls. We also performed concurrent recordings of MSNA and Blood Oxygen Level Dependent (BOLD) signal intensity of the brainstem, using high-resolution functional magnetic resonance imaging, in 15 subjects with OSA and 15 controls. OSA subjects had significantly elevated MSNA, which was correlated to altered BOLD signal intensity changes in the dorsolateral pons, rostral ventrolateral medulla, medullary raphe and midbrain. The medullary raphe, rostroventrolateral medulla and dorsolateral pons also had significantly increased grey matter volumes in subjects with obstructive sleep apnoea compared with controls. Furthermore, we also found that obstructive sleep apnoea was associated with increases in grey matter volume in the region of the hypoglossal nucleus. These data suggest that the elevated muscle vasoconstrictor drive in obstructive sleep apnoea may result from functional and anatomical changes within the dorsolateral pons, rostroventrolateral medulla and medullary raphe. These brainstem regions are known to modulate sympathetic output either directly or indirectly via sympathetic preganglionic neurons within the spinal cord. In addition, the known increase in genioglossus muscle activity in OSA may reflect the increase in grey matter volume of the hypoglossal nucleus.
•Obstructive sleep apnoea is associated with increased sympathetic activity.•This sympathoexcitation is associated with altered brainstem structure and function.•Effected sites include the ventrolateral and medial medulla and dorsolateral pons.