title: Reversal of functional changes in the brain associated with obstructive sleep apnoea following 6 months of CPAP.
abstract: Obstructive sleep apnoea (OSA) is associated with an increase in the number of bursts of muscle sympathetic nerve activity (MSNA), leading to neurogenic hypertension. Continuous positive airway pressure (CPAP) is the most effective and widely used treatment for preventing collapse of the upper airway in OSA. In addition to improving sleep, CPAP decreases daytime MSNA towards control levels. It remains unknown how this restoration of MSNA occurs, in particular whether CPAP treatment results in a simple readjustment in activity of those brain regions responsible for the initial increase in MSNA or whether other brain regions are recruited to over-ride aberrant brain activity. By recording MSNA concurrently with functional Magnetic Resonance Imaging (fMRI), we aimed to assess brain activity associated with each individual subject's patterns of MSNA prior to and following 6 months of CPAP treatment. Spontaneous fluctuations in MSNA were recorded via tungsten microelectrodes inserted into the common peroneal nerve in 13 newly diagnosed patients with OSA before and after 6 months of treatment with CPAP and in 15 healthy control subjects while lying in a 3 T MRI scanner. Blood Oxygen Level Dependent (BOLD) contrast gradient echo, echo-planar images were continuously collected in a 4 s ON, 4 s OFF (200 volumes) sampling protocol. MSNA was significantly elevated in newly diagnosed OSA patients compared to control subjects (55 ± 4 vs 26 ± 2 bursts/min). Fluctuations in BOLD signal intensity in multiple regions covaried with the intensity of the concurrently recorded bursts of MSNA. There was a significant fall in MSNA after 6 months of CPAP (39 ± 2 bursts/min). The reduction in resting MSNA was coupled with significant falls in signal intensity in precuneus bilaterally, the left and right insula, right medial prefrontal cortex, right anterior cingulate cortex, right parahippocampus and the left and right retrosplenial cortices. These data support our contention that functional changes in these suprabulbar sites are, via projections to the brainstem, driving the augmented sympathetic outflow to the muscle vascular bed in untreated OSA.
authors.affiliation: School of Medicine, University of Western Sydney, Sydney, Australia.
authors.forename: Rania H
authors.initials: RH
authors.lastname: Fatouleh
authors.affiliation: School of Medicine, University of Western Sydney, Sydney, Australia ; Neuroscience Research Australia, Sydney, Australia.
authors.forename: Linda C
authors.initials: LC
authors.lastname: Lundblad
authors.affiliation: UCLA School of Nursing and Brain Research Institute, University of California Los Angeles, USA.
authors.forename: Paul M
authors.initials: PM
authors.lastname: Macey
authors.affiliation: Department of Respiratory Medicine, Prince of Wales Hospital, Sydney, Australia.
authors.forename: David K
authors.initials: DK
authors.lastname: McKenzie
authors.affiliation: Discipline of Anatomy and Histology, University of Sydney, Sydney, Australia.
authors.forename: Luke A
authors.initials: LA
authors.lastname: Henderson
authors.affiliation: School of Medicine, University of Western Sydney, Sydney, Australia ; Neuroscience Research Australia, Sydney, Australia.
authors.forename: Vaughan G
authors.initials: VG
authors.lastname: Macefield
mesh_terms: D000328:Adult; D000368:Aged; D001921:Brain / Q000503:physiopathology*; D001931:Brain Mapping; D002540:Cerebral Cortex / Q000503:physiopathology; D045422:Continuous Positive Airway Pressure; D004569:Electroencephalography; D004576:Electromyography; D005260:Female; D059907:Functional Neuroimaging; D006179:Gyrus Cinguli / Q000503:physiopathology; D006801:Humans; D008279:Magnetic Resonance Imaging; D008297:Male; D008875:Middle Aged; D018482:Muscle, Skeletal / Q000294:innervation*; D020534:Parahippocampal Gyrus / Q000503:physiopathology; D010296:Parietal Lobe / Q000503:physiopathology; D010543:Peroneal Nerve / Q000503:physiopathology; D017286:Polysomnography; D017397:Prefrontal Cortex / Q000503:physiopathology; D011446:Prospective Studies; D020181:Sleep Apnea, Obstructive / Q000503:physiopathology / Q000628:therapy*; D013564:Sympathetic Nervous System / Q000503:physiopathology*; D016896:Treatment Outcome
keywords: Hypertension; Muscle sympathetic nerve activity; Obstructive sleep apnoea